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排序方式: 共有10000条查询结果,搜索用时 31 毫秒
91.
Patrick P. A. Humphrey Gary Buell Ian Kennedy Baljit S. Khakh Anton D. Michel Annmarie Surprenant Derek J. Trezise 《Naunyn-Schmiedeberg's archives of pharmacology》1995,352(6):585-596
Significant advances in understanding of P2X purinoceptor pharmacology have been made in the last few years. The limitations of nucleotide agonists as drug tools have now been amply demonstrated. Fortunately, inhibitors of the degrading ecto-ATPase enzymes are becoming available and it has become apparent that the complete removal of all divalent cations can be used experimentally in some systems to prevent nucleotide breakdown. Despite these issues, convincing evidence for P2X receptor heterogeneity, from data with agonists, has recently been reported.A number of new antagonists at P2X purinoceptors have also recently been described which to some degree appear to be more specific and useful than earlier antagonists like suramin. It is now apparent that suramin is a poor antagonist of ATP in many tissues because it potently inhibits ATPase activity at similar concentrations to those at which it blocks the P2X purinoceptor.Advances in the use of radiolabelled nucleotides as radioligands for binding studies has allowed the demonstration of P2X purinoceptors in a variety of tissues throughout the body including the brain. These studies have also provided evidence for receptor heterogeneity. Excitingly, two P2X purinoceptor genes have been cloned but operational studies suggest that more than two types exist. The cloning studies have also demonstrated a unique structure for the P2X purinoceptor which differentiates it from all other ligand-gated ion channel receptors. Further studies on P2X purinoceptor operation and structure are needed to help resolve controversies alluded to regarding the characterization and classification of nucleotide receptors. Hopefully such studies will also lead to a better understanding of the physiological and pathological importance of ATP and its activation of P2X purinoceptors. This will require the identification of better drug tools, in particular antagonists which may also provide the basis for novel therapeutic agents. 相似文献
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In Vivo Induction of Virulence and Antibiotic Resistance Transfer in Enterococcus faecalis Mediated by the Sex Pheromone-Sensing System of pCF10 总被引:1,自引:0,他引:1
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Enterococcus faecalis has become one of the most notable nosocomial pathogens in the last decade. Aggregation substance (AS) on the sex pheromone plasmids of E. faecalis has been implicated as a virulence factor in several model systems. We investigated the AS-encoding plasmid pCF10 for its ability to increase virulence in a rabbit endocarditis model. Cells containing pCF10 increased the virulence in the model significantly, as assessed by an increase in aortic valve vegetation size. The results confirmed in vivo induction of the normally tightly controlled AS. In addition to the expression of AS when E. faecalis cells were in contact with plasma, plasmid transfer of the tetracycline resistance-carrying plasmid was also activated in vitro and in vivo. In vivo, plasmid transfer reached remarkable frequencies of 8 x 10(-2) to 9 x 10(-2). These values are comparable to the highest frequencies ever observed in vitro. Cells harboring pCF10 had a significant survival advantage over plasmid-free cells indicated by pCF10 present in two-thirds of the recipient population. Plasma induction was dependent on the presence of the plasmid-encoded PrgZ protein, indicating the requirement of the pheromone-sensing system in the induction process. The data suggested that the mechanism of in vivo induction may involve interference of plasma with the normal function of the pheromone peptide and its inhibitor. 相似文献
95.
Cardia: study design, recruitment, and some characteristics of the examined subjects 总被引:28,自引:0,他引:28
Gary D. Friedman Gary R. Cutter Richard P. Donahue Glenn H. Hughes Stephen B. Hulley David R. Jacobs Jr. Kiang Liu Peter J. Savage 《Journal of clinical epidemiology》1988,41(11):1105-1116
In 1984, a prospective cohort study, Coronary Artery Risk Development in Young Adults (CARDIA) was initiated to investigate life-style and other factors that influence, favorably and unfavorably, the evolution of coronary heart disease risk factors during young adulthood. After a year of planning and protocol development, 5,116 black and white women and men, age 18-30 years, were recruited and examined in four urban areas: Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota, and Oakland, California. The initial examination included carefully standardized measurements of major risk factors as well as assessments of psychosocial, dietary, and exercise-related characteristics that might influence them, or that might be independent risk factors. This report presents the recruitment and examination methods as well as the mean levels of blood pressure, total plasma cholesterol, height, weight and body mass index, and the prevalence of cigarette smoking by age, sex, race and educational level. Compared to recent national samples, smoking is less prevalent in CARDIA participants, and weight tends to be greater. Cholesterol levels are representative and somewhat lower blood pressures in CARDIA are probably, at least in part, due to differences in measurement methods. Especially noteworthy among several differences in risk factor levels by demographic subgroup, were a higher body mass index among black than white women and much higher prevalence of cigarette smoking among persons with no more than a high school education than among those with more education. 相似文献
96.
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A restricted field of view (rFOV) approach for imaging a dynamic time series of volumes of limited spatial extent within a larger subject is described. The shorter readout with rFOV-MRI can be exploited to either limit image artifacts or increase spatial resolution. To accomplish rFOV imaging of a multislice volume for a dynamic series, an outer volume suppression (OVS) preparation that saturates signal external to a cylinder through the subject is followed by slice-selective excitation and a spiral readout. The pass- and stopband efficiencies of the OVS in an agar gel phantom were 97% (+/-1.5%) and 3% (+/-1%), respectively. Profiles of the temporal signal-to-noise ratio (SNR) were measured in a phantom and an adult brain. The rFOV sequence reduced distortions from off-resonance signal and T2*-induced blurring compared to a conventional sequence. Sequence utility is demonstrated for high-resolution rFOV functional MRI (fMRI) in the visual cortex. The rFOV sequence may prove to be useful for other multislice dynamic and high-resolution imaging applications. 相似文献
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99.
The present study investigated the specific ways by which cytotoxicity due to glutamate receptor stimulation could be attenuated by the administration of agonists and antagonists of the ionotropic and metabotropic glutamate receptors within the nucleus basalis magnocellularis (NBM) of rats as measured by cortical choline acetyltransferase activity. The results of these studies suggest that (1) the cytotoxicity of ibotenate to NBM cholinergic cells is not dependent upon stimulation of metabotropic glutamate receptors, but results from activation of
(NMDA) receptors, (2) the cytotoxicity of quisqualate to cholinergic cells within the NBM is not dependent upon stimulation of NMDA or metabotropic receptors, and (3) the cytotoxicity of NMDA was prevented by administration (i.p.) of the un-competitive NMDA antagonist memantine (30 mg/kg), resulting in plasma levels of 2.5 μg/ml, a concentration known to block efficiently NMDA receptors in vitro. Finally, performance of a food-motivated, delayed-alternation task on a T-maze was impaired by injections of NMDA into the NBM, but was prevented by co-administration of NMDA with memantine. 相似文献
100.
Jeffrey R. Rubin MD Enrique Labadie MD Gary Anderson BS James Persky MD Jerry Goldstone MD 《Annals of vascular surgery》1988,2(2):127-132
This study evaluates the effect of blood volume and hematocrit changes on brain tissue during temporary global ischemia. Normal saline was administered intravenously to 55 gerbils to achieve hypo-, normo-, and hypervolemic hemodilution and uniform 30% hematocrit reduction. Each group had unilateral carotid artery ligation and temporary (20 minute) contralateral carotid occlusion. After ten days or death, brains were harvested, preserved in formalin, sectioned in a manner which provided adequate samples of both cortex and hippocampus, and stained with H&E and luxol fast blue. They were then examined and staged microscopically for white and gray matter infarction, edema, and neuronal injury and loss. Histologic studies were performed in a randomized and blinded manner and were classified by one of four categories: normal, minimal, moderate, and severe changes. Three of ten (30%) controls survived ten days but had severe neuronal loss, minimal cerebral edema and a minimal to moderate number of white matter strokes. Survival was best in animals treated with hypovolemic hemodilution (43%). Other rates were: normovolemic (33%), controls (30%), and hypervolemic (8.3%). The degree of brain tissue damage was markedly less in the normovolemic group. In this model, normovolemic hemodilution followed by hypovolemic hemodilution offered the best overall cerebral protection during global ischemia. 相似文献