Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adhesions were demonstrated by small bowel meal in six patients with symptoms of intermittent small bowel obstruction following surgery for inflammatory bowel disease. The radiographic criteria for the diagnosis of adhesions and the distincton from recurrent Crohn's disease are discussed.
 ...
PMID:The radiological demonstration of adhesions following surgery for inflammatry bowel disease. 742 86

Adhesion of circulating cells to vascular endothelium occurs in the early phase of inflammation, and is mediated by specific cell adhesion molecules. Many such adhesion molecules are increased in inflamed regions of ulcerative colitis (UC) and Crohn's disease (CD) but there is limited knowledge of their expression in the uninvolved gut, adjacent to inflammation. We investigated immunohistochemically the expression of platelet endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen-1 (LFA-1) on resected specimens taken at a distance of 2-4 cm from the inflamed area and without histological signs of inflammation. Compared with normal gut, we found (i) a significant increase of PECAM-1-positive vessels in the mucosa of uninvolved UC (149.0 +/- 24.1 vessels/mm2 (mean +/- s.d.); normal colon = 123.1 +/- 21.6; P = 0.004); (ii) a significant decrease of ICAM-1-positive vessels in uninvolved CD (111.9 +/- 22.6 vessels/mm2; normal ileum = 136.9 +/- 27.6; P = 0.04); and (iii) a moderate but statistically insignificant increase of LFA-1-positive cells in the mucosa of uninvolved UC and Crohn's ileitis. This altered expression of cell adhesion molecules may contribute to the early lesion in inflammatory bowel disease and provide new therapeutic opportunities.
 ...
PMID:Altered expression of cell adhesion molecules in uninvolved gut in inflammatory bowel disease. 790 Sep 41

Adhesion molecules participate in a broad variety of biological processes, i.e. tumor progression and inflammation, through their involvement in cell-to-cell interactions and immunoinflammatory cell migration. This review describes the basic properties of adhesion molecules with reference to inflammatory bowel disease and colorectal carcinoma. Accumulating data suggest that adhesion molecules could be pathogenetically pertinent to other gastrointestinal disorders such as celiac disease (nontropical sprue) and gastroduodenal ulcer. Future therapeutic approaches in inflammatory and malignant disorders may possibly be development of principles targeting adhesion molecules.
 ...
PMID:Adhesion molecules in inflammatory and neoplastic intestinal diseases. 854 67

Adhesion molecules mediate the extravasation of leukocytes and their accumulation in inflamed tissues. In the present study, serum concentrations of the selectin (sP- and sE-selectin) and immunoglobulin supergene family (sICAM-1 and sVCAM-1) of adhesion molecules were measured in 93 patients with inflammatory bowel disease (Crohn's disease, n = 65; ulcerative colitis, n = 28) and 58 age-matched normal controls. sP-selectin serum concentrations (mean +/- SEM ng/ml) of patients with Crohn's disease (399 +/- 33 ng/ml) and ulcerative colitis (385 +/- 42 ng/ml) were increased (P = 0.0067 and P = 0.0193, respectively) compared to controls (251 +/- 33 ng/ml). In contrast, E-selectin serum levels of patients with Crohn's disease (58 +/- 5 ng/ml) and ulcerative colitis (64 +/- 12 ng/ml) were not significantly higher than those of controls (53 +/- 5 ng/ml). sICAM-1 serum concentrations of patients with Crohn's disease (420 +/- 19 ng/ml) and those with ulcerative colitis (375 +/- 40 ng/ml) were elevated (P = 0.0001 and P = 0.0473, respectively) compared to controls (297 +/- 8 ng/ml). Further, sVCAM-1 levels of patients with Crohn's disease (664 +/- 43 ng/ml) and ulcerative colitis (963 +/- 162 ng/ml) were increased (P = 0.0222 and P = 0.0121, respectively) compared to controls (510 +/- 31 ng/ml). With few exceptions, serum levels of soluble adhesion molecules were not significantly correlated to disease activity indices or disease localization. Elevated circulating selectin and immunoglobulin supergene type adhesion molecules may compete with membrane-bound forms for their cognate ligands and thereby limit the rolling and stable adhesion of leukocytes.
 ...
PMID:Elevated serum concentrations of soluble selectin and immunoglobulin type adhesion molecules in patients with inflammatory bowel disease. 925 Aug 94

Adhesion molecules participate in a broad variety of biological processes, i.e. tumour progression and inflammation, through their involvement in cell-to-cell interactions and immunoinflammatory cell migration. This review describes the basic properties of adhesion molecules with reference to inflammatory bowel disease and colorectal carcinoma. Future therapeutic approaches in inflammatory and malignant disorders may include development of principles targeting adhesion molecules.
 ...
PMID:[The role of cell adhesion molecules in inflammatory bowel disease and colorectal cancer]. 929 10

Pathological changes in inflammatory bowel disease include an increase in intestinal mucosal mononuclear leukocytes and hyperplasia of the muscularis mucosae smooth muscle cells (M-SMCs). Because virus infections have correlated with disease flare, we tested the response of cultured M-SMCs to respiratory syncytial virus, measles virus, and the viral analogue, poly(I.C). Adhesion of U937 cells and peripheral blood mononuclear cells was used to measure the leukocyte-interactive potential of M-SMCs. Untreated M-SMCs, only minimally adhesive for leukocytes, bound U937 cells after treatment with respiratory syncytial virus or measles virus. Mononuclear leukocytes also bound to poly(I.C)-treated M-SMCs. Although both vascular cell adhesion molecule-1 mRNA and protein increased 3-4-fold in poly(I.C)-treated M-SMC cultures, U937 cell adhesion was not blocked by an anti-vascular cell adhesion molecule-1 monoclonal antibody. However, hyaluronidase digestion of poly(I.C)- or virus-treated M-SMCs dramatically reduced leukocyte adhesion ( approximately 75%). Fluorophore-assisted carbohydrate electrophoresis demonstrated a approximately 3-fold increase in surface-bound hyaluronan on poly(I.C)-treated M-SMCs compared with untreated controls. In addition, pretreatment of mononuclear cells with a blocking anti-CD44 antibody, greatly decreased adhesion to poly(I.C)-treated M-SMCs. Recognition of this virus-induced hyaluronan/CD44 mechanism of mesenchymal cell/leukocyte interaction introduces a new avenue in the research of gut inflammation.
 ...
PMID:Mononuclear leukocytes preferentially bind via CD44 to hyaluronan on human intestinal mucosal smooth muscle cells after virus infection or treatment with poly(I.C). 1052 64

Adhesion molecule immunoneutralization is envisioned as a promising therapy for inflammatory bowel disease, but the relative value of selective blockade of different adhesion molecules has not been established. The aims of this study were to measure expression and functional relevance of endothelial intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) in leukocyte recruitment in experimental colitis and to compare the therapeutic effectiveness of their selective blockade. For this purpose, cell adhesion molecule expression was measured by the dual radiolabeled antibody technique in mice with dextran sulfate sodium-induced colitis and controls. Leukocyte-endothelial cell interactions were determined in colonic venules by fluorescence intravital microscopy. Therapeutic effects of chronic treatment with anti-ICAM-1, anti-VCAM-1, or anti-MAdCAM-1 antibodies were also assessed. Whereas colonic endothelial ICAM-1 was constitutively expressed and had a mild up-regulation in colitic animals, constitutive expression of VCAM-1 and MAdCAM-1 was low, but markedly increased after induction of colitis. Leukocyte adhesion was abrogated by immunoneutralization of VCAM-1 or MAdCAM-1 but not by treatment with an anti-ICAM-1 antibody. Chronic administration of anti-VCAM-1 antibody, but not anti-ICAM-1 or anti-MAdCAM-1, resulted in significant attenuation of colitis in terms of disease activity index, colon length, ratio of colon weight to length, and myeloperoxidase activity. In conclusion, VCAM-1 plays a central role in leukocyte recruitment in colitis and blockade of this adhesion molecule has higher therapeutic effect than immunoneutralization of ICAM-1 or MAdCAM-1 in this experimental model.
 ...
PMID:VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice. 1104 71

Adhesion molecules regulate the influx of leukocytes in normal and inflamed gut. Some of these molecules such as MadCAM-1 are specific for the gastrointestinal endothelium, but in inflammatory bowel diseases most of the adhesion factors are up-regulated. Adhesion molecules also are involved in local lymphocyte stimulation and antigen presentation within the intestinal mucosa. Recently, therapeutic compounds directed against trafficking of lymphocytes toward the gut mucosa have been designed, and are being developed as a novel class of drugs in the treatment of Crohn's disease (CD) and ulcerative colitis. This review deals with the immunological aspects of leukocyte trafficking focused on gut homing of T cells. Secondly, the changes in adhesion molecules and T-cell trafficking during intestinal inflammation are discussed. Finally, we review the clinical data that have been gathered in trials of biological therapies directed against adhesion molecules. Both antiintercellular adhesion molecule-1 (ICAM-1) and anti-alpha4 integrin strategies are being developed. Trials with the anti-ICAM-1 antisense oligonucleotide, ISIS-2302, in steroid-refractory CD have provided conflicting efficacy data. The anti-alpha4 integrin antibodies natalizumab (Antegren) and LDP-02 are in phase III and phase II trials, respectively. In the near future, these novel biological agents may prove valuable therapeutic tools in the management of refractory IBD.
 ...
PMID:Antiadhesion molecule therapy in inflammatory bowel disease. 1213 14

Adhesion molecules are known to be an important part of leukocyte migration and extravasation in both homeostatic and inflammatory conditions. Intracellular adhesion molecule-1 (ICAM-1 or CD54) is constitutively expressed on endothelial cells and is up-regulated during acute and chronic inflammation. We investigated the efficacy and consequences of interfering with CD54 after administration of an antisense oligonucleotide to ICAM-1 (CD54) in the transgenic HLA-B27/beta2 microglobulin rat model. One hundred percent of the HLA-B27 transgene + animals will spontaneously develop chronic inflammation (some more severely than others) in the gastric mucosa, cecum, and colon. We carried out two studies, i.p. injection and rectal administration of antisense. Following i.p. and rectal treatment, there were significant decreases in colonic mucosal wall thickness, histologic inflammation, CD54 expression in the colon and peripheral blood, and the percentage of colon weight per end body weight. Furthermore, decreased expression of CD49d, CD18, and tumor necrosis factor-alpha was observed in antisense treated rats. Therefore, the HLA-B27 transgenic model of spontaneous and chronic inflammatory bowel disease, which has increased expression of adhesion molecules, responds to both routes of administration of ICAM-1 antisense oligonucleotides. These studies support the regulatory role of adhesion molecules in chronic intestinal inflammation, the need for an understanding of how the route of drug delivery can alter the dose and area affected, and finally the role of antisense oligonucleotides as a therapeutic modality in chronic spontaneous inflammatory bowel diseases.
 ...
PMID:Amelioration of chronic and spontaneous intestinal inflammation with an antisense oligonucleotide (ISIS 9125) to intracellular adhesion molecule-1 in the HLA-B27/beta2 microglobulin transgenic rat model. 1218 46

Inflammatory disorders such as autoimmune diseases and graft rejection are mediated by activated leukocytes, particularly T lymphocytes, which penetrate the inflamed tissue and perpetuate or amplify the immune reaction. In an unstimulated state, leukocytes do not readily adhere to the vascular endothelium. However, inflammatory signals induce the expression of proteins on the endothelial cell surface that promote the adhesion and extravasation of activated immune cells from the circulation into the underlying tissues. Key among these molecules are P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cells, and their respective counter receptors, P-selectin glycoprotein ligand-1 (PSGL-1), leukocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), on the leukocytes. In vitro blockade of these molecules inhibits the adhesion of leukocytes. In many cases there is attenuation of leukocyte activation as well. Adhesion blockade in animal models prevents or ameliorates graft rejection and disease severity in autoimmune models. Clinical studies with humanised monoclonal antibodies which interfere with LFA-1/ICAM-1 or VLA-4/VCAM-1 interactions have shown significant efficacy and good safety profiles in autoimmune disease, including psoriasis, multiple sclerosis and inflammatory bowel disease. Thus, adhesion blockade is emerging as a useful therapeutic strategy in several inflammatory settings.
 ...
PMID:Adhesion molecules as therapeutic targets for autoimmune diseases and transplant rejection. 1271 33


1 2 3 Next >>