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)

We have described a novel macrophage-derived mucin secretagogue (MMS-68) that mediates mucin secretion in colon cancer cell lines and explants of normal and inflammatory bowel disease (IBD) mucosa. We compared MMS-68 induced mucin release with other known intestinal mucin secretagogues in normal colon explants and in the HT-29 colon cancer cell line, and to study the effects of MMS-68 on mucin release from inflamed and uninflamed ulcerative colitis (UC) and Crohn's disease (CD) mucosa. In normal colonic explants and HT-29 cells, each of the secretagogues including, MMS-68-induced mucin release two- to fivefold more than culture medium alone. In HT-29 cells, MMS-68 plus leukotriene C4 (LTC4) induced a 50% increase in mucin release over either secretagogue alone, and MMS-68 plus platelet-activating factor (PAF) markedly enhanced mucin release by eightfold over either secretagogue. In colonic explants from patients with UC and CD, the mucin release in response to MMS-68 was similar to that of normal colonic explants. Likewise, in isolated epithelial cells from CD and UC (whether involved or uninvolved), MMS-68-induced release was similar to that of epithelial cells isolated from normal colonic mucosa. The number of MMS-68-producing macrophages was lower in uninflamed UC mucosa compared with inflamed UC mucosa and CD mucosa. The mucin secretagogue activity of MMS-68 is comparable to that of other known secretagogues, and PAF can have a synergistic effect on this activity. Whole tissue explants and isolated colonic epithelial cells from patients with IBD respond at least as well as their normal counterparts to MMS-68. MMS-68 may play a role in mucin secretion in normal and inflamed colonic tissue.
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PMID:Mucin secretion in inflammatory bowel disease: comparison of a macrophage-derived mucin secretagogue (MMS-68) to conventional secretagogues. 955 23

The clinical and pathological features of carcinomas of the pancreas with DNA replication errors (RER+) have not been characterized. Eighty-two xenografted carcinomas of the pancreas were screened for DNA replication errors using polymerase chain reaction amplification of microsatellite markers. Cases with microsatellite instability in at least two markers of a minimum of five tested were considered RER+. RER status was correlated with histological appearance, karyotype of the carcinomas when available, K-ras mutational status, and patient outcome. Three (3.7%) of the eighty-two carcinomas were RER+. In contrast to typical gland-forming adenocarcinomas of the pancreas, all three RER+ carcinomas were poorly differentiated and had expanding borders and a prominent syncytial growth pattern. Neither a Crohn's-like lymphoid infiltrate nor extracellular mucin production were prominent. Ductal adenocarcinomas of the pancreas typically contain a mutant K-ras gene, yet all three RER+ carcinomas had wild-type K-ras. One of the three RER+ carcinomas was karyotyped and showed a near diploid pattern. All three of the RER+ tumors were removed via Whipple resection. One of the three patients is free of disease 16 months after pancreaticoduodenectomy, one is alive and free of tumor at 52 months but developed two colon carcinomas during this period, and the third died of pancreatic cancer at 4 months. None of the three patients had a family history of colorectal carcinoma. A review of the K-ras wild-type carcinomas in a previously characterized series of pancreatic carcinomas with known K-ras mutational status identified two additional cancers with poor differentiation, a syncytial growth pattern, and pushing borders. Both of the cancers were diploid and both patients were longterm survivors (over 5 years). The inclusion of such patients in previous prognostic studies of pancreas cancer may explain the failure of histological grade to be a predictor of prognosis. These data suggest that DNA replication errors occur in a small percentage of resected carcinomas of the pancreas and that wild-type K-ras gene status and a medullary phenotype characterized by poor differentiation, and expanding pattern of invasion, and syncytial growth should suggest the possibility of DNA replication errors in carcinomas of the pancreas.
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PMID:Pancreatic adenocarcinomas with DNA replication errors (RER+) are associated with wild-type K-ras and characteristic histopathology. Poor differentiation, a syncytial growth pattern, and pushing borders suggest RER+. 962 54

Alterations in the structure and/or quantity of mucins could alter the barrier function of mucus and play a role in initiating and maintaining mucosal inflammation in Crohn's disease. To investigate the hypothesis of a mucin gene defect in Crohn's disease, we analyzed the expression of the different mucin genes in the ileal mucosa of patients with Crohn's disease and controls. mRNA expression levels were assessed by a quantitative dot blot analysis and compared (i) between healthy and involved ileal mucosa of patients with Crohn's disease and (ii) between healthy mucosa of patients with Crohn's disease and controls. Expression of the different mucin genes was heterogeneous among controls and patients with Crohn's disease, except for MUC6 in controls. Nevertheless, MUC1 mRNA expression was significantly decreased in the involved ileal mucosa of patients with Crohn's disease when compared to the healthy mucosa (p = 0.02). Moreover, the expression levels of MUC3, MUC4, and MUC5B were significantly lower in both healthy and involved ileal mucosa of patients with Crohn's disease compared to controls (p < or = 0.05). The decrease of expression levels of some mucin genes (more particularly MUC3, MUC4, and MUC5B) in both healthy and involved ileal mucosa suggests a primary or very early mucosal defect of these genes in CD.
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PMID:Abnormalities in mucin gene expression in Crohn's disease. 1002 46

Ulcerative colitis (UC) and, to a lesser extent, Crohn's disease (CD) are associated with a reduction of the protective mucus layer in the large intestine; the role of this alteration in the pathogenesis of either disease is, however, not clear. To learn more about the molecular mechanism of the alteration of the mucus layer, the expression of the main intestinal mucin, MUC2, was investigated in relation to inflammation and dysplasia. Formalin-fixed, paraffin-embedded biopsies from 70 patients with UC and 16 patients with CD, and 13 biopsies from normal colonic mucosa, were used for detection of MUC2 mRNA by in situ hybridization with the SMUC41 probe, and MUC2 protein by immunohistochemistry with the antibody CCP58. The steady-state concentration of MUC2 mRNA was not affected by UC or CD. By contrast, the amount of the detectable MUC2 protein, assessed as the immunoreactive score (IRS), was significantly (p<0. 0001) increased in UC (IRS=8.0+/-3.8) and CD (8.0+/-3.7), compared with the normal colonic mucosa (IRS=2.0+/-1.5). This alteration occurred in the inactive phase of inflammation and persisted in the active phase of the disease. It was also observed during bacterial or protozoal inflammation (n=7). The IRS values did not correlate with the grade of inflammation or dysplasia. Simultaneous histochemistry with high iron diamine and immunohistochemistry indicated that the increase of detectable MUC2 is concomitant with low mucin sulphation in the same cells. These data indicate that the strong MUC2 protein staining in colonic mucosa of patients with UC or CD is due to a long-term alteration of the post-transcriptional modification of the MUC2 molecule, leading to its better detectability by the anti-MUC2 antibody CCP58. This alteration, induced by the inflammatory process, may affect the gel thickness and may contribute to a protracted autoimmune response.
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PMID:Defective post-transcriptional processing of MUC2 mucin in ulcerative colitis and in Crohn's disease increases detectability of the MUC2 protein core. 1041

To clarify the role of colonic mucin in the autoimmune process of ulcerative colitis, circulating antibodies against human colonic mucin were investigated. Purified colonic mucin, obtained from human colonic mucosa by gel filtration, using a Bio-Gel A-1.5-m column and CsCl equilibrium density gradient, was divided into soluble mucin (S-mucin) secreted extracellularly and membranous mucin (M-mucin) binding to cell membrane. Sodium dodecylsulfate polyacrylamide gel electrophoresis and Western blotting analysis showed that antibodies in the serum samples of some patients with ulcerative colitis recognized purified S- and M-mucin of >180-kD. By enzyme-linked immunosorbent assay (ELISA), anti-mucin antibodies were detected in 11 of 60 patients with ulcerative colitis (18%). In contrast, the antibodies were not detected in 22 patients with Crohn's disease. The titers of antimucin antibodies against S-mucin and M-mucin were not different in each patient. By ELISA using mucin in which the sugar chains were destroyed by neuraminidase or NaIO4 treatment, it was demonstrated that anti-mucin antibodies recognized the epitopes of either the sugar chain or the core protein exposed through destruction of the sugar chains. We then investigated the relationship between anti-mucin antibodies and the patients' clinical features. Anti-mucin antibodies were detected in 6 of 15 patients with chronic continuous type ulcerative colitis (40%) and in 5 of 26 patients with relapsing-remitting type (19%), but there was no antimucin antibody-positive serum in patients who had had only one attack without any relapse. These results suggest that anti-mucin antibodies could be a disease marker for ulcerative colitis and that immunological abnormalities in colonic mucin contribute to the persistence of colonic mucosal inflammation.
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PMID:Circulating autoantibodies against purified colonic mucin in ulcerative colitis. 1063 47

Patients with Crohn's disease are at increased risk of developing intestinal adenocarcinoma. Dysplasia is both a marker and a precursor of adenocarcinoma in this setting. In a review of our cases of Crohn's-related adenocarcinoma, we noted a peculiar hyperplastic-like mucosal change (HPC) in mucosa both adjacent to and distant from the adenocarcinoma in some cases. However, the significance of this change is unknown. We evaluated 30 cases of Crohn's-related adenocarcinoma and 30 age- and site-matched resection specimens with Crohn's disease without adenocarcinoma to determine the prevalence of this mucosal alteration in these groups. HPC was recognized by a diffuse expanse of flat mucosa with an architecture resembling that seen in colorectal hyperplastic polyps and composed of cells with cytologically bland basal nuclei and apical cytoplasmic mucin distention. The relationship of the HPC to the adenocarcinoma was noted in the Crohn's-related adenocarcinoma cases. An immunohistochemical stain for p53 (antibody DO7) was performed on all cases with HPC in both groups. HPC was identified in 10 of 30 (33%) cases of Crohn's-related adenocarcinoma compared with 3 of 30 (10%) cases in the control group (P = .03). In the 10 cases of Crohn's-related adenocarcinoma with HPC, this alteration was found adjacent to the adenocarcinoma in 3 cases, distant to the adenocarcinoma in 5 cases, and both adjacent to and distal from the adenocarcinoma in 2 cases. In two specimens, HPC was seen immediately adjacent to adenocarcinoma in the absence of adjacent dysplasia. p53 immunoreactivity was noted in HPC in 5 of 10 (50%) Crohn's-related adenocarcinomas. In contrast, p53 immunoreactivity was not seen in HPC in the three control cases with this mucosal alteration. In conclusion, HPC is found significantly more commonly in mucosa both adjacent to and distant from Crohn's-related adenocarcinoma when compared with age- and site-matched controls. In addition, p53 immunoreactivity is more commonly seen in HPC in cases of Crohn's-related adenocarcinoma compared with controls. These data suggest that this mucosal alteration may, in some cases, represent an unusual form of dysplasia in this setting.
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PMID:Hyperplastic-like mucosal change in Crohn's disease: an unusual form of dysplasia? 1091 40

The proper staging of colorectal cancer was discussed with emphasis on the most relevant pathological parameters. Standard staging classifications i.e. Dukes', Astler-Coller's and international TNM classifications are defined by a few basic parameters, namely local invasion and lymph node metastasis, along with the histological grade of differentiation. Advances in diagnosis and treatment and modern aspects of tumor biology introduced other prognostic factors regarding proliferative activity of tumor, its local and systemic effects, host defense mechanisms and metastatic potential. Independent prognostic significance was shown and/or new criteria recommended for: resection margin and peritoneal involvement, vascular invasion, tumoral mucin production activity, presence of extranodal (micro) metastasis, extent of presented (extra) mural tumor spread, peritumoral lymphocytic infiltration, character of tumoral invasive margin and presence of peritumoral Crohn's-like lymphoid reaction. The se pathological parameters, discussed in detail, were partly contained in new revision of TNM or other classifications, not widely accepted, such as Jass', Japanese JSCCR, British UKCCCR classification, or new prognostic categories proposed by Harrison and coworkers. Our own first experiences and primary results showed variable agreement most of the mentioned parameters with special respect to reproducibility of Harrison's new prognostic categories. Many newly developed methods and novel tumor markers with some predictive values on clinical outcome are recently recognized, still uncertain for routine clinical usage. We reviewed in brief most important and/or most studied pathobiological predictors, such as: DNA ploidy, markers of proliferative activity, expression of tumor-specific and tumor-associated antigens or receptors. Among many of hereditary and genetic markers we stressed the importance of RER phenotype, mutations of tumor suppressor genes and some oncogenes, allelic loss of 18q, 17p and other chromosomal alleles as prognostic and screening tools or therapeutic targets. In conclusion, more new insights in carcinogenesis and new therapeutic agents will require new classification systems, never considered as definitive.
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PMID:[New prognostic parameters and categories of colorectal carcinoma--correlation with standards]. 1095 90

Fractalkine (CX3CL1) is synthesized as a type I transmembrane protein. Its unique CX(3)C chemokine domain is attached to a 241-amino acid mucin stalk, a 19-amino acid transmembrane domain, and a 37-amino acid intracellular domain of unknown function. A soluble form of fractalkine can be generated by proteolytic cleavage at the base of the mucin stalk. Novel monoclonal and polyclonal antibodies that specifically recognize only the amino- or carboxyl-terminal ends of the human fractalkine molecule have revealed that epithelial cells are the predominant cell type expressing transmembrane forms of fractalkine in human skin, the tonsil, and the large intestine. Using these specific anti-fractalkine reagents we do not detect high-level expression of fractalkine on endothelial cells in normal or inflamed colon samples obtained from patients with Crohn's disease or ulcerative colitis. In contrast to previous reports we do not detect fractalkine expression by Langerhans cells or immature dendritic cells in mucosal-associated lymphoid tissues in vivo. We show that the reagent used in previous studies, an anti-fractalkine N-terminal peptide antisera, cross-reacts with human CD84. Finally we discuss potential roles for fractalkine in constitutive leukocyte trafficking based on its observed pattern of expression in epithelia.
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PMID:The transmembrane form of the CX3CL1 chemokine fractalkine is expressed predominantly by epithelial cells in vivo. 1123 35

We describe a case report of a 58-year-old woman presenting with acute intestinal obstruction in association with Crohn's disease. The terminal ileum was resected and was found to be heavily thickened and stenotic, with multiple, mucinous cysts in the bowel wall. Pathological findings were otherwise consistent with Crohn's disease. Enteritis cystica profunda was diagnosed. Diagnosis and differential diagnoses (mucin producing adenocarcinoma and pneumatosis cystoides intestinalis) are discussed.
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PMID:[Enteritis cystica profunda in a patient with Crohn disease]. 1157 53

Probiotics are living microorganisms that can affect the host in a beneficial manner. Prebiotics are nondigestible food ingredients that stimulate the growth and activity of probiotic bacteria already established in the colon. Efficacy of probiotic compounds has been shown in a wide range of gastrointestinal diseases. Lactobacillus GG alone, or the combination of Bifidobacterium bifidum and Streptococcus thermophilus, is effective in the treatment of Clostridium difficile, as well as in preventing the frequency and severity of infectious acute diarrhea in children. Prevention of antibiotic-induced diarrhea with the concomitant administration of either Lactobacillus GG or Saccharomyces boulardii has been demonstrated. The most successful studies involve the use of Lactobacillus GG at a dose of 1 x 1010 viable organisms per day and the yeast boulardii at a dose of 1 g/day. A probiotic preparation (VSL#3 - 6 g/day) that uses a combination of three species of Bifidobacterium, four strains of Lactobacillus and one strain of Streptocccus has shown promise in maintaining remission in ulcerative colitis and pouchitis, as well as in preventing the postoperative recurrence of Crohn's disease. The mechanism of action of probiotics may include receptor competition, effects on mucin secretion or probiotic immunomodulation of gut-associated lymphoid tissue. Oral administration of probiotic compounds has been demonstrated to be well tolerated and safe. However, while probiotics have the potential to improve human health and to prevent and treat some diseases, major improvements are needed in labelling and quality assurance procedures for probiotic compounds. In addition, well planned and controlled clinical studies are necessary to delineate fully the potential for probiotic compounds.
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PMID:The use of probiotics in gastrointestinal disease. 1177 48


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