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991.
Bourne Y Kolb HC Radić Z Sharpless KB Taylor P Marchot P 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(6):1449-1454
The 1,3-dipolar cycloaddition reaction between unactivated azides and acetylenes proceeds exceedingly slowly at room temperature. However, considerable rate acceleration is observed when this reaction occurs inside the active center gorge of acetylcholinesterase (AChE) between certain azide and acetylene reactants, attached via methylene chains to specific inhibitor moieties selective for the active center and peripheral site of the enzyme. AChE catalyzes the formation of its own inhibitor in a highly selective fashion: only a single syn1-triazole regioisomer with defined substitution positions and linker distances is generated from a series of reagent combinations. Inhibition measurements revealed this syn1-triazole isomer to be the highest affinity reversible organic inhibitor of AChE with association rate constants near the diffusion limit. The corresponding anti1 isomer, not formed by the enzyme, proved to be a respectable but weaker inhibitor. The crystal structures of the syn1- and anti1-mouse AChE complexes at 2.45- to 2.65-A resolution reveal not only substantial binding contributions from the triazole moieties, but also that binding of the syn1 isomer induces large and unprecedented enzyme conformational changes not observed in the anti1 complex nor predicted from structures of the apoenzyme and complexes with the precursor reactants. Hence, the freeze-frame reaction offers both a strategically original approach for drug discovery and a means for kinetically controlled capture, as a high-affinity complex between the enzyme and its self-created inhibitor, of a highly reactive minor abundance conformer of a fluctuating protein template. 相似文献
992.
BACKGROUND/AIMS: Alcohol drinking is responsible for a number of gastrointestinal diseases and cancers. Although heavy drinking episodes and chronic drinking are well linked to mechanisms of disease, moderate alcohol consumption and its effects are less well known. This review attempts to fill a gap in the literature surrounding moderate alcohol consumption. METHODS: A systematic review of the English literature using PubMed was used. RESULTS: A dose-response risk relationship exists between alcohol consumption and digestive disease risk. Acetaldehyde is the main factor in alcohol-related damage in moderate alcohol consumption and acts through numerous methods to exert damaging effects. CONCLUSION: Zero alcohol intake is recommended for lowest risk of alcohol-related digestive tract diseases and conditions. However, given the lowest overall mortality is associated with moderate drinking, moderate drinking with no bingeing episodes is recommended. 相似文献
993.
A total of 29 rheumatoid patients and 19 nonrheumatoid patients were tested for evidence of present or past infection by M pneumoniae, M hominis, M fermentans, M arthritidis, M pulmonis, and M hyorhinis. The techniques of lymphocye transformation, metabolic-inhibiting antibody test, and mycoplasmcidal antibody test indicated no significant difference in the response of rheumatoid as opposed to nonrheumatoid patients. 相似文献
994.
B. Joseph Elmunzer Rebecca L. Spitzer Lydia D. Foster Ambreen A. Merchant Eric F. Howard Vaishali A. Patel Mary K. West Emad Qayed Rosemary Nustas Ali Zakaria Marc S. Piper Jason R. Taylor Lujain Jaza Nauzer Forbes Millie Chau Luis F. Lara Georgios I. Papachristou Michael L. Volk Valerie Durkalski 《Clinical gastroenterology and hepatology》2021,19(7):1355-1365.e4
995.
996.
Genome rearrangements activate the Epstein-Barr virus gene whose product disrupts latency. 总被引:18,自引:2,他引:18
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C Rooney N Taylor J Countryman H Jenson J Kolman G Miller 《Proceedings of the National Academy of Sciences of the United States of America》1988,85(24):9801-9805
A defective Epstein-Barr virus (EBV) containing a deleted and rearranged genome (het DNA) causes latent EBV to replicate. This activity maps to the 2.7-kilobase-pair WZhet fragment. The BZLF1 open reading frame, present within WZhet as well as in the standard viral BamHI Z fragment, encodes the protein ZEBRA, which induces viral replication. Using gene transfers into Burkitt lymphoma cells, we now demonstrate that rearranged sequences juxtaposed to BZLF1 in het DNA facilitate expression of ZEBRA protein. Two stretches of EBV sequences within a palindromic region of het DNA contain positive regulatory elements. One set, derived from the viral large internal repeat, is newly positioned upstream of BZLF1; the second set is downstream of BZLF1 in het DNA. The capacity of defective HR-1 viruses to disrupt latency of the standard EBV genome is due to abnormal regulation of the BZLF1 gene as a result of genomic rearrangements. 相似文献
997.
H O Bushara B Y Majid A A Majid I Khitma A A Gameel E A Karib M F Hussein M G Taylor 《The American journal of tropical medicine and hygiene》1983,32(6):1370-1374
Studies in the White Nile area of the Sudan have shown that Zebu cattle acquire a high degree of resistance to Schistosoma bovis as a result of repeated natural exposures without, however, being able to eliminate their populations of adult schistosomes, although these do show greatly suppressed fecundity. To test whether these adult worms are necessary for the maintenance of resistance we cured six "naturally resistant" cattle (TC group) with a double treatment of 25 mg/kg praziquantel and compared their response to a 70,000 cercariae challenge with groups of "naturally resistant" but untreated cattle (UC group) and with previously unexposed, challenged cattle (CC group). Challenge was carried out 7 weeks after the second dose of praziquantel. The results confirmed that untreated cattle are "naturally resistant" and also showed that resistance was not abrogated by cure of the naturally-acquired infections. Thus, fecal egg counts after challenge reached mean maxima of 2,432 eggs per gram (epg) in the CC, but only 5 epg and 28 epg in the TC and UC groups, respectively. Similarly, mean worm counts were 85% and 69% lower in the TC and UC groups, respectively, and mean tissue egg densities were reduced by 72-99%, and 56-80%. Histopathologically, the TC and UC groups were also far less affected than the CC. Effective praziquantel treatment does therefore not destroy naturally acquired resistance to S. bovis, and may benefit infected livestock even in the absence of transmission control. The situation in human schistosomiasis is less clear, but there are several epidemiological and experimental indications of a similar conclusion for S. mansoni. 相似文献
998.
999.
Adhering to medication regimens has the potential to significantly improve clinical outcomes for persons with high blood pressure. A patient-related factor likely to affect adherence to treatment is the convenience of the prescribed drug regimen. The authors hypothesized that medication adherence would be superior and cost benefits would accrue in subjects who receive a once-daily, single-capsule, fixed-dose combination product for blood pressure control, compared with subjects who receive a similar regimen of separate components. A managed care organization that provides benefits for members enrolled in various health plans provided the data for this retrospective analysis. The database was used to assess medication adherence patterns for two groups of hypertensive subjects. Group 1 included subjects who had been prescribed the single-capsule, fixed-dose combination of amlodipine besylate/benazepril HCl. Group 2 comprised subjects who had been prescribed a regimen including an angiotensin-converting enzyme inhibitor and a dihydropyridine calcium channel blocker as separate drugs. Adherence was measured by the medication possession ratio, and medical resource utilization by the two groups was assessed during the study period. Group 1 (n=2754) and Group 2 (n=2978) were balanced with regard to age (mean, 53 years; range, 18-64 years) and sex (men, 50%; women, 50%). The overall medication possession ratio for Group 1 was significantly higher than that for Group 2 (80.8% vs. 73.8%; p<0.001). The average annual cost of cardiovascular-related care per subject was significantly lower in Group 1 compared with Group 2 (p<0.001). Subjects receiving the once-daily, single-capsule, fixed-dose combination of amlodipine/benazepril HCl demonstrated significantly better medication adherence and required fewer medical resources than did subjects receiving an angiotensin-converting enzyme inhibitor and a dihydropyridine calcium channel blocker as separate components. 相似文献
1000.
LDL and HDL became more fluid when health, free-living, premenopausal women were fed reduced fat diets with higher proportions of polyunsaturated fatty acids. Lipoproteins were isolated from plasma of 31 female subjects fed one of two sets of diets from typical U.S.A. foods with P/S ratios of 0.3 or 1.0. All subjects were fed high-fat diets (40% of energy) for the duration of four menstrual cycles followed by low-fat diets (20% of energy) for the next four cycles. Blood samples were collected during mid-follicular and mid-luteal phases of the fourth menstrual cycle of each diet period to assess interactive dietary and hormonal control of lipoprotein fluidity. LDL was significantly more fluid, as determined by DPH fluorescence, upon reducing fat consumption from 40 to 20% of energy for subjects eating foods with P/S = 1.0 or 0.3. Generally LDL was more fluid during the follicular phase than the luteal phase of the cycles, thus indicating hormonal influences on LDL fluidity. HDL results were similar but not as pronounced as with LDL. Lipoprotein phospholipid (PL) and cholesteryl ester (CE) fatty acyl compositions were also subject to dietary and hormonal influences. Effects were noted in several fatty acids depending upon diet and hormonal state; however, generally diet fat reduction resulted in reduced linoleate and increased oleate contents. Regression analyses showed that fluidity was more dependent upon the lipoprotein cholesterol content than upon fatty acyl composition. 相似文献