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Biomedical subjects

J E Smithson

Publications and source records attributed to J E Smithson.

6 recordsLinked to original sources

Altered expression of mucins throughout the colon in ulcerative colitis.

BACKGROUND/AIMS: Regional differences in the biology of the colonic epithelium may determine the extent of involvement by ulcerative colitis. Novel monoclonal antibodies (MAbs) were used in this study to investigate regional heterogeneity in the colonic mucosa. METHODS: MAbs generated using a method of tolerisation against common antigens in the proximal colon and distal colon were used for immunoperoxidase staining, comparative histochemistry, immunoblotting, and slot-blot analysis. RESULTS: The colon specific MAbs 5F1 (IgG3) and 6G4 (IgM) stained goblet cell contents throughout the normal distal colon but staining was markedly reduced in the proximal colon (p < 0.0001). In the distal colon of patients with ulcerative colitis, whether quiescent or actively inflamed, reactivity was reduced compared with controls (p < 0.05, p < 0.001 respectively). By contrast, an overall increase in staining was seen in the uninflamed proximal colon in ulcerative colitis compared with controls (p < 0.02). Comparative staining with high iron diamine and biochemical analyses indicated that MAb 6G4 was reactive with mucin bearing sulphate or O-acetylated sialic acid groups, or both. CONCLUSIONS: Regional differences in the staining characteristics of normal colonic mucin have been shown using novel monoclonal antibodies. The pattern of mucin expression throughout the colon in ulcerative colitis is altered even in the absence of histological changes.

Animals↗

Heterogeneous expression of carcinoembryonic antigen in the normal colon and upregulation in active ulcerative colitis.

Using a technique of tolerization, a murine monoclonal antibody (MAb 2E8) has been raised which displays regional differences in reactivity in the epithelium of the normal human colon and increased reactivity in active ulcerative colitis. MAb 2E8 (IgG1) was highly colon-specific and gave higher immunoperoxidase staining scores in the proximal colonic mucosa compared with paired rectal sections (P < 0.02). Expression of the antigen reactive with MAb 2E8 was enhanced in active ulcerative colitis compared with quiescent ulcerative colitis (P < 0.05) and normal controls (P < 0.001). Western blotting and indirect immunofluorescent screening on transfected cell lines established that MAb 2E8 was reactive with carcinoembryonic antigen (CEA). This is the first demonstration of regional differences in the expression of CEA in the normal colon and indicates upregulation of this molecule in active ulcerative colitis.

Adult↗

Appendectomy and tonsillectomy in patients with inflammatory bowel disease.

Recent reports of reduced appendectomy rates in patients with ulcerative colitis have not distinguished between primary appendectomy (surgery for appendicitis) and incidental appendectomy (removal of the appendix for other reasons). In the present case control study, we examined the frequency of primary appendectomy in subjects with ulcerative colitis (n = 197) and Crohn's disease (n = 117) compared to a control group of dermatology outpatients (n = 243). A reduced rate of primary appendectomy was found in the ulcerative colitis group (adjusted odds ratio 0.20, 95% confidence intervals 0.070-0.53, p < 0.0005) but not in the Crohn's disease patients (adjusted odds ratio 0.93, 95% confidence intervals 0.39-2.18, p = NS). These data suggest that appendicitis occurs less commonly than would be expected in individuals who develop ulcerative colitis. Environmental or immunoregulatory factors may be responsible. Tonsillectomy rates were also examined in each study group, but no overall differences were found between patients with inflammatory bowel disease and controls.

Adult↗