Prehistoric dental calculus gives evidence for coca in early coastal Ecuador.
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Biomedical subjects
Publications and source records attributed to J Thomas.
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71 recipients of cadaver primary and secondary renal transplants were investigated in a prospective randomised double-blind study. Patients were given one of two rabbit antilymphocyte globulin (A.L.G.) preparations made by similar techniques but differing in potency as measured by skin-graft prolongation in rhesus monkeys. Patient selection and management were otherwise similar. A statistically significant difference (P less than 0-05) in graft survival (78% vs. 42%) developed between the two groups at a mean follow-up of 18-4 months and patient entry into the study was terminated. After a 3-5 year interval from the start of the trial the double-blind code was broken. It was found that the high-potency-A.L.G. group had better graft survival and fewer rejection episodes (P less than 0-05) than the moderate-potency group. The results suggest that preclinical testing of A.L.G. by the primate skin graft test can be a valid indicator of the potential efficacy of an A.L.G. preparation in renal-transplant recipients. It is suggested that quality-control standards may improve the clinical results of A.L.G. therapy.
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Three comparable groups were studied : 100 patients with alcoholic cirrhosis, 100 alcoholics without cirrhosis, and 100 subjects without either alcoholism or cirrhosis. Dupuytren's contracture was noted in 43% of cases in group I, 34% in group 2, and in 14% of group 3. There was no parallel between the frequency of Dupuytren's contracture and the severity of the liver involvement. Palmar erythema was noted in 34% of cases of group 1, 23% of cases of group 2, 12% of cases of group 3. Dupuytren's contracture has a genetic background, but its clinical expression is facilitated by metabolic causes, the most frequent being chronic alcoholism. Palmar erythema appears to be a sign of severe liver disease.
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Analysis of x-ray diagrams of oriented hydrated cytoplasmic microtubules shows that the tubule wall extends from about 70 to 150 A radially. The central region of the wall appears homogeneous, but the outside surface is subdivided by vertical grooves separating the 13 protofilaments and by a steep 10-fold family of grooves. The inside surface is dominated by the 10-start grooves with no clear subdivision between the protofilaments.
Rat hepatic 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMG-CoA reductase) was found to be lower in rats fed a semipurified diet of sucrose, casein, and cellulose with a mixture of safflower oil and stripped lard than those fed a stock diet: 0.115 versus 0.447 nmoles mevalonic acid formed/minute/mg microsomal protein. Efforts were made to find the substances in the stock diet responsible for the higher enzyme activity. Neither the addition of small amounts of cholesterol or plant sterols to the semipurified diet, nor the substitution of corn oil or the lipids extracted from the stock diet for the safflower oil-stipped lard mixture, significantly raised the enzyme level. Replacement of sucrose by starch also had no effect on the enzyme activity. The substitution of soybean protein for the casein did increase the specific activity of the enzyme from 0.115 to 0.247, still well below the 0.447 level response to stock rat diet ingestion. Substitution of the safflower oil-stripped lard fat mixture for the extracted fat of the stock feed had no significant effect on the response of the rats to the stock feed. However, substitution of part of the cellulose in the semi-purified diet with citrus pectin resulted in HMG-CoA levels of 0.553, approximately equal to that produced by the stock diet. In the latter study, the total fecal bile acids of the rat fed the stock, semipurified-cellulose, and semipurified-pectin diets were 2.34, 1.28, and 2.22 mg/g feces respectively, and the total fecal neutral sterols 1.86, 1.50, and 2.42 mg/g feces. Thus, the constituent nonutritive fiber appears responsible for differences in steroid excretion and elevated hepatic HMG-CoA levels, possibly by binding bile acids and increasing the turnover rate of blood and liver cholesterol.
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In these studies, pretransplant testing of donor-recipient compatibility was performed in 10 related donor and 26 cadaveric renal transplants using a variety of cell-mediated immunity tests. Mixed lymphocyte culture results did not correlate with acute rejection (AR), acute irreversible rejection, or chronic rejection (CR). Lymphocyte-mediated cytolysis also did not correlate with AR, acute irreversible rejection, or CR. Cell-mediated lympholysis correlated with AR but not with acute irreversible rejection or CR. Antibody-dependent cell-mediated cytolysis (ADCMC) was positive pretransplant in 13 (36%) of the recipients. Of the positive patients, 4 had early severe AR and 9 developed typical CR. Of these 13 patients, 9 or 69% lost graft function to rejection whereas only 3 of 20 (15%) of ADCMC-negative patients lost graft function because of rejection (P less than 0.05). In summary, cell-mediated lympholysis testing demonstrated a capability to predict AR episodes. The most useful pretransplant monitoring assay in this patient series was the ADCMC assay. A positive ADCMC against donor cells pretransplant indicates a relatively poor prognosis for long-term graft survival.
A method is described for the isolation of metabolically active heterocysts from Anabaena cylindrica. These isolated heterocysts accounted for up to 34% of the acetylene-reducing activity of whole filaments and had a specific activity of up to 1,560 nmol of C2H4 formed per mg of heterocyst chlorphyll per min. Activity of glutamine synthetase was coupled to activity of nitrogenase in isolated heterocysts as shown by acetylene-inhibitable formation of [13N]NH3 and of amidelabeled [13N]glutamine form [13N]N2. A method is also described for the production of 6-mCi amounts of [13N]NH3. Isolated heterocysts formed [13N]glutamine from [13N]NH3 and glutamate, and [14C]glutamine from NH3 and [14C]glutamate, in the presence of magnesium adenosine 5'-triphosphate. Methionine sulfoximine strongly inhibited these syntheses. Glutamate synthase is, after nitrogenase and glutamine synthetase, the third sequential enzyme involved in the assimilation of N2 by intact filaments. However, the kinetics of solubilization of the activity of glutamate synthase during cavitation of suspensions of A. cylindrica indicated that very little, if any, of the activity of that enzyme was located in heterocysts. Concordantly, isolated heterocysts failed to form substantial amounts of radioactive glutamate from either [13N]glutamine or alph-[14C]ketoglutarate in the presence of other substrates and cofactors of the glutamate synthase reaction. However, they formed [14C]glutamate rapidly from alpha-[14C]ketoglutarate by aminotransferase reactions, with various amino acids as the nitrogen donor. The implication of these findings with regard to the identities of the substances moving between heterocysts and vegetative cells are discussed.
In the female rat intoxicated with ethylene glycol the oxaluria increases with the degree of intoxication. The increase is less in the animals treated with succinimide. The comparative study of the results of the dosages made with gas-liquid-chromatography and by various colorimetric methods show that this later gives varying results and underestimates high concentrations of oxalic acid. The result is that any study based on results of dosages of urinary oxalic acid made by colorimetry must be taken with some reserve, and this on whether the oxalic lithiasis is experimentally induced or human, or whether its evolution is spontaneous or influenced by a therapeutic.
It has been suggested previously that chlorpropamide and other hypoglycemic sulfonylureas interfere with hepatic triglyceride breakdown. Since ketogenesis from endogenous hepatic lipid stores is a measure of hepatic triglyceride hydrolysis, ketogenesis derived from endogenous lipids as well as ketogenesis derived from exogenously added isotopic oleate was determined in isolated hepatocytes from fasted rats in an attempt to identify the nature of the direct effects of sulfonylureas on hepatic lipid metabolism. Ketogenesis from endogenous lipids was inhibited by 1 mM chlorpropamide, while ketone production from exogenous oleate did not change. The effect of chlorpropamide on hepatic triglyceride metabolism was further studied in the isolated perfused liver of normal rats in the presence of a continuous [3H]oleate infusion and in isolated liver cells incubated in the presence of [3H]oleate. In liver perfusion experiments, 1 mM chlorpropamide enhanced the incorporation of tritium into triglycerides (but not other lipid classes) and increased both liver triglyceride content and triglyceride secretion. Using isolated cells similar effects could be demonstrated at 0.5 mM chlorpropamide. Chlorpropamide, tolbutamide, and carbutamide, all of which inhibited endogenous ketogenesis in isolated liver cells, also inhibited lysosomal triglyceride lipase activity in rat liver homogenates. The drugs were not inhibitory towards alkaline lipase activity. Demethylglycodiazin (2-benzolsulfonamid--5-(beta-hydroxyethoxy)-pyrimidin), which did not inhibit endogenous ketogenesis in isolated liver cells, did not affect lysosomal lipase activity. The lysosomotropic drug chloroquine was markedly antiketogenic when tested in liver cells. The reduction in endogenous ketogenesis, the enhanced accumulation of liver triglycerides, and the stimulation of hepatic triglyceride output by chlorpropamide are ascribed to an interference of the drug with hepatic triglyceride breakdown. The present results also suggest that the lysosomes play a significant role in hepatic lipolysis.
1. Three cyclic metabolites of etidocaine excreted in urine of man have been investigated by g.l.c.-mass spectrometry. 2. These metabolites have been identified as 3-(2,6-dimethylphenyl)-5-ethyl-2,4-imidazolidinedione, 1-(2,6-dimethylphenyl)-2-methyl-4-ethyl-2-imidazolin-5-one and 1-(2,6-dimethylphenyl)-2,4-diethyl-2-imidazoline-5-one. 3. Formation in vivo of two of the metabolites is proposed to proceed via carbinolamine intermediates.
In this study a variety of cell-mediated immunity responses were performed in long-term (2 to 12 year) human leukocyte antigen-A (HLA) nonidentical renal transplant patients. All patients showed mixed lymphocyte culture (MLC) stimulation against donor, indicating a lack of tolerance. Of successful long-term transplant patients, 73 percent showed high serum levels of MLC-blocking activity. A consistent association of successful long-term transplantation and a specific defect in recipient ability to generate cytotoxic cells against donor was seen at the 8 to 12 year level. A close association of lymphocyte-dependent activity (LDA) and clinical chronic rejection was found, and LDA could be identified prior to the onset of clinical chronic rejection in most cases. Four patients had a positive LDA assay prior to transplant and all four went on to develop chronic rejection. Recipients taking immunosuppressive drugs within 24 hours of testing had a deficient capability to generate cytotoxic effector cells against indifferent individuals. These findings demonstrate a consistent association of in vitro cell-mediated immunity parameters and in vivo transplant function and may represent a valuable immunological monitoring system for long-term recipient follow-up.
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