Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021390 (inflammatory bowel disease)
 23,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intestinal mucins are complex glycoproteins which are secreted from goblet cells, and form a gel-like covering over the mucosal surface. They are assumed to provide lubrication and protection of the underlying epithelium against potentially injurious chemicals, enzymes, bacteria and dietary constituents. Recent advances in our understanding of mucin structure, secretion and functional properties are reviewed in this paper. Implications for diseases such as cystic fibrosis, peptic ulcer, malignancy and inflammatory bowel disease are briefly discussed.
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PMID:Intestinal mucins in health and disease. 2 18

Previous reports of a selective mucin subclass defect in ulcerative colitis have been reassessed using high performance chromatography (Superose 6 and Mono Q) for mucin purification and fractionation coupled with analysis of the fractions obtained using a combination of enzyme linked lectin and mucin antibody assays. Mucin samples purified from snap frozen rectal biopsy specimens obtained from patients with ulcerative colitis (n = 12), Crohn's disease (n = 5), and non-inflammatory bowel disease control subjects (n = 9) were subject to ion exchange chromatography using a continuous 0-0.35 mol/l NaCl salt gradient with a final 2.5 mol/l NaCl step. In all samples the major proportion (mean (SD) 86.7 (8.9)%) of the mucin detectable by wheat germ agglutinin binding eluted between 0.15 and 0.35 mol/l NaCl with no significant difference in elution profile between ulcerative colitis and control subjects. Significant elution of glycoprotein at less than 0.15 mol/l NaCl did occur, however, when a lower molecular weight mucin containing fraction which contained concanavalin A positive (glucose or mannose containing) material was analysed similarly. Similar ion exchange profiles were obtained when (3H)N-acetylglucosamine labelled mucins were studied after tissue culture of rectal biopsy specimens. No significant alteration in the ion exchange profile of purified mucins in ulcerative colitis has been shown in these studies. It is possible that the previously reported relative depletion of mucin subclass IV (eluting with 0.20 mol/l NaCl) may simply have reflected mucin depletion.
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PMID:Ion exchange chromatography of purified colonic mucus glycoproteins in inflammatory bowel disease: absence of a selective subclass defect. 195 68

Colonic glycoprotein composition was evaluated in monozygotic twins with inflammatory bowel disease using ion-exchange chromatography. Fifty-three individuals, 12 pairs and 1 single twin with ulcerative colitis and 14 pairs with Crohn's disease, were evaluated. Seven twin pairs were concordant for the presence of ulcerative colitis or Crohn's disease, whereas twin siblings of 10 ulcerative colitis probands and 9 Crohn's disease probands were not known to have inflammatory bowel disease. Content of one chromatographically defined component of colonic mucin, designated HCM species IV, was reduced in both patients with ulcerative colitis (1040 +/- 300 cpm/10,000 cpm total HCM) and their apparently healthy twins (1340 +/- 540 cpm/10,000 cpm total HCM) compared with control subjects (4030 +/- 1,000 cpm/10,000 cpm total HCM). Composition of mucin in Crohn's disease patients and their nonaffected twins was not significantly different than in controls. These observations suggest that altered profiles of mucin glycoprotein may be present before the onset of ulcerative colitis and may be genetically defined. Conversely, it appears that alterations in glycoproteins only are not sufficient to initiate mucosal inflammation.
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PMID:Colonic glycoproteins in monozygotic twins with inflammatory bowel disease. 198 38

1. Mucolytic (mucus solubilizing) activity in human faeces has been characterized with both purified human and pig colonic mucin and shown to be mediated by proteolysis. 2. Mucolytic activity was demonstrated by: (i) a drop in mucin viscosity; (ii) a substantial reduction in mucin size, from polymer to degraded subunit, as assessed by Sepharose CL-2B gel filtration; (iii) formation of new N-terminal peptides. 3. Mucolytic activity was also followed in faecal extracts by its proteolytic activity using standard succinyl albumin substrate. Proteolysis extended over the pH range 4.5-11.0. Proteolysis was inhibited at pH 7.5 by soybean trypsin inhibitor and phenylmethanesulphonyl fluoride, suggesting the presence of serine proteinases. 4. The polyacrylate carbomer (934P) inhibited both mucolysis of pig colonic mucin and proteolysis of succinyl albumin. 5. Interaction between the polyacrylate (carbomer 934P) and purified human and pig colonic mucin was demonstrated by a marked synergistic increase in solution viscosity (360% above control). 6. The results demonstrate the presence of a mucolytic activity in the human colonic lumen that has the potential to degrade the mucus barrier, and that polyacrylates inhibit this mucolysis and interact to strengthen the colonic mucus barrier. Polyacrylates may therefore have therapeutic potential in inflammatory bowel disease where luminal proteolytic activity can be raised.
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PMID:Mucolysis of the colonic mucus barrier by faecal proteinases: inhibition by interacting polyacrylate. 215 46

A new screening test (Shamsuddin and Elsayed, 1988) based on the enzymatic detection of the disaccharide beta-D-Gal(1----3)-D-GalNAc in the rectal mucus of patients with colorectal (CR) cancer and precancerous conditions such as inflammatory bowel disease (IBD) and polyp (precancerous lesions) was evaluated in 85 Japanese patients. Following a 15-minute reaction, a sensitivity of 80.0% (8/10) for CR cancer and 72.2% (8/11) for precancerous lesions was obtained. The overall specificity for combined CR cancers and precancerous lesions was 62.2% (28/45). Correlation with abnormal mucin production in the tissues of CR cancer and precancerous lesions was studied by high-iron diamine-Alcian blue and/or periodic acid-Schiff-Alcian blue (pH = 1.0). The agreement of the results with this test was 77.8% (7/9) for CR cancers and 75.0% (6/8) for precancerous conditions. Because of the simplicity of this test, low cost, stability of the sample and reagents and accuracy for CR cancer and precancerous lesions, the test may have potential use for mass screening of cancer and high risk individuals, particularly CR cancer in Japan.
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PMID:A pilot study on the usefulness of a new test for mass screening of colorectal cancer in Japan. 221 Feb 17

Ulceration anywhere in the gastrointestinal tract induces a novel cell lineage, which grows from the bases of existing crypts, ramifies to form a new gland, and ultimately emerges onto the mucosal surface. The lineage produces neutral mucin, shows a unique lectin-binding profile and immunophenotype, and secretes abundant immunoreactive epidermal growth factor/urogastrone (EGF/URO). All gastrointestinal stem cells can produce this cell lineage following mucosal ulceration, secreting EGF/URO to stimulate cell proliferation, regeneration and ulcer healing. This cell lineage is very commonly associated with gastrointestinal ulceration, and we propose that a major in vivo role for EGF/URO is to stimulate ulcer healing throughout the gut via induction of this cell lineage in the adjacent mucosa. EGF/URO should therefore be assessed in the conservative management of inflammatory bowel disease.
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PMID:Ulceration induces a novel epidermal growth factor-secreting cell lineage in human gastrointestinal mucosa. 226 47

The mucin and gland content of 26 rectal biopsy specimens--five normal specimens, 10 from patients with ulcerative colitis, and 11 from patients with Crohn's disease--were measured using a Quantimet image analyser. There was significantly less mucin in the groups with ulcerative colitis compared with either those with Crohn's disease or the normal controls. The difference in the gland content between the groups with ulcerative colitis and Crohn's disease and between the group with Crohn's disease and the normal controls did not reach significance. The results suggest that it is worth while assessing the mucin content of rectal biopsy specimens from patients with inflammatory bowel disease. In routine practice this assessment can be made by eye using a suitably stained section.
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PMID:Mucin depletion in inflammatory bowel disease. 231 90

Monoclonal antibody (MAb) B72.3 reactive with the high-molecular-weight (Mr greater than 10(6) tumor-associated glycoprotein (TAG)-72 is being increasingly utilized in vivo and in vitro for a variety of purposes in colon cancer patients. Recent evidence has suggested that the TAG-72 antigen expression may be enhanced in inflammatory bowel disease, particularly ulcerative colitis (Thor et al., 1986a: Cancer Res., 46, 3118-3124). We have utilized 117 paraffin-embedded formalin-fixed colonic specimens from 56 ulcerative colitis patients which demonstrate a spectrum of epithelial abnormalities (reactive atypia, dysplasia, and carcinoma) as well as 11 inflammatory controls to evaluate TAG-72 expression. Our selected patient population all had pan-colitis and demonstrated a generally increasing incidence of dysplasia or carcinoma with duration of disease (20% at 0 to 10 years, 50% at 11 to 20 years, 59% at 21 to 30 years, and 100% at more than 31 years). TAG-72 expression was similar in the control and non-dysplastic colonic epithelia, and increased with low- or high-grade dysplasia as well as carcinomatous lesions (mean cellular reactivities 23.7%, 26.5%, 36.7%, 70% and 84.3%, respectively). Epithelium with low-grade dysplasia exhibited a focal perinuclear, superficial crypt staining (when present). High-grade dysplastic epithelium showed pancytoplasmic, pan-cryptic reactivity. Invasive disease showed cytoplasmic as well as extracellular mucin staining. Biopsies from patients with active disease showed significantly more immunoreactive cells for TAG-72 than patients with quiescent disease. For any given biopsy specimen the percentage of cells reactive did not always correlate with the degree of dysplasia. TAG-72 expression in quiescent disease generally increased with duration of disease, in contrast to active disease which showed no correlation between MAb B72.3 staining and duration of disease. The frequent expression of TAG-72 in actively inflamed colonic mucosa (ulcerative colitis and other colitides) may limit the clinical utility of this antigen for detecting colon cancer in ulcerative colitis patients by serological assay or in vivo radiolocalization techniques. The tendency for TAG-72 expression to correlate with disease duration in patients with quiescent disease and to increase with more severe degrees of dysplasia suggests that the expression of this gene product correlates with the dysplasia-to-carcinoma sequence.
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PMID:Tumor-associated glycoprotein (TAG-72) expression in ulcerative colitis. 265 25

Evidence is accumulating that colonic mucin glycoconjugates are altered in ulcerative colitis. In order to investigate this further, the lectin-binding properties of rectal glycoconjugates have been studied in ulcerative colitis, Crohn's disease, and controls using lectin-peroxidase histochemistry. Ten lectins were used including peanut agglutinin (PNA) which is known to bind to malignant and adenomatous but not normal colonic mucins. Eight of 21 ulcerative colitis rectal biopsies and 10 of 17 Crohn's disease rectal biopsies showed PNA positivity, particularly in the supranuclear region of surface epithelial cells. There was no correlation between PNA positivity and duration of disease or inflammation, and none of the biopsies showed evidence of dysplasia. This abnormality in epithelial cell glycoconjugates seems to be commonly present in nondysplastic mucosa and occurs in both ulcerative colitis and Crohn's disease. It may reflect a fundamental abnormality in mucus glycoprotein synthesis in inflammatory bowel disease.
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PMID:Altered lectin binding by colonic epithelial glycoconjugates in ulcerative colitis and Crohn's disease. 318 Sep 71

A total of 512 colectomy and endoscopic biopsy specimens were reviewed to define the prevalence and possibly the significance of dystrophic goblet cells (DGCs) in neoplastic and nonneoplastic colonic diseases. As compared with an incidence of 1% in disease-free specimens, DGCs were observed in 38% of cases of inflammatory bowel disease, 23% of colonic malignancies, 30% of nonneoplastic polyps, 22% of adenomas, and 8% of cases showing acute self-limited colitis. In contrast, no dystrophic cells were seen in a group of miscellaneous diseases including diverticulitis, diverticulosis, abscesses, fistulas, ischemia, pseudomembranous colitis, melanosis coli, amyloidosis, shock, and mechanical trauma. Although dystrophic cells occur in association with dysplasia and carcinoma, their presence in nonpremalignant lesions, including acute self-limited colitis, raises doubt as to their diagnostic significance. Histochemical studies of the mucin composition in DGCs were unrevealing, failing to show any differences between DGCs and their morphologically normal counterparts in the same region of the colon.
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PMID:The incidence and carbohydrate histochemistry of dystrophic goblet cells in colon. 323 12


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