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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study platelet activation as a phenomenon that may precede development of angiopathy in diabetes mellitus, we compared platelet adhesion and thrombus formation in a flow system with blood from insulin-dependent (type I) diabetic subjects with and without macroangiopathy and age- and sex-matched control subjects. Adhesion and thrombus formation on matrix of cultured human endothelial cells (ECM) and adhesion on matrix of human fibroblasts (FBM) were studied after exposure to flowing blood at shear rates of 300 and 1300 s-1 and exposure times of 1, 3, 5, and 10 min (and 20 min in adhesion experiments). Blood was anticoagulated with trisodium citrate (1:10 vol/vol, 110 mM) or low-molecular-weight heparin ([LMWH] 20 U/ml). Endothelial cell cultures were either unstimulated or stimulated with 4 beta-phorbol 12-myristate 13-acetate (PMA) 16 h before isolating their matrix. Platelet adhesion on ECM and FBM in citrated and LMWH-anticoagulated blood was identical in diabetic patients and control subjects, with comparable increases of adhesion with increasing perfusion times. Platelet aggregate formation on ECM of PMA-stimulated cells with LMWH-anticoagulated blood was similar in diabetic patients, whether macroangiopathy was present, compared with control subjects. Fibrin deposition and fibrinopeptide A generation during perfusion were comparable in diabetic and control subjects. Platelet thromboxane B2 formation after stimulation with arachidonic acid was increased in diabetic patients without macroangiopathy compared with age- and sex-matched control subjects. In the perfusion system, the patterns of platelet adhesion and aggregate formation on extracellular matrix in flowing blood of diabetic patients (with or without macroangiopathy), and healthy age- and sex-matched control subjects followed a similar pattern.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Nov
PMID:Platelet adhesion and aggregate formation in type I diabetes under flow conditions. 193 2

The adhesion of leukocytes to endothelium is a physiological phenomenon which is the first step for leukocyte emigration. The adhesion can be dramatically increased in pathological situations such as inflammation and vascular diseases. The molecular basis of leukocyte-endothelium interaction has been largely investigated in the last ten years. Using monoclonal antibodies it is possible to characterize the leukocyte adhesion molecule (LeuCAM) also named CD11/CD18 complex. These molecules responsible for leukocyte adhesion are heterodimers consisting of a common beta subunit and different subunit CD11a/CD18 corresponding to LFA-1; CD11b/CD18 to Mac1/Mol; CD11c/CD18 to GP150-95. Beside these receptors, other leukocyte structures such as the fibronectin receptors are involved in the adhesive process. On the endothelial cell side specialized structures implicated in leukocyte adhesion have been identified. Structures like Intercellular Adhesion Molecule (ICAM) are expressed on endothelial cells in the absence of stimulation, while other receptors Endothelial Leukocyte Adhesion Molecule (ELAM) are only detectable on activated endothelial cells. Cytokines such as IL-1 induced the expression of ELAM, increased the number of ICAM and Human Leukocyte Antigens (HLA) DR, DP, DQ. In various pathological circumstances, namely extracorporeal circulation, Acute Respiratory Distress Syndrome (ARDS), hypercholesterolemia and diabetes mellitus increased leukocyte adhesion has been reported and is potentially responsible for vascular damage. Therefore, the modulation of leukocyte-endothelial cell interactions is a possible target for antithrombotic and antiatherosclerotic therapy.
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PMID:Leukocyte adhesion to endothelial cells. 226 8

The effect of Tamm Horsfall protein (THP) of 18 healthy subjects and 14 diabetics on adherence of Escherichia coli (06:K13) 2699 strain to human kidney cells (HUK) was studied. Adhesion of bacteria (without additions: 100 bacteria per cell) was reduced dose-dependently by THP, half maximal inhibition occurring with 250 micrograms THP ml-1. Maximal inhibition (-84% at 1000 micrograms ml-1) exceeded inhibition by alpha-methyl-mannoside (36% at 50 mM), was specific (not reproduced by other glycoproteins, e.g. ovalbumin, mucin or thyroglobulin) and reversible (abolished by washing THP off HUK cells). Anti-adherence property of THP was not abolished by neuraminidase treatment. No significant difference of anti-adherence activity of THP was found between controls and diabetics, despite altered carbohydrate composition of THP in diabetes.
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PMID:Tamm Horsfall glycoprotein interferes with bacterial adherence to human kidney cells. 313 Feb 65

Adhesion of bovine endothelial cells on fibronectin and collagen before and after nonenzymatic glycation in vitro has been studied. Nonenzymatic glycation of these proteins reduced their ability to bind endothelial cells. Furthermore, nonenzymatically glycated fibronectin failed to bind to normal and nonenzymatically glycated gelatin and to fibrin. So gelatin and fibrin Sepharoses can be used to separate highly glycated fibronectins from fibronectins with a low degree of nonenzymatic glucose substitution. Sodium dodecylsulfate polyacrylamide gel electrophoresis did not demonstrate a covalent cross-link between nonenzymatically glycated fibronectins. These results present further evidences for the role of nonenzymatic glycation of proteins in the development of vascular complications in long-term diabetes and of atherosclerosis.
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PMID:Diminished adhesion of endothelial aortic cells on fibronectin and collagen layers after nonenzymatic glycation. 340 68

Adhesion molecules mediate the interaction between endothelium and platelets as well as other blood cells and the endothelium. The structure and function of some of these molecules will be reviewed and discussed. The expression of these molecules is largely affected by disease states such as hypertension, diabetes, and cardiac failure. Determination of adhesion molecules expressed on the surface of endothelial cells and platelets by cytoflowmetry enables a new approach to estimate the activity state of these cells and might be helpful to identify patients with an increased thrombotic risk.
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PMID:Adhesive proteins in platelet-endothelial interactions. 751 78

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

Erythrocyte-endothelial cell interactions were rediscovered using endothelial cells in culture and radiolabelled erythrocytes. Increased adherence of erythrocytes from patients with sickle cell anaemia was found to be related to the occurrence of vaso-occlusive episodes. In diabetes mellitus and sickle cell anaemia, the adhesion was shown to be potentiated by plasmatic factors such as fibrinogen and fibronectin and to induce endothelial cell activation and enhanced prostacyclin production. The molecular basis of the abnormal adherence of diabetic erythrocytes was shown to be linked to Advanced Glycosylated End-products (AGE) present on the cell membrane and to RAGE 35 receptors exposed by the endothelium. Intercellular Adhesion Molecule (ICAM) was identified as an ubiquitous receptor present on endothelium and involved in leucocyte adhesion and it was more recently demonstrated that erythrocytes infested by Plasmodium falciparum bind to ICAM. This adhesion may be important for the dissemination of Plasmodium falciparum and the complications of the disease. In summary, interactions between endothelium and erythrocytes appear to be involved in the pathophysiology of a number of affections and could constitute a new therapeutic target.
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PMID:Adhesion of erythrocytes to endothelium in pathological situations: a review article. 797 Dec 46

Since vascular complications in diabetes mellitus are attributed in part to blood platelets, our study tested the hypothesis that adhesion of platelets to collagen is enhanced in diabetic subjects. Platelet adhesion kinetics to type I collagen in the presence of plasma were evaluated by a new continuous-flow, micro-adhesion assay combined with resistive-particle counting to detect the loss of single platelets between 0.3 and 2.3 sec. Adhesion was also studied in a magnesium-containing Krebs-Ringer buffer to help assess whether the platelets themselves might be abnormal. We did not observe any differences in adhesion kinetics to collagen between the insulin-dependent (type I), the non-insulin dependent (type II) diabetics and the control subjects for platelets suspended in plasma or in washed platelets (p > 0.05). These findings suggest that platelet adhesiveness to type I collagen is not enhanced in diabetic subjects and is unlikely to contribute to the development of vascular complications.
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PMID:Platelet adhesion to collagen under flow conditions in diabetes mellitus. 804 94

Nonenzymatic glycation of proteins is involved in the pathogenesis of diabetes vascular complications. Extracellular matrix proteins are a prominent target for nonenzymatic glycation because of their slow turnover rates. The aim of this study was to investigate the influence of human fibronectin (F) nonenzymatic glycation on adhesion and proliferation of cultured human vascular smooth muscle cells (hVSMC). Incubation of human F with 500 mmol/L D-glucose at 37 degrees C induced a time-dependent increase in fluorescence detectable at 440 nm after excitation at 363 nm. Nonenzymatic glycation did not affect binding of F itself to the plates. Adhesion of hVSMC to F increased with the increase of incubation time of the cells on the protein from 30 minutes up to 120 minutes and remained stable thereafter. Adhesion to glycated fibronectin (GF) was reduced in comparison to control F at all the different adhesion times. Adhesion of hVSMC to GF was reduced when F was exposed to glucose for 4, 9, or 28 days (P=.0417 to .0025), but not when F was exposed for 1 day. Adhesion of hVSMC to GF was reduced compared with adhesion to nonglycated F at all coating concentrations from 0.2 to 10 micrograms/mL (P=.05 to .014). Thus, nonenzymatic glycation of F impairs adhesion of hVSMC in vitro. Proliferation of hVSMC on F increased with increasing concentrations of the protein as coating agent (ANOVA:P<.0001 for both nonglycated F and GF). Proliferation with F glycated for 4, 9, and 28 days was reduced at concentrations of 1, 3, and 10 micrograms/mL as compared with proliferation with nonglycated F (P=.0253 to .0001). Proliferation on F glycated for only 1 day was not significantly reduced. When the number of hVSMC plated on control F was reduced by 25% to take into account the reduced adhesion, the number of cells that proliferated on F was still reduced. In conclusion, nonenzymatic glycation of F impairs adhesive and proliferative properties of hVSMC.
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PMID:Nonenzymatic glycation of fibronectin impairs adhesive and proliferative properties of human vascular smooth muscle cells. 860 33

Adhesion of lymphocytes to the endothelial venules inside the islets of Langerhans seems to initiate the infiltration of islets in NOD mice. An overexpression of the lymphocyte surface molecule CD44 in infiltrated NOD islets compared with peripheral blood lymphocytes was recently reported. The CD44 protein family includes a variety of molecules generated by alternative RNA splicing from 10 variant exons (v1-v10). By using reverse transcriptase-polymerase chain reaction followed by Southern blotting and hybridization to exon-specific cDNA probes, we investigated the expression of CD44 isoforms in highly purified islets of Langerhans from 4- and 10-week-old NOD mice. At least six CD44 isoforms were strongly overexpressed in NOD islets at 4 and 10 weeks when compared with age-matched BALB/c islets. Controls in different tissues indicate that these variants are specifically increased in the islets from the NOD strain. Islets from the NOD-scid/scid strain also expressed these variant exons. Splenocytes from BALB/c did not express CD44 isoforms, whereas splenocytes from 4-week-old NOD mice did express CD44 variants. Treatment with inflammatory mediators induced new isoforms; however, these transcripts have a different variant exon composition from that found in NOD mice islets. These results suggest that some isoforms are expressed very early in the development of insulitis by a component of the NOD islet itself and underscore a possible role of CD44 in islet infiltration.
Diabetes 1996 Jun
PMID:Expression of a specific subset of CD44 variant transcripts in NOD pancreatic islets. 863 43


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