STUDIES ON SCHISTOSOMIASIS AND CHAGAS DISEASE

查加斯病，原虫锥虫引起的寄生虫感染 克鲁兹，主要影响中部和南部的1600-1800万人 美国。虽然本土病例在美国很少见，但 恰加斯病可能代表着一个日益严重的公共卫生问题 拉丁美洲移民人数不断增加。发病的主要原因 恰加斯病的死亡率仅次于心脏病和 胃肠道受累。这两种情况都发生在10年或更长时间之后 急性感染。病理上两者均表现为局灶性淋巴细胞 与心肌瘢痕形成和丢失相关的浸润物 查格斯氏心肌病中的细胞和神经元变性导致 查格斯克氏巨食症的失神经支配和病理性扩张 大冒号。在查格斯氏心肌病和肠道查加斯氏病中， 很少发现质疑寄生虫作用的生物体 晚期感染并发症持续存在。查格斯克性心肌病 巨大综合征通常不会发生在同一患者身上。 它们的相对频率在地理上有显著的差异。近期 分子遗传学研究已经证明了188个碱基的存在 炎性灶附近195个碱基的重复DNA序列片段 在18或21个石蜡包埋的心肌尸检切片中 查格西克心肌病患者。我们建议将这些措施延长 用于鉴定含有寄生虫DNA的细胞的研究 原位聚合酶链式反应技术及其对寄生虫DNA形态的研究 其他克氏锥虫特有的DNA序列。在巨大的综合症中 炎性病灶更加分散，我们将放大195个碱基 H&S显微切割病变刮片中的重复DNA序列 在尸检或手术中获得的E染色的食道或结肠切片。 一种可能的解释是相对地理位置的变化 晚期心脏和胃肠道表现的分布特点 恰加斯病是指不同的损伤病理机制可能 在工作中。我们之前已经鉴定出颗粒酶阳性的CD8 T细胞 作为心脏炎症性病变的优势细胞。其他内容 研究表明，MHC I类分子在 心肌细胞与MHC-II类抗原E的表达增强 血管内皮细胞表达选择素和CD44。我们会延长这些 巨综合征的免疫组织化学研究。最后，心外膜 心包积液的炎症几乎是一个不变的发现。 查格西克心肌病。这些积液包含有活性的淋巴细胞和 最近被证明含有克氏锥虫特异性抗体。 心包液为研究体液和细胞提供了一个窗口 查格西奇心肌病的免疫反应。我们会更早地延期 心包液中体液反应的初步研究 免疫组织化学方法检测淋巴细胞亚群及克隆 扩增B和T细胞淋巴细胞群的技术 B细胞特异性和T细胞功能及受体的研究 专一性。

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.