Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010346 (Crohn's disease)
 21,615 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown the presence in faeces of sulphatases, sialidases, glycosidases, and proteases relevant to mucus degradation, but the relative role of these enzymes in the degradation of colonic mucus has been unclear. A total mucinase assay using 14C threonine biologically labelled human colonic mucin as substrate was therefore developed in this study. Faecal mucinase activity of a pooled normal faecal filtrate was capable of removing 80% of the 14C threonine label from mucin within eight hours incubation, but 20% remained intact despite prolonged incubation. The pH profile of mucinase activity is broad (pH 4.5-9.5) suggesting contribution from multiple enzymes. Mucinase activity was reduced by preincubation with 100 micrograms/ml chymostatin (82.8%), 0.5 mg/ml EDTA (91.6%), and 4 g/l bismuth subsalicylate (72.0%). All 55 faecal samples studied contained detectable mucinase activity, measured as dpm release/micrograms protein/hour, which was greater in samples from patients with ulcerative colitis (n = 17, median 52.7, interquartile range 32.9-66.9), than controls (n = 26, 34.4, 26.8-40.4, p < 0.02) or patients with Crohn's disease (n = 12, 35.5, 17.5-55.7, p < 0.05). There was, however, no significant difference in faecal mucinase activity between inactive and active ulcerative colitis. These results suggest that faecal mucinase activity is one factor contributing to the thin mucus layer in ulcerative colitis and represents a potential target for drug treatment.
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PMID:Faecal mucinase activity assessed in inflammatory bowel disease using 14C threonine labelled mucin substrate. 767 82

Colonic mucin is heavily sulphated and it has been shown that enzymatic desulphation by faecal bacterial sulphatases greatly increases its susceptibility to degradation by faecal glycosidases. A possible role for faecal mucin sulphatase in the pathogenesis of inflammatory bowel disease has therefore been explored. Faecal mucin sulphatase activity assayed using 35S mucin as substrate was increased in ulcerative colitis (median 80.2 units/g pellet weight (range 6.9-1063; 95% confidence intervals (CI): 45.2 to 293.8, n = 22) compared with 11.3 units/g (range 3.0-53.5; 95% CI: 8.7 to 29.8, n = 17) in healthy controls (p < 0.01), where one unit released 1000 dpm free sulphate/hour from 35S mucin (1680 dpm/microgram). Patients with active ulcerative colitis had higher sulphatase activity (median 146; 95% CI: 98 to 253 units/g, n = 10) than those with inactive ulcerative colitis (median 42.2; CI: 22.5 to 81.6 units/g, n = 12) (p < 0.05). Longitudinal studies in patients with ulcerative colitis show fluctuations of faecal mucin sulphatase activity corresponding to clinical disease activity in six of seven patients. Faecal mucin sulphatase activity was not significantly increased in Crohn's disease (median 36.6, range 5.7-106.6; 95% CI: 22.9 to 65.3 units/g, n = 14). The bismuth salts, bismuth subcitrate and bismuth subsalicylate were found to inhibit faecal mucin sulphatase activity at concentrations achievable therapeutically. The increased faecal mucin sulphatase activity in ulcerative colitis could be the result of greater intraluminal substrate (mucin) availability leading to bacterial enzyme induction, but would probably result in more rapid degradation of secreted mucin and represents a potential target for treatment.
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PMID:Increased faecal mucin sulphatase activity in ulcerative colitis: a potential target for treatment. 773 66

It is clinically important to distinguish idiopathic inflammatory bowel disease (IBD) from other colitides, and ulcerative colitis (UC) from Crohn's disease (CD); however only a few histological criteria based on colonic biopsies have been established. We investigated 209 consecutive series of biopsies taken from 38 patients with UC, 12 with CD, and 105 with other colitides, to evaluate whether combinations of histological features, selected on the basis of our experience, and listed below, could be useful criteria for the differential diagnosis of IBD, and, more specifically, of UC: (A) chronic inflammation with a predominant increase of plasma cells, (B) crypt distortion, (C) crypt atrophy, (D) diffuse chronic inflammation within a biopsy and between biopsies, and (E) diffuse mucin depletion within a biopsy and between biopsies. Findings that fulfilled all or two of A-C distinguished IBD from the other colitides with high sensitivity (94.3%) and specificity (95.8%). When the findings fulfilled the additional criteria of D and/or E, UC was differentiated from CD or the other colitides with high sensitivity (86.4%) and specificity (99.3%).
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PMID:A study of the histological criteria for ulcerative colitis: retrospective evaluation of multiple colonic biopsies. 777 49

DNA replication errors (RERs) in repeated nucleotide sequences due to defective mismatch repair genes have been reported in a subset of sporadic colorectal carcinomas and in the majority of tumors from patients with hereditary nonpolyposis colorectal cancer syndrome (HNPCC). We detected RER in 18 cases (13%) in a prospective series of 137 sporadic stage II and III (Dukes' B and C) colorectal carcinomas. The clinical and pathological features of the RER-positive cases differed from those without RER. The patients with RER-positive cancers tended to be somewhat younger (60 +/- 5 years, range 22-83, versus 66 +/- 1, range 27-90, P = 0.2 with unequal variances) and had a marked preponderance of tumors proximal to the splenic flexure (17/18, 94%, versus 41/119, 34%, P < 0.0001). Only two RER-positive patients (11%) had a family history of colorectal cancer. In comparison to the 41 RER-negative proximal colonic cancers, RER-positive cancers had more frequent exophytic growth (P = 0.04), large size (P = 0.03), poor differentiation (P = 0.0004), extracellular mucin production (P = 0.003) and Crohn's-like lymphoid reaction (P = 0.003), and a trend toward less frequent p53 gene product overexpression by immunohistochemistry (3/17, 18%, versus 18/41, 44%, P = 0.06). We conclude that a subset of sporadic colorectal carcinomas has unique biological features that may indicate inherited germline mutation, de novo germline mutation, or somatic mutations of the mismatch repair genes involved in HNPCC.
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PMID:Clinical and pathological characteristics of sporadic colorectal carcinomas with DNA replication errors in microsatellite sequences. 1098 Jan 44

The six-cysteine P-domain motif forms the basic repeat unit of a growing family of mucin-associated peptides. A precursor for a human secretory polypeptide has been discovered by molecular cloning and deduced to have a single P-domain, termed hP1.B. The pre-pro-peptide has 67% amino acid identity with rat intestinal trefoil factor. We find, using the techniques of RNA analysis and in situ hybridization, that this P-domain peptide is expressed in the human gastrointestinal tract, where a number of pathological conditions affect its expression, and surprisingly find it is expressed in the uterus also. In the intestine, hP1.B is expressed by goblet cells, but in Crohn disease this peptide is synthesized and secreted additionally by the ulcer-associated cell lineage that is known to secrete two other trefoil peptides, pS2 and spasmolytic polypeptide (hSP). In the stomach, hP1.B mRNA is relatively scarce but is more abundant in foci of intestinal metaplasia and near to ulceration. Mucin-rich epithelial cells in hyperplastic polyps of the colon also express this peptide. The discovery of this P-domain peptide and its expression in association with mucins support the hypothesis that P-domains with mucins may subserve related functions in the maintenance and repair of mucosal function.
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PMID:hP1.B, a human P-domain peptide homologous with rat intestinal trefoil factor, is expressed also in the ulcer-associated cell lineage and the uterus. 834 3

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn's disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn's disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 +/- (SD) 7.1 dpm/microgram biopsy protein, incorporation was increased in patients with active Crohn's disease (mean 41.2 +/- (SD) 10.4 dpm/microgram biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 +/- 7.8 dpm/microgram biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 +/- 13.8 dpm/microgram biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n = 58, mean 31.0 +/- (SD) 7.52 dpm/microgram biopsy protein; smokers, n = 27, mean 31.8 +/- (SD) 6.1 dpm/microgram biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn's disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related to cigarette smoking.
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PMID:Abnormal mucosal glycoprotein synthesis in inflammatory bowel diseases is not related to cigarette smoking. 854 79

Monoclonal populations of mucosal T cells were established from the earliest visible lesions in eight patients with well defined Crohn's disease. The FACS phenotype of all the mucosal derived clones to date are TCR alpha/beta+, CD3+, CD4+, and CD45RO+ memory cells. TCR variable region Beta chain analysis revealed predominantly V beta families 1, 2, 5.1, 5.2, 6, 7 and 8, with V beta family analysis supporting antigen expansion in the diseased mucosa. Putative autoreactivity was evaluated by stimulating individual clones with a battery of antigens and determining proliferation and IL-2 production by thymidine incorporation at 72 h. Antigens tested included crude Crohn's diseased (CD) colon and small bowel homogenates, CD brush border preparations, crude CD colon and small bowel mucin, and purified CD small bowel mucin. Controls included clone, APC, tetanus toxoid and either PHA or Staphylococcus enterotoxin B. A total of 200 clones were studied with 29.5% or 59 clones demonstrating proliferation and/or IL-2 production. T cell receptor V beta gene usage evaluated in a small number of reactive clones correlated with the expanded patient families. Seven of the fifteen represented families revealed diverse T cell receptor gene use and no disease overlap.
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PMID:Analysis of function, specificity and T cell receptor expression of cloned mucosal T cell lines in Crohn's disease. 873 63

Whole-gut lavage fluid, collected by administering an electrolyte lavage solution orally, was found to be an excellent and easily collectable source of abundant mucin. Furthermore, the biochemical features of the mucin from patients with ulcerative colitis and Crohn's disease were investigated. The mucin was separated into four fractions by Sepharose CL-4B, Sepharose CL-2B, and DEAE Sephacel chromatography. Compared with healthy subjects, the total yields of mucin from ulcerative colitis patients were low due to a deficiency of neutral mucin, whereas those from Crohn's disease patients were high, which was attributable mainly to high-molecular-weight mucin. The fucose and sulfate contents were low in ulcerative colitis, but only the former was low in Crohn's disease. The different biochemical features of the mucin obtained from whole gut lavage fluid appear to reflect mucosal pathological changes associated with inflammatory bowel disease.
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PMID:Characterization of mucin in whole-gut lavage fluid obtained from patients with inflammatory bowel disease. 879 92

Mucus-secreting cells found at the site of ileac ulceration in Crohn's disease have been described as 'pyloric metaplasia'. Using mucin-histochemical methods and immunohistochemical stainings for Ki-67 antigen and foveolar-type mucin (M1) of the stomach, the characteristics of this type of metaplasia were studied in surgically resected ileac specimens from two Japanese patients with Crohn's disease. Not only pyloric-type cells but also foveolar-type cells were demonstrated; often displaying an organoid growth of the normal stomach mucosa. Stem cells of the ileac crypt may differentiate potentially to intestinal-, pyloric- and also to foveolar-type cells. The term 'pyloric metaplasia' is not appropriate and 'gastric metaplasia' should be used when describing this type of metaplasia.
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PMID:A new aspect of gastric metaplasia in Crohn's disease: bidirectional (foveolar and pyloric) differentiation in so-called 'pyloric metaplasia' in the ileum. 921 31

A series of 44 sporadic mucinous colorectal carcinomas was analysed for microsatellite instability; 30 consecutive sporadic non-mucinous colorectal cancers served as controls. Mucinous carcinomas showed microsatellite instability more frequently than non-mucinous cancers: 26/44 and 8/30, respectively (P = 0.005); the difference was higher for cancers with two or more microsatellite alterations: 12 of the 44 mucinous carcinomas versus one of the 30 non-mucinous carcinomas (P = 0.007). On comparing the clinico-pathological features of mucinous carcinomas with and without microsatellite instabilities, no differences were found with respect to the following variables; sex ratio, tumour localization, tumour size, peritumoural lymphocytic infiltration, Crohn's-like lymphoid reaction, peritumoural fibrosis, Dukes' stage, and relationship with adenoma. Mucinous cancers with DNA replication errors were characterized by three features: onset in younger patients (P < 0.05); exophytic gross shape (P = 0.03); and an expanding pattern of growth (P = 0.003). Of the 12 mucinous carcinomas with instability in two or more microsatellites, ten (83.3 per cent) exhibited an expanding pattern of growth, while mucinous cancers with instability in one microsatellite or without genomic instability showed no distinctive growth pattern. This study confirms the relationship between microsatellite instabilities and mucin production in colorectal carcinomas, but shows that replication error RER-positive and RER-negative mucinous cancers differ in few clinico-pathological features. These differences are only in part similar to those previously reported in RER-positive colorectal carcinomas. These data indicate that mucinous carcinoma of the large bowel could represent a histological subset separate from other histotypes.
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PMID:Microsatellite instability in sporadic mucinous colorectal carcinomas: relationship to clinico-pathological variables. 930 57


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