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51.
52.
Targeted disruption of the plasma membrane is a ubiquitous form of attack used in all three domains of life. Many bacteria secrete pore-forming proteins during infection with broad implications for pathogenesis. The cholesterol-dependent cytolysins (CDC) are a family of pore-forming toxins expressed predominately by Gram-positive bacterial pathogens. The structure and assembly of some of these oligomeric toxins on the host membrane have been described, but how the targeted cell responds to intoxication by the CDCs is not as clearly understood. Many CDCs induce lysis of their target cell and can activate apoptotic cascades to promote cell death. However, the extent to which intoxication causes cell death is both CDC- and host cell-dependent, and at lower concentrations of toxin, survival of intoxicated host cells is well documented. Additionally, the effect of CDCs can be seen beyond the plasma membrane, and it is becoming increasingly clear that these toxins are potent regulators of signaling and immunity, beyond their role in intoxication. In this review, we discuss the cellular response to CDC intoxication with emphasis on the effects of pore formation on the host cell plasma membrane and subcellular organelles and whether subsequent cellular responses contribute to the survival of the affected cell. 相似文献
53.
12(S)-Lipoxygenase (LOX) is regarded as a pro-tumorigenic enzyme and as a potential target for therapy and prevention of cancer so that the search for specific 12(S)-LOX inhibitors is part of drug development strategies. To facilitate the identification of specific 12(S)-LOX inhibitors we have created an assay cell line by introducing a12(S)-LOX expression vector into SW480 colorectal cancer cells. When arachidonic acid was supplied in the medium both transiently and stably overexpressing cells produced 12(S)-hydroxytetraenic acid (HETE) originating from the transfected gene at 4-5-fold the amount obtained from control transfectants. 12(S)-HETE production was 1913.7+/-17.2pg/ml and reached a steady state level 24h after addition of arachidonic acid. To demonstrate the models suitability of 12(S)-LOX overexpressing SW480 cells they were used to measure the inhibitory activity of the plant phenols baicalein, kaempferol, quercetin, nordihydroguaretic acid and resveratrol which are known for their chemopreventive as well as LOX-inhibitory activity in different tumour models. All 5 compounds inhibited 12(S)-HETE production at concentrations below those necessary for growth inhibition. 相似文献
54.
Smoking remains the leading cause of preventable disease in the United States. Exposure to tobacco smoke leads to cancer, heart and lung disease, and addiction. The origin of the tobacco and cigarette manufacturing practices of counterfeit cigarettes are unknown. Because toxic metals are incorporated into the tobacco lamina during cultivation, the ambient metal content of the soil could produce significant differences in metal levels in both the tobacco and smoke of counterfeit cigarettes. We compared mainstream smoke cadmium, thallium, and lead deliveries from counterfeit and authentic brands. Mainstream smoke levels of all three metals were far greater for counterfeit than the authentic brands, in some cases by an order of magnitude. Significant differences still existed even after normalizing mainstream smoke metal levels with nicotine delivery; the counterfeits typically delivered much higher levels of all three analytes. Our findings, based on 21 different counterfeit samples, suggest that counterfeit cigarettes potentially result in a markedly greater exposure to toxic heavy metals than authentic brands, even after correcting for differences in nicotine intake. In view of the unknown health risks associated with inhaling higher levels of toxic metals, it is prudent to minimize exposure to toxic substances whenever possible. 相似文献
55.
成都市市区级疾控工作人员心理健康与工作满意度及其相关性调查 总被引:1,自引:0,他引:1
[目的]了解疾病预防控制工作人员心理健康与工作满意度的状况,以及心理健康与工作满意度的相关性。[方法]2005年10~12月,采用精神症状自评量表(SCL-90)和自行设计的工作满意度调查表,对成都市及所辖5个区疾病预防控制中心的530名工作人员进行调查。[结果]调查498人,有心理问题者占13.25%。有心理问题组工作满意度得分均高于心理健康组(P〈0.01);心理健康各因子与工作满意度各因子得分均呈正相关关系(r=0.149~0.332,P〈0.01);对心理健康各因子都有影响的工作满意度因子是人际关系、个人发展、单位管理。[结论]心理健康与工作满意度密切相关,提高工作人员的工作满意度有利于提高其心理健康水平。 相似文献
56.
目的:研究CDC6、CDK1在宫颈癌组织中的表达及其与HPV16/18感染的相关性,以探讨宫颈癌的发生机制,进一步寻找宫颈癌诊断的新的分子标志物。方法:采用免疫组织化学方法对50例宫颈癌石蜡标本、宫颈上皮内瘤样病变CINI20例、CINⅡ-Ⅲ20例、正常宫颈组织20例进行CDC6、CDK1的检测,同时采用PCR技术检测HPV16/18感染情况。结果:在宫颈癌组织中CDC6、CDK1的阳性率高于CIN和正常宫颈组织,差异有显著性(均P〈0.05),且CDC6、CDKl阳性表达率与病理分级有关,差异有显著性(均P〈0.05),CDC6阳性表达率均与淋巴结转移有关(P〈0.05);CDK1阳性表达率均与淋巴结转移无关(P〉0.05);在宫颈癌组织中CDC6和CDK1的阳性表达率与年龄、临床分期无关(均P〉0.05)。HPV16/18在正常宫颈组织、CIN和宫颈癌中的阳性率逐渐升高,差异有显著性(P〈0.05),但与临床分期、病理分级、淋巴转移、年龄无关(均P〉0.05)。CDK1和CDC6的表达有正相关性(L=0.529,P〈0.05);CDC6与HPV16/18感染有关(r=0.386,P〈0.05);CDK1与HPV16/18感染无关(rs=0.145,P〉0.05)。结论:宫颈上皮内瘤样病变及宫颈癌组织中CDC6表达的改变可能与HPV16/18感染有关,且互相作用,共同影响CIN的发展及宫颈癌的发生。这些指标综合分析可能为阐明HPV16/18的恶性转化机制以及为提高宫颈癌及其癌前病变诊断率提供参考依据。CDC6、CDK1的异常表达与宫颈癌的恶变程度有关,可作为宫颈癌筛查、预后判断的有用指标。 相似文献
57.
目的:检测及讨论CDC 25A和CDC 25B基因在宫颈癌中的表达水平及其临床意义。分析CDC 25A和CDC 25B基因剪切变异分子CDC 25A1—2、CDC 2581—4在宫颈组织中的表达分布规律。方法:采用RT—PCR和Western印迹法检测61例宫颈癌组织、18例宫颈良性病变组织中CDC 25的表达情况,并分析CDC 25的表达水平与宫颈癌临床病理参数之间的关系。结果:CDC 25A和CDC 25B基因在宫颈癌组织和宫颈良性病变组织中的表达差异有统计学意义(P〈0.05);CDC 25的各剪切变异分子表达在宫颈癌患者不同年龄、癌组织病理类型、临床分期及癌细胞分化程度间差异有统计学意义(P〈0.05),而与宫颈癌的淋巴结转移无关(P〉0.05)。结论:宫颈癌组织中存在CDC 25A和B的高表达,CDC 25分子及其剪切变异体的表达异常可能是宫颈癌发生、发展的重要细胞内调控机制之一。 相似文献
58.
Veggi LM Crocenzi FA Roma MG Dawson PA Pellegrino JM Sánchez Pozzi EJ Mottino AD 《Biochemical pharmacology》2002,63(8):1553-1563
To evaluate the effect of dapsone (4,4'-diaminodiphenylsulfone, DDS) on biliary bile salt secretion, we administered the drug to male and female Wistar rats at a dose of 30 mg/kg body wt, twice a day, for 4 days. DDS decreased basal bile flow by about 20% in both male and female rats. In addition, basal biliary bile salt secretion was decreased by the drug in animals from both sexes (about 30% decrease). Bile salt maximum secretory rate, as evaluated by infusing tauroursodeoxycholate at stepwise-increasing rates, was not affected by DDS in either male or female rats, suggesting that the density of canalicular bile salt transporters is preserved. The size of the bile salt pool and the rate of de novo synthesis of bile salts, measured in bile salt-depleted animals, were decreased by about 33 and 35%, respectively; there was no difference in response between males and females. The ability of the ileum to reabsorb bile salts, as estimated by analysis of the expression of the ileal apical sodium-dependent bile salt transporter and of sodium taurocholate transport activity in brush border membrane vesicles, was not affected by DDS in either males or females. Overall, our findings suggest that an impairment of de novo synthesis mediated by a direct inhibition of CYP3A metabolism, rather than a decreased intestinal reabsorption of bile salts, accounts for the decrease in bile salt pool size. The dissociation between alteration of bile secretory function and the oxidative stress induced by DDS, which is known to be relevant only in male rats, is discussed. 相似文献
59.
目的:探讨细胞分裂周期蛋白6(Cell Division Cycle6,CDC6)在急性白血病中的异常表达及其临床意义。方法:以CDC6 mRNA为分子标志物,应用巢式PCR技术,分别检测未缓解及完全缓解的急性白血病患者和非肿瘤患者外周血待测基因的表达。结果:标志基因CDC6阳性表达率分别为,对照组27.66%,急性白血病完全缓解组56.25%,急性白血病未缓解组100%;CDC6在对照组的阳性表达率显著低于其它各组(P〈0.05);在急性白血病未缓解组的表达率显著高于急性白血病完全缓解组(P〈0.05)。结论:CDC6的异常高表达与急性白血病细胞增殖有关.可作为成人急性白血病病情监测的分子生物学指标。 相似文献
60.
目的:观察黄连素对人肝癌细胞Hep G2生长的影响及其可能机制。方法:将浓度分别为0,25,50,100,200μmol/L的黄连素与人肝癌细胞Hep G2共同培养24,48,72 h,用RSB法检测黄连素对人肝癌细胞HepG2生长的抑制率;用流式细胞分析仪分析细胞周期的变化、检测细胞凋亡率及Caspase-3、CyclinB1、CDC2、CDK4蛋白的表达。结果:黄连素对人肝癌细胞Hep G2生长抑制率随药物浓度和作用时间的增加而增大;流式细胞仪分析显示黄连素将人肝癌细胞Hep G2阻滞于S、G2/M期。黄连素作用48 h后人肝癌细胞Hep G2凋亡率明显增加,且随药物浓度的增加而加大。黄连素作用48 h后Hep G2细胞的Caspase-3、CDC2蛋白表达增加;而CDK4、Cy-clinB1蛋白表达降低。结论:黄连素可能通过增加Hep G2细胞CDC2蛋白表达,降低CDK4、CyclinB1蛋白表达使其阻滞于S、G2/M期;可能通过增加Caspase-3蛋白表达增加Hep G2细胞凋亡。 相似文献