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用单克隆抗体纯化的60kd为亚基的牛脑钙调素依赖性环核苷酸磷酸二酯酶的动力学研究表明,二氢吡啶类钙拮抗剂Nicardipine和Felodipine是该酶的“部分”竞争性抑制剂。因为近饱和浓度的药物抑制该酶活性仅能达到某限定值,且Dixon作图法不呈直线关系。该酶被一定浓度Felo-dipine抑制时,增加Nicardipine浓度可逆转酶的抑制而达到Nicardipine的最大抑制水平,Nicardipine不影响典型的竞争性抑制剂甲基异丁基黄嘌呤对该酶的抑制作用,说明该酶活性中心以外存在和二氢吡啶结合的部位。 相似文献
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ME Bromfield TN Gibson B Hanchard N Waugh D McNaughton 《The West Indian medical journal》2014,63(2):134-137
Objective
To evaluate the trends in vulvar cancer between 1978 and 2007 in Kingston and St Andrew, Jamaica, with respect to age-standardized rates and histologic types.Methods
All cases of vulvar cancer recorded in the Jamaica Cancer Registry from 1978 to 2007 were extracted and analysed for age distribution and histologic type.Results
There were 78 cases (one person of unknown age) of vulvar cancer recorded over the 30-year period. Sixty per cent of the affected patients were between 50 and 80 years old. The most common histologic type of vulvar malignancy was squamous cell carcinoma (82%). There was a decline in age-standardized incidence rates of both vulvar cancers overall and vulvar squamous cell carcinoma over the 30-year period.Conclusion
Squamous cell carcinoma is the most common vulvar malignancy in the Jamaican population, and affects primarily older women. Despite high prevalence rates of high-risk human papillomavirus infection, no increase in the age-standardized incidence of vulvar squamous cell carcinoma was identified. 相似文献67.
H Schleifer B Doleschal M Lichtenegger R Oppenrieder I Derler I Frischauf TN Glasnov CO Kappe C Romanin K Groschner 《British journal of pharmacology》2012,167(8):1712-1722
Background and purpose
Pyrazole derivatives have recently been suggested as selective blockers of transient receptor potential cation (TRPC) channels but their ability to distinguish between the TRPC and Orai pore complexes is ill-defined. This study was designed to characterize a series of pyrazole derivatives in terms of TRPC/Orai selectivity and to delineate consequences of selective suppression of these pathways for mast cell activation.Experimental approach
Pyrazoles were generated by microwave-assisted synthesis and tested for effects on Ca2+ entry by Fura-2 imaging and membrane currents by patch-clamp recording. Experiments were performed in HEK293 cells overexpressing TRPC3 and in RBL-2H3 mast cells, which express classical store-operated Ca2+ entry mediated by Orai channels. The consequences of inhibitory effects on Ca2+ signalling in RBL-2H3 cells were investigated at the level of both degranulation and nuclear factor of activated T-cells activation.Key Results
Pyr3, a previously suggested selective inhibitor of TRPC3, inhibited Orai1- and TRPC3-mediated Ca2+ entry and currents as well as mast cell activation with similar potency. By contrast, Pyr6 exhibited a 37-fold higher potency to inhibit Orai1-mediated Ca2+ entry as compared with TRPC3-mediated Ca2+ entry and potently suppressed mast cell activation. The novel pyrazole Pyr10 displayed substantial selectivity for TRPC3-mediated responses (18-fold) and the selective block of TRPC3 channels by Pyr10 barely affected mast cell activation.Conclusions and Implications
The pyrazole derivatives Pyr6 and Pyr10 are able to distinguish between TRPC and Orai-mediated Ca2+ entry and may serve as useful tools for the analysis of cellular functions of the underlying Ca2+ channels. 相似文献68.
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Autosomal dominant cerulean cataract is associated with a chain termination mutation in the human beta-crystallin gene CRYBB2 总被引:14,自引:2,他引:14
Litt M; Carrero-Valenzuela R; LaMorticella DM; Schultz DW; Mitchell TN; Kramer P; Maumenee IH 《Human molecular genetics》1997,6(5):665-668
Congenital cataracts are a common major abnormality of the eye that
frequently cause blindness in infants. At least a third of all cases are
familial; autosomal dominant congenital cataract (ADCC) appears to be the
most common familial form in the Western world. Cerulean cataracts have
peripheral bluish and white opacifications in concentric layers with
occasional central lesions arranged radially. Although the opacities may be
observed during fetal development and childhood, usually visual acuity is
only mildly reduced until adulthood, when lens extraction is generally
necessary. We have been studying a family (ADCC- 1) with cerulean blue
ADCC, in which the affected daughter of a first cousin mating was presumed
to be homozygous for the cataract gene. Recently, we mapped an ADCC gene in
this family to a region of chromosome 22 containing three beta-crystallin
genes. Here we report that a chain-termination mutation in CRYBB2 is
associated with ADCC in this family.
相似文献