Gene Polymorphisms Predisposing to Infectious Diarrhea

超出所提供的空间。暴露于肠道病原体后，感染性腹泻的表现是多变的，取决于宿主和病原体因素。多种宿主因素调节感染的可能性或症状的严重程度，可分为介导易感性（即宿主遗传因素、病原体受体）和损伤（即刺激流体和电解质通道、促炎细胞因子）的因素。感染的解决取决于控制和愈合阶段的因素（即抗炎细胞因子和特异性免疫）。我们的中心假设是，导致一种或几种介质的定性或定量差异的遗传多态性是暴露于肠道病原体后感染和疾病发展的部分原因。为此，我们将研究两个具有良好特征的感染性腹泻人群。第一个研究小组将由健康的成年人组成，他们从发达国家前往腹泻细菌感染的危险地区。第二个研究组将由在德克萨斯大学休斯顿临床研究中心实验暴露于隐孢子虫的健康成年人组成。对于这两种情况，我们建议研究宿主基因的单核苷酸多态性（snp），这些基因编码与易感性、疾病表现（损伤）调节、根除（控制）和感染后愈合相关的蛋白质。我们将重点关注三种具有潜在生物恐怖主义用途的药剂，它们通过水媒或食源性途径具有不同的病理生理学；产肠毒素大肠杆菌引起分泌性腹泻，肠聚集性大肠杆菌引起炎症性腹泻，隐孢子虫是细胞内病原体。snp与肠道病原菌的分离和临床疾病相关。snp的影响将在不同的种族背景下进行研究。了解感染的结果与宿主遗传因素的关系，将有助于设计旨在改善风险评估的生物防御干预措施。确定更容易受到肠道病原体影响的人群对于设计减少这些病原体在引起疾病方面可能产生的影响的战略和确定最有可能从预防、治疗和/或疫苗中受益的人群将是重要的。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. After exposure to an enteropathogen, the manifestations of infectious diarrhea are variable and depend on host and pathogen factors. A variety of host factors modulate the likelihood of infection or severity of symptoms and can be categorized as those that mediate susceptibility (i.e. host genetic factors, pathogen receptors), and injury (i.e. stimulation of fluid and electrolyte channels, pro inflammatory cytokines). Resolution of infection is determined by factors that contribute to the phases of control and healing (i.e. anti-inflammatory cytokines and specific immunity). Our central hypothesis is that genetic polymorphisms that lead to qualitative or quantitative differences in one or several- of these mediators are partially responsible for the development of infection and illness after exposure to enteric pathogens. To this end we will study two well-characterized populations of subjects with infectious diarrhea. The first study group will consist of healthy adults traveling from developed nations to areas of risk for infection with bacterial agents of diarrhea. The second study group will consist of healthy adults experimentally exposed to Cryptosporidium at the University of Texas - Houston Clinical Research Center. For both we propose to investigate host single nucleotide polymorphisms (SNPs) of genes that encode proteins that are associated with either susceptibility, modulation of disease manifestation (injury), eradication (control) and healing after infection. We will focus on three agents with potential for bioterrorism use by waterborne or food borne routes with distinct pathophysiology; enterotoxigenic E. coli a cause of secretory diarrhea, Enteroaggregative E. coli a cause of inflammatory diarrhea and Cryptosporidium an intracellular pathogen. SNPs will be correlated with the isolation of an enteropathogen and clinical illness. The impact of SNPs will be examined in the context of different ethnic backgrounds. The understanding of the outcome of infection as they relate to host genetic factors will be of use in designing biodefense interventions that are directed towards improving risk assessment. The identification of populations that are more susceptible or vulnerable to the effects of enteric pathogens will be important in the design of strategies to decrease the impact that these agents may have in causing disease and defining the populations most likely to benefit from prevention, treatment and or vaccines. PERFORMANCE SITE ========================================Section End===========================================