cefoxitin and Gastritis

Core 1-derived mucin-type O-glycans (O-glycans) are a major component of gastric mucus with an unclear role. To address this, we generated mice lacking gastric epithelial O-glycans (GEC C1galt1-/-). GEC C1galt1-/- mice exhibited spontaneous gastritis that progressed to adenocarcinoma with ∼80% penetrance by 1 yr. GEC C1galt1-/- gastric epithelium exhibited defective expression of a major mucus forming O-glycoprotein Muc5AC relative to WT controls, which was associated with impaired gastric acid homeostasis. Inflammation and tumorigenesis in GEC C1galt1-/- stomach were concurrent with activation of caspases 1 and 11 (Casp1/11)-dependent inflammasome. GEC C1galt1-/- mice genetically lacking Casp1/11 had reduced gastritis and gastric cancer progression. Notably, expression of Tn antigen, a truncated form of O-glycan, and CASP1 activation was associated with tumor progression in gastric cancer patients. These results reveal a critical role of O-glycosylation in gastric homeostasis and the protection of the gastric mucosa from Casp1-mediated gastric inflammation and cancer.

Topics: Animals; Antigens, Tumor-Associated, Carbohydrate; Carcinogenesis; Caspase 1; Female; Gastric Mucosa; Gastritis; Glycosylation; Homeostasis; Humans; Inflammation; Male; Mice; Mucins; Mucus; Neoplasms; Polysaccharides; Stomach Neoplasms

The simple mucin-type carbohydrate antigens Tn, sialyl-Tn and T represent the mucin core oligosaccharide structures that are produced in the initial steps of mucin biosynthetic pathway. Utilising monoclonal antibodies anti-Tn antigen, anti-sialyl-Tn antigen and anti-T antigen, we have investigated the expression of the simple mucin-type carbohydrate antigens in 47 biopsy specimens of antral mucosa with chronic active gastritis, 25 of which had Helicobacter pylori infection. The Tn immunoreactivity, localised at the supranuclear region of surface and glandular mucous cells, was observed in all samples, independently from H. pylori status. The sialyl-Tn antigen, mainly localised in the cytoplasm of glandular mucous cells and in goblet cells vacuoles, was seen in 56% of the cases with H. pylori infection and in 41% of the cases in the H. pylori-negative group. In addition, the T antigen was found in the cytoplasm of surface and glandular mucous cells in 16% of the H. pylori-positive group, whereas the percentage of positive cases was reduced to 5% in H. pylori-negative patients, with an exclusive localisation in the cytoplasm of glandular mucous cells; after neuraminidase treatment, the percentage of T antigen-positive cases was increased to 28% in H. pylori-positive cases and to 27% in negative cases. No significant relationships between H. pylori infection and Tn, sialyl-Tn or T antigen immunoexpression were encountered in our cases. Therefore, we maintain that the inflammatory infiltrate may itself play an important role in the expression of simple mucin-type carbohydrate antigens in chronic active antral gastritis.

Topics: Adult; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Antigens, Viral, Tumor; Biopsy; Chronic Disease; Female; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans; Immunoenzyme Techniques; Male; Middle Aged; Pyloric Antrum

Topics: Antigens, Tumor-Associated, Carbohydrate; Chronic Disease; Gastritis; Helicobacter Infections; Helicobacter pylori; Humans

In a previous report we suggested that T antigen appeared to be associated with gastric carcinoma. To verify this hypothesis and characterize the pattern of expression of simple-mucin type carbohydrate antigens (Tn,sialyl-Tn and T before and after neuraminidase) in normal gastric mucosa and precursor lesions of gastric carcinoma, we studied the mucosa adjacent to 100 cases of gastric carcinoma, gastric biopsies of 60 dyspeptic patients, eight adenomatous polyps and eight hyperplastic polyps. The expression of the antigens was more related to the cell type and underlying lesions than to the coexistence of carcinoma. The most distinctive findings concerned intestinal metaplasia, dysplasia and hyperplastic lesions. In intestinal metaplasia, Tn was found mostly in columnar cells and sialyl-Tn in goblet cells. T was more prevalent in incomplete intestinal metaplasia than in complete. A high prevalence of sialyl-Tn expression and cell membrane immunoreactivity for T antigen, similar to those previously found in gastric carcinomas, were observed in three adenomatous polyps, one hyperplastic polyp, five cases of adenomatous dysplasia in the neighbourhood of intestinal carcinomas and four cases of marked foveolar hyperplasia, three of which were from the mucosa adjacent to diffuse carcinomas. We conclude that adenomatous and hyperplastic lesions share with gastric carcinomas features of aberrant glycosylation, namely the cell membrane expression of T antigen.

Topics: Adenocarcinoma; Adenomatous Polyps; Antigens, Tumor-Associated, Carbohydrate; Carbohydrate Sequence; Dyspepsia; Gastric Mucosa; Gastritis; Gastritis, Atrophic; Glycosylation; Humans; Hyperplasia; Immunoenzyme Techniques; Metaplasia; Molecular Sequence Data; Polyps; Precancerous Conditions; Stomach Neoplasms

The activities of 11 antimicrobial agents, including two bismuth salts, against 70 strains of Campylobacter pyloridis isolated from gastric biopsy specimens were tested. The isolates were very susceptible to penicillin (the MIC for 90% of the strains tested [MIC90] was 0.03 microgram/ml), erythromycin, cefoxitin (MIC90, 0.12 microgram/ml), gentamicin, and ciprofloxacin (MIC90, 0.25 microgram/ml). The bismuth salts and nalidixic acid had moderate activity (MIC90, 16 to 64 micrograms/ml). Twenty percent of the isolates were resistant to metronidazole (MIC, greater than 1 micrograms/ml), and all were resistant to sulfamethoxazole and trimethoprim (MIC90, greater than 256 micrograms/ml).

Topics: Anti-Bacterial Agents; Bismuth; Campylobacter; Cefoxitin; Ciprofloxacin; Erythromycin; Gastritis; Gentamicins; Humans; Metronidazole; Nalidixic Acid; Organometallic Compounds; Penicillin Resistance; Penicillins; Quinolines; Sulfamethoxazole; Tartrates; Trimethoprim