Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By using two-color immunofluorescence with fluorescein isothiocyanate (FITC) and phycoerythrin (PE)-labelled monoclonal antibodies and multiparameter flow cytometry, we investigated lamina propria lymphocyte subsets of patients with ulcerative colitis (UC) and Crohn's disease (CD). Leu-3/Leu-2 (CD4/CD8) ratio of lamina propria lymphocytes (LPL) of CD (mean +/- SD: 1.9 +/- 0.8, P less than 0.01) was significantly decreased compared with controls (3.3 +/- 1.1), because of an increased number of CD8+ lymphocytes. The majority of lamina propria CD4+ cells were CD4+, Leu-8- and CD4+, CD45R- both in controls and IBD tissue. Many lamina propria T lymphocytes were activated, expressing HLA-DR antigen not only in IBD but also in controls. NK cells defined by CD16 and CD 56 (3.0 +/- 1.4%, P less than 0.01) were significantly decreased in patients with UC compared with controls (6.5 +/- 3.0%). A low proportion of B cells in the intestinal mucosa expressed Leu-8 antigen and CD23 antigen. The proportion of activated B cells of LPL was high in IBD mucosa as well as normal mucosa. These findings suggest that local activation of B cells leads to the loss of the expression of Leu-8 antigen and CD23.
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PMID:Two-color immunofluorescence and flow cytometric analysis of lamina propria lymphocyte subsets in ulcerative colitis and Crohn's disease. 191 70

Lymphoid cell subsets, including T cells as well as Ig-containing cells in the colonic mucosa and HLA-DR antigens on colonic epithelia, were examined in non-IBD colitis (colitis excluding ulcerative colitis (UC) and Crohn's disease) by the indirect immunoperoxidase staining method. Mouse anti-CD5, CD8, CD4, IgG, IgA1, IgA2, IgM, IgD, IgE, HLA-DR, and NuIa monoclonal antibodies were used as the first antibody. The results were compared to those of the normal controls and UC. T cell subsets in non-IBD colitis were almost similar to those of the controls and UC. The number of Ig-containing cells of all classes, except for IgA, tended to be increased in non-IBD colitis. In particular, both IgG- and IgE-containing cells were significantly increased compared to those in the controls. Compared to UC, IgG-containing cells were decreased in non-IBD colitis. Namely, in non-IBD colitis, as well as in UC, the change of Ig-containing cells (B cell lineage) was more pronounced than that of T cells. The frequency of the expression of HLA-DR antigens on colonic epithelia in non-IBD colitis was 70%, which was significantly higher than that in controls (0%), but significantly lower than that in UC (100%). Whether the differences in the number of IgG-containing cells, and the frequency of epithelial HLA-DR expression between non-IBD colitis and UC was due to the differences of the degree of local inflammation or due to the differences of the nature of the two diseases was not elucidated in this study.
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PMID:Lymphoid cell subsets in colonic mucosa and HLA-DR antigens on colonic epithelia in colitis excluding ulcerative colitis and Crohn's disease. 227 31

Prolonged antigenic stimulation results in lymphocyte shedding of CD27, a member of the tumour necrosis factor receptor (TNFR) family, and transformation to a stable phenotype capable of synthesizing interleukin-4 (IL-4). Co-expression of alpha4beta7 identifies those cells with gut-homing potential. We have investigated these cell populations in patients with inflammatory colonic disease. Circulating and lamina propria mononuclear cells were isolated from patients with Crohn's disease (CD), ulcerative colitis (UC), non-inflammatory bowel disease (non-IBD) colonic inflammation and healthy controls. Double and triple colour flow cytometry for CD3, CD4, CD27, alpha4beta7 and intracellular cytokines was performed. Circulating CD4+ CD27- populations were increased in patients with CD (8.8 +/- 0.8%, P < 0.001), UC (12.2 +/- 1.9%, P < 0.001) and non-IBD colitis (10.5 +/- 1.3%, P < 0.01) as compared with controls (6.1 +/- 0.5%). CD4+ CD27- alpha4beta7+ cells were increased in CD (P < 0.01). Lamina propria CD4+ CD27- populations were depressed significantly in CD (P < 0.05), UC (P < 0.02) and non-IBD colitis (P < 0.03). Mucosal CD4+ CD27- cells synthesized IL-4 in preference to interferon-gamma. Thus, colonic inflammation is associated with alterations in gut-tropic circulating and mucosal populations of differentiated memory T cells with the phenotype of predominantly IL-4-synthesizing cells.
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PMID:Variation in gut-homing CD27-negative lymphocytes in inflammatory colon disease. 974 20

Weight loss is a major component of the clinical syndrome in patients with acquired immunodeficiency syndrome (AIDS). The impact of malnutrition on the outcome of the disease has been unappreciated in many investigations. The authors evaluated the effects of oral nutritional supplementation on the morphology and immunology of the intestinal mucosa of patients with AIDS. Twelve patients with AIDS without diarrhea or opportunistic infections, with at least 10% of body weight loss over 1 year, were submitted to anthropometric measures, peripheral blood T-lymphocyte counts, and peroral jejunal biopsy before and after oral nutritional supplementation. An industrialized peptide-based formula containing omega-3 fatty acids was given for 6 weeks. Jejunal samples were analyzed by histomorphometry, including villous-to-crypt ratio, lamina propria, and intraepithelial lymphocyte count. Immunologic assessment of the intestinal mucosa was made by indirect immunoperoxidase using monoclonal antibodies against CD3, CD4, and CD8. Seven patients with irritable bowel syndrome and two healthy volunteers were selected as a control group for histologic and immunohistochemical comparisons. After 6 weeks the patient group maintained their body weight and increased their tricipital fold. The number of peripheral blood T cells, albumin, transferrin, and the number of CD3+, CD4+, and CD8+ cells in jejunal mucosa as well as the intestinal morphometry remained stable. Oral supplementation contributed to maintaining body weight and may constitute a reasonable adjuvant therapeutic tool against AIDS progression.
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PMID:Effects of oral nutritional supplementation on the intestinal mucosa of patients with AIDS. 1063 16

Cytokines are the key mediators of inflammation in the IBD and are focus of renewed interest to plan therapeutic strategies against this disease. However, there are gaps in our knowledge at present and a lot of questions need clear answers. Even with a therapy as specific as anti-TNF antibody, it is not clear if the benefit is attributable to simple binding and clearance of TNF-alpha or to binding on the cell surface and subsequent deletion of the activated macrophage. When a drug appears to be less effective than pre-clinical models suggest, can failures in effectiveness from delivery or dosing the differentiated? The disappointing results of clinical trials with IL-10 is at odds with the prediction of benefit from animal models. It even brings into question the validity of those models as well as the soundness of design of the clinical trials on which efficacy of IL-10 is assessed. Other exciting new methods to treat IBD could be use of monoclonal antibodies to effector T cell molecules (such as CD4 or CD44v7) removal of such cytokine secreting cells (apheresis), antibodies to proinflammatory cytokines (such as TNF-alpha, IFN-alpha, IFN-gamma, and IL-12) or administration of anti-inflammatory cytokines (such as IL-10, IL-11). Challenges in developing new therapeutic strategies include not only identifying novel agents, but also improving the definitions of clinical endpoints and defining efficacy at the biologic level. There is also need to further refine our knowledge about genetic elements and environment initiators to comprehensively manage IBD.
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PMID:Cytokines and inflammatory bowel disease. 1069 14

Intestinal epithelial cells seem to play a key role during IBD. The network of cellular interactions between epithelial cells and lamina propria mononuclear cells is still incompletely understood. In the following co-culture model we investigated the influence of intestinal epithelial cells on cytokine expression of T cytotoxic and T helper cells from patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMC) were purified by a Ficoll-Hypaque gradient followed by co-incubation with epithelial cells in multiwell cell culture insert plates in direct contact as well as separated by transwell filters. We used Caco-2 cells as well as freshly isolated colonic epithelia obtained from surgical specimens. Three-colour immunofluorescence flow cytometry was performed after collection, stimulation and staining of PBMC with anti-CD4, anti-CD8, anti-IFN-gamma and anti-IL-4. Patients with IBD (Crohn's disease (CD), n = 12; ulcerative colitis (UC), n = 16) and healthy controls (n = 10) were included in the study. After 24 h of co-incubation with Caco-2 cells we found a significant increase of IFN-gamma-producing CD8+ lymphocytes in patients with IBD. In contrast, healthy controls did not respond to the epithelial stimulus. No significant differences could be found between CD and UC or active and inactive disease. A significant increase of IFN-gamma+/CD8+ lymphocytes in patients with UC was also seen after direct co-incubation with primary cultures of colonic crypt cells. The observed epithelial-lymphocyte interaction seems to be MHC I-restricted. No significant epithelial cell-mediated effects on cytokine expression were detected in the PBMC CD4+ subsets. Patients with IBD-even in an inactive state of disease-exert an increased capacity for IFN-gamma induction in CD8+ lymphocytes mediated by intestinal epithelial cells. This mechanism may be important during chronic intestinal inflammation, as in the case of altered mucosal barrier function epithelial cells may become targets for IFN-gamma-producing CD8+ lymphocytes.
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PMID:Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-gamma) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells. 1116 92

A case is presented of a 34-year-old man with a 10-year history of HIV infection (CD4 counts 750-1100/mm3) who initially presented with upper right quadrant pain that was crampy, achy and periumbilical, not affected by food, and was indicative of early-stage acalculous cholecystitis. Over a three month period, tests failed to identify the cause of his pain. It was first labeled gastroenteritis and then irritable bowel syndrome. By the third month, his pain was mostly in the right upper quadrant. This area was sore when touched and worse after ingestion of fatty foods. A test detected elevated transaminases. It appeared that he had acalculous cholecystitis, which is one of several hepatobiliary complications of HIV. In HIV-infected individuals, acalculous cholecystitis is often an infectious disease of the biliary tract. Patients present with right upper quadrant and/or epigastric pain that is worse after fatty meals. Eventually, sonographs can detect a thickening of the gall bladder wall and dilation of the hepatic ducts, but early in the disease it is unlikely that the test result will be abnormal. The condition is often caused by CMV and cryptosporidium, but other pathogens may also cause acalculous cholecystitis. Perforation of the gall bladder and development of potentially irreversible abnormalities which complicate infection may result if the condition is left untreated. Although frequently connected with infectious diseases, cholecystitis may also occur in patients with high CD4 counts and no other HIV-related conditions.
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PMID:Abdominal pain in an HIV-infected man. 1136 36

Currently used standard treatment in IBD is effective and sufficient for the majority of patients. Published numbers regarding therapy refractoriness are probably related to referral centers and not representative. Pharmacological optimization of available drugs improves the standard situation further. Biological therapies in a larger meaning are studied intensively, but obviously hopes are to some extent not real. Biological and for some principles clinical effects (i.e. TNF antibodies, CD4 antibodies) are proven, the effects are, however, limited and long-term risks and results are not clarified. Numerous approaches are not clinically relevantly effective which is, in particular, true for those inhibiting single mediators. A number of alternative concepts such as hormones and growth factors could be effective and will be studied further. In particular probiotics may be a development of the future and they belong to the 'biologic treatments' in the true sense.
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PMID:Biological therapy in IBD. Anti-tumor necrosis factor-alpha and others. 1457 Nov 15

Inflammatory intestinal pathology has been reported in children with regressive autism (affected children). Detailed analysis of intestinal biopsies in these children indicates a novel lymphocytic enterocolitis with autoimmune features; however, links with cognitive function remain unclear. To characterize further, the nature and extent of this disease we examined the mucosal infiltrate using flow cytometry. Duodenal, ileal, and colonic biopsies were obtained from 52 affected children, 25 histologically normal, and 54 histologically inflamed, developmentally normal controls. Epithelial and lamina propria lymphocyte populations were isolated and examined by multicolor flow cytometry. Adjacent biopsies were assessed by semiquantitative histopathology. At all sites, CD3(+) and CD3(+)CD8(+) IEL as well as CD3(+) LPL were significantly increased in affected children compared with developmentally normal noninflamed control groups (p<0.01) reaching levels similar to inflamed controls. In addition, two populations--CD3(+)CD4(+) IEL and LP CD19(+) B cells--were significantly increased in affected children compared with both noninflamed and inflamed control groups including IBD, at all sites examined (p<0.01). Histologically there was a prominent mucosal eosinophil infiltrate in affected children that was significantly lower in those on a gluten- and casein-free diet, although lymphocyte populations were not influenced by diet. The data provide further evidence of a pan-enteric mucosal immunopathology in children with regressive autism that is apparently distinct from other inflammatory bowel diseases.
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PMID:Intestinal lymphocyte populations in children with regressive autism: evidence for extensive mucosal immunopathology. 1503 38

Products of arachidonic acid metabolism are important for mucosal homeostasis, because blockade of this pathway with an NSAID triggers rapid onset of severe colitis in the IL-10 knockout (IL-10(-/-)) model of IBD. Rag mice do not make T or B cells. This study determined whether reconstitution of Rag mice with T cells from IL-10(-/-) mice transferred NSAID colitis susceptibility. Rag mice were reconstituted by intraperitoneal injection with splenocytes from wild-type (WT) or IL-10(-/-) animals. Colitis was induced by using piroxicam and was graded histologically. Isolated lamina propria mononuclear cells (LPMC), lamina propria T cells, and LPMC depleted of T cells from reconstituted Rag mice were studied for cytokine production. Only animals reconstituted with IL-10(-/-) CD4(+) T cells and administered piroxicam developed severe colitis. LPMC from these colitic animals made IFN-gamma, whose production was dependent on T cells. Some IL-10 was produced but only from non-T cells. LPMC from the healthy Rag mice that were reconstituted with WT T cells and were piroxicam resistant made much more IL-10. This was mostly T cell dependent. In conclusion, only CD4(+) T cells from IL-10(-/-) animals leave Rag mice susceptible to NSAID-induced, Th1 colitis. Lamina propria T cells normally make large quantities of IL-10, suggesting that IL-10 from T cells may be protective.
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PMID:CD4+ T cells from IL-10-deficient mice transfer susceptibility to NSAID-induced Rag colitis. 1524 67


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