PATHOGENESIS OF GASTRIC ULCERATION DUE TO H PYLORI

这项提议的目标是研究幽门螺杆菌的作用 幽门螺杆菌在胃十二指肠溃疡发生中的作用 感染的可能性。幽门螺杆菌是一种新发现的细菌体。 引起人类胃炎，是消化性溃疡的重要辅助因素 疾病。因为与溃疡有很强的联系，而且因为 消化性溃疡疾病的频发和重要性， 生物体引起了人们极大的兴趣。然而，虚拟的 关于幽门螺杆菌易患幽门螺杆菌的机制尚不清楚 溃疡。灵知生猪模型是独一无二的，因为与其他 非灵长类动物，仔猪对人类幽门螺杆菌易感 起源。此外，幼猪的胃炎是淋巴细胞性的，但 感染幽门螺杆菌的免疫仔猪胃炎具有中性粒细胞 组成部分，在严重性和特征上与慢性活动性相似 与幽门螺杆菌相关的成人胃炎。因此，该模型 非常适合于研究胃炎的发病机制。 细菌。 这项提议的第一个目标将是确定淋巴细胞 或中性粒细胞胃炎导致诱导胃愈合延迟 仔猪的腐烂或溃疡。第二个目标将决定是否 细菌细胞毒素或细胞毒素相关蛋白对此有贡献 延迟愈合。这些研究将证实或否认总体上 幽门螺杆菌是人类胃部重要辅助因子的假说 溃疡形成。第三个目标是研究细菌 殖民因素。它的设计是为了确定幽门螺杆菌鞭毛 基因FlaA或Flab或两者都能促进幽门螺杆菌的定植。最后， 促进幽门螺杆菌菌株差异性定植的因素 将会被调查。

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.