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Attachment of 99mTc to lipid vesicles containing the lipophilic chelate dipalmitoylphosphatidylethanolamine-DTTA. The binding of 99mTc to negatively-charged and neutral unilamellar lipid vesicles was investigated in the absence and presence of the ligand diethylenetriaminepentaacetic acid (DTPA) covalently attached to the headgroup of phosphatidylethanolamine at the surface of the membrane. Even in the absence of DTPA on the membrane surface, 99mTc reduced by Sn bound to the membrane surface but rapidly dissociated from the vesicles in the presence of plasma in vitro. When DTPA was present on the membrane surface, dissociation of 99mTc from the vesicle surface in plasma was much reduced. The dissociation of 99mTc from the surface of negatively-charged vesicles was less than for neutral vesicles in the absence of ligand but was markedly greater than for vesicles containing the ligand DTPA, suggesting that the binding of 99mTc to vesicles with surface-attached DTPA could not be explained solely on the basis of the negative charge provided by the DTPA. In vitro experiments using 14C-labeled lipids as well as in vivo imaging studies indicated that dissociation of 99mTc from the surface of the vesicle did not arise predominantly because of lipid exchange with plasma components or due to cleavage of Tc-DTPA from the vesicle surface. For vesicles with surface-attached DTPA, 99mTc dissociation from the vesicle surface in plasma was further reduced by addition of the antioxidant ascorbate. | 20 |
Autoimmune disorders complicating adolescent Hodgkin's disease. Four adolescents with Hodgkin's disease also developed autoimmune diseases. There were two idiopathic thrombocytopenic purpura (ITP), one polymyositis, and one scleroderma. The first two patients developed ITP in the absence of a spleen, and with their Hodgkin's disease in remission. The first patient with Hodgkin's disease has been continuously free of cancer for over five years. The second patient was a 17-year-old male whoe Hodgkin's disease recurred, but whose disease was in remission at the time the ITP occurred. The polymyositis occurred in an 18-year-old youth when he was in his initial remission for his Hodgkin's disease, but his disease subsequently recurred two years later. This youth presented with Coombs positive autoimmune hemolytic anemia. The polymyositis did not respond to therapy, and he is left with severe muscle wasting and weakness; however, the polymyositis is now quiescent. The scleroderma occurred in an 18-year-old female who had been continuously free of Hodgkin's disease for eight years. The scleroderma did not respond to drug therapy and she now has moderate skin changes, but remains in continuous remission of her Hodgkin's disease. Although there are a few reports of Hodgkin's disease and concurrent autoimmune disorders, physicians dealing with cancer in adolescents should be aware of this association. | 13 |
Estradiol rapidly stimulates dopamine release from the posterior pituitary in vitro. Dopamine (DA) from both the posterior pituitary (PP) and stalk-median eminence (SME) inhibits prolactin (PRL) secretion from the anterior pituitary. Estradiol participates in the regulation of PRL release, in part by modulating DA release from the SME. However, little is known concerning the effects of estradiol on the release of DA from the PP. The objective of this study was to examine whether estradiol rapidly affects the potassium-evoked release of endogenous DA from the PP and SME in vitro. Tissues were dissected from ovariectomized rats and allowed to equilibrate in media for 30 min. Two pulses of 28 mM K+, 3 min each, were then given 30 min apart. Test substances were added 20 min before the second stimulus. DA in the media was determined by HPLC. Estradiol, at a concentration of 1 and 10 nM, significantly stimulated the potassium-evoked DA release from the PP by 34 and 47%, respectively. This stimulation was specific since 17 alpha-estradiol, a biologically inactive isomer, and testosterone, were without effects. Estradiol did not alter DA release from either the SME or isolated neural lobes of the PP. Naloxone, an opioid receptor antagonist, abolished the estradiol-induced stimulation of DA release from the PP. In contrast, amphetamine, a DA-releasing agent, significantly increased DA release in the presence of naloxone. In conclusion, (1) estradiol stimulates DA release from the PP but not the SME or neural lobe; this effect is rapid and stereospecific, and (2) the effects of estradiol appear to be mediated via an opioid(s) peptide(s) from the intermediate lobe. | 13 |
Urinary Tamm-Horsfall glycoprotein concentrations in normal and urolithiasis-affected male cats determined by an ELISA. A precise and reproducible enzyme-linked immunosorbent assay (ELISA) which measures urinary cat Tamm-Horsfall glycoprotein (cTHP) was developed in order to investigate the possible role of cTHP in the pathogenesis of feline urolithiasis. Reproducible quantification required that the cTHP be disaggregated with 2M urea and 0.05% Tween 20. It was necessary to standardize rigidly the handling of the samples prior to analysis, since the apparent cTHP concentration varied depending on the preanalysis protocols. Using the sample handling protocol of freezing urine at -70 degrees C before dialysis, urinary cTHP was quantified in male cats with no history of urolithiasis ("normal" cats) and in male cats with a history of urolith formation ("urolithiasis" cats). The mean cTHP concentration in adult, male "normal" cats of 49.2 +/- 35.5 micrograms/ml (N = 23) was significantly lower than the mean cTHP concentration of 95.4 +/- 34.1 micrograms/ml (N = 9) in "urolithiasis" cats (p < 0.01, Students' T-test). These findings indicate a correlation between urolithiasis and high urine cTHP concentrations in male cats which warrants further investigation. | 19 |
Light effects in yeast: inhibition by visible light of growth and transport in Saccharomyces cerevisiae grown at low temperatures. Growth rate, sugar transport, and amino acid transport of yeast cells grown at 12 degrees C were inhibited by cool-white fluorescent light. At light intensities below 1,250 lx, growth and membrane transport were only slightly inhibited. Above 1,250 lx, there was increasing inhibition of both processes. Transport of histidine was completely inhibited after 3 to 5 days in cultures grown at 12 degrees C under 3,500-lx illumination. Cells grown at 20 degrees C were not inhibited by light intensities that caused complete loss of viability and membrane transport activity in cells grown at 12 degrees C. | 12 |
Kinetics of thermal inactivation and quaternary structure symmetry of rabbit muscle glyceraldehyde 3-phosphate dehydrogenase. Kinetics of thermal inactivation of apo-glyceraldehyde 3-phosphate dehydrogenase have been investigated under various conditions. At most pH values, the loss of enzyme activity takes place in two phases, a fast and a slow phase. The data correspond to the rate equation A = Afast.e-kfast.t + Aslow.e-kslow, where A is the observed residual activity (expressed as % of initial activity) at time t, Afast and Aslow are amplitudes (expressed as % of initial activity, so that Afast + Aslow = 100) and kfast and kslow the rate constants of the fast and slow phases, respectively. At pH 9 or below, Afast = Aslow = 50%. As pH is increased above 9, Afast increases gradually till at pH 10 or above when it accounts for the entire initial activity (single exponential decay). The rate constants of the two phases are strongly affected by the nature of the buffer, temperature and pH, but the amplitudes depend on pH alone. It has been suggested that the tetrameric enzyme exists in two conformations of different molecular symmetry, namely C2 (two pairs of sites of unequal stability, predominating at pH 9 or below) and D2 symmetry (four equivalent sites, predominating at pH 10 or above). The C2 in equilibrium D2 transformation is found to be highly cooperative with midpoint at pH 9.6. | 17 |
The distribution of delta5-3beta-hydroxysteroid dehydrogenase in the graafian follicle of the mare. Graafian follicles of various sizes obtained from mares at different stages of the oestrous cycle were examined histologically and histochemically for delta5-3beta-hydroxysteroid dehydrogenase (3beta-HSD) activity and related enzymes. The 3beta-HSD activity was not found in the theca interna of any follicles but was present in the membrana granulosa of well-vascularized large follicles in the late luteal phase of the cycle and at oestrus. These findings indicate that pregnenolone cannot be converted into progesterone in the theca interna. It is suggested that this conversion occurs in the membrana granulosa and that progesterone then passes into the theca interna where it is converted into oestrogen. Participation of both granulosa and thecal cells in oestrogen production is also discussed from a morphological view-point. | 18 |
N-Acetylaminoacyl-p-nitranilidase from human placenta. Purification and some properties. An enzyme hydrolyzing N-acetylaminoacyl-p-nitroanilides has been isolated from mature human placentae by a six-step procedure comprising extraction from a placenta homogenate, ammonium sulfate fractionation, treatment with isopentyl alcohol, chromatography on CM-Sephadex, protamine sulfate precipitation and gel filtration on an Ultrogel AcA 34 column. About 2500-fold enrichement was achieved from placenta homogenate. The purified enzyme preparation showed a single band on polyacrylamide disc electrophoresis. The molecular weight was estimated to be 380,000 by gel filtration. Placental extracts contain two main isoenzymes of pI 3.9 and 4.5 respectively. Activity was strongly inhibited by chloromercuribenzoate, slightly inhibited by Ca2+ and cysteine; no activation could be detected. The enzyme exhibits an exopeptidase-like activity towards acetyl-dipeptides with a certain specifity towards N-acetylalanyl-alanine; N-acetylalanine-p-nitroanilide, however, is hydrolyzed four times faster. With N-acetylalanine-p-nitroanilide as substrate the pH optimum was 8.0--8.2; Km was 2.13 mmol/l. N-Acetylleucine-p-nitroanilide and N-acetyltyrosine-p-nitroanilide were split slowly; N-acetylalanyl-alanyl-alanine-p-nitroanilide, N-butyloxycarbonyl-alanyl-alanine-p-nitroanilide, unsubstituted analogous aminoacyl-p-nitroanilides and several protein substrates were not hydrolyzed. The functions of the enzyme are still unknown. | 16 |
Glucocorticoid modulation of adrenocorticotropin-induced melanogenesis in the Cloudman S-91 melanoma in vitro. The acute in vitro action of adrenocorticotropin (ACTH) and corticosterone alone and in combination were determined in the Cloudman S-91 melanoma grown in vivo. Hormone-treated melanoma dice (5-240 min) were analyzed for tyrosinase activity (EC 1.14.18.1), cyclic AMP (cAMP) and cyclic GMP (cGMP). ACTH elevated cAMP levels in the S-91 melanoma. However, these increases in cAMP were not accompanied by increased tyrosinase activity. Corticosterone depressed cAMP levels while stimulating tyrosinase activity. ACTH plus corticosterone produced an early cAMP peak followed by depression. ACTH plus corticosterone stimulated tyrosine activity coincident with the early cAMP peak followed by a drop in tyrosinase activity which was subsequently elevated. cGMP levels were not altered by any hormone treatment. The results indicate that cAMP is not the sole modulator of tyrosinase activity and suggest the interaction of ACTH, corticosterone and cAMP in the regulation of melanoma tyrosinase activity. | 15 |
A patient with pulseless extremities: an unusual manifestation of cardiac tamponade. We describe a 51-year-old man who came to our institution with cold cyanotic extremities. He was receiving radiation therapy for adenocarcinoma of the lung and superior vena cava syndrome. Findings on initial physical examination were notable for absent peripheral pulses and increased jugular venous pulsations. Shortly after admission, the patient experienced severe dyspnea and tachypnea. Arterial blood gas studies revealed mild metabolic acidosis. A chest roentgenogram showed an enlarged cardiac silhouette and the known mass in the right upper lobe of the lung. An electrocardiogram demonstrated no evidence of ischemia but low-voltage QRS complexes. An emergency echocardiogram disclosed a large pericardial effusion and evidence of hemodynamic compromise. With use of echocardiographic-guided pericardiocentesis, 600 ml of bloody fluid was removed; the pulses were immediately palpable in the patient's extremities. Although symptoms associated with the extremities are unusual as the initial complaint of patients with cardiac tamponade, we illustrate several key physical findings and abnormal results of laboratory test characteristic of this disorder. In addition, we underscore the importance of considering this diagnosis, especially in patients with a malignant tumor, and we describe the prompt response to therapy. | 16 |
Effect of cold exposure on the metabolism of immunoglobulins in rabbits. The effect of low environmental temperature on the metabolism of IgG and IgM was examined in unimmunized rabbits. The half-lives of both IgG and IgM were less in animals kept at 4 degrees C for 6 weeks than in animals kept at 22 degrees C. Serum concentration of IgM and GG were unaltered by cold exposure but intravascular pool sizes tended to increase as a consequence of an expanded serum volume. Fractional turnover rates of both IgM and IgG were greater in cold-exposed animals. At both 4 degrees C and 22 degrees C, the fractional catabolic rate of IgM was independent of its serum concentration whereas that of IgG was correlated directly with its serum concentration. Absolute turnover of both IgM and IgG was accelerated by cold exposure. It is suggested that increased synthesis of immunoglobulin could account for the higher levels of antibody reportedly found in cold-exposed rabbits. | 15 |
The safety of mesh repair for primary inguinal hernias: results of 3,019 operations from five diverse surgical sources. Initial attempts by surgical pioneers to repair hernias with prosthetic mesh met with failure because of faulty materials. As a result, surgeons experienced anxiety about performing this procedure. This anxiety persists, despite the present availability of new, safe patches and sutures. It was the unacceptably high failure rate of standard methods of repair for recurrent hernias that led to the use of plastic screens to bolster such repairs. However, persistent reluctance to use mesh for primary hernioplasty continued. Within the past two decades, true, tension-free patch repair of primary inguinal hernias without suture closure of hernial margins has been examined and clarified, and the technique has been perfected. In 3,019 reported primary inguinal hernias so treated by five different groups, there have been no mesh rejections, a 0.2 per cent recurrence rate, and insignificant incidence of infection. A new era of hernia repair appears to be at hand; therefore, such results warrant a new look at inguinal hernia repair. | 14 |
[Steroid and protein hormone concentrations in serum and follicular fluid after stimulation for in vitro fertilization]. Sixty patients with tubal infertility were stimulated for IVF with a fixed schedule consisting of clomiphene and pure follicle stimulating hormone. They responded with an optimal estradiol increase and 2 to 4 embryos were transferred. Conception cycles (n = 17) could be differentiated from non-conception cycles (n = 43) by serum estradiol, serum progesterone, the serum progesterone/estradiol-ratio and serum LH concentrations. Testosterone, androstenedione and FSH in serum and follicular fluid showed no significant relation to a possible therapy outcome. We conclude from our findings, that, during the peri-implantation period, certain LH patterns followed by an optimal progesterone/estradiol-ratio in the serum support an embryo survival after transfer to the uterus. | 16 |
Comparative value of L-, and D-methionine supplementation of an oat-based diet for humans. Total sulfur-containing amino acids have been found to be the first limiting amino acid in several foods in comparison with human amino acid requirements. Addition of methionine in appropriate amounts to these foods might be expected to improve protein value. Economically, DL-methionine would be preferable to L-methionine for this purpose. However, the comparative tuilization of L- DL-, and D-methionine is unclear. The objective of the current project was to compare the effectiveness of L-, DL-, and D-methionine supplementation of diets based on a food product known to be low in methionine value for human subjects. "Instant" oatmeal was fed to adult subjects to provide 4.0 g of nitrogen/day. In randomly arranged periods, these diets were supplemented with L-, DL-, or D-methionine at two levels (0.58 and 1.16 g of methionine/day). An unsupplemented diet was used in a control period. Diets were adequate in vitamins, minerals, and energy. Mean nitrogen balances of subjects while receiving the L-methionine supplements at the 0.58 and 1.16 g levels were minus0.10 and +0.06 g of nitrogen, respectively. At similar levels of DL-methionine supplementation, nitrogen balances were minus0.12 and minus0.15 g of nitrogen, respectively, and minus0.24 and minus0.18 g of nitrogen with D-methionine supplementation. The mean nitrogen balance when no supplement was used was minus0.22 g of nitrogen. Thus, D-methionine is seemingly poorly utilized by the human. Urinary methionine excretion data supported these results. | 12 |
[Why, when and how dietary fiber will be used in gastrointestinal disorders (author's transl)]. This paper reviews the current status of knowledge with relation to the effects of dietary fiber on intestinal physiology and pathology. Vegetable dietary fiber is a physical complex acting principally in the colon. Fibers have water-holding, cation exchange and absorptive properties and important effects on bacterial activity. Data on transit times, colonic intraluminal pressure and colonic motor activity, favour the view that fibers are interesting in the therapy of constipation, irrtable colon and diverticular disease. High residue diet must be recommended in this colonic disease. Indications are given for the choice, dosage and administration of dietary fibers. | 14 |
Daytime sleepiness after long-term continuous positive airway pressure (CPAP) treatment in obstructive sleep apnea syndrome. A modified maintenance of wakefulness test was performed in 58 patients with obstructive sleep apnea (OSA) syndrome before treatment and after long-term (554 +/- 28 days) home therapy with nasal continuous positive airway pressure (CPAP). Before treatment the patients had a shorter mean sleep latency than controls (16 +/- 1 vs. 27 +/- 1 min, mean +/- SEM, P less than 0.001). After treatment, the mean sleep latency increased to 20 +/- 1 min (P less than 0.002 as compared to baseline), but was still shorter than in controls (P less than 0.001). The incomplete normalization of the mean latency contrasted with the patients' claim that they no longer felt sleepy. The improvement in daytime alertness was significantly correlated with the reduction in sleep fragmentation after CPAP treatment and with the baseline mean sleep latency. These results support the hypothesis that sleep disruption related to respiratory events plays a role in the pathogenesis of daytime sleepiness. | 15 |
Lactose malabsorption and calcium intake as risk factors for osteoporosis in elderly New Zealand women. to evaluate the prevalence of lactose malabsorption and to assess dietary calcium intake, in elderly New Zealand women with hip fractures, in age matched case controls without hip fractures drawn from general practice, and in healthy young women. lactose malabsorption was assessed by measuring breath hydrogen after a 50 g oral lactose tolerance test. Dietary calcium was estimated from a food frequency questionnaire. the elderly fracture cases (n = 15), and their elderly controls (n = 16), showed a similar (60% and 63% respectively), but significantly higher prevalence (p less than 0.001), of lactose malabsorption than young women (12%, n = 50). Dietary calcium intake was similar in lactose absorbers and malabsorbers. malabsorption of lactose occurs commonly in elderly New Zealand women but is scarce in young adults. A high prevalence of lactose malabsorption may be a risk factor for exacerbation of type II osteoporosis in the elderly. | 14 |
Anal sphincter size measured by endosonography in healthy volunteers. Effect of age, sex, and parity. The anal sphincter muscles consist of the circular internal and external sphincters together with the sling-shaped associated puborectalis muscle. Ten men, 10 women with no vaginal deliveries, and 10 women with one or more vaginal deliveries were studied with anal endosonography using a 7 MHz multiplanar endoprobe. The thickness of the internal sphincter and the thickness, length, and cross-sectional area of the external sphincter were measured and related to age, sex, and parity. Reproducibility was assessed by similar measurements on different days in 10 volunteers. Anal sphincter size was the same in men and women and was not affected by the number of child births. Internal sphincter muscle thickness increased with age. Anal manometry and electromyography with an anal sponge were performed in all volunteers but the results did not correlate to any of the anal sphincter dimensions. Our conclusion is that although there are some limitations, endosonography can be used to determine the size of the anal sphincter muscles. | 13 |
Early thrombolysis by recombinant tissue-plasminogen activator is beneficial to the ischemic myocardium. We examined the effect of coronary thrombolysis by recombinant tissue-plasminogen activator (rtPA) on infarct size using a thrombin-induced thrombosis model of open-chest anesthetized dog. Occlusive thrombus was induced by injection of thrombin (100 U) in the left anterior descending coronary artery (LAD). The intravenous infusion of rtPA (10 micrograms/kg/min) was started at 30 min (30 min-ischemia group) or at 60 min (60 min-ischemia group) after the formation of thrombus, and was continued for 30 min. Spontaneous thrombolysis was not observed in the 360 min-ischemia (vehicle-treated) group. Intravenous infusion of rtPA elicited thrombolysis within 30 min in all the dogs except in one in the 60 min-ischemia group. The infarct size was significantly reduced by rtPA-induced thrombolysis. The shorter the duration of the ischemia, the longer the effect of the drug, and the infarct size after thrombolysis was smaller in the 30 min-ischemia group than in the 60 min-ischemia group. Ischemia-induced changes in ST-segment of electrocardiogram (ECG) were significantly ameliorated after thrombolysis in both 60 min- and 30 min-ischemia group. These results suggest that early reperfusion of coronary thrombosis by rtPA is beneficial to the ischemic myocardium. | 16 |
Observations on fifty distal splenorenal shunts. Fifty patients underwent conventional distal splenorenal shunts for bleeding esophageal varices. Five patient died within 30 days, giving an operative mortality of 10%. Three patients were lost of follow-up, but 47 patients were evaluated. Twelve patients died, 11 of liver failure, with more than half of the deaths occurring with 1 year, three fourths within 2 years, and all within 3 years after operation. Eleven patients rebled, and seven of these were among those who died. Sixteen patients had ascites prior to operation, but all responded to aggressive medical therapy. Twenty-two patients were available for study 2 or more years following operation. Eighteen (82%) are well with no encephalopathy, although the remaining four (18%) have had transient episodes of encephalopathy. Sixteen of the 18 patients judge their lifestyles to be productive. If the patient survived 24 months or longer, he had a four in five chance of living a normal life. | 10 |
Efficacy of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide against influenza virus infections in mice. 1-beta-d-Ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin) was effective against strains of influenza virus types A and F, whereas amantadine hydrochloride was effective only against strains of influenza virus type A. Dose-related protective effects against lethal influenza infections in mice were obtained with single oral doses of 25 to 400 mg of ribavirin per kg administered at the time of virus inoculation or up to 24 h thereafter. Therapeutic indexes (maximum tolerated dose/median effective dose) against various strains of influenza virus ranged from 5 to 35. With multiple-dose treatment initiated immediately after virus inoculation, oral doses as low as 12 to 25 mg/kg twice daily also afforded significant protection. Treatment with ribavirin inhibited the growth of influenza virus in the lungs of mice and delayed by about 24 h the attainment of maximal viral titers, which in nontreated mice were reached within 24 to 48 h. Inhibition of viral growth was correlated with a suppression of lung consolidation. Ribavirin appears to exert its protective effects against influenza infections by inhibiting virus growth, thereby preventing virus titers from reaching levels that result in massive lung tissue destruction and death of the mice. | 23 |
Developmental plasticity in neural circuits controlling birdsong: sexual differentiation and the neural basis of learning. In many species of passerine songbirds, males learn their song during defined periods of life. Female song is often reduced or absent, as are the brain regions controlling song. Sexual differences in the brain arise because of the action of sex steroids, which trigger the formation of some neural pathways (especially the pathway from the higher vocal center to the robust nucleus) and prevent the atrophy of others in males. These neural changes occur during periods of developmental song learning and can recur during periods of learning in adult birds. The process of learning is correlated with major increases or decreases in the numbers of neurons in specific neuronal populations, suggesting that the formation or loss of specific neural pathways regulates the ability to learn. Species differences in sexual differentiation and learning allow informative cross-species comparisons of neural structure and behavior. | 14 |
Purification and characterization of an ADP-ribosyltransferase produced by Clostridium limosum. We purified a novel ADP-ribosyltransferase produced by a Clostridium limosum strain isolated from a lung abscess and compared the exoenzyme with Clostridium botulinum ADP-ribosyltransferase C3. The C. limosum exoenzyme has a molecular weight of about 25,000 and a pI of 10.3. The specific activity of the ADP-ribosyltransferase is 3.1 nmol/mg/min with a Km for NAD of 0.3 microM. Partial amino acid sequence analysis of the tryptic peptides revealed about 70% homology with C3. The novel exoenzyme modifies selectively the small GTP-binding proteins of the rho family in human platelet membranes presumably at the same amino acid (asparagine 41) as known for C3. Recombinant rhoA and rhoB serve as substrates for C3 and the C. limosum exoenzyme. Whereas recombinant rac1 protein is only marginally ADP-ribosylated by C3 or by the C. limosum exoenzyme in the absence of detergent, in the presence of 0.01% sodium dodecyl sulfate rac1 is modified by C3 but not by the C. limosum exoenzyme. Recombinant CDC42Hs protein is a poor substrate for C. limosum exoenzyme and is even less modified by C3. The C. limosum exoenzyme is auto-ADP-ribosylated in the presence of 0.01% sodium dodecyl sulfate by forming an ADP-ribose protein bond highly stable toward hydroxylamine. The data indicate that ADP-ribosylation of small GTP-binding proteins of the rho family is not unique to C. botulinum C3 ADP-ribosyltransferase but is also catalyzed by a C3-related exoenzyme from C. limosum. | 16 |
Development of a congeneic line of the GR mouse strain without early mammary tumours. Based on the previous observation that Mtv-2 controls the appearance of pregnancy-dependent mammary tumours and the early expression of mammary tumour virus (MTV)-antigens in the milk, an attempt was made to develop a congeneic GR line, without this locus, by introducing genetic material of the C57BL/10 strain. The cross-intercross system was used for this purpose. The mice of the even-numbered generations were selected for the absence of the Mtv-2 locus with the early maammary tumour (EMT) test and during the later cycles with the immunodiffusion (ID) test for MTV-antigens in the milk. After six cycles of cross-intercross, brother-sister mating was started with mice selected for the absence of Mtv-2. After two brother-sister matings the milk-transmitted MTV was eliminated by foster-nursing. Of the foster-nursed subline 233 mice (16 of the first, 118 of the second and 99 of the third generation) were tested for the presence of Mtv-2 with one or two of the following three methods: (1) ID-test, (2) EMT-test and (3) by examination of the development of spontaneous mammary tumours in breeding females. The tests were negative in 226 mice. This indicates that Mtv-2 was absent in nearly all mice of the congeneic subline. The positive reactions in the seven other tested mice were weaker than that observed in the GR strain and in GR mice foster-nursed by BALB/c. The presence of the Mtv-2 gene in the seven positive mice of the congeneic line is doubtful. With the ID test, viral antigens were detectable in 50% of the milk samples from the first lactation period of mice of the segregating backcross I population [GR congeneic X (GR congeneic X GR)], indicating a one-gene difference between the congeneic GR line and the progenitor GR strain. | 15 |
A protein kinase is present in a complex with adenovirus E1A proteins. A kinase activity can be immunoprecipitated in a complex that includes adenovirus E1A proteins. In vitro, this activity phosphorylated other E1A-associated proteins, as well as added E1A and histone H1 proteins. The E1A-associated kinase activity was cleared from extracts with an antibody to cyclin A, but not with antibody to cyclin B. The formation of a complex that included the kinase activity required amino acids 30-60 and 122-129 on the E1A proteins, sequences needed for association of E1A proteins with cyclin A and the retinoblastoma protein and implicated in control of cell growth. The complex of E1A-associated proteins included a 33-kDa ATP-binding protein, similar in size to a cyclin A-associated cdc2 kinase family member. Sucrose gradient analysis revealed two distinct E1A-containing complexes with the kinase activity. We suggest that E1A proteins may affect cellular proliferation by interacting with a member of the cdc2 kinase family and thereby influencing its activity. | 15 |
Adriamycin in combination for the treatment of breast cancer: a Southwest Oncology Group study. Patients with advanced breast cancer who had not previously received chemotherapy were treated on a three-arm prospective study: adriamycin day 1 plus 5-FU on day 1 and 8 (AF), adriamycin day 1, plus 5-FU day 1 and 8, and cyclophosphamide day 1 (AFC), and adriamycin day 1 plus 5-FU day 1 and 8, cyclophosphamide day 1 and methotrexate day 1 (AFCM). These courses were repeated every 21 days. The response rate was 44/105 (42%) AF, 44/103 (43%) AFC and 52/105 (49%) AFCM. The length of response was 22, 33 and 35 weeks, respectively, for AF, AFC and AFCM (P = 0.21). The median survival, 64 weeks, was equal in all three limbs. The major toxicity was leukopenia. Twenty-eight percent developed a WBC of less than 2,000/microliter, which resulted in seven deaths (2.2%). | 11 |
Epidemiology of infectious syphilis at a tertiary hospital. In 19 of 20 patients in whom the correct diagnosis of primary or secondary syphilis was not obvious initially, a positive routine admission VDRL test result was the first indication of the correct diagnosis. A retrospective study during a one-month period to correlate hospital admissions by clinical service with required routine admission serologic tests for syphilis disclosed an overall compliance rate of only 37.1% (range, 94.6% to 8.0%). Of the 38 patients who did have a positive admission VDRL test result, 55.3% were falsely positive. The false-positive rate was slightly higher for weakly reactive titers than it was for higher titers. The routine serologic testing program uncovered 129 and 116 new cases of syphilis during 1976 and 1977, respectively. The decision to continue the routine admission VDRL screening program was made because the consequences of an incorrect diagnosis could be very great for an individual patient. | 16 |
Treatment of nonsteroidal antiinflammatory drug-induced gastric ulcers with misoprostol. A double-blind multicenter study. One hundred sixty-two patients chronically ingesting ibuprofen, piroxicam, or naproxen for osteoarthritis, who had abdominal pain and an endoscopically proven gastric ulcer were evaluated for eight weeks in a randomized, double-blind trial comparing misoprostol (200 micrograms four times daily with meals and at bedtime) (N = 77) with placebo (N = 85). Patients discontinued their usual daily dose of antiarthritic medication throughout the study period, and an endoscopy was performed at four weeks and eight weeks (if necessary) to assess ulcer healing. Gastric ulcers were defined as circumscribed breaks in the gastric mucosa of 0.3 cm in diameter or greater. Misoprostol therapy significantly accelerated the rate of gastric ulcer healing compared to placebo (P = 0.033). The cumulative percent healed after four and eight weeks of therapy for misoprostol versus placebo were: 83% vs 61% at four weeks and 96% vs 90% at eight weeks (P = 0.0028 and P = 0.0977, respectively by lifetable analysis). Relief of abdominal pain did not differ significantly between the treatment groups. Misoprostol significantly accelerates the healing of ibuprofen-, piroxicam-, or naproxen-induced gastric ulcers. | 16 |
Epidermal growth factor and bombesin differ strikingly in the induction of early responses in Swiss 3T3 cells. Swiss 3T3 cells express receptors for both the polypeptide epidermal growth factor (EGF) and the tetradecapeptide bombesin and respond mitogenically to these substances. These cells thus provide a system to analyze potential signal transduction pathways involved in mitogenic stimulation. Here we have determined and compared the early ionic responses elicited by EGF and bombesin and their relation to diacylglycerol (DG) and inositolphosphate (InsPn) production. Whereas EGF fails to cause any significant change in intracellular Ca2+, bombesin effectively induces prompt and transient Ca2+ mobilization from intracellular stores. Further support of the idea that these receptors utilize distinct signalling pathways comes from the measurements of cytoplasmic pH (pHi). As in most target cells, EGF induces a delayed (1 min) but sustained intracellular alkalinization that reaches a new steady state after approximately 10 min. Bombesin, in contrast, elicits a biphasic response; within seconds, a rapid but transient rise in pHi is observed, followed by a further slower sustained alkalinization. Inhibition of the Na+/H+ exchanger prevents both EGF as well as bombesin-induced alkalinization. However, under these conditions, bombesin evokes a rapid and sustained acidification related to the Ca2+ response. Apparently, bombesin initiates a Ca2(+)-dependent acidifying process immediately after binding of the hormone to its receptor. Furthermore, we could demonstrate that the bombesin-induced alkalinization depends on protein kinase C activation whereas the EGF response does not. Determination of the total DG and InsPn accumulation revealed that EGF is ineffective in stimulating phospholipase C-mediated production of these second messengers. In contrast, bombesin causes a rapid DG and InsPn production coinciding with the Ca2+ response and the first phase of the rise in pHi followed by a slower DG accumulation coinciding with the second alkalinization phase. Our results show that in Swiss 3T3 cells the bombesin receptor activates the hydrolysis of inositol lipids as a mechanism of signal transduction, which consequently causes changes in Ca2+i and pHi. Clearly, the EGF receptor utilizes different pathways to evoke mitogenesis and stimulates Na+/H+ exchange independently of DG production and protein kinase C activation. | 17 |
Dermal absorption of the phenoxy herbicide 2,4-D dimethylamine in humans: effect of DEET and anatomic site. Percutaneous absorption of the 14C-ring-labeled phenoxy herbicide 2,4-D-amine (2,4-dichlorophenoxyacetic acid dimethylamine) was examined following topical applications of the herbicide to the palm and forearm of human volunteers. The effect of two vehicles (water and acetone) and the mosquito repellent DEET (N,N-diethyl-m-toluamide) on dermal absorption of 2,4-D-amine also was investigated. The total percent dermal absorption was calculated from the mean percent urinary recoveries and was not corrected for nonurinary excretion. The data revealed 14 +/- 4.5% (standard deviation) and 10 +/- 11.5% palmar absorption of 2,4-D-amine applied in water, with and without DEET, respectively, and 7 +/- 6.2% and 13 +/- 5.0% forearm absorption of the herbicide applied in water or acetone, respectively. Soap-and-water skin washes conducted at 24 h posttreatment removed up to 34% of the applied dose. Successive tape strips of skin taken at 24 h posttreatment demonstrated generally decreasing herbicide levels in the outer layers. The data bring into question the complete validity of the rhesus monkey model to predict human dermal absorption. | 17 |
Coordinated leading- and lagging-strand synthesis at the Escherichia coli DNA replication fork. IV. Reconstitution of an asymmetric, dimeric DNA polymerase III holoenzyme. Individually purified subunits have been used to reconstitute the action of the Escherichia coli DNA polymerase III holoenzyme (Pol III HE) at a replication fork formed in the presence of the primosome, the single-stranded DNA binding protein, and a tailed form II DNA template. Complete activity, indistinguishable from that of the intact DNA Pol III HE, could be reproduced with a combination of the DNA polymerase III core (Pol III core), the gamma.delta complex, and the beta subunit. Experiments where the Pol III core in reaction mixtures containing active replication forks was diluted suggested that the lagging-strand Pol III core remained associated continuously with the replication fork through multiple cycles of Okazaki fragment synthesis. Since the lagging-strand Pol III core must dissociate from the 3' end of the completed Okazaki fragment, this suggests that its association with the fork is via protein-protein interactions, lending credence to the idea that it forms a dimeric complex with the leading-strand Pol III core. An asymmetry in the action of the subunits was revealed under conditions (high ionic strength) that were presumably destabilizing to the integrity of the replication fork. Under these conditions, tau acted to stimulate DNA synthesis only when the primase was present (i.e. when lagging-strand DNA synthesis was ongoing). This stimulation was reflected by an inhibition of the formation of small Okazaki fragments, suggesting that, within the context of the model developed to account for the temporal order of steps during a cycle of Okazaki fragment synthesis, the presence of tau accelerated the transit of the lagging-strand Pol III core from the 3' end of the completed Okazaki fragment to the 3' end of the new primer. | 18 |
Influence of lighting conditions on toxicity and genotoxicity of various PAH in the newt in vivo. We evaluated the influence of near-ultraviolet light (UVA) on the cytotoxicity and genotoxicity of 7 polycyclic aromatic hydrocarbons (PAH) in larvae of the amphibian Pleurodeles waltl. Benz[a]anthracene (BA), 7,12-benz[a]anthraquinone (BAQ) and anthracene (Ac) proved to be lethal at low doses (some ppb), and the following order of genotoxicity was observed: BA approximately BAQ > DMBA > DMA (9,10-dimethylanthracene). Ac, AQ (9,10-anthraquinone) and DBA (dibenz[a,h]anthracene) were not found to be clastogenic. In the larvae reared in normal conditions (subdued natural daylight/darkness alternation) or in continuous darkness, the BA derivatives were shown to be more genotoxic than BA itself: DMBA > BAQ > BA; BA (> or = 187.5 ppb) slightly increased the level of micronuclei in circulating erythrocytes, while DMBA was strongly clastogenic, in line with their reported carcinogenicity. In other experiments, rearing media alone (i.e., water containing BA, BAQ or DMBA) were UVA-irradiated for 24 h, and then tested on larvae in the dark ('IR-UV/dark' conditions). Photodegradation of BA (50 and 100 ppb) gave rise to clastogenic products. By contrast, DMBA (12.5, 25 or 50 ppb) was destroyed by UVA, and we suggested that any potentially mutagenic photoproducts formed were not in sufficient amounts to yield a positive response in the newt micronucleus test. | 18 |
The effect of intragastric neutralization on the gastric acid response to antral distension in man. The gastric acid secretion in response to graded antral distension was determined in healthy subjects and in peptic ulcer patients with water perfusion or alkaline buffer perfusion of the stomach, giving an intragastric pH of 1.8-3.0 and 6.2-8.3 respectively. Intragastric neutralization increased the basal acid secretion in healthy subjects and gastric ulcer patients but did not change the basal acid secretion in duodenal ulcer patients. Distension of the antrum produced the same secretory effect with and without intragastric neutralization: no increased acid response in healthy subjects, a slight acid response in patients with a quiescent duodenal ulcer or a gastric ulcer, and a more pronounced acid response in patients with an active ulcer, amounting to about 30% of the peak acid response to pentagastrin. The results show that: a) the peptic ulcer patients - and particularly patients with an active duodenal ulcer - are more sensitive to the acid secretory effect of antral distension than healthy subjects; b) increasing the intragastric pH above 20 does not enhance the acid response to antral distension; c) the acid secretory effect of antral distension is markedly less in man than the effect observed in the dog. | 24 |
Factors affecting survival in stage I and state II carcinoma of the cervix. Eighty-eight cases of Stage I and Stage II carcinoma of the cervix treated with radiotherapy at the University of North Carolina Memorial Hospital between April 1969 and July 1971 are reviewed. The question of whether the radiation time-dose-fraction relationship can be applied to the combination of external beam and intracavitary therapy used in the treatment of cervical carcinoma is studied. Formulas are outlined which enable one to calculate a total Rad Equivalent Therapy (RET) value, including the contribution from both the fractionated external beam and intracavitary therapy. Both the calculated RET value and the rad dose to Point A show good correlation with control of local disease in this retrospective analysis; however, the RET value may be more applicable when deviations from the standard time-dose-fraction relationship have occurred. | 20 |
Effect of drying with hot forced draft and of mincing bracken fern on its carcinogenic activity. The carcinogenic activity of young bracken dried at a high temperature or minced by a mechanical chopper was compared with that of unprocessed bracken dried at room temperature. Inbred strain ACI rats of both sexes were divided into 4 groups; Group 1 received a diet containing the unprocessed bracken dried at a room temperature of below 30 degrees, Group 2 received a diet containing bracken dried at 70 approximately 90 degrees with a hot, forced draft, and Group 3 received the diet containing processed bracken that had been minced to a paste-like consistency using a mechanical chopper. The control group was fed a normal diet. Rats fed a bracken-containing diet developed tumors most frequently in the ileum. Comparison of Group 1 with Groups 2 and 3 showed no significant difference in the latent period, incidence, histologic types, or multiplicity of the intestinal tumors found in each animal. | 17 |
Imaging of the pancreas with computed tomography. In this paper we present our experience with computerized tomographic imaging of the pancreas, both in normal and abnormal conditions. Eighty patients were studied for evaluation of pancreatic disease. A further 50 patients, all with a normal pancreas, were studied for abnormalities of other abdominal organs and served as the control group. Helpful signs in establishing the diagnosis of carcinoma of the pancreas were mass effect within the pancreas, alteration of organ contour and obliteration of retroperitoneal fat planes. We found that differentiation from pancreatitis or retroperitoneal lymphadenopathy may at times be difficult. Our results showed that in 22 out of 23 patients with proven normal pancreas, the pancreas size on the CT display was within the adopted normal range. In 30 patients with proven carcinoma of the pancreas, a pancreatic mass was seen in 24 (83%). Computerized tomography is clearly a valuable method for viewing both normal pancreatic anatomy and anatomical variations and pathologies. | 13 |
[A case of hypopituitarism associated with empty sella and agenesis of corpus callosum, a variant form of septo-optic-pituitary dysplasia]. A 41-year-old man was referred to Kyushu University Hospital for evaluation of hypothyroidism and hypocortisolemia. Pituitary function test revealed the deficiency of GH(growth hormone), ACTH(adrenocorticotropic hormone), prolactin and TSH(thyroid stimulating hormone). MRI showed empty sella and agenesis of corpus callosum. Clinical diagnosis was hypopituitarism with midline brain anomaly. Septo-optic-pituitary dysplasia (SOPD) is a syndrome characterized by agenesis of septum pellucidum or corpus callosum, optic nerve hypoplasia and congenital hypothalamic-pituitary insufficiency. Our case had no ocular anomalies, but today it is regarded as a variant form of SOPD. Evaluation of the integrity of midline brain structures in patients with congenital hypopituitarism is thus thought to be important for their etiology. | 15 |
Demonstration of processing and recycling of biologically active V1 vasopressin receptors in vascular smooth muscle. The present study examines the binding and postbinding cellular processing and recycling of the V1 arginine vasopressin (AVP) receptor in cultured vascular smooth muscle cells (VSMCs). The surface binding of AVP to VSMCs was temperature dependent and reached equilibrium within 60 min at 4 degrees C. Displacement studies with unlabeled AVP or a specific V1 AVP antagonist revealed a single class of V1 receptors (Bmax, 1.99 pmol [corrected] per mg of protein; Kd, 2.15 nM). Incubation of VSMCs with unlabeled 10 nM AVP to promote receptor internalization resulted in a time- and temperature-dependent loss of AVP surface binding. At 37 degrees C, maximum loss of binding sites (65%) occurred within 20 min. Recovery of AVP binding occurred rapidly (t1/2, 15-20 min at room temperature) and was uninfluenced by inhibiting protein synthesis with cycloheximide. Pretreating VSMCs with chloroquine prevented AVP receptor recycling, indicating that the AVP-receptor complex requires endosomal processing. The biological competence of the recycled AVP receptor was shown by AVP-induced Ca2+ uptake. The results of these studies therefore indicate that, after surface binding, the AVP-receptor complex internalizes and dissociates in an endosomal compartment. It is demonstrated that in VSMCs biologically active V1 AVP receptors recycle back to the cell surface, thus attenuating the loss of AVP surface binding sites. | 17 |
[Oral propagation of the circular muscle contraction induced by local distension of the isolated guinea pig ileum (author's transl)]. The local distension of the intestinal wall was carried out by inflating a thin rubber balloon which had been fixed in the lumen and the contractions of the circular muscle were recorded at the points of 5 mm (PO1) and 20 mm (PO2) oral to the fixed balloon. The contractions elicited by local distension was blocked by tetrodotoxin and atropine, or removing longitudinal muscle, with the myenteric plexus adhering to it, from the intestine at the distending region. When 2 to 3 mm length of longitudinal muscle was stripped off around the intestine between PO1 and PO2, the contraction initiated at PO1 never reached to PO2. That is, the oral contraction did not propagate beyond the myenteric plexus-free region of the segment. When drugs were applied exclusively to the region around PO2, tetrodotoxin and hexamethonium, but not atropine, abolished the contraction at PO2, while the contraction at PO1 was clearly observed. It is likely that the contraction observed at the point of PO2 was evoked by non-cholinergic nervous mechanisms. | 18 |
Glutamate neurotoxicity in rat auditory system: cochlear nuclear complex. In other systems such as the hypothalamus and hippocampus, it has been shown that cells postsynaptic with respect to glutamatergic inputs degenerate when exposed to large doses of glutamate ("glutamate neurotoxicity"). We have shown that large doses of glutamate administered intraperitoneally are toxic to spiral ganglion cells in the inner ear of the rat. In the present study, we have investigated whether similar levels of glutamate cause alterations in the neurons of the cochlear nuclei. Specifically, we have studied the morphology and size of the cochlear nuclear complex and its subdivisions as well as the size and density of cochlear nucleus neurons following administration of glutamate. The morphological evidence indicates that glutamate caused severe anatomical alteration of the cochlear nuclei. The changes were most pronounced in the anteroventral cochlear nucleus, especially in the neurons that receive terminals of the end bulbs of Held from the cochlear nerve. This could be a direct effect of glutamate in the cochlear nuclei or secondary to degeneration of cochlear nerve fibers in the inner ear. | 16 |
Infectious mononucleosis in adolescents. Infectious mononucleosis is a clinical manifestation of primary EBV infection in adolescents, characterized by a triad of clinical, laboratory, and serologic features. The classic signs and symptoms are not seen in every patient; rather, the presentations tend to fit into one of three clinical forms (pharyngeal, glandular, or febrile). Recognizing these syndromes provides a useful framework for anticipating the clinical course, complications, and differential diagnosis. Nonclassic presentations of IM include a wide variety of neurologic abnormalities, thrombocytopenic purpura, and splenic rupture. The laboratory features of IM include absolute lymphocytosis with a large percentage of atypical lymphocytes, and abnormal liver chemistries in 90% of patients. The diagnosis of IM is confirmed serologically, usually with the demonstration of heterophile antibodies; the test can conveniently be performed in office laboratories. If the heterophile antibody test is negative, EBV-specific serologic tests can identify whether the illness is due to primary EBV infection. Once the diagnosis of IM is made, appropriate guidelines for resumption of activity should be provided to patients, especially to those with evidence of splenomegaly. Medical management includes supportive therapy with adequate analgesia. Corticosteroids are indicated for patients with upper airway obstruction; they may be helpful in patients with neurologic, hematologic, or cardiac complications. Acyclovir may prove to be useful, but further studies are needed before its use can be recommended. | 18 |
111In platelet deposition following peripheral arterial thrombolysis. Streptokinase (Sk) and recombinant tissue plasminogen activator (rt-PA) have widely different effects on platelet aggregation. We have therefore undertaken a prospective evaluation of the deposition of indium-111 platelets following peripheral arterial thrombolysis. Seventeen patients were studied using autologous indium-111 labelled platelets. Patients were randomly allocated to receive 0.5 mg h-1 intra-arterial rt-PA (ten patients), or 5000 units h-1 Sk and 250 units h-1 heparin intra-arterially (seven patients). Initial uptake ratios (comparing affected limb to contra-lateral limb) at 24 h were usually low for both agents (medians: Sk 1.17; rt-PA 1.20) despite previous angioplasty or extensive thrombosis. There were minimally higher uptake ratios at 48 h and 72 h following Sk (1.64-1.45), than with intra-arterial rt-PA (0.93-1.43). Overall, two patients (one from each group) failed to achieve complete lysis or incurred early rethrombosis. Both were associated with a progressive increase in uptake ratio which was not present in those patients with successful initial lysis and continued patency at 30 days (1.18-0.94-1.19). We have been unable to demonstrate any significant difference in post-lysis platelet deposition between intra-arterial streptokinase and recombinant tissue plasminogen activator in this preliminary study. However, higher platelet deposition was associated with failure to achieve complete lysis and early rethrombosis. Concurrent therapy with antiplatelet agents may therefore be indicated in these patients. | 16 |
The effects of calcium and magnesium on the secretion of parathormone and parathyroid secretory protein by isolated porcine parathyroid cells. The preparation of dispersed parathyroid cells by collagenase digestion of porcine parathyroid glands, essentially as outlined by Brown et al. (Endocrinology 99: 1582, 1976), is described. The cells secrete parathormone linearly for at least 4 h of incubation and rapidly respond in inverse fashion to changes in the medium calcium and magnesium concentrations over the range 0.5-3.0 mM. In terms of inhibition of secretion, either ion was more effective in the presence of a minimum concentration of the other, indicating that calcium and magnesium affect separate cellular sites. Parathormone was identified both by immunoassay of the whole incubation medium and by its separation by polyacrylamide gels and carboxymethylcellulose chromatography. When the cells were incubated with radioactive amino acids and both the medium and cells were subsequently analyzed on gels, we found that parathyroid secretory protein as well as parathormone and some immunoactive fragments were present. Analysis of the radioactive protein contained in the cells at high and low calcium concentrations revealed that calcium decreased the formation of the secretory protein by approximately 40% without appreciably affecting the formation of proparathormone or parathormone. The secretion of both parathyroid secretory protein and parathormone were inversely proportional to the concentrations of medium calcium or magnesium. The secretion of the latter, however, was more sensitive (95% inhibition) than parathormone (40-60% inhibition) to changes in medium divalent cations. These results suggest that the synthesis, intracellular processing, or secretion of parathormone and parathyroid secretory protein utilize independent calcium- and magnesium-regulated pathways. | 19 |
[Cloning and molecular analysis of retrotransposon mdg4 from two Drosophila melanogaster strains, differing in genetic instability]. The copies of mobile element mdg4 (gypsy) were cloned from two different D. melanogaster strains. The first strain (stable) is characterized by small number of mdg4 copies and their constant localization in chromosomes. The second strain (unstable), which was originated from the first one, is characterized by increased number of mdg4 copies and higher frequency of its transpositions. The two copies of mdg4, cloned from stable and unstable strains differ in their structure and represent two different types of mdg4. Southern blot-analysis of structural organization of mdg4 in these two strains showed, that in the stable strain there are mdg4 copies of one type, and in the unstable strain there are both, but only the mdg4 copies of another type were amplified. In was shown by transient-expression experiments, that in spite of the structural differences both types of mdg4 were able to be transcribed. Nevertheless, in flies of stable strain the mdg4 transcripts were not detected. | 15 |
Amino acid sequence of honeybee prepromelittin synthesized in vitro. Translation of melittin messenger RNA from queen bee venom glands in a cell-free system from wheat germ yielded prepromelittin. Sequence analysis of the labeled in vitro product was performed by automatic Edman degradation of the intact polypeptide as well as by analysis of some of its proteolytic fragments. Prepromelittin was shown to be composed of 70 amino acids, two of which have not been identified. The sequence of melittin is located in the COOH-terminal third of the polypeptide chain (residues 44--69). Prepromelittin starts with a very hydrophobic pre-region, probably 21 residues long, followed by a pro-part of unusual sequence, containing only alanine, proline, and acidic residues. At least three post-translational reactions are required to convert prepromelittin to mellitin. | 15 |
Methylmercury-cholinesterase interactions in rats. The interaction of methylmercury hydroxide (MMH) and cholinesterases was studied in male and female rats. MMH administered subcutaneously in doses of 10 mg/kg for 2 days reduced the level of plasma cholinesterase (ButChE) by 68% in females and 47% in males while brain acetylcholinesterase (AChE) was unaffected. Normal females had higher but more variable ButChE levels than normal males. In a time-course experiment, a single dose of MMH (10 mg/kg) reduced ButChE levels when mercury levels reached 22 mug/ml in the blood. A 10% reduction in brain AChE was observed at 72 hours; however, mercury reached a concentration of only 2.0 mug/g in brain tissue. The determination of the Michaelis constant Km and maximum velocity value Vmax for butyrylcholine and ButChE in control and MMH-treated (1 mg/kg) animals indicated that MMH reduced Vmax only. Since no loss in ButChE activity occurred when MMH and control plasma were incubated in vitro, MMH is not a direct inhibitor of ButChE. Because only the inactive monomeric form of ButChE contains free sulfhydryl groups, it is postulated that MMH combines covalently with the sulfur, preventing formation of active enzyme. By analogy, it is believed this is also the case with AChE. | 14 |
Purification and characterization of six annexins from human placenta. Isolation of six calcium-binding proteins from human placenta is described by means of hydrophobic chromatography, calcium-dependent adsorption to heparin-Sepharose and ion-exchange chromatography. These proteins were characterized and identified as PP4, PP4-X, PAP III, p68 and lipocortins I and II belonging to the family of annexins. Antibodies raised against PP4, PAP III and p68 revealed to be highly specific, while those raised against PP4-X reacted with all investigated annexins, except PP4. Cross-reactivity was also observed between lipocortins I and II. All annexins inhibited in a concentration-dependent manner blood coagulation but with different potencies as was determined by means of a modified thromboplastin time test. The most potent inhibitors turned out to be PP4 and PAP III, followed by PP4-X, lipocortin I, p68 and lipocortin II. | 15 |
An audit of anticoagulation and endocarditis prophylaxis after heart valve surgery. to audit anticoagulant control and endocarditis prophylaxis following heart valve surgery. retrospective review of all 190 patients living in Canterbury who had heart valve surgery between January 1981 and December 1986 to determine the incidence of endocarditis and complications of anticoagulation. there were 35 late deaths, of which nine were attributed to thromboembolism (3), major bleeding (2), or endocarditis (4). The rate of thromboembolic events, and major bleeding was 4.6 and 3.3/100 patient years of warfarin therapy respectively, while the incidence of late endocarditis was 0.96/100 patient years. Two episodes of endocarditis occurred after minor dental procedures performed without antibiotic prophylaxis. Many dentists indicated that they would not have recommended prophylactic therapy for these procedures. Some patients had inadequate recall of important details of anticoagulant control or endocarditis prophylaxis. Only 24% knew their latest prothrombin ratio, yet a survey of general practitioners revealed that, in their view, the majority of patients may be capable of monitoring their own anticoagulant therapy. the incidence of potentially preventable long term complications of heart valve surgery is comparable to other series. Nevertheless, these complications could be reduced by better patient education possibly enhanced by greater involvement of the patient in their anticoagulant control. The indications for antibiotic prophylaxis for dental procedures should be broadened for this group of patients. | 16 |
Role of acetylcholine, histamine and gastrin in the acid response to intracisternal injection of TRH analog, RX 77368, in the rat. The role of gastrin, acetylcholine and histamine in the acid response to central vagal activation induced by intracisternal injection of the stable analog, RX 77368, was further investigated in urethane-anesthetized rats with gastric fistula. The gastrin monoclonal antibody 28-2 injected intravenously, at a dose previously shown to prevent gastrin-induced stimulation of acid secretion, did not alter the peak acid response to intracisternal injection of RX 77368 (15 ng). The TRH analog (30 ng) injected into the cisterna magna increased levels of histamine measured in the hepatic portal blood. Cimetidine administered at a dose which completely blocked the stimulation of gastric acid secretion produced by intravenous infusion of histamine, inhibited by 62% the stimulatory effect of intracisternal RX 77368 (30 ng). The M1 muscarinic antagonist, pirenzepine, completely prevented the acid secretion induced by intracisternal RX 77368 (30 ng). These results indicate that the acid response to central vagal activation by the TRH analog in rats involved M1 muscarinic receptors along with histamine release acting on H2 histaminergic receptors whereas gastrin does not appear to play an important role. | 21 |
The assessment in sheep of an inactivated vaccine of parainfluenza 3 virus incorporating double stranded RNA (BRL 5907) as adjuvant. The serological responses of conventionally reared sheep were compared after vaccination with inactivated parainfluenza 3 (PI3) virus incorporated in three different adjuvants. Inactivated PI3 virus with the double-stranded RNA, BRL 5907 in an oil emulsion was shown to stimulate higher serum antibody titres over the first 5 weeks after vaccination than virus with and without BCG emulsified in oil. The ability of this vaccine to protect specific pathogen-free lambs against challenge with PI3 virus was examined in a second experiment. In this experiment the vaccine stimulated virus neutralizing and haemagglutination inhibiting antibodies in the serum. After intranasal and intratracheal inoculation with PI3 virus at challenge, vaccinated lambs showed no clinical illness and virus isolation was confined, except in one lamb, to the first two days. In contrast, unvaccinated lambs developed respiratory disease and virus was isolated daily for 7 days after challenge. | 17 |
The shock liver. Clinical and biochemical findings in patients with centrilobular liver necrosis following cardiogenic shock. Five patients with severe heart disease developed cardiogenic shock of more than 24 hours' duration. As a sequela to the shock, severe liver affection was demonstrated. Serum aspartate aminotransferases and serum lactate dehydrogenases showed very high activities. The prothrombin-proconvertin index was reduced to less than 25% of the normal. Four of the patients were jaundiced. The condition gave rise to some differential diagnostic problems. Liver biopsies were available from four of the patients, and histological examination of an autopsy specimen of the liver was performed in each case. The liver histology showed centrilobular necrosis and haemorrhage in all patients. It seems that centrilobular fibrosis develops later in the condition. The pathogenesis of this liver affection is probably hypoxic injury to the centrilobular areas of the liver lobule due to reduced liver blood flow. | 12 |
Mechanisms of flow-mediated signal transduction in endothelial cells: kinetics of ATP surface concentrations. Intracellular free calcium ([Ca2+]i) was measured in single cells of a confluent endothelial monolayer subjected to defined flow. Flow medium containing adenosine triphosphate (ATP) was used to study the influence of flow forces upon agonist-response coupling as mediated via the P2y-purinoceptor. [Ca2+]i responses were highly sensitive to the fluid motion at the cell surface; consecutive small increases of flow stimulated large [Ca2+]i transients with the levels returning to baseline at the new flow rate within 250 s. The characteristics of [Ca2+]i transients were also influenced by decreasing flow. Since potent ectonucleotidases at the endothelial cell surface rapidly degrade ATP, we postulated that a combination of flow and degradative enzymes regulates the mass transport of ATP in the boundary layer. The hypothesis predicts that step increases of flow exceed the capacity of the ectonucleotidases and allow ATP to reach the receptor. Experiments were conducted to compare ATP and ADP beta S, a nonhydrolyzable ATP analog that resists degradation by surface ectonucleotidases, and calculations of ATP mass transport to the cell surface were compared to estimates of surface clearance rates. Calculations of mass transport coefficients for ATP in the boundary layer demonstrated that changes of flow which elicited a prominent [Ca2+]i response represented 26-73% changes in the mass transport of ATP from the bulk fluid. When steadystate mass transport coefficients for ATP under various flow conditions were compared with the estimated rate constant for surface degradation of ATP, ratios close to unity were obtained. These results suggest that both boundary layer mass transport and ATP clearance rates can be rate-limiting for flow-mediated activation of the P2y-receptor. The experiments provide evidence for differential signal transduction responses in the endothelium driven by diffusion gradients (derived from both the blood and the vessel wall), which are likely to vary widely in the complex flow fields encountered in vivo. | 19 |
Optimal hematocrit for canine skeletal muscle during rhythmic isotonic exercise. Contractile power, blood flow, O2-uptake, and O2-extraction during isotonic, rhythmic exercise were determined in the isolated canine gastrocnemius muscle during perfusion with blood with hematocrits between 0.21 and 0.81. The results obtained in 36 measurements on nine muscles showed that maximal O2-delivery to the muscle if found at hematocrits between 0.5 and 0.6. Both in the range of hemodilution, and in the range of extreme hemoconcentration, O2-delivery decreases significantly. O2-consumption and contractile power of the muscles are almost unaffected in the hematocrit range between 0.4 and 0.7; beyond and below this hematocrit range both parameters decrease. O2-extraction is virtually constant in the hematocrit range between 0.3 and 0.6, but increase both below and above these hematocrit levels. It is concluded that due to reduced vasodilatory reserve in working skeletal muscle compared to resting muscle the optimal hematocrit is shifted to higher values. | 16 |
A factor in serum and amniotic fluid is a substrate for the tRNA-modifying enzyme tRNA-guanine transferase. Q factor, a substance found in animal serum that enables cultured mammalian cells (L-M) to produce tRNA containing queuine (the base of "nucleoside Q", queuosine), has been purified to homogeneity from bovine amniotic fluid. Q factor causes the appearance of Q-containing tRNAAsp in the L-M cells cultivated in serum-free medium, and this was used as an assay to monitor the purification of Q factor. Q factor is a competitive inhibitor of guanine for rabbit reticulocyte tRNA-guanine trnsferase, with a K1 of 4.5 x 10(-8) M. Q factor is inactivated in both the L-M cell and tRNA-guanine transferase assays by treatment with periodate or cyanogen bromide, both of which react with queuine. In L-M cells, nearly complete conversion of Q-free to Q-containing tRNAAsp is observed within 24 hr after addition of pure Q factor to the medium; actinomycin D, cycloheximide, and cycloleucine, inhibitors of RNA synthesis, protein synthesis, and nucleic acid methylation, respectively, do not inhibit this conversion. The product of the reaction, catalyzed by pure rabbit reticulocyte tRNA-guanine transferase, between Q factor and rabbit reticulocyte Q-free tRNAHis is chromatographyically indistinguishable from Q-containing tRNAHis. | 21 |
The National Cholesterol Education Program: guidelines, status, and issues. The 1987 report of the Adult Treatment Panel (ATP) of the National Cholesterol Education Program (NCEP) was concerned with who should be treated for high blood cholesterol levels and how they should be treated. Total cholesterol levels were classified for identification of cases. Low-density lipoprotein cholesterol levels were classified for decisions about treatment. The ATP guidelines emphasize diet as the primary approach to treating patients with high blood cholesterol levels. The recommendations of the report are being widely publicized through physician and patient educational programs and the mass media. The report of the Population Panel of the NCEP provides recommendations and guidelines for the public health approach to the problem of high cholesterol levels. When the recommendations of both reports are fully implemented, it is expected that substantial reductions in the incidence of coronary heart disease will be achieved. | 14 |
Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit intestinal microorganisms. The behavior of salicylic acid-D-alanine conjugate (salicyl-D-alanine) following intravenous, oral and intracecal administration was examined in rabbits, then compared with that of salicylic acid-L-alanine conjugate (salicyl-L-alanine) as reported previously. Following intravenous administration, salicyl-D-alanine eliminated rapidly from the blood, and its blood concentration was almost identical with that of salicyl-L-alanine. In both cases, salicylic acid could not be detected in the blood, indicating that systemic de-conjugation of D-alanine might not occur. Unchanged salicyl-D-alanine was found in the blood mainly following oral and intracecal administration of salicyl-D-alanine. On the other hand, salicylic acid formed extensively following oral and intracecal administration of salicyl-L-alanine, suggesting that the presystemic de-conjugation of D-alanine and L-alanine was unequal. Furthermore, in vitro incubation of salicyl-D-alanine with cecal content, in which the major source of salicyl-L-alanine hydrolysis is found, showed that the hydrolysis of salicyl-D-alanine was negligible in rabbit intestinal microorganisms. | 20 |
Use of twenty-four hour infusions of intracoronary tissue plasminogen activator to increase the application of coronary angioplasty. Coronary arteries occluded by long lengths of thrombus are usually considered unattractive for angioplasty. Nine patients (8 male, mean age 50.1 years) undergoing angiography for unstable angina were found to have single vessel disease considered unsuitable for angioplasty as the vessel was occluded by a long length of thrombus. These patients were treated with 24 hr intracoronary infusions of 100 mg tPA in an attempt to make angioplasty feasible. Marked thrombolysis occurred in 7 patients who received uncomplicated infusions. One case was unsuccessful due to catheter displacement, while another had the infusion ceased due to an intracerebral bleed from a previously silent A-V malformation. This was the only major complication. Angioplasty was attempted in 6 of 7 cases where lysis had been achieved, with success in all lesions attempted. This reports shows that intracoronary tPA infused over prolonged periods produces excellent thrombolysis, making angioplasty feasible in some patients who were previously unsuitable. | 16 |
Development of the human sphenomandibular ligament. The development and arrangement of the sphenomandibular ligament of 60 human embryos and fetuses were studied. Meckel's cartilage appeared as a single, continuous fibrous structure lying between the mandibular lingula and the malleus of the middle ear in fetuses of 210 mm crown-rump length (22 weeks of age) and over. This structure constitutes the malleolomandibular ligament, and two clearly differentiated portions bound by the tympanosquamosal fissure could be seen: a juxtaarticular portion, inserted on the posterior edge of the interpterygoid aponeurosis, and a tympanic portion, onto which the disc of the temporomandibular joint inserted. Some of the authors consider that if tension is applied to the sphenomandibular ligament this may injure the middle ear. The anatomical arrangement of the sphenomandibular ligament could explain these injuries. | 16 |
Adrenocortical function in patients investigated for active tuberculosis. Previous reports have identified adrenal insufficiency in groups of patients with active pulmonary tuberculosis. To investigate this possibility, serum cortisol levels were measured in consecutive patients admitted to the hospital for investigation of active tuberculosis. Blood was drawn for cortisol determination promptly at the time of hospital admission, in the morning and afternoon before commencing chemotherapy for the suspected tuberculosis, and before the diagnosis was confirmed. Thirty-seven patients were assessed; 19 of these patients were subsequently proven to have active pulmonary tuberculosis, six had pulmonary disease caused by mycobacteria other than tuberculosis, and 12 had radiologic appearance indicating tuberculosis, accompanied by a significant tuberculin skin reaction but with negative sputum cultures and no change in roentgenographic appearance during the course of treatment. In evaluating the adrenocortical function, the morning and afternoon serum cortisol level was measured and the diurnal change in serum cortisol level (the difference between afternoon and morning levels) was calculated. There was no association of either morning cortisol levels or diurnal change in cortisol levels with age, gender, or race. There was no difference among the three groups in either cortisol determination. Although difference in morning cortisol levels between those with extensive as compared with limited disease was not statistically significant (p = 0.349 from analysis of variance), there was a significantly decreased diurnal change in cortisol levels in those with extensive disease as compared with those with limited disease (+2.7 +/- 188.3 vs -259.1 +/- 177.1). We conclude that patients in our hospital with active pulmonary tuberculosis do not exhibit decreased adrenocortical function as compared with groups of patients without active pulmonary tuberculosis. | 21 |
Organization and slow axonal transport of cytoskeletal proteins under normal and regenerating conditions. The organization of the axonal cytoskeleton was investigated by analyzing the solubility and transport profile of the major cytoskeletal proteins in motor axons of the rat sciatic nerve under normal and regenerating conditions. When extracted with the Triton-containing buffer at low temperature, 50% of tubulin and 30% of actin were recovered in the insoluble form resistant to further depolymerizing treatments. Most of this cold-insoluble form was transported in slow component a (SCa), the slower of the two subcomponents of slow axonal transport, whereas the cold-soluble form showed a biphasic distribution between SCa and SCb (slow component b). Changes in slow transport during regeneration were studied by injuring the nerve either prior to (experiment I) or after (experiment II) radioactive labeling. In experiment I where the transport of proteins synthesized in response to injury was examined, selective acceleration of SCb was detected together with an increase in the relative proportion of this component. In experiment II where the response of the preexisting cytoskeleton was examined, a shift from SCa to SCb of the cold-soluble form was observed. The differential distribution and response of the two forms of tubulin and actin suggest that the cold-soluble form may be more directly involved in axonal transport. | 19 |
The prevalence of toxoplasmosis on Pacific Islands, and the influence of ethnic group. The prevalence of Toxoplasma dye-test antibody was determined in inhabitants of a number of Pacific islands, in Melanesia, Micronesia and Polynesia, and on Taiwan. With the exception of one island in French Polynesia, two Hawaiian islands, and Taiwan, Toxoplasma antibody prevalences were high, ranging between 84% and 100% in the adult populations tested. On the Hawaiian islands of Oahu and Hawaii, populated by several ethnic groups, and where about 50% of the total adult populations were estimated to have been infected with Toxoplasma gondii, a marked variation in prevalence of infection by ethnic group was observed. The lowest prevalence in the Hawaiian islands estimated at about 15% to 20% in adults, was observed in Japanese. On Taiwan, only 6% of adult ethnic Chinese and 1% of aborigines tested had Toxoplasma antibody. | 16 |
Pulmonary hypertension and human immunodeficiency virus infection. Two reports and a review of the literature. Pulmonary hypertension may be primary (idiopathic) or secondary. While the etiologies for secondary pulmonary hypertension are diverse, infection with the human immunodeficiency virus (HIV) has not been included. To date there have been 16 reported cases of pulmonary hypertension in the HIV-infected population. Plexogenic arteriopathy was the most common pathologic finding. We report two HIV-infected patients who were concomitantly found to have pulmonary hypertension with plexogenic arteriopathy. One patient had lymphocytic interstitial pneumonitis, an entity not previously associated with pulmonary hypertension. We review the 16 previous cases of pulmonary hypertension and HIV infection and discuss this association. | 15 |
[Protective mechanism of Salvia miltiorrhiza and Paeonia lactiflora for experimental liver damage]. Experimental model of acute liver damage with D-galactosamine was made. Thereafter, Salvia miltiorrhiza (SM) and Paeonia lactiflora (PL) were given to the rats. Survival rate of rats and liver coefficient (liver weight/body weight) were observed. Changes of ALT and bilirubin in serum were detected. Level of plasma fibronectin (PFN) was determined at various times. Changes of pathological histology under microscope and electron-microscope were observed. The results showed that SM and PL could increase plasma fibronectin levels in rats, and improve the reticuloendothelial system function and plasma opsonic activity. Aggregation of microaggregated albumin, collagen fragment and immune complexes were markedly reduced. Liver immune damage and microcirculation disorder were avoided. Meanwhile, PFN could cause increase of phagocytosis of Kupffer cell to endotoxin. It is concluded that SM and PL play an important role in protective hepatocyte. | 11 |
Changes in case mix and outcomes of readmissions to nursing homes between 1980 and 1984. This study compares the personal characteristics, measures of functional status/case mix, and immediate discharge outcomes of two cohorts of nursing home patients (1980 and 1984). All of these patients had a prior history of nursing home care and all were readmitted to skilled nursing facilities from hospitals. In 1984, readmissions were more disabled, more debilitated, and significantly less likely to return home. They were almost twice as likely to be rehospitalized within 30 days of discharge from the hospital (26.7 percent versus 48.9 percent). Analyses showed poorer health status and an increased proportion of nursing home deaths and rehospitalizations in the 1984 group to be a function of time (1984 versus 1980) rather than of insurance coverage (Medicare versus other). Nursing home readmissions appear to be quite sensitive to cost-containment efforts, and they may require additional hospital days to stabilize their conditions in an effort to reduce the rate of hospital readmissions and the overall cost of care. | 15 |
[Metastases from cancers of unknown primary site. Data from 302 autopsies]. The autopsies of 302 patients who had metastases from cancers of unknown primary site were studied. In two-thirds of the cases the metastases were located in the lymph nodes, the lungs and the bones. The primary tumour was found in 82 patients when still alive (27 percent) and in 173 patients (57 percent) at autopsy. It could not be identified in 16 percent of the cases. The primary tumours most often discovered were in the pancreas (26.5 percent), the lungs (17.2 percent), the kidneys (4.6 percent) and the colorectal bowel (3.6 percent). On the whole, the paraclinical examinations performed for diagnostic purposes had been disappointing. The survival rate was the same whether or not the primary tumour had been identified. The number of inaugural metastases seems to be a major prognostic factor. These highly progressive tumours must represent a very distinct clinical and biological neoplastic entity. A simple approach and a unicist practical management are suggested. | 10 |
CD4+:neopterin ratio correlates with p24 antigenaemia in HIV infected patients. In an effort to improve the Walter Reed Staging System (WR), which mainly relies on immune depletion parameters, by introducing viral replication and T-cell activation markers, we examined by p24 antigenaemia and serum neopterin levels (SNL) 72 HIV positive PGL, ARC and AIDS patients (11 of whom classified as WR 2, 21 as WR 3, 16 as WR 5 and 24 as WR 6). While CD4 cell counts, already weakly correlating with the WR itself, did not significantly differ between p24 antigen (p24 AG) positive and negative patients, striking differences between the two groups, especially in PGL patients (p less than 0.0001), were found as far as SNL was concerned. In fact, SNL values, fluctuating around 10 and 30 nmol/l, respectively, in p24 Ag positive and negative patients regardless of their WR allocation, seemed rather to reflect, as global means of any given class, prevalence rate of p24 Ag positivity. We suggest, therefore, to use CD4/SNL ratio (R) for HIV infection and disease staging, as it not only may represent a compromise index between cellular immune depletion and T-cell activation, but also seems to take into account the viral replication component, already shown to be an important predictive marker of disease progression. | 25 |
The effects of alpha-methyl-p-tyrosine pretreatment on ethanol-induced narcosis and hypothermia, as well as in the development of tolerance to these effects in UChA and UChB rats. We have previously reported that UChA rats (genetically low ethanol consumer) develop tolerance to narcosis time easier than UChB rats (genetically high ethanol consumer). We also have reported that UChA rats develop tolerance to the hypothermic effect of ethanol, while in UChB rats the repeated administration of ethanol induces sensitization towards this effect. In the present paper the effects of alpha-methyl-p-tyrosine (AMPT)--a competitive inhibitor of norepinephrine synthesis--on ethanol-induced narcosis and hypothermia, as well as in the development of tolerance to these effects, were studied in both strains of rats. Results obtained show that AMPT pretreatment induced a significantly higher increase in narcosis time and hypothermia, as well as, greater susceptibility to ethanol toxicity in UChB than UChA rats. Furthermore, the simultaneous treatment with AMPT and ethanol did not change the development of tolerance to narcosis time in both strains and to hypothermia and sensitization in UChA and UChB rats respectively. | 21 |
Mechanical work and fatigue: their roles in the development of muscle work capacity. To compare the effects of mechanical work versus fatigue on the improvement of work capacity of muscle, young, healthy men were selected to life a 45-pound weight with their quadriceps for 30 sessions, followed by 5 sessions of testing. The study consisted of two phases. Subjects in the first phase did equal amounts of mechanical work with both quadriceps, but had different amounts of fatigue from side to side because the rate of work was different. Subjects in the second phase fatigued both quadriceps, but one quadriceps was fatigued with a rest period between contraction cycles, and one was fatigued without a rest period, thus allowing the side with the rest cycle to do more mechanical work. To test the relative effects of training, a transfer-of-training design was used in both phases. The results suggest that fatigue, defined operationally as the inability or unwillingness of the subject to continue the prescribed task under given reinforcement conditions, plays a larger role in the development of work capacity of muscle than the amount of mechanical work per se. | 17 |
Movement of biotin across the rat intestinal basolateral membrane. Studies with membrane vesicles. The characteristics of the transport process of the water-soluble vitamin biotin across the basolateral membrane (BLM) of rat intestine, i.e. the exit of biotin from rat enterocyte, were examined using established BLM vesicles (BLMV) techniques. Results of osmolarity and temperature studies have indicated that the majority of biotin taken up by these vesicles is the result of transport of the vitamin into the intravesicular spaces, with little membrane binding. Transport of biotin in these vesicles was found to be: (1) higher in BLMV of the jejunum than those isolated simultaneously from the ileum, (2) Na(+)-independent in nature, (3) saturable as a function of concentration, with an apparent Km of 3.51 microM and a Vmax. of 16.49 pmol/10 s per mg of protein, (4) inhibited by high concentrations of unlabelled biotin and its related compounds, but not by the unrelated taurocholate, (5) sensitive to the anion transport inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) and 4-acetamido-4-isothiocyanostilbene-2,2'-disulphonic acid (SITS), and (6) not affected by imposing a positive or a negative intravesicular space with the use of a valinomycin-induced K+ diffusion potential. Based on these findings, it is concluded that biotin transport across the rat intestinal BLM is mediated via a specialized carrier system which is Na(+)-independent, transports the vitamin by a process which is sensitive to the effects of anion transport inhibitors, and is electroneutral in nature. | 20 |
Generic screening as an integral part of quality management. Comprehensive quality management programs are vital to the evaluation and improvement of the delivery of health care today and in the future. These programs must address issues which include quality assurance, risk management, and utilization management. The programs should be designed to promote and assist in the safe delivery of patient care as well as the provision of a safe environment for all patients, visitors, and employees. Various methodologies have been advocated to ensure quality care, the majority of which are retrospective evaluations. One of the more recent methodologies developed is generic screening. The Boston Veterans Medical Center has utilized generic screening since 1986 in its Quality Management Program. Our generic screening program has been successful as a result of multidisciplinary collaboration, commitment, and support from the medical center's top management, both administrative and clinical. We have developed a credible system that may be used to fulfill many requirements of both internal and external reviews. The program is easily reproducible and provides a basis for trend analysis within specific groups in order to better plan and meet patient care needs, minimize risk, and maximize outcome. | 16 |
Iron chelation in myocardial preservation after ischemia-reperfusion injury: the importance of pretreatment and toxicity. Oxygen-derived free radicals have been implicated in myocardial ischemia-reperfusion injury. It has been proposed that deferoxamine, an iron chelator, improves myocardial preservation by reducing the iron-catalyzed production of the hydroxyl radical. The objectives of this study were to define the appropriate timing of iron chelation therapy and the dose-response properties of deferoxamine. Isolated working rat hearts were subjected to 25 minutes of normothermic global ischemia. Deferoxamine was given as pretreatment (n = 39; doses of 10 or 30 mg/kg), added to cardioplegic solution (n = 43; doses 0.46 to 1.90 mmol/L), or administered upon reperfusion (n = 52; doses 0.15 to 0.76 mmol/L) and compared with saline controls (n = 25). Deferoxamine pretreatment improved survival at each dose from a control value of 44% to 71% and 72% (p less than 0.05), respectively. A cardioplegia dose of 0.46 mmol/L improved survival from 48% to 75%. Higher doses reduced survival and implied a toxic effect. Reperfusion therapy did not alter survival. Regardless of time of administration, deferoxamine did not improve ventricular function or adenosine triphosphate levels. Deferoxamine given as pretreatment 1 hour before ischemia at doses of 30 mg/kg, and perhaps as low as 10 mg/kg, significantly improved survival. The addition of deferoxamine to cardioplegic solution was safe and may be protective at approximately 0.50 mmol/L; however, toxicity should be considered at concentrations greater than 0.76 mmol/L. These data support the postulate that iron catalysis is involved in the production of oxygen-derived free radicals during ischemia-reperfusion injury. We conclude that pretreatment before ischemia is an important component of iron chelation therapy in myocardial preservation. | 16 |
Lymphangiomyomatosis: morphogenetic study and ultrastructural confirmation of the histogenesis of the lung lesion. A 34-year old woman underwent a surgical intervention as a result of a retroperitoneal tumor. This tumor was excised and the pathological diagnosis was lymphangiomyoma. Two months later she developed a spontaneous right pneumothorax with a chylous pleural effusion. Roentgenograms showed that the lungs had developed a honeycomb pattern. She was treated surgically and at the same time a biopsy was performed. Sixteen months later she deveoped a left pneumothorax which necessitated additional surgery, and a further biopsy was taken. She died of respiratory insufficiency 2 years after the clinical onset of the symptoms. The pathologic material was studied by both electron and light microscopy in serial sections. The electron-microscopic study proved the muscular nature of this condition. The light microscopic study of the serial sections showed that the lung lesion was due to the proliferation of the muscle cells associated with the lymphatics surrounding the acini. | 13 |
Separate roles of androgen and oestrogen in the manipulation of growth and efficiency of food utilization in female rats. The roles of androgen and oestrogen in the perinatal and postpubertal stages of development on the masculinization of female patterns of growth have been investigated in several experiments in rats. A stimulatory effect of testosterone on subsequent growth and efficiency of food utilization was only observed when administered perinatally to intact females as the propionate ester. Thus females which were untreated (or androgenized) perinatally and ovariectomized at weaning failed to grow more rapidly or utilize food more efficiently when treated with mixed testosterone esters from 36 to 38 days of age. Also autoimmunity to luteinizing hormone releasing hormone (LH-RH) had little effect on the growth or efficiency of food utilization of male rats, although testicular development was grossly affected. An inhibitory effect of oestrogen on subsequent growth and efficiency of food utilization was demonstrated by surgical ovariectomy and by autoimmunity to LH-RH. Also perinatal administration of oestradiol benzoate to intact female rats depressed growth below that of untreated intact litter-mate females until about 50 days of age. Then oestradiol benzoate-treated female rats grew to a larger size than untreated intact litter-mates but not to a heavier weight than untreated litter-mate females which like the oestradiol benzoate-treated females, were ovariectomized at 18-21 days of age. Both of these groups of female rats differed markedly in weight gain from females which were perinatally androgenized and ovariectomized at weaning. The effects of androgenization and ovariectomy on weight gain were comparable and additive in female rats fed restrictedly or ad libitum. Nevertheless, androgenized + ovariectomized female rats fed restrictedly or ad libitum failed to grow as rapidly as male rats. Some additional factor(s) prevents complete masculinization of the female pattern of development. The stimulatory effects of androgenization and ovariectomy on the growth of females appear to be related to endocrine mechanisms controlling the onset of pubertal changes in somatic development. | 20 |
Induction of various cytokines in mice and activation of the complement system in rats as a part of the mechanism of action of the Corynebacterium granulosum-derived P40 immunomodulator. The capacity of the Corynebacterium granulosum-derived P40 immunomodulator to induce in mice the formation of various cytokines IFN, IL-1, IL-2, alpha-TNF as well as to activate the complement system in rats was investigated. The results showed that P40 injected by the intravenous route was capable of inducing the formation of all four cytokines. High levels of IFN were measured 2 h after P40 stimulation and were still present at 24 h. The kinetic study of IL-1, IL-2 and alpha-TNF induction showed that it was a biphasic phenomenon. The patterns of IL-1 and alpha-TNF induction were quite comparable, whereas the release of IL-2 was delayed with respect to that of IL-1 and alpha-TNF. Oral administration of P40 to rats strongly activated the alternative pathway of the complement system. It was concluded that most of the non-specific effects of P40 on the immune system are likely to be mediated by its capacity to induce cytokine formation and to activate the complement system. | 18 |
Hemangiopericytoma of the nasal cavity. Hemangiopericytomas are unusual vascular tumours that rarely occur in the paranasal sinuses and nasal cavity. They are thought to arise from pericytes that surround capillaries, however, there is no proven etiology of these tumours. The diagnosis cannot be made based on gross morphologic characteristics nor on frozen section biopsy. Instead, the diagnosis is dependent on careful histologic examination and reticulum staining. The diagnosis can be confirmed by electron microscopy. The histologic picture is greatly varied from tumour to tumour and within a given tumour itself. The clinical course of hemangiopericytomas ranges from benign to malignant with possible distant metastases and cannot be reliably predicted by histologic criteria. Hemangiopericytomas of the nose and paranasal sinuses are thought to behave less aggressively than those occurring in other parts of the body. Lymph node metastasis is rare and elective neck dissection is not indicated. The accepted treatment of these tumours is wide surgical excision, however adequate surgical margins are usually difficult in the sinonasal region. As a result, hemangiopericytomas can exhibit a high recurrence rate. Therefore, it is mandatory that these patients be followed carefully for the remainder of their lives. | 14 |
[Pathomorphologic studies of the endocrine cells in the gastrointestinal mucosa. Physiology, cytochemistry and ultrastructure (author's transl]. With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable electron density. According to most authors, they represent a distinct cell type and not just a variant of the G-cells. It may be very difficult, however, to separate certain forms of D1-cells from functionally altered G-cells. 5. The A-cell can be found in the gastric mucosa of certain animal species, where it has been demonstrated by immunocytochemistry with antisera to gut-glucagon. This cell type does not occur in the human gastric mucosa. 6... | 13 |
A nebulizer chronolog to monitor compliance with inhaler use. The Lung Health Study is a 10-center 5-year clinical trial sponsored by the National Heart, Lung, and Blood Institute to evaluate the effectiveness of early intervention in chronic obstructive pulmonary disease (COPD). The specific objectives of the trial are to determine whether the accelerated decline in lung function characteristic of COPD and morbidity due to COPD can be reduced by special intervention at a relatively early stage in the evolution of the disease. Special intervention consists of a smoking-cessation program and the use of an inhaled bronchodilator to suppress airway hyperreactivity. The use of the inhaler canister is monitored every 4 months by canister weighing and, at two of the 10 centers, by an electronic recording device, the Nebulizer Chronolog. Among trial participants assigned the latter device, results from the first 4 months of the study indicate that only 52% of trial participants who were uninformed as to the nature of the chronolog used their inhaler at least twice daily as measured by the chronolog, compared with 87% as determined by self-report. Satisfactory or good compliance was achieved by 52% of these subjects as measured by the chronolog compared with 85% as assessed by canister weighing. Eighteen percent of uninformed participants "dumped" their inhalers within a 3-hour time period, contributing to the inaccuracy of canister weights as an indicator of compliance. Feedback of information to the participants from the chronolog improved the level of compliance and eliminated the "dumping" phenomenon. We conclude that, when accurate determinations of compliance are important, as in a drug trial, objective medication monitors should be considered. Electronic monitoring of inhaler use can provide valuable feedback, which encourages improved compliance. | 18 |
Effect of fat tissue volume on the distribution kinetics of biperiden as a function of age in rats. The relationship between the volume of fat tissue and variations in the time course of plasma biperiden concentration in rats has been examined in three different groups (4-, 10-, and 50-week-old rats). The plasma concentrations at 24 hr after iv injection of 3.2 mg/kg varied between 0.8 ng/ml (4-week-old rats) and 5.0 ng/ml (50-week-old rats). The rank order of the steady state distribution volume of biperiden was: 50-week-old rats greater than 10-week-old rats greater than 4-week-old rats. The fat volume of the whole body, extracted from the dried carcass with ether, varied between 42 g/kg (4-week-old rats) and 167 g/kg (50-week-old rats). There was a good correlation between the steady state distribution volume of biperiden per lean mass body weight and the fat volume per lean mass body weight (r = 0.987). The fat/plasma concentration ratios at 8 hr after the iv injection varied between 600 (4-week-old rats) and 200 (50-week-old rats), whereas the brain/plasma concentration ratios were identical to those at steady state among the three groups. The time courses of biperiden concentration in plasma, brain, and fat were simulated using a physiological pharmacokinetic model. There was reasonable agreement between the model predictions and the observed data, suggesting that the change in the fat volume is a dominant determinant of the distribution volume of biperiden in rats. Age-related changes in tissue and plasma concentrations are discussed in relation to the clinical usefulness of the blood level monitoring. | 15 |
Biorhythms in toxicology and pharmacology. II. infradian biorhythms and general discussion. In man circaseptidian (weekly) rhythm has been established in certain employements where a delayed pulmonary allergic reaction is observed. Circatrigintan (monthly) rhythms related to the biological effects of the rotation of the moon around the earth or of the rotation of the sun around its axis have not been definitely pointed out in man. The demonstration of a circannual (seasonal) biorhythmicity of responses to drugs and toxins requires long runs of observations (5-7 years). However circannual, as well as infrannual rhythms, should not be dismissed as they are consequences of biometeorological factors the actions of which at least for temperature on toxic reactions are admitted. Besides the influences of endogenous factors such as sex and aging perturbate the endocrinological modulations of these biorhythms and complicate the scope of such a research. The cyclic action mechanism of therapeutic and toxic agents appears to be a direct impact on intrinsic enzymatic rhythms of different periods entrained by the physical, chemical and principally psychophysiological factors of man's environment. | 15 |
High cost technology in health care: a benefit or a burden? The influence of high cost technology goes beyond its consequences for the selected patient groups that benefit from its application. Past and future technological developments have a variety of social, economic and ethical implications which have to be taken into account when balancing its costs and benefits to society. Departing from an economic perspective we describe a number of mechanisms underlying the emergence of high cost technology which help us to understand some of the characteristics of high cost technology, such as its focus on quality enhancement rather than on economy. To assess the actual performance of high cost technology in terms of efficiency and equity is difficult as there may be debate about the perspective guiding such assessment and as there still is scarce information on high cost technology in terms of these economic indicators. The increasing technological opportunities have triggered a wider debate on the desired evolution of our health care systems. In some countries there is a tendency to diminish government involvement in health care and emphasize private (for profit) enterprise as a reaction to not being able to finance all new high cost technology. The risks of such strategies are discussed briefly. We conclude that the main actors in health care should adjust their behaviour in order to accomplish the introduction of more cost-effective technologies and to achieve a more socially efficient distribution of their benefits. | 18 |
Increased globotriaosylceramide in familial dysautonomia. Familial Dysautonomia (FD) is an autosomal recessive disease of unknown etiology, occurring primarily in Ashkenazi Jews. Patients are neurologically impaired, with deficits primarily in autonomic and sensory functions. The biochemical and genetic defects have remained elusive, precluding carrier detection and prenatal diagnosis. High-performance liquid chromatography data indicated up to a threefold increase in the neutral glycosphingolipid globotriaosylceramide in Dysautonomic fibroblasts and lymphoblasts. Total ganglioside values, measured by colorimetric, fluorometric or specific sodium borohydride incorporation, were decreased. Affected fibroblasts exhibited a range of pleomorphic phenotypes, such that the usual swirl-like confluent growth pattern of normal fibroblasts was distorted to varying degrees, suggesting abnormalities in the FD plasma membrane, possibly affecting cell-cell contacts. The glycosphingolipid increase could not be accounted for on the basis of markedly decreased alpha-galactosidase activity, as in Fabry's disease, where patients also display decreased autonomic function. | 19 |
Ischemia, reperfusion, and the determinants of tissue injury. Much of the damage arising during ischemia and reperfusion can be attributed to the consequences of flow deprivation. However, while reperfusion is a prerequisite for the survival of tissue, it may have an injurious component, which, if counteracted, might enhance postischemic recovery. The complex and dynamic changes that occur during ischemia in the diseased human heart are difficult to model in experimental preparations. As a consequence, much remains to be learned about the identity and manipulability of cellular changes leading to irreversible injury. Although the subject of most studies, injury to the myocyte may not be the primary determinant of tissue injury and changes in the endothelium or vascular smooth muscle may play an important role. Once critical ischemia-induced cellular changes have been identified, interventions can be developed to delay their progression such that at the time of reperfusion more cells are potentially salvable. Suboptimal reperfusion may limit the recovery of the tissue through the induction of "reperfusion injury." Much controversy surrounds the importance and even the existence of this phenomenon. It is proposed that reperfusion injury may express itself in four distinct forms: a) reperfusion-induced arrhythmias, which are potentially lethal (but preventable or reversible) events occurring in otherwise viable tissue; b) myocardial stunning, which is expressed as prolonged (but eventually fully reversible) contractile and metabolic dysfunction; c) the induction of lethal injury in tissue that was potentially viable in the moments before reperfusion; d) accelerated necrosis in tissue that is already irreversibly injured (the "oxygen paradox"). All but the third of these categories has been shown to exist experimentally and clinically, and can be advantageously manipulated. Although it is likely that lethal reperfusion injury also exists, there is as yet no definitive proof. Clarification of this issue is of considerable importance to those undergoing angioplasty or thrombolytic procedures. | 19 |
A psychometric study of chronic cerebellar stimulation in man. Groups of patients with intractable epilepsy or spasticity of varying etiologies underwent psychological testing before and during chronic cerebellar cortex stimulation, a neurosurgical technique designed for the relief of these symptoms. The battery of psychological tests permitted a standardized assessment of intellectual, memory, and perceptual functions. Other behavioral dimensions were assessed through structured interviews. No apparent declines in higher integrative functions followed shorter or longer term cerebellar stimulation. In contrast, stimulated patients tended to show increments in tests of recent memory and verbal output beyond that of unoperated comparison groups. Subjective reports of increased "alertness" and reduced depression and anxiety were also frequently given. Psychological and neural factors may both contribute to the observed behavioral alterations. It was concluded that the cerebellum participates in behavioral functions by modifying cortical and subcortical mechanisms relevant to integrative behavior and emotions. Specific hypotheses were presented. | 17 |
Effects of subconjunctival 5-fluorouracil injections on the corneal endothelium and ciliary epithelium. The effects of 14 successive daily subconjunctival 5-fluorouracil (5-FU) injections on corneal endothelial and ciliary epithelial cells were studied in pigmented rabbits. A total of 100 microliters 5% or 1.25% 5-FU was injected subconjunctivally in one eye and vehicle solution was injected in the other eye. At 12 h or 14 days after the 14th and last injection, both eyes were processed for observation with scanning or transmission electron microscopy. In other groups of rabbits injected with 5% 5-FU, effects on the corneal thickness, corneal endothelial permeability, blood-aqueous barrier permeability, intraocular pressure and aqueous flow rate were also studied. In the fellow eyes and treated eyes examined 14 days after the last injection, no significant morphological changes were seen. In eyes examined 12 h after the last injection, the following findings were obtained. The corneal endothelial cells showed moderate cytoplasmic swelling and mitochondrial swelling and vacuolation. The changes were dose-dependent and most marked in the area near the injection site, whereas they were minimal in the area apposing it. In the ciliary body adjacent to the injection site, disarrangement of the basal infoldings of non-pigmented epithelial cells was seen in eyes injected with 5% 5-FU, whereas no significant change was observed in those injected with 1.25% 5-FU. However, the physiological parameters examined remained unaltered. | 16 |
[Effect of low temperatures on the functional state of the membranes of the hepatic endoplasmic reticulum]. Oxidation of fluorescent substrates--NADPH and 4-dimethylamine chalcone (DMC) by microsomes from liver endoplasmic reticulum was studied after freezing and thawing of these cells organelles. Slow freezing to -25 degrees or quick freezing to -196 degrees did not affect distinctly the rate of NADPH oxidation after thawing, but oxidation of DMC by microsomes was decreased in both cases. Freezing and subsequent thawing of microsomes impaired apparently the terminal sites of electron transfer and/or the systems of hydroxylation, including cytochrome P-450. Slow freezing to -25 degrees impaired microsomes more markedly than quick freezing to -196 degrees. | 16 |
Explanation for the labeling of cervical motoneurons in young rats following the introduction of horseradish peroxidase into the calf. This study was carried out to determine whether cervical motoneurons, labeled following the introduction of horseradish peroxidase into the rat hind leg, belong to the cutaneous trunci motoneuron pool. The cutaneous trunci is a superficial muscle that extends from the axilla, over the flank, and into the thigh. Its nerve supply is derived from the brachial plexus. In experimental animals, horseradish peroxidase was either injected directly into the right gastrocnemius muscles, or applied to gelfoam and implanted over the calf muscles in the right leg of 5-, 10-, 15-day-old and adult rats. In control animals the cutaneous trunci was denervated prior to the administration of horseradish peroxidase. Labeled cervical motoneurons were present in the 5-, 10-, and 15-day-old but not the adult experimental groups and were located within the predetermined confines of the cutaneous trunci motoneuron pool. No labeling of cervical motoneurons was observed in any of the control groups in which the cutaneous trunci muscle was denervated. The most likely explanation for the labeling of cervical motoneurons in young rats was the local diffusion of horseradish peroxidase from the calf to the thigh, where it entered the cutaneous trunci muscle and was taken up by some of its motoneurons. The absence of such labeling in adult rats was probably due to the presence of connective tissue barriers to diffusion and to the greater distance between the site of horseradish peroxidase application and the cutaneous trunci muscle, which prevented the tracer from reaching the cutaneous trunci muscle and labeling its motoneurons. | 19 |
Effect of aprotinin on metastasis of Lewis lung tumor in mice. Kallikrein activity in human stomach tissue was measured and found to be about threefold higher in cancer tissue than in normal tissue. To clarify the physiological role of this tissue kallikrein, we investigated its effects on the spontaneous metastasis and tumor growth of Lewis tumors (3LL). Antiprotease, aprotinin, and gabexate mesilate (FOY) inhibited spontaneous metastasis but did not inhibit tumor growth, while tissue kallikrein and plasmin enhanced the spontaneous metastasis of 3LL. The results suggest that the inhibitory effects of aprotinin and FOY on metastasis are not only due to an inhibition of tumor cells released by tissue kallikrein, but that tissue kallikrein, a protease, also participates in metastasis. We thus conclude that aprotinin or FOY should be administered either before or immediately after operation to inhibit spontaneous metastasis. | 18 |
USAR Nurse Referral and Retention Program. In 1987, the 804th Hospital Center made alleviating the shortfall of registered nurses in the Command a priority. The Command had only 79% of its registered nurse positions filled at the time. Using the recruitment strategies of an employee referral program and a mailing list, the Command reached 100% fill in 2 years and maintained those gains for an additional year. Retention strategies were also implemented which lowered the attrition rate. This paper describes the Army Nurse Referral and Retention Program developed and implemented at the 804th Hospital Center that relieved the shortfall of registered nurses in the United States Army Reserve in New England. | 12 |
The clinical problem of hepatitis transmission;. Although blood banks in this country have been testing every unit of blood for hepatitis B surface antigen (HBSAg) by one of the highly sensitive "third generation" methods (radioimmunoassay or reversed passive hemagglutination) since September, 1975, post-transfusion hepatitis (PTH) still remains the major hazard to patients who require transfusion with blood and blood products. Since there may be an interval of many months between transfusion and onset of PTH and many cases are subclinical, the best data on the incidence of PTH have come from prospective studies with careful follow-up of transfused patients. Such studies first established the validity of HBSAg as a marker for the presence of hepatitis B virus (HBV), and they have shown a dramatic reduction in the incidence of post-transfusion type B hepatitis following the elemination of HBSAg positive blood from transfusion. Nevertheless, PTH cases not associated with HBV or HAV, which are termed non-A, non-B hepatitis, continue to occur commonly among transfused patients. Non-A, non-B hepatitis appears to be subclinical in many instances, but it can produce prolonged persistence of abnormal liver function tests, which may be associated with chronic liver disease. The outstanding risk factor responsible for the development of PTH has been shown to be blood from paid donors in every study which has evaluated this factor. HBSAg and anti-HBS prevalences were found to be much higher in paid donor groups than in voluntary donors. Accordingly, the Food and Drug Administration has proposed that all units of blood be labeled to indicate whether they were collected from voluntary or paid donors in order to inform consumers of the relative hepatitis risks of blood units from these different donor populations. In addition to HBSAg testing and reduced use of blood from paid donors, measures which may provide future reduction of the hepatitis hazard associated with blood transfusion include avoidance of unnecessary transfusions, identification of the agent(s) responsible for non-A non-B hepatitis and development of tests for these agents, idenfification and avoidance of blood from donors implicated in PTH cases, development of methods for immunizing transfused patients against the various agents responsible for PTH, and use of frozen-washed red blood cells for transfusion. Efforts to develop and/or evaluate these various approaches are currently being actively pursued in many laboratories. | 22 |
[Improvement in the healing of colonic anastomoses by vitamin B5 and C supplements. Experimental study in the rabbit]. To study the effects of vitamins B5 and C on the healing process of colonic anastomoses, 3 groups of 20 rabbits were given daily either placebo (group A), or vitamin B5 (100 mg/kg: group B) or vitamin C (100 mg/kg: group C). After 8 days of supplementation, via a midline incision and under general anaesthesia, 2 colonic segments were removed, and the continuity was restored. On the 3rd post-operative day, the rabbits were killed and the anastomoses were removed. Mechanical properties of both normal colon and anastomoses were determined by using bursting pressure tests, number of burst anastomoses, fibroblast count, hydroxyproline concentration and determination by microanalysis of trace element content: Mg, P, S, Ca, Fe, Cu, Zn and Mn. Vitamin B5 (p = 0.03) and vitamin C (p less than 0.01) both decreased the number of burst anastomoses. Furthermore the required bursting pressure values were higher with vitamin C (p = 0.01) than in controls. Both vitamins restored normal Zn levels at the anastomotic site, whereas these levels decreased on the 3rd post-operative day during the normal healing process of colonic anastomosis. Moreover, vitamins B5 and C increased Fe, Cu and Mn levels, which are intimately all involved in collagen synthesis. Vitamins B5 and C enhance the colonic wound healing process in the rabbit, acting together in synergy in vivo as well as in vitro, as previously demonstrated. | 15 |
Effects of flavonoids on cyclic AMP phosphodiesterase and lipid mobilization in rat adipocytes. Thirty-one flavonoids were tested for their effects on low Km phosphodiesterase with cyclic AMP as the substrate. Quercetin, luteolin, scutellarein, phloretin and genistein showed inhibitory potencies comparable to or greater than 3-isobutyl-2-methylxanthine (EC50 30-50 microM). Only four compounds namely, catechin, epicatechin, taxifolin and fustin stimulated the enzyme activity (stimulatory EC50 130-240 microM). The most potent phosphodiesterase (PDE) inhibitors were aglycones that had a C2.3 double bond, a keto group at C4 and hydroxyls at C3' and/or C4'. However, when the C-ring is opened then the requirement for the C2.3 double bond is eliminated. The same series of flavonoids were also tested for their lipolytic activity. The structural features required for effective synergistic lipolysis (with epinephrine) were generally similar to that required for potent PDE inhibition except that, for lipolytic activity, an intact C-ring was necessary. Fisetin and quercetin having the above-mentioned structure showed a dose- and time-dependent increase in lipolysis which was synergistic with epinephrine. Only butein and hesperetin showed inhibition of epinephrine-induced lipolysis, and their effect was dose-dependent. A time-course study indicated that hesperetin was able to delay the lipolytic action of epinephrine. It is most likely that the lipolytic effects of these compounds were not a result of PDE inhibition, as the orders of potency for the two activities had poor correlation. Apparently, the effective lipolytic flavonoids were also potent PDE inhibitors but not all the PDE inhibitors were able to induce lipolysis. | 16 |
Contribution of cyclic GMP formation to KRN2391-induced relaxation in coronary artery of the pig. 1. In the present study, we investigated the relationship between relaxation and guanosine 3':5'-cyclic monophosphate (cyclic GMP) formation induced by KRN2391, compared with those induced by nicorandil and nitroglycerin, in the coronary artery of the pig. 2. KRN2391 (10(-8)-3 X 10(-5) M), nicorandil (10(-8)-3 X 10(-4) M) and nitroglycerin (10(-9)-10(-5) M) antagonized the contraction caused by 25 mM KCl in a concentration-dependent manner. 3. The concentration-relaxation curves for KRN2391, nicorandil and nitroglycerin shifted rightward in the presence of methylene blue (10(-5) M). 4. KRN2391 (10(-6) M), nicorandil (10(-4) M) and nitroglycerin (10(-6) M) induced an increased in cyclic GMP. 5. The magnitude of the shift of the concentration-relaxation curve caused by methylene blue and the increase in cyclic GMP with KRN2391 were lower than those with nicorandil and nitroglycerin. 6. The adenosine 3':5'-cyclic monophosphate (cyclic AMP) level was not increased by KRN2391 even at a concentration that produced full relaxation. 7. The present results suggest that KRN2391-induced relaxation in the coronary artery of the pig is partly due to the increase in cyclic GMP formation through the stimulation of guanylate cyclase. | 11 |
Mannose-sensitive interaction of Escherichia coli with human peripheral leukocytes in vitro. The ability of Escherichia coli which possess or lack mannose-sensitive adherence factors (adhesins) to associate with human peripheral leukocytes in vitro in the absence of serum was studied. E. coli 19+, which have mannose-sensitive adhesins, were derived from E. coli strain 19 by culturing in static Trypticase soy broth at 37 degrees C. E. coli 19-, which lack mannose-sensitive adhesins, were derived from E. coli 19 by culturing in agitated Trypticase soy broth at 30 degrees C. E. coli 19+ attached to leukocytes and stimulated the release of lysozyme but not beta-glucuronidase or lactate dehydrogenase. In contrast, E. coli 19- showed poor attachment to the leukocytes and failed to stimulate lysosomal enzyme release. During a 60-min incubation with the leukocytes, the number of viable 19+ organisms decreased, whereas the number of viable 19- remained constant. Purified type 1 pili from E. coli 19+ agglutinated the leukocytes but did not stimulate lysosomal enzyme release. Pretreatment of leukocytes with type 1 pili failed to prevent the adherence of E. coli 19+. The association of 19+ with leukocytes and subsequent release of lysozyme could be blocked by alpha-methyl-D-mannoside but not by equivalent concentrations of dextrose and sucrose. These results show that mannose-sensitive adhesins on E. coli mediate association of the organisms with leukocytes in the absence of serum components. The identity of the adhesins involved in leukocyte association has yet to be determined. | 17 |
Amino acid sequence of the FV region of a human monoclonal IgM (NOV) with specificity for the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1, which cross-reacts with polynucleotides and with denatured DNA. The complete amino acid sequences of the VH and VL regions of a biologically significant Ig, IgMNOV, were determined. IgMNOV is reactive with the capsular polysaccharide of the group B meningococcus and of Escherichia coli K1. As reported earlier, it cross-reacts completely with polynucleotides poly(A) and poly(I) and to a lesser extent with denatured DNA and protects newborn rats against infection with E. coli K1, and is equal in potency to the standard horse anti-group B meningococcal serum. The reduced and alkylated chains were sequenced directly, identifying the L chain as lambda-subgroup II and the mu-H chain as subgroup III. The complete sequence of the VL region was determined by sequencing peptides generated by cleavage with Staphylococcus aureus protease, chymotrypsin, and trypsin. The H chain was cleaved with cyanogen bromide followed by enzymatic cleavages to obtain a large part of the VH region sequence. The structure was completed by sequencing tryptic peptides of the Fab fragment and by mass-spectrometric analysis. | 16 |
Multiple pathways for ligand internalization in rat hepatocytes. I: Effects of anoxia, phenylarsine oxide and monensin. It has been suggested that there are multiple pathways for the cellular internalization of insulin. To investigate these pathways we have examined the effects of three perturbations of endocytosis on the insulin internalization process and have compared these effects with those obtained using an asialoglycoprotein, asialofetuin (Afet), and epidermal growth factor (EGF). Freshly isolated hepatocytes were incubated with radiolabeled ligands and internalization measured under conditions of anoxia to deplete cellular ATP, in the presence of phenylarsine oxide (PAO) to inhibit endocytosis, and in the presence of monensin to interfere with endosomal acidification. Afet internalization essentially was blocked by all three treatment processes, while insulin internalization was inhibited approximately 40% in the presence of anoxia, and 54% in the presence of PAO. Monensin exhibited differential effects on internalization of high and low insulin concentrations. The effects of the treatment processes on EGF internalization were intermediate to those seen with Afet and insulin. These results suggest that insulin and EGF utilize routes of internalization exhibiting different energy requirements that may correspond to coated pit, non-coated pit, and fluid-phase internalization pathways. The observations with Afet internalization remain consistent with utilization of the coated pit pathway. | 18 |
Characterization of the hepatitis B virus EnhI enhancer and X promoter complex. The hepatitis B virus EnhI enhancer element overlaps the promoter of the X gene. By performing methylation interference experiments, four protein factor binding sites clustered in a 120-bp region were found to control the EnhI enhancer and X promoter activities. Deletion mapping experiments indicated that the two upstream protein factor binding sites constituted a basal enhancer module. This module, likely bound by a liver-specific factor and a ubiquitous factor, could activate the herpes simplex virus thymidine kinase gene promoter by 5- or 10-fold, depending on the orientation, in Huh7 cells, a liver-derived cell line, but not in other cell types tested. The two downstream protein factor binding sites interact with the upstream basal enhancer module in an orientation- and distance-dependent manner to increase the enhancer activity by another 10-fold. In addition, at least one of the two downstream protein factor binding sites is also essential for the X promoter activity. | 17 |
The pull in olympic weightlifting. Data from five experienced weightlifters on the vertical forces applied to the barbell and system (barbell and lifter) during the pull were in excellent agreement with earlier displacement-time descriptions of the double knee bend as consisting of two stages of extension interrupted by a period of realignment (second knee bend). The vertical component of the ground reaction force (Rz) consisted of three phases: Weighting I, Unweighting, and Weighting II. The relative magnitude of the Rz impulse with respect to the system weight impulse (as an indicant of the proportion of the Rz impulse contributing to system acceleration) ranged from 118--141% for Weighting I, 74--89% for Unweighting, and 122--135% for Weighting II. In agreement with published theoretical calculations the most experienced and successful lifter produced the larger phase of positive acceleration first. The rebending of the knees was associated with the Unweighting phase. Although this latter interval corresponded to a phase of barbell deceleration, it appeared that the concomitant enhancement of the back, hip, and knee extensor activity outweighed any adverse effects. | 17 |
Cyclin A is required at two points in the human cell cycle. Cyclins play a fundamental role in regulating cell cycle events in all eukaryotic cells. The human cyclin A gene was identified as the site of integration of hepatitis B virus in a hepatocarcinoma cell line; in addition, cyclin A is associated with the E2F transcription factor in a complex which is dissociated by the E1A oncogene product. Such findings suggest that cyclin A is a target for oncogenic signals. We have now found that DNA synthesis and entry into mitosis are inhibited in human cells microinjected with anti-cyclin A antibodies at distinct times. Cyclin A binds both cdk2 and cdc2, giving two distinct cyclin A kinase activities, one appearing in S phase, the other in G2. These results suggest that cyclin A defines novel control points of the human cell cycle. | 13 |
Indications for thoracotomy following penetrating thoracic injury. The treatment of penetrating thoracic injuries has been reviewed in both civilian and military series. Although most surgeons agree that closed that closed thoracostomy drainage is the initial treatment of choice, the timing of early thoracotomy and perhaps cardiorrhaphy upon patients with penetrating thoracic injuries remains controversial. The purpose of this study was to determine which patients will require immediate thoractomy or cardiorrhaphy following penetrating chest injury. Over a two-year period 190 patients with penetrating thoracic injuries were treated. Of 53 patients who required immediate thoracotomy, 31 suffered cardiac wounds. Seventy-nine patients required laparotomy for associated intra-abdominal injuries. The mortality rate was related to exsanguinating hemorrhage or postoperative intra-abdominal sepsis. Cardiopulmonary complications were rare in the absence of intra-abdominal sepsis and could not be attributed to the thoracic injury or thoracotomy. Indications for immediate cardiorrhaphy or thoracotomy are: 1) location of the entrance wound (70% in upper mediastinum); 2) blood pressure on admission less than 90; 3) initial thoracostomy blood loss greater than 800 cc; 4) radiographic evidence of retained hemothorax; and/or 5) clinical evidence of pericardial tamponade. | 17 |
Insulin-induced mitogenesis associated with transformation by the SV40 large T antigen. Simian virus 40 (SV40) large T antigen-transformed cells typically show a markedly reduced serum requirement for growth and the inability to growth arrest and differentiate. An SV40 large T antigen-transformed 3T3 T cell line, CSV3-1, that can growth arrest and differentiate into adipocytes with high efficiency has, however, recently been described (Scott et al: Proc. Natl. Acad. Sci. U.S.A. 86:1652-1656, 1989; Estervig et al: J. Virol. 63:2718-2725, 1989; J. Cell. Physiol. 142:552-558, 1990). The results of the current studies using these cells show that whereas quiescent 3T3 T cells show no mitogenic response to insulin, quiescent CSV3-1 cells show a highly significant insulin-induced mitogenic responsiveness in the absence of other added growth factors. Maximum mitogenesis was observed at an insulin concentration of 1 microgram/ml, which induced 40-70% of the cells to undergo DNA synthesis within 48 hours. The half maximum response was achieved with 1-10 ng/ml of insulin. Insulin's mitogenic effect on CSV3-1 cells was evident under several different culture conditions that induce quiescence and was not mediated by any detectable autocrine growth factors that might make CSV3-1 cells competent to respond to insulin. In CSV3-1 cells insulin appears to act on its own receptor rather than on the IGF-1 receptor, because at comparable dosages IGF-1 is 10- to 100-fold less effective than insulin. Insulin also is shown to be a mitogen for another SV40-transformed cell line, CSV3-35, which can be growth arrested; in contrast insulin has no mitogenic effect on two control cell lines that are stably transfected with pSV2neo, a plasmid containing SV40 early promoter/enhancer but lacking large T antigen gene: These results suggest a significant relationship between SV40 T antigen-associated transformation and the expression of mitogenic responsiveness to insulin. | 13 |
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