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91.
EE Brooks NS Gray A Joly SS Kerwar R Lum RL Mackman TC Norman J Rosete M Rowe SR Schow PG Schultz X Wang MM Wick D Shiffman 《Canadian Metallurgical Quarterly》1997,272(46):29207-29211
The activity of cyclin-dependent kinase 2 (CDK2) is essential for progression of cells from G1 to the S phase of the mammalian cell cycle. CVT-313 is a potent CDK2 inhibitor, which was identified from a purine analog library with an IC50 of 0.5 microM in vitro. Inhibition was competitive with respect to ATP (Ki = 95 nM), and selective CVT-313 had no effect on other, nonrelated ATP-dependent serine/threonine kinases. When added to CDK1 or CDK4, a 8.5- and 430-fold higher concentration of CVT-313 was required for half-maximal inhibition of the enzyme activity. In cells exposed to CVT-313, hyperphosphorylation of the retinoblastoma gene product was inhibited, and progression through the cell cycle was arrested at the G1/S boundary. The growth of mouse, rat, and human cells in culture was also inhibited by CVT-313 with the IC50 for growth arrest ranging from 1.25 to 20 microM. To evaluate the effects of CVT-313 in vivo, we tested this agent in a rat carotid artery model of restenosis. A brief intraluminal exposure of CVT-313 to a denuded rat carotid artery resulted in more than 80% inhibition of neointima formation. These observations suggest that CVT-313 is a promising candidate for evaluation in other disease models related to aberrant cell proliferation. 相似文献
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Improper assessment and treatment of asthma attacks have been identified as causes of increased morbidity and mortality: several pneumological societies have therefore created and published guidelines for facilitating decision making and for preventing unnecessary failures of therapy. The objective of this study was to examine emergency department compliance with such guidelines in our hospital, comparing the performance of pneumologists and other specialists. We reviewed the records of 117 patients treated for acute asthma attacks in 1994 (87 women and 30 men, mean age 46 years); 37 patients were treated by pneumologists and 80 by other specialists. The two physician groups differed significantly with respect to initial assessment of severity, particularly in the recording of vital signs (p < 0.05) and in the examination of some signs such as the use of accessory musculature (38% versus 10%, for pneumologists and other specialists, respectively) or the presence of cyanosis (81% versus 55%). Other factors associated with risk of death were noted only occasionally. Peak flow meters were used with only 5 patients, all examined by pneumologists; on the other hand, arterial blood samples for gasometric measurements were taken from 97%, although only 24% met the criteria stipulated in the guidelines. Treatment evaluated against the guidelines was incorrect in 24%, with no significant differences between pneumologists and other specialists. We conclude that: 1) the emergency clinical assessment and treatment of patients presenting with acute asthma attack is inadequate for a large proportion of patients, as the recommendations of consensual guidelines are habitually ignored, and 2) although there are differences in the management of these patients by pneumologists and other emergency room specialists, the former do not generally do a better job of following the guidelines. 相似文献
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Genetic variants of HCV may have different degrees of resistance to IFN and may therefore influence the outcome of IFN therapy. However, selection of HCV variants by IFN has not been investigated in detail. In this paper, heteroduplex analysis was used to monitor major changes of HCV populations in 4 chronically infected patients under IFN therapy. We found that a major variant of the HCV 5' non-coding region (5' NCR) emerged in a responder. In other patients although no new variant of the 5' NCR was identified, significant changes occurred within the core and E1 region of the HCV genome. Disappearance and emergence of HCV variants may reflect their different susceptibilities to IFN. Our results indicate that responses of HCV populations to IFN are complex and need to be characterized by analysis of multiple HCV genome regions. 相似文献
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