UMLS:C0001511 - FACTA Search

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Query: UMLS:C0001511 (Adhesion)
5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As decided in the protocol, the AICLA study ended when all the 604 patients had completed a follow up of three years. Adhesion to the protocol and drug compliance were excellent. Side effects, particularly peptic ulcers and bleedings of various origins were more frequent in the 2 treatment groups containing aspirin. The number of fatal and non fatal cerebral infarction was 31 in the P group, 17 in the ASA group, and 18 in the ASA + D group. Taking into account the duration of follow up for each patient, these figures correspond to cummulate rates of 18 p. 100 in the P group and 10.5 p. 100 in the 2 others. Analysis with the Mantel Method showed: 1 - a difference at the 6 p. 100 level between the 3 groups and between P an AD; 2 - A difference at the 5 p. 100 level between P and A; 3 - No difference between A and AD; 4 - A difference at the 2 p. 100 level between the P group and the two treated groups taken together. Among other diseases occurring during the trial, the only significant difference concerned myocardial infarction, less frequent in the 2 treated groups (p less than 0.05). Subgroup analysis failed to show a significant sex difference in the efficacy of aspirin. It is concluded that, in patients such as those defined in the protocol, Aspirin (1 g) has a significant beneficial effect in the secondary prevention of atherothrombotic cerebral infarction.
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PMID:[The A.I.C.L.A. controlled cooperative trial. Secondary prevention of cerebral ischemic accidents due to atherosclerosis by aspirin and dipyridamole. 3: Results]. 635 Dec 16

Chronic inflammatory cells are key components in the progression of atherosclerotic plaques and restenosis after coronary angioplasty. Adhesion molecules are fundamental in inflammatory processes. Therefore, the distributions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM) were investigated in directional coronary atherectomy specimens obtained from 14 patients, in 6 with acute coronary syndromes (myocardial infarction and unstable angina within 1 month), 6 with old myocardial infarction and 2 with stable effort angina. There were eight primary lesions and six restenotic lesions. Atherectomy tissue fragments were snap frozen and cut into 4 microns thick cryostat sections for immunohistochemical staining by avidin-biotin complex immunoperoxidase techniques using adhesion molecule specific monoclonal antibodies BBIG-I1 (ICAM-1) and BBIG-V1 (VCAM). The cells of lesions were characterized in sequential sections by macrophage marker KP1 (CD68), endothelial marker JC/70A (CD31), and smooth muscle cell marker 1A4 (alpha-smooth muscle actin). Four restenotic lesions that had undergone a prior balloon angioplasty within a few months consisted of intimal proliferation and the other lesions were atherosclerotic plaque. Macrophage-rich areas were seen in the lesions from acute coronary syndromes and/or early restenotic lesions. Expression of ICAM-1 or VCAM was strongly associated with macrophage-rich areas, but VCAM staining was weaker than ICAM-1 except in one restenotic lesion. Macrophages that express ICAM-1 and/or VCAM may be important in the unstable plaques and restenotic lesions related to disease activity of ischemic heart disease.
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PMID:[Immunohistochemical analysis of adhesion molecules in directional coronary atherectomy specimens]. 747 44

Magnesium deficiency and its association with platelet hyperreactivity has been well recognised in a variety of diseases including myocardial infarction, preeclampsia, and diabetes. In order to investigate potential effects of intravenous Mg2+ supplementation, platelet function was studied by measurements of in vitro bleeding time (BT) and of fibrinogen (Fg)-mediated aggregation of washed platelets. In addition, the effect of Mg2+ on platelet adhesion onto immobilised Fg, on Fg binding to activated platelets, and on surface expression of GMP-140 or GP53 was evaluated. Mg2+ (4 mM) prolonged in vitro BT by 30% and inhibited Fg-mediated aggregation significantly, independent of the agonist used to initiate platelet aggregation (ADP, collagen, epinephrine, thrombin, phorbol ester). Adhesion of resting platelets to immobilised Fg was reduced by 50% in the presence of 2 mM Mg2+. Moreover, Mg2+ reduced Fg binding to ADP- or collagen-stimulated platelets as well as surface expression of GMP-140 with an IC50 of approximately 3 mM. Intravenous administration of Mg2+ to healthy volunteers inhibited both ADP-induced platelet aggregation (p < 0.05) by 40% and binding of Fg or surface expression of GMP-140 by 30% (p < 0.05). Thus, pharmacological concentrations of Mg2+ effectively inhibit platelet function in vitro and ex vivo.
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PMID:Effects of magnesium on platelet aggregation and adhesion. Magnesium modulates surface expression of glycoproteins on platelets in vitro and ex vivo. 774 Apr 63

Aged garlic extract (AGE) has been shown previously to have moderate cholesterol-lowering and blood pressure-reducing effects. We have now investigated whether platelet function, a potential risk factor for cardiovascular disease, can be inhibited by AGE administration. In a randomized, double-blind study of normal healthy individuals (n = 34), both men and women, the effect of AGE was evaluated in doses between 2.4 and 7.2 g/d vs. equal amounts of placebo. Platelet aggregation and adhesion were measured at 2-wk intervals throughout the study. Threshold concentrations for epinephrine and collagen increased moderately during AGE administration compared with the placebo and baseline periods. Only at the highest supplementation level did AGE show a slight increase in the threshold level of ADP-induced aggregation. Platelet adhesion to collagen, fibrinogen and von Willebrand factor was investigated by perfusing whole blood through a laminar flow chamber under controlled flow conditions. Adherence of platelets was inhibited by AGE in a dose-dependent manner when collagen was the adhesive surface perfused at low shear rates ( approximately 30 s(-1)). At high shear rates (1200 s(-1)), AGE also inhibited platelet adhesion to collagen but only at higher intake levels. Adhesion to von Willebrand factor was reduced only at 7.2 g/d AGE, but adherence to fibrinogen was potently inhibited at all levels of supplementation. Thus, AGE exerts selective inhibition on platelet aggregation and adhesion, platelet functions that may be important for the development of cardiovascular events such as myocardial infarction and ischemic stroke. We briefly review the effect of garlic preparations in general on cardiovascular risk factors and point out differences between AGE and other garlic preparations that we feel are important to explain the efficacy of AGE.
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PMID:Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions. 1123 1

One of the major therapeutic goals of modern cardiology is to design strategies aimed at minimizing myocardial necrosis and optimizing cardiac repair following myocardial infarction. However, a sound understanding of the biology is necessary before a specific intervention is pursued on a therapeutic basis. This review summarizes our current understanding of the cellular and molecular mechanisms regulating the inflammatory response following myocardial ischemia and reperfusion. Myocardial necrosis induces complement activation and free radical generation, triggering a cytokine cascade initiated by Tumor Necrosis Factor (TNF)-alpha release. If reperfusion of the infarcted area is initiated, it is attended by an intense inflammatory reaction. Interleukin (IL)-8 synthesis and C5a activation have a crucial role in recruiting neutrophils in the ischemic and reperfused myocardium. Neutrophil infiltration is regulated through a complex sequence of molecular steps involving the selectins and the integrins, which mediate leukocyte rolling and adhesion to the endothelium. Marginated neutrophils exert potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. Despite this potential injury, substantial evidence suggests that reperfusion enhances cardiac repair improving patient survival; this effect may be in part related to the inflammatory response. Monocyte Chemoattractant Protein (MCP)-1 is also markedly upregulated in the infarcted myocardium inducing recruitment of mononuclear cells in the injured areas. Monocyte-derived macrophages and mast cells may produce cytokines and growth factors necessary for fibroblast proliferation and neovascularization, leading to effective repair and scar formation. At this stage expression of inhibitory cytokines such as IL-10 may have a role in suppressing the acute inflammatory response and in regulating extracellular matrix metabolism. Fibroblasts in the healing scar undergo phenotypic changes expressing smooth muscle cell markers. Our previous review in this journal focused almost exclusively on reduction of the inflammatory injury. The current update is prompted by the potential therapeutic opportunity that the open vessel offers. By promoting more effective tissue repair, it may be possible to reduce the deleterious remodeling, that is the leading cause of heart failure and death. Elucidating the complex interactions and regulatory mechanisms responsible for cardiac repair may allow us to design effective inflammation-related interventions for the treatment of myocardial infarction.
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PMID:The inflammatory response in myocardial infarction. 1174 11

Myocardial infarction is associated with an inflammatory response, ultimately leading to healing and scar formation. Reperfused myocardial infarcts exhibit an enhanced inflammatory reaction, and are associated with improved cardiac repair and patient survival. This review summarizes our current knowledge of the inflammatory mechanisms mediating injury and repair following myocardial ischemia and reperfusion. Myocardial necrosis is associated with complement activation and free radical generation, triggering a cytokine cascade and chemokine upregulation. Interleukin (IL)-8 and C5a are released in the ischemic myocardium, and may have a crucial role in neutrophil recruitment. Extravasated neutrophils may induce potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. However, despite these potentially injurious effects, the post-reperfusion inflammatory response may significantly enhance healing. Monocyte Chemoattractant Protein (MCP)-1 is induced in the infarcted area and may regulate mononuclear cell recruitment. Accumulation of monocyte-derived macrophages, and mast cells may increase expression of growth factors inducing angiogenesis and fibroblast accumulation in the infarct. In addition, expression of cytokines inhibiting the inflammatory response, such as Interleukin (IL)-10 may suppress injury. Matrix Metalloproteinases (MMPs) and their inhibitors regulate extracellular matrix deposition and play an important role in mediating ventricular remodeling. Inflammatory mediators may induce recruitment of blood-derived primitive stem cells in the healing infarct, which may differentiate into endothelial cells and even lead to limited myocardial regeneration. Understanding the cellular and molecular steps involved in regulating infarct healing may lead to specific interventions aimed at optimizing cardiac repair.
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PMID:Inflammatory mechanisms in myocardial infarction. 1456 Nov 59

Cigarette smoking adversely affects endothelial function and increases risk of coronary artery disease (CAD). The pathogenesis of coronary atherosclerosis is currently thought to involve interactions between inflammatory cells and vascular endothelium. Adhesion molecules play a pivotal role in the accumulation of inflammatory cells at the endothelium. Little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study was to evaluate the effects of cigarette smoking on the plasma concentrations of soluble vascular cell adhesion molecule-1 (VCAM-1) in patients with CAD. The soluble VCAM-1 level was quantified in smoking CAD patients (n = 19) in comparison to those from patients with CAD alone (n = 10). Plasma concentrations of soluble VCAM-1 were measured by enzyme-linked immunosorbent assay. The soluble VCAM-1 level was found significantly higher in smokers than in nonsmokers (32.1279 +/- 21.6421 vs 9.4570 +/- 7.8138 ng/mL, p < 0.01), and in patients with previous myocardial infarction (MI) than in those without previous MI, but not significant statistically (27.7279 +/- 22.8813 vs 17.8170 +/- 15.9172 ng/mL, p > 0.05). No significant difference was observed for soluble VCAM-1 levels between hypertensive and nonhypertensive patients, multivessel and one-vessel disease, or anterior and inferior MI localizations. The present study suggests that in patients with CAD, smoking leads to elevated levels of soluble VCAM-1 that may clarify one of the mechanisms of its accelerating effect on the atherosclerotic process.
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PMID:Cigarette smoking increases plasma concentrations of vascular cell adhesion molecule-1 in patients with coronary artery disease. 1525 85

The F11 receptor (F11R) (a.k.a. Junctional Adhesion Molecule, JAM) was first identified in human platelets as a 32/35 kDa protein duplex that serves as receptor for a functional monoclonal antibody that activates platelets. We have sequenced and cloned the F11R and determined that it is a member of the immunoglobulin (Ig) superfamily of cell adhesion molecules. The signaling pathways involved in F11R-induced platelet activation were examined in this investigation. The binding of M.Ab.F11 to the platelet F11R resulted in granule secretion and aggregation. These processes were found to be dependent on the crosslinking of F11R with the Fc gammaRII by M.Ab.F11. This crosslinking induced actin filament assembly with the conversion of discoidal platelets to activated shapes, leading to the formation of platelet aggregates. We demonstrate that platelet secretion and aggregation through the F11R involves actin filament assembly that is dependent on phosphoinositide-3 kinase activation, and inhibitable by wortmannin. Furthermore, such activation results in an increase in the level of free intracellular calcium, phosphorylation of the 32 and 35 kDa forms of the F11R, F11R dimerization coincident with a decrease in monomeric F11R, and association of the F11R with the integrin GPIIIa and with CD9. On the other hand, F11R-mediated events resulting from the binding of platelets to an immobilized surface of M.Ab.F11 lead to platelet adhesion and spreading through the development of filopodia and lammelipodia. These adhesive processes are induced directly by interaction of M.Ab.F11 with the platelet F11R and are not dependent on the Fc gammaRII. We also report here that the stimulation of the F11R in the presence of nonaggregating (subthreshold) concentrations of the physiological agonists thrombin and collagen, results in supersensitivity of platelets to natural agonists by a F11R-mediated process independent of the Fc gammaRII. The delineation of the two separate F11R-mediated pathways is anticipated to reveal significant information on the role of this cell adhesion molecule in platelet adhesion, aggregation and secretion, and F11R-dependent potentiation of agonist-induced platelet aggregation. The participation of F11R in the formation and growth of platelet aggregates and plaques in cardiovascular disorders, resulting in enhanced platelet adhesiveness and hyperaggregability, may serve in the generation of novel therapies in the treatment of inflammatory thrombosis, heart attack and stroke, and other cardiovascular disorders.
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PMID:Signaling pathways of the F11 receptor (F11R; a.k.a. JAM-1, JAM-A) in human platelets: F11R dimerization, phosphorylation and complex formation with the integrin GPIIIa. 1534 81

Inflammation has recently proven to be associated with the pathogenesis of atherosclerosis and inflammatory genes are good candidates for the risk of developing atherosclerosis. The early phase of atherosclerosis involves the recruitment of inflammatory cells from the circulation and their transendothelial migration. This process is mainly mediated by cellular adhesion molecules, which are expressed by the vascular endothelium and by circulating leukocytes in response to several inflammatory stimuli. Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leukocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule-1 (PECAM-1/CD31), involved in this migration, has been associated with the developmental course of atherosclerosis. Studies have investigated an association between coronary heart disease (CHD) and single nucleotide polymorphisms (SNP) located in functionally important domains of the PECAM-1/CD31 gene, with contrasting results. In particular, we previously analyzed for the following PECAM-1/CD31 SNP: Val125Leu, Asn563Ser, and Gly670Arg. The frequency of the Gly670Arg polymorphism was significantly higher in patients with myocardial infarction (MI), whereas the frequencies of the other two SNP (Leu125Val and Ser563Asn) were not significantly different between patients and controls. To check the validity of our results, we have analyzed the distribution of these SNP in centenarian men (age >99) from our homogeneous Sicilian population, since our previous studies have demonstrated that alleles associated with MI susceptibility are not included in the genetic background favoring longevity. We showed, as regard to polymorphisms of PECAM-1/CD31, that there were no significant differences between male patients affected by MI, male controls, and male centenarians. According to our hypothesis present results seemingly do not support a role for these SNP in conferring the susceptibility to MI at least in this Italian population.
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PMID:PECAM-1/CD31 in infarction and longevity. 1746 Jan 71

While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2) locus (rs1799969, rs5498 and rs281437) are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5x10(-8)), thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1x10(-29)) at the ABO (9q34.2) locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes.
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PMID:Novel association of ABO histo-blood group antigen with soluble ICAM-1: results of a genome-wide association study of 6,578 women. 1860 67

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