STUDIES ON SCHISTOSOMIASIS AND CHAGAS DISEASE

血吸虫病和恰加斯病的研究

• 批准号: 5205190
• 负责人: CLINT E CARTER
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5205190
• 关键词: Brazil; CD44 molecule; DNA; Trypanosoma cruzi; body fluids; cellular immunity; colon disorder; cooperative study; esophagus disorder; flow cytometry; histocompatibility antigens; histopathology; human tissue; humoral immunity; immunocytochemistry; in situ hybridization; inflammation; laboratory mouse; lymphocyte; microorganism genetics; myocardium disorder; nucleic acid sequence; pericardium; phenotype; polymerase chain reaction; trypanosomiasis

Chagas' Disease, parasitic infection caused by the protozoan Trypanosoma cruzi, affects 16-18 million people primarily in Central and South America. While autochthonous cases are rare in the United States, Chagas' Disease may represent an increasing public health problem with increasing immigration of Latin Americans. The major causes of morbidity and mortality in Chagas' Disease is secondary to cardiac and gastrointestinal involvement. Both occur, late, 10 or more years after acute infection. Pathologically both exhibit focal lymphocytic infiltrates which are associated with scarring and loss of myocardial cells in Chagasic cardiomyopathy and neuronal degeneration leading to deinnervation and pathologic dilatation in Chagasic megaesophagus and megacolon. In both Chagasic cardiomyopathy and intestinal Chagas', organisms are rarely found which has questioned the role of parasite persistence in late complications of infection. Chagasic cardiomyopathy and megasyndromes usually do not occur in the same patient and exhibit striking geographic variation in their relative frequency. Recent molecular genetic studies have demonstrated the presence of a 188-bp segment of a repetitive 195-bp DNA sequence adjacent to inflammatory foci in 18 or 21 paraffin-embedded autopsy sections of heart muscle from 7 patients with Chagasic cardiomyopathy. We propose to extend these investigations to identify the cells containing parasite DNAs using in situ PCR techniques and to study the form of parasite DNA by amplifying other T. cruzi-specific DNA sequences. In megasyndromes where inflammatory foci are much more dispersed we will amplify the 195 base repetitive DNA sequence in scrapings of lesions microdissected from H & E-stained sections of esophagus or colon obtained at autopsy or surgery. One possible explanation for the variation in the relative geographic distribution in the late cardiac and gastrointestinal manifestations of Chagas' Disease is that different pathologic mechanisms of injury may be at work. We have previously identified a granzyme-positive CD8 T-cell as the predominant cell in inflammatory cardiac lesions. Additional studies have demonstrated upregulation of MHC class I molecules on myocardial cells and enhanced-expression of MHC class II antigens, E Selectin and CD44 on endothelial cells. We would extend these immunohistochemical studies to the megasyndromes. Finally, epicardial inflammation with pericardial effusion is an almost invariant finding in Chagasic cardiomyopathy. These effusions contain viable lymphocytes and have been recently shown to contain T. cruzi-specific antibodies. Pericardial fluid could provide a window to study humoral and cellular immune responses in Chagasic cardiomyopathy. We would extend earlier studies of humoral responses in pericardial fluid first by characterizing lymphocyte populations immunohistochemically and then using cloning techniques to expand B- and T-cell lymphocyte populations for investigation of B-cell specificity and T-cell function and receptor specificity.

恰加斯病，由原生动物锥虫属引起的寄生虫感染 cruzi，影响16-18万人，主要在中部和南部 美国参考 虽然本土病例在美国很少见， 恰加斯病可能是一个日益严重的公共卫生问题， 增加拉丁美洲移民。 发病的主要原因 恰加斯病的死亡率是继发于心脏和 胃肠道受累。 两者都发生在10年或更晚的时候， 急性感染 病理学上均表现为局灶性淋巴细胞性 与瘢痕形成和心肌损失相关的浸润 恰格维什心肌病中的细胞和神经元变性导致 巨食管恰格虫的神经支配和病理性扩张， 巨结肠 在恰加斯病和肠恰加斯病中， 很少发现质疑寄生虫作用的微生物 晚期感染并发症的持续性。 胆固醇性心肌病 和巨同步通常不会发生在同一个病人身上， 它们的相对频率有着惊人的地理差异。 最近 分子遗传学研究表明，存在一个188 bp的 邻近炎症灶的一段重复的195 bp DNA序列 18或21例心肌石蜡包埋切片中， Chagglutinocytosis心肌病 我们建议延长这些 研究鉴定含有寄生虫DNA的细胞， 原位PCR技术，并通过扩增来研究寄生虫DNA的形式 其他T。克鲁兹特有的DNA序列 在超级同步中， 炎症灶更加分散，我们将放大195碱基 从H & 在尸检或手术中获得的食管或结肠的E染色切片。 一个可能的解释是相对地理位置的变化， 分布在晚期心脏和胃肠道表现 恰加斯病是不同的病理机制的损伤可能是 在工作中 我们之前已经鉴定出颗粒酶阳性CD 8 T细胞 作为炎性心脏病变的主要细胞。 额外 研究已经证实， 心肌细胞和MHC II类抗原表达增强，E 内皮细胞上的选择素和CD 44。 我们会把这些 免疫组织化学研究。 最后，心外膜 炎症伴心包积液是一个几乎不变的发现， 胆固醇性心肌病。 这些渗出液含有活的淋巴细胞， 最近被证明含有T.克鲁兹特异性抗体 心包液可以提供一个窗口，研究体液和细胞 霍乱弧菌心肌病的免疫反应 我们会更早地 心包液中体液反应的研究首先通过表征 淋巴细胞群，然后使用克隆 扩增B-和T-细胞淋巴细胞群的技术， B细胞特异性和T细胞功能及受体研究 的特异性