Background-In normal gastric epithelium, MUC5AC is detected in superficial epithelium associated with Lewis type 1 antigens and MUC6 is detected in antral glands with Lewis type 2. Therefore, the stomach constitutes an excellent model to examine the role of glycosyltransferases in determining the specificity of apomucin glycosylation. Aims-To determine the molecular basis of this association and to examine changes in expression of gastric and intestinal apomucins and their association with Lewis antigens during the gastric carcinogenesis process.
Methods-Fucosyltransferase(FUT1, FUT2, FUT3) and mucin (MUC5AC, MUC6) transcripts were detected using reverse transcription-polymerase chain reaction. Apomucin (MUC2, MUC4, MUC5AC, MUC6) and Lewis antigen (types 1 and 2) expression were analysed using single and double immunohistochemistry and in situ hybridisation. Results-In the normal stomach, FUT1 is exclusively detected associated with MUC6; FUT2 is only detected when MUC5AC is present. This co-regulation is lost in gastric tumours, as is diVerential expression of MUC5AC and MUC6 in normal gastric epithelial cells. In gastric tumours, especially those with the intestinal phenotype, MUC2 and MUC4 genes are upregulated, and gastric-type and intestinal-type mucins are coexpressed. These changes are early events in the gastric carcinogenesis process, as they are detected in intestinal metaplasia. Conclusions-The glycosylation pattern found in normal gastric epithelium is dictated by the specific set of fucosyltranferases expressed by the cells rather than by the apomucin sequence. The development of intestinal metaplasia and gastric cancer is associated with the appearance of cellular phenotypes that are absent from normal epithelium. (Gut 2000;47:349-356)
In addition to providing epidemiological data within the EPIC cohort on gastric and esophageal adenocarcinomas, the results reported here confirm the relevance of a validation study, notably for multicenter studies.
Background: to determine the epidemiological, clinical, diagnostic and therapeutic characteristics of Whipple's disease in Spain.Patients and method: cases of Whipple's disease reported in the Spanish literature between 1947 and 2001 which meet histological or PCR criteria are reviewed.Results: 91 cases were included, 87.5% of which were male. The maximum incidence was between 40 and 60 years of age (68%). There was no family clustering or susceptibility by profession or surroundings. The most common symptoms and signs were: weight loss (80%), diarrhoea (63%), adenopathies (35%), skin problems (32%), abdominal pain (27%), fever (23%), joint problems (20%) and neurological problems (16%). Arthralgias, diarrhoea and fever were noted prior to diagnosis in 58, 18 and 13% of patients, respectively. Diagnosis was histological in all cases except two, which were diagnosed by PCR. Intestinal biopsy was positive in 94%. Adenopathic biopsies (mesenteric or peripheral) were suggestive in 13% of cases, and treatment was effective in 89%. There were nine relapses, four of which were neurological, although all occurred before the introduction of cotrimoxazole.Conclusions: Whipple's disease is not uncommon, although it requires a high degree of suspicion to be diagnosed in the absence of digestive symptoms. The most common and most sensitive diagnostic method is duodenal biopsy. PCR is beginning to be introduced to confirm the diagnosis and as a therapeutic control. Initial antibiotic treatment with drugs that cross the blood-brain barrier, such as cotrimoxazole and ceftriaxone, is key to achieving a cure and avoiding relapses.
Our findings suggest that in the H. pylori-infected southern European population, the cagA genotype and the HLA-DQB1(*)0602 gene confer an increased risk for distal gastric cancer.
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