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Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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Mycosis fungoides (MF) is the most common cutaneous T-cell lymphoma. We report a case in which identical T-cell clones were identified in both patch and tumour stage lesions and in which the tumorous deposits, containing CD30-positive cells, repressed spontaneously. We discuss the differential diagnosis of the tumorous lesions and the spectrum of GD30-positive proliferative T-cell disorders. 相似文献
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A significant minority of medical and dental students fail their undergraduate courses. Early warning systems (EWSs) have been developed in some areas of higher education to predict 'at-risk' students at an early remedial stage. An attempt is made to develop an EWS to predict failure in the bacteriology component of the Batchelor of Dental Surgery course at Manchester Dental School. A system based on class tests and previous end-of-year performance is derived which is used to predict those students likely to fail or fall in the bottom 20-25% in their finals examination. The predictors are combined by a simple equal weights method, which is found to have the same predictive power as using multiple regression. Failure was correctly predicted in 60% of cases, at the expense of 71% false alarms. The high number of false alarms reflects the low failure rate rather than the lack of predictive information. The need for effective cross-validation of EWSs is discussed; many previous studies have not been tested on independent data. 相似文献
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BARBARA A. LEGGETT RUSSELL J. COLLINS W. GRAHAM E. COOKSLEY ROGER L. PRENTICE LAWRIE W. POWELL 《Journal of gastroenterology and hepatology》1987,2(3):205-211
The aim of this study was to determine if the Crithidia luciliae assay for auto-antibodies to double-stranded DNA, often positive in systemic lupus erythematosus, is always negative in auto-immune chronic active hepatitis (CAH) as has recently been suggested. Twenty-five patients were identified as having auto-immune CAH. Mean duration of follow-up was 10.5 years. Antinuclear antibodies were detected in 92%, smooth muscle antibodies in 76% and antimitochondrial antibodies in 16%. Antibodies to double-stranded DNA were detected by the Crithidia assay in four patients (16%). Two of these patients had positive tests on only one occasion and no features of systemic lupus erythematosus. In the other two the assay was persistently positive. During follow-up both developed arthritis and serositis but the liver lesion remained the dominant clinical feature. It was concluded that there is significant serological overlap between auto-immune CAH and systemic lupus erythematosus making the Crithidia assay unreliable in distinguishing between them. 相似文献
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SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a). 相似文献