Helicobacter pylori has been implicated as one of the most common causes of gastritis in man. This bacterium has been identified in 80-90% of adult patients with chronic gastritis and 90-100% of adult patients with peptic ulcer disease. Recent studies have shown that long-term infection by H. Pylori is associated with an increased risk of developing gastric carcinoma. However, the mechanism by which H. Pylori causes gastric epithelial cell injury is unknown and its role in the pathogenesis of peptic ulcer disease is even less understood. Infection with this bacterium is localized to the gastric mucosa, with the esophagus and duodenum only involved when heterotopic or metaplastic gastric epithelium is present in these areas. The prevalence of H. pylori infection of the gastric mucosa is very common in the United States. More than 50% of adults over 60 years of age are infected with this bacterium, and the prevalence in African Americans is approximately 38% higher than that of whites in all age groups. In this study, a human in vitro culture system is employed to identify the receptors to which H. Pylori binds on gastric epithelial cells is involved in its pathogenesis. Bacterial adherence, at least is part, may be responsible for H. pylori's predilection for gastric mucosa. Specific goals are to: (1) determine whether the differing pathology found in patients infected with this bacterium is secondary to the differences in toxin production between isolates or differences in host response to this bacterium; (2) identify the cytotoxin(s) produced by H. pylori; and (3) evaluate the mechanism of toxin induced cell injury on human gastric mucosa in vitro. Cell injury and viability is evaluated morphologically with light and electron microscopy and functionally by cell incorporation of neutral red dye and release of lactate dehydrogenase into culture media. Changes in epithelial cell proliferation associated with cell injury after exposure to this bacteria are being measured using bromodeoxyuridine. GCRC outpatient facilities will be useful in the acquisition of blood and other body secretions from clinical evaluations. GCRC inpatient facilities are not necessary for the early stages of this investigation, buy may become more critical as data are generated and subjects are in need of close monitoring and clinical evaluation.
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