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1.
The management of chronic viral hepatitis C is evolving rapidly. Monotherapy with interferon, the accepted standard of treatment until recently, achieves only a modest sustained virological response rate of 15%. Combination treatment with alpha-2b interferon and ribavirin has been shown to increase sustained response rates to 40% in patients who have never been treated with interferon and to 50% in those who have relapsed following monotherapy with interferon. However, side effects, which have led to the discontinuation of combination treatment in a significant proportion of patients, must be carefully monitored. Treatment with interferon alpha-2b and ribavirin has now been approved in Canada, but the selection and monitoring of patients suitable for combination treatment requires special expertise. Although improvements in current therapeutic options may be possible with more frequent, higher doses or long-acting forms of interferon together with ribavirin, low sustained response rates (i.e., below 30%) for patients with hepatitis C virus genotype 1 emphasize the need for novel antiviral medications that will target the functional sites of the HCV genome. 相似文献
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Identification and characterization of an {alpha}-mannosidase from Trypanosoma cruzi 总被引:1,自引:0,他引:1
Swanson Paul M.; Carter Clint E.; Hager Cindy; Kim Wan Joon; Obermeier Sarah; Oeltmann Thomas N. 《Glycobiology》1992,2(6):563-569
In this report we describe the first purification and characterizationof the acid -mannosidase from the human parasite Trypanosomacruzi. The purified enzyme exhibited a native mol. wt of 240000 Da and is apparently composed of four identical subunitsof mol. wt 58 000 Da. Each of the four subunits contains oneN-linked high-mannose-type oligosaccharide. The -mannosidaseexhibited a pH optimum of 3.5 and a pI of 5.9. This low pH optimumand the ability of swainsonine to inhibit its activity suggestthat the -mannosidase is a lysosomal enzyme. Antibodies againstthe T.cruzi enzyme did not react with mammalian lysosomal -mannosidaseand, conversely, antibody against a rat lysosomal -mannosidasedid not react with the T.cruzi enzyme. Thus, the T.cruzi enzymeappears to be distinct from its mammalian counterpart. -mannosidase lysosomal enzyme Trypanosoma cruzi 相似文献
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The effect of insulin and intermittent mechanical stretching on rates of protein synthesis and degradation in isolated rabbit muscle. 总被引:2,自引:2,他引:0
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Tyrosine balance and protein synthesis were studied during the same incubation in isolated rabbit forelimb muscles. From these measurements, protein degradation was calculated. Isolated muscles were usually in a state of negative amino acid balance, principally as a result of the 75% decrease in protein synthesis. Muscles from rabbits starved for 18 h had lower rates of both protein synthesis and degradation compared with muscles from normally fed rabbits. Intermittent mechanical stretching and the addition of insulin at 100 microunits/ml increased rates of both protein synthesis and degradation. Increases in the rate of protein synthesis were proportionately greater in the muscles from starved animals. In muscles from both fed and starved donors, increases in protein-synthesis rates owing to intermittent stretching and insulin were proportionately greater than the increases in degradation rates. For example, insulin increased the rate of protein synthesis in the muscles from starved donors by 111% and the rate of degradation by 31%. Insulin also increased the rate of protein synthesis when added at a higher concentration (100 munits/ml); at this concentration, however, the rate of protein degradation was not increased. The suppressive effect of insulin on high rates of protein degradation in other skeletal-muscle preparations may reflect a non-physiological action of the hormone. 相似文献
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The development potential of fertilized embryos isolated from female mice previously given a single dose of either a dilute solution of ethanol or distilled water (controls) by mouth was studied. Exposure to ethanol occurred at various times during the cycle leading to ovulation and shortly after fertilization. The chromosome constitution of all preimplantation embryos isolated from these females was determined either at the first cleavage mitosis or at the morula stage. The incidence of aneuploidy in the ethanol-exposed groups at these times was approximately 19% and 13.5%, respectively, with a similar number of monosomic and trisomic conceptuses observed at these times. In addition, about 2% of all conceptuses examined were triploid. Further females were autopsied on the 10th or 11th day of gestation, though the chromosome constitution of only the morphologically abnormal or developmentally retarded embryos was determined. Eight embryos out of a total of 16 studied in the ethanol-exposed group were either aneuploid or triploid, whereas in the control group only one out of 11 examined proved to be aneuploid. The triploids and ethanol-induced aneuploid conceptuses appeared to be capable of surviving to the morula stage but generally failed to survive to the 10th/11th day. No monosomics were in fact observed in the postimplantation series. The present findings are briefly discussed with reference to the possible pathogenesis of spontaneous abortions in man, which often possess similar types of chromosomal anomalies. 相似文献
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Insulin (100 U/ml) stimulated protein synthesis and PGF2 release in isolated rabbit muscle, but had little effect on the rate of protein degradation. The effect of insulin persisted for at least 5 h after removal of the hormone. Indomethacin, added at the start of the incubation, inhibited the stimulatory effect of insulin on protein synthesis and PGF2 release, but did not block the binding of iodinated insulin. When added 2 h after insulin, indomethacin did not inhibit the stimulation of protein synthesis but completely inhibited the increase in PGF2 release. The results suggest that the stimulation of protein synthesis by insulin is mediated by metabolites of membrane phospholipids but that these changes are involved during the phase of response that immediately follows the binding of insulin to its receptor. 相似文献
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Anita H. Payne Trent R. Clarke Paul A. Bain 《The Journal of steroid biochemistry and molecular biology》1995,53(1-6):111-118
The classical form of the enzyme 5-ene-3β-hydroxysteroid dehydrogenase/isomerase (3βHSD), expressed in adrenal glands and gonads, catalyzes the conversion of 5-ene-3β-hydroxysteroids to 4-ene-3-ketosteroids, an essential step in the biosynthesis of all active steroid hormones. To date, four distinct mouse 3βHSD cDNAs have been isolated and characterized. These cDNAs are expressed in a tissue-specific manner and encode proteins of two functional classes. Mouse 3βHSD I and III function as 3β-hydroxysteroid dehydrogenases and 5-en→4-en isomerases using NAD+ as a cofactor. The enzymatic function of 3βHSD II has not been completely characterized. Mouse 3βHSD IV functions only as a 3-ketosteroid reductase using NADPH as a cofactor. The predicted amino acid sequences of the four isoforms exhibit a high degree of identity. Forms II and III are 85 and 83% homologous to form I. Form IV is most distant from the other three with 77 and 73% sequence identity to I and III, respectively. 3βHSD I is expressed in the gonads and adrenal glands of the adult mouse. 3βHSD II and III are expressed in the kidney and liver with the expression of form II greater in kidney and form III greater in liver. Form IV is expressed exclusively in the kidney. Although the amino acid composition of forms I, III and IV predicts proteins of the same molecular weight, the proteins have different mobilities on SDS-polyacrylamide gel electrophoresis. This characteristic allows for differential identification of the expressed proteins. The four structural genes encoding the different isoforms are closely linked within a segment of mouse chromosome 3 that is conserved on human chromosome 1. 相似文献