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)

Tryptophan absorption was studied in 32 patients with Crohn's disease and 16 healthy controls. A non-parametric sorting process identified two distinct groups of patients; 19 with normal tryptophan absorption values and 13 with distinctly subnormal results. The patients with impaired tryptophan absorption ate less, had lost more weight, and had lower serum albumin levels and greater intestinal protein loss than the group with normal absorption. Bacterial colonization of the jejunum, liver disease, and steroid therapy did not seem to influence tryptophan values in these patients.
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PMID:Serum tryptophan in Crohn's disease. 99 40

Scleroderma developed in six women who were taking L-tryptophan. Fasciitis and morphea were most common, but one patient had pleural effusion, hypertension, and signs of cardiac and kidney failure. In five patients the biopsy findings were characteristic of scleroderma; the sixth patient had Crohn's disease and developed fasciitis; her biopsy specimen showed inflammatory arteritis. All patients' conditions improved after cessation of their L-tryptophan intake, initiation of corticosteroid therapy, or both. These findings confirm previous data that show altered tryptophan-kynurenine metabolism in some patients with scleroderma and fasciitis, particularly with tryptophan loading.
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PMID:Scleroderma and L-tryptophan: a possible explanation of the eosinophilia-myalgia syndrome. 221 43

A 47-year-old woman with seronegative polyarthritis, diarrhea, and photosensitivity dermatitis was found to have Crohn's disease and pellagra. The presence of high values of 5-hydroxyindolacetic acid in the urine began the exhaustive investigations and finally enterotomy. No mass lesion was found. Argyrophilic cells were not increased in areas of inflamed intestinal mucosa or the normal mucosa. The disagreement between biochemical and histologic findings was attributed to sampling error. Antiinflammatory treatment for Crohn's disease was given and the gastrointestinal and articular symptoms improved, excretion of 5-hydroxyindolacetic acid returned to normal and there was no relapse of pellagra. Pellagra as a complication of Crohn's disease has been described in 4 cases; malnutrition and intestinal malabsorption were the proposed mechanisms for the niacin deficiency and pellagra of those patients. In the current case, the pathogenesis of pellagra may be accounted to wastage of tryptophan by an increased pool of intestinal argyrophilic cells, suggested by increased urinary excretion of 5-hydroxyindolacetic acid.
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PMID:Crohn's disease associated with pellagra and increased excretion of 5-hydroxyindolacetic acid. 903 Jun 78

A role for cytokine regulated proteins in epithelial cells has been suggested in the pathogenesis of inflammatory bowel diseases (IBD). The aim of this study was to identify such cytokine regulated targets using a proteomic functional approach. Protein patterns from (35)S-radiolabeled homogenates of cultured colon epithelial cells were compared before and after exposure to interferon-gamma, interleukin-1beta and interleukin-6. Proteins were separated by two-dimensional polyacrylamide gel electrophoresis. Both autoradiographies and silver stained gels were analyzed. Proteins showing differential expression were identified by tryptic in-gel digestion and mass spectrometry. Metabolism related proteins were also investigated by Western blot analysis. Tryptophanyl-tRNA synthetase, indoleamine-2,3-dioxygenase, heterogeneous nuclear ribonucleoprotein JKTBP, interferon-induced 35kDa protein, proteasome subunit LMP2 and arginosuccinate synthetase were identified as cytokine modulated proteins in vitro. Using purified epithelial cells from patients, overexpression of indoleamine-2,3-dioxygenase, an enzyme involved in tryptophan metabolism, was confirmed in Crohn's disease as well as in ulcerative colitis, as compared to normal mucosa. No such difference was found in diverticulitis. Potentially, this observation opens new avenues in the treatment of IBD.
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PMID:Proteomic analysis of cytokine induced proteins in human intestinal epithelial cells: implications for inflammatory bowel diseases. 1198 29

The kynurenine metabolites of tryptophan may be involved in the regulation of neuronal activity and thus gut motility and secretion. We have now performed a pilot study to measure serum concentrations of purines and kynurenines in patients with mild inflammatory bowel disease, as well as in sex- and age-matched control subjects. For some analyses, the patients were subdivided into subgroups of those with Crohn's disease and those with ulcerative colitis. The analyses indicated an increased activity in one branch of the kynurenine pathway. While there was no demonstrable difference in neopterin levels in either of the patient groups compared with controls, indicating that the disorders were in an inactive quiescent phase, both groups showed significantly higher levels of lipid peroxidation products. This suggests the presence of increased oxidative stress even during relative disease inactivity. The increased level of kynurenic acid may represent either a compensatory response to elevated activation of enteric neurones or a primary abnormality which induces a compensatory increase in gut activity. In either case, the data may indicate a role for kynurenine modulation of glutamate receptors in the symptoms of inflammatory bowel disease.
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PMID:Purine, kynurenine, neopterin and lipid peroxidation levels in inflammatory bowel disease. 1221 59

T-cells are causally involved in the pathogenesis of inflammatory bowel disease (IBD). The tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase (IDO) regulates T-cell proliferation and survival. We show in this report that IDO mRNA is markedly induced in lesional colonic biopsies of IBD patients. IDO is primarily expressed in CD123(+) mononuclear cells infiltrating the submucosal areas of the inflamed lesions. In Crohn's disease (CD), IDO is also strongly expressed in perifollicular regions of lymphoid follicles. Upregulation of IDO is of functional significance, as we detected an increase of kynurenine and of the kynurenine/tryptophan ratio in supernatants from colonic explant cultures (CECs) of CD patients. Immunohistochemistry of colonic biopsies taken from CD patients prior and after treatment with the TNF-blocking antibody Infliximab revealed reduced IDO expression in patients with good clinical response to Infliximab. In summary, high local expression of IDO may represent an anti-inflammatory mechanism tempting to counterbalance the tissue-damaging effects of activated T-cells infiltrating the colonic mucosa in IBD.
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PMID:Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease. 1538 May 29

Nucleotide oligomerization domain (NOD) 2 functions as a mammalian cytosolic pathogen recognition molecule, and mutant forms have been genetically linked to Crohn's disease (CD). NOD2 associates with the caspase activation and recruitment domain of RIP-like interacting caspase-like apoptosis regulatory protein kinase (RICK)/RIP2 and activates nuclear factor (NF)-kappaB in epithelial cells and macrophages, whereas NOD2 mutant 3020insC, which is associated with CD, shows an impaired ability to activate NF-kappaB. To gain insight into the molecular mechanisms of NOD2 function, we performed a functional analysis of deletion and substitution NOD2 mutants. NOD2, but not NOD2 3020insC mutant, associated with cell surface membranes of intestinal epithelial cells. Membrane targeting and subsequent NF-kappaB activation are mediated by two leucine residues and a tryptophan-containing motif in the COOH-terminal domain of NOD2. The membrane targeting of NOD2 is required for NF-kappaB activation after the recognition of bacterial muramyl dipeptide in intestinal epithelial cells.
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PMID:Membrane recruitment of NOD2 in intestinal epithelial cells is essential for nuclear factor-{kappa}B activation in muramyl dipeptide recognition. 1599 97

Johne's disease, caused by Mycobacterium paratuberculosis infection, is a worldwide problem for the dairy industry and has a possible involvement in Crohn's disease in humans. To identify virulence determinants of this economically important pathogen, a library of 5,060 transposon mutants was constructed using Tn5367 insertion mutagenesis, followed by large-scale sequencing to identify disrupted genes. In this report, 1,150 mutants were analyzed and 970 unique insertion sites were identified. Sequence analysis of the disrupted genes indicated that the insertion of Tn5367 was more prevalent in genomic regions with G+C content (50.5 to 60.5%) lower than the average G+C content (69.3%) of the rest of the genome. Phenotypic screening of the library identified disruptions of genes involved in iron, tryptophan, or mycolic acid metabolic pathways that displayed unique growth characteristics. Bioinformatic analysis of disrupted genes identified a list of potential virulence determinants for further testing with animals. Mouse infection studies showed a significant decrease in tissue colonization by mutants with a disruption in the gcpE, pstA, kdpC, papA2, impA, umaA1, or fabG2_2 gene. Attenuation phenotypes were tissue specific (e.g., for the umaA1 mutant) as well as time specific (e.g., for the impA mutant), suggesting that those genes may be involved in different virulence mechanisms. The identified potential virulence determinants represent novel functional classes that could be necessary for mycobacterial survival during infection and could provide suitable targets for vaccine and drug development against Johne's and Crohn's diseases.
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PMID:Identification of novel virulence determinants in Mycobacterium paratuberculosis by screening a library of insertional mutants. 1679 Jul 54

We have investigated the possible role of the metabolism of tryptophan and activity of the enzyme indoleamine 2,3-dioxygenase (IDO) in the immune regulation of coeliac disease (CD). Serum concentrations of tryptophan and its metabolites kinurenines were determined by high performance liquid chromatography in 24 patients with CD, seven patients with Crohn's disease and five healthy patients. We detected an increase of kynurenine (4.2 micromol/l +/- 0.27 versus 2.6 micromol/l +/- 0.54, P < 0002) and of the kynurenine/tryptophan ratio in supernatants of coeliac patients (11.5 micromol/l +/- 1.01 versus 6.5 micromol/l +/- 1.57, P < 0005) in comparison with healthy patients, respectively, and we found no differences with Crohn's disease patients. Immunohistochemistry analysis of intestinal biopsies from CD patients showed an increased expression of IDO, interferon-gamma, interleukin-10 and transforming growth factor-beta. Our data suggest that a mechanism(s) dependent on tryptophan catabolism might regulate the immune responses in CD.
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PMID:Tryptophan metabolism and indoleamine 2,3-dioxygenase expression in coeliac disease. 1736 67

The impact of low-shear stress (LSS) was evaluated on an Adherent-invasive Escherichia coli clinical isolate (AIEC strain O83:H1) from a Crohn's disease patient. High-aspect ratio vessels (HARVs) were used to model LSS conditions to characterize changes in environmental stress resistance and adhesion/invasive properties. Low-shear stress-grown cultures exhibited enhanced thermal and oxidative stress resistance as well as increased adherence to Caco-2 cells, but no changes in invasion were observed. An AIEC rpoS mutant was constructed to examine the impact of this global stress regulator. The absence of RpoS under LSS conditions resulted in increased sensitivity to oxidative stress while adherence levels were elevated in comparison with the wild-type strain. TnphoA mutagenesis and rpoS complementation were carried out on the rpoS mutant to identify those factors involved in the LSS-induced adherence phenotype. Mutagenesis results revealed that one insertion disrupted the tnaB gene (encoding tryptophan permease) and the rpoS tnaB double mutant exhibited decreased adherence under LSS. Complementation of the tnaB gene, or medium supplemented with exogenous indole, restored adhesion of the rpoS tnaB mutant under LSS conditions. Overall, our study demonstrated how mechanical stresses such as LSS altered AIEC phenotypic characteristics and identified novel functions for some RpoS-regulated proteins.
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PMID:The effects of low-shear stress on Adherent-invasive Escherichia coli. 1831 96


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