Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endoscopic method--colonoscope, has become the tool of choice for diagnosing many colonic disorders, including the acute and chronic inflammatory bowel disease, lower gastrointestinal bleeding, benign and malignant tumors, and various others abnormalities appearing on the radiographs. The colonoscope is also useful and become the main confirmation method in screening for and monitoring colonic cancer. In the same time, colonoscopy offers numerous therapeutic options. The colonic polyps, well-known colonic precancerous lesions, with incidence ranges from 7 to 50%, can be removed completely during the colonoscopy, with a snare or biopsy forceps (polypectomy). Early cancers limited to the mucosal layer (intraepithelial cancer or carcinoma in situ) can be treated endoscopically too (mucosectomy), as well as various gastrointestinal bleeding (with sclerotherapy, electrocoagulation, APC, laser-fotocoagulation), inflammatory and postsurgical strictures (endoscopic dilation), and foreign bodies in the rectum and sigma (endoscopic extraction).
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PMID:[Endoscopic methods of treatment of precancerous lesions of the colon]. 1205 27

Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolic complications. Several mechanisms can be responsible, including abnormal regulation of coagulation activity, disturbances of fibrinolysis, inflammatory reactions and thrombocytosis. The aim of this study was to assess hemostatic alterations in these parameters during exacerbation of disease. We studied disease activity in 99 IBD patients receiving anti-inflammatory therapy, in relation to: procoagulant markers, i.e. prothrombin fragment F1 + 2 (F1 + 2), D-dimer and platelet count, anticoagulant markers, i.e. protein C, protein S and antithrombin, and a mediator of inflammation (IL-6). Coagulation activity and platelet count were increased during active disease in IBD patients compared with those in a state of remission. The IL-6 concentrations were positively correlated with disease activity and thrombocytosis in patients with ulcerative colitis, but no association with the anticoagulant capacity could be demonstrated except for a decrease in protein C during high disease activity.
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PMID:Platelets and anticoagulant capacity in patients with inflammatory bowel disease. 1221 55

The interaction between OX40 and OX40 ligand (OX40L) is suggested to provide T cells with an effective costimulatory signals during T cell-APC interaction. To examine the in vivo effect of constitutive OX40/OX40L interaction during immune regulation, we report the establishment of OX40L-transgenic (OX40L-Tg) mice that constitutively express OX40L on T cells. Markedly elevated numbers of effector memory CD4(+) T cells, but not CD8(+) T cells, were observed in the secondary lymphoid organs of OX40L-Tg mice. Upon immunization with keyhole limpet hemocyanin in the absence of adjuvant, profound T cell proliferative responses and cytokine productions were seen in the OX40L-Tg mice as compared with wild-type mice. Furthermore, in OX40L-Tg mice administrated with superantigen, this constitutive OX40/OX40L interaction on CD4(+) T cells completely prevented normal in vivo clonal T cell deletion. Interestingly, OX40L-Tg mice on the C57BL/6 background spontaneously developed interstitial pneumonia and inflammatory bowel disease that was accompanied with a significant production of anti-DNA Ab in the sera. Surprisingly, these diseases were not evident on the OX40L-Tg mice on the BALB/c strain. However, such inflammatory diseases were successfully reproducible in recombination-activating gene (RAG)2-deficient mice upon transfer of OX40L-Tg CD4(+) T cells. Blockade of OX40/OX40L interaction in the recipient RAG2-deficient mice completely prevented disease development. The present results orchestrated in this study indicate that OX40/OX40L interaction may be a vital link in our understanding of T cell-mediated organ-specific autoimmunity.
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PMID:Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases. 1237 Apr 2

Inflammatory bowel diseases (IBD)--ulcerative colitis and Crohn's disease--are associated with increased risk for thrombotic complications both in the arterial and venous system. Cerebral sinus thrombosis is a rare but potentially fatal consequence of these diseases. Modern imaging methods made this uncommon complication of IBD more frequently recognized. The link between IBDs and thrombosis has been extensively studied. Inherited coagulation disorders (APC resistance, antithrombin III and protein-S deficiency), acquired diseases (antiphospholipid syndrome), and the frequent use of corticosteroids were suspected. Two cases of ulcerative colitis associated with cerebral sinus thrombosis successfully treated are reported. The connection between IBD and thrombotic complications and the therapeutic risks are discussed as well.
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PMID:[Cerebral sinus thrombosis and ulcerative colitis: two cases]. 1271 83

Interactions between APC and T lymphocytes have been implicated as a major factor contributing to inflammatory bowel disease. To test whether OX40/OX40L interaction plays a role in chronic intestinal inflammation, we induced chronic colitis using dextran sulfate sodium and treated the mice with a murine fusion protein (OX40-IgG). Treatment resulted in a dose-dependent and significant reduction of intestinal inflammation (46%) as measured by a histologic score. IL-10 and IL-5 production from mesenteric lymph node cells increased 20-fold and 18-fold, respectively. In colonic tissue, IL-10 mRNA levels increased and the expression of T-bet was decreased to 30%. IL-10 neutralization partly inhibited the beneficial effects of OX40-IgG treatment. Surprisingly, despite the reduction of inflammation we found the number and size of colonic lymphoid follicles increased, with an accumulation of CD4(+) cells in the mantle area. In contrast, the number of CD4(+) cells infiltrating the mucosa was significantly reduced, as was their CXCR5 expression (24-fold). We conclude that OX40/OX40L interaction contributes to the perpetuation of chronic colitis partly by suppressing IL-10 production. Furthermore, our data suggest that the OX40/OX40L-induced CXCR5 expression on CD4(+) cells may be important for the inflammatory process by allowing migration to the germinal center for further differentiation of CD4(+) cells before they infiltrate the chronically inflamed mucosa.
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PMID:OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic colitis induced by dextran sulfate sodium in mice. 1463 34

Inflammatory bowel disease (IBD) is associated with an increased risk for thromboembolic events. Aim of this study was to examine the relationship of hyperhomocysteinemia and thrombosis in IBD patients and to assess the role of this factor in addition to other known prothrombotic abnormalities. IBD patients with a history of thrombosis (n = 22) and sex-, age-, and diagnosis-matched IBD controls (n = 23) were studied. Homocysteine (tHcy) was assessed before and after methionine loading. Plasma levels of protein C, protein S, antithrombin III, and fibrinogen and the presence of anticardiolipin and antiphospholipid antibodies were determined and genetic testing for factor V Leiden and the prothrombin gene mutation was performed. Results showed that fasting homocysteine levels in IBD patients with a history of arterial or venous thrombosis tended to be higher than in IBD controls, although not significantly. The increase in homocysteine levels after methionine loading was significantly higher in IBD patients in the arterial thrombosis group than in IBD controls (40.9 +/- 17.7 vs. 27.2 +/- 9.9 microM; P < 0.05). Among the other prothrombotic factors, only factor V Leiden was significantly associated with a history of venous thrombosis (20 vs. 0%). At least one risk factor was found in 64% of the IBD patients with previous thromboembolic complications. We conclude that there is an association between hyperhomocysteinemia and a history of arterial thrombosis in IBD patients. We confirm the high prevalence of factor V Leiden in IBD patients with a history of venous thrombosis. In the majority of IBD patients with previous thromboembolic complications, at least one prothrombotic risk factor is detected.
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PMID:Risk factors for thromboembolic complications in inflammatory bowel disease: the role of hyperhomocysteinaemia. 1574 78

B cells are typically characterized by their ability to produce Abs, including autoantibodies. However, B cells possess additional immune functions, including the production of cytokines and the ability to function as a secondary APC. As with T cells, the B cell population contains functionally distinct subsets capable of performing both pathogenic and regulatory functions. Recent studies indicate that regulatory B cells develop in several murine models of chronic inflammation, including inflammatory bowel disease, rheumatoid arthritis, and experimental autoimmune encephalomyelitis. The regulatory function may be directly accomplished by the production of regulatory cytokines IL-10 and TGF-beta and/or by the ability of B cells to interact with pathogenic T cells to dampen harmful immune responses. In this review, we make a case for the existence of regulatory B cells and discuss the possible developmental pathways and functional mechanisms of these B cells.
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PMID:A case for regulatory B cells. 1639 50

The clinical course of inflammatory bowel disease (IBD) is frequently associated with thromboembolic complications. The aim of this study was to investigate common thrombophilic markers in Turkish patients with active IBD. Twenty-seven consecutive patients with IBD who were followed-up at the Hacettepe University Hospital were recruited. All the patients were in the active disease state. International normalized ratio, activated partial thromboplastin time, lupus anticoagulant, anticardiolipin IgG, IgM antibodies, protein C, protein S, antithrombin-III, factor V, and factor II mutation of all the IBD patients and of a sex-matched and age-matched control group of non-IBD patients were measured. International normalized ratio, activated partial thromboplastin time, protein C, protein S, lupus anticoagulant, anticardiolipin IgG and IgM, and Proteins C and S mutations were comparable between the 2 groups, but antithrombin-III was significantly lower in the IBD group compared with healthy control group (P<0.0001). As a conclusion, it is reasonable to assume that there may be a subpopulation of the patients with IBD, in whom thrombophilic abnormalities might be important for either disease manifestation or for thrombotic complications. Those hemostatic abnormalities could be either inherited or secondary to the ongoing disease process. Routine screening for the common markers of thrombophilia does not seem to be warranted unless simultaneous arterial and venous thrombosis, major organ thrombosis, strong family history of thrombophilia, unusual and recurrent thrombosis resistant to standard anticoagulant therapy are present. Further studies are definitely required to clarify these complicated associations.
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PMID:The search for a common thrombophilic state during the active state of inflammatory bowel disease. 1701 37

A woman presenting with recurrent purpura fulminans was eventually found to have inflammatory bowel disease. We suggest the inflammatory state resulted in a deficiency of functional protein C.
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PMID:What may underlie recurrent purpura fulminans? 1740 38

Endothelial protein C receptor (EPCR) and thrombomodulin (TM) are expressed at high levels in the resting microvasculature and convert protein C (PC) into its activated form, which is a potent anticoagulant and antiinflammatory molecule. Here we provide evidence that in Crohn disease (CD) and ulcerative colitis (UC), the 2 major forms of inflammatory bowel disease (IBD), there was loss of expression of endothelial EPCR and TM, which in turns caused impairment of PC activation by the inflamed mucosal microvasculature. In isolated human intestinal endothelial cells, administration of recombinant activated PC had a potent antiinflammatory effect, as demonstrated by downregulated cytokine-dependent cell adhesion molecule expression and chemokine production as well as inhibited leukocyte adhesion. In vivo, administration of activated PC was therapeutically effective in ameliorating experimental colitis as evidenced by reduced weight loss, disease activity index, and histological colitis scores as well as inhibited leukocyte adhesion to the inflamed intestinal vessels. The results suggest that the PC pathway represents a new system crucially involved in governing intestinal homeostasis mediated by the mucosal microvasculature. Restoring the PC pathway may represent a new therapeutic approach to suppress intestinal inflammation in IBD.
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PMID:Crucial role of the protein C pathway in governing microvascular inflammation in inflammatory bowel disease. 1755 19


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