Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009324 (ulcerative colitis)
 17,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

pANCA is a marker antibody associated with inflammatory bowel disease (IBD), including most patients with ulcerative colitis and a subset with Crohn's disease. This study addressed the hypothesis that pANCA reacts with an antigen(s) of microbial agents potentially relevant to IBD pathogenesis. Using a pANCA monoclonal antibody, we have previously identified the C-terminal basic random-coil domain of histone H1 as a pANCA autoantigen. BLAST analysis of the peptide databases revealed H1 epitope homologues in open reading frames of the Mycobacterium tuberculosis genome. Western analysis of extracts from six mycobacterial species directly demonstrated reactivity to a single, conserved approximately 32-kDa protein. Direct protein sequencing, followed by gene cloning, revealed a novel 214-amino-acid protein, an iron-regulated protein recently termed HupB. Sequence analysis demonstrated its homology with the mammalian histone H1 gene family, and recombinant protein expression confirmed its reactivity with the 5-3 pANCA monoclonal antibody. Binding activity of patient serum immunoglobulin G (IgG) to HupB did not correlate with reactivity to histone H1 or pANCA, indicating the complex character of the pANCA antigen. However, anti-HupB IgA was strongly associated with Crohn's disease (P < 0.001). These findings indicate that the 5-3 pANCA monoclonal antibody detects a structural domain recurrent among mycobacteria and cross-reactive with a DNA-binding domain of histone H1. The association of HupB-binding serum IgA with IBD provides new evidence for the association of a mycobacterial species with Crohn's disease.
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PMID:Identification of a novel mycobacterial histone H1 homologue (HupB) as an antigenic target of pANCA monoclonal antibody and serum immunoglobulin A from patients with Crohn's disease. 1056 69

Iron deficiency anemia, autoimmune hemolytic anemia, folic acid deficiency megaloblastic anemia, granulocytopenia, acute or chronic leukemia, idiopathic thrombocytopenic purpura have been reported as blood diseases among the extra-intestinal complications with ulcerative colitis until now. Iron deficiency anemia is most frequently seen, and it often derives from apparent or inapparent continuous gastrointestinal bleeding. Autoimmune hemolytic anemia produces antierythrocyte membrane autoantibody while idiopathic thrombocytopenic purpura produces antithrombocyte autoantibody leading to anemia or thrombocytopenia. For folic acid deficiency megaloblastic anemia and granulocytopenia, adverse reaction of sulfasalazine being administered to the patients with ulcerative colitis has been pointed out. While the cases with acute or chronic leukemia are reported increasingly, its cause is still unknown. For treatment of ulcerative colitis, it is considered necessary to find blood complications by carrying out general examinations of peripheral blood and examinations of blood picture, serum iron and folic acid routinely.
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PMID:[Extra-intestinal complications of ulcerative colitis: hematologic complication]. 1057 30

Genome scans have identified a region spanning 40 cM on the long arm of chromosome 12 as a susceptibility locus for inflammatory bowel disease (IBD). This locus contains several candidate genes for IBD, one of which is the gene for the natural resistance associated macrophage protein 2 (NRAMP2). This protein is a divalent cation transporter and is expressed in many cells and tissues. The putative role of this protein in innate immunity prompted us to investigate a possible relationship between NRAMP2 and IBD. We assessed the frequency of four restriction fragment length polymorphisms (IVS2+11A/G, IVS4+44C/A, 1254T/C, and IVS15Ex16-16C/G) in a group of 155 Crohn's disease (CD) patients, 114 ulcerative colitis (UC) patients, and 189 healthy controls. Linkage analysis was performed in a group of 70 families with multiple members suffering from IBD. We searched for additional intragenic markers and mutations by sequence analysis of the natural resistance-associated macrophage 2 gene of 33 CD patients, with a positive family history for IBD. We identified one novel restriction fragment length polymorphism in intron 15 of the gene. The frequency of the rare allele is: 0.08 in our control population. An increased frequency of this allele was found in CD patients but this difference did not reach statistical significance. A weak association between CD and homozygosity for the G allele of the IVS2+11A/G was found (OR [odds ratio] = 2.2, CI [confidence interval] = 1.3-3.9, chi2 = 8.4, p = 1.013). Nonparametric linkage analysis and transmissions disequilibrium tests did not provide evidence for linkage of NRAMP2 to IBD, UC, or CD. Sequence analysis of the exons and the iron-responsive element in a panel of 33 CD patients did not reveal any mutations in NRAMP2. Our association, linkage, and sequence analysis in IBD shows that the putative genetic risk factor on chromosome 12 likely is not NRAMP2. The weak association between the G/G genotype of IVS2+11A/G and CD may be due to linkage disequilibrium with a nearby disease-causing gene.
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PMID:Analysis of a positional candidate gene for inflammatory bowel disease: NRAMP2. 1083 68

Anemia is a common problem in inflammatory bowel disease (IBD). It is related to low Karnofsky scores, loss of weight, impaired physical activity, low tolerance to the underlying disease, and a poor growth rate in children. Multiple factors can contribute to the anemia in IBD, such as iron, folic acid or B(12) deficiency, treatment with immunosuppressive drugs or sulfasalazine, hemolysis, and anemia of chronic disease. Anemia of chronic disease is characterized by impaired iron utilization, lower erythropoietin (EPO) production than needed, and a low response of bone marrow erythroid progenitor cells to EPO. In recent years, recombinant human erythropoietin (rhEPO) has been used in combination with iron for the correction of refractory anemia in IBD patients (adults or children) with good results. There is increasing evidence that rhEPO may correct refractory anemia in IBD (both ulcerative colitis (UC) and Crohn's disease (CD)). In addition, such therapy may give IBD patients the opportunity to predonate blood before surgery and to avoid blood transfusions. One must not forget to exclude or correct other causes of anemia in IBD patients before administering rhEPO. Furthermore, the enhancement of erythropoiesis by EPO makes it mandatory to administer oral or intravenous iron supplementation during therapy to meet the increased demand. rhEPO is safe in IBD patients. Further studies with larger numbers of patients are needed to optimize the therapy with rhEPO in the refractory anemia of IBD.
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PMID:Anemia in inflammatory bowel disease - the role of recombinant human erythropoietin. 1096 11

Chronic ulcerative colitis (UC) patients frequently require iron supplementation to remedy anemia due to blood loss. However, the effect of iron supplementation on UC-associated carcinogenesis is unknown. In this study, the effect of an iron-enriched diet on dextran sulfate sodium-induced acute and chronic colitis in mice was assessed. In a short-term study, mice administered 1% DSS in the drinking fluid and an AIN76A diet containing increasing levels of iron exhibited dose-dependent increases in the severity of acute UC as compared to mice fed a control diet. A marked increase in iron deposition on the epithelial surface of the colon and in the inflamed areas and immunostaining for iNOS and nitrotyrosine were observed in the animals supplemented with diets containing different levels of iron. In a long-term carcinogenesis experiment, a twofold iron-enriched diet significantly increased colorectal tumor incidence (14/16, 88%) as compared with animals fed the control diet (3/16, 19%; P < 0.001). The present findings have implications for the management of human UC and suggest that dietary iron can enhance UC and its associated carcinogenesis by augmenting oxidative and nitrosative stress.
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PMID:Dietary iron supplementation enhances DSS-induced colitis and associated colorectal carcinoma development in mice. 1206 1

Long-term ulcerative colitis (UC) patients are at increased risk for developing colorectal cancer. In order to develop strategies for preventing UC-associated carcinogenesis, we studied the effect of the antioxidant N-acetylcysteine (NAC) on UC-associated cancer development in a mouse model. Female C57BL/6J mice were subjected to long-term administration of dextran sulfate sodium (DSS) in the drinking fluid and 2-fold iron-enriched AIN76A diet, with or without NAC. In the DSS-plus-2-fold iron positive control group, gross tumor incidence was 88.5% (23/26 mice) after 12 DSS cycles (1 DSS cycle = 7 day DSS treatment period followed by 10 day recovery period). The tumor multiplicity was 2.1 +/- 0.2 tumors/tumor-bearing mouse, and the tumor volume was 0.054 +/- 0.019 cm3. With 0.2% NAC administration, tumor incidence was significantly reduced (68%, 17/25 mice; P < 0.05), as was the tumor multiplicity (1.5 +/- 0.1 tumors/tumor-bearing mouse; P < 0.05). The tumor volume was lower (0.014 +/- 0.004 cm3), but not significantly decreased. The proliferation index was significantly decreased in non-cancerous epithelia (48.5 +/- 6.0% vs 32.0 +/- 3.7%; P < 0.05), but not in tumor cells. NAC significantly induced apoptosis in both non-cancerous epithelia and colorectal adenocarcinoma. The number of cells immunostained-positive for nitrotyrosine was markedly decreased in the non-cancerous mucosa of NAC-treated mice (102.4 +/-16.6 positive cells/mm2 mucosa vs 53.6 +/- 14.9 cells/mm2; P < 0.05). In addition, the number of inducible nitric oxide synthase (iNOS)-positive inflammatory cells in the non-cancerous mucosa of the distal colon was markedly decreased by NAC. This study indicates that the antioxidant NAC has the potential to serve as a preventive agent for UC-associated colorectal cancer, possibly via inhibition of cellular proliferation and nitrosative stress-caused cellular damage.
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PMID:Inhibition of chronic ulcerative colitis-associated colorectal adenocarcinoma development in a murine model by N-acetylcysteine. 1208 21

The chronic inflammatory bowel disease ulcerative colitis (UC) occurs commonly in the US and other Western countries, but its etiology is unknown. An association between UC and an elevated risk for colorectal cancer is well established. UC-associated colorectal carcinogenesis is probably driven by chronic inflammation, but the mechanism is unclear. The morphological development of UC-associated cancer differs from that of its sporadic counterpart. Similarly, detailed molecular analyses have indicated that whereas many of the genetic alterations observed in sporadic colon cancers also occur in UC-associated neoplasms, the timing and frequency of those changes in the setting of UC are different. These histological and molecular signatures may very well be reflective of an inflammation-driven carcinogenesis process in UC patients. Studies in animal models of UC have helped to shed light on the mechanisms of inflammation-driven colorectal carcinogenesis. The available evidence suggests that DNA damage caused by oxidative stress in the characteristic damage-regeneration cycle is a major contributor to colorectal cancer development in UC patients. Based on this concept, iron over-nutrition is proposed as a risk factor and dietary antioxidants as protective factors for UC and associated carcinogenesis.
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PMID:Oxidative stress and ulcerative colitis-associated carcinogenesis: studies in humans and animal models. 1266 92

The assessment of disease activity in inflammatory bowel disease is done using clinical parameters and various biological disease markers. Classical disease markers including erythrocyte sedimentation rate, acute phase proteins, such as orosomucoid and CRP, leukocyte and platelet counts, play an important role in the monitoring of disease activity. Furthermore, the determination of zinc, iron, ferritin, vitamin B12, and folic acid is important to avoid deficiencies in patients with severe disease or after surgeries. Stool cultures are helpful to detect bacterial or parasitic infections mimicking inflammatory bowel disease. The detection of specific antibodies such as pANCA, PAB and ASCA is helpful for the differential diagnosis Crohn's disease--ulcerative colitis.
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PMID:[Laboratory diagnosis in inflammatory bowel disease]. 1269 15

Proinflammatory cytokines released from monocytes/macrophages, in particular tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, IL-6, and IL-8 seem to play an important role in Inflammatory Bowel Disease (ulcerative colitis and Crohn's disease). Endotoxins or lipopolysaccharides, derived from the outer membrane of Gram-negative bacteria interact with CD14 on surface membrane of macrophages, thus triggering a signal cascade, which leads to the production and release of proinflammatory cytokines, particularly TNF-alpha. Therefore, in IBD, lipopolysaccharides could play a pathogenic role. In this respect, plasma endotoxins have been demonstrated in a not negligible percentage of patients with ulcerative colitis and in their unaffected relatives. The presence of circulating endotoxins could be due, at least in part, to the impaired natural immunity in either patients with ulcerative colitis or in their first degree unaffected relatives. Lactoferrin is an iron-binding glycoprotein, which binds to the lipid A region of lipopolysaccharide with a high affinity and this interaction prevents the binding of lipopolysaccharide to CD14, thus inhibiting the release of proinflammatory cytokines. Therefore, based on the possible pathogenic role exerted by endotoxins in ulcerative colitis, lactoferrin may deserve attention as a possible therapeutical agent in experimental models of Inflammatory Bowel Disease.
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PMID:Immune abnormalities and endotoxemia in patients with ulcerative colitis and in their first degree relatives: attempts at neutralizing endotoxin-mediated effects. 1287 Nov 78

The prevalence of anemia in patients with inflammatory bowel disease ranges from 8.8% to 73.7% depending on the patient subpopulation. Anemia, one of many extraintestinal complications of ulcerative colitis and Crohn disease, is generally defined as a hemoglobin value <120 g/L or hematocrit <0.4; severe anemia is defined as a hemoglobin level <100 g/L. Many patients have been shown to be intolerant of oral iron replacement therapy or their anemia was refractory to such supplementation. Correction of anemia through the administration of intravenous iron saccharate and/or supplemental erythropoietin has been shown to improve patient hematologic indices and quality of life. Future studies are needed to determine the type of patients at highest risk of developing severe anemia as well as the treatment interventions with the most beneficial effect.
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PMID:Prevalence and outcomes of anemia in inflammatory bowel disease: a systematic review of the literature. 1505 Aug 85


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