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1.
2.
K Sudo Y Matsumoto M Matsushima M Fujiwara K Konno K Shimotohno S Shigeta T Yokota 《Canadian Metallurgical Quarterly》1997,238(2):643-647
This study evaluated the inhibitory effects of thiazolidine derivatives on hepatitis C virus (HCV) protease and other human serine proteases. The inhibition efficacy was tested with a reversed-phase high-performance liquid chromatography (HPLC) assay system using a NS3-NS4A fusion protein as the HCV protease and a synthetic peptide substrate that mimics the NS5A-5B junction. Nine thiazolidine derivatives showed more than 50% inhibition at 50 microg/ml. The most potent derivative was RD4-6250, with 50% inhibition at a concentration of 2.3 microg/ml; this concentration was lower than those of other protease inhibitors reported previously. The most selective derivative was RD4-6205, with 50% inhibition at a concentration of 6.4 microg/ml, a lower concentration than those on other serine proteases (chymotrypsin, trypsin, plasmin, and elastase). These results suggest that the RD4-6205 skeleton is an important structure for inhibitory activity on the HCV protease NS3-NS4A. 相似文献
3.
Ganglioside GT1b and, to a lesser extent, GD3, enhanced phosphorylation of a 36 kDa protein (the substrate of protein kinase
C) in the particulate fraction from bovine mammary gland. Sialic acids, asialogangliosides, and GM3 were without effect, and
GD1a conversely inhibited phosphorylation of the 36 kDa protein. The enhanced phosphorylation by GT1b required the simultaneous
presence of phosphatidylserine (PS) and Ca2+. The 36 kDa protein reacted with anti-annexin I in Western blot analysis. Addition of purified annexin I to the reaction
mixture containing the particulate fraction increased the extent of phosphorylated 36 kDa protein, and the phosphorylation
was further enhanced by GT1b. The enhanced phosphorylation of annexin I by GT1b was also dependent on PS and Ca2+. When annexin I was phosphorylated by purified protein kinase C, GT1b inhibited the annexin I phosphorylation. Addition of
epidermal growth factor or insulin to the particulate fraction had little effect on the enhancement. These results suggest
that an enzyme or enzymes other than protein kinase C, epidermal growth factor receptor kinase, or insulin receptor kinase
is responsible for the GT1b- and GD3-enhanced phosphorylation of annexin I in the presence of PS and Ca2+. 相似文献
4.
T Nakagawa S Konno T Maemura K Goto Y Hayashibe T Yoshida 《Canadian Metallurgical Quarterly》1993,41(11):2245-2249
A 45-year-old woman with atrial septal defect and pulmonary hypertension was admitted for surgical repair. Cardiac catheterization data revealed pulmonary to systemic flow ratio (Qp/Qs) of 1.81, pulmonary artery pressure (PAP) of 82/30 mmHg and pulmonary vascular resistance (PVR) of 10.8 unit. Open lung biopsy was added to evaluate pulmonary vascular obstructive disease (PVOD) which was shown Heath-Edwards grade 3 PVOD. Following closure of the defect, PAP (systolic) exceeded momentarily systemic level after cardiopulmonary bypass. Prostaglandin E1 drip was remarkably effective to bring down PAP during early postoperative period. Although PAP has not been shown significant decrease on catheterization of one year after surgery, great symptomatic improvement has been achieved. 相似文献
5.
OBJECTIVE: To assess whether hypertension is a risk factor for hysterectomy performed for benign diseases. METHODS: Self-report questionnaires were collected from 77% of 2301 Danish women aged 30, 40, 50, or 60 years selected at random in 1982 for a prevalence study. Information about cardiovascular diseases, hypertension, use of medicine, weight and dieting history, life-styles, psychologic factors, gynecologic history (including history of hysterectomy), and social background were recorded. Weight, height, and blood pressure were measured. In an incidence study, the cohort was followed during 1982-1990 via central registers to assess the incidence of hysterectomy. Logistic and Cox regressions were used to analyze data. RESULTS: In the prevalence study, history of hypertension partly explained the relation between hysterectomy and cardiovascular diseases. In the incidence study, history of hypertension and use of diuretics were significant risk factors for hysterectomy. After confounder control, use of diuretics was explained by weight-related variables, and hypertension was a risk factor for hysterectomy in educated women (adjusted relative risk [RR] 2.88, 95% confidence interval [CI] 1.07, 7.76) and in women with weight fluctuations (adjusted RR 3.31, 95% CI 1.35, 8.14). Weight cycling and lack of education remained significant risk factors for hysterectomy in women with and without hypertension, respectively. CONCLUSION: History of hypertension, weight cycling, and lack of education are closely related risk factors for premenopausal hysterectomy. These three risk factors contribute to women undergoing hysterectomy having an increased risk for cardiovascular diseases. We proposed that hypertension might be a plausible biological cause of menorrhagia and an indication for hysterectomy. 相似文献
6.
An elastic half plane with an oblique edge crack is considered in this paper. A pair of concentrated forces or point dislocations is assumed to act at an arbitrary point in the half plane. The half plane with an edge crack is first mapped into a unit circle by a rational mapping function so that the following analysis can be carried out on the mapped plane analytically. Then the complex stress functions are derived by separating the whole problem into two parts; one is the principal part corresponding to the infinite plane acted on by concentrated forces or dislocations, the other is the holomorphic part, which can be determined by making use of the property of regularity of complex stress functions. The stress intensity factors of the crack can be calculated with different inclined angles of the crack, and the displacement and stress components at an arbitrary position in the half plane can be expressed explicitly. 相似文献
7.
8.
Masaaki Miyamoto Hiroyuki Koike Toshio Sada Yasuteru Ijima Junichiro Fukushige Norio Nakamura 《Lipids》1991,26(12):1316-1319
Platelet-activating factor (PAF) is a potent inflammatory mediator which is released by various inflammatory cells and produced
by certain tissues, including the kidney. PAF has been shown to increase glomerular permeability to protein and to decrease
glomerular filtration rate (GFR) by contracting mesangium. On the basis of these observations, it has been suspected that
PAF may play a role as mediator of glomerular damage in glomerular nephritis. To examine this possibility, we studied the
effects of a specific PAF antagonist, R-75,317, on the development of an experimental model of anti-glomerular basement membrane
(anti-GBM) glomerulonephritis. Glomerulonephritis was initiated by injecting rabbit anti-rat GBM serum into rats. Proteinuria
gradually developed after serum injection, plateaued at week 2, and remained at the high level of week 2 throughout the experimental
period (6 wk). Chronic treatment with R-75,317 (10 mg/kg/day i.p.) tended to delay the onset of proteinuria and significantly
accelerated the recovery phase. Creatinine clearance (Ccr) fell to 40% at week 3. R-75,317 treatment completely prevented
this decline of Ccr. Histological changes in this model (glomerular hypertrophy, proliferation of mesangial matrix and interstitial
fibrosis) were also ameliorated by the R-75,317 treatment. The results suggest that PAF may play a role in the development
of glomerulonephritis and that PAF antagonists could be used in the treatment of human renal disease.
Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl
Ether Lipids, May 1989. 相似文献
9.
10.
M Hachisu H Chen T Soneda K Fujishima T Ishizuka F Konno 《Canadian Metallurgical Quarterly》1995,21(4):145-151
Pentisomide, 2-(2-diisopropylaminoethyl)-4-methyl-2-(pyridyl)- pentanamide, is a novel antiarrhythmic agent structurally related to disopyramide. Using a glass bead arrhythmic model, the authors studied the antiarrhythmic effect of pentisomide in dogs by monitoring the plasma concentrations. When pentisomide was infused at 1 mg/kg/min for 20 min, the ventricular tachycardia was significantly reduced at 5 min after starting the infusion; the arrhythmias were reduced to less than 5% at the end of the 20 min infusion. The plasma-free concentration of pentisomide was about 3 micrograms/ml at 5 min; it increased to about 10 micrograms/ml at the end of 20 min infusion. With 0.3 mg/kg/min infusion, the arrhythmias were reduced to about 60% but were not significant at 20 min of infusion. The plasma-free concentration of pentisomide did not reach 3 micrograms/ml until 20 min of infusion. The 3 micrograms/ml plasma-free concentration for pentisomide seems to be a critical concentration in inducing a significant antiarrhythmic effect. Pentisomide dose-dependently inhibited ischaemia-reperfusion arrhythmia at doses of 30 microM and higher concentrations in vitro. In conclusion, pentisomide inhibits arrhythmias dependent with the plasma concentration or with the concentration of the external solution. The critical plasma-free concentration for inhibition of arrhythmias was 3 micrograms/ml (not equal to 10 microM) and the in vitro effect also had a similar concentration. Therefore, the in vivo and in vitro antiarrhythmic concentrations were well correlated. 相似文献