Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0009319 (colitis)
 19,384 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During a 12-year period, 46 children and adolescents with inflammatory bowel disease were followed from the time of diagnosis with regular biochemical tests of liver function. Thirty-four patients had ulcerative colitis and 12 had Crohn's disease. Mean age at the time of diagnosis was 10.2 years (range 7 months-17 years) and the mean follow-up period was 5.2 years (range 1-11 years). Pathological liver function tests were found in 60% of the 34 patients with ulcerative colitis: 9 of these 20 patients demonstrated more severe disturbance, usually at the time of diagnosis. Liver damage was most frequent in patients with total colitis. Liver biopsy was performed in eight patients, demonstrating "pericholangitis", fibrosis and in one case cirrhosis. Morphometry of electron microscopical pictures revealed a significantly increased number of lysosomes and dilated cisternae of the rough endoplasmic reticulum. ERCP was performed in two patients, verifying primary sclerosing cholangitis in one. Four of the 12 patients with Crohn's disease had mildly pathological liver function tests. No correlation was found to the extent, duration or treatment of bowel disease. In our series of juvenile inflammatory bowel disease, liver damage occurred frequently, especially in ulcerative colitis. The more severe changes tended to coincide with the onset of bowel disease.
 ...
PMID:Liver damage in juvenile inflammatory bowel disease. 221 95

Sera with anti-mitochondrial autoantibodies detected by indirect immunofluorescence and/or enzyme-linked immunosorbent assay (ELISA) were examined by immunoblotting against pig heart mitochondria. Seven types of reactions were defined, according to the pattern of the labelled bands. Type I sera reacted with 12 bands located within four zones. The most intensively labelled bands were located at 70, 67, 58, 63 and 43 kDa. Other types gave decreasing band numbers. When beef heart mitochondria were used, sera belonging to each of the above types had a profile of labelled bands which sometimes differed from those obtained with pig heart mitochondria. When the chloroform extracted F1-ATPase from beef heart mitochondria was used to prepare the immunoblots, primary biliary cirrhosis (PBC) sera with anti-mitochondria antibodies reacted with all the bands although zone A bands were less labelled. Rat liver mitochondria gave seven bands with type I sera among which the 57 and 35 kDa bands were specific for rat liver mitochondria, as shown by absorption tests. Sera of PBC patients were also tested in immunoblotting against rat liver subcellular fractions including mitoplasts, submitochondrial particles, inner membrane, outer membrane, matrix proteins and inter-membrane proteins. Antigenic bands of A and B zones were localized in the inner membrane and/or in the matrix proteins and the 35 kDa band in inter-membrane proteins. The outer membrane gave no reaction. The most frequent anti-mitochondrial autoantibody types in PBC were type II, then I, whilst for chronic active hepatitis type III was the most common. Type V was only seen in a patient suffering from a typical PBC. Some sera from patients with syphilis, collagenous colitis or progressive systemic sclerosis labelled one or two bands distinct from those labelled by the PBC sera. Sera from patients with drug-induced hepatitis with endoplasmic reticulum antibodies and with systemic lupus erythematosus were generally found negative by immunoblotting.
 ...
PMID:Use of immunoblotting to characterize the mitochondrial antigens recognized by anti-mitochondrial autoantibodies. 317 Nov 87

The pathogenesis of Clostridium difficile enterocolitis appears to involve colonization of the bowel followed by release of toxin A, an enterotoxin, and toxin B, a cytotoxin. The purpose of this study was to determine the effect of purified toxins A and B on intestinal secretion, epithelial permeability, and morphology in perfused rabbit ileal loops. Intestinal permeability after toxin exposure was assessed by blood-to-lumen clearance of [3H]mannitol. Toxin A at doses of 5-100 micrograms/10 cm ileal loop caused a threefold to fivefold increase in [3H]mannitol permeability (p less than 0.001) vs. equal concentrations of toxin B or buffer control. In addition, perfusate from toxin A-exposed loops contained significantly more neutrophils (p less than 0.001) than toxin B or control loops. Toxin A caused severe epithelial cell necrosis with destruction of villi and polymorphonuclear infiltration. Electron microscopy of mucosa subjected to a low dose of toxin revealed widespread nonspecific dilatation of endoplasmic reticulum and mitochondrial swelling. In contrast to these effects of toxin A in ileal loops, in vitro experiments with ileal explants in short-term organ culture revealed that toxin A had no effect on epithelial cell permeability, protein synthesis, release of alkaline phosphatase, or morphology. Our results show that purified toxin A but not toxin B causes severe inflammatory enteritis in rabbit ileal loops, but has no discernable effect on rabbit ileum in vitro. We speculate that toxin A may contribute significantly to intestinal damage in C. difficile-associated colitis and diarrhea.
 ...
PMID:Differential effects of Clostridium difficile toxins A and B on rabbit ileum. 359 62

Protracted diarrhea is a clinical entity characterized by diarrhea lasting greater than 2 weeks, starting before 3 months of age, with severe nutritional aggravation and negative stool culture for enteropathogens. This report deals with the ultrastructural abnormalities found in the intestinal mucosa of children with protracted diarrhea. Forty children (mean age 5.1 months) were studied. They were submitted to the following tests of intestinal function: D-xylose, triglyceride tolerance, small bowel biopsy (light and electron microscope), sigmoidoscopy, and sweat test. D-Xylose absorption and triglyceride tolerance test in these patients were both significantly lower than controls. Ultrastructural analysis of the small bowel of 12 patients showed various degrees of alterations, mainly shortening of the microvilli, increased number of multivesicular bodies, and vacuolation of mitochondria and endoplasmic reticulum. These lesions were totally reversible after clinical and nutritional recovery as could be proven in two children. The most common cause of protracted diarrhea in these patients was secondary carbohydrate intolerance and dietary protein cow's milk and soy bean intolerance, which resulted in colitis or malabsorption as a consequence of intestinal mucosa injury due to acute gastroenteritis.
 ...
PMID:Protracted diarrhea in infancy: clinical aspects and ultrastructural analysis of the small intestine. 404 29

Verotoxin-producing Escherichia coli (VTEC) are pathogenic bacteria associated with diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Verotoxins (VTs) elaborated by these organisms produce cytopathic effects on a restricted number of cell types, including endothelial cells lining the microvasculature of the bowel and the kidney. Because human intestinal epithelial cells lack the globotriaosylceramide receptor for VT binding, it is unclear how the toxin moves across the intestinal mucosa to the systemic circulation. The aims of this study were to determine the effects of VT-1 on intestinal epithelial cell function and to characterize VT-1 translocation across monolayers of T84 cells, an intestinal epithelial cell line. VT-1 at concentrations up to 1 microgram/ml had no effect on the barrier function of T84 monolayers as assessed by measuring transmonolayer electrical resistance (102 +/- 8% of control monolayers). In contrast, both VT-positive and VT-negative VTEC bacterial strains lowered T84 transmonolayer resistance (45 +/- 7 and 38 +/- 6% of controls, respectively). Comparable amounts of toxin moved across monolayers of T84 cells, exhibiting high-resistance values, as monolayers with VTEC-induced decreases in barrier function, suggesting a transcellular mode of transport. Translocation of VT-1 across T84 monolayers paralleled the movement of a comparably sized protein, horseradish peroxidase. Immunoelectron microscopy confirmed transcellular transport of VT-1, since the toxin was observed within endosomes and associated with specific intracellular targets, including the Golgi network and endoplasmic reticulum. These data present a mode of VT-1 uptake by toxin-insensitive cells and suggest a general mechanism by which bacterial toxins lacking specific intestinal receptors can penetrate the intestinal epithelial barrier.
 ...
PMID:Translocation of verotoxin-1 across T84 monolayers: mechanism of bacterial toxin penetration of epithelium. 943 61

Verotoxin (VT) is involved in the etiology of both hemorrhagic colitis and the hemolytic uremic syndrome which are microvasculopathies of the colon and pediatric renal glomerulus respectively. Thus, VT can be considered a vasotoxin. Cell sensitivity in vitro varies according to the receptor glycolipid (globotriaosyl ceramide-Gb3) expression and also to intracellular trafficking of the receptor/toxin complex, such that in highly sensitive cells, the toxin is targeted to the endoplasmic reticulum and nuclear envelope. Such cells include tumor cells which have become drug resistant. Thus Gb3 is upregulated in certain tumors and when such tumor cells become drug resistant, their sensitivity to verotoxin increases. This may be due to a direct role of the MDRI drug efflux pump in glycolipid biosynthesis. In addition to the tumor tissue, the toxin receptor may also be expressed in the tumor neovasculature suggesting that activated endothelial cells may be verotoxin sensitive. Thus VT may have both a direct and indirect antineoplastic potential. VT has proved highly effective in a xenograft cancer model and the possible therapeutic use of VT is discussed.
 ...
PMID:Verotoxin/globotriaosyl ceramide recognition: angiopathy, angiogenesis and antineoplasia. 1076 2

The epithelial cells of the gastrointestinal tract are exposed to toxins and infectious agents that can adversely affect protein folding in the endoplasmic reticulum (ER) and cause ER stress. The IRE1 genes are implicated in sensing and responding to ER stress signals. We found that epithelial cells of the gastrointestinal tract express IRE1beta, a specific isoform of IRE1. BiP protein, a marker of ER stress, was elevated in the colonic mucosa of IRE1beta(-/-) mice, and, when exposed to dextran sodium sulfate (DSS) to induce inflammatory bowel disease, mutant mice developed colitis 3-5 days earlier than did wild-type or IRE1beta(+/-) mice. The inflammation marker ICAM-1 was also expressed earlier in the colonic mucosa of DSS-treated IRE1beta(-/-) mice, indicating that the mutation had its impact early in the inflammatory process, before the onset of mucosal ulceration. These findings are consistent with a model whereby perturbations in ER function, which are normally mitigated by the activity of IRE1beta, participate in the development of colitis.
 ...
PMID:Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice. 1123 59

CD1d is a major histocompatibility complex (MHC) class I-related molecule that functions in glycolipid antigen presentation to distinct subsets of T cells that express natural killer receptors and an invariant T-cell receptor-alpha chain (invariant NKT cells). The acquisition of glycolipid antigens by CD1d occurs, in part, in endosomes through the function of resident lipid transfer proteins, namely saposins. Here we show that microsomal triglyceride transfer protein (MTP), a protein that resides in the endoplasmic reticulum of hepatocytes and intestinal epithelial cells (IECs) and is essential for lipidation of apolipoprotein B, associates with CD1d in hepatocytes. Hepatocytes from animals in which Mttp (the gene encoding MTP) has been conditionally deleted, and IECs in which Mttp gene products have been silenced, are unable to activate invariant NKT cells. Conditional deletion of the Mttp gene in hepatocytes is associated with a redistribution of CD1d expression, and Mttp-deleted mice are resistant to immunopathologies associated with invariant NKT cell-mediated hepatitis and colitis. These studies indicate that the CD1d-regulating function of MTP in the endoplasmic reticulum is complementary to that of the saposins in endosomes in vivo.
 ...
PMID:CD1d function is regulated by microsomal triglyceride transfer protein. 1510 43

Intestinal epithelial cells (IEC) are constantly exposed to both high concentrations of the bacterial ligand LPS and the serine protease trypsin. MD-2, which contains multiple trypsin cleavage sites, is an essential accessory glycoprotein required for LPS recognition and signaling through TLR4. The aim of this study was to characterize the expression and subcellular distribution of intestinal epithelial MD-2 and to delineate potential functional interactions with trypsin and then alteration in inflammatory bowel disease (IBD). Although MD-2 protein expression was minimal in primary IEC of normal colonic or ileal mucosa, expression was significantly increased in IEC from patients with active IBD colitis, but not in ileal areas from patients with severe Crohn's disease. Endogenous MD-2 was predominantly retained in the calnexin-calreticulin cycle of the endoplasmic reticulum; only a small fraction was exported to the Golgi. MD-2 expression correlated inversely with trypsin activity. Biochemical evidence and in vitro experiments demonstrated that trypsin exposure resulted in extensive proteolysis of endogenous and soluble MD-2 protein, but not of TLR4 in IEC, and was associated with desensitization of IEC to LPS. In conclusion, the present study suggests that endoplasmic reticulum-associated MD-2 expression in IBD may be altered by ileal protease in inflammation, leading to impaired LPS recognition and hyporesponsiveness through MD-2 proteolysis in IEC, thus implying a physiologic mechanism that helps maintain LPS tolerance in the intestine.
 ...
PMID:Trypsin-sensitive modulation of intestinal epithelial MD-2 as mechanism of lipopolysaccharide tolerance. 1654 63

Infection with Shiga toxin (Stx)-producing Escherichia coli O157:H7 causes bloody diarrhea and hemorrhagic colitis in humans, sometimes resulting in fatal systemic complications. Among the known Stx family members, Stx2 is responsible for the most severe forms of disease. Stx2 binds to target cells via multivalent interactions between its B-subunit pentamer and globotriaosyl ceramide. After binding, it is first retrogradely transported to the Golgi and then to the endoplasmic reticulum (ER). Using a multivalent peptide library approach, we identified a tetravalent peptide that exhibits a high affinity for the Stx2 B-subunit pentamer (KD = 0.13 microM) and markedly inhibits Stx2 cytotoxicity. The tetravalent peptide exerted its inhibitory effects by inducing aberrant cellular transport of Stx2. Although the tetravalent peptide/Stx2 complex was incorporated into cells and translocated to the Golgi, this process was followed by the effective degradation of Stx2 in an acidic compartment rather than by its transfer to the ER. This peptide thoroughly protected mice from a fatal dose of E. coli O157:H7 even when administered after an established infection. Thus, the multivalent peptide library approach enabled the identification of a peptide-based Stx2 inhibitor that has remarkable therapeutic potency and appears to function by inducing aberrant cellular transport and degradation of Stx2.
 ...
PMID:A multivalent peptide library approach identifies a novel Shiga toxin inhibitor that induces aberrant cellular transport of the toxin. 1706 23


1 2 3 4 5 6 7 8 Next >>