Early Activation by Ethylene of the Tonoplast H-Pumping ATPase in the Latex from Hevea brasiliensis.,0
"The treatment of Hevea brasiliensis (rubber tree) bark by chloro-2-ethyl phosphonic acid (ethrel), an ethylene-producing compound, induces a significant increase in the tonoplast H(+)-translocating ATPase activity in the latex during the first 24 hours after the application of the stimulating agent. Moreover, the tonoplast-bound ATPase is highly activated when vacuoles (lutoids) are resuspended in ultrafiltrated cytosol. This effect is amplified during ethrel stimulation. Preliminary assays to characterize the endogenous effector(s) suggest that the activator(s) could be a heat-resistant compound with a low molecular weight, most likely an anion. The activation of the tonoplast-bound ATPase and the associated activation of the protons translocation across the lutoid membrane, could explain the cytosolic alkalinization observed in latex following the ethrel treatment of Hevea bark, which results in an enhanced rubber production.",1
"Gidrol, X, Chrestin, H, Mounoury, G, D'Auzac, J",2
N-terminus conservation in the terminal pigment of phycobilisomes from a prokaryotic and eukaryotic alga.,0
"High molecular weight polypeptides from phycobilisomes, believed to be involved in facilitating the energy flow from phycobilisomes to thylakoids, are conserved in the prokaryote Nostoc sp. and the eukaryote Porphyridium cruentum. Partial N-terminal sequence analysis of the phycobilisome-polypeptides of Nostoc (94 kilodalton) and Porphyridium (92 kilodalton) revealed 55% identity in the first 20 residues, but no significant homology with sequences of other phycobiliproteins or phycobilisome-linkers. Polypeptides (94 and 92 kilodalton) from Nostoc thylakoids free of phycobilisomes, previously presumed to be involved in the phycobilisome-thylakoid linkage (M Mimuro, CA Lipschultz, E Gantt 1986 Biochim Biophys Acta 852: 126) exhibit the same immunocrossreactivity but are different from the 94 kilodalton-phycobilisome polypeptide by having blocked N-termini and a different amino acid composition.",1
"Gantt, E, Cunningham, F X, Lipschultz, C A, Mimuro, M",2
Measurement of proton-linked transport activities in pyranine loaded chloroplast inner envelope vesicles.,0
"A method has been devised for loading chloroplast inner envelope vesicles prepared from pea (Pisum sativum L. var Progress No. 9) or spinach (Spinacia oleracea L.) with 8-hydroxypyrene-1,3,6-trisulfonate (pyranine), a membrane impermeant, fluorescent pH indicator. Two known proton-linked transport activities of the inner envelope, glycolate/H(+) co-transport and phosphate/phosphoglycerate exchange have been shown to cause quenching of the internal pyranine fluorescence. This represents the first demonstration that these vesicles are sealed and competent for transport measurements. The technique, as it now stands, is essentially qualitative. It does, however, offer advantages over transport measurements with intact chloroplasts, for example compatibility with rapid mixing techniques and accessibility of the transport proteins to antibodies.",1
"Howitz, K T, McCarty, R E",2
PEPCase Transcript Levels in Mesembryanthemum crystallinum Decline Rapidly upon Relief from Salt Stress.,0
"Mesembryanthemum crystallinum plants respond to water stress by changing their pathway of carbon assimilation from C(3) to Crassulacean acid metabolism (CAM). Stressed plants are characterized by elevated levels of phosphoenolpyruvate carboxylase (PEPCase) mRNA, protein, and enzyme activity. We wanted to determine whether CAM is a reversible response to environmental conditions or a developmentally programmed adaptation that is irreversibly expressed once induced. Plants were osmotically stressed by irrigation with 500 millimolar NaCl for 12 days to elicit CAM. Salt was then thoroughly flushed from the soil and PEPCase protein and transcript levels were monitored. PEPCase mRNA levels dropped by 77% within 2.5 hours after salt removal. PEPCase activity and polypeptide levels declined more slowly, with a half-life of 2 to 3 days. These results show that PEPCase expression in M. crystallinum is a reversible response to stress that is regulated at the level of transcription or stability of the PEPCase mRNA.",1
"Vernon, D M, Ostrem, J A, Schmitt, J M, Bohnert, H J",2
Differential Expression in Bundle Sheath and Mesophyll Cells of Maize of Genes for Photosystem II Components Encoded by the Plastid Genome.,0
"We have explored the cell-specific expression of plastid genes encoding five photosystem II proteins (PSII-A, -B, -C, -D and cytochrome (Cyt) b-559 encoded by plastid genes psbA, B, C, D and E plus F, respectively) and one encoding the photosystem I protein PSI-A1 in bundle sheath and mesophyll cells (BSC and MC) at different stages of photoregulated development in leaves of dark-grown maize seedlings. Two types of cell-specific mRNA ccumulation patterns have been discerned. First is the PSII-A type: the mRNA is present in small but about equal amounts in both cell types in etiolated leaves; then, upon illumination, the level of mRNA increases progressively and remains high in MC but not BSC of green leaves. Second is the Cyt b-559 type: MC of etiolated leaves have about twice as much of this mRNA as do BSC; about a twofold to threefold transient increase is induced by light in MC but not in BSC. The genes for the PSII-C and -D proteins are complementary to a sizable family of transcripts over a large range of sizes; the patterns of changes in pools of some of these transcripts are of the PSII-A type and others are of the Cyt b-559 type. The DNA region encoding the PSII-B protein also hybridizes to multiple transcripts; among them is a prominent 2.2 kilobase transcript that follows the Cyt b-559 accumulation pattern. In contrast, the pattern of PSI-A1 mRNA accumulation is the same in both cell types. Accumulation of the PSII-B and -D proteins is light-dependent and coordinate. Both are much more abundant in MC than in BSC. PSII-A is detectable in MC of etiolated leaves and increases during photoregulated chloroplast maturation in both cell types, however, to a much greater extent in MC. We conclude that the expression of each of these plastidencoded photosystem II genes in BSC and MC is photoregulated differently; both transcript abundance and translation are regulated.",1
"Sheen, J Y, Bogorad, L",2
Gradients of Intercellular CO(2) Levels Across the Leaf Mesophyll.,0
"Most current photosynthesis models, and interpretations of many wholeleaf CO(2) gas exchange measurements, are based on the often unstated assumption that the partial pressure of CO(2) is nearly uniform throughout the airspaces of the leaf mesophyll. Here we present measurements of CO(2) gradients across amphistomatous leaves allowed to assimilate CO(2) through only one surface, thus simulating hypostomatous leaves. We studied five species: Eucalyptus pauciflora Sieb. ex Spreng., Brassica chinensis L., Gossypium hirsutum L., Phaseolus vulgaris L., and Spinacia oleracea L. For Eucalyptus, maximum CO(2) pressure differences across the leaf mesophyll were 73 and 160 microbar when the pressures outside the lower leaf surface were 310 and 590 microbar, respectively. Using an approximate theoretical calculation, we infer that if the CO(2) had been supplied equally at both surfaces then the respective mean intercellular CO(2) pressures would have been roughly 12 and 27 microbar less than the pressures in the substomatal cavities in these cases. For ambient CO(2) pressures near 320 microbar, the average and minimum pressure differences across the mesophyll were 45 and 13 microbar. The corresponding mean intercellular CO(2) pressures would then be roughly 8 and 2 microbar less than those in the substomatal cavities. Pressure differences were generally smaller for the four agricultural species than for Eucalyptus, but they were nevertheless larger than previously reported values.",1
"Parkhurst, D F, Wong, S C, Farquhar, G D, Cowan, I R",2
Hormone action on transmembrane electron and h transport.,0
"A possible involvement of two different systems in proton translocation was investigated by simultaneous measurement of transmembrane electron flow and proton secretion in a pH-stat combined with a redoxstat. The pH gradient between cytoplasm and apoplast is probably maintained by an H(+) -pumping ATPase and by a second proton extrusion system, which seems to be linked to a redox chain with NAD(P)H as electron donor. Indole acetic acid inhibits both e(-) and H(+) efflux, but only if the ;electron draw' from the outside is not too high. The electron draw depends on the hexacyanoferrate level at the plasmalemma surface and on the Ca(2+) concentration. The inhibiting effect of auxin on e(-) and H(+) efflux in the presence of hexacyanoferrate can be only detected at low levels of bivalent cations and of the artificial electron acceptor. The inhibition of e(-) and H(+) efflux by auxin requires high oxygen levels. The influence of auxin on both e(-) and H(+) transfer disappears below 2 kilopascals O(2), a level which does not influence respiration. Ethanol and fusicoccin do not increase the e(-) flux, probably because the electron transfer from the plasma membrane to HCF III is the limiting step. If electron transfer is reduced by IAA pretreatment, ethanol increases e(-) flux. Fusicoccin decreases e(-) and increases H(+) efflux if the rates have been lowered previously by indole acetic acid pretreatment. This effect depends on high oxygen levels and is reversible by lowering oxygen pressure. Auxin and Ca(2+) change e(-) flow and H(+) ejection in a 1:1 ratio.",1
"Böttger, M, Hilgendorf, F",2
Hexachloroiridate IV as an Electron Acceptor for a Plasmalemma Redox System in Maize Roots.,0
"Hexachloroiridate IV, a new artificial electron acceptor for the constitutive plant plasma membrane redox system has been investigated. It appeared not to permeate through biological membranes. Due to its higher redox potential, it is a more powerful electron acceptor than hexacyanoferrate III (ferricyanide) and even micromolar concentrations are rapidly reduced. Hexachloroiridate IV increased H(+) efflux over a concentration range of 0.05 to 0.1 millimolar. Lower concentrations slightly inhibited proton extrusion. Calcium stimulated both proton and electron transfer rates. Like hexacyanoferrate III-reduction, irridate reduction was inhibited by auxin.",1
"Lüthen, H, Böttger, M",2
Induction and Accumulation of Heat Shock-Specific Poly(A) RNAs and Proteins in Soybean Seedlings during Arsenite and Cadmium Treatments.,0
"Northern blot hybridization analyzes revealed that poly(A(+)) RNAs homologous to eight heat shock (HS)-specific cDNA clones were induced by arsenite (As) or Cd treatments. The mRNAs accumulated slower, and maximum accumulations were consistently lower than HS-induced levels. Prolonged treatment with low concentrations (50-100 micromolar) of As for 6 hours, or Cd for 12 hours, resulted in decreased accumulations of HS-specific mRNAs. This response resembled the ;autoregulation' observed during continuous 40 degrees C HS. However, no autoregulation was evident when soybean seedlings were exposed to high concentrations of As (250 micromolar) or Cd (1 millimolar) for 12 hours. The cDNA probe pCE54 detected a second higher molecular weight poly(A(+)) RNA following As or Cd treatments which accumulated concomitantly with the lower molecular weight HS-specific poly(A(+)) RNA. The patterns of low molecular weight HS polypeptides from in vitro translations induced by HS, As, and Cd, and analyzed by one-dimensional and two-dimensional SDS-PAGE, were similar but temporal differences were apparent. In addition to HS proteins, many control proteins were also detected in both in vitro and in vivo labeling patterns from As and, to a lesser extent, Cd treatments. The chemical agents used in this study apparently induced the accumulation and translation of HS messages in vivo but not in the selective manner as observed during HS treatment.",1
"Edelman, L, Czarnecka, E, Key, J L",2
In vitro synthesis and processing of tomato fruit polygalacturonase.,0
"The in vitro processing of tomato fruit polygalacturonase (PG) (poly[1,4-alpha-d-galacturonide]glucanohydrolase, EC 3.2.1.15) was studied. Complete chemical deglycosylation of a mixture of mature, purified PG 2A and PG 2B isozymes (45 and 46 kilodaltons; respectively) with trifluoromethane sulfonic acid yielded a single polypeptide of 42 kilodaltons. Similarly, N-terminal amino acid sequencing of the PG 2A/2B isozyme mixture yielded a single 21 amino acid N-terminal sequence, suggesting that the two isozymes result from differential post-translational processing of a single polypeptide. Translation of PG mRNA in vitro results in the synthesis of a single polypeptide with an apparent molecular weight of 54 kilodaltons. Nucleotide sequence analysis of a full-length PG cDNA clone indicates that the large size difference between the PG in vitro translation product and the mature isozymes is due to the presence of a 71 amino acid (8.2 kilodaltons) domain at the N-terminus of in vitro translated PG, consisting of a hydrophobic signal sequence followed by a highly charged prosequence. To determine the precise cleavage site of the signal sequence, PG mRNA was translated in vitro in the presence of canine pancreas microsomal membranes. This resulted in the production of two glycosylated PG processing intermediates with apparent molecular weights of 58 and 61 kilodaltons. The PG processing intermediates were shown to be sequestered within the lumen of the microsomal membranes by protease protection and centrifugational analysis. Deglycosylation of the PG processing intermediates with endoglycosidase H yielded a single polypeptide with an apparent molecular weight of 54 kilodaltons. The production of two distinct, glycosylated processing intermediates from the single in vitro translated PG polypeptide suggests a mechanism by which the differential glycosylation observed for the mature PG 2A and PG 2B isozymes may occur. Edman degradation of (3)H-labeled 58 and 61 kilodalton PG processing intermediates indicates that the site of signal sequence cleavage is after amino acid 24 (serine). These results suggest that the proteolytic processing of PG occurs in at least two steps, the first being the co-translational removal of the 24 amino acid signal sequence and the second being the presumed post-translational removal of the remaining highly charged 47 amino acid prosequence.",1
"Dellapenna, D, Bennett, A B",2
"Diurnal growth of tall fescue leaf blades : I. Spatial distribution of growth, deposition of water, and assimilate import in the elongation zone.",0
"Tall fescue leaf blades elongate at near constant rates during most of the light and dark periods of the diurnal cycle, with the dark rate being higher by 60 to 65%. Our objective was to determine relationships among diurnal rates of leaf elongation, deposition of water and deposition of dry matter (DM) into the elongation zone. Two separate experiments were conducted, both with a 15-hour photoperiod and constant 21 degrees C at the growth zone. Increased rates of leaf elongation in darkness were due to proportionally increased rates of elongation of 4-millimeter segments of the elongation zone. Length of the total elongation zone was 30 millimeters in both light and darkness. The spatial distribution of water contents in the elongation zone varied little during the diurnal cycle. Thus, dark stimulation of leaf elongation rate (+65%) and of water deposition (+77%) into elongation zones were similar. Water content per unit leaf length increased by 50% between the basal and distal limits of the elongation zone, indicating that tissue also grew in the lateral and vertical dimensions. Longitudinal growth of tissue, however, allowed 5 to 7 times more water deposition into the elongation zone than growth in cross-sectional area. This relationship was similar in light and darkness. In both light and darkness net rates of DM deposition (microgram per millimeter leaf length per hour) increased from the zone of cell division towards the region of most active elongation, 10 to 15 millimeters from the ligule, then decreased towards the distal end of the elongation zone. Net DM deposition rates (microgram per hour) integrated over the 30-millimeter elongation zone were similar during light and darkness. Thus, DM in the elongation zone was diluted during darkness as a result of increased water deposition. Net DM deposition rates at and above the distal end of the elongation zone were clearly positive during the light, but were close to zero or negative in darkness. Thus, DM deposition into the elongation zone and the adjacent recently expanded tissue was differentially affected in the diurnal cycle, DM deposition occurred in both tissues in light, but was restricted to the elongation zone in darkness.",1
"Schnyder, H, Nelson, C J",2
Diurnal Growth of Tall Fescue Leaf Blades : II. Dry Matter Partitioning and Carbohydrate Metabolism in the Elongation Zone and Adjacent Expanded Tissue.,0
"The spatial distributions of net deposition rates of water soluble carbohydrate-free dry matter (WSC-free DM) and WSC were evaluated within and above the elongation zone of tall fescue (Festuca arundinacea Schreb.) leaf blades during light and darkness. Imported DM used for WSC-free DM synthesis during darkness (67% of the total in experiment I and 59% in experiment II) was greater than during light (47% in both experiments), suggesting that the 65% higher leaf elongation rate during darkness was accompanied by higher rates of synthesis of cellular structural components. Deposition rates of WSC in the basal and central part of the elongation zone (0-20 mm from the ligule) were similar during light and darkness, but above 20 millimeters WSC deposition occurred during light and WSC loss occurred during darkness. WSC deposition and loss throughout the elongation zone and the recently expanded tissue were mostly due to net synthesis and degradation of fructan. Fructan was predominantly low molecular weight and contributed about 50% of the total osmotic partial pressure of WSC. In the most actively growing region, where fructan synthesis was most rapid, no diurnal change occurred in molecular weight distribution of fructan. WSC solute concentrations were diluted in the most actively growing tissue during darkness because net monosaccharide and fructan deposition were unaltered and sucrose deposition was decreased, but growth-associated water deposition was increased by 77%. Net rates of fructan synthesis and degradation were not related to tissue sucrose concentration, but appeared to respond to the balance between assimilate import and assimilate use in synthesis of cellular structural components (i.e. WSC-free DM) and deposition of monosaccharides. Fructan synthesized in tissue during most active elongation was degraded when the respective tissue reached the distal limit of the elongation zone where assimilate import in darkness was insufficient to maintain synthetic processes associated with further differentiation of cells.",1
"Schnyder, H, Nelson, C J, Spollen, W G",2
"The regulation of gelation of Phloem exudate from cucurbita fruit by dilution, glutathione, and glutathione reductase.",0
"The average glutathione equivalent concentration in phloem exudate collected from squash fruit (Cucurbita moschata [Duchesne] Poir. var Butternut) and pumpkin fruit (Cucurbita pepo [L.] var Jack-o-lattern) was 1.02 and 0.60 millimolar, respectively. Glutathione reductase (EC 1.6.4.2) activity in phloem exudate from squash and pumpkin fruit averaged 0.48 and 1.74 micromole NADPH oxidized per minute per milliliter, respectively. Protein concentrations in fruit phloem exudates averaged 67 milligrams per milliliter for squash and 57 milligrams per milliliter for pumpkin. The phloem-specific P-proteins account for most of the protein content of exudate. Pure exudate from fruit does not gel for hours or days, but when diluted with neutral or alkaline aqueous solutions, exudate gels rapidly. Exudate solutions undergo biphasic pH changes with dilution. We suggest that P-protein undergoes conformational change upon dilution, exposing titratable groups and sulfhydryl residues. Oxidation of the latter forms the intermolecular disulfide bridges of the gel. The gelation of diluted exudate is regulated by factors (oxygen, pH, glutathione, NADPH) which affect the maintenance of reduced sulfhydryl residues and the activity of glutathione reductase. While these factors may also act in vivo to regulate redox conditions in phloem, their relationship to hypothetical sol/gel transitions or motile and nonmotile phases in the transport conduit is unknown.",1
"Alosi, M C, Melroy, D L, Park, R B",2
beta-Glucoside Activators of Mung Bean UDP-Glucose: beta-Glucan Synthase : II. Comparison of Effects of an Endogenous beta-Linked Glucolipid with Synthetic n-Alkyl beta-d-Monoglucopyranosides.,0
"n-Alkyl (C(6)-C(12)) beta-d-monoglucopyranosides have been found to be highly potent activators of mung bean beta-glucan synthase in vitro, increasing the V(max) of the enzyme as much as 60-fold and with K(a) values as low as 10 micromolar. Activation is highly specific for the beta-linked terminal glucose residue; other alkyl glycosides such as, octyl-alpha-glucoside, dodecyl beta-maltoside, 6-lauryl sucrose, 6-lauryl glucose, which lack this structure, are ineffective as activators. Based on the similarities in their structure and effects on beta-glucan synthesis under a variety of conditions, it is proposed that the alkyl beta-glucosides are structural analogs of the native glucolipid activator of beta-glucan synthase isolated from mung bean extracts.",1
"Callaghan, T, Ross, P, Weinberger-Ohana, P, Benziman, M",2
"Light-Harvesting Chlorophyll a/b Protein : Membrane Insertion, Proteolytic Processing, Assembly into LHC II, and Localization to Appressed Membranes Occurs in Chloroplast Lysates.",0
"The apoprotein of the light-harvesting chlorophyll a/b protein (LHCP) is a major integral thylakoid membrane protein that is normally complexed with chlorophyll and xanthophylls and serves as the antenna complex of photosystem II. LHCP is encoded in the nucleus and synthesized in the cytosol as a higher molecular weight precursor that is subsequently imported into chloroplasts and assembled into thylakoids. In a previous study it was established that the LHCP precursor can integrate into isolated thylakoid membranes. The present study demonstrates that under conditions designed to preserve thylakoid structure, the inserted LHCP precursor is processed to mature size, assembled into the LHC II chlorophyll-protein complex, and localized to the appressed thylakoid membranes. Under these conditions, light can partially replace exogenous ATP in the membrane integration process.",1
"Cline, K",2
Early Inhibition of Photosynthesis during Development of Mn Toxicity in Tobacco.,0
"Early physiological effects of developing Mn toxicity in young leaves of burley tobacco (Nicotiana tabacum L. cv KY 14) were examined in glass-house/water cultured plants grown at high (summer) and low (winter) photon flux. Following transfer of plants to solutions containing 1 millimolar Mn(2+), sequential samplings were made at various times for the following 9 days, during which Mn accumulation by leaves increased rapidly from approximately 70 on day 0 to approximately 1700 and approximately 5000 microgram per gram dry matter after 1 and 9 days, respectively. In plants grown at high photon flux, net photosynthesis declined by approximately 20 and approximately 60% after 1 and 9 days, respectively, and the onset of this decline preceded appearance (after 3 to 4 days) of visible foliar symptoms of Mn toxicity. Intercellular CO(2) concentrations and rates of transpiration were not significantly affected; moreover, the activity of the Hill and photosystem I and II partial reactions of chloroplasts remained constant despite ultimate development of severe necrosis. Though the activity of latent or activated polyphenol oxidase increased in parallel with Mn accumulation, neither leaf respiration nor the activity of catalase [EC 1.11.1.6] and peroxidase [EC 1.10.1.7] were greatly affected. These effects from Mn toxicity could not be explained by any changes in protein or chlorophyll abundance. Additionally, they were not a consequence of Mn induced Fe deficiency. Therefore, inhibition of net photosynthesis and enhancement of polyphenol oxidase activity are early indicators of excess Mn accumulation in tobacco leaves. These changes, as well as leaf visual symptoms of Mn toxicity, were less severe in plants cultured and treated at low photon flux even though the rates of leaf Mn accumulation at high and low photon flux were essentially equivalent.",1
"Nable, R O, Houtz, R L, Cheniae, G M",2
Positive selection for male-sterile mutants of Arabidopsis lacking adenine phosphoribosyl transferase activity.,0
"Three mutants of Arabidopsis thaliana deficient in adenine phosphoribosyl transferase activity were isolated by selecting for germination of seeds on a medium containing 0.1 millimolar 2,6-diaminopurine. In each of the mutants, diaminopurine resistance was due to a recessive nuclear mutation at a locus designated apt. The mutants grow more slowly than wild type, and are male sterile due to abortion of pollen development after the meiotic divisions of the pollen mother cells. The reliability and ease with which the mutants can be selected should afford novel opportunities to investigate purine metabolism, pollen development, and genetic problems which require the ability to select for loss-of-function mutations.",1
"Moffatt, B, Somerville, C",2
Role of Photosynthetic Reactions in the Activity of Carbonic Anhydrase in Synechococcus sp. (UTEX 2380) in the Light : Inhibitor Studies Using the O-Exchange in C/O-Labeled Bicarbonate.,0
"The role of the photosystems in the exchange of (18)O between species of inorganic carbon and water was studied in suspensions of the cyanobacterium Synechococcus sp. (UTEX 2380) using membrane-inlet mass spectrometry. This (18)O exchange is caused by the hydration-dehydration cycle of CO(2) and is catalyzed by carbonic anhydrase. We observed the complex (18)O exchange kinetics including dark-light-dark transients in suspensions of whole cells and found these to be identical to the (18)O exchange kinetics of physiologically fully active spheroplast preparations. There was no enhancement effect of inorganic nitrogen on inorganic carbon accumulation. Membrane preparations exhibited no uptake of inorganic carbon and very little carbonic anhydrase activity, although these membranes were photosynthetically fully competent. DCMU, the inhibitor of photosystem II, eliminated almost entirely the (18)O exchange activity of whole cells in the light. But this effect of DCMU could be reversed by addition of the electron donor couple 3,6-diaminodurene/ascorbate, suggesting the involvement of photosystem I in the events leading to (18)O exchange. Iodoacetamide, an inhibitor of CO(2) fixation, enhanced the (18)O exchange in whole cell suspensions and inhibited neither the uptake of inorganic carbon nor the dehydration of bicarbonate in the light. The proton carrier carbonylcyanide m-chlorophenylhydrazone and the inhibitors diethylstilbestrol and N,N' -dicyclohexyl carbodiimide affecting the membrane potential, totally abolished (18)O exchange in the light. From (18) O-labeled inorganic carbon experiments we conclude that one of the roles of photosystem I is to provide the active uptake of inorganic carbon into the cells, where carbonic anhydrase catalyzes the interconversion between CO(2) and HCO(3) (-) resulting in the (18)O exchange from inorganic carbon to water.",1
"Spiller, H, Wynns, G C, Tu, C",2
Effects of Elevated CO(2) Concentrations on Glycolysis in Intact ;Bartlett' Pear Fruit.,0
"Mature intact ;Bartlett' pear fruit (Pyrus communis L.) were stored under a continuous flow of air or air + 10% CO(2) for 4 days at 20 degrees C. Fruit kept under elevated CO(2) concentrations exhibited reduced respiration (O(2) consumption) and ethylene evolution rates, and remained firmer and greener than fruit stored in air. Protein content, fructose 1,6-bisphosphate levels, and ATP:phosphofructokinase and PPi:phosphofructokinase activities declined, while levels of fructose 6-phosphate and fructose 2,6-bisphosphate increased in fruit exposed to air + 10% CO(2). These results are discussed in light of a possible inhibitory effect of CO(2) at the site of action of both phosphofructokinases in the glycolytic pathway, which could account, at least in part, for the observed reduction in respiration.",1
"Kerbel, E L, Kader, A A, Romani, R J",2
Development of a plant transformation selection system based on expression of genes encoding gentamicin acetyltransferases.,0
The development of selectable markers for transformation has been a major factor in the successful genetic manipulation of plants. A new selectable marker system has been developed based on bacterial gentamicin-3-N-acetyltransferases [AAC(3)]. These enzymes inactivate aminoglycoside antibiotics by acetylation. Two examples of AAC(3) enzymes have been manipulated to be expressed in plants. Chimeric AAC(3)-III and AAC(3)-IV genes were assembled using the constitutively expressed cauliflower mosaic virus 35S promoter and the nopaline synthase 3' nontranslated region. These chimeric genes were engineered into vectors for Agrobacterium-mediated plant transformation. Petunia hybrida and Arabidopsis thaliana tissue transformed with these vectors grew in the presence of normally lethal levels of gentamicin. The transformed nature of regenerated Arabidopsis plants was confirmed by DNA hybridization analysis and inheritance of the selectable phenotype in progeny. The chimeric AAC(3)-IV gene has also been used to select transformants in several additional plant species. These results show that the bacterial AAC(3) genes will serve as useful selectable markers in plant tissue culture.,1
"Hayford, M B, Medford, J I, Hoffman, N L, Rogers, S G, Klee, H J",2
Changes in the Level of [C]Indole-3-Acetic Acid and [C]Indoleacetylaspartic Acid during Root Formation in Mung Bean Cuttings.,0
"Changes in the levels of [(14)C]indole-3-acetic acid (IAA) and [(14)C]indole-acetylaspartic acid (IAAsp) were examined during adventitious root formation in mung bean (Vigna radiata [L.] R. Wilcz. ;Berken') stem cuttings. IAAsp was identified by GC-MS as the primary conjugate in IAA-treated cuttings. During root formation in IAA-treated cuttings, the level of [(14)C]IAAsp increased rapidly the first day and then declined; [(14)C]IAA was rapidly metabolized and not detected after 12 hours.",1
"Norcini, J G, Heuser, C W",2
Fructan Content and Synthesis in Leaf Tissues of Festuca arundinacea.,0
"The concentration of fructan in tall fescue (Festuca arundinacea Schreb.) changes during growth and in response to environment. The objective of this research was to compare the fructan concentration and fructosyl-transferase activity of tall fescue leaf tissues. Expanding leaves, inner and outer sheaths, and expanded blades of greenhouse-grown tall fescue plants were assayed for fructan concentration and fructosyl-transferase activity. Leaf sheaths contained significantly more nonstructural carbohydrate than did the expanded blade. Sheaths also contained a greater percentage of fructan with more than six sugar residues (long chain fructan), than either the expanded blade or expanding leaf. Expanding leaves contained a greater concentration of fructose and oligosaccharides than did sheath or blade tissues. Expanding leaves also had the greatest fructosyl-transferase activity measured either as radiolabel incorporated into fructans in tissue pieces or protein extracts. Activity of fructosyl-transferase was greater in expanding leaf tissue than in sheath tissues.",1
"Housley, T L, Volenec, J J",2
Quantitative and rapid estimation of h fluxes in membrane vesicles : software for analysis of fluorescence quenching and relaxation.,0
Proton transport is often visualized in membrane vesicles by use of fluorescent monoamines which accumulate in acidic intravesicular compartments and undergo concentration-dependent fluorescence quenching. Software for an IBM microcomputer is described which permits logging and editing of changes in fluorescence monitored by a Perkin-Elmer LS-5 luminescence spectrometer. An accurate estimate of the instantaneous rate of fluorescence quenching or recovery is then facilitated by least squares fitting of fluorescence data to a nonlinear function. The software is tested with tonoplast vesicles from Beta vulgaris. Quenching of acridine orange fluorescence by ATP-driven (primary) transport and relaxation of quenching by Na(+)/H(+) antiport can both be fitted with single exponential functions. Initial rates of ATP- and Na(+) -dependent fluorescence changes are derived and can be used for K(m) determinations. The method constitutes a simple and efficient alternative to manual analysis of analog fluorescence traces and results in a reliable quantitative measurement of the relative rate of proton transport in membrane vesicle preparations.,1
"Jennings, I R, Rea, P A, Leigh, R A, Sanders, D",2
Indole-3-acetic Acid oxidation and crocin bleaching by horseradish peroxidase.,0
"During indoleacetic acid (IAA) oxidation by horseradish peroxidase the water soluble model polyene, crocin, is bleached. IAA-oxidation and crocin bleaching are stimulated at acidic pH as well as by the monophenol p-hydroxyacetophenone. IAA oxidation and crocin bleaching are neither influenced by catalase or superoxide dismutase nor by different OH-radical scavengers, whereas both ascorbate and propylgallate are inhibitory.",1
"Osswald, W F, Schütz, W, Elstner, E F",2
Superoxide free radicals are produced in glyoxysomes.,0
"The production of superoxide free radicals in pellet and supernatant fractions of glyoxysomes, specialized plant peroxisomes from watermelon (Citrullus vulgaris Schrad.) cotyledons, was investigated. Upon inhibition of the endogenous superoxide dismutase, xanthine, and hypoxanthine induced in glyoxysomal supernatants the generation of O(2) (-) radicals and this was inhibited by allopurinol. In glyoxysomal pellets, NADH stimulated the generation of superoxide radicals. Superoxide production by purines was due to xanthine oxidase, which was found predominantly in the matrix of glyoxysomes. The generation of O(2) (-) radicals in glyoxysomes by endogenous metabolites suggests new active oxygen-related roles for glyoxysomes, and for peroxisomes in general, in cellular metabolism.",1
"Sandalio, L M, Fernández, V M, Rupérez, F L, Del Río, L A",2
Three Phases of Plant Response to Atmospheric CO(2) Enrichment.,0
"Several years of research on seven different plants (five terrestrial and two aquatic species) suggest that the beneficial effects of atmospheric CO(2) enrichment may be divided into three distinct growth response phases. First is a well-watered optimum-growth-rate phase where a 300 parts per million increase in the CO(2) content of the air generally increases plant productivity by approximately 30%. Next comes a nonlethal water-stressed phase where the same increase in atmospheric CO(2) is more than half again as effective in increasing plant productivity. Finally, there is a water-stressed phase normally indicative of impending death, where atmospheric CO(2) enrichment may actually prevent plants from succumbing to the rigors of the environment and enable them to maintain essential life processes, as life ebbs from corresponding ambient-treatment plants.",1
"Idso, S B",2
"Inhibition of phytochrome synthesis by the transaminase inhibitor, 4-amino-5-fluoropentanoic Acid.",0
"Gardner and Gorton (1985 Plant Physiol 77: 540-543) demonstrated that the transaminase inhibitor gabaculine (5-amino-1,3-cyclohexadienyl-carboxylic acid) inhibits the initial synthesis and resynthesis of spectrophotometrically detectable phytochrome in vivo. Another mechanism-based transaminase inhibitor, 4-amino-5-fluoropentanoic acid (AFPA), is examined in this report for its effects on phytochrome synthesis in developing etiolated seedlings. Preemergence treatment with AFPA was found to inhibit initial phytochrome synthesis in peas (Pisum sativum L.), corn (Zea mays L.), and oats (Avena sativa L.). In general, reduction in phytochrome correlated with reduction in chlorophyll. However, the extent of inhibition of phytochrome synthesis was not as great as that of chlorophyll synthesis. These results confirm those with gabaculine, indicating that both initial synthesis and resynthesis of phytochrome require de novo synthesis of chromophore as well as apoprotein. AFPA was a more effective inhibitor of both chlorophyll and phytochrome synthesis than was gabaculine, suggesting that AFPA may be the preferred tool with which to probe the physiological consequences of the inhibition of phytochrome biosynthesis.",1
"Gardner, G, Gorton, H L, Brown, S A",2
Zeaxanthin and the Heat Dissipation of Excess Light Energy in Nerium oleander Exposed to a Combination of High Light and Water Stress.,0
"Upon termination of watering of plants of Nerium oleander exposed to high light, photochemical efficiency became reduced as leaf water content decreased. Evidence is presented that this type of photoinhibition reflects to a substantial degree radiationless dissipation of excitation energy, probably mediated by the carotenoid zeaxanthin. During the imposition of water stress, the zeaxanthin content of leaves increased at the expense of violaxanthin and beta-carotene as a water deficit developed over a period of several days. The increase in zeaxanthin content was linearly related to an increase in the rate of radiationless energy dissipation in the antenna chlorophyll as calculated from the characteristics of chlorophyll a fluorescence measured with a pulse amplitude modulated fluorometer at room temperature. The increase in the rate of radiationless dissipation was also linearly related to a decrease in PSII photochemical efficiency as indicated by the ratio of variable to maximum fluorescence. Leaves of well-watered shade plants of N. oleander exposed to strong light showed a similar increase in zeaxanthin content as sun leaves of the same species subjected to drought in strong light. Shade leaves possessed the same capacity as sun leaves to form zeaxanthin at the expense of both violaxanthin and beta-carotene. The resistance of this species to the destructive effects of excess light appears to be related to interconversions between beta-carotene and the three carotenoids of the xanthophyll cycle.",1
"Demmig, B, Winter, K, Krüger, A, Czygan, F C",2
Nucleoside diphosphatase and 5'-nucleotidase activities of soybean root nodules and other tissues.,0
"Nucleoside diphosphatase and 5'-nucleotidase activities were both found to be very high in extracts of soybean (Glycine max L.) root nodules. Both activities increased early in soybean nodule development, prior to the rise in leghemoglobin, and both were found at equivalent levels in nitrogenfixing and nonfixing nodules. Based on a survey of other tissues, these activities were both highest in soybean nodules (1300 nanomoles per milligram protein per minute, nucleoside diphosphatase and 500 nanomoles per milligram protein per minute, 5'-nucleotidase), but they were not always associated with each other; in some tissues one was high and the other low. Neither activity correlated well with ureide production; both seem, rather, to be primarily involved in some other metabolic function. Both the nucleoside diphosphatase and 5'-nucleotidase of soybean nodules were soluble proteins, and neither appeared to be associated with plastids, mitochondria, or bacteroids.",1
"Doremus, H D, Blevins, D G",2
Regulation of photosynthesis in nitrogen deficient wheat seedlings.,0
"Nitrogen effects on the regulation of photosynthesis in wheat (Triticum aestivum L., cv Remia) seedlings were examined. Ribulose 1,5-bisphosphate carboxylase/oxygenase was rapidly extracted and tested for initial activity and for activity after incubation in presence of CO(2) and Mg(2+). Freeze clamped leaf segments were extracted for determinations of foliar steady state levels of ribulose 1,5-bisphosphate, triose phosphate, 3-phosphoglycerate, ATP, and ADP. Nitrogen deficient leaves showed increased ATP/ADP and triose phosphate/3-phosphoglycerate ratios suggesting increased assimilatory power. Ribulose 1,5-bisphosphate levels were decreased due to reduced pentose phosphate reductive cycle activity. Nevertheless, photosynthesis appeared to be limited by ribulose 1,5-bisphosphate carboxylase/oxygenase, independent of nitrogen nutrition. Its degree of activation was increased in nitrogen deficient plants and provided for maximum photosynthesis at decreased enzyme protein levels. It is suggested that ribulose 1,5-bisphosphate carboxylase/oxygenase activity is regulated according to the amount of assimilatory power.",1
"Mächler, F, Oberson, A, Grub, A, Nösberger, J",2
Growth of the maize primary root at low water potentials : I. Spatial distribution of expansive growth.,0
"Seedlings of maize (Zea mays L. cv WF9 x Mo 17) were grown in vermiculite at various water potentials. The primary root continued slow rates of elongation at water potentials which completely inhibited shoot growth. To gain an increased understanding of the root growth response, we examined the spatial distribution of growth at various water potentials. Time lapse photography of the growth of marked roots revealed that inhibition of root elongation at low water potentials was not explained by a proportional decrease in growth along the length of the growing zone. Instead, longitudinal growth was insensitive to water potentials as low as - 1.6 megapascal close to the root apex, but was inhibited increasingly in more basal locations such that the length of the growing zone decreased progressively as the water potential decreased. Cessation of longitudinal growth occurred in tissue of approximately the same age regardless of spatial location or water status, however. Roots growing at low water potentials were also thinner, and analysis revealed that radial growth rates were decreased throughout the elongation zone, resulting in greatly decreased rates of volume expansion.",1
"Sharp, R E, Silk, W K, Hsiao, T C",2
Pathogenesis-related proteins of tomato : p-69 as an alkaline endoproteinase.,0
"An endoproteinase induced by citrus exocortis viroid has been purified from tomato (Lycopersicon esculentum Mill, cv ""Rutgers"") leaves. The proteinase corresponds to one of the major pathogenesis-related proteins of tomato plants and was designated proteinase P-69 as it has a molecular weight of 69,000 to 70,000. The proteinase was purified in four steps: (NH(4))(2)SO(4) fractionation, chromatography on Bio-Gel P-60, DEAE-Sepharose chromatography, and casein-Sepharose affinity chromatography. The proteinase had a pH optimum of 8.5 to 9.0 when assayed with either fluorescein thiocarbamoyl derivative (FTC)-casein or FTC-ribulose 1,5-bisphosphate carboxylase/oxygenase as substrates. The proteinase activity was inhibited by pCMB and strongly activated by calcium and magnesium ions as well as by DTT. When analyzed by electrofocusing, the activity showed a pI around 9.0.",1
"Vera, P, Conejero, V",2
Transport of Phosphoenolpyruvate by Chloroplasts from Mesembryanthemum crystallinum L. Exhibiting Crassulacean Acid Metabolism.,0
"Chloroplasts from CAM-Mesembryanthemum crystallinum can transport phosphoenolpyruvate (PEP) across the envelope. The initial velocities of PEP uptake in the dark at 4 degrees C exhibited saturation kinetics with increasing external PEP concentration. PEP uptake had a V(max) of 6.46 (+/-0.05) micromoles per milligram chlorophyll per hour and an apparent K(mpep) of 0.148 (+/-0.004) millimolar. The uptake was competitively inhibited by Pi (apparent K(i) = 0.19 millimolar), by glycerate 3-phosphate (apparent K(i) = 0.13 millimolar), and by dihydroxyacetone phosphate, but malate and pyruvate were without effect. The chloroplasts were able to synthesize PEP when presented with pyruvate. PEP synthesis was light dependent. The prolonged synthesis and export of PEP from the chloroplasts required the presence of Pi or glycerate 3-phosphate in the external medium. It is suggested that the transport of pyruvate and PEP across the chloroplasts envelope is required during the gluconeogenic conversion of carbon from malate to storage carbohydrate in the light.",1
"Neuhaus, H E, Holtum, J A, Latzko, E",2
Modifications of extracellular electric and ionic gradients preceding the transition from tip growth to isodiametric expansion in the apical cell of the fern gametophyte.,0
"Fern (Onoclea sensibilis L.) gametophytes exposed to blue light are induced to undergo a morphological transition from a tip-growing filament to a planar prothallus. Extracellular measurements of electric currents and localized ion activities around the apical cell of 8 to 10 day-old gametophytes were made with a vibrating probe and ion selective electrodes. In darkness, we observed exit current densities of an average of 75 nanoamperes per square centimeter near the tip and 2 to 15 nanoamperes per square centimeter along the lateral walls of this cell. Measurements with ion selective electrodes for H(+), K(+), and Ca(2+) showed that this cell was bounded by a thin layer of medium that was depleted in K(+) and Ca(2+) and exhibited a lower pH than the bulk solution. Both the K(+) and Ca(2+) depletion zones and the zone of higher acidity were particularly pronounced at the tip end of the cell; the pH at 2 micrometers from the tip was nearly 0.5 units more acid than the bulk medium at pH 6. Disruption of steady state, external gradients with media that contained lower concentrations of H(+), K(+), Ca(2+), or Cl(-) produced certain differences in the rates of restoration of particular ion zones, raising the possibility that some of the ion migrations are interdependent. Within 15 minutes after irradiation with blue light, current leaving the tip declined to levels which were indistinguishable from those leaving the lateral walls and there was a rapid lowering in the rates of tip acidification and K(+) depletion near the tip. The rapid dissipation of both the longitudinally aligned electrical field and the tip-localized asymmetries in external cation distribution in blue light suggest that loss of electrical polarity in this tip growing cell may be an initial step in the chain of events which govern changes in cell shape.",1
"Racusen, R H, Ketchum, K A, Cooke, T J",2
"Chloroplast Biogenesis 60 : Conversion of Divinyl Protochlorophyllide to Monovinyl Protochlorophyllide in Green(ing) Barley, a Dark Monovinyl/Light Divinyl Plant Species.",0
"In higher plants, most of the chlorophyll a is formed via the divinyl and monovinyl chlorophyll monocarboxylic biosynthetic routes. These two routes are strongly interconnected prior to protochlorophyllide formation in barley (Hordeum vulgare L. cv Morex), a dark monovinyl-light divinyl plant species, but not in cucumber (Cucumis sativus L. cv Beit Alpha MR), a dark divinyl-light divinyl plant species (BC Tripathy, CA Rebeiz, 1986 J Biol Chem 261: 13556-13564). It is shown that in dark monovinyl-light divinyl plant species such as barley, the divinyl and monovinyl monocarboxylic routes become interconnected at the level of protochlorophyllide during transition from the divinyl to the monovinyl protochlorophyllide biosynthetic mode. In cucumber, a dark divinyl-light divinyl plant species, in which the monovinyl monocarboxylic biosynthetic route becomes preponderant only after an abnormally long sojourn in darkness, the conversion of divinyl to monovinyl protochlorophyllide does not take place on the barley time-scale of incubation.",1
"Tripathy, B C, Rebeiz, C A",2
Purification and characterization of gibberellic Acid-induced cysteine endoproteases in barley aleurone layers.,0
"Using in series ammonium sulfate precipitation, gel filtration, and DEAE anion exchange high performance liquid chromatography, we have purified to homogeneity a protease of M(r) 37,000 secreted from barley (Hordeum vulgare L. cv Himalaya) embryoless half-seeds. This protease exists in three isozymic forms whose synthesis and secretion from barley aleurone layers was shown to be a gibberellic acid (GA(3))-dependent process (R Hammerton, T-HD Ho 1986 Plant Physiol 80: 692-697). This protease constitutes a major portion of the protease activity secreted from half-seeds between 72 to 96 hours of incubation in the presence of GA(3) as detected on activity gels containing hemoglobin as the substrate. Analysis of digestion products by urea/sodium dodecyl sulfate-polyacrylamide gel electrophoresis and gel filtration indicated that this protease is an endoprotease, therefore it is designated as barley endoprotease-A (EP-A). Inhibitor studies demonstrated that EP-A belongs to the cysteine class of endoproteases. The optimum pH for EP-A activity was 5.0, and the temperature optimum was 45 degrees C. Comparison of cyanogen bromide generated peptide fragments and NH(2)-terminal sequence analyses of the three individual EP-A isozymes demonstrates that they are very similar to each other. The NH(2)-terminal sequence shows extensive sequence homology to the NH(2)-terminal sequence of papain and several other cysteine proteinases. We also provide evidence that EP-A is not ;aleurain,' a putative cysteine proteinase encoded by a GA(3)-induced barley cDNA clone (JC Rogers, D Dean, GR Heck 1985 Proc Natl Acad Sci USA 82:6512-6516).",1
"Koehler, S, Ho, T H",2
Freezing of water in dormant vegetative apple buds in relation to cryopreservation.,0
"Various empirical prefreezing protocols have been used to facilitate cryopreservation of dormant buds from woody plants. The objective of this research was to determine the quantity of water remaining in liquid phase, under different prefreezing conditions using pulsed nuclear magnetic resonance spectroscopy of dormant apple (Malus domestica Mill.) buds from three cultivars. During prefreezing, the quantity of water remaining in the liquid phase was less at -40 degrees C<-30 degrees C<-20 degrees C for all cultivars tested. The prefreezing temperature had a greater influence on reducing the quantity of liquid water than the duration of prefreezing. Prefreezing to -40 degrees C for 24 hours was optimal for ;Patterson' and ;McIntosh,' the hardiest cultivars, compared to -30 degrees C for 24 hours with ;Red Delicious.' Cryopreservation of dormant apple buds depends upon the quantity of liquid water during prefreezing, prior to immersion in liquid nitrogen, and upon the cultivar.",1
"Tyler, N, Stushnoff, C, Gusta, L V",2
Purification and Properties of 5-Enolpyruvylshikimate-3-Phosphate Synthase from Dark-Grown Seedlings of Sorghum bicolor.,0
"5-Enolpyruvylshikimate-3-phosphate (EPSP) synthase (3-phospho-shikimate 1-carboxyvinyltransferase; EC 2.5.1.19) was purified 1300-fold from etiolated shoots of Sorghum bicolor (L.) Moench. Native polyacrylamide gel electrophoresis revealed three barely separated protein bands staining positive for EPSP synthase activity. The native molecular weight was determined to be 51,000. Enzyme activity was found to be sensitive to metal ions and salts. Apparent K(m) values of 7 and 8 micromolar were determined for the substrates shikimate-3-phosphate and phosphoenolpyruvate (PEP), respectively. The herbicide glyphosate was found to inhibit the enzyme competitively with respect to PEP (K(i) = 0.16 micromolar). Characterization studies support the conclusion of a high degree of similarity between EPSP synthase from S. bicolor, a monocot, and the enzyme from dicots. A similarity to bacterial EPSP synthase is also discussed. Three EPSP synthase isozymes (I, II, III) were elucidated in crude homogenates of S. bicolor shoots by high performance liquid chromatography. The major isozymes, II and III, were separated and partially characterized. No significant differences in pH activity profiles and glyphosate sensitivity were found. This report of isozymes of EPSP synthase from S. bicolor is consistent with other reports for shikimate pathway enzymes, including EPSP synthase.",1
"Ream, J E, Steinrücken, H C, Porter, C A, Sikorski, J A",2
Stachyose Synthesis in Source Leaf Tissues of the CAM Plant Xerosicyos danguyi H. Humb.,0
"Leaf tissues from Xerosicyos danguyi H. Humb., a succulent member of the Cucurbitaceae, were found to possess both galactinol synthase activity and the capacity for photosynthetic production of stachyose, the phloem transport oligosaccharide common to other nonsucculent cucurbits. The amounts of stachyose isolated from leaf tissues, and the extractable activity of galactinol synthase, were somewhat higher in leaf tissues obtained from plants operating in the Crassulacean acid metabolism (CAM) mode (well watered plants) compared to leaf tissues from plants operating in the CAM-idling mode (water-stressed plants). In contrast, in leaf discs, the photosynthetic incorporation of label into stachyose following pulse labeling with (14)CO(2) was similar for stressed and for nonstressed tissues. Stachyose could be extracted from, and was synthesized photosynthetically by, leaf discs which contained no vascular tissues, indicating that synthesis of stachyose can occur in photosynthetic mesophyll cells of Xerosicyos.",1
"Madore, M A, Mitchell, D E, Boyd, C M",2
Molecular characterization of oat seed globulins.,0
"We have isolated full-length cDNA clones that encode oat (Avena sativa) seed storage globulin mRNAs from a cDNA library in the expression vector lambda gtll. The longest of these clones, pOG2, has an 1840-base pair insert that encodes a complete precursor subunit with a signal peptide of 24 amino acids followed by an acidic polypeptide of 293 amino acids and a basic polypeptide of 201 amino acids. Near the C terminus of the acidic polypeptide are four repeats of a highly conserved, glutamine-rich octapeptide. Other oat globulin cDNA clones contain five of these repeats. Nucleotide sequence comparisons between these clones indicate that the genes encoding these proteins are highly conserved. We estimate there to be 7 to 10 genes for the oat globulin per haploid genome. Comparisons of amino acid sequences show that the oat globulin is 30 to 40% homologous with storage globulins of legumes and about 70% homologous with the rice seed storage globulin (glutelin).",1
"Shotwell, M A, Afonso, C, Davies, E, Chesnut, R S, Larkins, B A",2
Localization of alpha-Amylase in the Apoplast of Pea (Pisum sativum L.) Stems.,0
"Most of the activity of an alpha-amylase present in crude pea (Pisum sativum L. cv Laxton's Progress No. 9) leaf preparations cannot be found in isolated pea leaf protoplasts. The same extrachloroplastic alpha-amylase is present in pea stems, representing approximately 6% of total stem amylolytic activity and virtually all of the alpha-amylase activity. By a simple infiltration-extraction procedure, the majority (87%) of this alpha-amylase activity was recovered from the pea stem apoplast without significantly disrupting the symplastic component of the tissue. Only 3% of the beta-amylase activity and less than 2% of other cellular marker enzymes were removed during infiltration-extraction.",1
"Beers, E P, Duke, S H",2
"Purification and Characterization of a Chloroplast Outer-Envelope-Bound, ATP-Dependent Protein Kinase.",0
"An ATP-dependent protein kinase was partially purified from isolated outer envelope membranes of pea (Pisum sativum L., Progress No. 9) chloroplasts. The purified kinase had a molecular weight of 70 kilodaltons, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was of the cyclic nucleotide and Ca(2+), calmodulin-independent type. The purification involved the detergent solubilization of purified outer envelopes by 0.5% cholate and 1% octylglycoside, followed by centrifugation on a linear 6 to 25% sucrose gradient. Active enzyme fractions were further purified by affinity chromatography on histone III-S Sepharose 4B and ion exchange chromatography on diethylaminoethyl cellulose. The protein kinase eluted at 100 millimolar and 50 millimolar NaCl, respectively. The protein kinase was essentially pure as judged by Western blot analysis. The enzyme has a K(M) of 450 micromolar for ATP and a V(max) of 25 picomoles of (32)P incorporated into histone III-S per minute per microgram. Inhibition by ADP is competitive (K(i) 150 micromolar).",1
"Soll, J",2
Highly nonrandom features of synaptic connectivity in local cortical circuits.,0
"How different is local cortical circuitry from a random network? To answer this question, we probed synaptic connections with several hundred simultaneous quadruple whole-cell recordings from layer 5 pyramidal neurons in the rat visual cortex. Analysis of this dataset revealed several nonrandom features in synaptic connectivity. We confirmed previous reports that bidirectional connections are more common than expected in a random network. We found that several highly clustered three-neuron connectivity patterns are overrepresented, suggesting that connections tend to cluster together. We also analyzed synaptic connection strength as defined by the peak excitatory postsynaptic potential amplitude. We found that the distribution of synaptic connection strength differs significantly from the Poisson distribution and can be fitted by a lognormal distribution. Such a distribution has a heavier tail and implies that synaptic weight is concentrated among few synaptic connections. In addition, the strengths of synaptic connections sharing pre- or postsynaptic neurons are correlated, implying that strong connections are even more clustered than the weak ones. Therefore, the local cortical network structure can be viewed as a skeleton of stronger connections in a sea of weaker ones. Such a skeleton is likely to play an important role in network dynamics and should be investigated further.",1
"Song, Sen, Sjöström, Per Jesper, Reigl, Markus, Nelson, Sacha, Chklovskii, Dmitri B",2
Dissociation of cohesin from chromosome arms and loss of arm cohesion during early mitosis depends on phosphorylation of SA2.,0
"Cohesin is a protein complex that is required to hold sister chromatids together. Cleavage of the Scc1 subunit of cohesin by the protease separase releases the complex from chromosomes and thereby enables the separation of sister chromatids in anaphase. In vertebrate cells, the bulk of cohesin dissociates from chromosome arms already during prophase and prometaphase without cleavage of Scc1. Polo-like kinase 1 (Plk1) and Aurora-B are required for this dissociation process, and Plk1 can phosphorylate the cohesin subunits Scc1 and SA2 in vitro, consistent with the possibility that cohesin phosphorylation by Plk1 triggers the dissociation of cohesin from chromosome arms. However, this hypothesis has not been tested yet, and in budding yeast it has been found that phosphorylation of Scc1 by the Polo-like kinase Cdc5 enhances the cleavability of cohesin, but does not lead to separase-independent dissociation of cohesin from chromosomes. To address the functional significance of cohesin phosphorylation in human cells, we have searched for phosphorylation sites on all four subunits of cohesin by mass spectrometry. We have identified numerous mitosis-specific sites on Scc1 and SA2, mutated them, and expressed nonphosphorylatable forms of both proteins stably at physiological levels in human cells. The analysis of these cells lines, in conjunction with biochemical experiments in vitro, indicate that Scc1 phosphorylation is dispensable for cohesin dissociation from chromosomes in early mitosis but enhances the cleavability of Scc1 by separase. In contrast, our data reveal that phosphorylation of SA2 is essential for cohesin dissociation during prophase and prometaphase, but is not required for cohesin cleavage by separase. The similarity of the phenotype obtained after expression of nonphosphorylatable SA2 in human cells to that seen after the depletion of Plk1 suggests that SA2 is the critical target of Plk1 in the cohesin dissociation pathway.",1
"Hauf, Silke, Roitinger, Elisabeth, Koch, Birgit, Dittrich, Christina M, Mechtler, Karl, Peters, Jan-Michael",2
Predictive spatial dynamics and strategic planning for raccoon rabies emergence in Ohio.,0
"Rabies is an important public health concern in North America because of recent epidemics of a rabies virus variant associated with raccoons. The costs associated with surveillance, diagnostic testing, and post-exposure treatment of humans exposed to rabies have fostered coordinated efforts to control rabies spread by distributing an oral rabies vaccine to wild raccoons. Authorities have tried to contain westward expansion of the epidemic front of raccoon-associated rabies via a vaccine corridor established in counties of eastern Ohio, western Pennsylvania, and West Virginia. Although sporadic cases of rabies have been identified in Ohio since oral rabies vaccine distribution in 1998, the first evidence of a significant breach in this vaccine corridor was not detected until 2004 in Lake County, Ohio. Herein, we forecast the spatial spread of rabies in Ohio from this breach using a stochastic spatial model that was first developed for exploratory data analysis in Connecticut and next used to successfully hind-cast wave-front dynamics of rabies spread across New York. The projections, based on expansion from the Lake County breach, are strongly affected by the spread of rabies by rare, but unpredictable long-distance translocation of rabid raccoons; rabies may traverse central Ohio at a rate 2.5-fold greater than previously analyzed wildlife epidemics. Using prior estimates of the impact of local heterogeneities on wave-front propagation and of the time lag between surveillance-based detection of an initial rabies case to full-blown epidemic, specific regions within the state are identified for vaccine delivery and expanded surveillance effort.",1
"Russell, Colin A, Smith, David L, Childs, James E, Real, Leslie A",2
Recombination every day: abundant recombination in a virus during a single multi-cellular host infection.,0
"Viral recombination can dramatically impact evolution and epidemiology. In viruses, the recombination rate depends on the frequency of genetic exchange between different viral genomes within an infected host cell and on the frequency at which such co-infections occur. While the recombination rate has been recently evaluated in experimentally co-infected cell cultures for several viruses, direct quantification at the most biologically significant level, that of a host infection, is still lacking. This study fills this gap using the cauliflower mosaic virus as a model. We distributed four neutral markers along the viral genome, and co-inoculated host plants with marker-containing and wild-type viruses. The frequency of recombinant genomes was evaluated 21 d post-inoculation. On average, over 50% of viral genomes recovered after a single host infection were recombinants, clearly indicating that recombination is very frequent in this virus. Estimates of the recombination rate show that all regions of the genome are equally affected by this process. Assuming that ten viral replication cycles occurred during our experiment-based on data on the timing of coat protein detection-the per base and replication cycle recombination rate was on the order of 2 x 10(-5) to 4 x 10(-5). This first determination of a virus recombination rate during a single multi-cellular host infection indicates that recombination is very frequent in the everyday life of this virus.",1
"Froissart, Remy, Roze, Denis, Uzest, Marilyne, Galibert, Lionel, Blanc, Stephane, Michalakis, Yannis",2
Audit of bronchial artery embolisation in a specialist respiratory centre.,0
To audit the use of bronchial arteriography and embolisation for controlling haemoptysis.,1
"Currie, D C, Prendergast, C M, Pearson, M C",2
Measuring patient satisfaction: a test of construct validity.,0
To establish the validity of two patient satisfaction questionnaires (surgery satisfaction questionnaire (SSQ) and consultation satisfaction questionnaire (CSQ)) developed for use in general practice.,1
"Baker, R, Whitfield, M",2
Impact of an interest in asthma on prescribing costs in general practice.,0
To examine the effect on total prescribing costs and prescribing costs for respiratory drugs for practices with at least one general practitioner with a special interest in asthma.,1
"Jones, K",2
Audit in general practice: students and practitioners learning together.,0
To describe and evaluate the use of medical audit in general practice as an educational activity shared by undergraduate medical students and general practitioners.,1
"Campion, P, Stanley, I, Haddleton, M",2
Failure of many ophthalmologists to use lasers safely.,0
"In 1990, after the detection of impairment of colour discrimination in laser operators, the College of Ophthalmologists recommended safety guidelines for the use of lasers. We measured the effectiveness of these guidelines and their impact on ophthalmological practice in the United Kingdom. Previously, in ophthalmologists not following the guidelines, there was a deterioration in colour discrimination after a laser session. No such deterioration was found in 10 ophthalmologists tested who adhered to the guidelines, but their colour discrimination was significantly worse than that of controls. Replies to a questionnaire disclosed that one third of senior ophthalmologists were unaware of the practices recommended.",1
"Hardy, K J, Lipton, J R, Foster, D H, Scarpello, J H",2
Development of indicators for quality assurance in public health medicine.,0
"To develop structure, process, and outcome indicators within a quality rating index for audit of public health medicine.",1
"Johnston, N H, Narayan, K M, Ruta, D A",2
Development of clinical guidelines in a health district: an attempt to find consensus.,0
To formulate consensus based guidelines for antenatal care in a health district.,1
"Armstrong, D, Tatford, P, Fry, J, Armstrong, P",2
Reducing bruising after venepuncture.,0
"Bruising after venepuncture is undesirable. To verify an apparent increase in bruising after introducing a new venepuncture system in a small district general hospital and to improve the venepuncture service two prospective audits of the incidence and severity of bruising after venepuncture were performed in two groups of 100 consecutive inpatients undergoing venepuncture by phlebotomists. In the first audit bruising was detected in 45 patients, of whom 34(76%) had bruises > 100 mm2 in area. After modification of the technique, whereby the phlebotomists ensured that haemostasis had been attained before leaving the patient, bruising was significantly reduced, occurring in 25 patients only 9 of whom (36%) had bruises > 100mm2 in area (both p < 0.01) in the second audit. Monitoring of standards and simple modification of technique resulted in significant reduction in incidence and severity of bruising, improving the quality of the venepuncture service.",1
"Godwin, P G, Cuthbert, A C, Choyce, A",2
Diabetes care.,0
"Providing good quality diabetes care is complex but achievable. Many aspects of the care do not require high tech medicine but, rather, good organisation. Diabetes is a costly disease, consuming 1500 pounds per diabetic patient per year versus 500 pounds on average for a non-diabetic member of the population in health service costs. Investment now in good quality diabetes care is sound: patients will benefit from a better quality of life associated with a reduced incidence of the complications of diabetes and the direct costs to the health service in treating these complications and the indirect costs to employers will be reduced. Physical and clinical assessments--measurements of blood glucose and glycosylated haemoglobin concentrations, weight, and blood pressure and assessment of eyes, kidneys, feet, and heart--are clearly important, but quality must include consideration of people and their reactions to life and diabetes--a lifelong entanglement--for which much more support should be provided.",1
"Ward, J D, MacKinnon, M",2
Towards measurement of outcome for patients with varicose veins.,0
To develop a valid and reliable outcome measure for patients with varicose veins.,1
"Garratt, A M, Macdonald, L M, Ruta, D A, Russell, I T, Buckingham, J K, Krukowski, Z H",2
"Safe working practices and HIV infection: knowledge, attitudes, perception of risk, and policy in hospital.",0
"OBJECTIVES--To assess the knowledge, attitudes, and perceptions of risk of occupational HIV transmission in hospital in relation to existing guidelines. DESIGN--Cross sectional anonymous questionnaire survey of all occupational groups. SETTING--One large inner city teaching hospital. SUBJECTS--All 1530 staff working in the hospital in October 1991 and 22 managers. MAIN MEASURES--Knowledge of safe working practices and hospital guidelines; attitudes towards patients with AIDS; perception of risk of occupational transmission of HIV; availability of guidelines. RESULTS--The response rate in the questionnaire survey was 63% (958/1530). Although staff across all occupational groups knew of the potential risk of infection from needlestick injury (98%, 904/922), significantly more non-clinical staff (ambulance, catering, and domestic staff) than clinical staff (doctors, nurses, and paramedics) thought HIV could be transmitted by giving blood (38%, 153/404 v 12%, 40/346; chi 2 = 66.1 p < 0.001); one in ten clinical staff believed this. Except for midwives, half of staff in most occupational groups and 19% (17/91) of doctors and 22% (28/125) of nurses thought gloves should be worn in all contacts with people with AIDS. Most staff (62%, 593/958), including 38% (36/94) of doctors and 52% (67/128) of nurses thought patients should be routinely tested on admission, 17% of doctors and 19% of nurses thought they should be isolated in hospital. One in three staff perceived themselves at risk of HIV. Midwives, nurses, and theatre technicians were most aware of guidelines for safe working compared with only half of doctors, ambulance, and paramedical staff and no incinerator staff. CONCLUSIONS--Policy guidelines for safe working practices for patients with HIV infection and AIDS need to be disseminated across all occupational groups to reduce negative staff attitudes, improve knowledge of occupational transmission, establish an appropriate perception of risk, and create a supportive and caring hospital environment for people with HIV. IMPLICATIONS--Managers need to disseminate policy guidelines and information to all staff on an ongoing basis.",1
"Davidson, G, Gillies, P",2
An audit of distribution and use of guidelines for management of head injury.,0
"Ensuring effective distribution of guidelines is an important step towards their implementation. To examine the effectiveness of dissemination of a guidelines card on management of head injury and determine its usefulness to senior house officers (SHOs), a questionnaire survey was performed in May 1990, after distribution of the cards in induction packs for new doctors and at postgraduate lectures and displaying the guidelines in accident and emergency departments and wards. A further survey, in March 1992, assessed the impact of modifying the distribution. All (175) SHOs working in general surgery, accident and emergency medicine, orthopaedics, and neurosciences on 1 February 1990 in 19 hospitals including two neurosurgical units in Northern region were sent self completion questionnaires about awareness, receipt, use, and perceived usefulness of the guidelines. 131 of 163(80%) SHOs in post responded (median response from hospitals 83% (range 50%-100%)). Over three quarters (103, 79%) of SHOs were aware of the guidelines and 82(63%) had ever possessed a guidelines card. Only 36(44%) acquired the card in the induction pack. 92%(98/107) found them useful and 81% (89/110) referred to them to some extent. Owning and carrying the card and referring to guidelines were associated with departmental encouragement to use the guidelines. Increasing the displays of guidelines in wards and departments and the supply of cards to consultants in accident and emergency medicine as a result of this survey did not increase the number of SHOs who received cards (52/83, 63%), but more (71/83, 86%) were aware of the guidelines. The guidelines were welcomed by SHOs and used in treating patients with head injury, but their distribution requires improvement. Increased use of the guidelines may be achieved by introducing other distribution methods and as a result of encouragement by senior staff.",1
"Madhok, R, Thomson, R G, Mordue, A, Mendelow, A D, Barker, J",2
Assessing introduction of spinal anaesthesia for obstetric procedures.,0
"To assess the impact of introducing spinal anaesthesia for obstetric operative procedures on use of general anaesthesia and quality of regional anaesthesia in a unit with an established epidural service a retrospective analysis of routinely collected data on method of anaesthesia, efficacy, and complications was carried out. Data were collected from 1988 to 1991 on 1670 obstetric patients requiring an operative procedure. The introduction of spinal anaesthesia in 1989 significantly reduced the proportion of operative procedures performed under general anaesthesia, from 60% (234/390) in 1988 to 30% (124/414) in 1991. The decrease was most pronounced for manual removal of the placenta (88%, 48/55 v 9%, 3/34) and emergency caesarean section (67%, 129/193) v 38%, 87/229). Epidural anaesthesia decreased in use most significantly for elective caesarean section (65%, 77/118 v 3% 3/113; x2=139, p<0.0001). The incidence of severe pain and need for conversion to general anaesthesia was significantly less with spinal anaesthesia (0%, 0/207 v 3%, 5/156; p<0.05). Hypotension was not a problem, and the incidence of headache after spinal anaesthetic decreased over the period studied. Introducing spinal anaesthesia therefore reduced the need for general anaesthesia and improved the quality of regional anaesthesia.",1
"Madej, T H, Jackson, I J, Wheatley, R G, Wilson, J",2
Cooperation or conflict over child health surveillance? Views of key actors.,0
"To describe the views of general practitioners, health visitors, and clinical medical officers on child health surveillance, recent changes, perceptions of each other's roles, and attitudes to audit.",1
"Gillam, S, Glickman, M, Boyle, G, Woodroffe, C",2
Use of laboratory testing for genital chlamydial infection in Norway.,0
To assess the use of laboratory tests for genital chlamydial infection in Norway.,1
"Aavitsland, P",2
Referral of patients to an anticoagulant clinic: implications for better management.,0
"The quality of anticoagulant treatment of ambulatory patients is affected by the content of referral letters and administrative processes. To assess these influences a method was developed to audit against the hospital standard the referral of patients to one hospital anticoagulant clinic in a prospective study of all (80) new patients referred to the clinic over eight months. Administrative information was provided by the clinic coordinator, and the referral letters were audited by the researchers. Referral letters were not received by the clinic for 10% (8/80) of patients. Among the 72 referral letters received, indication for anticoagulation and anticipated duration of treatment were specified in most (99%, 71 and 81%, 58 respectively), but only 3% (two) to 46% (33) reported other important clinical information (objective investigations, date of starting anticoagulation, current anticoagulant dose, date and result of latest international normalised ratio, whether it should be the anticoagulant clinic that was eventually to stop anticoagulation, patients' other medical problems and concurrent treatment. Twenty two per cent (16/80) of new attenders were unexpected at the anticoagulant clinic. Most patients' case notes were obtained for the appointment (61%, 47/77 beforehand and 30% 23/77 on the day), but case notes were not obtained for 9% (7/77). The authors conclude that health professionals should better appreciate the administrative and organisational influences that affect team work and quality of care. Compliance with a well documented protocol remained below the acceptable standard. The quality of the referral process may be improved by using a more comprehensive and helpful referral form, which has been drawn up, and by educating referring doctors. Measures to increase the efficiency of the administrative process include telephoning the clinic coordinator directly, direct referrals through a computerised referral system, and telephone reminders by haematology office staff to ward staff to ensure availability of the hospital notes. The effect of these changes will be assessed in a repeat audit.",1
"Tan, G B, Cohen, H, Taylor, F C, Gabbay, J",2
Evaluating a policy of reduced consultant antenatal clinic visits for low risk multiparous women.,0
"To evaluate a change in antenatal care policy to reduce antenatal clinic visits, whereby low risk multiparous women were managed by the primary care team and seen at booking and at 41 weeks' gestation at the consultant antenatal clinic.",1
"Hill, A M, Yudkin, P L, Bull, D J, Barlow, D H, Charnock, F M, Gillmer, M D",2
Agreeing criteria for audit of the management of induced abortion: an approach by national consensus survey.,0
To obtain a national consensus view of suggested criteria for good quality care in induced abortion to serve as a basis for standards for audit to assess current clinical practice.,1
"Penney, G C, Glasier, A, Templeton, A",2
Clinicians' satisfaction with a hospital blood transfusion service: a marketing analysis of a monopoly supplier.,0
"One of the objectives of the NHS reforms is to improve customer focus within the health service. In a study to assess the quality of customer service provided by the Edinburgh and South East Scotland Blood Transfusion Service a 19 item questionnaire survey of the main clinical users of the service was performed to ascertain their satisfaction, measured on a 5 point anchored scale, with important aspects of the service, including medical consultation, diagnostic services, blood and blood components or products and their delivery, and general satisfaction with the service. Of 122 clinicians in medical and surgical disciplines in five hospitals in Edinburgh, 72 (59%) replied. Fourteen (22%) indicated dissatisfaction with any aspect of the medical consultation service, owing to inadequate follow up of clinical contacts and unsatisfactory routing of incoming calls. Diagnostic services were criticised for the presentation, communication, and interpretation of results. The restricted availability of whole blood, the necessity to order platelets and plasma through the duty blood transfusion service doctor, and the use of a group and screen policy, attracted criticism from a small number of clinicians. Ten of 68 respondents expressed dissatisfaction with delivery of blood and components to the wards and theatres. The findings indicate that the clinicians served by this blood transfusion service are largely satisfied with the service. Changes are being implemented to improve reporting of laboratory results and measures taken to improve liaison with clinicians.",1
"Pennington, S J, McClelland, D B, Murphy, W G",2
Comparative hospital databases: value for management and quality.,0
To establish an accurate and reliable comparative database of discharge abstracts and to appraise its value for assessments of quality of care.,1
"Cleary, R, Beard, R, Coles, J, Devlin, B, Hopkins, A, Schumacher, D, Wickings, I",2
"Measuring handicap: the London Handicap Scale, a new outcome measure for chronic disease.",0
"To develop a handicap measurement scale in a self completion questionnaire format, with scale weights allowing quantification of handicap at an interval level of measurement.",1
"Harwood, R H, Rogers, A, Dickinson, E, Ebrahim, S",2
Is choice of general practitioner important for patients having coronary artery investigations?,0
To determine whether particular sociodemographic characteristics of patients with stable angina affected their general practitioners' (GPs') decisions to refer them for revascularisation assessment.,1
"Kee, F, Gaffney, B, Canavan, C, Little, J, McConnell, W, Telford, A M, Watson, J D",2
Effects of a computerised protocol management system on ordering of clinical tests.,0
"To assess the effects of a computerised protocol management system on the number, cost, and appropriateness of laboratory investigations requested.",1
"Nightingale, P G, Peters, M, Mutimer, D, Neuberger, J M",2
Views of survivors of stroke on benefits of physiotherapy.,0
To describe the components of physiotherapy valued by survivors of a stroke.,1
"Pound, P, Bury, M, Gompertz, P, Ebrahim, S",2
Lack of knowledge in health professionals: a barrier to providing information to patients?,0
To assess obstetricians' and midwives' knowledge of routine prenatal screening tests for fetal abnormality and factors associated with such knowledge.,1
"Smith, D K, Slack, J, Shaw, R W, Marteau, T M",2
Effect of guidelines on management of head injury on record keeping and decision making in accident and emergency departments.,0
To compare record keeping and decision making in accident and emergency departments before and after distribution of guidelines on head injury management as indices of implementation.,1
"Thomson, R, Gray, J, Madhok, R, Mordue, A, Mendelow, A D",2
SF 36 health survey questionnaire: I. Reliability in two patient based studies.,0
To assess the reliability of the SF 36 health survey questionnaire in two patient populations.,1
"Ruta, D A, Abdalla, M I, Garratt, A M, Coutts, A, Russell, I T",2
Involving consumers in assessing service quality: benefits of using a qualitative approach.,0
"Although important to users, practice standards rarely incorporate users' views of care provided. These views are a valuable source of information, even though there are limits to their value. To improve the standards of care in a 20 bed hospital elderly care unit caring for acute medical conditions a qualitative approach was used. Patients' and carers' perceptions of care and problems with the process of care in the unit were elicited with a specially designed semistructured interview schedule in 83 separate tape recorded interviews with a research nurse in patients' homes. In all, 50 patients and 35 carers were interviewed between 6 June 1991 and 28 May 1992. Of the 50 patients, 33 were female; seven patients were aged less than 80 years, 16, 80-85; 21, 86-90; and six over 90. A total of 16 patients lived with spouses or other carers, two with non-carers, and 32 lived alone, 18 of whom received informal care. Content analysis of the interviews disclosed patients' and carers' general satisfaction with individualised professional care and planning of follow up services on discharge but dissatisfaction in the lack of information about and involvement in treatment and care and about specific staff notes. These findings have prompted remedial changes in clinical practice in the unit; they have also formed the structure of a criterion based survey of practice. The authors conclude that the qualitative approach suited elderly users and also provided the basis for the findings to be incorporated into a continuous audit cycle through a process of feedback and standard setting.",1
"Powell, J, Lovelock, R, Bray, J, Philp, I",2
Comparison of short term outcomes of open and laparoscopic cholecystectomy.,0
To compare the three month outcome of open and laparoscopic cholecystectomy.,1
"Cleary, R, Venables, C W, Watson, J, Goodfellow, J, Wright, P D",2
Comparison of patients' needs for information on prostate surgery with printed materials provided by surgeons.,0
"To identify strengths, weaknesses, and omissions in existing leaflets and factsheets on prostatectomy given by surgeons to patients.",1
"Meredith, P, Emberton, M, Wood, C, Smith, J",2
"National audit of acute severe asthma in adults admitted to hospital. Standards of Care Committee, British Thoracic Society.",0
To ascertain the standard of care for hospital management of acute severe asthma in adults.,1
"Pearson, M G, Ryland, I, Harrison, B D",2
Understanding adverse events: human factors.,0
"(1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional ""capture"" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with forgetting. States of mind contributing to error are thus extremely difficult to manage; they can happen to the best of people at any time. (7) People do not act in isolation. Their behaviour is shaped by circumstances. The same is true for errors and violations. The likelihood of an unsafe act being committed is heavily influenced by the nature of the task and by the local workplace conditions. These, in turn, are the product of ""upstream"" organisational factors. Great gains in safety can ve achieved through relatively small modifications of equipment and workplaces. (8) Automation and increasing advanced equipment do not cure human factors problems, they merely relocate them. In contrast, training people to work effectively in teams costs little, but has achieved significant enhancements of human performance in aviation. (9) Effective risk management depends critically on a confidential and preferable anonymous incident monitoring system that records the individual, task, situational, and organisational factors associated with incidents and near misses. (10) Effective risk management means the simultaneous and targeted deployment of limited remedial resources at different levels of the system: the individual or team, the task, the situation, and the organisation as a whole.",1
"Reason, J",2
Feasibility of monitoring patient based health outcomes in a routine hospital setting.,0
To assess the feasibility of monitoring health outcomes in a routine hospital setting and the value of feedback of outcomes data to clinicians by using the SF 36 health survey questionnaire.,1
"Ruta, D, Coutts, A, Abdalla, M, Masson, J, Russell, E, Brunt, P, McKinlay, A, Mowat, A, Sinclair, T",2
Audit activity and quality of completed audit projects in primary care in Staffordshire.,0
To survey audit activity in primary care and determine which practice factors are associated with completed audit; to survey the quality of completed audit projects.,1
"Chambers, R, Bowyer, S, Campbell, I",2
Reliability of data of the Thames cancer registry on 673 cases of colorectal cancer: effect of the registration process.,0
To measure the reliability of data collected by the Thames cancer registry and to identify factors in the registration process affecting reliability.,1
"Pollock, A M, Vickers, N",2
Assessing the work of medical audit advisory groups in promoting audit in general practice.,0
"Objectives--To determine the role of medical audit advisory groups in audit activities in general practice. Design--Postal questionnaire survey. Subjects--All 104 advisory groups in England and Wales in 1994. Main measures--Monitoring audit: the methods used to classify audits, the methods used by the advisory group to collect data on audits from general practices, the proportion of practices undertaking audit. Directing and coordinating audits: topics and number of practices participating in multipractice audits. Results--The response rate was 86-5%. In 1993-4, 54% of the advisory groups used the Oxfordshire or Kirklees methods for classifying audits, or modifications of them. 99% of the advisory groups collected data on audit activities at least once between 1991-2 and 1993-4. Visits, questionnaires, and other methods were used to collect information from all or samples of practices in each of the advisory group's areas. Some advisory groups used different methods in different years. In 1991-2, 57% of all practices participated in some audit, in 1992-3, 78%, and in 1993-4, 86%. 428 multipractice audits were identified. The most popular topic was diabetes. Conclusions--Advisory groups have been active in monitoring audit in general practice. However, the methods used to classify and collect information about audits in general practices varied widely. The number of practices undertaking audit increased between 1991-2 and 1993 1. The large number of multipractice audits supports the view that the advisory groups have directed and coordinated audit activities. This example of a national audit programme for general practice may be helpful in other countries in which the introduction of quality assurance is being considered.",1
"Baker, R, Hearnshaw, H, Cooper, A, Cheater, F, Robertson, N",2
Medication errors during hospital drug rounds.,0
"Objective--To determine the nature and rate of drug administration errors in one National Health Service hospital. Design--Covert observational survey be tween January and April 1993 of drug rounds with intervention to stop drug administration errors reaching the patient. Setting--Two medical, two surgical, and two medicine for the elderly wards in a former district general hospital, now a NHS trust hospital. Subjects--37 Nurses performing routine single nurse drug rounds. Main measures--Drug administration errors recorded by trained observers. Results--Seventy four drug rounds were observed in which 115 errors occurred during 3312 drug administrations. The overall error rate was 3.5% (95% confidence interval 2.9% to 4.1%). Errors owing to omissions, because the drug had not been supplied or located or the prescription had not been seen, accounted for most (68%, 78) of the errors. Wrong doses accounted for 15% (17) errors, four of which were greater than the prescribed dose. The dose was given within two hours of the time indicated by the prescriber in 98.2% of cases. Conclusion--The observed rate of drug administration errors is too high. It might be reduced by a multidisciplinary review of practices in prescribing, supply, and administration of drugs.",1
"Ridge, K W, Jenkins, D B, Noyce, P R, Barber, N D",2
Policy priorities in diabetes care: a Delphi study.,0
To produce policy priorities for improving care of diabetes based on the findings of original research into patient and professional opinions of diabetes care in South Tyneside. To judge the feasibility of implementing these priorities as policy.,1
"Gallagher, M, Bradshaw, C, Nattress, H",2
Investigation into the attitudes of general practitioners in Staffordshire to medical audit.,0
"To investigate the attitudes of general practitioners to medical audit, and any associations between their attitudes and their personal characteristics.",1
"Chambers, R, Bowyer, S, Campbell, I",2
Primary hip and knee replacement surgery: Ontario criteria for case selection and surgical priority.,0
"To develop, from simple clinical factors, criteria to identify appropriate patients for referral to a surgeon for consideration for arthroplasty, and to rank them in the queue once surgery is agreed.",1
"Naylor, C D, Williams, J I",2
Bone densitometry at a district general hospital: evaluation of service by doctors and patients.,0
To assess doctors' and patients' views about a district general hospital bone densitometry service and to examine existing practice to influence future provision.,1
"Madhok, R, Kirby, P, Fordham, J, Stamp, P, Green, S, Cooper, C",2
Comparison of measures to assess outcomes in total hip replacement surgery.,0
To compare the performance of a disease specific and a general health questionnaire in assessing changes resulting from total hip replacement.,1
"Dawson, J, Fitzpatrick, R, Murray, D, Carr, A",2
Does a dedicated discharge coordinator improve the quality of hospital discharge?,0
To evaluate the effectiveness of the role of a discharge coordinator whose sole responsibility was to plan and coordinate the discharge of patients from medical wards.,1
"Houghton, A, Bowling, A, Clarke, K D, Hopkins, A P, Jones, I",2
Clinical audit and the purchaser-provider interaction: different attitudes and expectations in the United Kingdom.,0
"To explore and describe the views on clinical audit of healthcare purchasers and providers, and in particular the interaction between them, and hence to help the future development of an appropriate interaction between purchasers and providers.",1
"Thomson, R, Elcoat, C, Pugh, E",2
Adapting total quality management for general practice: evaluation of a programme.,0
Assessment of the benefits and limitations of a quality improvement programme based on total quality management principles in general practice over a period of one year (October 1993-4).,1
"Lawrence, M, Packwood, T",2
Identification and analysis of randomised controlled trials in nursing: a preliminary study.,0
To describe preliminary work undertaken for development of a nursing contribution to the Cochrane Collaboration. To ascertain whether there are randomised controlled trials (RCTs) on nursing care which need to be identified for inclusion in systematic reviews of the effects of health care.,1
"Cullum, N",2
Randomised controlled trial of reminders to enhance the impact of audit in general practice on management of patients who use benzodiazepines.,0
To determine whether reminder cards in medical records enhance the effectiveness of audit with feedback in improving the care of patients taking long term benzodiazepine drugs.,1
"Baker, R, Farooqi, A, Tait, C, Walsh, S",2
Practitioner based quality improvement: a review of the Royal College of Nursing's dynamic standard setting system.,0
"To explore and describe the implementation of the Royal College of Nursing's approach to audit--the dynamic standard setting system--within the current context of health care, in particular to focus on how the system has developed since its inception in the 1980s as a method for uniprofessional and multiprofessional audit.",1
"Morrell, C, Harvey, G, Kitson, A",2
"Essential dataset for ambulatory ear, nose, and throat care in general practice: an aid for quality assessment.",0
"To describe the documentation of care for the usual range of ear, nose, and throat (ENT) problems seen in primary care as a basis for developing a computerised information system to aid quality assessment.",1
"af Klercker, T, Trell, E, Lundquist, P G",2
Quality of contraceptive services in Finland.,0
To investigate whether the quality of contraceptive services in Finland varies by the type of care provider.,1
"Hemminki, E, Sihvo, S, Koponen, P, Kosunen, E",2
Adherence by midwives to the Dutch national guidelines on threatened miscarriage in general practice: a prospective study.,0
To determine the feasibility for midwives to adhere to Dutch national guidelines on threatened miscarriage in general practice.,1
"Fleuren, M, Grol, R, de Haan, M, Wijkel, D, Oudshoorn, C",2
The reliability of patients' judgements of care in general practice: how many questions and patients are needed?,0
To estimate the number of questions and patients that are needed to achieve reliable measurements of patients' judgements of care in general practice.,1
"Wensing, M, van de Vleuten, C, Grol, R, Felling, A",2
Outcome measures for routine use in dementia services: some practical considerations.,0
To work with specialist community teams to assess the practicality and acceptability of identified outcome measures for routine use in dementia services.,1
"Higginson, I J, Jefferys, P M, Hodgson, C S",2
Risks and benefits of coronary angioplasty: the patients perspective: a preliminary study.,0
To describe what cardiac patients in Northern Ireland understand to be the benefits of coronary angioplasty and assess the extent to which they have been able to make informed choices about their treatment.,1
"Kee, F, McDonald, P, Gaffney, B",2
Satisfaction with telephone advice from an accident and emergency department: identifying areas for service improvement.,0
"Members of the public often telephone general practice, accident and emergency departments, and other health services for advice. However, satisfaction related to telephone consultation has received relatively little attention. This study aimed to describe the views of callers to an accident and emergency department who expressed any element of dissatisfaction about their telephone consultation. This was part of a larger study intended to help identify areas for service improvement.",1
"Patel, A, Dale, J, Crouch, R",2
Putting continuous quality improvement into accreditation: improving approaches to quality assessment.,0
"The accreditation systems of the United States, Canada, and Australia have been restructured to reflect the adoption by health services of the industrial model of continuous quality improvement. The industrial model of quality makes assumptions about management structures and the relation of process to outcome which are not readily transferable to the assessment of quality in health care. The accreditation systems have therefore had to adapt the principles of continuous quality improvement to reflect the complex nature of health service organisations and the often untested assumptions about the relation between process and outcome.",1
"Scrivens, E",2
Was Rodney Ledward a statistical outlier? Retrospective analysis using routine hospital data to identify gynaecologists' performance.,0
"To investigate whether routinely collected data from hospital episode statistics could be used to identify the gynaecologist Rodney Ledward, who was suspended in 1966 and was the subject of the Ritchie inquiry into quality and practice within the NHS.",1
"Harley, Mike, Mohammed, Mohammed A, Hussain, Shakir, Yates, John, Almasri, Abdullah",2
Incidence and risk factors for non-alcoholic steatohepatitis: prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial.,0
"To assess the incidence, cofactors, and excess risk of development of non-alcoholic fatty liver disease, including non-alcoholic steatohepatitis, attributable to tamoxifen in women.",1
"Bruno, Savino, Maisonneuve, Patrick, Castellana, Paola, Rotmensz, Nicole, Rossi, Sonia, Maggioni, Marco, Persico, Marcello, Colombo, Alberto, Monasterolo, Franco, Casadei-Giunchi, Donata, Desiderio, Franco, Stroffolini, Tommaso, Sacchini, Virgilio, Decensi, Andrea, Veronesi, Umberto",2
Model of outcomes of screening mammography: information to support informed choices.,0
"To provide easy to use estimates of the benefits and harms of biennial screening mammography for women aged 40, 50, 60, and 70 years.",1
"Barratt, Alexandra, Howard, Kirsten, Irwig, Les, Salkeld, Glenn, Houssami, Nehmat",2
Coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and prevalence of infection in the United Kingdom general population: cross sectional study.,0
To measure the coverage and uptake of systematic postal screening for genital Chlamydia trachomatis and the prevalence of infection in the general population in the United Kingdom. To investigate factors associated with these measures.,1
"Macleod, John, Salisbury, Chris, Low, Nicola, McCarthy, Anne, Sterne, Jonathan A C, Holloway, Aisha, Patel, Rita, Sanford, Emma, Morcom, Andrea, Horner, Paddy, Davey Smith, George, Skidmore, Susan, Herring, Alan, Caul, Owen, Hobbs, F D Richard, Egger, Matthias",2
Ribosomal frameshifting in plants: a novel signal directs the -1 frameshift in the synthesis of the putative viral replicase of potato leafroll luteovirus.,0
"The 5.8 kb RNA genome of potato leafroll luteovirus (PLRV) contains two overlapping open reading frames, ORF2a and ORF2b, which are characterized by helicase and RNA polymerase motifs, respectively, and possibly represent the viral replicase. Within the overlap, ORF2b lacks an AUG translational start codon and is therefore presumably translated by -1 ribosomal frameshifting as a transframe protein with ORF2a. This hypothesis was studied by introducing the putative frameshift region into an internal position of the beta-glucuronidase (GUS) gene and testing for the occurrence of frameshifting in vivo by transient expression of GUS activity in potato protoplasts as well as in vitro by translation in the reticulocyte system. Both experimental approaches demonstrate that a -1 frameshift occurs at a frequency of approximately 1%. Site-directed mutagenesis identified the frameshift region and the involvement of the novel heptanucleotide motif UUUAAAU in conjunction with an adjacent stem-loop structure. Part of this stem-loop encodes a basic region in the ORF2b moiety of the transframe protein which was shown by binding experiments with PLRV RNA to represent a nucleic acid-binding domain. These data support a possible biological significance of the frameshift to occur at this position of the large overlap by including the putative RNA template-binding site of the PLRV replicase in the ORF2a/ORF2b transframe protein.",1
"Prüfer, D, Tacke, E, Schmitz, J, Kull, B, Kaufmann, A, Rohde, W",2
Effectiveness of statins for secondary prevention in elderly patients after acute myocardial infarction: an evaluation of class effect.,0
"Clinical trials have shown the benefits of statins after acute myocardial infarction (AMI). However, it is unclear whether different statins exert a similar effect in reducing the incidence of recurrent AMI and death when used in clinical practice.",1
"Zhou, Zheng, Rahme, Elham, Abrahamowicz, Michal, Tu, Jack V, Eisenberg, Mark J, Humphries, Karin, Austin, Peter C, Pilote, Louise",2
Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training.,0
"Persistent low-grade inflammation, as indicated by higher circulating levels of inflammatory mediators such as C-reactive protein, interleukin-6 and tumour necrosis factor-alpha, is a strong risk factor for several chronic diseases. There are data indicating that decreasing energy intake and increasing physical activity may be effective therapies for reducing overall inflammation. Evidence is strong that circulating levels of inflammatory markers are elevated with total and abdominal obesity, possibly owing to a higher secretion rate of cytokines by adipose tissue in obese people. Moreover, very-low-energy dietary weight loss reduces both circulating markers of inflammation and adipose-tissue cytokine production. Data from several large population-based cohorts show an inverse association between markers of systemic inflammation and physical activity or fitness status; small-scale intervention studies support that exercise training diminishes inflammation. Dietary weight loss plus exercise is likely more effective than weight reduction alone in reducing inflammation. To date, data from randomized, controlled trails designed to definitively test the effects of weight loss or exercise training, or both, on inflammation are limited. Future studies are required to define the amount of weight loss needed for clinically meaningful reductions of inflammation; in addition, fully powered and controlled studies are necessary to clarify the effect of exercise training on chronic, systemic inflammation.",1
"Nicklas, Barbara J, You, Tongjian, Pahor, Marco",2
Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study.,0
"Thrombolysis for acute ischemic stroke has remained controversial. The Canadian Alteplase for Stroke Effectiveness Study, a national prospective cohort study, was conducted to assess the effectiveness of alteplase therapy for ischemic stroke in actual practice.",1
"Hill, Michael D, Buchan, Alastair M",2
Women's sexual dysfunction: revised and expanded definitions.,0
"Acceptance of an evidence-based conceptualization of women's sexual response combining interpersonal, contextual, personal psychological and biological factors has led to recently published recommendations for revision of definitions of women's sexual disorders found in the American Psychiatric Association's Diagnostic and Statistical Manual (DSM-IV-TR). DSM-IV definitions have focused on absence of sexual fantasies and sexual desire prior to sexual activity and arousal, even though the frequency of this type of desire is known to vary greatly among women without sexual complaints. DSM-IV definitions also focus on genital swelling and lubrication, entities known to correlate poorly with subjective sexual arousal and pleasure. The revised definitions consider the many reasons women agree to or instigate sexual activity, and reflect the importance of subjective sexual arousal. The underlying conceptualization of a circular sex-response cycle of overlapping phases in a variable order may facilitate not only the assessment but also the management of dysfunction, the principles of which are briefly recounted.",1
"Basson, Rosemary",2
Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study.,0
"To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans.",1
"Trichopoulou, Antonia, Orfanos, Philippos, Norat, Teresa, Bueno-de-Mesquita, Bas, Ocké, Marga C, Peeters, Petra H M, van der Schouw, Yvonne T, Boeing, Heiner, Hoffmann, Kurt, Boffetta, Paolo, Nagel, Gabriele, Masala, Giovanna, Krogh, Vittorio, Panico, Salvatore, Tumino, Rosario, Vineis, Paolo, Bamia, Christina, Naska, Androniki, Benetou, Vassiliki, Ferrari, Pietro, Slimani, Nadia, Pera, Guillem, Martinez-Garcia, Carmen, Navarro, Carmen, Rodriguez-Barranco, Miguel, Dorronsoro, Miren, Spencer, Elizabeth A, Key, Timothy J, Bingham, Sheila, Khaw, Kay-Tee, Kesse, Emmanuelle, Clavel-Chapelon, Francoise, Boutron-Ruault, Marie-Christine, Berglund, Goran, Wirfalt, Elisabet, Hallmans, Goran, Johansson, Ingegerd, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Hundborg, Heidi H, Riboli, Elio, Trichopoulos, Dimitrios",2
Comparison of descriptions of allocation concealment in trial protocols and the published reports: cohort study.,0
"To compare how allocation concealment is described in publications of randomised clinical trials and corresponding protocols, and to estimate how often trial publications with unclear allocation concealment have adequate concealment according to the protocol.",1
"Pildal, Julie, Chan, An-Wen, Hróbjartsson, Asbjørn, Forfang, Elisabeth, Altman, Douglas G, Gøtzsche, Peter C",2
The carbohydrates of mouse hepatitis virus (MHV) A59: structures of the O-glycosidically linked oligosaccharides of glycoprotein E1.,0
"Two size classes of O-glycosidically linked oligosaccharides were liberated from glycoprotein E1 of mouse hepatitis virus (MHV) A59 by reductive beta-elimination and separated by h.p.l.c. The structures of the reduced oligosaccharides were determined by successive exoglycosidase digestions and by methylation analyses involving combined capillary gas chromatography-mass spectrometry and mass fragmentography after chemical ionization with ammonia. Oligosaccharide A (Neu5Ac alpha 2----3 Gal beta 1----3 GalNAc) comprised 35% of the total carbohydrate side chains, while the remaining 65% of the oligosaccharides of E1 had the branched structure B: Neu5Ac alpha 2----3 Gal beta 1----3 (Neu5Ac alpha 2----6) GalNAc. Both oligosaccharides were linked to the E1 polypeptide via N-acetylgalactosamine, and 20% of the sialic acids present in E1 glycopeptides were found to consist of N-acetyl-9-mono-O-acetylneuraminic acid. The reported structures of the O-linked glycans are discussed in the context of the amino acid sequence of E1, which exhibits a cluster of four hydroxyamino acids (Ser-Ser-Thr-Thr) as potential O-glycosylation sites at the amino terminus. Oligosaccharides with identical structures and an identical O-glycosylated tetrapeptide sequence are present in the blood group M-active glycophorin A of the human erythrocyte membrane.",1
"Niemann, H, Geyer, R, Klenk, H D, Linder, D, Stirm, S, Wirth, M",2
Inhibition of proteolytic cleavage of the hemagglutinin of influenza virus by the calcium-specific ionophore A23187.,0
"At calcium-specific ionophore A23187 concentrations of approximately 0.25 microM [which still allow assembly and release of fowl plague virus (FPV) particles] post-translational proteolytic cleavage of the viral hemagglutinin precursor HA into the fragments HA1 and HA2 is inhibited. The resulting virus particles with uncleaved hemagglutinin, that cannot be obtained under normal conditions, provide a suitable substrate for in vitro assays of the protease sensitivity of the FPV hemagglutinin. Proteolytic activation is accomplished with trypsin. Treatment with cathepsin B at low pH yields aberrant cleavage products suggesting that the cellular cleavage enzyme is not of lysosomal origin. A protease that cleaves the FPV hemagglutinin in the correct place can be detected in lysates of MDBK cells. This enzyme is calcium dependent and has a neutral pH optimum.",1
"Klenk, H D, Garten, W, Rott, R",2
"Antioxidant supplementation for the prevention of kwashiorkor in Malawian children: randomised, double blind, placebo controlled trial.",0
To evaluate the efficacy of antioxidant supplementation in preventing kwashiorkor in a population of Malawian children at high risk of developing kwashiorkor.,1
"Ciliberto, Heather, Ciliberto, Michael, Briend, Andreé, Ashorn, Per, Bier, Dennis, Manary, Mark",2
Understanding resolution of deliberate self harm: qualitative interview study of patients' experiences.,0
"To explore the accounts of those with a history of deliberate self harm but who no longer do so, to understand how they perceive this resolution and to identify potential implications for provision of health services.",1
"Sinclair, Julia, Green, Judith",2
Longitudinal study of birth weight and adult body mass index in predicting risk of coronary heart disease and stroke in women.,0
"To determine whether birth weight and adult body size interact to predict coronary heart disease in women, as has been observed for men. To determine whether birth weight and adult body size interact to predict risk of stroke.",1
"Rich-Edwards, Janet W, Kleinman, Ken, Michels, Karin B, Stampfer, Meir J, Manson, JoAnn E, Rexrode, Kathryn M, Hibert, Eileen N, Willett, Walter C",2
Patients' and health professionals' views on primary care for people with serious mental illness: focus group study.,0
To explore the experience of providing and receiving primary care from the perspectives of primary care health professionals and patients with serious mental illness respectively.,1
"Lester, Helen, Tritter, Jonathan Q, Sorohan, Helen",2
"Nephropathy induced by contrast media: pathogenesis, risk factors and preventive strategies.",0
"With the increasing use of contrast media in diagnostic and interventional procedures, nephropathy induced by contrast media has become the third leading cause of hospital-acquired acute renal failure. It is also associated with a significant risk of morbidity and death. The current understanding of the pathogenesis indicates that contrast-medium nephropathy is caused by a combination of renal ischemia and direct toxic effects on renal tubular cells. Patients with pre-existing renal insufficiency, diabetes mellitus and congestive heart failure are at highest risk. Risk factors also include the type and amount of contrast medium administered. Therapeutic prevention strategies are being extensively investigated, but there is still no definitive answer. In this article, we review the current evidence on the causes, pathogenesis and clinical course of contrast-medium nephropathy as well as therapeutic approaches to its prevention evaluated in clinical trials.",1
"Goldenberg, Ilan, Matetzky, Shlomi",2
Optimal search strategies for retrieving scientifically strong studies of treatment from Medline: analytical survey.,0
To develop and test optimal Medline search strategies for retrieving sound clinical studies on prevention or treatment of health disorders.,1
"Haynes, R Brian, McKibbon, K Ann, Wilczynski, Nancy L, Walter, Stephen D, Werre, Stephen R",2
Role of radiography in predicting progression of osteoarthritis of the hip: prospective cohort study.,0
To investigate which variables identify people at high risk of progression of osteoarthritis of the hip.,1
"Reijman, Max, Hazes, J M W, Pols, H A P, Bernsen, R M D, Koes, B W, Bierma-Zeinstra, S M A",2
Chronic fatigue in developing countries: population based survey of women in India.,0
"To describe the prevalence of and risk factors for chronic fatigue in a developing country; in particular, to determine the association of anaemia, mental health, and gender disadvantage factors with chronic fatigue.",1
"Patel, Vikram, Kirkwood, Betty R, Weiss, Helen, Pednekar, Sulochana, Fernandes, Janice, Pereira, Bernadette, Upadhye, Medha, Mabey, David",2
Randomised controlled trial to compare surgical stabilisation of the lumbar spine with an intensive rehabilitation programme for patients with chronic low back pain: the MRC spine stabilisation trial.,0
To assess the clinical effectiveness of surgical stabilisation (spinal fusion) compared with intensive rehabilitation for patients with chronic low back pain.,1
"Fairbank, Jeremy, Frost, Helen, Wilson-MacDonald, James, Yu, Ly-Mee, Barker, Karen, Collins, Rory",2
Surgical stabilisation of the spine compared with a programme of intensive rehabilitation for the management of patients with chronic low back pain: cost utility analysis based on a randomised controlled trial.,0
"To determine whether, from a health provider and patient perspective, surgical stabilisation of the spine is cost effective when compared with an intensive programme of rehabilitation in patients with chronic low back pain.",1
"Rivero-Arias, Oliver, Campbell, Helen, Gray, Alastair, Fairbank, Jeremy, Frost, Helen, Wilson-MacDonald, James",2
Systematic review and meta-analysis of studies of the timing of tracheostomy in adult patients undergoing artificial ventilation.,0
To compare outcomes in critically ill patients undergoing artificial ventilation who received a tracheostomy early or late in their treatment.,1
"Griffiths, John, Barber, Vicki S, Morgan, Lesley, Young, J Duncan",2
Perceptions and experiences of taking oral hypoglycaemic agents among people of Pakistani and Indian origin: qualitative study.,0
To explore British Pakistani and British Indian patients' perceptions and experiences of taking oral hypoglycaemic agents (OHAs).,1
"Lawton, Julia, Ahmad, Naureen, Hallowell, Nina, Hanna, Lisa, Douglas, Margaret",2
Use of SPRAT for peer review of paediatricians in training.,0
"To determine whether a multisource feedback questionnaire, SPRAT (Sheffield peer review assessment tool), is a feasible and reliable assessment method to inform the record of in-training assessment for paediatric senior house officers and specialist registrars.",1
"Archer, Julian C, Norcini, John, Davies, Helena A",2
Day care in infancy and risk of childhood acute lymphoblastic leukaemia: findings from UK case-control study.,0
To test the hypothesis that reduced exposure to common infections in the first year of life increases the risk of developing acute lymphoblastic leukaemia. Design and setting The United Kingdom childhood cancer study (UKCCS) is a large population based case-control study of childhood cancer across 10 regions of the UK.,1
"Gilham, C, Peto, J, Simpson, J, Roman, E, Eden, T O B, Greaves, M F, Alexander, F E",2
Cost utility analysis of co-prescribed heroin compared with methadone maintenance treatment in heroin addicts in two randomised trials.,0
"To determine the cost utility of medical co-prescription of heroin compared with methadone maintenance treatment for chronic, treatment resistant heroin addicts.",1
"Dijkgraaf, Marcel G W, van der Zanden, Bart P, de Borgie, Corianne A J M, Blanken, Peter, van Ree, Jan M, van den Brink, Wim",2
Epidemiological modelling of routine use of low dose aspirin for the primary prevention of coronary heart disease and stroke in those aged > or =70.,0
To investigate the routine use of low dose aspirin in people aged > or = 70 without overt cardiovascular disease.,1
"Nelson, Mark R, Liew, Danny, Bertram, Melanie, Vos, Theo",2
"Adult socioeconomic, educational, social, and psychological outcomes of childhood obesity: a national birth cohort study.",0
"To assess adult socioeconomic, educational, social, and psychological outcomes of childhood obesity by using nationally representative data.",1
"Viner, Russell M, Cole, Tim J",2
Early life risk factors for obesity in childhood: cohort study.,0
To identify risk factors in early life (up to 3 years of age) for obesity in children in the United Kingdom.,1
"Reilly, John J, Armstrong, Julie, Dorosty, Ahmad R, Emmett, Pauline M, Ness, A, Rogers, I, Steer, Colin, Sherriff, Andrea",2
Outcomes of planned home births with certified professional midwives: large prospective study in North America.,0
"To evaluate the safety of home births in North America involving direct entry midwives, in jurisdictions where the practice is not well integrated into the healthcare system.",1
"Johnson, Kenneth C, Daviss, Betty-Anne",2
Treatment of head louse infestation with 4% dimeticone lotion: randomised controlled equivalence trial.,0
To evaluate the efficacy and safety of 4% dimeticone lotion for treatment of head louse infestation.,1
"Burgess, Ian F, Brown, Christine M, Lee, Peter N",2
Evacuation decisions in a chemical air pollution incident: cross sectional survey.,0
To compare the health outcomes in sheltered and evacuated populations after a chemical incident in a plastics factory.,1
"Kinra, S, Lewendon, G, Nelder, R, Herriott, N, Mohan, R, Hort, M, Harrison, S, Murray, V",2
Long term effects of hysterectomy on mortality: nested cohort study.,0
"To investigate the long term risk (mean > 20 years) of death from all causes, cardiovascular disease, and cancer in women who had or had not had a hysterectomy.",1
"Iversen, Lisa, Hannaford, Philip C, Elliott, Alison M, Lee, Amanda J",2
Fate of biomedical research protocols and publication bias in France: retrospective cohort study.,0
"To describe the fate of protocols approved by the French research ethics committees, a national system created by the French 1988 Huriet-Sérusclat Act; to assess publication bias at a national level.",1
"Decullier, Evelyne, Lhéritier, Véronique, Chapuis, François",2
Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries.,0
"To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures.",1
"Cardis, E, Vrijheid, M, Blettner, M, Gilbert, E, Hakama, M, Hill, C, Howe, G, Kaldor, J, Muirhead, C R, Schubauer-Berigan, M, Yoshimura, T, Bermann, F, Cowper, G, Fix, J, Hacker, C, Heinmiller, B, Marshall, M, Thierry-Chef, I, Utterback, D, Ahn, Y-O, Amoros, E, Ashmore, P, Auvinen, A, Bae, J-M, Solano, J Bernar, Biau, A, Combalot, E, Deboodt, P, Diez Sacristan, A, Eklof, M, Engels, H, Engholm, G, Gulis, G, Habib, R, Holan, K, Hyvonen, H, Kerekes, A, Kurtinaitis, J, Malker, H, Martuzzi, M, Mastauskas, A, Monnet, A, Moser, M, Pearce, M S, Richardson, D B, Rodriguez-Artalejo, F, Rogel, A, Tardy, H, Telle-Lamberton, M, Turai, I, Usel, M, Veress, K",2
Should treatment of (sub)acute low back pain be aimed at psychosocial prognostic factors? Cluster randomised clinical trial in general practice.,0
To compare the effects of a minimal intervention strategy aimed at assessment and modification of psychosocial prognostic factors and usual care for treatment of (sub)acute low back pain in general practice.,1
"Jellema, Petra, van der Windt, Daniëlle A W M, van der Horst, Henriëtte E, Twisk, Jos W R, Stalman, Wim A B, Bouter, Lex M",2
"Impact on patients of expanded, general practice based, student teaching: observational and qualitative study.",0
To compare patients' enablement and satisfaction after teaching and non-teaching consultations. To explore patients' views about the possible impact that increased community based teaching of student doctors in their practice may have on the delivery of service and their attitudes towards direct involvement with students.,1
"Benson, John, Quince, Thelma, Hibble, Arthur, Fanshawe, Thomas, Emery, Jon",2
Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials.,0
"Open angle glaucoma is one of the most common causes of blindness in industrialised nations. Treatments to lower ocular pressure are widely used in glaucoma prevention and treatment, despite conflicting evidence.",1
"Maier, Philip C, Funk, Jens, Schwarzer, Guido, Antes, Gerd, Falck-Ytter, Yngve T",2
Selective chromosome analysis in couples with two or more miscarriages: case-control study.,0
"To identify additional factors, such as maternal age or factors related to previous reproductive outcome or family history, and the corresponding probability of carrying a chromosome abnormality in couples with two or more miscarriages.",1
"Franssen, Maureen T M, Korevaar, Johanna C, Leschot, Nico J, Bossuyt, Patrick M M, Knegt, Alida C, Gerssen-Schoorl, Klasien B J, Wouters, Cokkie H, Hansson, Kerstin B M, Hochstenbach, Ron, Madan, Kamlesh, van der Veen, Fulco, Goddijn, Mariette",2
Response to antibiotics of women with symptoms of urinary tract infection but negative dipstick urine test results: double blind randomised controlled trial.,0
To assess the effectiveness of antibiotic treatment of women with symptoms of urinary tract infection but negative urine dipstick testing.,1
"Richards, Dee, Toop, Les, Chambers, Stephen, Fletcher, Lynn",2
"Neutrophil chemotaxis in rheumatoid arthritis. Effect of D-penicillamine, gold salts, and levamisole.",0
"The effect of therapeutic concentrations of D-penicillamine, sodium aurothiomalate, and levamisole on in vitro neutrophil chemotaxis and random migration in normal subjects and patients with rheumatoid arthritis was studied. D-penicillamine produced no changes. Sodium aurothiomalate produced dose-related reductions in chemotaxis in normal subjects and in patients who had a good clinical response to gold therapy, while patients who had failed to respond to gold showed a minimal nondose dependent reduction. Levamisole produced dose-dependent stimulation of chemotaxis, a greater effect found with the patients cells. Neutrophil chemotaxis improved to normal values in most patients responding to several months of D-penicillamine treatment but showed an immediate and marked stimulation in patients treated with levamisole.",1
"Mowat, A G",2
"Neutrophil chemotaxis in ankylosing spondylitis, Reiter's disease, and polymyalgia rheumatica.",0
"Neutrophil chemotaxis was found to be normal in 14 patients with ankylosing spondylitis, in 10 patients with Reiter's disease, and in 8 patients with polymyalgia rheumatica.",1
"Mowat, A G",2
Antigammaglobulin (rheumatoid factor) activity of human IgG subclasses.,0
"A sensitive radioimmunoassay has been applied to the study of rheumatoid factor activity of IgM and IgG subclasses in serum and synovial fluid of patients with rheumatoid arthritis. Although rheumatoid factor activity was found in all four subclasses, its distribution was not the same as that of the total subclasses in normal sera. Results are discussed in relation to the possible clinical value of measuring IgG rheumatoid factor in sera and synovial fluids of patients with rheumatoid arthritis.",1
"Shakib, F, Stanworth, D R",2
Ankylosing spondylitis and inflammatory bowel disease. I. Prevalence of inflammatory bowel disease in patients suffering from ankylosing spondylitis.,0
"To establish the prevalence of inflammatory bowel disease in ankylosing spondylitis (AS), 79 AS patients underwent detailed medical screening, including sigmoidoscopic and roentgenological examination, 48 had gastrointestinal symptoms and the others did not. In 3 patients a diagnosis of Crohn's disease was made which was previously established. In all other patients inflammatory bowel disease could be excluded. The prevalence of inflammatory bowel disease in this series of patients with AS therefore was 3.8%.",1
"Meuwissen, S G, Dekker-Saeys, B J, Agenant, D, Tytgat, G N",2
"Ankylosing spondylitis and inflammatory bowel disease. II. Prevalence of peripheral arthritis, sacroiliitis, and ankylosing spondylitis in patients suffering from inflammatory bowel disease.",0
"To establish the prevalence of peripheral arthritis, radiographic sacroiliitis, and ankylosing spondylitis in patients with inflammatory bowel disease, 58 consecutive patients suffering from ulcerative colitis (UC) and 51 with Crohn's disease (CD) underwent a detailed rheumatological examination. In addition, all patients were screened for the presence of the antigen HLA B27. Peripheral arthritis was found in 14 (8 UC, 6 CD) patients (12.8%); radiographic sacroiliitis was diagnosed in 11 (5 UC, 6 CD) (10.1%), of whom 10 were asymptomatic; and ankylosing spondylitis was diagnosed in 2 UC and 2 CD patients (3.7%). 18.9% of the UC and 3.9% of the CD patients were HLA B27 positive. One of the 11 patients with radiographic sacroiliitis and 2 of the 4 with ankylosing spondylitis had the HLA B27 antigen. Peripheral arthritis, radiographic sacroiliitis, and ankylosing spondylitis are apparently frequent manifestations in patients suffering from inflammatory bowel disease. Asymptomatic radiographic sacroiliitis in these patients appears to differ from idiopathic ankylosing spondylitis, both clinically and genetically. Evaluation of subjective rheumatological complaints, necessary for a confident diagnosis of ankylosing spondylitis, according to the New York criteria is difficult during a flare-up of the inflammatory bowel process, as was shown in 4 CD cases with marked limitation of lumbovertebral function and chest expansion, but no radiological abnormalities of the SI joints.",1
"Dekker-Saeys, B J, Meuwissen, S G, Van Den Berg-Loonen, E M, De Haas, W H, Agenant, D, Tytgat, G N",2
Synovial fluid copper and related variables in rheumatoid and degenerative arthritis.,0
"Copper, caeruloplasmin, transferrin, albumin, and total protein were measured in the serum and synovial fluid of 40 patients with rheumatoid arthritis and 40 patients with osteoarthrosis. A raised synovial fluid copper and caeruloplasmin have been found to be characteristic of rheumatoid effusions. The relation between copper and caeruloplasmin in synovial fluid differs from that in serum. Synovial fluid caeruloplasmin was increased disproportionately in relation to other plasma proteins present in rheumatoid effusions.",1
"Scudder, P R, McMurray, W, White, A G, Dormandy, T L",2
Radioisotope scanning using a gamma camera.,0
"Sixteen outpatients with rheumatoid arthritis took part in a placebo controlled double-blind crossover study. In addition to conventional measurements, a radioactive index was measured using a gamma camera that indicated a radioactive count over the measured joints and a comparable area of normal adjacent bone. This index showed poor correlation with other conventional measurements of change in the clinical trial.",1
"Berry, H, Barrett, J J, Ford-Hutchinson, A, Hamilton, E B",2
Double-blind trial of naproxen and phenylbutazone in ankylosing spondylitis.,0
In a double-blind double-placebo crossover study naproxen (500-750 mg daily) was found to be equivalent to phenylbutazone (400-600 mg daily) in the control of disease activity in 20 patients suffering from ankylosing spondylitis during a two times 5-week trial period. No serious side effects were observed during the trial period. Gastric complaints occurred twice as often under phenylbutazone as under naproxen.,1
"Van Gerwen, F, Van der Korst, J K, Gribnau, F W",2
Intra-articular and circulating immune complexes and antiglobulins (IgG and IgM) in rheumatoid arthritis; correlation with clinical features.,0
"Solid phase radioimmunometric methods have been used to assay immune complexes and IgG and IgM antiglobulins in paired samples of synovial fluid and serum from patients with rheumatoid arthritis (RA) or osteoarthrosis. Over 60% of RA patients had some increase in complexes in their sera, while nearly 90% had synovial fluid complexes. Moreover, the levels of complexes within the joint were much higher than in the serum. Both IgG and IgM antiglobulins were raised in most RA patients. The levels of IgG antiglobulins--and to a less extent IgM antiglobulins--were nearly always higher in synovial fluid than in the corresponding serum sample.A strong correlation was found between the levels of immune complex and IgG antiglobulin. A marked association was seen between the presence of subcutaneous nodules and increased IgG antiglobulins.",1
"Hay, F C, Nineham, L J, Perumal, R, Roitt, I M",2
Rheumatoid arthritis in Kenya. II. Serological observations.,0
"Sera from 48 Kenyan Africans with rheumatoid arthritis, 43 patients with other diseases, and 98 blood donors were tested for the presence of rheumatoid factor by latex fixation tests using human European, human African, and rabbit immunoglobulin, and a sheep cell haemagglutination test. In the patients with rheumatoid arthritis the frequency of rheumatoid factor was comparable to that reported in series from Europe and the USA, thus differing from the findings in West Africa. In the control patients and blood donors a high frequency of positive tests for rheumatoid factor was found; a similar result has been obtained from population studies in other African countries. Broadly similar results were obtained with each of the latex tests, and these were found to be less specific for rheumatoid arthritis than the sheep cell haemagglutination test.",1
"Houba, V, Bagg, L R, Hansen, D P, Bowry, T",2
Prevalence and incidence of the diagnosis of gout in Great Britain.,0
"A study in gout of the incidence of diagnosis from 1971 to 1975 and of the prevalence at 31 December 1975 was carried out in a representative general practice sample comprising 64 practices and a population numbering 1 in 145 of the total population of Great Britain. The results show an annual incidence in Great Britain from 1971 to 1975 varying from 0.25 to 0.35 per 1000 and an overall prevalence at 31 December 1975 of 2.6 per 1000. The prevalence in England was found to be significantly greater than in the rest of Great Britain and that in Wales to be significantly greater than in Scotland. In 10% of the cases the gout was believed to be secondary, with induction by diuretics being the most frequent cause. The prevalence of primary gout was estimated to be 2.3 per 1000.",1
"Currie, W J",2
Osteomalacia in rheumatoid arthritis.,0
"Fifty-four patients with rheumatoid arthritis and severe osteomalacia were found to have considerable bone and general deficiency problems. In 46 of them 14 stress fractures occurred and 32 minimal trauma fractures necessitating admission to hospital. Radiological abnormalities of absorption were found in nearly 25% of the total, implying that dietary factors alone are not always responsible for osteomalacia in patients with rheumatoid arthritis. A high index of suspicion is necessary in the diagnosis of osteomalacia in patients with rheumatoid arthritis, so they may benefit from treatment.",1
"O'Driscoll, S, O'Driscoll, M",2
Levamisole-associated neutropenia and autoimmune granulocytotoxins.,0
"To investigate possible immune mechanisms responsible for levamisole-associated neutropenia we tested patients with bladder cancer on levamisole therapy. Autoimmune and complement-dependent granulocytotoxic antibodies were detected in 3 patients with levamisole-induced neutropenia. The granulocytopenia appeared to be causally related to the presence of autoantibodies in that pretreatment serum or serum obtained after the restoration of neutrophil counts showed diminished or no granulocytotoxic reactivity. In addition, granulocytotoxins were found in 6 out of 20 (30%) patients receiving levamisole compared to only 2 out of 28 (7.1%) patients on no levamisole or placebo (P less than 0.06). Hence, screening for granulocytotoxins may forewarn of neutropenia in patients receiving levamisole for a variety of clinical diseases.",1
"Drew, S I, Carter, B M, Nathanson, D S, Terasaki, P I",2
Membrane and transformation characteristics of lymphocytes isolated from the synovial membrane and paired peripheral blood of patients with rheumatoid arthritis.,0
"Membrane and transformation characteristics of lymphocytes isolated from the synovial membrane and from paired peripheral blood samples, obtained from patients with classical rheumatoid arthritis, were studied. Synovial tissue lymphocytes were isolated by a new technique. Two suspensions of peripheral blood lymphocytes were studied: one isolated by Ficoll-Isopaque density gradient centrifugation, the other enriched in T cells by an additional step of 1 hour nylon wool column filtration. All suspensions were characterised by the percentages of mononuclear phagocytic cells, and T and B lymphocytes. The spontaneous (3)H-thymidine uptake of synovial tissue lymphocyte suspensions always exceeded that of the peripheral blood lymphocyte suspensions. The in-vitro responsiveness of synovial tissue lymphocytes to PHA, Con-A, and PWM, as measured by (3)H-thymidine uptake, was always consistently lower than that of paired peripheral blood lymphocytes whether or not enriched in T cells. The responsiveness to antigens, including PPD, varidase, and an antigen cocktail consisting of varidase, trychophyton, and Staphylococcus aureus antigen, showed the same effect. No dissociation was found between the response to PPD and the other antigens studied. These results suggest that the relative unresponsiveness to mitogens and antigens of synovial tissue lymphocytes in comparison with blood lymphocytes is not caused by mononuclear phagocyte contamination, but either by different subsets of T lymphocytes or by different functional states of T lymphocytes present in the synovial membrane and peripheral blood of patients with rheumatoid arthritis.",1
"Meijer, C J, van de Putte, L B, Lafeber, G J, de Haas, E, Cats, A",2
Prognosis and management of polymyalgia rheumatica.,0
"Polymyalgia rheumatica (PMR) is considered to be a benign disease by some, while others think it is a more serious illness which required similar treatment to giant cell arteritis (GCA). The progress of 85 patients with PMR who presented to a district general hospital has been studied in an attempt to study this relationship. Thirty-eight patients had PMR alone, and 14 developed PMR and GCA within 1 month. Five patients presented with GCA and then developed PMR, and 28 patients developed symptoms of GCA after presenting with PMR (PMR leads to GCA). Arteritis and complications developed up to 9 years after the onset of PMR (mean 1 year). Twenty-two patients (26%) developed some cerebral or visual complication. Fifteen of these patients were in the PMR leads to GCA group. All 6 patients with permanent loss of vision were in this group. Seven patients developed complications while on corticosteroids. 97% of patients required corticosteroids for at least 1 year; 32% of patients still required 10 mg of prednisone or more after 1 year. PMR is not a benign disease.",1
"Jones, J G, Hazleman, B L",2
Incidence and correlation between serum IgG and IgM antibodies to native type II collagen in patients with chronic inflammatory arthritis.,0
"Raised serum IgG and IgM antibody levels to native type II collagen were found in patients with rheumatoid arthritis and in patients with juvenile chronic arthritis. There was a good correlation between the serum IgG and the IgM antibody levels in rheumatoid arthritis and a weaker correlation in juvenile chronic arthritis. Raised serum IgM antibody levels to native type II collagen were found in only 1 patient each with ankylosing spondylitis and psoriatic arthritis, and in these groups here was no correlation between the serum IgG and the IgM antibody levels. The highest serum IgG and IgM antibody levels to native type II collagen were found in rheumatoid arthritis. These results, together with the results on serum antiglobulin levels, indicate that patients with rheumatoid arthritis produce antibodies of both IgG and IgM immunoglobulin class which may have pathogenetic significance in the more severe arthritis found in this condition.",1
"Clague, R B, Shaw, M J, Holt, P J",2
Antibody-dependent and phytohaemagglutinin-induced lymphocyte cytotoxicity in systemic lupus erythematosus.,0
"An investigation of cell-mediated cytotoxicity in 22 patients with systemic lupus erythematosus (SLE), using both whole blood and purified peripheral blood mononuclear cells (PBM) to measure antibody-dependent (ADCC) and phytohaemagglutinin (PHA)-induced lymphocyte cytotoxicity for Chang liver cells, has revealed 2 distinct abnormalities in patients with active disease. PHA-induced cytotoxicity was found to be selectively reduced in whole blood assays only (P less than 0.05), whereas ADCC was impaired in both whole blood (P = 0.02) and PBM (P less than 0.05) assays, when comparison was made with 52 normal controls. The addition of patients' sera to corresponding assays utilizing control PBM confirmed that the impaired PHA-induced cytotoxicity resulted from circulating inhibitory serum factors. Surprisingly little effect, however, was exerted on ADCC assays. These findings suggest that there is a reduction in numbers and/or functional capacity of Fc-receptor cells in active SLE, which may have pathogenetic implications.",1
"Wright, J K, Hughes, P, Gelsthorpe, K, Ward, A M, Rowell, N R",2
Narrowing of knee joint space in patients with pseudogout.,0
Abnormalities of joint space in knee roentgenograms were compared among 28 symptomatic patients with pseudogout and 2 control groups consisting of spouses of patients and hospital based patients with knee pain. Joint space narrowing was significantly more frequent in the pseudogout patients than in the 2 control groups. Division of patients and controls into 3 age groups revealed a striking degree of joint space narrowing in the youngest patients with pseudogout. Our study suggests that symptomatic patients with pseudogout have joint destruction beginning at a relatively early age. We speculated that this may reflect concurrence of chondrocalcinosis and another disease such as osteoarthritis.,1
"Ellman, M H, Brown, N L, Levin, B",2
Morphea-like reaction to D-penicillamine therapy.,0
"We report the case of a 48-year-old woman who developed morphea-like plaques after 1 year of treatment with D-penicillamine at 250 mg daily for a seronegative erosive arthritis of rheumatoid type. The rash began as several red itchy patches on the trunk; these became thickened and shiny over about 3 months. The histological appearance was of increased dermal fibrosis with an inflammatory infiltrate round dermal capillaries. However, epidermal changes were not typical of morphea. New lesions ceased to appear within a few months of stopping penicillamine, and by 1 year all the plaques were pale and symptomless.",1
"Bernstein, R M, Hall, M A, Gostelow, B E",2
Chronic sarcoid synovitis in the Caucasian: an arthroscopic and histological study.,0
"Chronic synovitis is a rare complication of sarcoidosis, virtually confined to the black population. Synovial histology may be nonspecific or show typical sarcoid granulomata. We report 2 cases of chronic sarcoid synovitis in Caucasians. Histology showed typical granulomata in one patient, whose distinctive arthroscopic appearance is discussed.",1
"Scott, D G, Porto, L O, Lovell, C R, Thomas, G O",2
Tuberculosis in patients with systemic lupus erythematosus.,0
"Tuberculosis associated with systemic lupus erythematosus (SLE) was studied in a cohort of 311 patients seen between 1963 to 1979. There were 16 such patients, giving rise to a prevalence rate of 5%. The characteristics of SLE-associated tuberculosis include a high incidence of miliary and far-advanced pulmonary disease, delay in establishing diagnosis, especially the extrapulmonary form, and tendency to attribute symptoms like fever, malaise, and weight loss to the lupus process. Treatment was successful in 9 patients. Of the 7 death 5 were attributed directly to the mycobacterial infection and 2 to complications of SLE.",1
"Feng, P H, Tan, T H",2
Pulmonary necrobiotic nodules as a presenting feature of rheumatoid arthritis.,0
"In rheumatoid disease only 4 cases have been reported in which lung nodules preceded arthritis. Two further cases are presented in which intrapulmonary nodules were noted at the onset of the disease, thus provoking a diagnostic dilemma. In the first patient rheumatoid factor tests were initially negative, and diagnostic thoracotomy was performed. In the second patient serological tests were positive, and biopsy was avoided. It therefore seems that detection of circulating rheumatoid factor in patients with lung shadows can be a useful aid to diagnosis and management.",1
"Hull, S, Mathews, J A",2
A study of migraine in systemic lupus erythematosus.,0
"An increased prevalence of classical migraine was found in 30 female patients with systemic lupus erythematosus (SLE) compared with an age and sex-matched control group by means of a detailed questionnaire. No significant difference were found between the patients and controls, who had classical and common migraine or visual auras without headache, with regard to a family history of migraine, the age of onset of the migraine, Raynaud's phenomenon, or use of oral contraceptives. Increased activity of the lupus was not generally associated with an increase in migraine attacks. It is suggested that migrainous phenomena may be a feature of SLE.",1
"Isenberg, D A, Meyrick-Thomas, D, Snaith, M L, McKeran, R O, Royston, J P",2
Neutrophil function in systemic lupus erythematosus and other collagen diseases.,0
"Using a whole blood technique we assessed neutrophil migration, phagocytosis, and killing in a group of 20 patients with systemic lupus erythematosus (SLE) and in 8 patients with other connective tissue disorders. In the untreated cases of SLE neutrophil migration was significantly depressed, but it was usually normal in the treated group. This may be attributable either to an intrinsic neutrophil abnormality or to a humoral factor. Although isolated abnormalities of phagocytosis and killing were observed in SLE, these functions were normal when the patients were considered as a group. The treated patients with other collagen diseases showed enhanced migration in both autologous and control plasma, normal phagocytosis, and enhanced killing in autologous plasma only. The small group of untreated, non-SLE patients showed some depression of all 3 functions. There was no correlation between neutrophil function and clinical activity of disease. In the SLE patients there was no correlation between neutrophil function and circulating immune complexes.",1
"Al-Hadithy, H, Isenberg, D A, Addison, I E, Goldstone, A H, Snaith, M L",2
Another hazard of gold therapy?,0
"A patient with seropositive rheumatoid developed a bullous eruption localised to the jewellery areas 12 hours after a test dose of sodium aurothiomalate (Myocrisin). Investigation showed that she was allergic to nickel rather than gold. Small quantities of nickel were found in the Myocrisin solution after a short contact with a metal needle, suggesting an explanation for the reaction.",1
"Fulton, R A, Sturrock, R D, Capell, H",2
Chronic arthritis associated with the presence of intrasynovial rubella virus.,0
"In this report we present 21 instances in which live rubella virus was isolated from synovial fluid obtained from 6 cases of inflammatory oligoarthritis or polyarthritis over a period of 2 years in the absence of firm clinical evidence of rubella. In 3 cases (cases 1, 2, 6,) a persistent oligoarthritis predominantly affecting the knee joints occurred in 2 adult women and one man, lasting to date 27, 29, and 18 months respectively, and in one of these cases virions were found in cells of the synovial membrane. In case 3 a boy of 9 presented with an illness indistinguishable from the systemic variety of juvenile chronic arthritis (Still's disease). In case 4 a young man with persistent monoarthritis was found to have ankylosing spondylitis, and in case 5 a progressive erosive polyarthritis developed 5 years after an attack of rubella complicated by rubella arthritis. The virus was identified by a variety of virological techniques and infection confirmed by immunofluorescence and (in one case) electron microscopy.",1
"Grahame, R, Armstrong, R, Simmons, N, Wilton, J M, Dyson, M, Laurent, R, Millis, R, Mims, C A",2
Monocyte-induced inhibition of lymphocyte response to phytohaemagglutinin in progressive systemic sclerosis.,0
"In patients with progressive systemic sclerosis (PSS) lymphocyte responses to phytohaemagglutinin (PHA) are abnormal (27.2 +/- 3.5 X 10(-3) counts per minute (cpm) versus 69.8 +/- 4.4 X 10(-3) for normal persons, p less than 0.005). Removal of adherent peripheral blood mononuclear cells improves the response of PSS lymphocytes (42.3 +/- 3.4 X 10(-3) cpm, 155% of control) but diminishes the response of normal lymphocytes (60.3 +/- 5.9 +/- 10(-3), 86% of control). Supernatant fluids from cultures of PSS unfractionated and adherent cells depress normal T cell response to PHA (64% and 55% of control respectively), but supernatant fluids from normal unfractionated and adherent cells do not (104% and 101% of control). Supernatant fluids of PSS and normal adherent cells, cultured in the presence of indomethacin, are not inhibitory to normal T cells (109 +/- 15% and 124 +/- 14% of control respectively). Supernatant fluids from PSS patients are more inhibitory than comparable fluids from patients with systemic lupus erythematosus (60 +/- 8% of control versus 80 +/- 5% of control). These data support the hypothesis that cellular immunity is abnormal in patients with PSS and indicate that adherent mononuclear cells mediate at least one component of the abnormality via an indomethacin-sensitive mechanism.",1
"Lockshin, M D, Markenson, J A, Fuzesi, L, Kazanjian-Aram, S, Joachim, C, Ordene, M",2
Aorto-atrial fistula in rheumatoid arthritis.,0
A patient with severe deforming rheumatoid arthritis presented with a short history of chest pain. The clinical signs were of an unusual diastolic murmur and profound shock unresponsive to therapy. Post-mortem examination disclosed the unexpected finding of a large aorto-atrial fistula.,1
"Crean, P A, Reid, D S, Buchanan, J",2
Coexistence of Reiter's syndrome and rheumatoid arthritis in a genetically susceptible individual.,0
"A patient is presented who had features of Reiter's syndrome for 10 years before developing features of rheumatoid arthritis. Diagnostic criteria for both diseases are fulfilled, and HLA typing revealed the presence of both B27 and DR4 antigens. The coexistence of Reiter's syndrome and rheumatoid arthritis appears to have occurred in an individual genetically susceptible to both diseases.",1
"Fallahi, S, Miller, R K, Halla, J T",2
Infection and interferon production in systemic juvenile chronic arthritis: a prospective study.,0
"Twenty-four episodes of disease exacerbation in 19 children suffering from systemic juvenile chronic arthritis were studied. Sixteen of these were preceded by an infection (chi 2 = 20.14, p less than 0.001), mostly of the upper respiratory tract. In the 10 cases seen during an infection causative agents were identified in 5 (herpes simplex, rhinovirus, and on 3 occasions streptococcus). The total number of infections was not increased when compared with infection rates predicted by several reported studies. In the absence of clinical infection, specific antibody titres to a panel of microbial antigens were similar to those of a control group but with a trend toward higher titres in patients with hypergammaglobulinaemia. Interferon (IFN) responses were not defective, though sequential in-vitro IFN production from peripheral blood mononuclear cells (PBM) fluctuated considerably in the same patients, occasionally being absent with no obvious clinical correlate. IFN-alpha was induced by stimulation with Newcastle disease virus (NDV), and the mean responses of the patients were significantly greater than those of controls. IFN-gamma production on phytohaemagglutinin (PHA) stimulation was similar in patients and control groups. IFN was not detected in any of the sera from patients or controls.",1
"de Vere-Tyndall, A, Bacon, T, Parry, R, Tyrrell, D A, Denman, A M, Ansell, B M",2
Progression of radiological changes in rheumatoid arthritis.,0
"A prospective study over one year of patients who had active rheumatoid arthritis discovered 64 who had received treatment for an adequate time with second-line drugs. In these patients there was evidence of continuing joint destruction as shown by radiological progression. During the year there were highly significant correlations between improvements in clinical and laboratory measurements, but neither group of tests was related to the degree of radiological change. However, in the second 6 months of treatment there was evidence that radiological progression was reduced. In a second prospective study of 88 patients with rheumatoid arthritis given prolonged, intensive therapy with second-line drugs and followed up for 10 years two-thirds showed radiological progression. However, the number of joints damaged per year fell significantly during the study period. There was a divergence between deterioration in radiological features and improvements in the ESR and functional capacity, though patients with a persistently low ESR had less radiological progression. These studies provide evidence that treatment may be associated with a reduced rate of radiological progression but suggest that changes in radiological progression and clinical and laboratory measurements may result from different mechanisms.",1
"Scott, D L, Grindulis, K A, Struthers, G R, Coulton, B L, Popert, A J, Bacon, P A",2
Does second-line therapy affect the radiological progression of rheumatoid arthritis?,0
"The effect of 'second-line' drugs on radiological progression in rheumatoid arthritis is not clear, and previous studies have yielded contradictory results. Sixty-seven patients with rheumatoid arthritis have been followed up clinically and radiologically for approximately 2 years (26 patients were receiving intramuscular gold, 21 penicillamine, 10 levamisole, and there were 10 controls who had consistently refused second-line therapy). Patients on gold and penicillamine showed improvement in erythrocyte sedimentation rate and haemoglobin over 2 years which was not seen in levamisole and control patients, but hand radiograph scores in all 4 groups showed statistically significant deterioration. There was a trend towards slowing of the rate of erosion in the gold and penicillamine groups in comparison with controls, but healing of erosions was extremely unusual.",1
"Pullar, T, Hunter, J A, Capell, H A",2
Acute psoriatric arthropathy precipitated by oxprenolol.,0
A previously normal 58-year-old woman developed a widespread psoriatic rash and asymmetrical peripheral polyarthritis a week after beginning treatment with oxprenolol for hypertension. Skin and joint disease resolved simultaneously after drug withdrawal and have not recurred.,1
"Macfarlane, D G, Settas, L",2
Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. II. Phenotypic characterisation of mononuclear cells forming Facb rosettes in RA.,0
"We have previously reported an increased proportion of Facb-rosette forming cells in the peripheral blood of patients with rheumatoid arthritis in comparison with healthy controls. The present study investigates the surface phenotype of these cells by means of monoclonal antibodies and a variety of rosetting and lymphocyte fractionation techniques. Facb-R+ cells were found to lack surface markers characteristic of T and B lymphocytes. Studies with monoclonal reagents showed a positive reaction with OKIa1, OKM1, and another monocyte-specific antibody. Fac-R+ cells were recognised by anti-HLA-DR reagents but did not bind the monoclonal antibody 17.15 that recognises a determinant on HLA-DR antigens expressed by lymphocytes but not monocytes. These results show that Facb-R+ cells share certain surface characteristics with monocytes, though they are not phagocytic. These observations are consistent with an accessory role for Facb-R+ cells in the immune response.",1
"Winrow, V R, Eales, L J, Hall, N D, Goulding, N J, Hunneyball, I M",2
Lymphocytes bearing Fc gamma receptors in rheumatoid arthritis. III. Immunoregulatory function associated with Facb rosette-forming cells.,0
"A subpopulation of mononuclear cells (PBMNC) that expresses Fc receptors with specificity for the C gamma 2 region of IgG may be detected by rosette formation with calf erythrocytes coated with the Facb fragment of rabbit IgG. These Facb-R+ cells are found in increased numbers in the peripheral blood of patients with rheumatoid arthritis (RA). Studies have been carried out to identify the functional properties of these cells in healthy and rheumatoid subjects. Facb-R+ cells were shown to lack both natural killer and antibody-dependent cytotoxic activity. Depletion of Facb-R+ cells from both healthy and rheumatoid PBMNC resulted in a marked suppression of pokeweed mitogen (PWM) stimulated IgG synthesis but had no effect on T cell proliferation induced by phytohaemagglutinin, concanavalin A, or PWM. The addition of Facb fragments to PBMNC cultures also caused inhibition of PWM-driven IgG production. In this assay rheumatoid PBMNC were significantly less sensitive to Facb-mediated suppression than healthy control cells. Our results suggest that Facb-R+ cells are involved in the antibody-mediated feedback regulation of immunoglobulin synthesis and that this mechanism is impaired in patients with RA.",1
"Eales, L J, Goulding, N J, Hall, N D, Winrow, V R, Hunneyball, I M",2
Measurement of rheumatoid factors by an enzyme-linked immunosorbent assay (ELISA) and comparison with other methods.,0
"IgM rheumatoid factor (RF) was measured in the sera of 48 rheumatoid patients and of 48 age and sex-matched normal controls by the Rose-Waaler and latex agglutination tests, a rate nephelometer, and an enzyme-linked immunosorbent assay (ELISA). Good correlation was obtained between all assays. The rate nephelometer assay was the easiest and quickest to perform and gave results in international units/ml. The Rose-Waaler was the least sensitive assay and the most difficult to perform and interpret. Both the latex agglutination and the ELISA were sensitive, though some overlap of patient and control sera was seen with all the assays. In addition to IgM RF the ELISA was used to measure IgG RF and IgA RF in both rheumatoid and control sera. Although some normal sera had detectable amounts of IgG and IgA RF, the levels of both were significantly raised in the rheumatoid sera. IgG RF levels were lower after pepsin digestion of the sera, suggesting that IgM RF interfered with the assay for IgG RF unless this treatment was included.",1
"Bampton, J L, Cawston, T E, Kyle, M V, Hazleman, B L",2
Salivary secretion and connective tissue disease in man.,0
"Parotid and submandibular gland secretions collected from patients with rheumatoid arthritis or systemic sclerosis have been analysed and the results compared with those obtained from a matched group of healthy individuals. Flow rates were measured and the saliva samples assayed for amylase, kallikrein, protein, and salivary IgA concentration. The results showed that only patients with rheumatoid arthritis had a reduced salivary flow, especially parotid flow, with a significantly increased concentration of salivary IgA in both parotid and submandibular saliva. Patients with systemic sclerosis did not show significantly altered salivary flow rates, but there was a marked depletion of salivary IgA content in both parotid and submandibular saliva. Neither disease states appeared to alter the kallikrein or amylase content of saliva. The possible clinical value of these findings is discussed.",1
"Matthews, R W, Bhoola, K D, Rasker, J J, Jayson, M I",2
A randomised double-blind trial of diltiazem in the treatment of Raynaud's phenomenon.,0
"The efficacy of diltiazem in the treatment of Raynaud's phenomenon was assessed in a prospective double-blind randomised cross-over trial in 16 patients (7 progressive systemic sclerosis, 2 rheumatoid arthritis, 1 systemic lupus erythematosus, and 6 idiopathic Raynaud's phenomenon). Each patient received diltiazem 120 mg and placebo three times a day for two weeks. The attack frequency of Raynaud's phenomenon was measured by a diary count; its severity was assessed by means of a 10 cm visual analogue scale with 0 representing minimum and 10 representing maximum severity. Diltiazem significantly decreased the frequency and severity of Raynaud's phenomenon as compared with placebo. This improvement was striking in patients with idiopathic Raynaud's phenomenon but did not reach statistical significance in patients with associated systemic disease. We conclude that diltiazem is effective in the treatment of Raynaud's phenomenon, especially in patients with idiopathic vasospastic disease.",1
"Kahan, A, Amor, B, Menkes, C J",2
Chrysotherapy and thrombocytopenia.,0
"In a study of the clinical and immunogenetic profiles of 17 patients with rheumatoid arthritis and thrombocytopenia (platelet count less than 150 000/mm3 (150 x 10(9)/l)) due to gold therapy two clinical patterns were distinguished without knowledge of HLA type: group I, an early precipitous thrombocytopenia (10 patients), and group II, a less dramatic fluctuant fall (seven patients). In group I patients the clinical and laboratory features suggested an immune mediated, peripheral destruction of platelets, and all patients in this group were found to be HLA-DR3 positive. Two patients subsequently received penicillamine without toxicity. In group II the basis of thrombocytopenia appeared to be different, and only two patients in this group were HLA-DR3 positive. All group II patients had received penicillamine; four developed a thrombocytopenia. Mechanisms of toxicity in both groups are discussed. It would appear that HLA typing in unlikely to help in predicting all those patients at risk of toxicity during chrysotherapy.",1
"Madhok, R, Pullar, T, Capell, H A, Dawood, F, Sturrock, R D, Dick, H M",2
Articular manifestations of familial hypercholesterolaemia.,0
"Familial hypercholesterolaemia is characterised by a decreased removal of low density lipoproteins and premature coronary artery disease. Tendinous xanthomata are a hallmark of the disease. The affected joints may also be the sites of inflammation and pain. Arthropathy has been associated mainly with the homozygous form of familial hypercholesterolaemia, but it is also known to occur in the heterozygous form. We report on the articular manifestations in 73 patients with heterozygous familial hypercholesterolaemia. About 40% of these patients had at least one episode of articular symptoms. The observed articular manifestations may be classified into four types: Achilles pain (18%), Achilles tendinitis (11%), oligoarticular arthritis (7%), polyarticular or rheumatic fever-like arthritis (4%). It is concluded that in heterozygous familial hypercholesterolaemia articular manifestations are frequent, diverse, and may be the first symptom of this metabolic disorder.",1
"Mathon, G, Gagné, C, Brun, D, Lupien, P J, Moorjani, S",2
Bidirectional erosion of cartilage in the rheumatoid knee joint.,0
"Specimens of cartilage with contiguous bone and overlying synovial pannus were obtained from 22 rheumatoid knee joints and examined histologically using specific histochemical staining techniques. All showed significant erosions of cartilage by synovial cells, but seven specimens also showed substantial cartilage erosion by cells from the subchondral bone region. This bidirectional attack on rheumatoid knee cartilage did not represent an 'underpinning' of cartilage by synovial pannus, as judged by serial sectioning and the identification of specific cells. Whereas cartilage-pannus junctions had mainly macrophagic or fibroblastic cells, cartilage-bone lesions were usually characterised by chondroclasts and blood vessels. Lymphocytes were generally absent from all sites of cartilage erosion. The bidirectional attack on articular knee cartilage suggests that changes have occurred within the cartilage that make it vulnerable to cellular invasion and erosion. Such changes might reflect a deficiency in 'anti-invasion factors', or the exposure of hidden epitopes and subsequent immunogenicity, or a combination of both.",1
"Bromley, M, Bertfield, H, Evanson, J M, Woolley, D E",2
Walking activities and wear of prostheses.,0
"A study of the walking activities of 243 individuals was carried out. The individuals came from four different occupations and had an age range of 17-83 years. The survey carried out in this investigation showed surprisingly little correlation between variables such as age, height, and weight of individuals and their speed of walking, length of stride, or distance walked. Correlation matrices were obtained for the whole sample and then for each sex, showing similar trends. The most significant correlation was between the height of an individual and the length of the stride, and there was a lesser correlation between age and the number of steps walked by an individual per day. Further statistical analyses showed that males in manual occupations walked most and those in sedentary occupations walked least. On the other hand, in the female groups housewives seemed to walk least and those in technical occupations walked most. The average number of steps walked per day by a male individual for the whole sample was 9537; that for females was 9839. The corresponding distances walked per day were 6.7 and 6.5 km. The differences were not statistically significant. Predictions of wear of prosthetic components made of ultrahigh molecular weight polyethylene were made on the basis of the above data and other variables affecting wear, such as the weight of the subject and the area available for contact during walking. Charts have been constructed of the penetration of the metallic component into the plastic one for both hip knee prostheses, thus enabling predictions of the wear of the plastic components of these two most widely used prostheses. Owing to the wide ranging values of the variables used in making the predictions of wear, these latter should be regarded only as 'safe' first estimates.",1
"Seedhom, B B, Wallbridge, N C",2
Cytidine deaminase activity as a measure of acute inflammation in rheumatoid arthritis.,0
"Cytidine deaminase (CD), a cytoplasmic enzyme, is thought to leak out of damaged cells and can be measured in fluids by a simple biochemical assay. This study has shown that serum CD activity is raised in rheumatoid arthritis (RA) compared with osteoarthritis (OA). Synovial fluid (SF) CD activity was always less than the corresponding serum activity (mean SF/serum ratio = 0.6) in OA but up to 22 times greater than the corresponding serum activity in RA (mean SF/serum ratio = 13.1), suggesting CD production in inflammatory joints. Evidence to support the SF neutrophil as a cell of CD origin is provided by the CD gradient running from cells to SF to synovium. The close correlation between SF CD activity and neutrophil count (r = 0.93) indicates that SF CD activity is an accurate measure of acute synovial inflammation. Weak correlation of serum CD activity with erythrocyte sedimentation rate (ESR) (r = 0.44) and C-reactive protein (CRP) (r = 0.49) implies that CD estimations supply different though related information about rheumatoid disease activity. We suggest that CD released from damaged neutrophils diffuses from all inflamed joints into the blood, so that serum CD activity may provide an integrated measure of joint inflammation more specific than traditional measures such as the ESR.",1
"Thompson, P W, Jones, D D, Currey, H L",2
Rubella-associated arthritis. I. Comparative study of joint manifestations associated with natural rubella infection and RA 27/3 rubella immunisation.,0
"Joint manifestations observed during the course of a prospective RA 27/3 rubella immunisation trial were compared with those observed during an intercurrent wild rubella epidemic in an outlying community. Among 44 rubella haemagglutination inhibition (HAI) negative females ranging in age from 17 to 33 years who received rubella vaccine, six (13.6%) developed acute polyarticular arthritis within two to four weeks postvaccine and two (4.5%) had continuing or recurrent arthropathy lasting longer than 18 months. In contrast, among 23 females ranging in age from 11 to 39 years undergoing wild rubella infection, 12 (52.2%) developed acute polyarticular arthritis and seven (30.4%) had recurrent arthropathy 18 months postinfection. Among 23 males ranging in age from 13 to 54 years undergoing wild rubella infection, only two (8.7%) developed acute arthritis and both individuals had continuing joint manifestations 18 months postinfection. Wild rubella infection in adult populations is associated with a higher incidence, increased severity, and more prolonged duration of joint manifestations than is seen after RA 27/3 rubella immunisation.",1
"Tingle, A J, Allen, M, Petty, R E, Kettyls, G D, Chantler, J K",2
Thyroid disorders in systemic lupus erythematosus.,0
"Of 319 patients with systemic lupus erythematosus (SLE), nine had thyrotoxicosis, three had hypothyroidism, and two had thyroiditis. This prevalence seems greater than that of similar thyroid disorders seen in the general population. It is suggested that patients with autoimmune thyroid disorders may develop SLE or vice versa. This association requires confirmation by prospective study.",1
"Goh, K L, Wang, F",2
Amyloid deposits in the knee joint at autopsy.,0
"Joint capsule, meniscus, and cartilage from the patella and medial femoral condyle from 30 non-selected autopsies have been investigated for amyloid deposits with light and electron microscopy. Both right and left knee joints from 28 of the 30 autopsy specimens contained amyloid deposits (93%). The amyloid characteristically showed green dichroism in polarised light after staining with alkaline Congo red. The ultrastructural features were also characteristic of amyloid. Amyloid in capsule tissue was found in a subsynovial location, as well as deeper in the capsule tissue, while in the cartilage amyloid was localised along the surface. The meniscus tissue, in particular, contained heavy deposits of amyloid--mainly along the inner margin. Osteoarthritic changes, with fibrillation of the cartilage, were significantly related to amyloid deposition. No pathogenetic correlation between the osteoarthritic changes and amyloid deposition could be shown in the present investigation.",1
"Ladefoged, C",2
Immune complexes and the pathogenesis of neutropenia in Felty's syndrome.,0
"The effect of the injection of serum from patients with rheumatoid arthritis (RA) and Felty's syndrome (FS) into mice on the number of circulating polymorphonuclear cells (PMN) was studied. The number of circulating PMN dropped to 61% (range 34-98%) of the initial counts after the injection of FS serum. This phenomenon was observed less frequently after injection of RA serum. In contrast, injection of serum from healthy controls always resulted in an immediate increase in the number of circulating PMN. No decrease in PMN counts was found after injection of FS sera pretreated with polyethylene glycol to precipitate immune complexes (IC). Gel filtration of FS sera on Sepharose 4B showed that the effect on the PMN counts in mice did not coincide with the 7S peak but occurred only in fractions containing larger material. Serum fractions from FS patients that contained IC were more active in producing neutropenia than the corresponding fractions from patients with RA. Microscopic and immunohistochemical examination of the organs from mice injected with FS serum showed sequestration of PMN and deposition of human IgG, IgA, and IgM in the vascular bed of the lungs. These results indicate that the interaction between PMN and IC of patients with FS leads to sequestration of PMN in mice and suggests that this interaction in humans may have a role in the pathogenesis of FS.",1
"Breedveld, F C, Lafeber, G J, de Vries, E, van Krieken, J H, Cats, A",2
Scanning electron microscopy of rheumatoid arthritis peripheral blood polymorphonuclear leucocytes.,0
"Peripheral blood polymorphonuclear leucocytes (PMNs) were isolated from six normal individuals and from 27 patients with rheumatoid arthritis (RA) by the Ficoll-Hypaque rapid single step centrifugation technique, fixed in suspension, and examined by scanning electron microscopy (SEM). In addition, four of the preparations from normal individuals and eight from patients with RA were examined by transmission electron microscopy (TEM). Most PMNs in preparations from normal subjects were spherical, unpolarised, and had their surface membrane elaborated into irregular ridges and small ruffles; they contained few phagocytic vacuoles and large numbers of electron dense primary and secondary granules. A minority of the cells were non-spherical, polarised, and had portions of their surface membrane elaborated into ruffled pseudopodia. In contrast, preparations of RA PMNs frequently contained fewer unpolarised PMNs and a higher number of polarised PMNs than did preparations of normal PMNs. Some preparations of RA PMNs also contained substantial numbers of spherical cells whose surface was covered mainly by bulges and blebs. Concurrent examination by TEM showed that RA PMNs frequently contained more phagocytic vacuoles and fewer electron dense primary and secondary granules than normal PMNs. The morphological and ultrastructural changes seen in RA PMNs resembled those which normal PMNs are known to undergo on exposure to C5a in vitro, during adherence to endothelial cells in vivo, or during phagocytosis in vivo or in vitro. Our observations, therefore, provide a useful morphological correlation to those in vitro studies in which differences in the functional activity of RA and normal PMNs have been shown. The possibility that the difference seen between RA and normal PMNs is artefactual and does not represent the genuine in vivo states of these cells is discussed.",1
"McCarthy, D A, Holburn, C M, Pell, B K, Moore, S R, Kirk, A P, Perry, J D",2
"Measurement of the cross linking compound, pyridinoline, in urine as an index of collagen degradation in joint disease.",0
"An enzyme linked immunoassay (ELISA) for the collagen cross link, pyridinoline, has been developed using affinity purified antibodies, with a sensitivity down to about 0.1 ng of cross link. Measurements of urinary pyridinoline were made in patients with rheumatoid arthritis (RA), osteoarthritis (OA), and a control group showing no signs of joint disease. Expressed relative to creatinine values, pyridinoline was significantly increased in both RA and OA groups compared with controls: these differences were much larger than could be attributed to any age related effects or to changes in urinary creatinine concentrations. These findings were confirmed by analysis of a series of 24 h urine collections which showed that the total pyridinoline excretions were significantly higher in both RA and OA groups than in the controls. As pyridinoline is much more prevalent in cartilage than in bone collagen, measurement of this compound in urine may provide an index for monitoring the increased joint destruction that occurs in arthritic disease.",1
"Robins, S P, Stewart, P, Astbury, C, Bird, H A",2
Remarkably similar response to gold therapy in HLA identical sibs with rheumatoid arthritis.,0
"Two pairs of sibs with definite rheumatoid arthritis responded in a remarkably similar way to parenteral gold therapy, in terms of both toxicity and efficacy. Both pairs proved to be HLA identical. One of the pairs possessed the HLA antigens B8 and DR3, which have been associated with both drug toxicity and excellent clinical response. The other pair did not possess either of these antigens, suggesting that the reaction to gold therapy in patients with rheumatoid arthritis may be determined by other HLA or genetic factors coded for by chromosome 6, or both.",1
"van de Putte, L B, Speerstra, F, van Riel, P L, Boerbooms, A M, van't Pad Bosch, P J, Reekers, P",2
"Low dose intravenous 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD) for the treatment of Paget's disease of bone.",0
"Twenty patients with severe symptomatic Paget's disease were treated with a series of 15 mg intravenous infusions of 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (APD). A regimen of either five consecutive days of treatment (regimen 1) or a course of 12 weekly infusions was administered (regimen 2). In five cases regimen 2 followed regimen 1 after a three month interval. Alkaline phosphatase levels fell in all patients and returned to the normal range in 12. All but one of the patients obtained symptomatic improvement. There was a median fall in alkaline phosphatase activity of 63%. Eight patients observed a transient increase in bone pain starting about 24 hours after the first infusion. Intravenous APD was well tolerated, and we conclude that it is an effective treatment for Paget's disease; this route of administration avoids the problem of poor and unpredictable gastrointestinal absorption seen when a bisphosphonate is given orally. The optimal dose and duration of APD therapy, frequency of relapse, requirement for further courses, and merits relative to other second generation bisphosphonates remain to be established.",1
"Cantrill, J A, Buckler, H M, Anderson, D C",2
Anticardiolipin antibodies: isotype distribution and phospholipid specificity.,0
"Quantitative isotype specific enzyme linked immunosorbent assay (ELISA) was used to determine the distribution of immunoglobulin isotypes and phospholipid specificities of anticardiolipin (anti-CL) antibodies in 40 patients with one or more of the following 'antiphospholipid (anti-PL) antibody associated clinical complications'--namely, thrombosis, fetal loss, thrombocytopenia. Twelve of 40 patients had IgG, IgM, and IgA anti-CL antibodies. Ten patients had IgG and IgM, five patients had IgG and IgA, and three patients had IgM and IgA anti-CL antibodies. There was no statistical association between any single isotype or any group of isotypes with thrombosis, fetal loss, or thrombocytopenia. The presence of IgG anti-CL antibodies in 36 of the 40 patients suggests that this isotype may be most important in determining clinical complications, but there were four patients without IgG anti-CL antibodies who also appeared susceptible to thrombosis, fetal loss, and thrombocytopenia. IgG, IgM, and IgA anti-CL antibodies bound the negatively charged phospholipids, phosphatidylserine and phosphatidylinositol, but not the zwitterionic phospholipid, phosphatidylcholine. There was no significant difference between binding to cardiolipin and binding to other negatively charged phospholipids, suggesting that the specificity of these antibodies is for negatively charged phospholipids in general rather than for cardiolipin in particular.",1
"Gharavi, A E, Harris, E N, Asherson, R A, Hughes, G R",2
Depressed superoxide radical generation by neutrophils from patients with rheumatoid arthritis and neutropenia: correlation with neutrophil reactive IgG.,0
"Neutrophils of 31 patients with neutropenia and rheumatoid arthritis (RA) have been studied to assess their ability to generate superoxide radicals (O-2) on activation. Seventeen patients had classical Felty's syndrome and 14 presumed chrysotherapy related neutropenia. Results were compared with those from age and sex matched controls with uncomplicated RA and from normal subjects. Neutrophils from patients with Felty's syndrome had a significantly reduced ability to generate superoxide radicals when compared with the other three groups. In addition, serum levels of IgG polymorphonuclear leucocyte binding activity (IgG PBA) were also raised in the group with Felty's syndrome. A statistically significant inverse correlation existed between O-2 generation and IgG PBA. It is concluded that neutrophil reactive IgG may have an important role in both quantitative and qualitative defects in neutrophil function in Felty's syndrome.",1
"Davis, P, Johnston, C, Bertouch, J, Starkebaum, G",2
Assessment of disability caused by rheumatic diseases in general practice.,0
"At present general practitioners lack a tool for defining the level of disability of individual patients and groups of patients with arthritis. An assessment technique (health assessment questionnaire) developed in the United States is described, and its use in general practice evaluated. Sixty two patients agreed to be visited at home to compare their observed abilities when performing the tasks of the health assessment questionnaire. The health assessment questionnaire (HAQ) is easily understood and takes patients only 10-15 minutes to complete. The numerical scores (range 0-3) for disability obtained on the postal questionnaire are close to the observed scores when patients are visited at home.",1
"Sullivan, F M, Eagers, R C, Lynch, K, Barber, J H",2
Chronic predominant interstitial nephritis in a patient with systemic lupus erythematosus: a follow up of three years and review of the literature.,0
"Predominant interstitial nephritis is a rare manifestation of systemic lupus erythematosus. Only seven cases have been reported in the literature. Owing to the rarity of this entity, the natural history of predominant interstitial nephritis in lupus has not been adequately recorded and an appropriate therapeutic approach has yet to be defined. In this report we present the case of a 25 year old woman with active systemic lupus erythematosus complicated by kidney failure and renal tubular acidosis due to predominant interstitial nephritis. We describe the course of her disease over a three year period. Seven additional patients with systemic lupus erythematosus and predominant interstitial nephritis are reviewed.",1
"Gur, H, Kopolovic, Y, Gross, D J",2
Comparison of phenytoin and gold as second line drugs in rheumatoid arthritis.,0
"Phenytoin has known immunosuppressive properties, and a recent pilot study has indicated that it may have a second line effect in rheumatoid arthritis (RA). To evaluate this role 60 patients with active RA were randomly allocated to receive either oral phenytoin or intramuscular gold. The two treatment groups were comparable at the outset (Mann-Whitney U test). Twenty four patients completed 24 weeks of therapy in each group and no unexpected side effects were encountered. All variables except haemoglobin (Hb) improved significantly in the gold group while in the phenytoin group significant improvement was limited to articular index, erythrocyte sedimentation rate (ESR), and Hb. Between group comparison (Mann-Whitney) at week 24 showed a significant advantage of gold over phenytoin for pain score and morning stiffness. Thus phenytoin appears to exert a less potent second line effect than gold and is unusual in influencing laboratory indicators of disease activity more than clinical variables. This is likely to limit its usefulness as a second line drug in RA.",1
"Richards, I M, Fraser, S M, Hunter, J A, Capell, H A",2
Clinical and laboratory studies of inflammatory polyarthritis in patients with leprosy in Papua New Guinea.,0
The results of a combined clinical and laboratory study in 55 patients throughout the leprosy spectrum are reported. Thirty one of these patients suffered from an inflammatory peripheral polyarthritis which has not been previously described and which was unassociated with the characteristics of erythema nodosum leprosum reactions or with Charcot's joints. alpha 2 Macroglobulin was raised significantly only in those patients with leprosy and arthritis.,1
"Atkin, S L, Welbury, R R, Stanfield, E, Beavis, D, Iwais, B, Dick, W C",2
Antibody producing capacity to the bacteriophage phi X174 in rheumatoid arthritis.,0
"A study of antibody production in response to a primary immunogen, the bacteriophage phi X174, was performed in 27 patients with rheumatoid arthritis and 15 controls. All patients produced a primary (IgM) response to initial immunisation. The frequency distribution of peak antibody titres after secondary immunisation showed a marked difference between the patients and controls, with 10 patients having peak titres below 5000. The IgG component of the antibody response expressed as a percentage of total phage antibody on the 10th day after secondary immunisation was less in the patients than in the control group. There was no correlation between antibody titres and indices of disease activity, rheumatoid factor titres, or the presence of DRw4, DRw3, and DRw2. After secondary immunisation the patients with rheumatoid arthritis were treated with D-penicillamine, azathioprine, levamisole, or maintained on a non-steroidal anti-inflammatory drug. Assessment of response to tertiary immunisation again showed an impairment of antibody production in the rheumatoid group receiving non-steroidal anti-inflammatory drugs compared with the controls. None of the drugs, D-penicillamine, azathioprine, or levamisole, produced further suppression or augmentation of antibody production in response to the immunogen.",1
"Bucknall, R, Bacon, P, Elson, C, Jones, J V",2
Conditioned medium from stimulated mononuclear leucocytes potentiates the ability of human neutrophils to damage human articular cartilage.,0
Human neutrophils were able to degrade proteoglycan and inhibit its synthesis when incubated with human articular cartilage coated with heat aggregated immunoglobulin G. These effects were potentiated when culture medium conditioned by mononuclear leucocytes stimulated with killed Staphylococcus aureus was also present during the incubations. Neutrophils preincubated with this conditioned medium and washed before incubation with cartilage also showed an increased ability to degrade proteoglycan and inhibit its synthesis. The percentage of neutrophils binding to cartilage was significantly increased in the presence of this conditioned medium.,1
"Bates, E J, Kowanko, I C, Ferrante, A",2
Circulating inhibitor bound elastase in patients with ankylosing spondylitis and rheumatoid arthritis and the influence of sulphasalazine treatment.,0
"The plasma concentration of granulocyte elastase in complex with alpha 1 proteinase inhibitor was determined in 42 patients with ankylosing spondylitis (AS) and 33 patients with rheumatoid arthritis (RA). Significantly raised levels of plasma elastase were found in patients with RA, whereas patients with AS had normal values. No correlation was seen between the elastase values and erythrocyte sedimentation rate (ESR), serum haptoglobin, immunoglobulins, or polymorphonuclear cell (PMN) count in either of the patient groups. A correlation was found between the Ritchie index and plasma elastase in patients with RA. After three months' treatment with sulphasalazine a clinical improvement was seen and this paralleled a reduction of the acute phase reaction in both patient groups. A reduction of the circulating elastase values was seen in the patients with RA, whereas no change was seen in patients with AS.",1
"Feltelius, N, Hällgren, R",2
Effect of dietary restrictions on disease activity in rheumatoid arthritis.,0
"Additions in five steps were made, as a possible therapeutic measure, to the diet of 27 patients with rheumatoid arthritis (RA) after a period of two weeks of a basal isocaloric diet free from pulses, cereals, milk, and non-vegetarian protein foods. Fourteen patients finally took part in the trial, 10 (71%) of whom showed significant clinical improvement. Only three patients (11%) adhered to the diet for a period of 10 months. The others discontinued the diet and were then treated with conventional disease modifying drugs. The study indicates that dietary factors may influence inflammatory response in RA.",1
"Beri, D, Malaviya, A N, Shandilya, R, Singh, R R",2
Effects of altering dietary essential fatty acids on requirements for non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a double blind placebo controlled study.,0
"In rheumatoid arthritis (RA) benefit from non-steroidal anti-inflammatory drugs (NSAIDs) is mediated through inhibition of the cyclo-oxygenase enzyme, thereby decreasing production of the 2 series prostaglandins (PGs). The lipoxygenase enzyme is intact, however, allowing leucotriene (LT) production, e.g., LTB4 (an inflammatory mediator). Treatment with evening primrose oil (EPO) which contains gamma-linolenic acid (GLA) leads to production of the 1 series PGs, e.g., PGE1, which has less inflammatory effects. Also LT production is inhibited. Eicosapentaenoic acid (EPA, fish oil) treatment provides a substrate for PGs and LTs, which are also less inflammatory. In this study 16 patients with RA were given 540 mg GLA/day (EPO), 15 patients 240 mg EPA and 450 mg GLA/day (EPO/fish oil), and 18 patients an inert oil (placebo). The aim of this study was to determine if EPO or EPO/fish oil could replace NSAID treatment in RA. The initial 12 month treatment period was followed by three months of placebo for all groups. Results at 12 months showed a significant subjective improvement for EPO and EPO/fish oil compared with placebo. In addition, by 12 months the patients receiving EPO and EPO/fish oil had significantly reduced their NSAIDs. After 3 months of placebo those receiving active treatment had relapsed. Despite the decrease in NSAIDs, measures of disease activity did not worsen. It is suggested that EPO and EPO/fish oil produce a subjective improvement and allow some patients to reduce or stop treatment with NSAIDs. There is, however, no evidence that they act as disease modifying agents.",1
"Belch, J J, Ansell, D, Madhok, R, O'Dowd, A, Sturrock, R D",2
Bacterial endocarditis presenting as acute monoarthritis.,0
"The presentation of a pig farmer with acute arthritis of the shoulder, cardiac murmurs, and Streptococcus suis growing on blood cultures highlights one of the rheumatological presentations of bacterial endocarditis. The need for a thorough general medical examination together with synovial fluid and blood culture in patients with acute monarthritis is emphasised. The suggestion that acute arthritis related to endocarditis is in nature truly septic, rather than mediated by circulating immune complexes, is supported.",1
"Doube, A, Calin, A",2
Specificity of anti-Sm antibodies by ELISA for systemic lupus erythematosus: increased sensitivity of detection using purified peptide antigens.,0
"Sm antigen was purified by immunoaffinity chromatography using a murine monoclonal anti-Sm antibody and was confirmed to be free from contaminating polypeptides. This was then used to detect anti-Sm antibodies in patients' sera by enzyme linked immunosorbent assay (ELISA). Antibodies against Sm were detected in only 9/52 (17%) patients with systemic lupus erythematosus (SLE) by immunodiffusion, but 15/52 (29%) were positive for IgG anti-Sm antibodies by ELISA. The presence of anti-Sm antibodies remained disease specific despite the increase in sensitivity of this assay and validates its potential use for clinical application. There was no correlation between the presence of anti-Sm antibodies and any clinical features of SLE. In 23 renal biopsies a membranous component to the glomerulonephritis correlated with anti-Sm antibodies (p less than 0.05). Patients from West Africa, the Carribean Islands, and Asia had a higher prevalence of anti-Sm antibodies than the local Caucasian population.",1
"Field, M, Williams, D G, Charles, P, Maini, R N",2
Reaction of rheumatoid factors with IgG3 monoclonal anti-Rh(D) antibodies: more frequent reactivity to a monoclonal antibody of the Gm allotype G3m(5) in rheumatoid patients negative for G3m(5).,0
"Human monoclonal anti-Rh(D) antibodies of known IgG isotype and Gm allotype were bound to erythrocytes and then used as the target IgG antigens for rheumatoid factors (RFs) in a direct haemagglutination test. When serum samples from patients with rheumatoid arthritis (RA) were tested for RF specificity towards these IgG monoclonal anti-D antibodies the incidence and titre of reactivity towards an IgG3 monoclonal anti-D antibody was considerably greater than for a polyclonal anti-D antibody of the same Gm allotype, G3m(5). This difference was not explained by the amount of each anti-D antibody which bound to erythrocytes. Furthermore, when patients with RA were divided into groups according to their Gm phenotype, sera from a greater proportion of patients negative for the phenotype G3m(5) reacted to the G3m(5) monoclonal anti-D antibodies than sera from those patients positive for this allotype. Analysis of RF reactivities towards two IgG3 and three IgG1 monoclonal anti-D antibodies, each with different Gm allotypic epitopes, indicated, however, that individual serum samples contained RFs with a spectrum of specificities; some sera appeared to react to a single set of Gm alleles, whereas others also reacted to isotypic or iso-allotypic epitopes, or both. Our data suggest that RFs with specificity for Gm allotypes do not arise in patients who carry that particular allotype owing to tolerance induced in fetal-neonatal life. Conversely, RFs with apparent specificity for a Gm allotype formed in patients negative for that allotype may be reacting to a closely related but different epitope. Final proof requires precise specificities for each RF formed, and IgG3 monoclonal anti-D antibodies would be useful reagents for this purpose.",1
"Puttick, A H, Williamson, E A, Merry, A H, Kumpel, B M, Thompson, K M, Jones, V E",2
Adverse reproductive outcomes in women who subsequently develop rheumatoid arthritis.,0
"The rates of adverse reproductive outcomes in 40 women with rheumatoid arthritis (RA) were compared with 67 of their unaffected female relatives. All women were aged between 35 and 65 years at the time of inquiry. Seven of the women with RA reported a perinatal death (six stillbirths, one early neonatal death) compared with one women in the unaffected group: estimated age adjusted relative risk (R) = 12.4, 95% confidence interval (95% CI) 1.6-91.1. The rate of spontaneous abortions was, however, not significantly different between the two groups (R = 1.2, 95% CI 0.5-2.9). All the perinatal deaths occurred before clinical disease onset in the women with RA. It is possible that in these two groups of women with a similar genetic background perinatal loss may be related, at least in part, to disease expression.",1
"Silman, A J, Roman, E, Beral, V, Brown, A",2
Ankylosing spondylitis without B27: no evidence for gene conversion.,0
Isoelectric focusing gel electrophoresis was used to look for variant HLA molecules in five patients with HLA-B27 negative ankylosing spondylitis (AS). The isoelectric points of the HLA-A and B antigens from these patients and HLA paired controls were identical. This implies that the HLA-A and B antigens from the patients with AS and the controls are similar. Gene conversion of a nucleotide sequence from a B27 positive gene is thus unlikely to be the explanation for the existence of AS in patients who are HLA-B27 negative by alloantisera typing.,1
"Pease, C T, Ellis, S A, McMichael, A J, Brewerton, D A",2
Immunoglobulin A in the skin of patients with ankylosing spondylitis.,0
"Cutaneous immunofluorescence studies were carried out in 21 patients with ankylosing spondylitis (AS) and the results compared with those for 18 healthy subjects. The most prominent finding was the presence of IgA in dermal vessels of patients with AS (71% compared with 17% of the control group). IgG and IgM cutaneous deposits were also observed in patients with AS, but these results did not differ from those of the control group. A renal biopsy was performed in three of the patients presenting with unexplained microscopic haematuria. One of them had an IgA nephropathy, but no correlation was found between kidney and skin deposits of IgA. These findings suggest that IgA cutaneous deposits in AS are not a marker of IgA nephropathy but stress the role of immunoglobulin A in the pathogenesis of this disease.",1
"Collado, A, Sanmarti, R, Bielsa, I, Castel, T, Kanterewicz, E, Cañete, J D, Brancós, M A, Rotes-Querol, J",2
Relapsing polychondritis mimicking rheumatoid arthritis.,0
A woman with relapsing polychondritis presented with progressive and deforming polyarthritis (but always negative for rheumatoid factor) 14 years before the appearance of typical clinical and histological changes of nasal and auricular cartilage destruction.,1
"Schlapbach, P, Gerber, N J, Ramser, P, van't Hooft, F M",2
Steroid resistant pleural effusion in systemic lupus erythematosus treated with tetracycline pleurodesis.,0
A 26 year old woman had recurrent unilateral pleural effusions secondary to active systemic lupus erythematosus. The effusions were resistant to conventional treatment with steroids but did not recur after tetracycline pleurodesis.,1
"Gilleece, M H, Evans, C C, Bucknall, R C",2
Factors predicting a poor life prognosis in rheumatoid arthritis: an eight year prospective study.,0
"This prospective study evaluates the usefulness of clinical features and measurements of circulating immune complexes and autoantibodies for identification of patients with rheumatoid arthritis with a poor life prognosis. One hundred and seven hospital clinic patients, 64 with extra-articular manifestations, were followed up for a mean period of eight years, during which 50 deaths occurred. Comparison with an age and sex matched control population showed an increased incidence of deaths from myocardial infarction, pneumonia, and complications of rheumatoid arthritis. Patients with cutaneous ulcers, vasculitic rash, neuropathy, and scleritis had a higher mortality than patients whose disease was confined to the joints. Positive serological tests for precipitating antibodies to soluble cellular antigens and cryoglobulinaemia also predicted a poor prognosis. Eleven out of 12 patients (92%) with antibodies to soluble cellular antigens died compared with 21 out of 64 patients (33%) without antibodies. The presence of cryoglobulinaemia was associated with almost a twofold higher mortality. The laboratory measurements may reflect immunopathogenic mechanisms which lead to the occurrence of extra-articular disease features and reduce life expectancy.",1
"Erhardt, C C, Mumford, P A, Venables, P J, Maini, R N",2
Rheumatoid arthritis in blacks in South Africa.,0
"The spectrum of rheumatoid arthritis (RA) was studied in a group of 52 blacks who attended a rheumatology unit in Cape Town, South Africa. The mean age of the patients was 44.6 years, and the female to male ratio was 3.7:1. Significant radiographic changes were frequently noted, and the mean Larsen scores were 34.9 for the hands, 19.6 for the feet, and 6.6 for the wrists. About two thirds of the patients had received an immunomodulatory drug and 20 (38%) had had one or more surgical procedures for their RA. Anaemia was the commonest extra-articular manifestation, and although the other extra-articular features were uncommon, a variety of features had been detected during the course of the disease. Earlier studies on blacks in Africa suggested that RA was a mild disease; our findings, however, are in agreement with the more recent surveys, which suggest that severe disease is not uncommon.",1
"Mody, G M, Meyers, O L",2
Skeletal brucellosis in Iraqi patients.,0
"The clinical features of 21 episodes of skeletal brucellosis in 17 Iraqi patients are reported. Six had monarthritis of a large joint, six had spondylitis, and five had spondarthritis. Brucellosis remains a major health problem in Iraq. The disease is transmitted to man through the ingestion of unpasteurised milk or milk products but can also be acquired through physical contact.",1
"al-Rawi, T I, Thewaini, A J, Shawket, A R, Ahmed, G M",2
"Serum IgA, acute phase proteins, and glycosylation of alpha 1-acid glycoprotein in ankylosing spondylitis.",0
"Several investigators have suggested that gastrointestinal inflammation has a role in the pathogenesis of ankylosing spondylitis. To test this hypothesis markers of gastrointestinal immunostimulation, as manifested by serum IgA concentrations, were compared with serum markers of inflammation, as manifested by acute phase proteins. Serum samples from 45 unrelated Caucasian patients with ankylosing spondylitis (AS) were tested for correlation of serum IgA and six acute phase proteins: C reactive protein (CRP), alpha 1-antitrypsin, alpha 1-antichymotrypsin, caeruloplasmin, alpha 1-acid glycoprotein (AGP), and haptoglobin. Serum IgA was shown to be significantly positively correlated with four of these six acute phase proteins: CRP (r = 0.58, p less than 0.001), alpha 1-antitrypsin (r = 0.29, p less than 0.05), AGP (r = 0.61, p less than 0.01), and haptoglobin (r = 0.58, p less than 0.001), suggesting that gastrointestinal immunostimulation does have a role in the pathogenesis of inflammation in AS. In addition, the microheterogeneity of the pattern of glycosylation of AGP, expressed as reactivity coefficients, was examined. The AGP reactivity coefficient has been shown to increase in infection, remain the same in systemic lupus erythematosus, and decrease in rheumatoid arthritis. It was found that the AGP reactivity coefficient was significantly decreased in patients with AS as compared with healthy controls (p less than 0.006). As recent studies have indicated that patterns of glycosylation reflect intrahepatocellular biosynthetic processes induced by cytokines our data suggest that cytokine-hepatocellular mechanisms in AS may be similar to those occurring in rheumatoid arthritis, but different from those in systemic lupus erythematosus or infection.",1
"Mackiewicz, A, Khan, M A, Reynolds, T L, van der Linden, S, Kushner, I",2
"Seronegative rheumatoid arthritis, rheumatoid factor cross reactive idiotype expression, and hidden rheumatoid factors.",0
"The major rheumatoid factor cross reactive idiotype (RCRI), defined by prototypic monoclonal rheumatoid factors (RFs), is expressed as a dominant idiotype by pokeweed mitogen induced plasma cells obtained from seropositive (RF+) patients with rheumatoid arthritis (RA). Some patients who meet clinical diagnostic criteria for RA set by the American Rheumatism Association fail to express RFs at any time during their clinical course. To determine if seronegative (RF-) patients with RA, so designated by the latex fixation, Rose-Waaler classic binding assays, or a RF enzyme linked immunosorbent assay (ELISA), express the RCRI in the absence of detectable RFs we examined pokeweed mitogen plasma cells from these patients by indirect immunofluorescence. In addition, we used an inhibition ELISA to detect RCRI bearing molecules in the sera of RF- patients with RA. Five of 10 RF- patients with RA had a high prevalence of RCRI+ plasma cells (16-49% of total pokeweed mitogen plasma cells in culture). Six of 20 RF- patients with RA had high serum concentrations of molecules marked by the RCRI, equivalent to 21-110 micrograms/ml of RCRI+ reference monoclonal IgM RF. Four of five patients who expressed the RCRI in high prevalence in pokeweed mitogen plasma cells, also demonstrated high concentrations of RCRI in their sera detected by inhibition ELISA. There was significant concordance of RCRI expression determined by the two different assays. Four RF- patients with RA who expressed RCRI in their whole sera had hidden RFs detected in their 19S and, in one case, 7S serum fraction. Detection of RF related molecules in whole sera by the expression of RCRI in RF- patients with RA identifies a subgroup of RF- patients with RA who possess hidden RFs. Some RF- patients with RA can express the major RCRI in pokeweed mitogen plasma cells and in their sera and therefore are related to patients with prototypic Waldenstrom's macroglobulinaemia, who produce RCRI+ 19S IgM monoclonal RFs.",1
"Bonagura, V R, Wedgwood, J F, Agostino, N, Hatam, L, Mendez, L, Jaffe, I, Pernis, B",2
Upper limb pyrophosphate tenosynovitis outside the carpal tunnel.,0
Three cases of calcium pyrophosphate dihydrate (CPPD) crystal deposits in tendon sheaths outside the carpal tunnel are reported. Crystals were shown by x ray diffraction analysis in one case and by compensated light microscopy in the other two. Surgical excision of the tendon synovial sheath had to be done in two cases (one case with CPPD crystal deposits).,1
"Gerster, J C, Lagier, R",2
Behçet's syndrome: severe proctitis with rectovaginal fistula formation.,0
The development of severe proctitis and a rectovaginal fistula two months after the onset of Behçet's syndrome in a 41 year old woman is reported.,1
"Teh, L S, Green, K A, O'Sullivan, M M, Morris, J S, Williams, B D",2
Fetal loss treatment in patients with antiphospholipid antibodies.,0
"A group of seven young women with antiphospholipid antibodies, histories of recurrent fetal loss, and no live births is reported. Two patients had systemic lupus erythematosus, and the other five fulfilled criteria for the primary antiphospholipid syndrome. A false Venereal Disease Research Laboratory (VDRL) test was present in four of the patients, three had a previous episode of arterial or venous thrombosis, or both, and two had thrombocytopenia. Prednisone and acetylsalicylic acid were given, and monthly controls of lupus anticoagulant activity were carried out. The dose of acetylsalicylic acid was fixed while the dose of steroids was adjusted according to the degree of lupus anticoagulant activity. A fetal survival was obtained in 7/9 (78%) of the pregnancies. Three of the newborn infants had transitory lupus anticoagulant activity. A search for antiphospholipid antibodies should be carried out in patients with otherwise unexplained fetal losses, falsely positive VDRL tests, thrombosis, or thrombocytopenia as the treatment of such patients with prednisone and acetylsalicylic acid is highly effective.",1
"Ordi, J, Barquinero, J, Vilardell, M, Jordana, R, Tolosa, C, Selva, A, Genover, E",2
Avidity of antibodies against released proteins of Yersinia spp: comparison of patients with or without reactive arthritis.,0
"The avidity of IgM, IgG, and IgA class antibodies against virulence plasmid encoded proteins of yersinia, so called released proteins (RPs), was studied in the serum samples of 22 patients with yersinia triggered reactive arthritis and 22 with uncomplicated yersiniosis. The avidity of anti-RP antibodies did not differ significantly between the patient groups, even though the total amount of IgA class anti-RP antibodies was significantly higher in patients with arthritis than in those with uncomplicated yersiniosis at the early stage of infection. Earlier results with whole bacterial extracts or lipopolysaccharide as the antigens have shown an increased avidity of IgA class anti-yersinia antibodies in patients with yersinia triggered reactive arthritis. This phenomenon was not observed in antibody response against RPs, and thus production of these proteins seems unimportant at later stages of infection for the yersinia organisms stimulating the persisting and maturing antibody response in the yersinia triggered reactive arthritis.",1
"Lahesmaa-Rantala, R, Heesemann, J, Lehtonen, O P, Granfors, K, Toivanen, A",2
Magnetic resonance imaging of the shoulder in patients with rheumatoid arthritis.,0
"To evaluate the ability of magnetic resonance imaging (MRI) to detect shoulder abnormalities 18 patients (36 shoulders) with rheumatoid arthritis (RA) and shoulder complaints were studied. Osseous abnormalities of the glenoid and humeral head were readily detected with MRI. The imaging planes used were not suitable for the evaluation of acromioclavicular joint involvement. Magnetic resonance imaging depicted soft tissue abnormalities that were not clearly visualised by plain film radiography, such as involvement of rotator cuff tendons and subacromial bursae, joint effusion, and muscular atrophy. Magnetic resonance imaging appears to be a sensitive method for evaluation of glenohumeral joint changes in patients with RA.",1
"Kieft, G J, Dijkmans, B A, Bloem, J L, Kroon, H M",2
Sulphur bath and mud pack treatment for rheumatoid arthritis at the Dead Sea area.,0
"Forty patients with classical or definite rheumatoid arthritis in a stage of active disease were treated for two weeks at a spa hotel. The patients were divided into four groups of 10. Group I was treated with daily mud packs, group II with daily hot sulphur baths, group III with a combination of mud packs and hot sulphur baths, and group IV served as a control group. The patients were assessed by a rheumatologist who was blinded to the treatment modalities. Statistically significant improvement for a period of up to three months was observed in the three treatment groups in most of the clinical indices. Improvement in the control group was minor in comparison and not statistically significant. No significant improvement was observed in any of the laboratory variables measured. Except for three mild cases of thermal reaction there were no side effects.",1
"Sukenik, S, Buskila, D, Neumann, L, Kleiner-Baumgarten, A, Zimlichman, S, Horowitz, J",2
Monocyte activation in early onset rheumatoid arthritis.,0
"Monocytes from peripheral blood and synovial fluid of patients with definite and classic rheumatoid arthritis spontaneously produced significantly greater amounts of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and interleukin-1 beta (IL-1 beta) than samples of peripheral blood from normal controls. Peripheral blood monocytes from patients with rheumatoid arthritis produced significantly greater amounts of PGE2 than control samples when stimulated with lipopolysaccharide. There were no significant differences in the spontaneous release of superoxide or N-acetyl-beta-D-glucosaminidase by peripheral blood monocytes between patients and healthy controls. Both stimulated and unstimulated peripheral blood monocytes from patients with definite or classic rheumatoid arthritis produced significantly greater amounts of PGE2 than samples from normal controls. This was true, regardless of the stage of disease and the presence or absence of roentgenological joint abnormalities. Amounts of N-acetyl-beta-D-glucosaminidase released by peripheral blood monocytes from patients correlated positively with the erythrocyte sedimentation rate (ESR) and negatively with duration of disease. Amounts of IL-1 beta and N-acetyl-beta-D-glucosaminidase released from the peripheral blood monocytes of patients who had had their disease for less than one year were significantly higher than those of normal controls. There were no significant correlations between the types of treatment and the amounts of PGE2, LTB4, IL-1 beta or N-acetyl-beta-D-glucosaminidase released by peripheral blood monocytes in patients with rheumatoid arthritis. The findings suggest that monocytes are activated in patients with rheumatoid arthritis both at the onset of disease and during its chronic phase, and that they produce large amounts of mediators which may have a role in the induction and extension of the inflammatory process which leads to tissue damage.",1
"Fujii, I, Shingu, M, Nobunaga, M",2
Cardiac tamponade in juvenile chronic arthritis: report of two cases and review of publications.,0
"Two cases of systemic juvenile chronic arthritis, complicated by cardiac tamponade and eight previously reported cases are described. The clinical features and radiological, electrocardiographic, and echocardiographic findings were similar for all cases. One patient in this series was treated with corticosteroids and underwent pericardiectomy, dying of sepsis 30 days after surgery. The other patient was also treated with corticosteroids, underwent pericardiocentesis and developed fatal ventricular tachycardia. Of the 10 cases, only six were successfully treated. Early diagnosis and appropriate treatment are essential for a favourable outcome.",1
"Goldenberg, J, Pessoa, A P, Roizenblatt, S, Pávoa, R M, Hilário, M O, Atra, E, Ferraz, M B",2
Effects of capsaicin on the metabolism of rheumatoid arthritis synoviocytes in vitro.,0
"The effects of capsaicin, the ingredient of hot pepper, on rheumatoid arthritis synoviocytes have been studied. Capsaicin was shown to have a direct action on the metabolism of synovial cells. Thus at 10(-6) mol/l and at higher doses DNA synthesis was restored to the control level. Capsaicin at both doses induced an increase in the synthesis of collagenase and at the lower concentration (10(-8) mol/l) only of prostaglandins. These results indicate that the different effects of capsaicin on cellular proliferation and on metabolic activities are dependent on dose. The responses seen in rheumatoid arthritis synoviocytes in vitro might not be mediated by tachykinins if the synovial tissue is still able to produce neuropeptides in the absence of neuronal afferents. These results suggest that capsaicin, in addition to its direct action on the afferent nervous fibres and the consequent release of tachykinins, may also have a direct action on the cells. The mechanisms by which capsaicin stimulates DNA synthesis and production of collagenase and prostaglandin E2, in a manner dependent on dose, remain to be determined.",1
"Matucci-Cerinic, M, Marabini, S, Jantsch, S, Cagnoni, M, Partsch, G",2
Significance of low molecular weight C1q in systemic lupus erythematosus.,0
"The significance of high serum concentrations of low molecular weight C1q (LMW-C1q) in patients with systemic lupus erythematosus (SLE) was studied. Concentrations of LMW-C1q were increased in SLE, but not in rheumatoid arthritis or acute poststreptococcal glomerulonephritis. Concentrations of LMW-C1q in SLE serum samples correlated with titres of anti-dsDNA and were inversely related to concentrations of normal C1q and C3. Serial studies in six patients, who had rising anti-dsDNA titres and who developed a major exacerbation requiring admission to hospital, showed that LMW-C1q increased in parallel with anti-dsDNA, reaching peak values of more than 2000% of normal just before or at the time of clinical relapse and decreasing during convalescence. Most marked increases in LMW-C1q were noted in the three patients in whom C1q concentrations remained normal, whereas increases were less in the three patients who had strongly depressed concentrations of normal C1q. A study of C1q biosynthesis by macrophages cultured from patients with SLE and high serum concentrations of LMW-C1q did not show impaired secretion of normal C1q in favour of LMW-C1q, but indicated that serum concentrations of LMW-C1q may reflect the synthetic rate of C1q in vivo. The results show that increased serum concentrations of LMW-C1q may be helpful in diagnosing SLE and suggest that serial determination of LMW-C1q in serum may have predictive value in monitoring patients with SLE.",1
"Hoekzema, R, Swaak, A J, Brouwer, M C, van Rooijen, A, Nieuwenhuys, E J, Hack, C E",2
Munchausen's syndrome simulating reflex sympathetic dystrophy.,0
"A 15 year old girl who had pain, oedema of her left hand, and fever of four months' duration is described. Marked demineralisation of her hand was shown by radiography, and increased articular uptake by technetium-99m bone scan. All these changes were indistinguishable from reflex sympathetic dystrophy. After two admissions to hospital and multiple explorations we discovered that she had induced her symptoms herself and a diagnosis of Munchausen's syndrome was made. As far as we know this presentation has not been previously reported and might help to explain the physiopathology of some signs of reflex sympathetic dystrophy.",1
"Rodriguez-Moreno, J, Ruiz-Martin, J M, Mateo-Soria, L, Rozadilla, A, Roig-Escofet, D",2
Magnetic resonance imaging in osteoarthritis of the knee: correlation with radiographic and scintigraphic findings.,0
"Twelve knees with a range of severity of knee osteoarthritis were assessed by magnetic resonance imaging (MRI) and technetium-99m labelled hydroxymethylene diphosphonate scintigraphy. Five magnetic resonance pulse sequences were evaluated. Proton density (TR = 1000, TE = 26 ms) and STIR (TR = 1500, TI = 100, TE = 30 ms) were chosen for further use. Abnormalities shown by MRI included joint effusions, meniscal disruption, hyaline cartilage thinning, subchondral signal changes, pseudocysts, and heterogeneity of signal from osteophytes. Certain MRI and scintigraphic appearances correlated: (a) 'hyperintense osteophytosis' and ipsilateral 'tramline' scintigraphic uptake, suggesting increased fat content in 'active' osteophytes; (b) subchondral signal change and 'extended' pattern, possibly reflecting inflammation, synovial leak, or fibrovascular repair; (c) patellofemoral joint signal changes and patellar isotope uptake.",1
"McAlindon, T E, Watt, I, McCrae, F, Goddard, P, Dieppe, P A",2
Pattern of osteoarthritis in a West African teaching hospital.,0
"The study of the pattern of osteoarthritis in different populations may yield valuable aetiological clues and also allow subtypes to be defined. Over one year 252 osteoarthritic joints from 140 patients seen at a West African teaching hospital were prospectively reviewed. The knee was the joint most often affected. Hip and hand disease, as well as Heberden's nodes, were uncommon. Joint disease was predominantly monoarticular; no patient had three or more sites affected.",1
"Adebajo, A O",2
Muscle cramps in the calf as presenting symptom of sarcoidosis.,0
"A patient is described, who presented with pain in the calf due to a palpable nodule as the presenting symptom of sarcoidosis. The patient was treated with rest and diclofenac, followed by intralesional injections with triamcinolone hexacetonide and became free from pain.",1
"Janssen, M, Dijkmans, B A, Eulderink, F",2
Diagnostic value of synovial fluid microscopy: a reassessment and rationalisation.,0
"This study is in two parts. In the first synovial fluid from 1892 patients with 14 different arthropathies was examined microscopically. Crystals of different types were identified and the disease distribution of these and various cell types, including several not previously reported in synovial fluid, have been described. These features have been used to derive a series of microscopic diagnostic criteria for each arthropathy. The criteria have been used in the second part of the study to examine synovial fluids from 200 patients without knowledge of any clinical diagnosis. Cytological and clinical diagnoses were compared at the end of the study. Matching diagnoses were made in 71 (35.5%) and a short list of differential diagnoses (based on cytological criteria), which included the clinical diagnosis, was made in a further 43 (21.5%). Of the rest, 63 (31.5%) were correctly described as inflammatory or non-inflammatory and in five (2.5%) no diagnosis could be made. Only in seven cases (3.5%) was an inaccurate (false positive) cytological diagnosis made. The results indicate that synovial fluid microscopy is a potentially more important diagnostic screening test in rheumatological and orthopaedic practice than it would at first appear from published reports.",1
"Freemont, A J, Denton, J, Chuck, A, Holt, P J, Davies, M",2
Prevalence and distribution of osteoarthritis in a population from Georgian and early Victorian London.,0
"The prevalence of osteoarthritis was calculated in adult skeletons excavated from the crypt of Christ Church, Spitalfields in east London, which was used for burial between 1729 and 1869. Age and sex specific prevalences were also calculated for a subsample of the group for whom age and sex were accurately known from surviving coffin plates. Prevalences were slightly higher in men than in women, except for generalised osteoarthritis. The principal sites affected were the acromioclavicular joints, the facet joints of the spine, and the hands. Osteoarthritis of the large joints was relatively uncommon; osteoarthritis of the hip occurred in 4/360 (1.1%) of men and 10/346 (2.9%) of women and of the knee in 3/360 (0.8%) of men and 18/346 (5.2%) of women. This last difference was statistically significant. A comparison with modern data suggests that the prevalence of osteoarthritis at Spitalfields was lower than in the contemporary population, and some explanations for this apparent difference are considered.",1
"Waldron, H A",2
"Hypoxanthine, xanthine, and urate in synovial fluid from patients with inflammatory arthritides.",0
"As nucleotide catabolism increases during tissue injury the appearance of purine metabolites in inflamed synovial fluid might be of value in understanding the joint damage in inflammatory arthritides. In this study, therefore, synovial and plasma concentrations of hypoxanthine, xanthine, and urate in 16 patients with rheumatoid arthritis (three with psoriatic arthropathy) were analysed. It was found that their plasma concentrations of hypoxanthine were greater than those of a reference group of healthy subjects. The synovial fluid concentrations of hypoxanthine, xanthine, and urate were higher than corresponding concentrations in plasma. Positive correlations were found between the respective plasma and synovial fluid values of xanthine and urate. These findings indicate a local enhanced purine metabolism in inflamed joint tissue and diffusion of oxypurines from joint cavity to plasma. No relation was found between measured metabolites and disease duration, radiological joint findings, or synovial fluid cells. Except for a weak correlation between plasma urate and serum haptoglobin, measured purine metabolites were not related to laboratory measures of systemic inflammation.",1
"Gudbjörnsson, B, Zak, A, Niklasson, F, Hällgren, R",2
Comparative study of C reactive protein and serum amyloid A protein in experimental inflammation.,0
"The responses of C reactive protein, measured by radial immunodiffusion and radioimmunoassay, and serum amyloid A protein, measured by radial immunodiffusion, were compared in eight subjects with inflammation induced experimentally by intradermal injection of monosodium urate crystals. A significant increase in serum amyloid A was noted after a lag phase of eight hours, the increase in median concentration at 48 hours being about eightfold. A parallel but less marked increase was found in C reactive protein when measured by radioimmunoassay (fourfold increase in median concentration at 48 hours) after a small but significant decrease during the lag phase. The changes in C reactive protein remained within the reference range and were not detectable by radial immunodiffusion.",1
"Chambers, R E, Hutton, C W, Dieppe, P A, Whicher, J T",2
Neutrophil function in patients with primary Sjögren's syndrome: relation to infection propensity.,0
"The function of neutrophils was studied in 23 consecutive patients with primary Sjögren's syndrome and in 35 healthy controls. Nineteen patients (83%) had extraglandular symptoms and nine patients (39%) had recurrent bacterial infections. The patients had a marked reduction of neutrophil adherence, especially those with recurrent bacterial infections, and reduced opsonic activity of plasma. Increased random migration of isolated neutrophils was found in the patients with a propensity for bacterial infections. Chemotaxis and chemokinesis, phagocytosis, chemiluminescence production, and the intracellular neutrophil contents of lactoferrin and lysozyme were normal. The various aspects of neutrophil function tested in this study were not related to disease duration or to inflammatory disease activity. The impaired neutrophil adherence may play a part in the increased propensity for bacterial infections seen in patients with primary Sjögren's syndrome.",1
"Gudbjörnsson, B, Feltelius, N, Hällgren, R, Venge, P",2
Late complications after a Yersinia enterocolitica epidemic: a follow up study.,0
"Ninety four Finnish conscripts were affected by a Yersinia enterocolitica epidemic in 1973. Thirteen years later 75 men completed a questionnaire about their present health. One half had no health problems, and the most common complaints in the other subjects were musculoskeletal disorders. Sixteen men wanted to be re-examined. In three cases a chronic connective tissue disease was diagnosed. Two men had ankylosing spondylitis. The most notable results of this study were (a) the fairly low number of late complications, (b) the close correlation between complications and the HLA-B27 antigen, and (c) the correlation between raised yersinia antibody titres and the late complications. The nature of the primary causative agent may affect the development of late complications.",1
"Lindholm, H, Visakorpi, R",2
Systemic lupus erythematosus in the elderly: clinical and immunological characteristics.,0
"Systemic lupus erythematosus (SLE) predominantly affects young women in their 20s. In 40 out of 250 (16%) patients with SLE seen in our hospital disease onset occurred after the age of 50. The interval between the time of onset and diagnosis was five years in this older group compared with three years in the younger group. Arthritis, as a first symptom, was less common in the older onset group. During the follow up a lower incidence of arthritis, malar rash, photosensitivity, and nephropathy was found in the older onset group. In contrast, this group showed an increased incidence of myositis. High titres of anti-dsDNA tended to occur less often and the incidence of anti-Ro antibodies was lower in the older onset group. These features seem to distinguish patients with older onset SLE as a particular subset.",1
"Font, J, Pallarés, L, Cervera, R, López-Soto, A, Navarro, M, Bosch, X, Ingelmo, M",2
Serum soluble interleukin 2 receptor in systemic lupus erythematosus: effects of disease activity and infection.,0
"Serum soluble interleukin 2 receptor (sIL2R) was measured in patients with active and inactive systemic lupus erythematosus (SLE). The concentration of sIL2R was higher in inactive SLE than in normal controls and was significantly increased in active compared with inactive SLE. When patients with active SLE were followed up serially it was found that the sIL2R concentration fell when the disease became inactive. There was no statistically significant association between sIL2R and the grades of disease activity, however. In patients with either active or inactive SLE and infection the sIL2R concentration was much higher than in those without infection. Chronic infection (tuberculosis or candida) was associated with a much higher concentration of sIL2R than pyogenic or herpes zoster infection. The sIL2R concentration helps to distinguish infection in patients with SLE.",1
"Wong, K L, Wong, R P",2
Pneumococcal septic arthritis after splenectomy in Felty's syndrome.,0
"A patient with Felty's syndrome who developed bilateral knee septic arthritis and septicaemia due to Streptococcus pneumoniae is described. She had had a previous splenectomy for symptomatic thrombocytopenia, having received pneumococcal vaccine before the operation. Measurement of antibody to the 23 vaccine serotypes showed protective concentrations before infection to just two. The infecting serotype was not represented in the vaccine, but a vigorous antibody response to this serotype occurred. The patient also developed glomerulonephritis due to immune complex deposition.",1
"Brzeski, M, Smart, L, Baird, D, Jackson, R, Sturrock, R",2
Paraspinal muscle fibrosis: a specific pathological component in ankylosing spondylitis.,0
"The histological appearance of percutaneous superficial paraspinal muscle biopsy specimens from eight patients with ankylosing spondylitis was compared with that of biopsy specimens from 13 control patients with similar degrees of disability and spinal immobility due to severe, chronic mechanical back pain. In both groups marked type II muscle fibre atrophy was shown. Additionally, in patients with ankylosing spondylitis there were obvious increases in perifibre connective tissue in association with central migration of cell nuclei but without evidence of inflammation. Qualitative electromyography failed to show denervation changes in either group. Paraspinal muscle fibrosis, occurring over and above atrophic changes due to disuse, seems to be a specific pathological component of ankylosing spondylitis which may be of particular importance in early disease as it may contribute towards back stiffness and weakness.",1
"Cooper, R G, Freemont, A J, Fitzmaurice, R, Alani, S M, Jayson, M I",2
Localisation of xanthine oxidase to synovial endothelium.,0
"The presence of the xanthine oxidase enzyme system has been demonstrated in the rheumatoid synovium. This supplies a reactive oxygen species generating system to synovium that is subjected to hypoxic-reperfusion cycles (cf inflamed rheumatoid synovium). An antibody to bovine milk xanthine oxidase has been used to localise the enzyme by immunohistochemistry to synovial endothelium. This implicates the endothelial cell as playing a major part in exacerbations of synovitis, induced by radicals.",1
"Stevens, C R, Benboubetra, M, Harrison, R, Sahinoglu, T, Smith, E C, Blake, D R",2
Absence of autoimmunity to type II collagen in generalised nodal osteoarthritis.,0
"A cardinal feature of generalised nodal osteoarthritis is the loss of articular cartilage. To determine if autoimmunity to these cartilage collagens occurred, serum antibodies to native and denatured type II collagen were measured by enzyme linked immunosorbent assay (ELISA) in 96 patients (90 women, six men, aged 47-91 years) with generalised nodal osteoarthritis. Generalised nodal osteoarthritis was diagnosed by typical clinical and radiological features. Serum samples from 42 blood donors were assayed as controls. No significant difference was found between the patients with generalised nodal osteoarthritis and the controls. Furthermore, the 20 patients who were HLA-A1, B8 positive had similar antibody levels to the group as a whole. One woman patient with generalised nodal osteoarthritis (HLA-A1, B8 negative) had markedly increased antibody levels to native and denatured type II collagen in a pattern similar to that seen in patients with rheumatoid arthritis. This patient did not develop super added rheumatoid arthritis during a three year follow up period. Autoimmunity to type II collagen is therefore rare in generalised nodal osteoarthritis. A lack of collagen antibodies in a condition characterised by hyaline cartilage loss suggests that the presence of such antibodies in rheumatoid arthritis is more than a secondary event to joint damage.",1
"Clague, R B, Morgan, K, Collins, I, Pattrick, M, Doherty, M",2
"Cross reaction of antibodies to a glycine/alanine repeat sequence of Epstein-Barr virus nuclear antigen-1 with collagen, cytokeratin, and actin.",0
"P62 is a synthetic peptide which corresponds to the glycine/alanine repeat sequence of Epstein-Barr virus nuclear antigen-1. It is the main epitope recognised by anti-rheumatoid arthritis nuclear antigen antibodies. It was shown previously that anti-P62 antibodies were raised fourfold in patients with rheumatoid arthritis compared with controls. To examine the possibility that this increase was due to cross reactive autoantibodies binding to P62, anti-P62 antibodies from serum samples taken from 10 patients with rheumatoid arthritis and five healthy controls were purified by affinity chromatography. Immunoglobulin G anti-P62 antibodies purified from four of 10 serum samples from patients with rheumatoid arthritis also reacted with human epidermal keratin, denatured collagen type II and actin, but not with influenza antigens, as determined by enzyme linked immunosorbent assay (ELISA). Anti-P62 antibodies in serum samples from healthy controls and patients with rheumatoid arthritis reacted with epidermal keratin by immunoblotting. It is suggested that antibodies to the glycine/alanine repeat sequence of Epstein-Barr nuclear antigen-1 recognise homologous epitopes on keratin, actin, and collagen. It is also possible that molecular mimicry between a major epitope on the Epstein-Barr virus and several autoantigens might contribute to the breakdown of tolerance and autoimmunity in patients with rheumatoid arthritis.",1
"Baboonian, C, Venables, P J, Williams, D G, Williams, R O, Maini, R N",2
"Coexisting Pneumocystis carinii pneumonia, cytomegalovirus pneumonitis and salmonellosis in systemic lupus erythematosus.",0
"Infection with opportunistic organisms, either singly or in combination, is known to occur in immunocompromised patients. A patient with systemic lupus erythematosus who developed Pneumocystis carinii pneumonia, cytomegalovirus pneumonitis, and salmonellosis is reported. She responded to early treatment with intravenous trimethoprim-sulphamethoxazole (20 mg/kg).",1
"Leong, K H, Boey, M L, Feng, P H",2
Inhibitory effects of anticardiolipin antibodies on lymphocyte proliferation and neutrophil phagocytosis.,0
"Anticardiolipin antibodies purified from serum from patients with systemic lupus erythematosus (SLE) by cardiolipin micelles were studied for their effects on lymphocytes and neutrophils. At a concentration of 160 micrograms/ml they markedly suppressed the [3H]thymidine incorporation of mononuclear cells stimulated by phytohaemagglutinin (4.9 (SEM 1.9%) of the control) and pokeweed mitogen (26.7 (10.5%) of the control). In addition, anticardiolipin antibodies changed the cell cycle of phytohaemagglutinin stimulated lymphocytes such that the S and G2+M phases were significantly diminished (G0/G1 = 64.62%, S = 20.59%, G2+M = 14.78% in the presence of normal human IgG v G0/G1 = 86.07%, S = 10.32%, G2+M = 3.59% in the presence of anticardiolipin antibodies). The suppression of lymphocyte proliferation by anticardiolipin antibodies was shown not to be caused by an alteration of T cell subpopulations. However, the interleukin 2 receptors on the cell surface and the soluble interleukin 2 receptors in the supernatant of phytohaemagglutinin stimulated mononuclear cells were decreased in the presence of anticardiolipin antibodies. On the other hand, the phagocytic activity of neutrophils was 40% inhibited at a higher concentration of anticardiolipin antibodies (300 micrograms/ml) through suppression of C3b/C4b and Fc receptors on polymorphonuclear leucocytes. These results suggest that anticardiolipin antibodies exert inhibitory effects on both lymphocytes and phagocytes in addition to the coagulation cascade. These newly found activities of anticardiolipin antibodies were mediated by the non-specific membranotropic property of the antibodies.",1
"Yu, C L, Sun, K H, Tsai, C Y, Wang, S R",2
Exacerbation of rheumatoid arthritis in patients treated with methotrexate after administration of folinic acid.,0
"A double blind, placebo controlled trial examined the effects of folinic acid on the efficacy and toxicity of methotrexate in 27 patients with rheumatoid arthritis. Clinical and laboratory indices of disease activity worsened significantly in the 13 patients treated with folinic acid after four weeks of treatment, but not in the 14 patients treated with placebo. Exacerbation of rheumatoid arthritis led to withdrawal of the test drug in seven of the patients treated with folinic acid but in none of those treated with placebo. It is concluded that excerbation of rheumatoid arthritis is likely when folinic acid is given shortly after the weekly dose of methotrexate.",1
"Joyce, D A, Will, R K, Hoffman, D M, Laing, B, Blackbourn, S J",2
Clinical experience with pamidronate in the treatment of Paget's disease of bone.,0
"Bisphosphonates have been shown to be effective in treating the increased bone turnover associated with Paget's disease of bone. In this study two groups of patients were treated with pamidronate by intravenous infusion. In group 1 (n = 15) 30 mg of pamidronate was given once a week for six weeks. A subgroup (group 1A, n = 6) of more severely affected patients (pretreatment serum alkaline phosphatase (ALP) greater than 1000 U/l, normal range 80-280 U/l) received a further 60 mg weekly for three weeks. Group 2 (n = 24) received 45 mg of pamidronate every three months for one year. In both groups the level of ALP in serum samples decreased steadily throughout the year. In group 1 the level decreased to a mean value of 230 U/l (95% confidence interval 188-281) and in group 2 to 297 U/l (227-389). Four of the six patients in group 1A achieved normal ALP, whereas ALP remained at an increased level in all of the 10 patients in group 2 whose pretreatment ALP was greater than 1000 U/l, suggesting that a dose-response effect exists. The lowest hydroxyproline to creatinine ratios (normal ratio less than 0.033) were observed at the end of treatment in group 1, with a mean ratio of 0.022 (range 0.015-0.033) and at three months after the start of treatment in group 2 with a mean ratio of 0.029 (range 0.022-0.037). There was a significant decrease in the turnover of bone, as measured by whole body retention of radiolabelled bisphosphonate, from a mean of 49.3 to 41.0% (p less than 0.01). These data confirm that pamidronate is effective in the management of Paget's disease of bone. For patients with levels of ALP in serum samples of up to four times above the upper limit of the normal reference range, an effective and convenient regimen is 45 mg every three months for one year. For patients with higher levels of ALP higher doses may be more effective.",1
"Gallacher, S J, Boyce, B F, Patel, U, Jenkins, A, Ralston, S H, Boyle, I T",2
Survival of calcium pyrophosphate crystals in stored synovial fluids.,0
"Eleven synovial fluids containing calcium pyrophosphate dihydrate (CPPD) were examined repeatedly over an eight week period to assess whether storage conditions and duration influenced the number of crystals present. Aliquots of each fluid were stored at room temperature, 4 degrees C, and -70 degrees C. At -70 degrees C there was no change in crystal count after eight weeks' storage. At room temperature and 4 degrees C crystal counts declined slowly over the eight week period, though CPPD crystals were still readily apparent after eight weeks in 10/11 (4 degrees C) and 8/11 (room temperature) fluids. No change in crystal morphology was detected and, apart from one fluid kept at room temperature in which fungal hyphae were noted at six weeks, no new crystals were seen. Calcium pyrophosphate dihydrate crystals in synovial fluid can be maintained for prolonged periods by freezing.",1
"McGill, N W, Swan, A, Dieppe, P A",2
Treatment of polymyalgia rheumatica with intramuscular injections of depot methylprednisolone.,0
"Although the treatment of patients with polymyalgia rheumatica by corticosteroids given by mouth is effective, it is often accompanied by multiple side effects. Various studies have shown that the steroid related complications are proportional to the cumulative dose of steroids administered. In a prospective study of 16 patients with polymyalgia rheumatica the effects of regular intramuscular injections of methylprednisolone over 12 months were evaluated. Remission of disease was achieved with injections of 120 mg of methylprednisolone every three weeks for 12 weeks. Subsequent disease remission was maintained by monthly injections of methylprednisolone on a reducing schedule of dose. The treatment was efficacious, safe, well tolerated over one year, and showed no suppression of the hypothalamic pituitary adrenal axis at 12 weeks after initiation of treatment. Such a mode of steroid treatment results in a considerably lower cumulative steroid dose than with conventional doses of prednisolone given by mouth. These results will be further evaluated in a controlled trial using intramuscular injections of methylprednisolone and prednisolone given by mouth for the treatment of polymyalgia rheumatica.",1
"Dasgupta, B, Gray, J, Fernandes, L, Olliff, C",2
Coexistent Felty's syndrome and palindromic rheumatism.,0
"Palindromic rheumatism is a syndrome of intermittent abrupt onset monoarthritis with asymptomatic intercritical periods of variable duration, which commonly evolves into rheumatoid arthritis. Felty's syndrome consists of leucopenia (selective neutropenia) and splenomegaly, usually occurring in longstanding classic rheumatoid arthritis. Felty's syndrome can be confused with the more recently recognised rheumatoid arthritis associated large granular lymphocyte proliferative disease. This paper describes a patient with palindromic rheumatism presenting with Felty's syndrome in whom large granular lymphocyte proliferative disease was ruled out by lymphocyte phenotyping.",1
"Alvillar, R E, O'Grady, L, Robbins, D",2
Bronchiolitis obliterans in systemic lupus erythematosus: beneficial effect of intravenous cyclophosphamide.,0
"A 49 year old white woman with systemic lupus erythematosus and bronchiolitis obliterans was treated with prednisone (1 mg/kg daily), which led to a transitory improvement in pulmonary status. Cyclophosphamide was then added--4 mg/kg daily intravenously for five days, then 2 mg/kg daily orally--and this was followed by a dramatic and prolonged improvement.",1
"Godeau, B, Cormier, C, Menkes, C J",2
Two gamma interferon-activated site-like elements in the human cytomegalovirus major immediate-early promoter/enhancer are important for viral replication.,0
"Human cytomegalovirus (HCMV) infection directly initiates a signal transduction pathway that leads to activation of a large number of cellular interferon-stimulated genes (ISGs). Our previous studies demonstrated that two interferon response elements, the interferon-stimulated response element and gamma interferon-activated site (GAS), in the ISG promoters serve as HCMV response sites (VRS). Interestingly, two GAS-like VRS elements (VRS1) were also present in the HCMV major immediate-early promoter-enhancer (MIEP/E). In this study, the importance of these VRS elements in viral replication was investigated. We demonstrate that the expression of the major IE genes, IE1 and IE2, is interferon inducible. To understand the biological significance of this signal transduction pathway in HCMV major IE expression, the two VRS1 in the MIEP/E were mutated. Mutant HCMVs in which the VRS elements were deleted or that contained point mutations grew dramatically more slowly than wild-type virus at a low multiplicity of infection (MOI). Insertion of wild-type VRS1 into the mutant viral genome rescued the slow growth phenotype. Furthermore, the expression levels of major IE RNAs and proteins were greatly reduced during infection with the VRS mutants at a low MOI. HCMV microarray analysis indicated that infection of host cells with the VRS mutant virus resulted in a global reduction in the expression of viral genes. Collectively, these data demonstrate that the two VRS elements in the MIEP/E are necessary for efficient viral gene expression and replication. This study suggests that although the HCMV-initiated signal transduction pathway results in induction of cellular antiviral genes, it also functions to stimulate viral major IE gene expression. This might be a new viral strategy in which the pathway is used to regulate gene expression and play a role in reactivation.",1
"Netterwald, James, Yang, Shaojun, Wang, Weijia, Ghanny, Salena, Cody, Michael, Soteropoulos, Patricia, Tian, Bin, Dunn, Walter, Liu, Fenyong, Zhu, Hua",2
The p92 polymerase coding region contains an internal RNA element required at an early step in Tombusvirus genome replication.,0
"The replication of positive-strand RNA viral genomes involves various cis-acting RNA sequences. Generally, regulatory RNA sequences are present at or near genomic termini; however, internal replication elements (IREs) also exist. Here we report the structural and functional characterization of an IRE present in the readthrough portion of the p92 polymerase gene of Tomato bushy stunt virus. Analysis of this element in the context of a noncoding defective interfering RNA revealed a functional core structure composed of two noncontiguous segments of sequence that interact with each other to form an extended helical conformation. IRE activity required maintenance of several base-paired sections as well as two distinct structural features: (i) a short, highly conserved segment that can potentially form two different and mutually exclusive structures and (ii) an internal loop that contains a critical CC mismatch. The IRE was also shown to play an essential role within the context of the viral genome. In vivo analysis with novel RNA-based temperature-sensitive genomic mutants and translationally active subgenomic viral replicons revealed the following about the IRE: (i) it is active in the positive strand, (ii) it is dispensable late in the viral RNA replication process, and (iii) it is functionally inhibited by active translation over its sequence. Together, these results suggest that IRE activity is required in the cytosol at an early step in the viral replication process, such as template recruitment and/or replicase complex assembly.",1
"Monkewich, Sandra, Lin, Han-Xin, Fabian, Marc R, Xu, Wei, Na, Hong, Ray, Debashish, Chernysheva, Olena A, Nagy, Peter D, White, K Andrew",2
Ex vivo stimulation of B cells latently infected with gammaherpesvirus 68 triggers reactivation from latency.,0
"Murine gammaherpesvirus 68 (gammaHV68) infection of mice results in the establishment of a chronic infection, which is largely maintained through latent infection of B lymphocytes. Acute virus replication is almost entirely cleared by 2 weeks postinfection. Spontaneous reactivation of gammaHV68 from latently infected splenocytes upon ex vivo culture can readily be detected at the early stages of infection (e.g., day 16). However, by 6 weeks postinfection, very little spontaneous reactivation is detected upon explant into tissue culture. Here we report that stimulation of latently infected splenic B cells harvested at late times postinfection with cross-linking surface immunoglobulin (Ig), in conjunction with anti-CD40 antibody treatment, triggers virus reactivation. As expected, this treatment resulted in B-cell activation, as assessed by upregulation of CD69 on B cells, and ultimately B-cell proliferation. Since anti-Ig/anti-CD40 stimulation resulted in splenic B-cell proliferation, we assessed whether this reactivation stimulus could overcome the previously characterized defect in virus reactivation of a v-cyclin null gammaHV68 mutant. This analysis demonstrated that anti-Ig/anti-CD40 stimulation could drive reactivation of the v-cyclin null mutant virus in latently infected splenocytes, but not to the levels observed with wild-type gammaHV68. Thus, there appears to be a role for the v-cyclin in B cells following anti-Ig/anti-CD40 stimulation independent of the induction of the cell cycle. Finally, to assess signals that are not mediated through the B-cell receptor, we demonstrate that addition of lipopolysaccharide to explanted splenocyte cultures also enhanced virus reactivation. These studies complement and extend previous analyses of Epstein-Barr virus and Kaposi's sarcoma-associated virus reactivation from latently infected cell lines by investigating reactivation of gammaHV68 from latently infected primary B cells recovered from infected hosts.",1
"Moser, Janice M, Upton, Jason W, Gray, Kathleen S, Speck, Samuel H",2
Plateau levels of viremia correlate with the degree of CD4+-T-cell loss in simian immunodeficiency virus SIVagm-infected pigtailed macaques: variable pathogenicity of natural SIVagm isolates.,0
"Simian immunodeficiency virus from African green monkeys (SIVagm) results in asymptomatic infection in its natural host species. The virus is not inherently apathogenic, since infection of pigtailed (PT) macaques (Macaca nemestrina) with one isolate of SIVagm results in an immunodeficiency syndrome characterized by progressive CD4+-T-cell depletion and opportunistic infections. This virus was passaged once in a PT macaque and, thus, may not be entirely reflective of the virulence of the parental strain. The goal of the present study was to assess the pathogenicity of the PT-passaged isolate (SIVagm9063) and two primary SIVagm isolates in PT macaques, including the parental strain of the PT-passaged variant. Infection of macaques with any of the three isolates resulted in high levels of primary plasma viremia by 1 week after inoculation. Viremia was quickly controlled following infection with SIVagm155; these animals have maintained CD4+-T-cell subsets and remain healthy. The plateau levels among SIVagm90- and SIVagm9063-inoculated macaques varied widely from 100 to 1 million copies/ml of plasma. Three of four animals from each of these groups progressed to AIDS. Setpoint viremia and the degree of CD4+-T-cell loss at 6 months postinfection were not significantly different between macaques inoculated with SIVagm90 and SIVagm9063. However these parameters were significantly different in SIVagm155-inoculated macaques (P values of <0.01). Considering all the macaques, the degree of CD4+-T-cell loss by 6 months postinfection correlated with the plateau levels of viremia. Thus, similar to SIVsm/mac infection of macaques and human AIDS, viral load is an excellent prognostic indicator of disease course. The inherent pathogenicity of natural SIVagm isolates varies, but such natural isolates are capable of inducing AIDS in macaques without prior macaque passage.",1
"Goldstein, Simoy, Ourmanov, Ilnour, Brown, Charles R, Plishka, Ronald, Buckler-White, Alicia, Byrum, Russell, Hirsch, Vanessa M",2
Penetration of enveloped double-stranded RNA bacteriophages phi13 and phi6 into Pseudomonas syringae cells.,0
"Bacteriophages phi6 and phi13 are related enveloped double-stranded RNA viruses that infect gram-negative Pseudomonas syringae cells. phi6 uses a pilus as a receptor, and phi13 attaches to the host lipopolysaccharide. We compared the entry-related events of these two viruses, including receptor binding, envelope fusion, peptidoglycan penetration, and passage through the plasma membrane. The infection-related events are dependent on the multiplicity of infection in the case of phi13 but not with phi6. A temporal increase of host outer membrane permeability to lipophilic ions was observed from 1.5 to 4 min postinfection in both virus infections. This enhanced permeability period coincided with the fast dilution of octadecyl rhodamine B-labeled virus-associated lipid molecules. This result is in agreement with membrane fusion, and the presence of temporal virus-derived membrane patches on the outer membrane. Similar to phi6, phi13 contains a thermosensitive lytic enzyme involved in peptidoglycan penetration. The phage entry also caused a limited depolarization of the plasma membrane. Inhibition of host respiration considerably decreased the efficiency of irreversible virus binding and membrane fusion. An active role of cell energy metabolism in restoring the infection-induced defects in the cell envelope was also observed.",1
"Daugelavicius, Rimantas, Cvirkaite, Virginija, Gaidelyte, Ausra, Bakiene, Elena, Gabrenaite-Verkhovskaya, Rasa, Bamford, Dennis H",2
Role of the varicella-zoster virus gene product encoded by open reading frame 35 in viral replication in vitro and in differentiated human skin and T cells in vivo.,0
"Although genes related to varicella-zoster virus (VZV) open reading frame 35 (ORF35) are conserved in the herpesviruses, information about their contributions to viral replication and pathogenesis is limited. Using a VZV cosmid system, we deleted ORF35 to produce two null mutants, designated rOkaDelta35(#1) and rOkaDelta35(#2), and replaced ORF35 at a nonnative site, generating two rOkaDelta35/35@Avr mutants. ORF35 Flag-tagged recombinants were made by inserting ORF35-Flag at the nonnative Avr site as the only copy of ORF35, yielding rOkaDelta35/35Flag@Avr, or as a second copy, yielding rOka35Flag@Avr. Replication of rOkaDelta35 viruses was diminished in melanoma and Vero cells in a 6-day analysis of growth kinetics. Plaque sizes of rOkaDelta35 mutants were significantly smaller than those of rOka in melanoma cells. Infection of melanoma cells with rOkaDelta35 mutants was associated with disrupted cell fusion and polykaryocyte formation. The small plaque phenotype was not corrected by growth of rOkaDelta35 mutants in melanoma cells expressing the major VZV glycoprotein E, gE. The rOkaDelta35/35@Avr viruses displayed growth kinetics and plaque morphologies that were indistinguishable from those of rOka. Analysis with ORF35-Flag recombinants showed that the ORF35 gene product localized predominantly to the nuclei of infected cells. Evaluations in the SCIDhu mouse model demonstrated that ORF35 was required for efficient VZV infection of skin and T-cell xenografts, although the decrease in infectivity was most significant in skin. These mutagenesis experiments indicated that ORF35 was dispensable for VZV replication, but deleting ORF35 diminished growth in cultured cells and was associated with attenuated VZV infection of differentiated human skin and T cells in vivo.",1
"Ito, Hideki, Sommer, Marvin H, Zerboni, Leigh, Baiker, Armin, Sato, Bunji, Liang, Ruibin, Hay, John, Ruyechan, William, Arvin, Ann M",2
The cellular protein daxx interacts with avian sarcoma virus integrase and viral DNA to repress viral transcription.,0
"The cellular protein Daxx was identified as an interactor with avian sarcoma virus (ASV) integrase (IN) in a yeast two-hybrid screen. After infection, Daxx-IN interactions were detected by coimmunoprecipitation. An association between Daxx and viral DNA, likely mediated by IN, was also detected by chromatin immunoprecipitation. Daxx was not required for early events in ASV replication, including integration, as Daxx-null cells were transduced as efficiently as Daxx-expressing cells. However, viral reporter gene expression from ASV-based vectors was substantially higher in the Daxx-null cells than in Daxx-complemented cells. Consistent with this observation, histone deacetylases (HDACs) were found to associate with viral DNA in Daxx-complemented cells but not in Daxx-null cells. Furthermore, Daxx protein was induced in an interferon-like manner upon ASV infection. We conclude that Daxx interacts with an IN-viral DNA complex early after infection and may mediate the repression of viral gene expression via the recruitment of HDACs. Our findings provide a novel example of cellular immunity against viral replication in which viral transcription is repressed via the recruitment of antiviral proteins to the viral DNA.",1
"Greger, James G, Katz, Richard A, Ishov, Alexander M, Maul, Gerd G, Skalka, Anna Marie",2
Human immunodeficiency virus (HIV) gp41 escape mutants: cross-resistance to peptide inhibitors of HIV fusion and altered receptor activation of gp120.,0
"Human immunodeficiency virus (HIV) infects cells by fusing with cellular membranes. Fusion occurs when the envelope glycoprotein (Env) undergoes conformational changes while binding to cellular receptors. Fusogenic changes involve assembly of two heptad repeats in the ectodomain of the gp41 transmembrane subunit to form a six-helix bundle (6HB), consisting of a trimeric N heptad repeat (N-HR) coiled-coil core with three antiparallel C heptad repeats (C-HRs) that pack in the coiled-coil grooves. Peptides corresponding to the N-and C-HRs (N and C peptides, respectively) interfere with formation of the 6HB in a dominant-negative manner and are emerging as a new class of antiretroviral therapeutics for treating HIV infection. We generated an escape mutant virus with resistance to an N peptide and show that early resistance involved two mutations, one each in the N- and C-HRs. The mutations conferred resistance not only to the selecting N peptide but also to C peptides, as well as other types of N-peptide inhibitors. Moreover, the N-HR mutation altered sensitivity to soluble CD4. Biophysical studies suggest that the 6HB with the resistance mutations is more stable than the wild-type 6HB and the 6HB formed by inhibitor binding to either wild-type or mutant C-HR. These findings provide new insights into potential mechanisms of resistance to HIV peptide fusion inhibitors and dominant-negative inhibitors in general. The results are discussed in the context of current models of Env-mediated membrane fusion.",1
"Desmezieres, Emmanuel, Gupta, Nidhi, Vassell, Russell, He, Yong, Peden, Keith, Sirota, Lev, Yang, Zhongning, Wingfield, Paul, Weiss, Carol D",2
"Enfuvirtide resistance mutations: impact on human immunodeficiency virus envelope function, entry inhibitor sensitivity, and virus neutralization.",0
"Enfuvirtide (ENF/T-20/Fuzeon), the first human immunodeficiency virus (HIV) entry inhibitor to be licensed, targets a structural intermediate of the entry process. ENF binds the HR1 domain in gp41 after Env has bound CD4, preventing conformational changes needed for membrane fusion. Mutations in HR1 that confer ENF resistance can arise following ENF therapy. ENF resistance mutations were introduced into an R5- and X4-tropic Env to examine their impact on fusion, infection, and sensitivity to different classes of entry inhibitors and neutralizing antibodies. HR1 mutations could reduce infection and fusion efficiency and also delay fusion kinetics, likely accounting for their negative impact on viral fitness. HR1 mutations had minimal effect on virus sensitivity to other classes of entry inhibitors, including those targeting CD4 binding (BMS-806 and a CD4-specific monoclonal antibody [MAb]), coreceptor binding (CXCR4 inhibitor AMD3100 and CCR5 inhibitor TAK-779), or fusion (T-1249), indicating that ENF-resistant viruses can remain sensitive to other entry inhibitors in vivo. Some HR1 mutations conferred increased sensitivity to a subset of neutralizing MAbs that likely target fusion intermediates or with epitopes preferentially exposed following receptor interactions (17b, 48D, 2F5, 4E10, and IgGb12), as well as sera from some HIV-positive individuals. Mechanistically, enhanced neutralization correlated with reduced fusion kinetics, indicating that, in addition to steric constraints, kinetics may also limit virus neutralization by some antibodies. Therefore, escape from ENF comes at a cost to viral fitness and may confer enhanced sensitivity to humoral immunity due to prolonged exposure of epitopes that are not readily accessible in the native Env trimer. Resistance to other entry inhibitors was not observed.",1
"Reeves, Jacqueline D, Lee, Fang-Hua, Miamidian, John L, Jabara, Cassandra B, Juntilla, Marisa M, Doms, Robert W",2
Association of ebola virus matrix protein VP40 with microtubules.,0
"Viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear that use of host cell microtubules is a vital part of the infection process for many viruses. A variety of viral proteins have been identified that interact with microtubules, either directly or via a microtubule-associated motor protein. Here, we report that Ebola virus associates with microtubules via the matrix protein VP40. When transfected into mammalian cells, a fraction of VP40 colocalized with microtubule bundles and VP40 coimmunoprecipitated with tubulin. The degree of colocalization and microtubule bundling in cells was markedly intensified by truncation of the C terminus to a length of 317 amino acids. Further truncation to 308 or fewer amino acids abolished the association with microtubules. Both the full-length and the 317-amino-acid truncation mutant stabilized microtubules against depolymerization with nocodazole. Direct physical interaction between purified VP40 and tubulin proteins was demonstrated in vitro. A region of moderate homology to the tubulin binding motif of the microtubule-associated protein MAP2 was identified in VP40. Deleting this region resulted in loss of microtubule stabilization against drug-induced depolymerization. The presence of VP40-associated microtubules in cells continuously treated with nocodazole suggested that VP40 promotes tubulin polymerization. Using an in vitro polymerization assay, we demonstrated that VP40 directly enhances tubulin polymerization without any cellular mediators. These results suggest that microtubules may play an important role in the Ebola virus life cycle and potentially provide a novel target for therapeutic intervention against this highly pathogenic virus.",1
"Ruthel, Gordon, Demmin, Gretchen L, Kallstrom, George, Javid, Melodi P, Badie, Shirin S, Will, Amy B, Nelle, Timothy, Schokman, Rowena, Nguyen, Tam L, Carra, John H, Bavari, Sina, Aman, M Javad",2
The majority of currently circulating human immunodeficiency virus type 1 clade B viruses fail to prime cytotoxic T-lymphocyte responses against an otherwise immunodominant HLA-A2-restricted epitope: implications for vaccine design.,0
"Human immunodeficiency virus type 1 (HIV-1) mutates to escape immune selection pressure, but there is little evidence of selection mediated through HLA-A2, the dominant class I allele in persons infected with clade B virus. Moreover, HLA-A2-restricted responses are largely absent in the acute phase of infection as the viral load is being reduced, suggesting that circulating viruses may lack immunodominant epitopes targeted through HLA-A2. Here we demonstrate an A2-restricted epitope within Vpr (Vpr59-67) that is targeted by acute-phase HIV-1-specific CD8+ T cells, but only in a subset of persons expressing HLA-A2. Individuals in the acute stage of infection with viruses containing the most common current sequence within this epitope (consensus sequence) were unable to mount epitope-specific T-cell responses, whereas subjects infected with the less frequent I60L variant all developed these responses. The I60L variant epitope was a stronger binder to HLA-A2 and was recognized by epitope-specific T cells at lower peptide concentrations than the consensus sequence epitope. These data demonstrate that HLA-A2 is capable of contributing to the acute-phase cytotoxic T-lymphocyte response in infected subjects, but that most currently circulating viruses lack a dominant immunogenic epitope presented by this allele, and suggest that immunodominant epitopes restricted by common HLA alleles may be lost as the epidemic matures.",1
"Altfeld, Marcus, Allen, Todd M, Kalife, Elizabeth T, Frahm, Nicole, Addo, Marylyn M, Mothe, Bianca R, Rathod, Almas, Reyor, Laura L, Harlow, Jason, Yu, Xu G, Perkins, Beth, Robinson, Loren K, Sidney, John, Alter, Galit, Lichterfeld, Mathias, Sette, Alessandro, Rosenberg, Eric S, Goulder, Philip J R, Brander, Christian, Walker, Bruce D",2
"Nuclear localizations of the herpes simplex virus type 1 tegument proteins VP13/14, vhs, and VP16 precede VP22-dependent microtubule reorganization and VP22 nuclear import.",0
"Herpes simplex virus type 1 (HSV-1) induces microtubule reorganization beginning at approximately 9 h postinfection (hpi), and this correlates with the nuclear localization of the tegument protein VP22. Thus, the active retention of this major virion component by cytoskeletal structures may function to regulate its subcellular localization (A. Kotsakis, L. E. Pomeranz, A. Blouin, and J. A. Blaho, J. Virol. 75:8697-8711, 2001). The goal of this study was to determine whether the subcellular localization patterns of other HSV-1 tegument proteins are similar to that observed with VP22. To address this, we performed a series of indirect immunofluorescence analyses using synchronously infected cells. We observed that tegument proteins VP13/14, vhs, and VP16 localized to the nucleus as early as 5 hpi and were concentrated in nuclei by 9 hpi, which differed from that seen with VP22. Microtubule reorganization was delayed during infection with HSV-1(RF177), a recombinant virus that does not produce full-length VP22. These infected cells did not begin to lose microtubule-organizing centers until 13 hpi. Repair of the unique long 49 (UL49) locus in HSV-1(RF177) yielded HSV-1(RF177R). Microtubule reorganization in HSV-1(RF177R)-infected cells occurred with the same kinetics as HSV-1(F). Acetylated tubulin remained unchanged during infection with either HSV-1(F) or HSV-1(RF177). Thus, while alpha-tubulin reorganized during infection, acetylated tubulin was stable, and the absence of full-length VP22 did not affect this stability. Our findings indicate that the nuclear localizations of tegument proteins VP13/14, VP16, and vhs do not appear to require HSV-1-induced microtubule reorganization. We conclude that full-length VP22 is needed for optimal microtubule reorganization during infection. This implies that VP22 mainly functions to reorganize microtubules later, rather than earlier, in infection. That acetylated tubulin does not undergo restructuring during VP22-dependent, virus-induced microtubule reorganization suggests that it plays a role in stabilizing the infected cells. Our results emphasize that VP22 likely plays a key role in cellular cytopathology during HSV-1 infection.",1
"Yedowitz, Jamie C, Kotsakis, Anna, Schlegel, Elisabeth F M, Blaho, John A",2
Development and assessment of human adenovirus type 11 as a gene transfer vector.,0
"Adenovirus vectors based on human serotype 5 (Ad5) have successfully been used as gene transfer vectors in many gene therapy-based approaches to treat disease. Despite their widespread application, many potential therapeutic applications are limited by the widespread prevalence of vector-neutralizing antibodies within the human population and the inability of Ad5-based vectors to transduce important therapeutic target cell types. In an attempt to circumvent these problems, we have developed Ad vectors based on human Ad serotype 11 (Ad11), since the prevalence of neutralizing antibodies to Ad11 in humans is low. E1-deleted Ad11 vector genomes were generated by homologous recombination in 293 cells expressing the Ad11-E1B55K protein or by recombination in Escherichia coli. E1-deleted Ad11 genomes did not display transforming activity in rodent cells. Transduction of primary human CD34+ hematopoietic progenitor cells and immature dendritic cells was more efficient with Ad11 vectors than with Ad5 vectors. Thirty minutes after intravenous injection into mice that express one of the Ad11 receptors (CD46), we found, in a pattern and at a level comparable to what is found in humans, Ad11 vector genomes in all analyzed organs, with the highest amounts in liver, lung, kidney, and spleen. Neither Ad11 genomes nor Ad11 vector-mediated transgene expression were, however, detected at 72 h postinfusion. A large number of Ad11 particles were also found to be associated with circulating blood cells. We also discovered differences in in vitro transduction efficiencies and in vivo biodistributions between Ad11 vectors and chimeric Ad5 vectors possessing Ad11 fibers, indicating that Ad11 capsid proteins other than fibers influence viral infectivity and tropism. Overall, our study provides a basis for the application of Ad11 vectors for in vitro and in vivo gene transfer and for gaining an understanding of the factors that determine Ad tropism.",1
"Stone, Daniel, Ni, Shaoheng, Li, Zong-Yi, Gaggar, Anuj, DiPaolo, Nelson, Feng, Qinghua, Sandig, Volker, Lieber, André",2
Expression of the full-length form of gp2 of equine herpesvirus 1 (EHV-1) completely restores respiratory virulence to the attenuated EHV-1 strain KyA in CBA mice.,0
"Wild-type equine herpesvirus 1 (EHV-1) strains express a large (250-kDa) glycoprotein, gp2, that is encoded by EUs4 (gene 71) located within the unique short region of the genome. DNA sequence analysis revealed that EUs4 of the pathogenic EHV-1 strain RacL11 is an open reading frame of 2,376 bp that encodes a protein of 791 amino acids. The attenuated EHV-1 vaccine strain KyA harbors an in-frame deletion of 1,242 bp from bp 222 to 1461 and expresses a truncated gp2 of 383 amino acids. To determine the relative contribution of gp2 to EHV-1 pathogenesis, we compared the course of respiratory infection of CBA mice infected with either wild-type RacL11, attenuated KyA, or a recombinant KyA that expresses the full-length gp2 protein (KyARgp2F). Mice infected with KyA lost a negligible amount of body weight (0.18% total weight loss) on day 1 postinfection and regained weight thereafter, whereas mice infected with KyARgp2F or RacL11 steadily lost weight beginning on day 1 and experienced a 20 and 18% loss in body weight, respectively, by day 3. Immunohistochemical and flow cytometric analyses revealed higher numbers of T and B lymphocytes and an extensive consolidation consisting of large numbers of Mac-1-positive cells in the lungs of animals infected with KyARgp2F compared to animals infected with KyA. RNase protection analyses revealed increased expression of numerous cytokines and chemokines, including interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha, macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, MIP-2, interferon gamma-inducible protein, monocyte chemotactic protein 1, and T-cell activation gene 3 at 12 h postinfection with KyARgp2F. Three independent DNA array experiments confirmed these results and showed a 2- to 13-fold increase in the expression of 31 inflammatory genes at 8 and 12 h postinfection with KyARgp2F compared to infection with KyA. Taken together, the results indicate that expression of full-length gp2 is sufficient to restore full respiratory virulence to the attenuated KyA strain and raise caution concerning the inclusion of full-length gp2 in the development of EHV-1 vaccines.",1
"Smith, Patrick M, Kahan, Shannon M, Rorex, Colin B, von Einem, Jens, Osterrieder, Nikolaus, O'Callaghan, Dennis J",2
Host and viral proteins in the virion of Kaposi's sarcoma-associated herpesvirus.,0
"Infection of cultured cells with Kaposi's sarcoma associated herpesvirus (KSHV) typically establishes a latent infection, in which only a few viral genes are expressed. Recently, it has been reported that a subset of lytic genes are transiently expressed very early after viral entry but that this burst of abortive lytic gene expression is terminated with the supervention of latency (H. H. Krishnan, P. P. Naranatt, M. S. Smith, L. Zeng, C. Bloomer, and B. Chandran, J. Virol. 78:3601-3620, 2004). To identify molecules imported into cells by KSHV that might influence this gene expression program, we have examined the protein composition of the KSHV particle. Immunoblotting of virus particles demonstrated that RTA, the lytic switch protein, and RAP, a viral protein that is a transcriptional and cell cycle modulator, were both incorporated into virus particles. In a second approach, polypeptides isolated from purified virions were identified by mass-spectrometric analysis of their constituent tryptic peptides. With this approach we were able to identify 18 major virion proteins, including structural, regulatory, and signaling proteins of both viral and cellular origin.",1
"Bechtel, Jill T, Winant, Richard C, Ganem, Don",2
Inhibition of murine leukemia virus envelope protein (env) processing by intracellular expression of the env N-terminal heptad repeat region.,0
"A conserved structural motif in the envelope proteins of several viruses consists of an N-terminal, alpha-helical, trimerization domain and a C-terminal region that refolds during fusion to bind the N-helix trimer. Interaction between the N and C regions is believed to pull viral and target membranes together in a crucial step during membrane fusion. For several viruses with type I fusion proteins, C regions pack as alpha-helices in the grooves between N-helix monomers, and exogenously added N- and C-region peptides block fusion by inhibiting the formation of the six-helix bundle. For other viruses, including influenza virus and murine leukemia virus (MLV), there is no evidence for comparably extended C-region alpha-helices, although a short, non-alpha-helical interaction structure has been reported for influenza virus. We tested candidate N-helix and C-region peptides from MLV for their ability to inhibit cell fusion but found no inhibitory activity. In contrast, intracellular expression of the MLV N-helix inhibited fusion by efficiently blocking proteolytic processing and intracellular transport of the envelope protein. The results highlight another mechanism by which the N-helix peptides can inhibit fusion.",1
"Ou, Wu, Silver, Jonathan",2
Inhibition of flavivirus infections by antisense oligomers specifically suppressing viral translation and RNA replication.,0
"RNA elements within flavivirus genomes are potential targets for antiviral therapy. A panel of phosphorodiamidate morpholino oligomers (PMOs), whose sequences are complementary to RNA elements located in the 5'- and 3'-termini of the West Nile (WN) virus genome, were designed to anneal to important cis-acting elements and potentially to inhibit WN infection. A novel Arg-rich peptide was conjugated to each PMO for efficient cellular delivery. These PMOs exhibited various degrees of antiviral activity upon incubation with a WN virus luciferase-replicon-containing cell line. Among them, PMOs targeting the 5'-terminal 20 nucleotides (5'End) or targeting the 3'-terminal element involved in a potential genome cyclizing interaction (3'CSI) exhibited the greatest potency. When cells infected with an epidemic strain of WN virus were treated with the 5'End or 3'CSI PMO, virus titers were reduced by approximately 5 to 6 logs at a 5 muM concentration without apparent cytotoxicity. The 3'CSI PMO also inhibited mosquito-borne flaviviruses other than WN virus, and the antiviral potency correlated with the conservation of the targeted 3'CSI sequences of specific viruses. Mode-of-action analyses showed that the 5'End and 3'CSI PMOs suppressed viral infection through two distinct mechanisms. The 5'End PMO inhibited viral translation, whereas the 3'CSI PMO did not significantly affect viral translation but suppressed RNA replication. The results suggest that antisense PMO-mediated blocking of cis-acting elements of flavivirus genomes can potentially be developed into an anti-flavivirus therapy. In addition, we report that although a full-length WN virus containing a luciferase reporter (engineered at the 3' untranslated region of the genome) is not stable, an early passage of this reporting virus can be used to screen for inhibitors against any step of the virus life cycle.",1
"Deas, Tia S, Binduga-Gajewska, Iwona, Tilgner, Mark, Ren, Ping, Stein, David A, Moulton, Hong M, Iversen, Patrick L, Kauffman, Elizabeth B, Kramer, Laura D, Shi, Pei-Yong",2
"The Autographa californica multiple nucleopolyhedrovirus ie0-ie1 gene complex is essential for wild-type virus replication, but either IE0 or IE1 can support virus growth.",0
"The immediate-early ie0-ie1 gene complex expresses the only baculovirus spliced gene that produces an alternate protein product. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) IE1 is a potent transcriptional transactivator that is essential for viral replication in transient assays. IE1 contains 582 amino acids that are arranged into different domains, including an acidic activation domain at the N terminus, a DNA binding domain, and an oligomerization domain at the C terminus. IE0 is a 52-amino-acid N-terminally elongated form of IE1. We investigated the functions of IE0 and IE1 in virus-infected cells by constructing the first ie1 open reading frame knockout virus. An infectious AcMNPV bacmid was used to generate the ie1 knockout, and the resulting virus, AcBacIE1KO, effectively deletes both ie0 and ie1. AcBacIE1KO does not infect Spodoptera frugiperda cells, showing that the ie0-ie1 gene complex is essential for viral infection. Rescue viruses of AcBacIE1KO were constructed that express only IE1, IE1 and IE0, or only IE0. Our results show that both IE0 and IE1 can function independently, but not equivalently, to support replication, producing infectious virus. Viruses expressing predominately, or only, IE0 produced significantly fewer cells with polyhedra than either the IE1 counterpart or wild-type virus. In addition, DNA replication was prolonged and budded virus and late gene expression were delayed. Viruses expressing only IE1 also produced fewer polyhedra, but replication was slightly faster and achieved higher levels than that of the wild-type virus. Both IE0 and IE1 are therefore required and must be expressed in the correct quantitative ratios to achieve a wild-type infection.",1
"Stewart, Taryn M, Huijskens, Ilse, Willis, Leslie G, Theilmann, David A",2
Regions of the varicella-zoster virus open reading frame 63 latency-associated protein important for replication in vitro are also critical for efficient establishment of latency.,0
"Varicella-zoster virus (VZV) open reading frame 63 (ORF63) is one of the most abundant transcripts expressed during VZV latency in humans, and ORF63 protein has been detected in human ganglia by several laboratories. Deletion of over 90% of the ORF63 gene showed that the protein is required for efficient establishment of latency in rodents. We have constructed viruses with a series of mutations in ORF63. While prior experiments showed that transfection of cells with a plasmid expressing ORF63 but lacking the putative nuclear localization signal of the protein resulted in increased expression of the protein in the cytoplasm, we found that ORF63 protein remained in the nucleus in cells infected with a VZV ORF63 nuclear localization signal deletion mutant. This mutant was not impaired for growth in cell culture or for latency in rodents. Replacement of five serine or threonine phosphorylation sites in ORF63 with alanines resulted in a virus that was impaired for replication in vitro and for latency. A series of ORF63 carboxy-terminal mutants showed that the last 70 amino acids do not affect replication in vitro or latency in rodents; however, the last 108 amino acids are important for replication and latency. Thus, regions of ORF63 that are important for replication in vitro are also required for efficient establishment of latency.",1
"Cohen, Jeffrey I, Krogmann, Tammy, Bontems, Sebastien, Sadzot-Delvaux, Catherine, Pesnicak, Lesley",2
Characterization of DC-SIGN/R interaction with human immunodeficiency virus type 1 gp120 and ICAM molecules favors the receptor's role as an antigen-capturing rather than an adhesion receptor.,0
"The dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin binding receptor (DC-SIGN) was shown to bind human immunodeficiency virus type 1 (HIV-1) viral envelope protein gp120 and proposed to function as a Trojan horse to enhance trans-virus infection to host T cells. To better understand the mechanism by which DC-SIGN and DC-SIGNR selectively bind HIV-1 gp120, we constructed a series of deletion mutations in the repeat regions of both receptors. Different truncated receptors exist in different oligomeric forms. The carbohydrate binding domain without any repeats was monomeric, whereas the full extracellular receptors existed as tetramers. All reconstituted receptors retained their ability to bind gp120. The dissociation constant, however, differed drastically from micromolar values for the monomeric receptors to nanomolar values for the tetrameric receptors, suggesting that the repeat region of these receptors contributes to the avidity of gp120 binding. Such oligomerization may provide a mechanism for the receptor to selectively recognize pathogens containing multiple high-mannose-concentration carbohydrates. In contrast, the receptors bound to ICAMs with submicromolar affinities that are similar to those of two nonspecific cell surface glycoproteins, FcgammaRIIb and FcgammaRIII, and the oligomerization of DC-SIGNR resulted in no increase in binding affinity to ICAM-3. These findings suggest that DC-SIGN may not discriminate other cell surface glycoproteins from ICAM-3 binding. The pH dependence in DC-SIGN binding to gp120 showed that the receptor retained high-affinity gp120 binding at neutral pH but lost gp120 binding at pH 5, suggesting a release mechanism of HIV in the acidic endosomal compartment by DC-SIGN. Our work contradicts the function of DC-SIGN as a Trojan horse to facilitate HIV-1 infection; rather, it supports the function of DC-SIGN/R (a designation referring to both DC-SIGN and DC-SIGNR) as an antigen-capturing receptor.",1
"Snyder, Greg A, Ford, Jennifer, Torabi-Parizi, Parizad, Arthos, James A, Schuck, Peter, Colonna, Marco, Sun, Peter D",2
Requirements at the 3' end of the sindbis virus genome for efficient synthesis of minus-strand RNA.,0
"The 3'-untranslated region of the Sindbis virus genome is 0.3 kb in length with a 19-nucleotide conserved sequence element (3' CSE) immediately preceding the 3'-poly(A) tail. The 3' CSE and poly(A) tail have been assumed to constitute the core promoter for minus-strand RNA synthesis during genome replication; however, their involvement in this process has not been formally demonstrated. Utilizing both in vitro and in vivo analyses, we have examined the role of these elements in the initiation of minus-strand RNA synthesis. The major findings of this study with regard to efficient minus-strand RNA synthesis are the following: (i) the wild-type 3' CSE and the poly(A) tail are required, (ii) the poly(A) tail must be a minimum of 11 to 12 residues in length and immediately follow the 3' CSE, (iii) deletion or substitution of the 3' 13 nucleotides of the 3' CSE severely inhibits minus-strand RNA synthesis, (iv) templates possessing non-wild-type 3' sequences previously demonstrated to support virus replication do not program efficient RNA synthesis, and (v) insertion of uridylate residues between the poly(A) tail and a non-wild-type 3' sequence can restore promoter function to a limited extent. This study shows that the optimal structure of the 3' component of the minus-strand promoter is the wild-type 3' CSE followed a poly(A) tail of at least 11 residues. Our findings also show that insertion of nontemplated bases can restore function to an inactive promoter.",1
"Hardy, Richard W, Rice, Charles M",2
Tissue-resident macrophages are productively infected ex vivo by primary X4 isolates of human immunodeficiency virus type 1.,0
"Infection of macrophages has been implicated as a critical event in the transmission and persistence of human immunodeficiency virus type 1 (HIV-1). Here, we explore whether primary X4 HIV-1 isolates can productively infect tissue macrophages that have terminally differentiated in vivo. Using immunohistochemistry, HIV-1 RNA in situ hybridization, and confocal immunofluorescence microscopy, we demonstrate that macrophages residing in human tonsil blocks can be productively infected ex vivo by primary X4 HIV-1 isolates. This challenges the model in which macrophage tropism is a key determinant of the selective transmission of R5 HIV-1 strains. Infection of tissue macrophages by X4 HIV-1 may be highly relevant in vivo and contribute to key events in HIV-1 pathogenesis.",1
"Jayakumar, Prerana, Berger, Irina, Autschbach, Frank, Weinstein, Mark, Funke, Benjamin, Verdin, Eric, Goldsmith, Mark A, Keppler, Oliver T",2
Inhibition of dengue virus serotypes 1 to 4 in vero cell cultures with morpholino oligomers.,0
"Five dengue (DEN) virus-specific R5F2R4 peptide-conjugated phosphorodiamidate morpholino oligomers (P4-PMOs) were evaluated for their ability to inhibit replication of DEN virus serotype 2 (DEN-2 virus) in mammalian cell culture. Initial growth curves of DEN-2 virus 16681 were obtained in Vero cells incubated with 20 microM P4-PMO compounds. At 6 days after infection, a P4-PMO targeting the 3'-terminal nucleotides of the DEN-2 virus genome and a random-sequence P4-PMO showed relatively little suppression of DEN-2 virus titer (0.1 and 0.9 log10, respectively). P4-PMOs targeting the AUG translation start site region of the single open reading frame and the 5' cyclization sequence region had moderate activity, generating 1.6- and 1.8-log10 reductions. Two P4-PMO compounds, 5'SL and 3'CS (targeting the 5'-terminal nucleotides and the 3' cyclization sequence region, respectively), were highly efficacious, each reducing the viral titer by greater than 5.7 log10 compared to controls at 6 days after infection with DEN-2 virus. Further experiments showed that 5'SL and 3'CS inhibited DEN-2 virus replication in a dose-dependent and sequence-specific manner. Treatment with 10 microM 3'CS reduced the titers of all four DEN virus serotypes, i.e., DEN-1 (strain 16007), DEN-2 (16681), DEN-3 (16562), and DEN-4 (1036) viruses by over 4 log10, in most cases to below detectable limits. The extent of 3'CS efficacy was affected by the timing of compound application in relation to viral infection of the cells. The 5'SL and 3'CS P4-PMOs did not suppress the replication of West Nile virus NY99 in Vero cells. These data indicate that further evaluation of the 5'SL and 3'CS compounds as potential DEN virus therapeutics is warranted.",1
"Kinney, Richard M, Huang, Claire Y-H, Rose, Becky C, Kroeker, Andrew D, Dreher, Theo W, Iversen, Patrick L, Stein, David A",2
Characterization of homologous and heterologous rotavirus-specific T-cell responses in infant and adult mice.,0
"During primary rotavirus (RV) infection, CD8+ T cells play an important role in viral clearance as well as providing partial protection against reinfection. CD4+ T cells are essential for maximal development of RV-specific intestinal immunoglobulin A. In this study, we took advantage of the cytokine flow cytometry technique to obtain a detailed map of H-2b- and H-2d-restricted CD8+ and CD4+ T-cell epitopes from the RV proteins VP6 and VP7. Three new CD8+ T-cell epitopes (H-2d and H-2b restricted) and one new CD4+ T-cell epitope (H-2d and H-2b restricted) were identified. Using these newly identified targets, we characterized the development and specificity of cellular immune responses in C57BL/6 and BALB/c mice during acute infection of infants and adults. We found that both the CD4+ and CD8+ responses peaked on days 5 to 7 after infection and then declined rapidly. Interestingly, both the response kinetics and tissue distributions were different when epitopes on VP6 and VP7 were compared. VP6 elicited a response which predominated in the intestine, while the response to VP7 was more systemic. Additionally, the T-cell responses elicited after homologous versus heterologous infection differed substantially. We found that during homologous infection, there was a greater response toward VP6 than that toward VP7, especially in the intestine, while after heterologous infection, this was not the case. Finally, in suckling mice, we found two peaks in the CD8 response on days 7 and 14 postinfection, which differed from the single peak found in adults and likely mimics the biphasic pattern of rotavirus shedding in infant mice.",1
"Jaimes, María C, Feng, Ningguo, Greenberg, Harry B",2
The murine gammaherpesvirus 68 ORF27 gene product contributes to intercellular viral spread.,0
"Herpesviruses remain predominantly cell associated within their hosts, implying that they spread between cells by a mechanism distinct from free virion release. We previously identified the efficient release of murine gammaherpesvirus 68 (MHV-68) virions as a function of the viral gp150 protein. Here we show that the MHV-68 ORF27 gene product, gp48, contributes to the direct spread of viruses from lytically infected to uninfected cells. Monoclonal antibodies to gp48 identified it on infected cell surfaces and in virions. gp48-deficient viruses showed no obvious deficit in virion cell binding, single-cycle replication, or virion release but had reduced lytic propagation between cells. After intranasal infection of mice, ORF27-deficient viruses were impaired predominantly in lytic replication in the lungs. There was a small deficit in latency establishment, but long-term latency appeared normal. Since ORF27 has homologs in both Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus, it is likely part of a conserved mechanism employed by gammaherpesviruses to disseminate lytically in their hosts.",1
"May, Janet S, Walker, Jennifer, Colaco, Susanna, Stevenson, Philip G",2
"Wing-to-Leg homeosis by spineless causes apoptosis regulated by Fish-lips, a novel leucine-rich repeat transmembrane protein.",0
"Growth, patterning, and apoptosis are mutually interactive during development. For example, cells that select an abnormal fate in a developing field are frequently removed by apoptosis. An important issue in this process that needs to be resolved is the mechanism used by cells to discern their correct fate from an abnormal fate. In order to examine this issue, we developed an animal model that expresses the dioxin receptor homolog Spineless (Ss) ectopically in the Drosophila wing. The presence of mosaic clones ectopically expressing ss results in a local transformation of organ identity, homeosis, from wing into a leg or antenna. The cells with misspecified fates subsequently activate c-Jun N-terminal kinase to undergo apoptosis in an autonomous or nonautonomous manner depending on their position within the wing, suggesting that a cell-cell interaction is, at least in some cases, involved in the detection of misspecified cells. Similar position dependence is commonly observed when various homeotic genes controlling the body segments are ectopically expressed. The autonomous and nonautonomous apoptosis caused by ss is regulated by a novel leucine-rich repeat family transmembrane protein, Fish-lips (Fili) that interacts with surrounding normal cells. These data support a mechanism in which the lack of some membrane proteins helps to recognize the presence of different cell types and direct these cells to an apoptotic fate in order to exclude them from the normal developing field.",1
"Adachi-Yamada, Takashi, Harumoto, Toshiyuki, Sakurai, Kayoko, Ueda, Ryu, Saigo, Kaoru, O'Connor, Michael B, Nakato, Hiroshi",2
Novel functions of the phospholipase D2-Phox homology domain in protein kinase Czeta activation.,0
"It has been established that protein kinase Czeta (PKCzeta) participates in diverse signaling pathways and cellular functions in a wide variety of cells, exhibiting properties relevant to cellular survival and proliferation. Currently, however, the regulation mechanism of PKCzeta remains elusive. Here, for the first time, we determine that phospholipase D2 (PLD2) enhances PKCzeta activity through direct interaction in a lipase activity-independent manner. This interaction of the PLD2-Phox homology (PX) domain with the PKCzeta-kinase domain also induces the activation loop phosphorylation of PKCzeta and downstream signal stimulation, as measured by p70 S6 kinase phosphorylation. Furthermore, only the PLD2-PX domain directly stimulates PKCzeta activity in vitro, and it is necessary for the formation of the ternary complex with phosphoinositide-dependent kinase 1 and PKCzeta. The mutant that substitutes the triple lysine residues (Lys101, Lys102, and Lys103) within the PLD2-PX domain with alanine abolishes interaction with the PKCzeta-kinase domain and activation of PKCzeta. Moreover, breast cancer cell viability is significantly affected by PLD2 silencing. Taken together, these results suggest that the PLD2-mediated PKCzeta activation is induced by its PX domain performing both direct activation of PKCzeta and assistance of activation loop phosphorylation. Furthermore, we find it is an important factor in the survival of breast cancer cells.",1
"Kim, Jong Hyun, Kim, Jung Hwan, Ohba, Motoi, Suh, Pann-Ghill, Ryu, Sung Ho",2
The phosphoinositide phosphatase Sjl2 is recruited to cortical actin patches in the control of vesicle formation and fission during endocytosis.,0
"The Saccharomyces cerevisiae synaptojanin-like proteins (Sjl1, Sjl2, and Sjl3) are phosphoinositide (PI) phosphatases that regulate PI metabolism in the control of actin organization and membrane trafficking. However, the primary sites of action for each of the yeast synaptojanin-like proteins remain unclear. In this study, we show that Sjl2 is localized to cortical actin patches, sites of endocytosis. Cortical recruitment of Sjl2 requires the actin patch component Abp1. Consistent with this, the SH3 domain-containing protein Abp1 physically associates with Sjl2 through its proline-rich domain. Furthermore, abp1Delta mutations confer defects resembling loss of SJL2; sjl1Delta abp1Delta double-mutant cells exhibit invaginated plasma membranes and impaired endocytosis, findings similar to those for sjl1Delta sjl2Delta mutant cells. Thus, Abp1 acts as an adaptor protein in the localization or concentration of Sjl2 during late stages of endocytic vesicle formation. Overexpression of the Hip1-related protein Sla2 delayed the formation of extended plasma membrane invaginations in sjl2ts cells, indicating that Sla2 may become limiting or misregulated in cells with impaired PI phosphatase activity. Consistent with this, the cortical actin patch protein Sla2 is mislocalized in sjl1Delta sjl2Delta mutant cells. Together, our studies suggest that PI metabolism by the synaptojanin-like proteins coordinately directs actin dynamics and membrane invagination, in part by regulation of Sla2.",1
"Stefan, Christopher J, Padilla, Steven M, Audhya, Anjon, Emr, Scott D",2
Phosphorylation of p21 in G2/M promotes cyclin B-Cdc2 kinase activity.,0
"Little is known about the posttranslational control of the cyclin-dependent protein kinase (CDK) inhibitor p21. We describe here a transient phosphorylation of p21 in the G2/M phase. G2/M-phosphorylated p21 is short-lived relative to hypophosphorylated p21. p21 becomes nuclear during S phase, prior to its phosphorylation by CDK2. S126-phosphorylated cyclin B1 binds to T57-phosphorylated p21. Cdc2 kinase activation is delayed in p21-deficient cells due to delayed association between Cdc2 and cyclin B1. Cyclin B1-Cdc2 kinase activity and G2/M progression in p21-/- cells are restored after reexpression of wild-type but not T57A mutant p21. The cyclin B1 S126A mutant exhibits reduced Cdc2 binding and has low kinase activity. Phosphorylated p21 binds to cyclin B1 when Cdc2 is phosphorylated on Y15 and associates poorly with the complex. Dephosphorylation on Y15 and phosphorylation on T161 promotes Cdc2 binding to the p21-cyclin B1 complex, which becomes activated as a kinase. Thus, hyperphosphorylated p21 activates the Cdc2 kinase in the G2/M transition.",1
"Dash, Bipin C, El-Deiry, Wafik S",2
Transforming growth factor beta facilitates beta-TrCP-mediated degradation of Cdc25A in a Smad3-dependent manner.,0
"Ubiquitin-dependent degradation of Cdc25A is a major mechanism for damage-induced S-phase checkpoint. Two ubiquitin ligases, the Skp1-cullin-beta-TrCP (SCFbeta-TrCP) complex and the anaphase-promoting complex (APCCdh1), are involved in Cdc25A degradation. Here we demonstrate that the transforming growth factor beta (TGF-beta)-Smad3 pathway promotes SCF(beta-TrCP)-mediated Cdc25A ubiquitination. Cells treated with TGF-beta, as well as cells transfected with Smad3 or a constitutively active type I TGF-beta receptor, exhibit increased ubiquitination and markedly shortened half-lives of Cdc25A. Furthermore, Cdc25A is stabilized in cells transfected with Smad3 small interfering RNA (siRNA) and cells from Smad3-null mice. TGF-beta-induced ubiquitination is associated with Cdc25A phosphorylation at the beta-TrCP docking site (DS82G motif) and physical association of Cdc25A with Smad3 and beta-TrCP. Cdc25A mutant proteins deficient in DS82G phosphorylation are resistant to TGF-beta-Smad3-induced degradation, whereas a Cdc25A mutant protein defective in APCCdh1 recognition undergoes efficient degradation. Smad3 siRNA inhibits beta-TrCP-Cdc25A interaction and Cdc25A degradation in response to TGF-beta. beta-TrCP2 siRNA also inhibits Smad3-induced Cdc25A degradation. In contrast, Cdh1 siRNA had no effect on Cdc25A down-regulation by Smad3. These data suggest that Smad3 plays a key role in the regulation of Cdc25A ubiquitination by SCFbeta-TrCP and that Cdc25A stabilization observed in various cancers could be associated with defects in the TGF-beta-Smad3 pathway.",1
"Ray, Dipankar, Terao, Yasuhisa, Nimbalkar, Dipali, Chu, Li-Hao, Donzelli, Maddalena, Tsutsui, Tateki, Zou, Xianghong, Ghosh, Asish K, Varga, John, Draetta, Giulio F, Kiyokawa, Hiroaki",2
Akt-dependent cell size regulation by the adhesion molecule on glia occurs independently of phosphatidylinositol 3-kinase and Rheb signaling.,0
"The role of cell adhesion molecules in mediating interactions with neighboring cells and the extracellular matrix has long been appreciated. More recently, these molecules have been shown to modulate intracellular signal transduction cascades critical for cell growth and proliferation. Expression of adhesion molecule on glia (AMOG) is downregulated in human and mouse gliomas, suggesting that AMOG may be important for growth regulation in the brain. In this report, we examined the role of AMOG expression on cell growth and intracellular signal transduction. We show that AMOG does not negatively regulate cell growth in vitro or in vivo. Instead, expression of AMOG in AMOG-deficient cells results in a dramatic increase in cell size associated with protein kinase B/Akt hyperactivation, which occurs independent of phosphatidylinositol 3-kinase activation. AMOG-mediated Akt phosphorylation specifically activates the mTOR/p70S6 kinase pathway previously implicated in cell size regulation, but it does not depend on tuberous sclerosis complex/Ras homolog enriched in brain (Rheb) signaling. These data support a novel role for a glial adhesion molecule in cell size regulation through selective activation of the Akt/mTOR/S6K signal transduction pathway.",1
"Scheidenhelm, Danielle K, Cresswell, Jennifer, Haipek, Carrie A, Fleming, Timothy P, Mercer, Robert W, Gutmann, David H",2
The p53 tumor suppressor protein represses human snRNA gene transcription by RNA polymerases II and III independently of sequence-specific DNA binding.,0
"Human U1 and U6 snRNA genes are transcribed by RNA polymerases II and III, respectively. While the p53 tumor suppressor protein is a general repressor of RNA polymerase III transcription, whether p53 regulates snRNA gene transcription by RNA polymerase II is uncertain. The data presented herein indicate that p53 is an effective repressor of snRNA gene transcription by both polymerases. Both U1 and U6 transcription in vitro is repressed by recombinant p53, and endogenous p53 occupancy at these promoters is stimulated by UV light. In response to UV light, U1 and U6 transcription is strongly repressed. Human U1 genes, but not U6 genes, contain a high-affinity p53 response element located within the core promoter region. Nonetheless, this element is not required for p53 repression and mutant p53 molecules that do not bind DNA can maintain repression, suggesting a reliance on protein interactions for p53 promoter recruitment. Recruitment may be mediated by the general transcription factors TATA-box binding protein and snRNA-activating protein complex, which interact well with p53 and function for both RNA polymerase II and III transcription.",1
"Gridasova, Anastasia A, Henry, R William",2
Strong polyadenylation and weak pausing combine to cause efficient termination of transcription in the human Ggamma-globin gene.,0
"The human gamma-globin genes form part of a 5-kb tandem duplication within the beta-globin gene cluster on chromosome 11. Despite a high degree of identity between the two genes, we show that while the upstream Ggamma-globin gene terminates transcription efficiently, termination in the Agamma gene is inefficient. This is primarily due to the different strengths of the polyA signals of the two genes; Ggamma-globin has a functionally stronger polyA signal than the Agamma gene. The probable cause of this difference in polyA efficiency characteristics lies with a number of base changes which reduce the G/U content of the GU/U-rich region of the Agamma polyA signal relative to that of Ggamma. The 3' flanking regions of the two gamma-globin genes have similar abilities to promote transcription termination. We found no evidence to suggest a cotranscriptional cleavage event, such as that seen in the human beta-globin gene, occurs in either gamma-globin 3' flank. Instead we find evidence that the 3' flank of the Ggamma-globin gene contains multiple weak pause elements which, combined with the strong polyA signal the gene possesses, are likely to cause gradual termination across the 3' flank.",1
"Plant, Kathryn E, Dye, Michael J, Lafaille, Celina, Proudfoot, Nick J",2
Human progesterone receptor displays cell cycle-dependent changes in transcriptional activity.,0
"The human progesterone receptor (PR) contains multiple Ser-Pro phosphorylation sites that are potential substrates for cyclin-dependent kinases, suggesting that PR activity might be regulated during the cell cycle. Using T47D breast cancer cells stably transfected with an mouse mammary tumor virus (MMTV) chloramphenicol acetyltransferase reporter (Cat0) synchronized in different phases of the cell cycle, we found that PR function and phosphorylation is remarkably cell cycle dependent, with the highest activity in S phase. Although PR expression was reduced in the G2/M phase, the activity per molecule of receptor was markedly reduced in both G1 and G2/M phases compared to the results seen with the S phase of the cell cycle. Although PR is recruited to the MMTV promoter equivalently in the G1 and S phases, recruitment of SRC-1, SRC-3, and, consequently, CBP is reduced in G1 phase despite comparable expression levels of SRC-1 and SRC-3. In G2/M phase, site-specific phosphorylation of PR at Ser162 and at Ser294, a site previously reported to be critical for transcriptional activity and receptor turnover, was abolished. Treatment with the histone deacetylase inhibitor trichostatin A elevated G1 and G2/M activity to that of the S phase, indicating that the failure to recruit sufficient levels of active histone acetyltransferase is the primary defect in PR-mediated transactivation.",1
"Narayanan, Ramesh, Edwards, Dean P, Weigel, Nancy L",2
"Identification of a novel, intraperoxisomal pex14-binding site in pex13: association of pex13 with the docking complex is essential for peroxisomal matrix protein import.",0
"The peroxisomal docking complex is a key component of the import machinery for matrix proteins. The core protein of this complex, Pex14, is thought to represent the initial docking site for the import receptors Pex5 and Pex7. Associated with this complex is a fraction of Pex13, another essential component of the import machinery. Here we demonstrate that Pex13 directly binds Pex14 not only via its SH3 domain but also via a novel intraperoxisomal site. Furthermore, we demonstrate that Pex5 also contributes to the association of Pex13 with Pex14. Peroxisome function was affected only mildly by mutations within the novel Pex14 interaction site of Pex13 or by the non-Pex13-interacting mutant Pex5(W204A). However, when these constructs were tested in combination, PTS1-dependent import and growth on oleic acid were severely compromised. When the SH3 domain-mediated interaction of Pex13 with Pex14 was blocked on top of that, PTS2-dependent matrix protein import was completely compromised and Pex13 was no longer copurified with the docking complex. We conclude that the association of Pex13 with Pex14 is an essential step in peroxisomal protein import that is enabled by two direct interactions and by one that is mediated by Pex5, a result which indicates a novel, receptor-independent function of Pex5.",1
"Schell-Steven, Annette, Stein, Katharina, Amoros, Mara, Landgraf, Christiane, Volkmer-Engert, Rudolf, Rottensteiner, Hanspeter, Erdmann, Ralf",2
17beta-estradiol inhibits inflammatory gene expression by controlling NF-kappaB intracellular localization.,0
"Estrogen is an immunoregulatory agent, in that hormone deprivation increases while 17beta-estradiol (E2) administration blocks the inflammatory response; however, the underlying mechanism is still unknown. The transcription factor p65/relA, a member of the nuclear factor kappaB (NF-kappaB) family, plays a major role in inflammation and drives the expression of proinflammatory mediators. Here we report a novel mechanism of action of E2 in inflammation. We observe that in macrophages E2 blocks lipopolysaccharide-induced DNA binding and transcriptional activity of p65 by preventing its nuclear translocation. This effect is selectively activated in macrophages to prevent p65 activation by inflammatory agents and extends to other members of the NF-kappaB family, including c-Rel and p50. We observe that E2 activates a rapid and persistent response that involves the activation of phosphatidylinositol 3-kinase, without requiring de novo protein synthesis or modifying Ikappa-Balpha degradation and mitogen-activated protein kinase activation. Using a time course experiment and the microtubule-disrupting agent nocodazole, we observe that the hormone inhibits p65 intracellular transport to the nucleus. This activity is selectively mediated by estrogen receptor alpha (ERalpha) and not ERbeta and is not shared by conventional anti-inflammatory drugs. These results unravel a novel and unique mechanism for E2 anti-inflammatory activity, which may be useful for identifying more selective ligands for the prevention of the inflammatory response.",1
"Ghisletti, Serena, Meda, Clara, Maggi, Adriana, Vegeto, Elisabetta",2
Matrix metalloproteinases are not essential for aggrecan turnover during normal skeletal growth and development.,0
"The growth plate is a transitional region of cartilage and highly diversified chondrocytes that controls long bone formation. The composition of growth plate cartilage changes markedly from the epiphysis to the metaphysis, notably with the loss of type II collagen, concomitant with an increase in MMP-13; type X collagen; and the C-propeptide of type II collagen. In contrast, the fate of aggrecan in the growth plate is not clear: there is biosynthesis and loss of aggrecan from hypertrophic cartilage, but the mechanism of loss is unknown. All matrix metalloproteinases (MMPs) cleave aggrecan between amino acids N341 and F342 in the proteinase-sensitive interglobular domain (IGD), and MMPs in the growth plate are thought to have a role in aggrecanolysis. We have generated mice with aggrecan resistant to proteolysis by MMPs in the IGD and found that the mice develop normally with no skeletal deformities. The mutant mice do not accumulate aggrecan, and there is no significant compensatory proteolysis occurring at alternate sites in the IGD. Our studies reveal that MMP cleavage in this key region is not a predominant mechanism for removing aggrecan from growth plate cartilage.",1
"Little, Christopher B, Meeker, Clare T, Hembry, Rosalind M, Sims, Natalie A, Lawlor, Kate E, Golub, Sue B, Last, Karena, Fosang, Amanda J",2
Identification of neuronal enhancers of the proopiomelanocortin gene by transgenic mouse analysis and phylogenetic footprinting.,0
"The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypothalamus. POMC arcuate neurons play a central role in the control of energy homeostasis, and rare loss-of-function mutations in POMC cause obesity. Moreover, POMC is the prime candidate gene within a highly significant quantitative trait locus on chromosome 2 associated with obesity traits in several human populations. Here, we identify two phylogenetically conserved neuronal POMC enhancers designated nPE1 (600 bp) and nPE2 (150 bp) located approximately 10 to 12 kb upstream of mammalian POMC transcriptional units. We show that mouse or human genomic regions containing these enhancers are able to direct reporter gene expression to POMC hypothalamic neurons, but not the pituitary of transgenic mice. Conversely, deletion of nPE1 and nPE2 in the context of the entire transcriptional unit of POMC abolishes transgene expression in the hypothalamus without affecting pituitary expression. Our results indicate that the nPEs are necessary and sufficient for hypothalamic POMC expression and that POMC expression in the brain and pituitary is controlled by independent sets of enhancers. Our study advances the understanding of the molecular nature of hypothalamic POMC neurons and will be useful to determine whether polymorphisms in POMC regulatory regions play a role in the predisposition to obesity.",1
"de Souza, Flávio S J, Santangelo, Andrea M, Bumaschny, Viviana, Avale, María Elena, Smart, James L, Low, Malcolm J, Rubinstein, Marcelo",2
Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo.,0
"Inhibitor of apoptosis proteins (IAPs) c-IAP1 and c-IAP2 were identified as part of the tumor necrosis factor receptor 2 (TNFR2) signaling complex and have been implicated as intermediaries in tumor necrosis factor alpha signaling. Like all RING domain-containing IAPs, c-IAP1 and c-IAP2 have ubiquitin protein ligase (E3) activity. To explore the function of c-IAP1 in a physiologic setting, c-IAP1-deficient mice were generated by homologous gene recombination. These animals are viable and have no obvious sensitization to proapoptotic stimuli. Cells from c-IAP1(-/-) mice do, however, express markedly elevated levels of c-IAP2 protein in the absence of increased c-IAP2 mRNA. In contrast to reports implicating c-IAPs in the activation of NF-kappaB, resting and cytokine-induced NF-kappaB activation was not impaired in c-IAP1-deficient cells. Transient transfection studies with wild-type and E3-defective c-IAP1 revealed that c-IAP2 is a direct target for c-IAP1-mediated ubiquitination and subsequent degradation, which are potentiated by the adaptor function of TRAF2. Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posttranscriptional and E3-dependent mechanism.",1
"Conze, Dietrich B, Albert, Lori, Ferrick, David A, Goeddel, David V, Yeh, Wen-Chen, Mak, Tak, Ashwell, Jonathan D",2
A novel SR-related protein is required for the second step of Pre-mRNA splicing.,0
"The SR family proteins and SR-related polypeptides are important regulators of pre-mRNA splicing. A novel SR-related protein of an apparent molecular mass of 53 kDa was isolated in a gene trap screen that identifies proteins which localize to the nuclear speckles. This novel protein possesses an arginine- and serine-rich domain and was termed SRrp53 (for SR-related protein of 53 kDa). In support for a role of this novel RS-containing protein in pre-mRNA splicing, we identified the mouse ortholog of the Saccharomyces cerevisiae U1 snRNP-specific protein Luc7p and the U2AF65-related factor HCC1 as interacting proteins. In addition, SRrp53 is able to interact with some members of the SR family of proteins and with U2AF35 in a yeast two-hybrid system and in cell extracts. We show that in HeLa nuclear extracts immunodepleted of SRrp53, the second step of pre-mRNA splicing is blocked, and recombinant SRrp53 is able to restore splicing activity. SRrp53 also regulates alternative splicing in a concentration-dependent manner. Taken together, these results suggest that SRrp53 is a novel SR-related protein that has a role both in constitutive and in alternative splicing.",1
"Cazalla, Demian, Newton, Kathryn, Cáceres, Javier F",2
Early embryonic lethality in mice with targeted deletion of the CTP:phosphocholine cytidylyltransferase alpha gene (Pcyt1a).,0
"CTP:phosphocholine cytidylyltransferase (CCT) catalyzes a rate-controlling step in the biosynthesis of phosphatidylcholine (PtdCho). Multiple CCT isoforms, CCTalpha, CCTbeta2, and CCTbeta3, are encoded by two genes, Pcyt1a and Pcyt1b. The importance of CCTalpha in mice was investigated by deleting exons 5 and 6 in the Pcyt1a gene using the Cre-lox system. Pcyt1a-/- zygotes failed to form blastocysts, did not develop past embryonic day 3.5 (E3.5), and failed to implant. In situ hybridization in E11.5 embryos showed that Pcyt1a is expressed ubiquitously, with the highest level in fetal liver, and CCTalpha transcripts are significantly more abundant than transcripts encoding CCTbeta or phosphatidylethanolamine (PtdEtn) N-methyl transferase, two other enzymes capable of producing PtdCho. Reduction of the CCTalpha transcripts in heterozygous E11.5 embryos was accompanied by upregulation of CCTbeta and PtdEtn N-methyltransferase transcripts. In contrast, enzymatic and real-time PCR data revealed that CCTbeta (Pcyt1b) expression is not upregulated to compensate for the reduction in CCTalpha expression in adult liver and other tissues from Pcyt1a+/- heterozygous mice. PtdCho biosynthesis measured by choline incorporation into isolated hepatocytes was not compromised in the Pcyt1a+/- mice. Liver PtdCho mass was the same in Pcyt1a+/+ and Pcyt1a+/- adult animals, but lung PtdCho mass decreased in the heterozygous mice. These data show that CCTalpha expression is required for early embryonic development, but that a 50% reduction in enzyme activity has little detectable impact on the operation of the CDP-choline metabolic pathway in adult tissues.",1
"Wang, Limin, Magdaleno, Susan, Tabas, Ira, Jackowski, Suzanne",2
Coupling of human circadian and cell cycles by the timeless protein.,0
"The Timeless protein is essential for circadian rhythm in Drosophila. The Timeless orthologue in mice is essential for viability and appears to be required for the maintenance of a robust circadian rhythm as well. We have found that the human Timeless protein interacts with both the circadian clock protein cryptochrome 2 and with the cell cycle checkpoint proteins Chk1 and the ATR-ATRIP complex and plays an important role in the DNA damage checkpoint response. Down-regulation of Timeless in human cells seriously compromises replication and intra-S checkpoints, indicating an intimate connection between the circadian cycle and the DNA damage checkpoints that is in part mediated by the Timeless protein.",1
"Unsal-Kaçmaz, Keziban, Mullen, Thomas E, Kaufmann, William K, Sancar, Aziz",2
Genome-wide prediction and analysis of yeast RNase III-dependent snoRNA processing signals.,0
"In Saccharomyces cerevisiae, the maturation of both pre-rRNA and pre-small nucleolar RNAs (pre-snoRNAs) involves common factors, thereby providing a potential mechanism for the coregulation of snoRNA and rRNA synthesis. In this study, we examined the global impact of the double-stranded-RNA-specific RNase Rnt1p, which is required for pre-rRNA processing, on the maturation of all known snoRNAs. In silico searches for Rnt1p cleavage signals, and genome-wide analysis of the Rnt1p-dependent expression profile, identified seven new Rnt1p substrates. Interestingly, two of the newly identified Rnt1p-dependent snoRNAs, snR39 and snR59, are located in the introns of the ribosomal protein genes RPL7A and RPL7B. In vitro and in vivo experiments indicated that snR39 is normally processed from the lariat of RPL7A, suggesting that the expressions of RPL7A and snR39 are linked. In contrast, snR59 is produced by a direct cleavage of the RPL7B pre-mRNA, indicating that a single pre-mRNA transcript cannot be spliced to produce a mature RPL7B mRNA and processed by Rnt1p to produce a mature snR59 simultaneously. The results presented here reveal a new role of yeast RNase III in the processing of intron-encoded snoRNAs that permits independent regulation of the host mRNA and its associated snoRNA.",1
"Ghazal, Ghada, Ge, Dongling, Gervais-Bird, Julien, Gagnon, Jules, Abou Elela, Sherif",2
Cotranscriptional recruitment of the pseudouridylsynthetase Cbf5p and of the RNA binding protein Naf1p during H/ACA snoRNP assembly.,0
"H/ACA small nucleolar ribonucleoprotein particles (snoRNPs) are essential for the maturation and pseudouridylation of the precursor of rRNAs and other stable RNAs. Although the RNA and protein components of these RNPs have been identified, the mechanisms by which they are assembled in vivo are poorly understood. Here we show that the RNA binding protein Naf1p, which is required for H/ACA snoRNPs stability, associates with RNA polymerase II-associated proteins Spt16p, Tfg1p, and Sub1p and with H/ACA snoRNP proteins. Chromatin immunoprecipitation experiments show that Naf1p and the pseudouridylsynthetase Cbf5p cross-link specifically with the chromatin of H/ACA small nucleolar RNA (snoRNA) genes. Naf1p and Cbf5p cross-link predominantly with the 3' end of these genes, in a pattern similar to that observed for transcription elongation factor Spt16p. Cross-linking of Naf1p to H/ACA snoRNA genes requires active transcription and intact H/ACA snoRNA sequences but does not require the RNA polymerase II CTD kinase Ctk1p. These results suggest that Naf1p and Cbf5p are recruited in a cotranscriptional manner during H/ACA snoRNP assembly, possibly by binding to the nascent H/ACA snoRNA transcript during elongation or termination of transcription of H/ACA snoRNA genes.",1
"Yang, Pok Kwan, Hoareau, Coralie, Froment, Carine, Monsarrat, Bernard, Henry, Yves, Chanfreau, Guillaume",2
YB-1 autoregulates translation of its own mRNA at or prior to the step of 40S ribosomal subunit joining.,0
"YB-1 is a member of the numerous families of proteins with an evolutionary ancient cold-shock domain. It is involved in many DNA- and RNA-dependent events and regulates gene expression at different levels. Previously, we found a regulatory element within the 3' untranslated region (UTR) of YB-1 mRNA that specifically interacted with YB-1 and poly(A)-binding protein (PABP); we also showed that PABP positively affected YB-1 mRNA translation in a poly(A) tail-independent manner (O. V. Skabkina, M. A. Skabkin, N. V. Popova, D. N. Lyabin, L. O. Penalva, and L. P. Ovchinnikov, J. Biol. Chem. 278:18191-18198, 2003). Here, YB-1 is shown to strongly and specifically inhibit its own synthesis at the stage of initiation, with accumulation of its mRNA in the form of free mRNPs. YB-1 and PABP binding sites have been mapped on the YB-1 mRNA regulatory element. These were UCCAG/ACAA for YB-1 and a approximately 50-nucleotide A-rich sequence for PABP that overlapped each other. PABP competes with YB-1 for binding to the YB-1 mRNA regulatory element and restores translational activity of YB-1 mRNA that has been inhibited by YB-1. Thus, YB-1 negatively regulates its own synthesis, presumably by specific interaction with the 3'UTR regulatory element, whereas PABP restores translational activity of YB-1 mRNA by displacing YB-1 from this element.",1
"Skabkina, Olga V, Lyabin, Dmitry N, Skabkin, Maxim A, Ovchinnikov, Lev P",2
T cell epitope immunotherapy induces a CD4+ T cell population with regulatory activity.,0
"Synthetic peptides, representing CD4(+) T cell epitopes, derived from the primary sequence of allergen molecules have been used to down-regulate allergic inflammation in sensitised individuals. Treatment of allergic diseases with peptides may offer substantial advantages over treatment with native allergen molecules because of the reduced potential for cross-linking IgE bound to the surface of mast cells and basophils.",1
"Verhoef, Adrienne, Alexander, Clare, Kay, A Barry, Larché, Mark",2
Structural basis for the interaction between pectin methylesterase and a specific inhibitor protein.,0
"Pectin, one of the main components of the plant cell wall, is secreted in a highly methyl-esterified form and subsequently deesterified in muro by pectin methylesterases (PMEs). In many developmental processes, PMEs are regulated by either differential expression or posttranslational control by protein inhibitors (PMEIs). PMEIs are typically active against plant PMEs and ineffective against microbial enzymes. Here, we describe the three-dimensional structure of the complex between the most abundant PME isoform from tomato fruit (Lycopersicon esculentum) and PMEI from kiwi (Actinidia deliciosa) at 1.9-A resolution. The enzyme folds into a right-handed parallel beta-helical structure typical of pectic enzymes. The inhibitor is almost all helical, with four long alpha-helices aligned in an antiparallel manner in a classical up-and-down four-helical bundle. The two proteins form a stoichiometric 1:1 complex in which the inhibitor covers the shallow cleft of the enzyme where the putative active site is located. The four-helix bundle of the inhibitor packs roughly perpendicular to the main axis of the parallel beta-helix of PME, and three helices of the bundle interact with the enzyme. The interaction interface displays a polar character, typical of nonobligate complexes formed by soluble proteins. The structure of the complex gives an insight into the specificity of the inhibitor toward plant PMEs and the mechanism of regulation of these enzymes.",1
"Di Matteo, Adele, Giovane, Alfonso, Raiola, Alessandro, Camardella, Laura, Bonivento, Daniele, De Lorenzo, Giulia, Cervone, Felice, Bellincampi, Daniela, Tsernoglou, Demetrius",2
Functional reassembly of the Escherichia coli maltose transporter following purification of a MalF-MalG subassembly.,0
"Taking advantage of a chaperone-like function of MalK, a stable complex of MalF-MalG could be solubilized from the Escherichia coli membrane and purified in high yield in the absence of MalK. This MalF-MalG complex was competent for efficient reassembly of a functional MalFGK(2) maltose transporter complex both in detergent solution and in proteoliposomes.",1
"Sharma, Susan, Davis, Johnny A, Ayvaz, Tulin, Traxler, Beth, Davidson, Amy L",2
Translational control of tetracycline resistance and conjugation in the Bacteroides conjugative transposon CTnDOT.,0
"The tetQ-rteA-rteB operon of the Bacteroides conjugative transposon CTnDOT is responsible for tetracycline control of the excision and transfer of CTnDOT. Previous studies revealed that tetracycline control of this operon occurred at the translational level and involved a hairpin structure located within the 130-base leader sequence that lies between the promoter of tetQ and the start codon of the gene. This hairpin structure is formed by two sequences, designated Hp1 and Hp8. Hp8 contains the ribosome binding site for tetQ. Examination of the leader region sequence revealed three sequences that might encode a leader peptide. One was only 3 amino acids long. The other two were 16 amino acids long. By introducing stop codons into the peptide coding regions, we have now shown that the 3-amino-acid peptide is the one that is essential for tetracycline control. Between Hp1 and Hp8 lies an 85-bp region that contains other possible RNA hairpin structures. Deletion analysis of this intervening DNA segment has now identified a sequence, designated Hp2, which is essential for tetracycline regulation. This sequence could form a short hairpin structure with Hp1. Mutations that made the Hp1-Hp2 structure more stable caused nearly constitutively high expression of the operon. Thus, stalling of ribosomes on the 3-amino-acid leader peptide could favor formation of the Hp1-Hp2 structure and thus preclude formation of the Hp1-Hp8 structure, releasing the ribosome binding site of tetQ. Finally, comparison of the CTnDOT tetQ leader regions with upstream regions of five tetQ genes found in other elements reveals that the sequences are virtually identical, suggesting that translational attenuation is responsible for control of tetracycline resistance in these other cases as well.",1
"Wang, Yanping, Rotman, Ella R, Shoemaker, Nadja B, Salyers, Abigail A",2
"cse, a Chimeric and variable gene, encodes an extracellular protein involved in cellular segregation in Streptococcus thermophilus.",0
"The isolation of a Streptococcus thermophilus CNRZ368 mutant displaying a long-chain phenotype allowed us to identify the cse gene (for cellular segregation). The N terminus of Cse exhibits high similarity to Streptococcus agalactiae surface immunogenic protein (SIP), while its C terminus exhibits high similarity to S. thermophilus PcsB. In CNRZ368, deletion of the entire cse open reading frame leads to drastic lengthening of cell chains and altered colony morphology. Complementation of the Deltacse mutation with a wild-type allele restored both wild-type phenotypes. The central part of Cse is a repeat-rich region with low sequence complexity. Comparison of cse from CNRZ368 and LMG18311 strains reveals high variability of this repeat-rich region. To assess the impact of this central region variability, the central region of LMG18311 cse was exchanged with that of CNRZ368 cse. This replacement did not affect chain length, showing that divergence of the central part does not modify cell segregation activity of Cse. The structure of the cse locus suggests that the chimeric organization of cse results from insertion of a duplicated sequence deriving from the pcsB 3' end into an ancestral sip gene. Thus, the cse locus illustrates the module-shuffling mechanism of bacterial gene evolution.",1
"Borges, Frédéric, Layec, Séverine, Thibessard, Annabelle, Fernandez, Annabelle, Gintz, Brigitte, Hols, Pascal, Decaris, Bernard, Leblond-Bourget, Nathalie",2
Expression of the bmpB gene of Borrelia burgdorferi is modulated by two distinct transcription termination events.,0
"bmp gene family 36 of Borrelia burgdorferi, the agent of Lyme disease, comprises four paralogs: bmpA, bmpB, bmpC, and bmpD. The bmpA and bmpB genes constitute an operon. All four genes have been found to be transcribed in cultured spirochetes. Expression from the bmpAB operon results in three distinct transcripts of 1.1, 1.6, and 2.4 kb, and the relative expression of bmpA mRNA is three- to fourfold greater than that of bmpB mRNA. However, thus far only expression of the BmpA protein has been demonstrated. Therefore, in this study we characterized the origins of the three transcripts and compared the relative expression of the BmpA and BmpB proteins. Northern blotting revealed that the three distinct transcripts originated from a single promoter located upstream of bmpA but terminated either 3' to the bmpA (1.1-kb RNA) or bmpB (2.4-kb RNA) gene or, most unusually, within the bmpB gene (1.6-kb RNA). Termination within the bmpB gene was associated with a functional Rho-independent transcription terminator. At the protein level, we also observed a 4.3-fold greater abundance of BmpA compared to that of BmpB. These studies identify a transcription termination mechanism in B. burgdorferi resulting in the disparate expression of the two genes of the bmpAB operon.",1
"Ramamoorthy, Ramesh, McClain, Natalie A, Gautam, Aarti, Scholl-Meeker, Dorothy",2
Regulation of NAD synthesis by the trifunctional NadR protein of Salmonella enterica.,0
"The three activities of NadR were demonstrated in purified protein and assigned to separate domains by missense mutations. The N-terminal domain represses transcription of genes for NAD synthesis and salvage. The C-terminal domain has nicotinamide ribose kinase (NmR-K; EC 2.7.1.22) activity, which is essential for assimilation of NmR, converting it internally to nicotinamide mononucleotide (NMN). The central domain has a weak adenylyltransferase (NMN-AT; EC 2.7.7.1) activity that converts NMN directly to NAD but is physiologically irrelevant. This central domain mediates regulatory effects of NAD on all NadR activities. In the absence of effectors, pure NadR protein binds operator DNA (the default state) and is released by ATP (expected to be present in vivo). NAD allows NadR to bind DNA in the presence of ATP and causes repression in vivo. A superrepressor mutation alters an ATP-binding residue in the central (NMN-AT) domain. This eliminates NMN-AT activity and places the enzyme in its default (DNA binding) state. The mutant protein shows full NmR kinase activity that is 10-fold more sensitive to NAD inhibition than the wild type. It is proposed that NAD and the superrepressor mutation exert their effects by preventing ATP from binding to the central domain.",1
"Grose, Julianne H, Bergthorsson, Ulfar, Roth, John R",2
Comprehensive characterization of the contribution of individual SigB-dependent general stress genes to stress resistance of Bacillus subtilis.,0
"The sigma(B)-dependent general stress regulon of Bacillus subtilis comprises more than 150 members. Induction of this regulon by imposition of environmental or metabolic stress confers multiple, nonspecific, and preemptive stress resistance to nongrowing, nonsporulated cells of B. subtilis. In this study we performed a regulon-wide phenotypic screening analysis to determine the stress sensitivity profiles of 94 mutants defective in candidate members of the general stress regulon that were previously identified in our transcriptional profiling study of the general stress response of B. subtilis. The phenotypic screening analysis included analysis of adaptation to a growth-inhibiting concentration of ethanol (10%, vol/vol) or NaCl (10%, wt/vol), severe heat shock (54 degrees C), and low temperature (survival at 4 degrees C and growth at 12.5 degrees C). Surprisingly, 85% of the mutants tested displayed increased sensitivity at an alpha confidence level of < or =0.01 to at least one of the four stresses tested, and 62% still exhibited increased sensitivity at an alpha of < or =0.001. In essence, we were able to assign 63 genes (28 genes with an alpha of < or =0.001) to survival after ethanol shock, 37 genes (28 genes with an alpha of < or =0.001) to protection from NaCl shock, 34 genes (24 genes with an alpha of < or =0.001) to survival at 4 degrees C, and 10 genes (3 genes with an alpha of < or =0.001) to management of severe heat shock. Interestingly, there was a substantial overlap between the genes necessary for survival during ethanol shock and the genes necessary for survival at 4 degrees C, and there was also an overlap between genes required for survival during ethanol shock and genes required for survival during NaCl shock. Our data provide evidence for the importance of the sigma(B) regulon at low temperatures, not only for growth but also for survival. Moreover, the data imply that a secondary oxidative stress seems to be a common component of the severe stresses tested.",1
"Höper, Dirk, Völker, Uwe, Hecker, Michael",2
"MinC mutants deficient in MinD- and DicB-mediated cell division inhibition due to loss of interaction with MinD, DicB, or a septal component.",0
"The min locus encodes a negative regulatory system that limits formation of the cytokinetic Z ring to midcell by preventing its formation near the poles. Of the three Min proteins, MinC is the inhibitor and prevents Z-ring formation by interacting directly with FtsZ. MinD activates MinC by recruiting it to the membrane and conferring a higher affinity on the MinCD complex for a septal component. MinE regulates the cellular location of MinCD by inducing MinD, and thereby MinC, to oscillate between the poles of the cell, resulting in a time-averaged concentration of MinCD on the membrane that is lowest at midcell. MinC can also be activated by the prophage-encoded protein DicB, which targets MinC to the septum without recruiting it first to the membrane. Previous studies have shown that the C-terminal domain of MinC is responsible for the interaction with MinD, DicB, and the septal component. In the present study, we isolated mutations in the C-terminal domain of MinC that affected its interaction with MinD, DicB, and the septal component. Among the mutations isolated, R133A and S134A are specifically deficient in the interaction with MinD, E156A is primarily affected in the interaction with DicB, and R172A is primarily deficient in the interaction with the septum. These mutations differentiate the interactions of MinC with its partners and further support the model of MinCD- and MinC-DicB-mediated cell division inhibition.",1
"Zhou, Huaijin, Lutkenhaus, Joe",2
Diversity of genome structure in Salmonella enterica serovar Typhi populations.,0
"The genomes of most strains of Salmonella and Escherichia coli are highly conserved. In contrast, all 136 wild-type strains of Salmonella enterica serovar Typhi analyzed by partial digestion with I-CeuI (an endonuclease which cuts within the rrn operons) and pulsed-field gel electrophoresis and by PCR have rearrangements due to homologous recombination between the rrn operons leading to inversions and translocations. Recombination between rrn operons in culture is known to be equally frequent in S. enterica serovar Typhi and S. enterica serovar Typhimurium; thus, the recombinants in S. enterica serovar Typhi, but not those in S. enterica serovar Typhimurium, are able to survive in nature. However, even in S. enterica serovar Typhi the need for genome balance and the need for gene dosage impose limits on rearrangements. Of 100 strains of genome types 1 to 6, 72 were only 25.5 kb off genome balance (the relative lengths of the replichores during bidirectional replication from oriC to the termination of replication [Ter]), while 28 strains were less balanced (41 kb off balance), indicating that the survival of the best-balanced strains was greater. In addition, the need for appropriate gene dosage apparently selected against rearrangements which moved genes from their accustomed distance from oriC. Although rearrangements involving the seven rrn operons are very common in S. enterica serovar Typhi, other duplicated regions, such as the 25 IS200 elements, are very rarely involved in rearrangements. Large deletions and insertions in the genome are uncommon, except for deletions of Salmonella pathogenicity island 7 (usually 134 kb) from fragment I-CeuI-G and 40-kb insertions, possibly a prophage, in fragment I-CeuI-E. The phage types were determined, and the origins of the phage types appeared to be independent of the origins of the genome types.",1
"Kothapalli, Sushma, Nair, Satheesh, Alokam, Suneetha, Pang, Tikki, Khakhria, Rasik, Woodward, David, Johnson, Wendy, Stocker, Bruce A D, Sanderson, Kenneth E, Liu, Shu-Lin",2
Catabolite repression of the propionate catabolic genes in Escherichia coli and Salmonella enterica: evidence for involvement of the cyclic AMP receptor protein.,0
"Previous studies with Salmonella enterica serovar Typhimurium LT2 demonstrated that transcriptional activation of the prpBCDE operon requires the function of transcription factor PrpR, sigma-54, and IHF. In this study, we found that transcription from the prpBCDE and prpR promoters was down-regulated by the addition of glucose or glycerol, indicating that these genes may be regulated by the cyclic AMP (cAMP)-cAMP receptor protein (CRP) complex. Targeted mutagenesis of a putative CRP-binding site in the promoter region between prpR and prpBCDE suggested that these genes are under the control of CRP. Furthermore, cells with defects in cya or crp exhibited reduced transcriptional activation of prpR and prpBCDE in Escherichia coli. These results demonstrate that propionate metabolism is subject to catabolite repression by the global transcriptional regulator CRP and that this regulation is effected through control of both the regulator gene prpR and the prpBCDE operon itself. The unique properties of the regulation of these two divergent promoters may have important implications for mechanisms of CRP-dependent catabolite repression acting in conjunction with a member of the sigma-54 family of transcriptional activators.",1
"Lee, Sung Kuk, Newman, Jack D, Keasling, Jay D",2
Protein diversity confers specificity in plasmid segregation.,0
"The ParG segregation protein (8.6 kDa) of multidrug resistance plasmid TP228 is a homodimeric DNA-binding factor. The ParG dimer consists of intertwined C-terminal domains that adopt a ribbon-helix-helix architecture and a pair of flexible, unstructured N-terminal tails. A variety of plasmids possess partition loci with similar organizations to that of TP228, but instead of ParG homologs, these plasmids specify a diversity of unrelated, but similarly sized, partition proteins. These include the proteobacterial pTAR, pVT745, and pB171 plasmids. The ParG analogs of these plasmids were characterized in parallel with the ParG homolog encoded by the pseudomonal plasmid pVS1. Like ParG, the four proteins are dimeric. No heterodimerization was detectable in vivo among the proteins nor with the prototypical ParG protein, suggesting that monomer-monomer interactions are specific among the five proteins. Nevertheless, as with ParG, the ParG analogs all possess significant amounts of unordered amino acid residues, potentially highlighting a common structural link among the proteins. Furthermore, the ParG analogs bind specifically to the DNA regions located upstream of their homologous parF-like genes. These nucleoprotein interactions are largely restricted to cognate protein-DNA pairs. The results reveal that the partition complexes of these and related plasmids have recruited disparate DNA-binding factors that provide a layer of specificity to the macromolecular interactions that mediate plasmid segregation.",1
"Fothergill, Timothy J G, Barillà, Daniela, Hayes, Finbarr",2
An FNR-type regulator controls the anaerobic expression of hyn hydrogenase in Thiocapsa roseopersicina.,0
"The purple sulfur photosynthetic bacterium Thiocapsa roseopersicina BBS contains a heat-stable membrane-associated hydrogenase encoded by the hyn operon. Expression from the hyn operon regulatory region is up-regulated under anaerobic conditions. cis elements were mapped between positions -602 and -514 upstream from the hynS gene. Within this region two sequences that resemble DNA sites for FNR were recognized. The gene of an FNR homologue, FnrT, was identified in the genome of T. roseopersicina, and an fnrT knockout mutant was constructed. Anaerobic induction of hynS expression was abolished in the fnrT mutant, suggesting that FnrT is an activator of the hynS promoter. The T. roseopersicina hynS promoter could be activated in Escherichia coli, and this regulation was dependent on E. coli FNR. In vitro experiments with purified E. coli Ala154 FNR protein and purified E. coli RNA polymerase showed that FNR bound to two sites in the hyn regulatory region, that FNR could activate transcription initiation at the hynS promoter, and that FNR bound at the two target sites activated to different extents.",1
"Kovács, Akos T, Rákhely, Gábor, Browning, Douglas F, Fülöp, András, Maróti, Gergely, Busby, Stephen J W, Kovács, Kornél L",2
Import of the transfer RNase colicin D requires site-specific interaction with the energy-transducing protein TonB.,0
"The transfer RNase colicin D and ionophoric colicin B appropriate the outer membrane iron siderophore receptor FepA and share a common translocation requirement for the TonB pathway to cross the outer membrane. Despite the almost identical sequences of the N-terminal domains required for the translocation of colicins D and B, two spontaneous tonB mutations (Arg158Ser and Pro161Leu) completely abolished colicin D toxicity but did not affect either the sensitivity to other colicins or the FepA-dependent siderophore uptake capacity. The sensitivity to colicin D of both tonB mutants was fully restored by specific suppressor mutations in the TonB box of colicin D, at Ser18(Thr) and Met19(Ile), respectively. This demonstrates that the interaction of colicin D with TonB is critically dependent on certain residues close to position 160 in TonB and on the side chains of certain residues in the TonB box of colicin D. The effect of introducing the TonB boxes from other TonB-dependent receptors and colicins into colicins D and B was studied. The results of these and other changes in the two TonB boxes show that the role of residues at positions 18 and 19 in colicin D is strongly modulated by other nearby and/or distant residues and that the overall function of colicin D is much more dependent on the interaction with TonB involving the TonB box than is the function of colicin B.",1
"Mora, Liliana, Diaz, Nancy, Buckingham, Richard H, de Zamaroczy, Miklos",2
Crystal structure of the flagellar rotor protein FliN from Thermotoga maritima.,0
"FliN is a component of the bacterial flagellum that is present at levels of more than 100 copies and forms the bulk of the C ring, a drum-shaped structure at the inner end of the basal body. FliN interacts with FliG and FliM to form the rotor-mounted switch complex that controls clockwise-counterclockwise switching of the motor. In addition to its functions in motor rotation and switching, FliN is thought to have a role in the export of proteins that form the exterior structures of the flagellum (the rod, hook, and filament). Here, we describe the crystal structure of most of the FliN protein of Thermotoga maritima. FliN is a tightly intertwined dimer composed mostly of beta sheet. Several well-conserved hydrophobic residues form a nonpolar patch on the surface of the molecule. A mutation in the hydrophobic patch affected both flagellar assembly and switching, showing that this surface feature is important for FliN function. The association state of FliN in solution was studied by analytical ultracentrifugation, which provided clues to the higher-level organization of the protein. T. maritima FliN is primarily a dimer in solution, and T. maritima FliN and FliM together form a stable FliM(1)-FliN(4) complex. Escherichia coli FliN forms a stable tetramer in solution. The arrangement of FliN subunits in the tetramer was modeled by reference to the crystal structure of tetrameric HrcQB(C), a related protein that functions in virulence factor secretion in Pseudomonas syringae. The modeled tetramer is elongated, with approximate dimensions of 110 by 40 by 35 Angstroms, and it has a large hydrophobic cleft formed from the hydrophobic patches on the dimers. On the basis of the present data and available electron microscopic images, we propose a model for the organization of FliN subunits in the C ring.",1
"Brown, Perry N, Mathews, Michael A A, Joss, Lisa A, Hill, Christopher P, Blair, David F",2
The Bacillus subtilis SinR and RapA developmental regulators are responsible for inhibition of spore development by alcohol.,0
"Even though there is a large body of information concerning the harmful effects of alcohol on different organisms, the mechanism(s) that affects developmental programs, at a single-cell level, has not been clearly identified. In this respect, the spore-forming bacterium Bacillus subtilis constitutes an excellent model to study universal questions of cell fate, cell differentiation, and morphogenesis. Here, we demonstrate that treatment with subinhibitory concentrations of alcohol that did not affect vegetative growth inhibited the initiation of spore development through a selective blockage of key developmental genes under the control of the master transcription factor Spo0A approximately P. Isopropyl-beta-D-thiogalactopyranoside-directed expression of a phosphorylation-independent form of Spo0A (Sad67) and the use of an in vivo mini-Tn10 insertional library permitted the identification of the developmental SinR repressor and RapA phosphatase as the effectors that mediated the inhibitory effect of alcohol on spore morphogenesis. A double rapA sinR mutant strain was completely resistant to the inhibitory effects of different-C-length alcohols on sporulation, indicating that the two cell fate determinants were the main or unique regulators responsible for the spo0 phenotype of wild-type cells in the presence of alcohol. Furthermore, treatment with alcohol produced a significant induction of rapA and sinR, while the stationary-phase induction of sinI, which codes for a SinR inhibitor, was completely turned off by alcohol. As a result, a dramatic repression of spo0A and the genes under its control occurred soon after alcohol addition, inhibiting the onset of sporulation and permitting the evaluation of alternative pathways required for cellular survival.",1
"Gottig, Natalia, Pedrido, María Eugenia, Méndez, Marcelo, Lombardía, Esteban, Rovetto, Adrián, Philippe, Valeria, Orsaria, Lelia, Grau, Roberto",2
"Characterization of LtsA from Rhodococcus erythropolis, an enzyme with glutamine amidotransferase activity.",0
"The nocardioform actinomycete Rhodococcus erythropolis has a characteristic cell wall structure. The cell wall is composed of arabinogalactan and mycolic acid and is highly resistant to the cell wall-lytic activity of lysozyme (muramidase). In order to improve the isolation of recombinant proteins from R. erythropolis host cells (N. Nakashima and T. Tamura, Biotechnol. Bioeng. 86:136-148, 2004), we isolated two mutants, L-65 and L-88, which are susceptible to lysozyme treatment. The lysozyme sensitivity of the mutants was complemented by expression of Corynebacterium glutamicum ltsA, which codes for an enzyme with glutamine amidotransferase activity that results from coupling of two reactions (a glutaminase activity and a synthetase activity). The lysozyme sensitivity of the mutants was also complemented by ltsA homologues from Bacillus subtilis and Mycobacterium tuberculosis, but the homologues from Streptomyces coelicolor and Escherichia coli did not complement the sensitivity. This result suggests that only certain LtsA homologues can confer lysozyme resistance. Wild-type recombinant LtsA from R. erythropolis showed glutaminase activity, but the LtsA enzymes from the L-88 and L-65 mutants displayed drastically reduced activity. Interestingly, an ltsA disruptant mutant, which expressed the mutated LtsA, changed from lysozyme sensitive to lysozyme resistant when NH(4)Cl was added into the culture media. The glutaminase activity of the LtsA mutants inactivated by site-directed mutagenesis was also restored by addition of NH(4)Cl, indicating that NH(3) can be used as an amide donor molecule. Taken together, these results suggest that LtsA is critically involved in mediating lysozyme resistance in R. erythropolis cells.",1
"Mitani, Yasuo, Meng, Xianying, Kamagata, Yoichi, Tamura, Tomohiro",2
"Identification of rcnA (yohM), a nickel and cobalt resistance gene in Escherichia coli.",0
"We report here on the isolation and primary characterization of the yohM gene of Escherichia coli. We show that yohM encodes a membrane-bound polypeptide conferring increased nickel and cobalt resistance in E. coli. yohM was specifically induced by nickel or cobalt but not by cadmium, zinc, or copper. Mutation of yohM increased the accumulation of nickel inside the cell, whereas cells harboring yohM in multicopy displayed reduced intracellular nickel content. Our data support the hypothesis that YohM is the first described efflux system for nickel and cobalt in E. coli. We propose rcnA (resistance to cobalt and nickel) as the new denomination of yohM.",1
"Rodrigue, Agnès, Effantin, Géraldine, Mandrand-Berthelot, Marie-Andrée",2
Genetic and structural analysis of the Bacteroides conjugative transposon CTn341.,0
"The genetic structure and functional organization of a Bacteroides conjugative transposon (CTn), CTn341, were determined. CTn341 was originally isolated from a tetracycline-resistant clinical isolate of Bacteroides vulgatus. The element was 51,993 bp long, which included a 5-bp coupling sequence that linked the transposon ends in the circular form. There were 46 genes, and the corresponding gene products fell into three major functional groups: DNA metabolism, regulation and antibiotic resistance, and conjugation. The G + C content and codon usage observed in the functional groups suggested that the groups belong to different genetic lineages, indicating that CTn341 is a composite, modular element. Mutational analysis of genes representing the different functional groups provided evidence for the gene assignments and showed that the basic conjugation and excision genes are conserved among Bacteroides spp. A group IIA1 intron, designated B.f.I1, was found to be inserted into the bmhA methylase gene. Reverse transcriptase PCR analysis of CTn341 RNA showed that B.fr.I1 was functional and was spliced out of the bmhA gene. Six related CTn-like elements were found in the genome sequences of Bacteroides fragilis NCTC9343 and Bacteroides thetaiotaomicron VPI5482. The putative elements were similar to CTn341 primarily in the tra and mob regions and in the exc gene, and several appeared to contain intron elements. Our data provide the first reported sequence for a complete Bacteroides CTn, and they should be of considerable benefit to further functional and genetic analyses of antibiotic resistance elements and genome evolution in Bacteroides.",1
"Bacic, M, Parker, A C, Stagg, J, Whitley, H P, Wells, W G, Jacob, L A, Smith, C J",2
Enhanced synthesis of internalin A in aro mutants of Listeria monocytogenes indicates posttranscriptional control of the inlAB mRNA.,0
"Listeria monocytogenes mutants with deletions in aroA, aroB, or aroE exhibited strong posttranscriptional upregulation of internalin A (InlA) and InlB synthesis, which resulted in a more-than-10-fold increase in InlA-mediated internalization by epithelial Caco-2 cells and a 4-fold increase in InlB-mediated internalization by microvascular endothelial cells (human brain microvascular endothelial cells) compared to the wild-type strain. The increase in InlA and InlB production was not due to enhanced PrfA- and/or sigma factor B (SigB)-dependent inlAB transcription but was caused by enhanced translation of the inlAB transcripts in the aro mutants. All inlA(B) transcripts had a 396-nucleotide upstream 5' untranslated region (UTR). Different deletions introduced into this UTR led to significant reductions in InlA and InlB synthesis; enhanced translation of all of the truncated transcripts in the aro mutants was, however, still observed. Thus, translation of the inlAB transcripts was subject to two modes of posttranscriptional control, one mediated by the UTR structure and the other mediated by the aro mutation. The latter mode of control seemed to be related to the predominantly anaerobic metabolism of the aro mutants.",1
"Stritzker, Jochen, Schoen, Christoph, Goebel, Werner",2
Surprising dependence on postsegregational killing of host cells for maintenance of the large virulence plasmid of Shigella flexneri.,0
"Low-copy-number plasmids all encode multiple systems to ensure their propagation, including replication, partition (active segregation), and postsegregational killing (PSK) systems. PSK systems kill those rare cells that lose the plasmid due to replication or segregation errors. PSK systems should not be used as the principle means of maintaining the plasmid. The metabolic cost of killing the many cured cells that would arise from random plasmid segregation is far too high. Here we describe an interesting exception to this rule. Maintenance of the large virulence plasmid of Shigella flexneri is highly dependent on one of its PSK systems, mvp, at 37 degrees C, the temperature experienced during pathogenesis. At 37 degrees C, the plasmid is very unstable and mvp efficiently kills the resulting cured bacterial cells. This imposes a major growth disadvantage on the virulent bacterial population. The systems that normally ensure accurate plasmid replication and segregation are attenuated or overridden at 37 degrees C. At 30 degrees C, a temperature encountered by Shigella in the outside environment, the maintenance systems function normally and the plasmid is no longer dependent on mvp. We discuss why the virulent pathogen tolerates this self-destructive method of propagation at the temperature of infection.",1
"Sayeed, Sameera, Brendler, Therese, Davis, Michael, Reaves, Lucretia, Austin, Stuart",2
Identification of cyclic AMP-regulated genes in Mycobacterium tuberculosis complex bacteria under low-oxygen conditions.,0
"Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), which kills approximately 2 million people a year despite current treatment options. A greater understanding of the biology of this bacterium is needed to better combat TB disease. The M. tuberculosis genome encodes as many as 15 adenylate cyclases, suggesting that cyclic AMP (cAMP) has an important, yet overlooked, role in mycobacteria. This study examined the effect of exogenous cAMP on protein expression in Mycobacterium bovis BCG grown under hypoxic versus ambient conditions. Both shaking and shallow standing cultures were examined for each atmospheric condition. Different cAMP-dependent changes in protein expression were observed in each condition by two-dimensional gel electrophoresis. Shaking low-oxygen cultures produced the most changes (12), while standing ambient conditions showed the fewest (2). Five upregulated proteins, Rv1265, Rv2971, GroEL2, PE_PGRS6a, and malate dehydrogenase, were identified from BCG by mass spectrometry and were shown to also be regulated by cAMP at the mRNA level in both M. tuberculosis H37Rv and BCG. To our knowledge, these data provide the first direct evidence for cAMP-mediated gene regulation in TB complex mycobacteria.",1
"Gazdik, Michaela A, McDonough, Kathleen A",2
Cytochrome oxidase deficiency protects Escherichia coli from cell death but not from filamentation due to thymine deficiency or DNA polymerase inactivation.,0
"Temperature-sensitive DNA polymerase mutants (dnaE) are protected from cell death on incubation at nonpermissive temperature by mutation in the cydA gene controlling cytochrome bd oxidase. Protection is observed in complex (Luria-Bertani [LB]) medium but not on minimal medium. The cydA mutation protects a thymine-deficient strain from death in the absence of thymine on LB but not on minimal medium. Both dnaE and Deltathy mutants filament under nonpermissive conditions. Filamentation per se is not the cause of cell death, because the dnaE cydA double mutant forms long filaments after 24 h of incubation in LB medium at nonpermissive temperature. These filaments have multiply dispersed nucleoids and produce colonies on return to permissive conditions. The protective effect of a deficiency of cydA at high temperature is itself suppressed by overexpression of cytochrome bo3, indicating that the phenomenon is related to energy metabolism rather than to a specific effect of the cydA protein. We propose that filamentation and cell death resulting from thymine deprivation or slowing of DNA synthesis are not sequential events but occur in response to the same or a similar signal which is modulated in complex medium by cytochrome bd oxidase. The events which follow inhibition of replication fork progression due to either polymerase inactivation, thymine deprivation, or hydroxyurea inhibition differ in detail from those following actual DNA damage.",1
"Strauss, Bernard, Kelly, Kemba, Ekiert, Damian",2
A novel mutation in kaiC affects resetting of the cyanobacterial circadian clock.,0
"Light is the most important factor controlling circadian systems in response to day-night cycles. In order to better understand the regulation of circadian rhythms by light in Synechococcus elongatus PCC 7942, we screened for mutants with defective phase shifting in response to dark pulses. Using a 5-h dark-pulse protocol, we identified a mutation in kaiC that we termed pr1, for phase response 1. In the pr1 mutant, a 5-h dark pulse failed to shift the phase of the circadian rhythm, while the same pulse caused a 10-h phase shift in wild-type cells. The rhythm in accumulation of KaiC was abolished in the pr1 mutant, and the rhythmicity of KaiC phosphorylation was reduced. Additionally, the pr1 mutant was defective in mediating the feedback inhibition of kaiBC. Finally, overexpression of mutant KaiC led to a reduced phase shift compared to that for wild-type KaiC. Thus, KaiC appears to play a role in resetting the cellular clock in addition to its documented role in the feedback regulation of circadian rhythms.",1
"Kiyohara, Yota B, Katayama, Mitsunori, Kondo, Takao",2
Nucleotide substitution and recombination at orthologous loci in Staphylococcus aureus.,0
"The pattern of nucleotide substitution was examined at 2,129 orthologous loci among five genomes of Staphylococcus aureus, which included two sister pairs of closely related genomes (MW2/MSSA476 and Mu50/N315) and the more distantly related MRSA252. A total of 108 loci were unusual in lacking any synonymous differences among the five genomes; most of these were short genes encoding proteins highly conserved at the amino acid sequence level (including many ribosomal proteins) or unknown predicted genes. In contrast, 45 genes were identified that showed anomalously high divergence at synonymous sites. The latter genes were evidently introduced by homologous recombination from distantly related genomes, and in many cases, the pattern of nucleotide substitution made it possible to reconstruct the most probable recombination event involved. These recombination events introduced genes encoding proteins that differed in amino acid sequence and thus potentially in function. Several of the proteins are known or likely to be involved in pathogenesis (e.g., staphylocoagulase, exotoxin, Ser-Asp fibrinogen-binding bone sialoprotein-binding protein, fibrinogen and keratin-10 binding surface-anchored protein, fibrinogen-binding protein ClfA, and enterotoxin P). Therefore, the results support the hypothesis that exchange of homologous genes among S. aureus genomes can play a role in the evolution of pathogenesis in this species.",1
"Hughes, Austin L, Friedman, Robert",2
Genome-wide transcriptional profiling of the steady-state response of Pseudomonas aeruginosa to hydrogen peroxide.,0
"The steady-state response of Pseudomonas aeruginosa to the oxidative-stress-generating agent hydrogen peroxide was analyzed by PAO1 transcriptome profiling. In total, 694, 411, and 237 genes were upregulated and 668, 576, and 468 genes were downregulated in P. aeruginosa strains TB, 892, and PAO1, respectively. The expression profiles of the two variants of the TB clone were significantly more related to each other than the expression profile of either strain was to that of PAO1. Exposure to H(2)O(2) activated by more than 10-fold the expression of the cyoABCD operon, which is key for aerobic respiration, and of oxidative-stress response elements such as the catalase KatB, the alkyl hydroperoxide reductase AhpF, and the thioredoxin reductase 2 operon. Genes for iron and sulfur homeostasis were upregulated. Most enzymes necessary for the conversion of amino acids into the citric acid cycle were globally downregulated at the transcriptional level. Nitrate respiration and arginine fermentation were shut off in the clone TB strains and attenuated in the PAO strain. The transcriptional profiles indicate that the two clone TB strains are more proficient in coping with H(2)O(2)-mediated oxidative stress than the reference strain PAO. According to this data, we recommend study of the transcriptome of strain PAO1 in parallel with those of at least two strains of another clone in order to differentiate common responses from clone- and strain-specific responses and to minimize overinterpretations of microarray data.",1
"Salunkhe, Prabhakar, Töpfer, Tanja, Buer, Jan, Tümmler, Burkhard",2
Mycobacterial lipid II is composed of a complex mixture of modified muramyl and peptide moieties linked to decaprenyl phosphate.,0
"Structural analysis of compounds identified as lipid I and II from Mycobacterium smegmatis demonstrated that the lipid moiety is decaprenyl phosphate; thus, M. smegmatis is the first bacterium reported to utilize a prenyl phosphate other than undecaprenyl phosphate as the lipid carrier involved in peptidoglycan synthesis. In addition, mass spectrometry showed that the muropeptides from lipid I are predominantly N-acetylmuramyl-L-alanine-D-glutamate-meso-diaminopimelic acid-D-alanyl-D-alanine, whereas those isolated from lipid II form an unexpectedly complex mixture in which the muramyl residue and the pentapeptide are modified singly and in combination. The muramyl residue is present as N-acetylmuramic acid, N-glycolylmuramic acid, and muramic acid. The carboxylic functions of the peptide side-chains of lipid II showed three types of modification, with the dominant one being amidation. The preferred site for amidation is the free carboxyl group of the meso-diaminopimelic acid residue. Diamidated species were also observed. The carboxylic function of the terminal D-alanine of some molecules is methylated, as are all three carboxylic acid functions of other molecules. This study represents the first structural analysis of mycobacterial lipid I and II and the first report of extensive modifications of these molecules. The observation that lipid I was unmodified strongly suggests that the lipid II intermediates of M. smegmatis are substrates for a variety of enzymes that introduce modifications to the sugar and amino acid residues prior to the synthesis of peptidoglycan.",1
"Mahapatra, Sebabrata, Yagi, Tetsuya, Belisle, John T, Espinosa, Benjamin J, Hill, Preston J, McNeil, Michael R, Brennan, Patrick J, Crick, Dean C",2
"Smx nuclease is the major, low-pH-inducible apurinic/apyrimidinic endonuclease in Streptococcus mutans.",0
"The causative agent of dental caries in humans, Streptococcus mutans, outcompetes other bacterial species in the oral cavity and causes disease by surviving acidic conditions in dental plaque. We have previously reported that the low-pH survival strategy of S. mutans includes the ability to induce a DNA repair system that appears to involve an enzyme with exonuclease functions (K. Hahn, R. C. Faustoferri, and R. G. Quivey, Jr., Mol. Microbiol 31:1489-1498, 1999). Here, we report overexpression of the S. mutans apurinic/apyrimidinic (AP) endonuclease, Smx, in Escherichia coli; initial characterization of its enzymatic activity; and analysis of an smx mutant strain of S. mutans. Insertional inactivation of the smx gene eliminates the low-pH-inducible exonuclease activity previously reported. In addition, loss of Smx activity renders the mutant strain sensitive to hydrogen peroxide treatment but relatively unaffected by acid-mediated damage or near-UV irradiation. The smx strain of S. mutans was highly sensitive to the combination of iron and hydrogen peroxide, indicating the likely production of hydroxyl radical by Fenton chemistry with concomitant formation of AP sites that are normally processed by the wild-type allele. Smx activity was sufficiently expressed in E. coli to protect an xth mutant strain from the effects of hydrogen peroxide treatment. The data indicate that S. mutans expresses an inducible, class II-like AP endonuclease, encoded by the smx gene, that exhibits exonucleolytic activity and is regulated as part of the acid-adaptive response of the organism. Smx is likely the primary, if not the sole, AP endonuclease induced during growth at low pH values.",1
"Faustoferri, Roberta C, Hahn, Kristina, Weiss, Kellie, Quivey, Robert G",2
Positive selection for loss-of-function tat mutations identifies critical residues required for TatA activity.,0
"The Tat system, found in the cytoplasmic membrane of many bacteria, is a general export pathway for folded proteins. Here we describe the development of a method, based on the transport of chloramphenicol acetyltransferase, that allows positive selection of mutants defective in Tat function. We have demonstrated the utility of this method by selecting novel loss-of-function alleles of tatA from a pool of random tatA mutations. Most of the mutations that were isolated fall in the amphipathic region of TatA, emphasizing the pivotal role that this part of the protein plays in TatA function.",1
"Hicks, Matthew G, Lee, Philip A, Georgiou, George, Berks, Ben C, Palmer, Tracy",2
Clonal distribution and phase-variable expression of a major histocompatibility complex analogue protein in Staphylococcus aureus.,0
The mapW gene of Staphylococcus aureus strain N315 contains a poly(A) tract which truncates translation of the protein. This study demonstrates that mapW is an allelic variant of the map/eap genes found in other strains and that the variation in the length of this poly(A) tract suggests that it is a contingency locus.,1
"Buckling, Angus, Neilson, James, Lindsay, Jodi, ffrench-Constant, Richard, Enright, Mark, Day, Nicholas, Massey, Ruth C",2
Polarity of enteropathogenic Escherichia coli EspA filament assembly and protein secretion.,0
"Type III secretion systems (TTSS) are sophisticated macromolecular structures that play an imperative role in bacterial infections and human disease. The TTSS needle complex is conserved among bacterial pathogens and shows broad similarity to the flagellar basal body. However, the TTSS of enteropathogenic and enterohemorrhagic Escherichia coli, two important human enteric pathogens, is unique in that it has an approximately 12-nm-diameter filamentous extension to the needle that is composed of the secreted translocator protein EspA. EspA filaments and flagellar structures have very similar helical symmetry parameters. In this study we investigated EspA filament assembly and the delivery of effector proteins across the bacterial cell wall. We show that EspA filaments are elongated by addition of EspA subunits to the tip of the growing filament. Moreover, EspA filament length is modulated by the availability of intracellular EspA subunits. Finally, we provide direct evidence that EspA filaments are hollow conduits through which effector proteins are delivered to the extremity of the bacterial cell (and subsequently into the host cell).",1
"Crepin, Valérie F, Shaw, Robert, Abe, Cecilia M, Knutton, Stuart, Frankel, Gad",2
Expression of fnr is constrained by an upstream IS5 insertion in certain Escherichia coli K-12 strains.,0
"FNR is a global transcriptional regulator that controls anaerobic gene expression in Escherichia coli. Through the use of a number of approaches it was shown that fnr gene expression is reduced approximately three- to fourfold in E. coli strain MC4100 compared with the results seen with strain MG1655. This reduction in fnr expression is due to the insertion of IS5 (is5F) in the regulatory region of the gene at position -41 relative to the transcription initiation site. Transcription of the fnr gene nevertheless occurs from its own promoter in strain MC4100, but transcript levels are reduced approximately fourfold compared with those seen with strain MG1655. Remarkably, in strains bearing is5F the presence of Hfq prevents IS5-dependent transcriptional silencing of fnr expression. Thus, an hfq mutant of MC4100 is devoid of FNR protein and has the phenotype of an fnr mutant. In strain MG1655, or a derivative of MC4100 lacking is5F, mutation of hfq had no effect on fnr transcript levels. This finding indicates that IS5 mediates the effect of Hfq on fnr expression in MC4100. Western blot analysis revealed that cellular levels of FNR were reduced threefold in strain MC4100 compared with strain MG1655 results. A selection of FNR-dependent genes fused to lacZ were analyzed for the effects of reduced FNR levels on anaerobic gene expression. Expression of some operons, e.g., focA-pfl and fdnGHJI, was unaffected by reduction in the level of FNR, while the expression of other genes such as ndh and nikA was clearly affected.",1
"Sawers, R Gary",2
Cross-resistance of Escherichia coli RNA polymerases conferring rifampin resistance to different antibiotics.,0
"In this study we further defined the rifampin-binding sites in Escherichia coli RNA polymerase (RNAP) and determined the relationship between rifampin-binding sites and the binding sites of other antibiotics, including two rifamycin derivatives, rifabutin and rifapentine, and streptolydigin and sorangicin A, which are unrelated to rifampin, using a purified in vitro system. We found that there is almost a complete correlation between resistance to rifampin (Rif(r)) and reduced rifampin binding to 12 RNAPs purified from different rpoB Rif(r) mutants and a complete cross-resistance among the different rifamycin derivatives. Most Rif(r) RNAPs were sensitive to streptolydigin, although some exhibited weak resistance to this antibiotic. However, 5 out of the 12 Rif(r) RNAPs were partially resistant to sorangicin A, and one was completely cross-resistant to sorangicin A, indicating that the binding site(s) for these two antibiotics overlaps. Both rifampin and sorangicin A inhibited the transition step between transcription initiation and elongation; however, longer abortive initiation products were produced in the presence of the latter, indicating that the binding site for sorangicin A is within the rifampin-binding site. Competition experiments of different antibiotics with (3)H-labeled rifampin for binding to wild-type RNAP further confirmed that the binding sites for rifampin, rifabutin, rifapentine, and sorangicin A are shared, whereas the binding sites for rifampin and streptolydigin are distinct. Because Rif(r) mutations are highly conserved in eubacteria, our results indicate that this set of Rif(r) mutant RNAPs can be used to screen for new antibiotics that will inhibit the growth of Rif(r) pathogenic bacteria.",1
"Xu, Ming, Zhou, Yan Ning, Goldstein, Beth P, Jin, Ding Jun",2
The metalloprotease of Listeria monocytogenes controls cell wall translocation of the broad-range phospholipase C.,0
"Listeria monocytogenes is a gram-positive bacterial pathogen that multiplies in the cytosol of host cells and spreads directly from cell to cell. During cell-to-cell spread, bacteria become temporarily confined to secondary vacuoles. The broad-range phospholipase C (PC-PLC) of L. monocytogenes contributes to bacterial escape from secondary vacuoles. PC-PLC requires cleavage of an N-terminal propeptide for activation, and Mpl, a metalloprotease of Listeria, is involved in the proteolytic activation of PC-PLC. Previously, we showed that cell wall translocation of PC-PLC is inefficient, resulting in accumulation of PC-PLC at the membrane-cell wall interface. In infected cells, rapid cell wall translocation of PC-PLC is triggered by a decrease in pH and correlates with cleavage of the propeptide in an Mpl-dependent manner. To address the role of the propeptide and of Mpl in cell wall translocation of PC-PLC, we generated a cleavage site mutant and a propeptide deletion mutant. The intracellular behavior of these mutants was assessed in pulse-chase experiments. We observed efficient translocation of the proform of the PC-PLC cleavage site mutant in a manner that was pH sensitive and Mpl dependent. However, the propeptide deletion mutant was efficiently translocated into host cells independent of Mpl and pH. Overall, these results suggest that Mpl regulates PC-PLC translocation across the bacterial cell wall in a manner that is dependent on the presence of the propeptide but independent of propeptide cleavage. In addition, similarly to Mpl-mediated cleavage of PC-PLC propeptide, Mpl-mediated translocation of PC-PLC across the bacterial cell wall is pH sensitive.",1
"Yeung, P S Marie, Zagorski, Nicholas, Marquis, Hélène",2
"Dual roles of an E-helix residue, Glu167, in the transcriptional activator function of CooA.",0
"CooA is a transcriptional activator that mediates CO-dependent expression of the genes responsible for CO oxidation in Rhodospirillum rubrum. In this study, we suggest in vitro and in vivo models explaining an unusual requirement of CooA for millimolar levels of divalent cations for high-affinity DNA binding. Several lines of evidence indicate that an E-helix residue, Glu167, plays a central role in this requirement by inhibiting sequence-specific DNA binding via charge repulsion in the absence of any divalent cation and that divalent cations relieve such repulsion in the process of DNA binding by CooA. Unexpectedly, the Glu167 residue is the optimal residue for in vivo transcriptional activity of CooA. We present a model in which the Glu167 from the downstream subunit of CooA helps the protein to interact with RNA polymerase, probably through an interaction between activating region 3 and sigma subunit. The study was further extended to a homologous protein, cyclic AMP receptor protein (CRP), which revealed similar, but not identical, roles of the residue in this protein as well. The results show a unique mechanism of CooA modulating its DNA binding and transcriptional activation in response to divalent cations among the CRP/FNR (fumarate and nitrate reductase activator protein) superfamily of regulators.",1
"Youn, Hwan, Thorsteinsson, Marc V, Conrad, Mary, Kerby, Robert L, Roberts, Gary P",2
Participation of 3'-to-5' exoribonucleases in the turnover of Bacillus subtilis mRNA.,0
"Four 3'-to-5' exoribonucleases have been identified in Bacillus subtilis: polynucleotide phosphorylase (PNPase), RNase R, RNase PH, and YhaM. Mutant strains were constructed that were lacking PNPase and one or more of the other three ribonucleases or that had PNPase alone. Analysis of the decay of mRNA encoded by seven small, monocistronic genes showed that PNPase was the major enzyme involved in mRNA turnover. Significant levels of decay intermediates, whose 5' ends were at the transcriptional start site and whose 3' ends were at various positions in the coding sequence, were detected only when PNPase was absent. A detailed analysis of rpsO mRNA decay showed that decay intermediates accumulated as the result of a block to 3'-to-5' processivity at the base of stem-loop structures. When RNase R alone was present, it was also capable of degrading mRNA, showing the involvement of this exonuclease in mRNA turnover. The degradative activity of RNase R was impaired when RNase PH or YhaM was also present. Extrapolation from the seven genes examined suggested that a large number of mRNA fragments was present in the PNPase-deficient mutant. Maintenance of the free ribosome pool in this strain would require a high level of activity on the part of the tmRNA trans translation system. A threefold increase in the level of peptide tagging was observed in the PNPase-deficient strain, and selective pressure for increased tmRNA activity was indicated by the emergence of mutant strains with elevated tmRNA transcription.",1
"Oussenko, Irina A, Abe, Teppei, Ujiie, Hiromi, Muto, Akira, Bechhofer, David H",2
Flavobacterium johnsoniae GldJ is a lipoprotein that is required for gliding motility.,0
"Cells of Flavobacterium johnsoniae glide rapidly over surfaces by an unknown mechanism. Eight genes required for gliding motility have been described. Complementation of the nonmotile mutant UW102-48 identified another gene, gldJ, that is required for gliding. gldJ mutants formed nonspreading colonies, and individual cells were completely nonmotile. Like previously described nonmotile mutants, gldJ mutants were deficient in chitin utilization and were resistant to bacteriophages that infect wild-type cells. Cell fractionation and labeling studies with [(3)H]palmitate indicated that GldJ is a lipoprotein. Mutations in gldA, gldB, gldD, gldF, gldG, gldH, or gldI resulted in normal levels of gldJ transcript but decreased levels of GldJ protein. Expression of truncated GldJ protein in wild-type cells resulted in a severe motility defect. GldJ was found in regular bands that suggest the presence of a helical structure within the cell envelope.",1
"Braun, Timothy F, McBride, Mark J",2
Systemic lupus erythematosus serum IgG increases CREM binding to the IL-2 promoter and suppresses IL-2 production through CaMKIV.,0
"Systemic lupus erythematosus (SLE) T cells express high levels of cAMP response element modulator (CREM) that binds to the IL-2 promoter and represses the transcription of the IL-2 gene. This study was designed to identify pathways that lead to increased binding of CREM to the IL-2 promoter in SLE T cells. Ca(2+)/calmodulin-dependent kinase IV (CaMKIV) was found to be increased in the nucleus of SLE T cells and to be involved in the overexpression of CREM and its binding to the IL-2 promoter. Treatment of normal T cells with SLE serum resulted in increased expression of CREM protein, increased binding of CREM to the IL-2 promoter, and decreased IL-2 promoter activity and IL-2 production. This process was abolished when a dominant inactive form of CaMKIV was expressed in normal T cells. The effect of SLE serum resided within the IgG fraction and was specifically attributed to anti-TCR/CD3 autoantibodies. This study identifies CaMKIV as being responsible for the increased expression of CREM and the decreased production of IL-2 in SLE T cells and demonstrates that anti-TCR/CD3 antibodies present in SLE sera can account for the increased expression of CREM and the suppression of IL-2 production.",1
"Juang, Yuang-Taung, Wang, Ying, Solomou, Elena E, Li, Yansong, Mawrin, Christian, Tenbrock, Klaus, Kyttaris, Vasileios C, Tsokos, George C",2
Distinct roles for the kidney and systemic tissues in blood pressure regulation by the renin-angiotensin system.,0
"Angiotensin II, acting through type 1 angiotensin (AT(1)) receptors, has potent effects that alter renal excretory mechanisms. Control of sodium excretion by the kidney has been suggested to be the critical mechanism for blood pressure regulation by the renin-angiotensin system (RAS). However, since AT(1) receptors are ubiquitously expressed, precisely dissecting their physiological actions in individual tissue compartments including the kidney with conventional pharmacological or gene targeting experiments has been difficult. Here, we used a cross-transplantation strategy and AT(1A) receptor-deficient mice to demonstrate distinct and virtually equivalent contributions of AT(1) receptor actions in the kidney and in extrarenal tissues to determining the level of blood pressure. We demonstrate that regulation of blood pressure by extrarenal AT(1A) receptors cannot be explained by altered aldosterone generation, which suggests that AT(1) receptor actions in systemic tissues such as the vascular and/or the central nervous systems make nonredundant contributions to blood pressure regulation. We also show that interruption of the AT(1) receptor-mediated short-loop feedback in the kidney is not sufficient to explain the marked stimulation of renin production induced by global AT(1) receptor deficiency or by receptor blockade. Instead, the renin response seems to be primarily determined by renal baroreceptor mechanisms triggered by reduced blood pressure. Thus, the regulation of blood pressure by the RAS is mediated by AT(1) receptors both within and outside the kidney.",1
"Crowley, Steven D, Gurley, Susan B, Oliverio, Michael I, Pazmino, A Kathy, Griffiths, Robert, Flannery, Patrick J, Spurney, Robert F, Kim, Hyung-Suk, Smithies, Oliver, Le, Thu H, Coffman, Thomas M",2
An inversion involving the mouse Shh locus results in brachydactyly through dysregulation of Shh expression.,0
"Short digits (Dsh) is a radiation-induced mouse mutant. Homozygous mice are characterized by multiple defects strongly resembling those resulting from Sonic hedgehog (Shh) inactivation. Heterozygous mice show a limb reduction phenotype with fusion and shortening of the proximal and middle phalanges in all digits, similar to human brachydactyly type A1, a condition caused by mutations in Indian hedgehog (IHH). We mapped Dsh to chromosome 5 in a region containing Shh and were able to demonstrate an inversion comprising 11.7 Mb. The distal breakpoint is 13.298 kb upstream of Shh, separating the coding sequence from several putative regulatory elements identified by interspecies comparison. The inversion results in almost complete downregulation of Shh expression during E9.5-E12.5, explaining the homozygous phenotype. At E13.5 and E14.5, however, Shh is upregulated in the phalangeal anlagen of Dsh/+ mice, at a time point and in a region where WT Shh is never expressed. The dysregulation of Shh expression causes the local upregulation of hedgehog target genes such as Gli1-3, patched, and Pthlh, as well as the downregulation of Ihh and Gdf5. This results in shortening of the digits through an arrest of chondrocyte differentiation and the disruption of joint development.",1
"Niedermaier, Michael, Schwabe, Georg C, Fees, Stephan, Helmrich, Anne, Brieske, Norbert, Seemann, Petra, Hecht, Jochen, Seitz, Volkhard, Stricker, Sigmar, Leschik, Gundula, Schrock, Evelin, Selby, Paul B, Mundlos, Stefan",2
MEF2A sequence variants and coronary artery disease: a change of heart?,0
"Rare mutations in MEF2A have been proposed as a cause of coronary artery disease (CAD) and myocardial infarction (MI). In this issue of the JCI, Pennacchio and colleagues report sequencing MEF2A in 300 patients with premature CAD and in controls. Only 1 CAD patient was found to carry a missense mutation not found in controls. The specific 21-bp deletion in MEF2A previously proposed as causal for CAD and/or MI was observed in unaffected individuals and did not segregate with CAD in families. These results do not support the hypothesis that mutations in MEF2A are a cause of CAD and/or MI but do illustrate general principles regarding the difficulty of connecting genetic variation to common diseases.",1
"Altshuler, David, Hirschhorn, Joel N",2
Toxicology and pathology of deaths related to methadone: retrospective review.,0
"To clarify the mechanisms and risk factors of methadone toxicity and to describe the findings of deaths related to methadone use Design Retrospective review of case notes in the records of the San Francisco Medical Examiner comparing the findings in cases where methadone was deemed the cause of death with findings in decedents where methadone was an incidental finding, and with 50 age-matched, disease and drug free, trauma victims.",1
"Karch, S B, Stephens, B G",2
Effects of an educational intervention for general practitioners in adolescent health care principles: a randomized controlled study.,0
"Objective To evaluate the effectiveness of an educational intervention in adolescent health designed for general practitioners, in accordance with evidence-based practice in continuing medical education. Design Randomized, controlled trial with baseline testing and 7- and 13-month follow-ups. Setting The intervention was delivered in local community settings to general practitioners in metropolitan Melbourne, Australia. Participants A total of 108 self-selected general practitioners. Intervention A multifaceted educational program (2.5 hours per week for 6 weeks) in the principles of adolescent health care, followed 6 weeks later by a 2-hour session of case discussion and debriefing. Outcome measures Objective ratings of videotaped consultations with standardized adolescent patients and self-completion questionnaires were used to measure general practitioners' knowledge, skill, and self-perceived competency; satisfaction with the program; and self-reported change in practice. Results 103 of 108 physicians (95%) completed all phases of the intervention and evaluation protocol. The intervention group showed significantly greater improvements than the control group in all outcomes at the 7-month follow-up (all subjects P<0.03), except for the standardized patients' rating of rapport and satisfaction (P=0.12). 104 participants (96%) found the program appropriate and relevant. At the 13-month follow-up, most improvements were sustained, the standardized patients' rating of confidentiality fell slightly, and the objective assessment of competence further improved. 106 physicians (98%) reported a change in practice attributable to the intervention. Conclusions General practitioners were willing to complete continuing medical education in adolescent health and its evaluation. The design of the intervention, using evidence-based educational strategies, proved effective and expeditious in achieving sustainable and large improvements in knowledge, skill, and self-perceived competency.",1
"Sanci, L A, Coffey, C M, Veit, F C, Carr-Gregg, M, Patton, G C, Bowes, G, Day, N",2
Active management of labor: a cost analysis of a randomized controlled trial.,0
To compare the costs of a protocol of active management of labor with those of traditional labor management.,1
"Rogers, R G, Gardner, M O, Tool, K J, Ainsley, J, Gilson, G",2
"Survivors of torture in a general medical setting: how often have patients been tortured, and how often is it missed?",0
To measure the frequency of people reporting torture among patients in a medical outpatient clinic and to determine primary care physicians' awareness of their patients' exposure to torture.,1
"Eisenman, D P, Keller, A S, Kim, G",2
Extent and determinants of error in physicians' prognoses in terminally ill patients: prospective cohort study.,0
"Objectives To describe physicians' prognostic accuracy in terminally ill patients and to evaluate the determinants of that accuracy. Design Prospective cohort study. Setting Five outpatient hospice programs in Chicago. Participants A total of 343 physicians provided survival estimates for 468 terminally ill patients at the time of hospice referral. Main outcome measures Patients' estimated and actual survival. Results Median survival was 24 days. Of 468 predictions, only 92 (20%) were accurate (within 33% of actual survival); 295 (63%) were overoptimistic, and 81 (17%) were overpessimistic. Overall, physicians overestimated survival by a factor of 5.3. Few patient or physician characteristics were associated with prognostic accuracy. Male patients were 58% less likely to have overpessimistic predictions. Medical specialists excluding oncologists were 326% more likely than general internists to make overpessimistic predictions. Physicians in the upper quartile of practice experience were the most accurate. As the duration of the doctor-patient relationship increased and time since last contact decreased, prognostic accuracy decreased. Conclusions Physicians are inaccurate in their prognoses for terminally ill patients, and the error is systematically optimistic. The inaccuracy is, in general, not restricted to certain kinds of physicians or patients. These phenomena may be adversely affecting the quality of care given to patients near the end of life.",1
"Christakis, N A, Lamont, E B",2
Analysis of questions asked by family physicians regarding patient care.,0
"Objectives To characterize the information needs of family physicians by collecting the questions they asked about patient care during consultations and to classify these in ways that would be useful to developers of knowledge bases. Design An observational study in which investigators visited physicians for two half-days and collected their questions. Taxonomies were developed to characterize the clinical topic and generic type of information sought for each question. Setting Eastern Iowa. Participants Random sample of 103 family physicians. Main outcome measures Number of questions posed, pursued, and answered; topic and generic type of information sought for each question; time spent pursuing answers; and information resources used. Results Participants asked a total of 1,101 questions. Questions about drug prescribing, obstetrics and gynecology, and adult infectious disease were most common, comprising 36% of the total. The taxonomy of generic questions included 69 categories; the three most common types, comprising 24% of all questions, were ""What is the cause of symptom X?"" ""What is the dose of drug X?"" and ""How should I manage disease or finding X?"" Answers to most questions (n = 702 [64%]) were not immediately pursued, but of those pursued, most (n = 318 [80%]) were answered. Physicians spent an average of less than 2 minutes pursuing an answer, and they used readily available print and human resources. Only two questions led to a formal literature search. Conclusions Family physicians in this study did not pursue answers to most of their questions. Questions about patient care can be organized into a limited number of generic types, which could help guide the efforts of knowledge-base developers.",1
"Ely, J W, Osheroff, J A, Ebell, M H, Bergus, G R, Levy, B T, Chambliss, M L, Evans, E R",2
Visual associative agnosia: a clinico-anatomical study of a single case.,0
"A single case study of a patient with visual associative agnosia is described. The patient had well preserved language, spatial, visual, and perceptual abilities but nevertheless was impaired in recognising visually presented common objects. It is argued that his deficit cannot be accounted for in terms of a disconnection syndrome. Behavioural and anatomical (MRI scan) evidence for focal unilateral dysfunction is presented. It is concluded that the left hemisphere plays a crucial role in recognising the meaning of common objects.",1
"McCarthy, R A, Warrington, E K",2
"A comparative study of progabide, valproate, and placebo as add-on therapy in patients with refractory epilepsy.",0
"A three way single blind cross-over comparison of progabide, valproate and placebo, as adjunctive therapy, was undertaken in 64 patients with therapy-resistant partial and generalised seizures. The study was not completed because of the incidence of elevated hepatic enzymes on progabide. Analysis of efficacy showed progabide to be inferior to valproate against all seizure types, particularly against tonic-clonic seizures. Valproate was superior to placebo against all seizure types, partial and tonic-clonic seizures. Progabide did not differ significantly from placebo in any instance. In addition progabide caused elevation of hepatic enzymes which was symptomatic in one case, and was associated with an interaction with phenytoin which resulted in symptoms of intoxication in some cases.",1
"Crawford, P, Chadwick, D",2
Scaling of the size of the first agonist EMG burst during rapid wrist movements in patients with Parkinson's disease.,0
"Rapid wrist flexion movements were studied in a group of 10 patients with Parkinson's disease both on and off their normal drug therapy, and were compared with the same movements made by a group of eight normal individuals. When normal subjects made movements through 60 degrees, the first agonist burst of EMG activity in the wrist flexor muscles was longer and larger than that seen in movements of 15 degrees. If a large opposing load of 2.2 Nm was added, this also increased the size and duration of the first agonist EMG burst. Although the movements made by the patients were slower than those of normals, the size and duration of the first agonist EMG burst changed with movement size and added load in the normal way. This shows that patients can produce large, long bursts of EMG activity, but that there is a failure to match these parameters appropriately to the size of movement required. The effect of levodopa therapy on the movements was not dramatic. Although patients produced faster wrist movements when on medication than when off, the change was relatively small compared with the change seen in their overall clinical rating. Changes in the velocity of movements at a single joint are not a good reflection of the overall clinical state of patients with Parkinson's disease.",1
"Berardelli, A, Dick, J P, Rothwell, J C, Day, B L, Marsden, C D",2
"Regional cerebral blood flow in patients with Parkinson's disease under chronic levodopa therapy: measurements during ""on"" and ""off"" response fluctuations.",0
"In ten Parkinsonians who developed dose-related response fluctuations under long-term levodopa therapy, regional cerebral blood flow (rCBF) and plasma levodopa levels were measured simultaneously, once during an ""off"" phase and again at an ""on"" stage of clinical benefit induced by a single oral dose of levodopa. Although plasma levodopa increased threefold during the ""on"" period, rCBF and the degree of its reduction from normal age-matched control values remained unchanged and similar to those in the ""off"" phase. Study suggests that the rCBF decreases in Parkinson's disease are unaffected by levodopa and are not due to deficient dopaminergic neurotransmission in the brain.",1
"Melamed, E, Globus, M, Mildworf, B",2
"Oligoclonal ""fingerprint"" of CSF IgG in multiple sclerosis patients is not modified following intrathecal administration of natural beta-interferon.",0
"The IgG pattern in CSF was studied in 11 patients with multiple sclerosis who exhibited an oligoclonal banding upon thin-layer polyacrylamide gel isoelectric focusing followed by silver stain of unconcentrated CSF. Each patient received beta-interferon intrathecally during a 2 month period. No modification was observed over a 6 month period. In addition, the oligoclonal pattern was remarkably unique for each individual representing a typical ""fingerprint"" which allowed the identification of any single CSF.",1
"Confavreux, C, Chapuis-Cellier, C, Arnaud, P, Robert, O, Aimard, G, Devic, M",2
The clinical spectrum of inflammatory-angiopathic neuropathy.,0
"Thirty-three patients with inflammatory-angiopathic neuropathy diagnosed by sural nerve biopsy, were investigated to determine the underlying disease. Twenty-six patients had symmetrical sensorimotor polyneuropathy and seven had mononeuropathy multiplex. An aetiology for inflammatory-angiopathic neuropathy was found in only eight patients: typical collagen vascular disease in five and malignant tumour in three. Sixteen patients received prednisone and/or immunosuppressive drug therapy and 12 (75%) responded to treatment. This study demonstrates that typical collagen vascular diseases are not the most common cause of inflammatory-angiopathic neuropathy, that symmetrical polyneuropathy is seen in 75.8% of inflammatory-angiopathic neuropathy patients. Prednisone and/or immunosuppressive agents appear effective regardless of aetiology.",1
"Harati, Y, Niakan, E",2
Intracranial calcified deposits in neurofibromatosis.,0
"Three patients with the central type of neurofibromatosis, who on CT showed multiple subependymal calcified deposits, are presented. The literature on intracranial non-tumourous calcifications in neurofibromatosis is briefly reviewed. On the basis of our findings and the literature, it is proposed that such intracranial calcified deposits may be part of the neurofibromatosis syndrome and are caused by calcium deposits in glial proliferations, analogous to the calcified deposits seen in tuberous sclerosis.",1
"Arts, W F, Van Dongen, K J",2
Magnetic resonance imaging of experimental cerebral oedema.,0
"Triethyl tin(TET)-induced cerebral oedema has been studied in cats by magnetic resonance imaging (MRI), and the findings correlated with the histology and fine structure of the cerebrum following perfusion-fixation. MRI is a sensitive technique for detecting cerebral oedema, and the distribution and severity of the changes correlate closely with the morphological abnormalities. The relaxation times, T1 and T2 increase progressively as the oedema develops, and the proportional increase in T2 is approximately twice that in T1. Analysis of the magnetisation decay curves reveals slowly-relaxing and rapidly-relaxing components which probably correspond to oedema fluid and intracellular water respectively. The image appearances taken in conjunction with relaxation data provide a basis for determining the nature of the oedema in vivo.",1
"Barnes, D, McDonald, W I, Tofts, P S, Johnson, G, Landon, D N",2
The in-vitro chemosensitivity of three cell lines derived from the VM/DK spontaneous murine astrocytoma.,0
"Three cell lines, VM/Dk P497 P540 and P560 derived from the VM spontaneous murine astrocytoma have previously been fully characterised and found to differ in their degree of astrocytic differentiation. The in vitro chemosensitivity of the three lines has been investigated using the 35S-methionine uptake assay. Differential chemosensitivity was found to exist between the cell lines. The pattern of chemosensitivity in relation to astrocytic differentiation was complex but the least differentiated cell line, P497, tended to be the least chemosensitive.",1
"Bradford, R, Darling, J L, Thomas, D G",2
Somatosensory evoked potentials in syringomyelia.,0
"The two types of upper limb somatosensory evoked potential abnormality observed in nine patients with syringomyelia were reduced amplitude or absent cervical potentials and an abnormal central conduction time. Although this pattern of abnormalities resembles that observed in other intrinsic spinal cord lesions, it differs from peripheral nerve diseases and cervical radiculopathy in which the central conduction time is normal.",1
"Anderson, N E, Frith, R W, Synek, V M",2
Electrophysiological observations on the human pudendo-anal reflex.,0
"A reproducible electrophysiological technique is described to determine the latency of reflex contraction of the external anal sphincter in response to stimulation of the dorsal genital nerve: the pudendo-anal reflex. This was studied in 38 asymptomatic control subjects and 20 women with neurogenic faecal incontinence, supplemented by determination of the mean motor unit potential duration (MUPD) of the external anal sphincter and anorectal manometry. The reflex latency in the control group was 38.5 +/- 5.8 (SD) ms and appeared to be independent of age or sex. Three patients with faecal incontinence had absent reflexes; the remainder showed significant prolongation of latency (56 +/- 12.2 SD ms) and diminution of amplitude. MUPD was prolonged in incontinence and showed significant correlation with the corresponding reflex latency determination (tau = 0.56, p less than 0.001). The latency of this polysynaptic spinal reflex hence provides a reliable index of neuropathy of the external anal sphincter.",1
"Varma, J S, Smith, A N, McInnes, A",2
Familial lethal cardiomyopathy with mental retardation and scapuloperoneal muscular dystrophy.,0
"A family is described with a neuromuscular disorder characterised by possible X-linked recessive inheritance, a benign, slowly progressive muscular dystrophy with predominant humeroperoneal distribution and lack of contractures or pseudohypertrophy, central nervous system involvement, myopia and lethal cardiomyopathy. The possibility of cardiac transplant as life-saving therapy is suggested.",1
"Bergia, B, Sybers, H D, Butler, I J",2
Pure dysarthria due to anterior internal capsule and/or corona radiata infarction: a report of five cases.,0
Five cases with a sudden onset of dysarthria in the setting of hypertension are presented. No case had limb weakness or other neurological deficits. Computed tomographic scan demonstrated a small low density lesion in the anterior part of the internal capsule or the adjacent corona radiata. All cases showed a good recovery from dysarthria within two to four weeks.,1
"Ozaki, I, Baba, M, Narita, S, Matsunaga, M, Takebe, K",2
Non-obstructive idiopathic pachymeningitis cervicalis hypertrophica.,0
"Two young men had similar nonobstructive idiopathic pachymeningitis cervicalis hypertrophica, causing chronic (13 and 11 years respectively) C8-T1 radiculomyelopathy proved by surgical and pathological findings. The preoperative Queckenstedt tests and myelography showed no evidence of CSF obstruction. These unusual findings contrast with previous reports which all described complete or at least partial, block. The findings on metrizamide computed tomogram have not been described before. In the two patients it revealed diffuse cord atrophy from C7 to T2 and hemiatrophy with lateral beaking from C4 to C7. The patients benefited from multiple transverse durotomies. The main pathogenesis of the cord atrophy was the compromizing of feeding radicular arteries rather than direct compression.",1
"Kao, K P, Huang, C I, Shan, D E, Ho, J T, Chang, T, Chu, F L",2
Accuracy of stereotaxic localisation using MRI and CT.,0
"The accuracy of stereotaxic coordinates determined using the Leksell apparatus with CT and MRI was investigated using an Agar filled head phantom. Both imaging techniques were found to produce an accuracy of better than 2 mm with the exception of the Z coordinate as measured by CT (2.3 mm). This latter error is greater because of the 3 mm slice width used. Direct coronal views were used to determine Z more accurately using MRI. The measurement procedures are described and it is shown that the Leksell system of using orthogonal coordinates enables the scaling of images, which is particularly necessary with MRI, to be done easily.",1
"Wyper, D J, Turner, J W, Patterson, J, Condon, B R, Grossart, K W, Jenkins, A, Hadley, D M, Rowan, J O",2
Repeated facial palsies after chlorocresol inhalation.,0
A 42-year-old woman who experienced more than 50 attacks of left-sided facial palsies after exposure to chlorocresol was studied. Only muscles around the left side of the mouth were affected. On neurophysiological testing during chlorocresol provocation the only abnormality was a loss of motor units during maximal contraction of the left orbicularis oris muscle. This could be explained by a peripheral as well as a central effect. Extensive electrophysiological examination without chlorocresol provocation excluded a preexisting generalised nerve disorder and other diagnostic procedures did not give evidence of pathology involving the left facial nerve. A hyperreactive mechanism causing a transient block of the left facial nerve is proposed.,1
"Døssing, M, Wulff, C H, Olsen, P Z",2
Pulmonary gas exchange immediately after birth in spontaneously breathing infants.,0
"The pulmonary gas exchange (rate of oxygen consumption, VO2 and rate of carbon dioxide production, VCO2), heart rate, and transcutaneously measured oxygen saturation were measured during the first five minutes after birth in healthy newborn infants. Fifteen full term infants who were vaginally delivered, 15 full term infants born by caesarean section, and 10 preterm infants born by caesarean section were studied. VO2 tended to be slightly higher than VCO2 during the first minutes, with a gradual change to a respiratory exchange ratio above 1.0. VO2 and VCO2 were significantly higher in vaginally delivered infants than in those born by caesarean section during the second minute after birth, partly due to a higher number of cries/minute. During periods of calm breathing, VO2 and VCO2 were significantly higher in vaginally delivered infants than in those born by caesarean section, with low gas exchange levels in infants born by caesarean section during the second minute after birth. Decreased ventilation was reflected by a significant drop in oxygen saturation within 30-45 seconds.",1
"Palme-Kilander, C, Tunell, R, Chiwei, Y",2
Pulmonary gas exchange during facemask ventilation immediately after birth.,0
"The rate of carbon dioxide production (VCO2), heart rate, and oxygen saturation were recorded during resuscitation in 30 newborn infants. Twenty eight infants were ventilated through a facemask only and two were intubated after initial facemask ventilation. Five neonates were born at full term, eight had a gestational age of 32-36 weeks, and 17 of 27-31 weeks. Towards the end of the five minute study period, the VCO2 in ventilated infants, born after 32 weeks or more, was not different from that of spontaneously breathing infants. Neonates with a gestational age of 27-31 weeks showed a low VCO2, particularly when no reflex response from the baby was recorded, with a significant increase if a reflex response was elicited. Ventilation was found to be satisfactory if the heart rate increased to 130 beats/min or more within 5-15 seconds or if the oxygen saturation, measured in the right hand, was 70% or more.",1
"Palme-Kilander, C, Tunell, R",2
Echocardiographic assessment of cardiac function in shocked very low birthweight infants.,0
"The contribution of abnormal cardiac function to hypotension and metabolic acidosis, which affect approximately 40% of ventilated very low birthweight infants in the first 24 hours after birth was assessed using M mode, two dimensional, and Doppler echocardiography in 75 very low birthweight infants during the first few hours after birth. Thirty four infants whose blood pressure was less than the 10th centile or who had a metabolic acidosis in the first 24 hours were compared with 41 who showed neither feature. The median shortening fraction was significantly lower in the hypotensive/acidotic (shocked) group than in the controls. In 16 of 34 (47%) shocked infants left ventricular contractility and output were significantly worse than in the control subjects. One and five minute Apgar scores were also significantly lower in the shock group when compared with controls. Cardiac dysfunction was an important feature in the shocked very low birthweight infants. It is speculated that volume expansion may not always be the most appropriate first line treatment for such infants.",1
"Gill, A B, Weindling, A M",2
Urological anomalies in the Northern Region Fetal Abnormality Survey.,0
"From 1 January 1985 to 31 December 1990, the Northern Region Fetal Abnormality Survey received 736 notifications of fetuses with suspected urological abnormalities; a prevalence of three per 1000 births. There was a male:female ratio of 2:1, the ratio was higher in obstructive than in intrinsic renal parenchymal lesions. Overall diagnostic sensitivity was 68.9% and positive predictive value 50.8%. Hydronephrosis was the most frequent antenatal diagnosis (421 cases, 57.2%): 233 (55.3%) of these were found to be normal postnatally. There were 52 other false positive diagnoses. Of 113 babies with confirmed hydronephrosis antenatal diagnosis was correct in 97, sensitivity 85.8%, specificity 48.1%; 1.8% of these had chromosome defects. In 33 cases of bilateral renal agenesis antenatal diagnosis was correct or potentially correct in 24, sensitivity 72.7%, specificity 98.9%. Only six of 26 babies with posterior urethral valves were suspected, sensitivity 23%, specificity 98.7%. Mortality rate in 91 babies with unsuspected abnormalities was 39.6%: overall mortality was 24.2%. Unsuspected abnormalities occurred more frequently when mothers were not scanned after the 16th week of pregnancy.",1
"Scott, J E, Renwick, M",2
Transcutaneous application of oil and prevention of essential fatty acid deficiency in preterm infants.,0
"The topical application of vegetable oil was assessed as an alternative means of providing essential fatty acids (EFA) to parentally fed preterm infants who were not receiving lipid. Three infant pairs ranging in gestational age from 26-32 weeks were studied. Safflower oil or safflower oil esters (1 g linoleic acid/kg/day) were applied to available areas daily. All infants rapidly developed biochemical EFA deficiency. The plasma fatty acid profiles were similar in infants with or without topical oil, and all returned to normal once parenteral lipid was introduced. We found no evidence to suggest that the transdermal route is of use in the nutritional management of preterm infants.",1
"Lee, E J, Gibson, R A, Simmer, K",2
Changes in plasma cortisol and catecholamine concentrations in response to massage in preterm infants.,0
"The biochemical and clinical response to massage in preterm infants was assessed. Eleven stable infants, of 29 weeks' median gestational age, median birth weight 980 g, and median postnatal age 20 days, were studied. Blood samples were obtained for the determination of adrenaline, noradrenaline, and cortisol 45 minutes before the start of massage and approximately one hour after completion of massage. Cortisol, but not catecholamine, concentrations decreased consistently after massage (median difference -35.8 nmol/l; 95% confidence interval -0.5 to -94.0, Wilcoxon matched pairs). There was a slight decrease in skin temperature (median difference -0.36 degrees C, 95% confidence interval -0.09 to -0.65) but there was no change in oxygenation or oxygen requirement. This study has shown that it is possible to detect an objective hormonal change following a supposedly 'non-therapeutic' intervention in preterm infants. The development of such methods of assessment are likely to be of particular relevance in the extremely immature or ill neonate in whom behavioural evaluation cannot play more than a limited part.",1
"Acolet, D, Modi, N, Giannakoulopoulos, X, Bond, C, Weg, W, Clow, A, Glover, V",2
Biased assessment of gestational age at birth when obstetric gestation is known.,0
"The gestational age of 302 neonates whose obstetric gestational age was known was assessed at birth using the Dubowitz method; it was obtained from Dubowitz score both graphically from a nomogram and by calculation from the corresponding equation. The values obtained graphically differed to a lesser extent from the obstetric gestational age than did the gestation derived algebraically. With infants small for gestational age (SGA) the difference between the methods was smaller and not significant. It is concluded that the concurrent knowledge of obstetric gestational age introduced a bias in the graphic step; this did not happen in SGA infants probably because in these cases the available information is sometimes less certain. These data demonstrate that even simple procedures are influenced by concurrent information; as a philosophical point about the interpretation of data in general, this study provides an empirical example of the 'theory-ladenness of facts' in medicine.",1
"Gagliardi, L, Brambilla, C, Bruno, R, Martinelli, S, Console, V",2
Fetal anaemia and its relation with increased concentrations of adenosine.,0
"Adenosine concentrations were measured in umbilical venous blood obtained by cordocentesis from 14 fetuses of 19-34 weeks' gestation. The concentration did not change significantly with gestational age, but anaemic fetuses showed significantly increased concentrations of adenosine and there was a positive association with blood oxygen tension. These findings suggest that the fetus responds to tissue hypoxia by increasing blood adenosine concentrations from at least 19 weeks' gestation.",1
"Ross Russell, R I, Greenough, A, Lagercrantz, H, Dahlin, I, Nicolaides, K",2
Endoscopic balloon dilatation of acquired airway stenosis in newborn infants: a promising treatment.,0
"Acquired stenosis of the trachea or bronchus in newborn infants is a possible complication of perinatal intubation and mechanical ventilation. Although the exact pathophysiology is unknown, stenosis formation seems to be initiated by pressure necrosis. Prematurity is thought to be an important risk factor for acquired airway stenosis. Management of stenotic lesions may be conservative, surgical, or endoscopic. Four patients were treated with endoscopic balloon dilatation with satisfactory results. Endoscopic balloon dilatation is the method of choice in most newborn infants with acquired bronchial or tracheal stenosis.",1
"Elkerbout, S C, van Lingen, R A, Gerritsen, J, Roorda, R J",2
Intussusception in preterm infants.,0
"Two cases of intussusception in infants born at 26 and 30 weeks' gestation are described. The two infants presented in the neonatal period with abdominal distension, intolerance of feeds, and rectal bleeding. An initial diagnosis of necrotising enterocolitis was made and the infants were treated medically. This led to a delay in the diagnosis of the intussusception. Published work on neonatal intussusception is reviewed and attention is drawn to the fact that the presenting signs and symptoms can be similar to those of necrotising enterocolitis. A diagnosis of intussusception should therefore be considered in any preterm infant with suspected necrotising enterocolitis.",1
"Price, K J, Roberton, N R, Pearse, R G",2
Gall bladder contractility in preterm infants.,0
"Postnatal response of the gall bladder to feeding was studied in 28 preterm infants (gestational age 24-37 weeks) by ultrasonography immediately before feeding and one hour after feeding. Nineteen of the infants were studied once during the first week of life, and nine infants were studied weekly from a postconceptional age of 27-31 until a postprandial gall bladder contraction was seen. A contraction index was calculated as a percentage decrement of the surface area of the gall bladder from its initial value. All preterm infants of more than 33 weeks' gestation showed a gall bladder response to feeding with a contraction index of at least 50%. Very preterm infants (gestational age 27-32 weeks) showed no postprandial gall bladder contraction or the contraction index was under 50%. In a follow up study of nine very preterm infants, the contraction index exceeded 50% at a postconceptional age of 29 to 32 weeks. One infant with prolonged feeding problems had no postprandial gall bladder response before the postconceptional age of 38 weeks. The contraction index increase was dependent on gestational age at birth and on the bolus volume of feeds.",1
"Lehtonen, L, Svedström, E, Kero, P, Korvenranta, H",2
Plasma cholecystokinin concentrations after breast feeding in healthy 4 day old infants.,0
"The aim of the present study was to characterise plasma concentrations of cholecystokinin (CCK) after breast feeding in newborn infants. Fifty eight healthy full term exclusively breast fed infants were investigated at 4 (1) (2-6) days of age. Each infant contributed one blood sample collected just before, immediately after, or 10, 30, and 60 minutes after breast feeding. Plasma concentrations of CCK were measured with a technique consisting of high pressure liquid chromatography separation of gastrins and CCKs and consequent analysis with radioimmunoassay. Mean (SD) preprandial plasma concentrations of CCK (CCK8+CCK-33,39) were 68 (17) pmol/l. A significant increase was seen immediately after breast feeding, which was followed by a decline at 10 minutes and a secondary rise was seen at 30 and 60 minutes. The first peak is likely to be due to a suckling related activation of the vagal nerve and the second to a stimulatory effect of food on CCK-producing cells. An inverse relationship between basal concentrations of CCK and age of the infant was found. In rats peripheral injections of CCK reduce food intake and cause postprandial sedation and sleepiness via activation of an afferent vagal mechanism. CCK release in response to breast feeding may therefore in addition to exerting stimulatory effects on digestion and metabolism contribute to relaxation and sleepiness seen after breast feeding. The high CCK concentrations seen in younger infants may help the infant to remain satiated and calm despite receiving very little food during the first days of life.",1
"Uvnäs-Moberg, K, Marchini, G, Winberg, J",2
The development of anti-HLA antibodies in multiply transfused preterm infants.,0
"The development of antihuman leucocyte antigen antibodies (aHLAA) in response to multiple transfusions in preterm infants was studied prospectively. Fifty seven infants requiring a minimum of two blood transfusions were recruited after obtaining informed written parental consent. They were randomised to receive either whole blood or blood that had been passed through a leucocyte filter. Anti-HLAA were sought in maternal and cord blood so as to ensure that any aHLAA detected after transfusion had not been passively transferred antenatally, and in 1 ml samples drawn monthly from the baby, at least 10 days from a previous transfusion, until discharge from hospital. Anti-HLAA were detected by microlymphocytotoxicity assay. Results were obtained in 42 babies, 19 in the filter and 23 in the no filter group. Fifteen babies had to be excluded because of protocol violation or because they died. None of the babies receiving filtered blood developed aHLAA, but seven babies in the no filter group developed aHLAA. In conclusion, multiply transfused preterm infants have the ability to elaborate antibodies to HLA and leucocyte filters may prevent this.",1
"Bedford Russell, A R, Rivers, R P, Davey, N",2
Delayed umbilical cord separation in alloimmune neutropenia.,0
Delayed umbilical cord separation in association with neonatal alloimmune neutropenia is reported. Delayed umbilical cord separation has been described in association with defects in neutrophil function. The present case indicates that deficiency in neutrophil number should also be considered as a cause of delayed cord separation.,1
"Kemp, A S, Lubitz, L",2
Transplacental transfer of cefuroxime in uncomplicated pregnancies and those complicated by hydrops or changes in amniotic fluid volume.,0
"The transplacental transfer of cefuroxime was determined at antenatal fetal blood sampling in a cross sectional study of 78 patients between 15-35 weeks' gestation, 8-138 minutes after a maternal intravenous dose of 750 mg. Mean serum cefuroxime concentration, measured by high performance liquid chromatography, was 7.4 (95% confidence interval (CI) 6.8 to 8.1) mg/l in control fetuses; concentrations in hydropic fetuses were similar (6.2 mg/l, CI 4.7 to 7.7) but in fetuses with oligohydramnios they were significantly lower, (4.9 mg/l, CI 3.6 to 6.2). Antibiotic concentration did not correlate with gestational age and remained unchanged by transfusion of packed red cells. We conclude that (i) fetal serum concentrations of cefuroxime obtained after a maternal dose of 750 mg are only adequate for prophylaxis against organisms with a minimum inhibitory concentration of < 4 mg/l and (ii) transplacental passage of cefuroxime is significantly reduced in the presence of oligohydramnios.",1
"Holt, D E, Fisk, N M, Spencer, J A, de Louvois, J, Hurley, R, Harvey, D",2
Secondary thrombocytosis.,0
"To estimate the incidence and causes of secondary thrombocytosis in children, a 12 month study of all patients attending a children's hospital and discovered to have a platelet count over two times the upper normal limit (> 800 x 10(9)/l) was undertaken. Data so obtained were analysed both separately and together with those from two previous studies to gain as broad a perspective as possible. Of 7916 children who had platelet counts during the study period, 36 (0.5%) produced a value > 800 x 10(9)/l; there were 19 boys and 17 girls. There was a preponderance of young infants (median age 13 months). Twenty seven of the 36 had some sort of associated infection, bacterial in 18 and viral in nine. The other nine were either recovering from anti-neoplastic chemotherapy (n = 6), were post-operative (n = 2), or simply iron deficient (n = 1). Combining these patients with those described in previous studies allowed a review of 139 unselected children with very high platelet counts. Fifty three (38%) had infections, 29 (20%) had traumatic or surgical tissue damage, 16 (11%) had malignant disease undergoing chemotherapy or surgery, and 13 (9%) had connective tissue or autoimmune disorders. Secondary thrombocytosis is not rare and is most frequently seen in very young infants after infection. It can arise in a wide variety of other circumstances including rebound from myelosuppression, iron lack, or as part of an acute phase response. It is clinically unimportant in terms of morbidity and requires no treatment other than that for the primary condition.",1
"Vora, A J, Lilleyman, J S",2
Extracorporeal life support in paediatrics.,0
"Extracorporeal membrane oxygenation (ECMO) is a life support technique based on modifications of heart-lung bypass technology. It is used to support severe but potentially reversible pulmonary or cardiopulmonary failure. There is increasing use of the technique for neonates and a return of interest in its use for adults. The number of non-neonatal paediatric patients receiving pulmonary support with ECMO worldwide is, however, small, and survival rates average less than 50%. Initial experience in 15 patients aged 3 months to 5 years with a high survival and low morbidity is reported.",1
"Pearson, G A, Grant, J, Field, D, Sosnowski, A, Firmin, R K",2
Pulmonary veno-occlusive disease: diagnosis during life in four patients.,0
"Pulmonary veno-occlusive disease is a rare form of primary pulmonary hypertension of unknown aetiology. Four cases were diagnosed in young patients. The diagnosis was suspected on the basis of clinical, radiological, echocardiographic, and catheter evidence and confirmed by taking a lung biopsy sample. In all patients the histology showed obstruction of the pulmonary veins by intimal fibrosis. The clinical course of all patients has been one of progressive deterioration. Although there is no specific treatment for this disease, to establish the diagnosis during life is of great importance in overall clinical management, including counselling the patient and family.",1
"Justo, R N, Dare, A J, Whight, C M, Radford, D J",2
Cerebral blood flow velocity monitoring in pyogenic meningitis.,0
"Transcranial Doppler ultrasound monitoring of cerebral blood flow velocity (CBFV) was performed on 17 children (age range 8 days to 6 years) with pyogenic meningitis. Serial measurements of the peak systolic, end diastolic, mean flow velocity, and resistance index (equal to peak systolic velocity minus end diastolic velocity divided by peak systolic velocity) were obtained over the period of their hospital admission. In all 16 survivors there was a significant decrease in the final resistance index compared with the initial resistance index due to a significant increase in the end diastolic velocity. There was a significant increase in the final mean flow velocity. In four patients the decrease in intracranial pressure and increase in cerebral perfusion pressure after mannitol infusions was accompanied by a corresponding decrease in resistance index and increase in mean flow velocity. A pressure passive CBFV response with a significant linear correlation for resistance index/mean arterial pressure may suggest a loss of cerebrovascular autoregulation. These results suggest that in the early phase increased cerebrovascular resistance may contribute to a relative impairment of cerebral perfusion. Non-invasive monitoring by transcranial Doppler ultrasound may be helpful for early detection of deterioration in cerebral haemodynamic trends.",1
"Goh, D, Minns, R A",2
Nursing staff requirements for neonatal intensive care.,0
"A study to estimate the number of nursing staff required for neonatal nursing was undertaken. Certain nursing tasks, such as transporting any infant, caring for the dying infant, and looking after the very unstable infant required continuous attention by one nurse (5.5 whole time equivalent (wte) nurses for each cot). The stable ventilated infant required 10.5 nursing hours each day-that is, 2.4 wte/cot. Infants with intravenous infusions, but not ventilated, required only slightly less nursing time: 9.25 nursing hours each day or 2.12 wte/cot. Each special care patient needed 6.50 nursing hours each day, or 1.49 wte/cot. It is emphasised that each neonatal unit will have to take its own practices into account when calculating neonatal nursing requirements.",1
"Williams, S, Whelan, A, Weindling, A M, Cooke, R W",2
Measuring neonatal nursing workload. Northern Neonatal Network.,0
"A dependency scale has been devised for the assessment of the needs of neonates for nursing time. It has been validated by work studies which have shown that non-surgical babies can be grouped into one of two categories: high dependency babies generating a mean (SD) 25 (5) minutes and low dependency babies generating 12 (3) minutes of nursing work per hour, when the work is averaged out over the whole shift. Any one of five simple and unambiguous criteria serve as robust markers for identifying more than 95% of babies regularly generating more than 15 minutes of nursing work per hour. The scale is simpler, can be applied more rapidly, and with greater consistency, than other currently available neonatal dependency scales. Additional allowance needs to be made for miscellaneous activity not attributable to individual babies, for the occasional baby who requires almost continuous undivided nursing attention, for the possibility of new admissions, and for the provision of an emergency interhospital transport service. A formula is suggested by which safe staffing levels for any given nursing shift can be determined, based upon the number of babies present and their dependency levels as determined by the scale.",1
Pneumonia in neonates: can it be managed in the community?,0
"Neonatal pneumonia kills about two million children a year worldwide. The World Health Organisation recommends hospitalisation of all cases of pneumonia in the first two months of infancy. In a field trial of community based management of childhood pneumonia in Gadchiroli, India, neonatal pneumonia contributed more than half of the pneumonia deaths. Parents refused referral even when advised therefore community based health workers and traditional birth attendants managed cases of neonatal pneumonia with co-trimoxazole. Case fatality was 15% (10/65) in all cases and 6% (3/52) in cases without high risk or referral indications. Case fatality in 56 babies aged 30-59 days treated for pneumonia was zero. During the two years of the trial, pneumonia specific mortality rate in the intervention area was 40% less in the neonates and about 80% less in the second month and rest of infancy compared with the control area. Pneumonia in the second month of infancy and uncomplicated cases of neonatal pneumonia can be safely and effectively managed in the community using co-trimoxazole.",1
"Bang, A T, Bang, R A, Morankar, V P, Sontakke, P G, Solanki, J M",2
Decreased plasma fibronectin concentrations in preterm infants with septicaemia.,0
"Changes in plasma fibronectin concentrations were determined during bacterial septicaemia in extremely preterm infants. The study was a prospective study of fibronectin concentrations in infants of less than 30 weeks' gestation. Concentrations were determined at birth, before sepsis, and throughout the episode of sepsis. Fibronectin concentrations at birth or immediately before sepsis were not significantly different between those infants who developed septicaemia and those who did not (98 (15) v 97 (10) micrograms/ml). In the infants with septicaemia, fibronectin concentrations decreased significantly on day 1 (106 (13) v 173 (18) micrograms/ml for the controls) and remained significantly lower on day 2 (123 (26) v 201 (17) micrograms/ml). By day 5 fibronectin concentrations had increased and were no longer statistically different from controls. Fibronectin is a key modulator of the immune response, with important functions in neutrophil adhesion, bacterial opsonisation, T cell activation, and vascular integrity. Acute depletion of plasma fibronectin during sepsis in preterm neonates may further abrogate their ability to control sepsis.",1
"Dyke, M P, Forsyth, K D",2
Diversity in regulation of adhesion molecules (Mac-1 and L-selectin) in monocytes and neutrophils from neonates and adults.,0
"The surface expression and regulation of the adhesion promoting glycoproteins Mac-1 and L-selectin was measured on monocytes and neutrophils from neonates and adults. A significant decrease in Mac-1 up regulation on both monocytes and neutrophils was found in neonates after both high (10(-7)M) and low (10(-9)M) concentrations of the chemotactic factor N-formyl-methionyl-phenylalanine (FMLP). A significant difference was obtained after incubation for five minutes, which was further enhanced after incubation for 15 minutes. Factors related to bacterial infections, lipopolysaccharides, activated sera (C5a), and aggregated IgG induced an impaired Mac-1 up regulation on both monocytes and neutrophils from neonates compared with adults. The expression of L-selectin was significantly lower on neutrophils from neonates and was less down regulated upon stimulation with a low concentration (10(-12)M) of FMLP. On monocytes from neonates, the expression and down regulation of L-selectin did not differ from monocytes from adults. Mode of delivery did not influence the regulation of Mac-1 and L-selectin in neonates. Diversity in expression and regulation of Mac-1 and L-selectin on monocytes and neutrophils may contribute to the increased susceptibility to infections observed in neonates.",1
"Török, C, Lundahl, J, Hed, J, Lagercrantz, H",2
Dexamethasone treatment in preterm infants at risk for bronchopulmonary dysplasia.,0
"A randomised double blind placebo controlled study was conducted to determine whether a one week course of dexamethasone could reduce the severity of bronchopulmonary dysplasia in preterm infants without compromising their adrenal function. Forty one infants with a mean birth weight of 880 g and a gestational age of 27 weeks who were ventilator dependent at 10 days of age were enrolled. At the age of 28 days pulmonary outcome was significantly better in the girls treated with dexamethasone but not in all infants. There was no difference between the groups in the long term outcome, except for a shorter duration of supplemental oxygen in dexamethasone treated female infants. After the one week dexamethasone treatment there was a significant but short lived suppression of the basal cortisol concentrations and the adrenal response to corticotrophin (ACTH). No serious side effects were observed. It is concluded that early one week dexamethasone treatment improves short term pulmonary outcome in premature infants, but there is no clear evidence of long term benefits.",1
"Kari, M A, Heinonen, K, Ikonen, R S, Koivisto, M, Raivio, K O",2
Randomised trial of methods of extubation in acute and chronic respiratory distress.,0
"Sixty infants (median gestational age 29 weeks) with acute and 60 infants (median gestational age 25 weeks) with chronic respiratory distress were randomised to be extubated either directly into a headbox or onto 3 cm H2O nasal continuous positive airway pressure (CPAP). Our aim was to test the hypothesis that extubation onto nasal CPAP rather than directly into a headbox was more likely to be associated with successful extubation in infants with acute rather than chronic respiratory distress. Overall the failure rate of extubation was approximately 33%, with no significant difference between the infants with acute and chronic respiratory distress. There was no significant difference in the failure rate of extubation among infants randomised to receive nasal CPAP or headbox oxygen in either the acute or chronic respiratory distress groups.",1
"Chan, V, Greenough, A",2
Increased bone mineral content of preterm infants fed with a nutrient enriched formula after discharge from hospital.,0
"Bone disease with persistent reduced bone mineralisation is common in premature infants. To test the hypothesis that enhancement of nutritional intake after discharge from hospital improves bone mineralisation, 31 formula fed preterm infants were randomly assigned to receive standard or multinutrient enriched milk from the time of discharge. The calcium and phosphorus contents of the enriched milk were 70 and 35 mg/100 ml v 35 and 29 mg/100 ml for the standard formula. Bone mineral content was measured before discharge from hospital in 21 of the infants; there was no difference in the bone mineral content between the groups at that time (35 mg/cm for the two groups). There was a significant increase in bone mineral content for those infants receiving the enriched v standard formula at 3 and 9 months corrected postnatal age: at 3 months the bone mineral content was 83 v 63 mg/cm and at 9 months 115 v 95 mg/cm. The difference between the groups was thus maintained although not increased at a corrected age of 9 months, when the bone mineral content of infants fed the enriched but not the standard formula was no longer significantly different from that of normal infants after adjusting for body size. The difference was not explained by the larger body size in infants fed the enriched formula. The results suggest that the use of a special nutrient enriched postdischarge formula has a significant positive effect on bone growth and mineralisation during a period of rapid skeletal development.",1
"Bishop, N J, King, F J, Lucas, A",2
Hyperphenylalaninaemia and outcome in intravenously fed preterm neonates.,0
"Hyperphenylalaninaemia is likely to have occurred in many infants fed the intravenous amino acid solution Vamin 9. In this study of 336 preterm infants plasma phenylalanine was measured weekly during their hospital stay. Reference data on plasma phenylalanine were prepared for 243 infants who did not receive Vamin. Only 1% of these infants had a peak plasma phenylalanine concentration greater than 150 mumol/l (maximum 202 mumol/l) compared with 23% in 93 infants fed Vamin 9, seven of whom had concentrations > 300 mumol/l (maximum 704 mumol/l). High concentrations only occurred when the total energy to protein energy ratio in the intravenous solutions decreased to less than 8.5:1 and always occurred with a ratio less than 6.5:1, implying that hyperphenylalaninaemia may be minimised with an intravenous energy intake of greater than 34 kcal (142 kJ)/g protein. Nevertheless, follow up at 18 months post-term showed that increased plasma phenylalanine in this instance was not associated with any impairment of the Bayley mental development index (or subscales including fine motor, cognitive, or language development), the psychomotor development index, or the social maturity quotient. Thus, despite theoretical concern, an adverse outcome after hyperphenylalaninaemia induced by intravenous feeding has not been observed.",1
"Lucas, A, Baker, B A, Morley, R M",2
Change in blood pressure after treatment of patent ductus arteriosus with indomethacin.,0
"The effect of indomethacin treatment of patent ductus arteriosus (PDA) on blood pressure was studied in 24 preterm infants. PDA was diagnosed clinically and confirmed by echocardiography; the effect of treatment was monitored echocardiographically. Hourly intra-arterial recordings of systolic, diastolic, and mean blood pressure were averaged for the 48 hours before the first dose of indomethacin and for each of the three 24 hour periods after the first dose. In the 16 infants in whom treatment was successful, the average mean blood pressure increased significantly over the three days after the first dose. On the third day after beginning treatment with indomethacin the average increase in mean blood pressure was 10.4 mm Hg. Fourteen of 16 infants showed an increase of 4 mm Hg or more. Systolic and diastolic blood pressure increased significantly by similar amounts, so the pulse pressure did not change. In the eight infants treated unsuccessfully, there was no consistent change in any of the blood pressure parameters. The maximum increase in mean blood pressure was 3 mm Hg. These findings confirm that PDA is one of the determinants of blood pressure in preterm infants. The effect is general and there is no consistent change in pulse pressure when a PDA is closed. A general increase in blood pressure is a useful additional indicator of successful medical ductal closure.",1
"Evans, N, Iyer, P",2
Renal artery blood flow velocity in very low birthweight infants with intrauterine growth retardation.,0
"Doppler ultrasound was used to measure left renal artery blood flow velocity and pulsatility index on the first, third, and seventh day of postnatal life in 18 very low birthweight small for gestational age (SGA) infants. The values were compared with those from 18 weight matched and 18 gestation matched controls. SGA infants had significantly lower blood flow velocity than their gestation matched controls throughout the first postnatal week (day 1: SGA 10 cm/s, controls 15 cm/s; day 7: SGA 17 cm/s, controls 28 cm/s). These data suggest that abnormalities of renal artery blood flow velocity persist after delivery in the SGA infant.",1
"Kempley, S T, Gamsu, H R, Nicolaides, K H",2
Scarring alopecia in neonates as a consequence of hypoxaemia-hypoperfusion.,0
"Scarring alopecia is relatively uncommon in infants and children and rarely discussed in the paediatric literature. It does not appear to have been previously documented as a consequence of compromised oxygenation and blood supply in the neonatal population or as a complication of extracorporeal membrane oxygenation (ECMO) treatment. During a six month period, we observed five patients who presented to our neonatal intensive care unit with pressure ulcers that eventuated in scarring alopecia. The patients were all > or = 2500 g at birth, had some disruption of the cardiac circulation, were hypoxaemic and acidotic, and required vasopressor treatment. Institution of a positioning schedule and use of a thermostable Spenco gel pad during the subsequent six month period eliminated the presence of pressure ulceration and scarring alopecia in this at-risk population. Although scarring alopecia is a permanent condition, skin changes preceding its development in this setting are recognisable and follow a predictable pattern and time course, and should therefore allow for intervention at an earlier stage. Neonatal ECMO patients, as well as those who suffer hypoxaemia-hypoperfusion, but do not require circulatory bypass, appear to be at increased risk for development of the pressure ulcers that precede scarring alopecia. Paediatricians should consider this possibility and seek the appropriate historical information when confronted with a case of scarring alopecia after the neonatal period.",1
"Gershan, L A, Esterly, N B",2
What cord care--if any?,0
The use of antiseptic treatment during cord care varies from unit to unit. Although it may reduce bacterial colonisation it may also delay cord separation. Where antiseptic treatment is used there is uncertainty as to the best agent. Hexachlorophane powder (0.3%) and 4% chlorhexidene detergent were each compared with dry cord care as a control on a two ward maternity unit in a six month open study. Of 133 infants treated with hexachlorophane 44 (33%) became heavily colonised with Staphylococcus aureus compared with 80 (47%) of 171 controls; a reduction of one third. Chlorhexidene reduced colonisation by more than half; 17 (16%) of 104 compared with 41 (42%) of 98 controls. Chlorhexidene was associated with cord attachment at 10 days in 29 (28%) infants compared with 31 of 515 (6%) infants when it was not used. Hexachlorophane was more acceptable to the nursing staff. The reduction in colonisation with the two compounds was largely due to the suppression of cross infection.,1
"Verber, I G, Pagan, F S",2
Parental costs of neonatal visiting.,0
"Interviews with 93 mothers of 109 low birthweight infants admitted to a regional neonatal intensive care unit showed that, although 82 (88%) mothers visited on a daily basis, some families faced considerable travelling difficulties. Five families travelled more than 100 miles and three families had twin siblings in different neonatal units. Analysis of the travelling and associated expenditure strongly indicates that the parents in most need received little or no help from the statutory authorities and only 26 (28%) families received financial help from any source. There emerges a strong case for offering appropriate financial help to parents on low incomes to facilitate visiting and increase family contact.",1
"McLoughlin, A, Hillier, V F, Robinson, M J",2
Isolated single umbilical artery--the case for routine renal screening.,0
"To determine the incidence of silent renal anomalies in infants with isolated single umbilical artery (SUA), all infants with SUA and without other obvious congenital anomalies, identified over a six year period, were screened using renal ultrasonography. Over 35,000 placentas were examined. An isolated single umbilical artery was identified in 112 (0.32%). Nineteen infants had abnormal renal imaging. Eight of 112 (7.1%) had significant persisting abnormalities. Vesicoureteric reflux was found in five infants (4.5%). It is recommended that renal ultrasonography be performed for all infants with isolated SUA.",1
"Bourke, W G, Clarke, T A, Mathews, T G, O'Halpin, D, Donoghue, V B",2
Ranitidine pharmacokinetics in newborn infants.,0
"Few data are available for ranitidine pharmacokinetics in the first few days of life. Twenty seven newborn infants were treated with intravenous ranitidine because they were vomiting blood, although they had a negative Apt's test. Each infant provided two blood samples at randomly selected times 30-360 minutes after a 2.4 mg/kg intravenous bolus of ranitidine. A single exponential equation for the concentration-time graph was fitted to the mean serum concentrations at different times. From this model the following mean (SD) measurements wer derived: elimination half life, 207.1 (19.1) minutes; total volume of distribution, 1.52 (0.91) l/kg; and total plasma clearance, 5.02 (0.46) ml/kg/min. Assuming that these measurements do not change with different administered doses, regimens can be derived to assist in planning ranitidine treatment in newborn infants.",1
"Fontana, M, Massironi, E, Rossi, A, Vaglia, P, Gancia, G P, Tagliabue, P, Principi, N",2
Do preterm infants always have flattened heads?,0
"It has previously been shown that a soft mattress lessens the degree of head flattening that occurs in preterm infants in the early weeks of life. A follow up study of 31 infants of < 32 weeks' gestation found head flattening had resolved by 3-4 years of age, regardless of the type of mattress used in the neonatal period, and the children had heads similar in shape to full term controls.",1
"Rutter, N, Hinchliffe, W, Cartlidge, P H",2
Severe unconjugated hyperbilirubinaemia with infradiaphragmatic total anomalous pulmonary venous connection.,0
"An 8 day old girl with infradiaphragmatic total anomalous pulmonary venous connection presented with severe unconjugated hyperbilirubinaemia; exchange transfusion resulted in haemodynamic deterioration. Hyperbilirubinaemia is a rare complication of this condition, however exchange transfusion should be avoided. The diagnosis can be made on the neonatal unit by ultrasound demonstration of dilated hepatic portal veins.",1
"Burch, M, Dyamenahalli, U, Sullivan, I D",2
Adenovirus type 8 conjunctivitis outbreak in a neonatal intensive care unit.,0
"An outbreak of adenovirus type 8 conjunctivitis occurred in seven premature infants who had undergone ophthalmological examination four to seven days previously. Three of the affected infants, treated with steroids because of bronchopulmonary dysplasia, showed systemic manifestations and deterioration of their respiratory disease. Second and third waves affected nine staff and 12 family members.",1
"Birenbaum, E, Linder, N, Varsano, N, Azar, R, Kuint, J, Spierer, A, Reichman, B",2
Postpartum changes in maternal blood lead concentrations.,0
"Studies of lead concentrations in blood during pregnancy are of interest because of the possibility of adverse effects on the fetus. One report of a single case suggested that blood lead concentrations are raised during pregnancy. This is consistent with the hypothesis of a pregnancy induced mobilisation of lead from bone. Data presented herein, however, indicate that blood lead measures are appreciably lower at delivery than they are at six months post partum. Other factors including but not limited to transmission to the fetus, may be influencing lead concentrations during pregnancy.",1
"Ernhart, C B, Greene, T",2
A report of two cases of chronic serious manganese poisoning treated with sodium para-aminosalicylic acid.,0
Two cases of chronic manganese poisoning were treated with sodium para-aminosalicylic acid (PAS-Na; 6 g/day in 500 ml of 10% glucose solution by intravenous drip). The results indicated that one had been clinically cured and that the other had obviously improved in clinical symptoms and signs. Thus PAS-Na appears to be an effective drug for treatment of serious chronic manganese poisoning.,1
"Ky, S Q, Deng, H S, Xie, P Y, Hu, W",2
Dust exposure and pneumoconiosis in a South African pottery. 1. Study objectives and dust exposure.,0
"Dust exposure and pneumoconiosis were investigated in a South African pottery that manufactured wall tiles and bathroom fittings. This paper describes the objectives of the investigation and presents dust measurement data. x Ray diffraction showed that the clays used by the pottery had a high quartz content (range 58%-23%, mean 38%). Exposure to respirable dust was measured for 43 workers and was highest (6.6 mg/m3) in a bathroom fitting fettler. Quartz concentrations in excess of 0.1 mg/m3 were found in all sections of the manufacturing process from slip production to biscuit firing and sorting. The proportion of quartz in the respirable dust of these sections was 24% to 33%. This is higher than is usually reported in English potteries. Four hundred and six (80%) of the 509 workers employed at the pottery were potentially at risk of occupational lung disease. The finding of large numbers of pottery workers exposed to unacceptable dust concentrations is not surprising as poor dust control was found in all six wall tile and sanitary ware factories surveyed by the National Centre for Occupational Health between 1973 and 1989. Dust related occupational disease can be expected in potters for many years to come.",1
"Rees, D, Cronje, R, du Toit, R S",2
Radiographic osteoarthrosis in the acromioclavicular joint resulting from manual work or exposure to vibration.,0
"The hypothesis that manual work and exposure to vibration are antecedents to the development of osteoarthrosis was assessed employing a cross sectional study design. The frequency of osteoarthrosis in the acromioclavicular joint was studied in three groups of workers in the construction industry. Two groups were manual workers (54 bricklayers and 55 rock blasters); the third group consisted of 98 foremen. The radiographic appearance of the right and left acromioclavicular joints was classified into one of five grades of osteoarthrosis. A protocol was developed to assess exposure on the basis of job title, years of manual work, total weight lifted during working life, and total hours of exposure to vibrating tools. Odds ratios for job titles (manual worker v foreman) and for years of manual work as indicators of exposure were of similar magnitude of around 2.5. Construction workers who had lifted more than 709 tonnes had an increased risk of developing severe osteoarthrosis of the right acromioclavicular joint, odds ratio: 2.62 (95% confidence interval (95% CI), 1.13-6.06). The odds ratio for the left side was 7.67 (95% CI, 2.76-21.34). In the analysis of vibration exposure, workers who had been highly exposed to vibration had an odds ratio of 1.99 (95% CI, 1.00-3.92) on the right side and 2.20 (95% CI, 1.07-4.56) on the left. This effect almost disappeared after simultaneous adjustment for manual work. Occupational and ergonomic factors, such as the sum of lifted tonnes during working life, job title, and the sum of years of manual work seem to be risk factors for osteoarthrosis of the acromioclavicular joint, whereas vibration alone was a weaker risk factor.",1
"Stenlund, B, Goldie, I, Hagberg, M, Hogstedt, C, Marions, O",2
A new treatment for congenital nystagmus.,0
"Congenital nystagmus is a disorder of eye movement with an associated reduction in visual acuity. The latter is mainly due to the intensity of the nystagmus (amplitude times frequency) allowing the object of regard to spend only a short time on the fovea. Training patients by an auditory feedback technique to control the nystagmus enables visual sensitivity to improve. This method is compared with present alternatives, and further studies are suggested.",1
"Abadi, R V, Carden, D, Simpson, J",2
Buckling procedures for retinal detachment caused by retrolental fibroplasia in premature babies.,0
"Three premature babies with advanced stages of retrolental fibroplasia underwent retinal surgery by buckling procedures, with satisfactory results. The indications and surgical technical problems are discussed.",1
"Grunwald, E, Yassur, Y, Ben-Sira, I",2
The questionably dry eye.,0
"This paper is concerned with the recognition of the dry eye when the clinical diagnosis is in doubt and other external eye diseases may be present. Papillary conjunctivitis is common to the dry eye as well as other pathological conditions and confuses the diagnosis. We have correlated the factors involved in the assessment for dryness. We have shown that particulate matter in the unstained tear film is associated with low tear lysozyme concentration. Tear flow and tear lysozyme are not necessarily interrelated, but a low lysozyme concentration (tear lysozyme ratio < 1.0) is associated with keratoconjunctivitis sicca. The Schirmer I test can produce false positive results, and we have suggested a modification to overcome this. This modified test will detect the eye with severely depleted lysozyme secretion, but it is unreliable for detecting the eye with moderately depleted secretion. We find that its lowest normal limit should be considered as 6 mm.",1
"Mackie, I A, Seal, D V",2
Development of quantitative methods of measuring antifungal drug effects in the rabbit cornea.,0
By means of multiple inoculation in each cornea with microtrephination a highly reproducible quantitative model of fungal infection of the rabbit corneal stroma has been produced. A known suspension of the chosen pathogen was systematically implanted into the trephine sites in the cornea. The degree of infectivity was monitored in both the preinoculation treated corneae (prophylaxis) and the postinoculation treated corneae (therapy). Examples measuring and comparing the antifungal effect of various imidazole drugs against Candida albicans are discussed.,1
"Oji, E O",2
Clinical aspects of the measurement of oxygen flux into the cornea.,0
"A comparison was firstly done of the oxygen flux through the Bausch and Lomb Plano T lens, the Bausch & Lomb U3 lens, and the Duragel 75 lens with a sensor on the normal eye. The results showed that the Bausch and Lomb Plano T lens was the best for use with the sensor probe. The sensor was then used to obtain a comparison with the normal oxygen flux through a therapeutic lens on keratoplastic eyes and eyes with bullous keratopathy. The results showed that both conditions had a lower oxygen consumption than normal and that eyes with bullous keratopathy predictably had the lowest value.",1
"Morris, J, Ruben, M",2
Retinal pigment epithelial detachments in the elderly: a controlled trial of argon laser photocoagulation.,0
"A prospective randomised trial of argon laser photocoagulation of retinal pigment epithelial detachments in the elderly is presented. The results based on 18 months' follow-up show that, in terms of visual acuity, photocoagulation is not beneficial as carried out in this study. The morphological outcome of the treated and untreated eyes is discussed. Stricter entry criteria would not have affected the conclusions. Tearing of the pigment epithelium occurred earlier in the treated than in the untreated eyes.",1
Prevalence and aetiology of cataract in Punjab.,0
"Three districts in the Punjab plains were surveyed in 1976-7 for senile cataract and potential risk factors. The prevalence of senile cataract was 15.3% among 1269 persons examined who were aged 30 ang older, and 4.3% for all ages. These figures confirmed previous reports of high prevalence. The prevalence was 1% for ages 30-49 and increased markedly in the sixth and seventh decades to 67% for ages 70 and older. Univariate age-adjusted analyses of selected socioeconomic, demographic, dietary, and other variables suggested that a higher prevalence was associated with being widowed, low education, use of rock salt in cooking, infrequent consumption of various protein foods (beans and lentils, milk, eggs, and curd), short height, and low weight. Multivariate analysis further suggested low total protein consumption as a risk factor that may account for as much as 40% of the excess prevalence of Punjab cataract over that in a US population study.",1
"Chatterjee, A, Milton, R C, Thyle, S",2
Unusual clinical and histopathological findings in ocular sarcoidosis.,0
"A 37-year-old Caucasian woman presented with a blind left eye and granulomatous panuveitis in the right eye. There was a subretinal neovascular membrane with haemorrhage beneath the macula and widespread subretinal lesions that were interpreted as choroidal granulomas in the right eye. A chest x-ray that showed diffuse pulmonary fibrosis without hilar lymphadenopathy was the only contributory clinical finding. Systemic and subconjunctival steroids and photocoagulation to the right macula brought about temporary remission. The painful left eye was enucleated. Histopathological examination revealed diffuse, noncaseating granulomas in the iris and ciliary body, retina, choroid, optic nerve, sclera and scleral emissaria, and inferior oblique muscle. A preretinal membrane was studied by electron microscopy. It was composed of a collagenous matrix containing fibroblasts and fibrous astrocytes. Some vessels, surrounded by a multilaminar basement membrane, revealed many features of normal retinal vasculature. Others were lined by markedly attenuated endothelial cells with occasional ""open' junctions and fenestrations.",1
"Frank, K W, Weiss, H",2
Blue fleck corneal iridescence: an occasional feature of Cogan's microcystic corneal dystrophy.,0
"Flecks consisting of brilliant reflective blue dots and streaks were a prominent biomicroscopical feature in three patients with Cogan's microcystic corneal dystrophy. Two patients required epithelial debridement. We used the material obtained to investigate their histology and ultrastructure. A subepithelial accumulation of basement membrane-like material composed of ultrastructurally fine granules was deposited in alternating layers of compaction and rarefaction. The layers lie mostly parallel to the anterior corneal surface, but in some places they are folded. Such foldings are possibly the sites of multilaminar reflection and constructive interference, giving rise to the blue iridescence.",1
"Dark, A J, Proctor, J",2
Autosomal dominant vitreoretinochoroidopathy (ADVIRC).,0
"We report the second family recognised to have autosomal dominant vitreoretinochoroidopathy. The clinical features were (1) autosomal dominant inheritance; (2) peripheral, coarse pigmentary degeneration of the fundus for 360 degrees, with a relatively discrete posterior border in the equatorial region (this finding may be pathognomonic); (3) superficial punctate yellowish-white opacities in the retina; (4) various vascular abnormalities; (5) breakdown of the blood-retinal barrier; (6) retinal neovascularisation; (7) vitreous abnormalities; and (8) choroidal atrophy. Visual reduction was mainly due to macular oedema or vitreous haemorrhage.",1
"Blair, N P, Goldberg, M F, Fishman, G A, Salzano, T",2
Supernormal scotopic ERG in cone dystrophy.,0
"Three patients with a bull's-eye macular lesion and other signs characteristic of cone dystrophy gave an unusual ERG finding. In response to a white flash of moderate intensity the scotopic b-wave amplitude was considerably larger than normal. One patient had elevated rod thresholds and nyctalopia, while the other 2 had normal rod sensitivity associated with the supernormal scotopic b-wave amplitude. In the latter 2 patients the abnormal ERG pattern was unchanged for 4 years and 7 years respectively. This atypical finding, of a supernormal scotopic b-wave amplitude in response to light of moderate intensity, appears to characterise a subgroup of patients with cone dystrophy, probably of autosomal recessive inheritance. The pathogenesis of the abnormal ERG remains uncertain.",1
"Alexander, K R, Fishman, G A",2
Experimental ocular toxocariasis: a mouse model.,0
"Male mice, strain C57 black, were infected with Toxocara canis by a single intragastric dose of 1500 infective eggs. The eyes were studied at sequential time periods after infection (6 to 63 days) by conventional microscopic techniques, and the histological characteristics of the inflammatory response were recorded. In the majority of animals the disease was unilateral. Twenty-six larvae were found in the retina, in the retinal vessels, and in the subretinal space in 20 eyes, while in 29 eyes there were inflammatory changes which were not related to the presence of intact or fragmented larval forms. The inflammatory reaction began as a polymorphonuclear response but after day 13 became a granulomatous reaction. This suggests that the inflammatory phenomenon may be propagated by the secreted surface antigens in the absence of the living or dead larvae.",1
"Ghafoor, S Y, Smith, H V, Lee, W R, Quinn, R, Girdwood, R W",2
Astigmatism following cataract surgery.,0
"The changes in corneal curvature were determined at regular intervals over a one-year period following intracapsular cataract extraction by microsurgical techniques. During the first postoperative month photokeratometric measurements showed rapid changes in astigmatism associated with large changes in the direction of the axis. Thereafter astigmatism against-the-rule predominated. Data from the small group of patients who underwent surgery in which the technique of phacoemulsification was used show that the smaller changes in corneal curvature are attributable to the smaller incision size and reduced number of sutures. With patients who underwent intracapsular extraction a comparison has been made between the effects of large and small section sizes, and a procedure is outlined whereby surgically induced astigmatism may be minimised.",1
"Reading, V M",2
Eye disease in the West Bank and Gaza strip.,0
"A random sample of 9548 Palestinian Arabs living in the West Bank and Gaza Strip was identified, and 9054 (95.7%) were examined. Particular attention was directed to reduced visual acuity (VA) and its cause and to trachoma. Low visual acuity was defined as less than 6/18 in both eyes and binocular blindness as a VA less than 3/60 in both eyes. The overall incidence of low VA was 6.8% and of binocular blindness 1.7%. The three principal causes of blindness in order of frequency were cataract, trachoma, and corneal leucoma. These three conditions accounted for 66.7% of binocular blindness. Trachoma was present in 2568 (28.4%) of the 9054 people examined.",1
"Thomson, I M, Chumbley, L C",2
Subretinal neovascularisation in eyes with localised inferior posterior staphylomas.,0
"We report seven cases of subretinal neovascularisation with inferior posterior staphyloma. The upper border of the shallow staphyloma, detected by B-mode echography, invaded the macular area, and there was a neovascular net at the edge of the staphyloma. Three of the cases showed chorioretinal atrophy at the upper edge of the staphyloma in the same location as the neovascular net. Our cases were identical to those of subretinal neovascularisation in high myopic eyes in which the rupture of Bruch's membrane was related to the deformity of the scleral shell. As our cases included not-high-myopic eyes, the results suggest that the identical mechanism might be involved in the occurrence of neovascular maculopathy in the pathological high myopic eye and in the not-high-myopic eye with posterior staphyloma. Localised inferior posterior staphyloma may be an important cause of 'idiopathic' subretinal neovascularisation.",1
"Tsuboi, S, Uchihori, Y, Manabe, R",2
"Low-contrast letter charts in early diabetic retinopathy, ocular hypertension, glaucoma, and Parkinson's disease.",0
"Diabetes can cause visual loss that is not detected by standard reading tests such as the Snellen test but can be detected by low-contrast letter charts. This visual loss is quite different from loss caused by refractive error. These low-contrast charts are diagnostically at least as sensitive as the sinewave grating contrast sensitivity test. They are inexpensive, and the test is brief and simple. Preliminary evidence is that patients with diabetes who have abnormal low-contrast chart results give abnormal intravenous fluorescein (IVF) test results, even though visual acuity is normal. Low-contrast charts also detect visual loss in patients with ocular hypertension, glaucoma, and Parkinson's disease, including patients with normal visual acuity.",1
"Regan, D, Neima, D",2
Histiocytosis X: an ophthalmological review.,0
"Of 76 children with histiocytosis X 18 had orbital involvement, and four developed additional neuro-ophthalmic complications. No instance of intraocular involvement was detected. Among those patients with ophthalmic involvement the main problems were bilateral or unilateral proptosis, ptosis, papilloedema, optic atrophy, and seventh nerve palsy. Only one patient developed a severe visual defect. Management of the ophthalmological complications depends not only on the extent of the orbital disease but also on the degree of systemic involvement. Overall management by a paediatric oncologist is mandatory.",1
"Moore, A T, Pritchard, J, Taylor, D S",2
Giant retinal tears after central vitrectomy.,0
Giant retinal breaks developed in four eyes within two months of pars plana vitrectomy. The pathogenesis and implications of this serious complication are discussed.,1
"McLeod, D",2
"Glaucoma triple procedure of extracapsular cataract extraction, posterior chamber lens implantation, and trabeculectomy.",0
"Thirty-four consecutive glaucoma triple procedures with a minimum follow up of six months have been shown to be effective and safe. Satisfactory control of the glaucoma was achieved in each case, and 91% of eyes were returned to an acuity of 6/12 or better. 1% sodium hyaluronate was found to be beneficial by preventing scleral or corneal collapse during surgery and ensuring an even filtration postoperatively without hypotony.",1
"Percival, S P",2
Family studies in glaucoma.,0
"Two groups of patients with a family history of chronic open-angle glaucoma were compared with a normal population of 5919 individuals studied during the Bedford Glaucoma Survey. The mean screening intraocular pressure was significantly raised in both groups with a family history of chronic open-angle glaucoma. The prevalence rate of a raised intraocular pressure was 3.81 times that found in the normal population. This relationship was maintained when age-dependent prevalence rates were evaluated. No correlation between raised intraocular pressure and type of familial involvement could be determined. A 10- to 12-year follow-up of one group with a family history for open-angle glaucoma (101 patients) showed that 3% developed confirmed glaucoma, while an additional 5.9% were diagnosed as suspected chronic open-angle glaucoma. A letter survey of this group showed that 9 out of 63 respondents knew of additional family members who developed glaucoma over this 10-12-year period.",1
"Rosenthal, A R, Perkins, E S",2
The ocular pulse and intraocular pressure as a screening test for carotid artery stenosis.,0
"The ocular pulse and applanation tension were measured with a recording applanation tonometer in 38 patients suspected of having internal carotid artery stenosis. Abnormalities of the ocular pulse amplitude, intraocular pressure, or combinations of these two measurements were found in 23 (82%) of 28 patients who were subsequently found to have angiographic evidence of 50% or more stenosis of one or both internal carotid arteries. Of 10 patients without angiographic evidence of carotid stenosis the ocular pulse amplitude, intraocular pressure, or both were abnormal in five, but two patients had an ocular cause for abnormality and two of the remaining three had evidence of carotid disease in the form of atheromatous plaques. These results suggest that measurement of the amplitude of the ocular pulse in addition to the intraocular pressure can predict the presence of carotid artery stenosis and indicate the need for further investigation. If a tonometer capable of measuring the pulse amplitude was used routinely in ophthalmic examinations, it would provide a useful screening test for the early diagnosis and treatment of carotid artery disease and might thereby reduce the frequency of strokes.",1
"Perkins, E S",2
Transient monocular obscuration--?amaurosis fugax: a case report.,0
"A 73-year-old white man with pseudophakia experienced repeated bouts of transient visual loss associated with erythropsia and colour desaturation. A diagnosis of atheromatous carotid vascular disease was considered, prompting carotid angiography, during which time the patient experienced transient aphasia. Subsequent examination during an episode of visual loss showed that a spontaneous anterior chamber haemorrhage was the cause of the visual complaints.",1
"Kosmorsky, G S, Rosenfeld, S I, Burde, R M",2
Results of 100 aphakic detachments treated with a temporary balloon buckle: a case against routine encircling operations.,0
"One hundred patients with aphakic detachment were treated with temporary balloon buckles. The balloons were deflated and withdrawn after seven to 10 days. Permanent attachment depended on cryo- or laser-induced adhesions round the break. The procedure was initially successful in 79 patients. Ten retinas became detached again after the balloon was withdrawn and required a more permanent buckle. Sixty-nine retinas remained attached. The final results after additional operations were equivalent to those obtained by traditional methods, but significantly fewer complications occurred. The balloon procedure tests the validity of routinely encircling aphakic detachment.",1
"Lincoff, H, Kreissig, I, Farber, M",2
Treatment and visual prognosis in Behçet's disease.,0
"For the last decade we have observed and regularly followed 49 patients with the ocular type of Behçet's disease. Thirty-six patients were males and 13 were females. Regardless of whether the initial ocular presenting symptoms were in the anterior or posterior segment, both segments were involved within two years. Sterile hypopyon was recorded in 17 out of the 49 patients during the process of follow-up. In three of the patients hypopyon was the presenting symptom. Characteristically there was a lack of corneal or scleral involvement in the disease process. All patients responded initially to treatment with steroids, but 42 had a course of treatment with cytotoxic-immunosuppressive drugs for various lengths of time after 'resistance' to steroids developed. Although definitely effective in reducing the intensity of the ocular inflammatory processes, it is not clear yet whether these modes of treatment have any dramatic effect of the visual prognosis of the affected eyes. Despite intensive follow-up and treatment, loss of useful visual acuity has occurred in 74% of the eyes six to 10 years after the start of the ocular symptoms.",1
"Benezra, D, Cohen, E",2
Association between optic disc haemorrhages in glaucoma and abnormal glucose tolerance.,0
"Data concerning the results of glucose tolerance tests and levels of intraocular pressure were analysed for 120 patients with primary open-angle glaucoma, many of whom had been under observation for a period of four to five years. The patients consisted of two groups: in 62 patients a disc haemorrhage had been recorded at some time during the observation period, and in 58 no haemorrhages had been seen. Patients with disc haemorrhages had a higher incidence of abnormal glucose tolerance or frank diabetes and lower intraocular pressures than those without haemorrhages.",1
"Poinoosawmy, D, Gloster, J, Nagasubramanian, S, Hitchings, R A",2
Detection of optic nerve damage in ocular hypertension.,0
"Thirty patients with ocular hypertension were tested for contrast sensitivity loss. Seventeen were not on treatment, and thirteen were receiving some form of pressure reducing therapy. The contrast sensitivity results of 63% of ocular hypertensive eyes were abnormal (greater than 2 SDs from the age matched norm). Thus it appears that contrast sensitivity can detect early visual loss in patients who have normal visual fields and it is suggested that this test might be used as a criterion for therapy in ocular hypertension. There was no significant difference in the intraocular pressures between patients who gave abnormal contrast sensitivity results and those who did not in the untreated group (p greater than 0.05), suggesting that intraocular pressure level is a poor predictor of optic nerve fibre damage in patients with ocular hypertension.",1
"Ross, J E, Bron, A J, Reeves, B C, Emmerson, P G",2
A blind randomised cross-over trial comparing metipranolol 0.3% with timolol 0.25% in open-angle glaucoma: a pilot study.,0
"A blind randomised cross-over study was conducted on 10 patients (20 eyes) to compare the effect in patients with open-angle glaucoma of metipranolol 0.3% with that of timolol 0.25% on intraocular pressure following one month's topical instillation with each preparation alone. There was no statistically significant difference in intraocular pressure reduction between these two preparations, and the ocular tolerance of both was good. There was no significant difference in the blood pressure, pulse, or pupil diameters of patients receiving either preparation.",1
"Mills, K B, Wright, G",2
Risk of sudden visual loss following trabeculectomy in advanced primary open-angle glaucoma.,0
We studied the postoperative course of two groups of patients with primary open-angle glaucoma and small residual visual fields undergoing trabeculectomy. We found that there is a considerable risk of sudden loss of visual field after operation on these patients.,1
"Aggarwal, S P, Hendeles, S",2
Luxation of the eyeball.,0
Luxation of the eyeball in two African patients is reported for its rarity. It followed minor trauma to the face and was reduced in both cases without permanent visual disability.,1
"Chhabra, H N, Kawuma, A M",2
Unilateral Kayser-Fleischer ring.,0
A patient is presented who had unrecognised Wilson's disease. He had developed a clinically obvious Kayser-Fleischer ring in only one eye. The eye without the corneal ring had been injured in childhood and had a low intraocular pressure. Possible mechanisms for formation of a Kayser-Fleischer ring are reviewed and the lack of Kayser-Fleischer ring in this case is discussed.,1
"Innes, J R, Strachan, I M, Triger, D R",2
Treatment of Mooren's ulcer with cyclosporin A: report of three cases.,0
"Three patients with severe, bilateral, progressive Mooren's ulcers, unresponsive to medical and surgical therapy, were treated with cyclosporin A. All three responded rapidly to the drug and there has been no recurrence of the Mooren's ulcers since (average follow-up 14 months). Peripheral blood T lymphocyte subsets were estimated prior to and during treatment. No significant abnormalities were found initially. Suppressor cells increased on treatment, and a corresponding drop of the helper/suppressor cell ratio occurred in two patients.",1
"Hill, J C, Potter, P",2
Ocular findings in a double-blind study of ivermectin versus diethylcarbamazine versus placebo in the treatment of onchocerciasis.,0
"The effect of ivermectin, a new microfilaricide, was assessed in a double blind trial against diethylcarbamazine citrate (DEC) and placebo. Fifty-nine adult males with moderate to heavy infection with Onchocerca volvulus and with eye involvement were recruited from an area under Onchocerciasis Control Programme (OCP) vector control in Northern Ghana. They were randomly assigned to an eight-day treatment with ivermectin as a single dose of 12 mg on day 1 followed by placebo for the remaining seven days, or DEC, total dose 1.3 g, or placebo, and ophthalmological review was undertaken over a period of one year. DEC acted quickly to eliminate microfilariae from the eye and was associated with reactive ocular changes and in a few cases functional deficit. Ivermectin eliminated microfilariae slowly from the anterior chamber of the eye over a period of six months. The ocular inflammatory reaction was minimal and no functional deficit occurred. It is postulated that the observed slow action of ivermectin on the eye may be attributed in part to its instability to cross the blood-aqueous humour barrier because of its molecular size as a macrocyclic lactone causing microfilariae to leave the eye gradually along a newly created gradient. Ivermectin is an effective microfilaricide with minimal ocular adverse effect and could therefore be suitable for widespread application without strict supervision.",1
"Dadzie, K Y, Bird, A C, Awadzi, K, Schulz-Key, H, Gilles, H M, Aziz, M A",2
Rational acyclovir therapy in herpetic eye disease.,0
"Acyclovir has been widely used against the various manifestations of eye disease due to herpes simplex since it first became generally available in the UK nearly five years ago. This paper discusses the rational indications for its use, through considerations of its pharmacology and pharmacokinetics, and through results of the many clinical trials that have been carried out to investigate its effects since its clinical efficacy was first demonstrated in 1979.",1
"Falcon, M G",2
"Blindness in schoolchildren: importance of heredity, congenital cataract, and prematurity.",0
"Of 99 children in the Royal Blind School, Edinburgh (which serves Scotland and part of N E England), 15 had optic atrophy (hydrocephalus 4, intracranial haemorrhage 2, prematurity 2, fetal distress 2, birth asphyxia 2, cerebral atrophy 1, cardiac arrest during hernia operation 1, and leukaemia 1). Fourteen had congenital cataract, 12 congenital retinal aplasia (Leber's congenital amaurosis) and 11 retinopathy of prematurity. There were small numbers in many other diagnostic categories, including three with non-accidental head injury. Mental retardation, spasticity, and nystagmus were frequent other correlates in all diagnostic categories. 'Very probably hereditary' was a conservative attribution in 36, while 'probable' seemed appropriate for 12-that is, almost 48% were hereditary. Only about 11 cases might have been prevented through genetic counselling, which testifies to the frequency of autosomal recessive hereditary disease, although no parents were consanguineous.",1
"Phillips, C I, Levy, A M, Newton, M, Stokoe, N L",2
Corneal and intraocular penetration of topical and subconjunctival fusidic acid.,0
"Corneal tissue absorption and intraocular penetration of fusidic acid were assessed in the rabbit after topical or subconjunctival application. Corneal tissue levels of fusidic acid one hour after the last topical application of the drug were well above the minimum inhibitory concentrations (MICs) for most Gram-positive and many Gram-negative organisms. Adequate levels were achieved in the aqueous at one hour following the last topical application, but no significant levels were detected in the vitreous. The corneal tissue and aqueous levels declined at 12 and 24 hours following the last drug application, however, corneal tissue levels at 24 hours were considered to be above the MICs for most Gram-positive organisms. A single subconjunctival injection of 100 mg of fusidic acid produced levels above the MICs of most organisms in the cornea, aqueous, and vitreous which persisted over 24 hours, but subconjunctival injection of fusidic acid at this concentration resulted in conjunctival necrosis and corneal decompensation. Fusidic acid penetrates well into avascular tissue and fully penetrates corneas with both intact and debrided epithelium, as evidenced by the intracameral drug levels. Good corneal penetration and absence of known topical toxicity make fusidic acid suitable for the treatment of microbial keratitis caused by susceptible organisms.",1
"Taylor, P B, Burd, E M, Tabbara, K F",2
"A comparison of the effects of oral nadolol and topical timolol on intraocular pressure, blood pressure, and heart rate.",0
"We compared the effects of oral nadolol 20 mg once daily and topical timolol 0.25% twice daily on the intraocular pressures of 22 glaucoma suspects, in a 12 week double-masked crossover study. Both nadolol and timolol reduced intraocular pressure (p less than 0.001). The reductions in intraocular pressure did not differ significantly after two weeks and four weeks of treatment. Nine of these subjects underwent treadmill exercise tests in order to compare the effects of nadolol and timolol on the cardiovascular system. The effects of the two treatments on blood pressure were comparable, but nadolol caused a significantly greater reduction in heart rate than timolol at rest (p less than 0.05). Nadolol reduces intraocular pressure effectively and may prove a useful alternative treatment for chronic simple glaucoma.",1
"Duff, G R, Watt, A H, Graham, P A",2
Anterior segment ischaemia following laser photocoagulation in a patient with systemic lupus erythematosus.,0
The authors report the occurrence of occlusive retinal arterial disease and retinal neovascularisation in a 44-year-old woman with systemic lupus erythematosus (SLE). Two days after uncomplicated panretinal photocoagulation the patient developed an acute anterior segment ischaemic syndrome. To our knowledge this complication has not been reported in any other patient following laser photocoagulation or in association with SLE.,1
"Jost, B F, Olk, R J, Patz, A, Fine, S L, Murphy, R P",2
On the management of retained airgun pellets: a survey of 11 orbital cases.,0
"Relevant factors determining the management of inaccessible retained lead airgun pellets are discussed in relation to 11 orbital cases. Although the injuries were of between one month's and 26 years' standing, serum lead levels were normal at under 350 micrograms/l in all instances. This is attributable to the modern alloy composition of the ammunition in question. It is concluded that surgical intervention may be indicated only where there is a mechanical disturbance of ocular motility allied with good visual function.",1
"Jacobs, N A, Morgan, L H",2
"Retinoblastoma in Great Britain 1969-80: incidence, treatment, and survival.",0
"Patients with retinoblastoma diagnosed from 1969 to 1980 have been followed up for periods of up to 17 years. Data from a previous study of patients diagnosed from 1962 to 1968 have been included for analysis of incidence and second primary tumours, and for study of trends in treatment. The registration rate in Britain (which may be about 10% less than the true incidence) is about one in 23,000 live births, approximately 40% of cases being known to be genetic. There is no apparent trend in incidence during the period covered by these two studies. The three-year survival rate in 88%. Patients with bilateral tumours have a better survival rate than those with unilateral tumours for the first few years, but their long-term survival rate is worse because of later deaths from ectopic intracranial retinoblastoma or second primary neoplasms. Older children tend to have a worse prognosis, which is related to the fact that their tumours are diagnosed at a more advanced stage. There is a significantly higher survival rate for boys than for girls; this is partly accounted for by difference in age and stage at diagnosis between the sexes. Children referred to units specialising in the treatment of retinoblastoma have a higher three-year survival rate than those treated at other hospitals. Comparing methods of treatment between the periods 1962-8 and 1969-80, we find there has been a trend towards more conservative treatment. The use of chemotherapy is now usually reserved for recurrences and metastases and for palliative treatment in terminal retinoblastoma.",1
"Sanders, B M, Draper, G J, Kingston, J E",2
Prevalence and causes of blindness in the northern Transvaal.,0
"During November 1985 a survey was carried out to determine the prevalence and causes of blindness in the Elim Hospital district of Gazankulu in the Northern Transvaal, South Africa, and to assess the Eye Department's effectiveness in preventing blindness. Using a random cluster sample technique, we screened 18,962 of the estimated 71,200 inhabitants of the district (26.6%). We found 109 blind people. The prevalence of blindness was 0.57% (95% confidence interval 0.46%-0.68%). The main causes of blindness were senile cataract (55%), corneal scarring due to trachoma (10%), uncorrected aphakia (9%), and open-angle glaucoma (6%). There were 14 aphakic blind persons who did not have aphakia glasses (43% of all persons operated on for cataract). Women had a significantly higher prevalence of blindness than men. After the age of 60 years the prevalence of blindness increased sharply. Women were 1.6 times less likely to have undergone cataract surgery than men. The two most effective steps to reduce the prevalence of blindness in the Elim district further are to provide aphakia glasses to all aphakic patients and to improve the accessibility of the Eye Department's surgical services.",1
"Bucher, P J, Ijsselmuiden, C B",2
Epithelial downgrowth: a 30-year clinicopathological review.,0
"We performed a retrospective clinicopathological review of 124 patients with epithelial downgrowth seen over a 30-year-period at the Massachusetts Eye and Ear Infirmary. The purpose of this study was to determine predisposing factors in the development of epithelial downgrowth, diagnostic symptoms and signs, and the results of various types of treatments. The incidence of this condition after cataract surgery was 0.12%, decreasing to 0.08% over the latter decade. 82% of postsurgical patients with epithelial downgrowth presented to the ophthalmologist within one year following surgery, commonly complaining of decreasing visual acuity, red eye, and pain. The most common presenting signs of epithelial downgrowth were retrocorneal membrane, which was seen in 45% of patients, glaucoma in 43%, corneal oedema in 21%, and a positive Seidel test in 23%. We found that a variety of conditions predispose to epithelial downgrowth but that no one factor was present in all cases. Damage to the underlying endothelium, corneal stromal vascularisation, and stromal downgrowth appeared to be important events not emphasised in prior studies. The angle was partially or totally closed in 87% of enucleation specimens. Patients treated surgically underwent fewer enucleations than those treated medically or not treated.",1
"Weiner, M J, Trentacoste, J, Pon, D M, Albert, D M",2
Mesectodermal leiomyoma of the ciliary body: case report.,0
"The clinical, light microscopical, and electron microscopical features of a mesectodermal leiomyoma of the ciliary body are presented. This exceptionally rare and apparently benign tumour is considered to be of neural crest origin. In the case described the tumour cells were seen to contain thin filaments with focal densities and conspicuous numbers of mitochondria, and smooth muscle protein was demonstrated by immunohistochemical means.",1
"White, V, Stevenson, K, Garner, A, Hungerford, J",2
Recent trends in the registration of blindness and partial sight in Leicestershire.,0
"A study is reported of all new registrations for blindness and partial sight in the county of Leicestershire, England, for the years 1965, 1975, and 1985. The number of new registrations for blindness has risen considerably over this period, but the increase is shown to be attributable to changes in the age structure of the population and under-registration in 1965. The number of new registrations for partial sight has also increased over the study period but by significantly more than would be expected, even after changes in the population structure are allowed for. The registration rates for Leicestershire when analysed by age, sex, and cause are shown to be broadly in line with available national figures. Registration rates for macular degeneration and glaucoma are increasing in both males and females, and rates for cataract are at a significantly higher level for women than for men.",1
"Thompson, J R, Du, L, Rosenthal, A R",2
Is padding necessary after cataract extraction?,0
"The results of a prospective study to assess the value of padding eyes following cataract surgery are reported. A group of eyes dressed with a petroleum jelly mesh, gauze pad, and cartella shield were compared with a group dressed only with a cartella shield. Study of the eyes and lids before and after operation, including the taking of lid margin and fornix swabs for culture, suggested that there was no significant difference in the bacterial presence between the two groups. The eyes dressed with a cartella shield alone appeared less prone to discharge. The relative merits of different types of dressing are discussed.",1
"Laws, D E, Watts, M T, Kirkby, G R, Lawson, J",2
Long-term follow-up of acute multifocal posterior placoid pigment epitheliopathy.,0
Eleven patients with acute multifocal posterior placoid pigment epitheliopathy were followed up for 47 to 175 months (mean 106 months). Seven of 18 affected eyes (39%) developed progressive mild alterations in the retinal pigment epithelium. Seventeen eyes (94%) had a final visual acuity of 20/30 or better. One eye with progressive retinal pigment atrophy involving the fovea lost visual acuity from 20/25 to 20/60.,1
"Williams, D F, Mieler, W F",2
Retinochoroiditis in acute Epstein-Barr virus infection.,0
The case is reported of a 17-year-old male with secondary glaucoma and retinochoroiditis complicating acute clinical infectious mononucleosis. The diagnosis was confirmed by Epstein-Barr virus specific serology. Toxoplasmic infection was initially suspected. The differential diagnosis and relevant literature are discussed.,1
"Kelly, S P, Rosenthal, A R, Nicholson, K G, Woodward, C G",2
Effect of donor parameters on primary graft failure and the recovery of acuity after keratoplasty.,0
A retrospective evaluation was made of 983 penetrating corneal grafts. Donor corneas stored in either K-Sol or McCarey-Kaufman media had a significantly greater rate of primary graft failure (about 2%) than those kept in moist chamber storage (0%). Selected subgroups of 50 corneas from each storage system were studied to determine the time taken to reach a postoperative acuity of 6/12. No significant correlation was found between this time and either the duration of storage of donor corneas or the age of donor. A significant delay in recovery of visual acuity was found with increasing age of recipient. The increased average time from donor death to surgery for K-Sol (56 hours) and McCarey-Kaufman (40 hours) corneas compared with moist chamber corneas (15 hours) facilitated the scheduling of surgery at the cost of increased chance of primary graft failure.,1
"Halliday, B L, Ritten, S A",2
Retinal dysfunction as an initial ophthalmic sign in AIDS.,0
Three cases of patients with AIDS in whom severe retinal dysfunction preceded the development of widespread funduscopic abnormalities are presented. The disparity between the minimal extent of visible retinal lesions and the severe loss of retinal function was confirmed by visual field and electroretinographic studies. This pattern of early visual loss in AIDS patients may represent infection of the retina by the HIV virus.,1
"Brodie, S E, Friedman, A H",2
"Microphthalmos with colobomatous orbital cyst: clinical, histological, immunohistological, and electronmicroscopic findings.",0
"A case of unilateral microphthalmos with orbital cyst is presented. This rare and severe malformation is a non-hereditary disorder. Pathologically it represents a failure in the closure of the embryonic fissure at the 7-14 mm stage of gestation. Staining for neurofilaments permitted the identification of rudimentary optic nerve fibers within the gliomatous cyst wall. Special stains for glial fibrillary acidic protein as well as scanning and transmission electron microscopy were used to characterise the neuroglial cell lining of the cyst wall, and to show microvilli on its inner surface.",1
"Lieb, W, Rochels, R, Gronemeyer, U",2
"Epikeratophakia for aphakia, keratoconus, and myopia.",0
"A series of 67 cases of epikeratophakia is presented with an average time from surgery of 12.2 months. For aphakia there was a delay in the recovery of vision, but by nine months 83% of 57 patients achieved an acuity equal to, or within 1 line of, the preoperative value. 57% were corrected to within 3 dioptres of emmetropia, but in the latter part of the series 75% were within this range. Astigmatism and reduced contrast sensitivity, especially in the presence of glare, were important complications. For keratoconus, 86% of seven patients with over two months of follow-up achieved a spectacle corrected acuity of 6/9 or better. One patient had surgery for myopia and obtained the desired refractive correction.",1
"Halliday, B L",2
"An outbreak of acute haemorrhagic conjunctivitis in Kaduna, Nigeria.",0
"Clinical studies were carried out on two groups of patients with acute haemorrhagic conjunctivitis (AHC) during an epidemic in 1985 in Northern Nigeria. Group 1 consisted of 99 students attending a girls' boarding school, group 2 of 200 patients selected randomly from 1000 examined at the local clinic. Moderate to severe hyperaemia and papillary responses were present in the palpebral conjunctiva of all patients, and 234 (66%) had subconjunctival haemorrhages. Transient superficial punctate keratitis was noted in over 60% of patients. A transient flare suggestive of a low grade iritis was seen in five patients. No neurological disorders were noted. Serological studies were carried out on patients from group 2. Fifteen paired and 20 single serum samples were titrated against adenovirus type 4 (Ad-4) and enterovirus type 70 (EV-70). Two pairs of sera showed a 4-fold rise in antibody levels to EV-70, whereas the antibody titres to EV-70 in the rest of the sera ranged from 1:20 (no antibody) to 1:160. None of the paired serum samples showed a 4-fold rise in antibody levels to adenovirus. The results of clinical studies and serological findings support EV-70 as a probable cause of AHC in Nigeria.",1
"Babalola, O E, Amoni, S S, Samaila, E, Thaker, U, Darougar, S",2
Chorioretinal neovascular membranes complicating contusional eye injuries with indirect choroidal ruptures.,0
"Chorioretinal neovascular membranes are a recognised but rare cause of late visual loss in eyes suffering contusional injuries. A series of eight cases is presented all with indirect choroidal ruptures involving the perifoveal region. Two main patterns of 'at risk' rupture were noted: a temporally situated rupture passing almost directly through the fovea, and a rupture which curves inferior or superior to the optic disc stopping just short of the fovea. In six of eight cases there was only a partial thickness rupture of the choroid. These neovascular membranes may present at any time after the original injury, either early (within six months of the injury), which could be related to persistence of the normal reparative neovascular response, or late (at least one year after the injury), which are more likely to have resulted from a secondary breakdown of the outer blood-retina barrier.",1
"Wood, C M, Richardson, J",2
Anterior ischaemic optic neuropathy and intraocular pressure.,0
"Anterior ischaemic optic neuropathy is a stroke syndrome of the distal optic nerve, characterised by disc oedema and optic nerve dysfunction--loss of central vision, loss of colour vision, a relative afferent pupillary defect, and nerve fibre layer field loss. We prospectively evaluated the changes of intraocular pressure throughout the day in 16 patients with non-arteritic anterior ischaemic optic neuropathy and 15 normal control subjects of similar age and race. The peak intraocular pressure exceeded 21 mm Hg in five of the ischaemic optic neuropathy patients but none of the controls. The mean peak intraocular pressure was 19.9 mm Hg for the ischaemic optic neuropathy group versus 17.6 mm Hg for controls (p = 0.034). The range of intraocular pressure was also greater for the ischaemic optic neuropathy group (p = 0.030). Eight of 16 ischaemic optic neuropathy patients had a range of intraocular pressure of 6 mm Hg or more, compared with three of 15 control subjects. The intraocular pressure exceeded 21 mm Hg during a subsequent visit in two additional patients in whom the hourly determined intraocular pressure peaked at less than 21 mm Hg. Thus, seven of 16 of our ischaemic optic neuropathy group had an intraocular pressure exceeding 21 mm Hg during the study period. Raised intraocular pressure may be a predisposing factor in some patients who develop anterior ischaemic optic neuropathy.",1
"Katz, B, Weinreb, R N, Wheeler, D T, Klauber, M R",2