PATHOGENESIS OF GASTRIC ULCERATION DUE TO H PYLORI

这项建议的目的是调查螺杆菌的作用 幽门螺杆菌在胃十二指肠溃疡形成中的作用 感染 H.幽门螺杆菌是一种新发现的细菌， 引起人类胃炎，是消化性溃疡的重要辅助因子 疾病 由于与溃疡的强烈关联，并且由于 消化性溃疡的常见发病率和重要性，这 有机体引起了人们极大的兴趣。然而，实际上， 目前还不清楚H.幽门螺杆菌易患 溃疡 非生物仔猪模型是独一无二的，因为，与其他模型不同， 在非灵长类动物中，仔猪对H.人幽门螺杆菌 起源此外，幼稚仔猪的胃炎是淋巴细胞性的，但 感染H. pylori有一个嗜酸性的 成分，严重程度和特征与慢性活性成分相似 胃炎伴H. pylori在成年人中 因此，该模型 非常适合于研究胃炎的发病机制， 细菌。 本提案的第一个目标是确定淋巴细胞是否 或嗜酸性胃炎引起诱导性胃溃疡愈合延迟 仔猪的糜烂或溃疡。 第二个目标将确定， 细菌细胞毒素或细胞毒素相关蛋白有助于这种 延迟愈合这些研究将证实或否认整体 假设H.幽门螺杆菌是人类胃肠道疾病的重要辅助因子， 溃疡形成 第三个目标是研究细菌 殖民因素 它的目的是确定是否H。幽门鞭毛 基因flaA或flaB或两者促进H.幽门。最后， 促进H.幽门 将被调查。

The goal of this proposal is to investigate the role of Helicobacter pylori in gastroduodenal ulcerogenesis using a gnotobiotic piglet model of infection. H. pylori is a newly described bacterial organism which causes gastritis in humans and is an important co-factor in peptic ulcer disease. Because of the strong association with ulcers, and because of the frequent occurrence and importance of peptic ulcer disease, this organism has engendered a great deal of interest. However, virtually nothing is known about the mechanisms by which H. pylori predisposes to ulceration. The gnotobiotic piglet model is unique because, unlike other non-primate species, piglets are susceptible to H. pylori of human origin. Furthermore, gastritis in naive piglets is lymphocytic, but gastritis in immune piglets infected with H. pylori has a neutrophilic component, similar in severity and character to the chronic active gastritis associated with H. pylori in adult humans. Thus, this model is ideally suited to studies of the pathogenesis of gastritis due to this bacterium. The first objective of this proposal will be to determine if lymphocytic or neutrophilic gastritis cause delayed healing of induced gastric erosions or ulcers in piglets. The second objective will determine if bacterial cytotoxin or cytotoxin-associated proteins contribute to such delayed healing. These studies will confirm or deny the overall hypothesis that H. pylori is a crucial co-factor in human gastric ulcerogenesis. The third objective will investigate bacterial colonization factors. It is designed to determine if H. pylori flagellar genes flaA or flaB or both promote colonization by H. pylori. Finally, factors which promote differential colonization by strains of H. pylori will be investigated.