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1.
Angiotensin II receptor type 1 mRNA is upregulated in atria of patients with end-stage heart failure
RR Kaprielian E Dupont S Hafizi PA Poole-Wilson A Khaghani MH Yacoub NJ Severs 《Canadian Metallurgical Quarterly》1997,29(8):2299-2304
There is increasing evidence that pathological changes in the myocardium during chronic heart failure (CHF) are partly regulated through the activation of the renin-angiotensin system (RAS), an effect mediated by the angiotensin II type 1 receptor (AT1R). We examined the expression of cardiac AT1R mRNA in normal (atria, n=7; ventricle, n=3) and end-stage CHF human hearts (atria, n=8; ventricle, n=14). Tissue was snap-frozen immediately after explantation during orthotopic cardiac transplantation; control specimens were obtained from healthy donor hearts rejected for technical reasons. Northern blots of purified total mRNA from each tissue were hybridized with a random primed radiolabeled probe for the coding sequence of AT1R. Stringent conditions were used for both hybridization (5X SSC, 65 degrees C) and washing (0.5X SSC, 0.1% SDS, 65 degrees C) of the membrane. Left and right atrial tissue showed low levels of AT1R mRNA expression in the controls, with statistically significant upregulation of expression in tissue from pathological hearts; CHF atria 1.28+/-0.86 optical density (OD) units, control atria 0.56+/-0.31 OD units, P=0.05 (mean+/-s.d.). There were undetectable levels in ventricles from either control (2/2) or dilated hearts (7/7). The results were independent of the etiology of the heart failure and suggest that increased levels of atrial AT1R mRNA may occur in response to elevated atrial pressures in heart failure. 相似文献
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The aim of this study was to gauge the effect of an artificially established flora, unnatural for mice, on the induction of oral candidosis in mice. Four groups of BALB/c mice were compared; conventional Candida albicans-free mice, "germ-free" mice which had been inoculated with Candida-free human saliva, germ-free mice which had been exposed to a cocktail of Streptococcus mitis, S. sobrinus and S. sanguis, and uncontaminated germ-free mice. After exposure to C. albicans via drinking water, the four groups of mice were killed and their oral cavities examined for candidal growth and oral lesions. Conventional mice yielded significantly less candidal growth and exhibited significantly fewer oral lesions than the other three groups. Candidal lesions in the two groups of contaminated germ-free mice were significantly fewer than in the uncontaminated germ-free mice. The latter exhibited extensive candidal lesions with little inflammatory infiltrate. It is concluded that mice with human oral micro-organisms have some resistance against candidal infection albeit at a reduced level, that mice with natural oral flora are highly resistant, and that germ-free mice are extremely susceptible to C. albicans infection. 相似文献
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AIM: The study of clinical running of gastric or duodenal ulcer in associated coronary heart disease (CHD). MATERIALS AND METHODS: 209 CHD patients with gastric ulcer (GU) or duodenal ulcer (DU) were examined clinically plus histological examination of gastric or duodenal mucosa biopsies was made. RESULTS: In CHD patients GU occurred more frequently (56%) than DU. The lesions involved more frequently lesser curvature of the stomach and pyloric part of the stomach. Males developed ulcers 3.5 times more frequently than females. Ulcers tended to a painless course without season exacerbations. The disease manifested first with gastric bleeding in 52% of the patients. GU and DU ran with frequent recurrences and long-term exacerbations (76% of patients) which coincided in time with CHD exacerbations. 68% of patients developed exacerbations within 10 days after myocardial infarction or aortocoronary bypass operation. Helicobacter pylori was present as a resolving factor in arising ulcer in 26% of patients. Microcirculatory disorders, reduced blood flow speed in gastric or duodenal mucosa, hypocoagulation syndrome, dyslipidemia provoked exacerbations in 62% of patients. Examinations of biopsies from gastric and duodenal mucosa showed marked dystrophic changes in the mucosa, its connective tissue basis in the vessels in the presence of mild inflammation at ulcer site. CONCLUSION: The onset of ulcers and erosions in the mucosa of the gastrointestinal tract in CHD may be due to circulatory disorders in gastric mucosa. The main factors of aggression are hypoxia, hypoxia-induced trophic defects in gastric and duodenal mucosa, circulatory disorders. 相似文献
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Complex traits are generally taken to be under the influence of multiple genes, which may interact with each other to confer susceptibility to disease. Statistical methods in current use for localizing such genes essentially work under single-gene models, either implicitly or explicitly. In genomic screens for complex disease genes, some of the marker loci must be in tight linkage with disease susceptibility genes. We developed a general multi-locus approach to identify sets of such marker loci. Our approach focuses on affected sib pair data and employs a nonparametric pattern recognition technique using artificial neural networks. This technique analyzes all markers simultaneously in order to detect patterns of locus interactions. When applied to previously published sib pair data on type I diabetes, our approach finds the same genes as in the published report in addition to some new loci. For a specific two-locus model of inheritance, the power of our approach is higher than that of the currently used analysis standard. 相似文献
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