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991.
SR Presnell GS Patil C Mura KM Jude JM Conley JA Bertrand CM Kam JC Powers LD Williams 《Canadian Metallurgical Quarterly》1998,37(48):17068-17081
Novel aryl derivatives of benzamidine were synthesized and tested for their inhibitory potency against bovine trypsin, rat skin tryptase, human recombinant granzyme A, human thrombin, and human plasma kallikrein. All compounds show competitive inhibition against these proteases with Ki values in the micromolar range. X-ray structures were determined to 1.8 A resolution for trypsin complexed with two of the para-substituted benzamidine derivatives, 1-(4-amidinophenyl)-3-(4-chlorophenyl)urea (ACPU) and 1-(4-amidinophenyl)-3-(4-phenoxyphenyl)urea (APPU). Although the inhibitors do not engage in direct and specific interactions outside the S1 pocket, they do form intimate indirect contacts with the active site of trypsin. The inhibitors are linked to the enzyme by a sulfate ion that forms an intricate network of three-centered hydrogen bonds. Comparison of these structures with other serine protease structures with noncovalently bound oxyanions reveals a pair of highly conserved oxyanion-binding sites in the active site. The positions of noncovalently bound oxyanions, such as the oxygen atoms of sulfate, are distinct from the positions of covalent oxyanions of tetrahedral intermediates. Noncovalent oxyanion positions are outside the "oxyanion hole." Kinetics data suggest that protonation stabilizes the ternary inhibitor/oxyanion/protease complex. In sum, both cations and anions can mediate Ki. Cation mediation of potency of competitive inhibitors of serine proteases was previously reported by Stroud and co-workers [Katz, B. A., Clark, J. M., Finer-Moore, J. S., Jenkins, T. E., Johnson, C. R., Ross, M. J., Luong, C., Moore, W. R., and Stroud, R. M. (1998) Nature 391, 608-612]. 相似文献
992.
In potassium-free solutions some types of K channels enter a long-lasting nonconducting or "defunct" state. It is known that Shaker K channels must open in K+-free solutions to become defunct. Gating current studies presented here indicate an abnormal conformation in the defunct state that restricts S4 movement and alters its kinetics. Thus an abnormality initiated in the P region spreads to the gating apparatus. We find that channels most readily become defunct on repolarization to an intermediate voltage, thus prolonging occupancy of one of the several intermediate closed states. The state dependence of becoming defunct was further dissected by using the gating mutant L382A. Simply closing this channel at 0 mV (reversing the last activation step) does not make the mutant channel defunct. Instead, it is necessary to move further left (more fully closed) in the activation sequence. This was confirmed with ShIR experiments showing that channels become defunct only if there is inward gating charge movement. Rapid transit through the intermediate states, achieved at very negative voltage, is relatively ineffective at making channels defunct. Several mutations that removed C-type inactivation also made the channels resistant to becoming defunct. Our results show that normal gating current cannot be stably recorded in the absence of K+. 相似文献
993.
DE Yount TD Kunkle JS D'Arrigo FW Ingle CM Yeung EL Beckman 《Canadian Metallurgical Quarterly》1977,48(3):185-189
Gas bubbles are the primary agent in producing the pathogenic effects of decompression sickness. Numerous experiments indicate that bubbles originate in water, and probably also in man, as pre-existing gas nuclei. This is surprising considering that gas phases larger than 1 micron should rise to the surface of a standing liquid, whereas smaller ones should dissolve rapidly due to surface tension. Several stabilizing mechanisms have been suggested, and each has been refuted on experimental grounds. In this article, we propose a new model that arises out of a systematic study of the earlier theories. We review these theories and conclude that gas cavitation nuclei must be held intact by surface-active skins that are initially permeable. The first quantitative analysis of bubble formation data from supersaturated gelatin is summarized and leads to the further conclusion that skins can become impermeable if the ambient pressure is increased rapidly by a sufficient amount. Our model owes much to Sirotyuk, who "demonstrated experimentally that stabilization of gas bubbles acting as cavitation nuclei in water is always attributable to the presence of surface-active substances in the water". 相似文献
994.
The effects of oxidation at 1400°C for 100 h on both surface and internal composition of commercial and laboratory hot-pressed Si3 N4 with MgO or ZrO2 additives as well as chemically vapor deposited (CVD) Si3 N4 were studied using X-ray diffraction. Samples were also compared to the same temperature treatments in Ar. The results indicate the grain boundaries act as rapid diffusion paths for the transport of oxygen. 相似文献
995.
CM Owczarek MJ Layton LG Robb NA Nicola CG Begley 《Canadian Metallurgical Quarterly》1996,271(10):5495-5504
996.
MF Weiner RC Risser CM Cullum L Honig C White S Speciale RN Rosenberg 《Canadian Metallurgical Quarterly》1996,153(10):1269-1273
OBJECTIVE: The authors compared clinical findings of Alzheimer's disease and the so-called Lewy body variant of Alzheimer's disease. METHOD: Available data were analyzed on the clinical features of 58 patients with Alzheimer's disease and 24 patients with the Lewy body variant of Alzheimer's disease who underwent postmortem examination. RESULTS: The proportion of men was significantly larger in the Lewy body variant group than in the Alzheimer's disease group (66.7% versus 34.5%), and, concordantly, the Lewy body variant group was slightly taller. The prevalence of hallucinations and delusions was significantly higher in Lewy body variant subjects than the Alzheimer's disease subjects, but there were no significant differences between the two groups in educational attainment, family history of dementia, age at onset, duration of illness, cognitive impairment, overall severity of illness, or neuropsychological findings. Patients with the Lewy body variant of Alzheimer's disease tended to experience more frequent extrapyramidal side effects of neuroleptics than did the patients with Alzheimer's disease, but for patients in the two groups who were not exposed to neuroleptics, there was little difference in frequency of extrapyramidal side effects. CSF concentration of homovanillic acid (HVA) was significantly lower in the Lewy body variant patients, even when correction was made for height. CONCLUSIONS: The Lewy body variant of Alzheimer's disease may be suspected in elderly male dementia patients who otherwise meet criteria for Alzheimer's disease but who manifest significant psychiatric symptoms and neuroleptic-induced extrapy-ramidal side effects and have low levels of CSF HVA. 相似文献
997.
CM Juliani 《Canadian Metallurgical Quarterly》1995,29(3):267-285
The study present analyse the process to buy and distribution of medicaments for the Basic Unit of Health in municipal district of state S?o Paulo. To achieve some general considerations about the National Politic of Medicaments in Brazil, to emphasize feature relative the its structuration in the Unique System of Health. 相似文献
998.
999.
1000.
Cutaneous electrogastrography (EGG) allows the measurement of gastric electrical activity. An association of EGG with gastrointestinal motility disorders has been shown. Abnormalities of electrical rate or rhythm are accepted as the most important parameters in EGG. However, the reliability of the magnitude of electrical amplitude in the assessment of motility is discussed controversially. Therefore in a prospective study we investigated the relation between amplitude and antral contractions by means of ultrasonography. 8 healthy volunteers (4 men, 4 women, 24-31 years) ingested 400 ml carbonated mineral water after an overnight fast at two separate study days. Over a period of 10 min preprandial and 10 min postprandial small and intense antral contractions were measured employing sagittal antral planimetry. Simultaneous amplitudes were determined during contractions and at 1 min intervals (average amplitude) by cutaneous electrogastrography. Data were analyzed by Wilcoxon's rank sum test and Spearman rank correlation test. The coefficient of variation of the postprandial/preprandial amplitude ratio was nearly two times greater between subjects than between recordings in the same subject, which reflects a moderate intraindividual reproducibility. We found a significant increase in the average amplitude postprandially (p < 0.05). Although postprandial contractions (n = 243) predominated preprandial contractions (n = 127) significantly (p = 0.02), no significant correlation between the number of contractions and the average amplitude existed (R = 0.1; p = 0.7). Moreover the average amplitude did not differ from amplitudes during intense and small contractions significantly (p = 0.7; p = 0.1). The magnitude of the amplitude measured by EGG does not correlate with the mechanical gastral activity significantly.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献