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1.
N Pasetto V Petrozza C Ticconi A Zicari F Carpino E Piccione M Melis 《Canadian Metallurgical Quarterly》1993,35(2):99-102
Ten patients with biopsy verified chronic hepatitis C virus (HCV) infection were treated with oral ribavirin at a dose of 1,000-1,200 mg per day in two divided doses for 12 weeks. Serum alanine aminotransferase (ALT) levels and hepatitis C viral ribonucleic acid (RNA) levels in serum were followed prior to, during, and 12 weeks posttreatment. ALT levels decreased significantly in all patients during therapy from a mean level of 3.21 mukat/l (range 1.22 to 7.79) before, to 1.25 mukat/l (range 0.78 to 2.04) at the end of treatment (P < 0.005). Hereafter, relapse to pretreatment levels was seen within 12 weeks after treatment stop. The hepatitis C viral RNA levels decreased from a mean 10 log titer of 4.1 (range 1-6) before treatment to 3.4 (range 1-5) at treatment stop. Five patients did not change their HCV RNA titers during treatment. Twelve weeks posttreatment only 3 patients had lower titers than prior to treatment. We conclude that oral ribavirin seems to reduce the viral load, at least temporarily, in some patients with chronic viremic HCV infection. Further studies are needed to evaluate fully the effect of oral ribavirin on chronic HCV infection. 相似文献
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S Modi DE Gilham MJ Sutcliffe LY Lian WU Primrose CR Wolf GC Roberts 《Canadian Metallurgical Quarterly》1997,36(15):4461-4470
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism symptoms in man, has been examined as a substrate of recombinant human cytochrome P450 2D6. When cumene hydroperoxide is used as an oxygen and electron donor, a single product is formed, identified as 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) for formation of this product (130 microM) is in agreement with the dissociation constants for MPTP binding to the enzyme determined by optical and nuclear magnetic resonance (NMR) spectroscopy. When the reaction is carried out with nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and recombinant human NADPH-cytochrome P450 reductase, a second product, identified as 1-methyl-4-(4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine, is formed in addition to 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) values for formation of these two products are 19 microM and 120 microM, respectively. Paramagnetic relaxation experiments have been used to measure distances between the protons of bound MPTP and the heme iron, and these have been used to construct models for the position and orientation of MPTP in the active site. For the cytochrome alone, a single mode of binding was observed, with the N-methyl close to the heme iron in a position appropriate for the observed N-demethylation reaction. In the presence of the reductase, the data were not consistent with a single mode of binding but could be explained by the existence of two alternative orientations of MPTP in the active site. One of these, characterized by a dissociation constant of 150 microM, is essentially identical to that observed in the absence of the reductase. In the second, which has a K(d) of 25 microM, the MPTP is oriented so that the aromatic ring is close to the heme iron, in a position appropriate for p-hydroxylation leading to the formation of the product seen only in the presence of the reductase. In the case of codeine, another substrate for cytochrome P450 2D6, the addition of reductase had no effect on the nature of the product formed, the dissociation constant, or the orientation in the binding site. These observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cytochrome P450 2D6 that affects the binding of some substrates but not others. 相似文献
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Two forms of glutathione synthetase deficiency have been described. While one form is mild, causing hemolytic anemia, the other more severe form causes 5-oxo-prolinuria with secondary neurological involvement. Despite the existence of two deficiency phenotypes, Southern blots hybridized with a glutathione synthetase cDNA suggest that there is a single glutathione synthetase gene in the human genome. Analysis of somatic cell hybrids showed the human glutathione synthetase gene (GSS) to be located on chromosome 20, and this assignment has been refined to subband 20q11.2 using in situ hybridization. 相似文献
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V. K. Arya M. E. Melis G. R. Halford 《Fatigue & Fracture of Engineering Materials & Structures》1991,14(10):967-977
Results are presented of elastic, elastic-plastic and elastic-plastic-creep analyses of an actively cooled cowl lip. A cowl lip is part of the leading edge of an engine inlet of proposed hypersonic aircraft and is subject to severe thermal loadings and gradients during flight. Values of stresses calculated by elastic analysis are well above the yield strength of the cowl lip material. Such values are highly unrealistic, and thus elastic stress analyses are inappropriate. The inelastic (elastic-plastic and elastic-plastic-creep) analyses produce more reasonable and acceptable stress and strain distributions in the component. Finally, using the results from these analyses, predictions are made for the cyclic crack initiation life of a cowl lip. A comparison of predicted cyclic lives shows the cyclic life prediction from the elastic-plastic-creep analysis to be the lowest and, hence, most realistic. 相似文献
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It was for the first time that of the fifth year of monitoring of Plantago lanceolata L., reproduced within the thirty-kilometer zone of Chernobyl NPP disaster, the authors discovered high incidence of seedlings with various morphological abnormalities. It is suggested that the damages observed are related to the cumulative effect of radiation. 相似文献