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Biomedical subjects

M Dechavanne

Publications and source records attributed to M Dechavanne.

At least 37 records · Page 2Linked to original sources
PubMed1991

Osteonectin is an alpha-granule component involved with thrombospondin in platelet aggregation.

We previously showed that thrombospondin, a major alpha-granule glycoprotein of human platelets, forms a specific complex with osteonectin, a phosphoglycoprotein originally described in bone that is also present in human platelets. The storage organelles and the function of osteonectin in platelets are still unknown. In this study, using electron microscopy in combination with immunogold staining, the major storage organelle for platelet-secreted proteins, the alpha-granules. Furthermore, osteonectin was qualitatively and quantitatively assessed by studying normal platelets and the platelets from a patient with gray platelet syndrome. Gray platelet syndrome is a rare congenital bleeding disorder characterized by a selective deficiency in morphologically recognizable platelet alpha-granules and in the alpha-granule secretory proteins. Binding of an iodinated antiosteonectin monoclonal antibody to gray platelet proteins transferred to nitrocellulose from SDS-polyacrylamide gels showed no band corresponding to osteonectin compared to control platelets. Using a polyclonal antiosteonectin antibody-based radioimmunoassay, gray platelets contained 0.2 +/- 0.03 ng osteonectin per 10(6) platelets, which is only 20% of the normal platelet content of osteonectin (0.93 +/- 0.16 ng per 10(6) platelets). Study of the localization of osteonectin to the surface of human platelets demonstrated that a radioiodinated antiosteonectin polyclonal antibody bound specifically to thrombin-stimulated platelets but not to resting platelets. Binding was concentration-dependent, saturable (1710 +/- 453 binding sites per platelet, Kd = 1 microM), and inhibited by an excess of cold antiosteonectin polyclonal antibody. No binding was observed on the surface of thrombin-stimulated gray platelets. To gain further insights into the role of osteonectin released from activated platelets, the effect of an antiosteonectin polyclonal antibody was tested on the aggregation of washed platelets. F(ab')2 fragments from the antiosteonectin polyclonal antibody inhibited in a dose-dependent manner the aggregation of collagen-stimulated, washed human platelets without affecting collagen-induced platelet serotonin release. To characterize the mechanism through which antiosteonectin F(ab')2 fragments inhibit platelet aggregation, the expression of endogenous thrombospondin (TSP) on the surface of thrombin-activated platelets was studied using 125I-labeled anti-TSP monoclonal antibody P10. The endogenous surface expression of TSP to thrombin-stimulated platelets was significantly inhibited in the presence of antiosteonectin F(ab')2 fragments (6286 +/- 2065 molecules of P10 per platelet) compared to 11,230 +/- 766 molecules of P10 per platelet in the presence of nonimmune F(ab')2 fragments.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1991

Successful treatment of acquired factor VIII antibody by extracorporeal immunoadsorption.

We report the successful treatment of a 59-year-old woman with acquired factor VIII inhibitor. The patient who had an extensive leg hematoma with a resultant neurologic defect was treated with extracorporeal immunoadsorption (IA) using protein A-Sepharose, factor VIII concentrates, azathioprine, and methyl-prednisolone. Extracorporeal IA reduced the titers of the inhibitor so that factor VIII concentrates could raise the level of factor VIII coagulant activity and stop the bleeding.

Autoantibodies↗
PubMed1991

Comparison of hemostasis with two high-flux hemocompatible dialysis membranes.

Eight adults with chronic renal failure were dialyzed using polyacrylonitrile (AN 69) or polysulfone (PS) membranes with a high (HHR) or low (LHR) continuous non-fractionated heparin regimen--a total of either 90 or 50 IU/kg body weight. With the HHR, for a mean anti-Xa (aXa) activity of around 0.40 IU/ml, no plasma activation of coagulation was observed; fibrinopeptide A (FPA) was in agreement with the residual blood volume (RBV) and the state of the bubble trap, especially with the PS membrane. With the LHR, for a mean aXa below 0.21 IU/ml, there was only moderate activation of coagulation. The PS membrane gave different results from the AN 69 membrane, RBV values on the HHR and aXa being lower on both the HHR and LHR, with FPA values being regularly lower on the LHR. The decrease in plasma beta-TG on the LHR was more marked with the PS than with the AN 69 membrane due to loss on dialysis or adsorption, as shown by the arterio-venous difference. The increase in plasma PF4 was related to the effect of heparin. However, there was no platelet activation. On the LHR, platelet count and intraplatelet beta-TG and PF4 levels remained very stable. The two high-flux membranes were very hemocompatible and require only low doses of heparin, but the dialyzer with AN 69 membrane need its geometry improving.

Acrylic Resins↗
PubMed1990

Functions and tocopherol content of blood platelets from elderly people after low intake of purified eicosapentaenoic acid.

Elderly people present an increased incidence of atherosclerosis and vascular cerebral damages, associated with blood platelet hyperactivity and a stimulation of arachidonic acid metabolism in vivo. The effects of a low intake of purified eicosapentaenoic acid (EPA) on platelet hyperactivity in old human subjects has been investigated. In a randomized, double blind study, 8 people took during 2 months a daily intake of 100 mg of eicosapentaenoic acid (EPA) given as a triglyceride (1,3-dioctanoyl,2-eicosapentaenoyl-glycerol), and 8 other subjects ingested a placebo. A slight, but significant reduction of platelet-rich plasma aggregation in response to epinephrine and arachidonic acid occurred after EPA intake, as well as a decreased aggregation of washed platelets induced by thrombin, although collagen- and U-46619-induced aggregations were not significantly modified. EPA intake failed to affect arachidonic acid metabolism in thrombin-stimulated platelets or in clotted venous blood. The urinary excretion of thromboxane, 6-keto-PGF1 alpha and their 2,3-dinor-metabolites was also not modified. Similarly, no change in the plasma and platelet lipid fatty acid compositions could be observed. Platelet, but not plasma, alpha- and gamma-tocopherol were enhanced by EPA intake. An increase of platelet vitamin E has been associated with a decrease of aggregation, especially in vitamin E-deficient subjects, like elderly people. Therefore, low intake of EPA might have contributed to inhibit platelet aggregation by increasing cellular vitamin E.

Administration, Oral↗
PubMed1990

Increased plasma tissue-type plasminogen activator levels in patients with chronic thrombocytopenia.

Plasma fibrinolytic factors were measured in 14 patients with chronic idiopathic thrombocytopenic purpura (ITP), in 5 patients with chronic central thrombocytopenia and in 16 healthy volunteers. The von Willebrand factor (vWF), tissue-type plasminogen activator (t-PA) and D-dimer (DD) antigens were found to be significantly higher in both patient groups than in the control group. No difference appeared in euglobulin fibrinolytic activity and plasminogen activator inhibitor activity. The increases in both t-PA and vWF suggest the occurrence of an endothelial cell stimulation, associated with the reduction of circulating platelet number. The correlation of increased DD and t-PA levels during ITP can be the proof of a fibrinolysis activation and suggest an antifibrinolytic role of platelets at physiological concentrations. These results can justify antifibrinolytic therapy in bleeding thrombocytopenic patients.

Adult↗
PubMed1989

Aggregation to thrombin and collagen of platelets from a Glanzmann thrombasthenic patient lacking glycoproteins IIb and IIIa.

The aim of this study was to investigate the platelets of a Glanzmann thrombasthenic patient, which in citrated PRP failed to respond to various agonists, but aggregated and secreted to high concentrations of thrombin (0.36, 0.72 and 1 U/ml) and collagen (4, 10 and 20 micrograms/ml) when washed and resuspended in a Tyrode-albumin solution (containing 2 mM Ca2+). Aggregation of the patient platelets was not affected by anti-IIb/IIIa monoclonal antibody (P18) which strongly inhibits thrombin or collagen induced aggregation of normal platelets. Washed platelets of this patient did not aggregate to ADP (10-100 microM) in the presence of added fibrinogen (2 mg/ml) nor bind 125I-labelled fibrinogen (40 to 320 micrograms/ml) when thrombin-stimulated. Different anti-IIb/IIIa monoclonal antibodies (P2, P18) when used in binding or crossed immunoelectrophoretic studies showed a complete absence of the IIb-IIIa glycoprotein complex on the patient platelets. Moreover, glycoproteins IIb or IIIa were absent on silver-stained two-dimensional (non-reduced/reduced) polyacrylamide gel separations of the patient platelets and were not detected by Western blots used in combination with anti-PLA1 (antigen present on IIIa), anti-Leka (antigen present on IIb). This study shows that platelets lacking glycoproteins IIb or IIIa can aggregate in response to high concentrations of collagen or thrombin when resuspended in the presence of physiological concentrations of calcium. Results obtained in this study could indicate the existence of other mechanisms (other than the IIb-IIIa glycoprotein complex) involving glycolipids, heparans, proteoglycans, and/or unknown membrane glycoproteins to mediate platelet aggregation of stimulated thrombasthenic platelets.

Adult↗
PubMed1989

[Influence of diet and life habits on platelet functions].

The measurement of platelet activation utilizes relatively complex and ill-standardized tests which vary from one laboratory to another. A long-term diet rich in saturated fatty acids is associated with platelet hyperaggregability which is suppressed after dietary changes, with an increased intake of polyunsaturated fatty acids, especially linoleic acid. However, the linoleic acid intake must not be too high. It is advised to maintain the polyunsaturated/saturated fatty acid ratio at 0.6 to 1 in subjects that are apparently in good health. Both 20:5 n-3 and 22:6 n-3, the main n-3 fatty acids of marine fish oils, inhibit platelet aggregation, but they do it weakly and only after a high intake. On the other hand, both emotional stress and tobacco smoking induce platelet activation, while a physical exercise of moderate intensity seems to be beneficial. Finally, there is no evidence that oral contraceptives with low oestrogen content induce platelet aggregation in women who have no other risk factor of coronary artery disease.

Blood Platelets↗
PubMed1989

Rapid purification and partial characterization of human platelet glycoprotein IIIb. Interaction with thrombospondin and its role in platelet aggregation.

Glycoprotein IIIb (also known as glycoprotein IV) is a major glycoprotein present on the surface of human platelets. Recent studies suggest that glycoprotein IIIb may be a receptor site for thrombospondin. Thrombospondin, a multifunctional adhesive glycoprotein released from stimulated platelets, plays an important role in the stabilization of platelet aggregates. In this study, a new method for the purification of glycoprotein IIIb is described. Glycoprotein IIIb was isolated from Triton X-114 platelet membrane extracts, under nondenaturing conditions, by tandem anion-exchange and size exclusion fast protein liquid chromatography. The purified glycoprotein had the same apparent molecular mass (88 kDa) under nonreducing or reducing conditions. The tryptic peptide map of the purified protein was identical to that of bona fide glycoprotein IIIb as isolated from two-dimensional polyacrylamide gels of platelet membrane proteins. In addition, the purified glycoprotein was recognized by an anti-GPIIIb monoclonal antibody (OKM5). The purified glycoprotein specifically bound to thrombospondin in the presence of calcium. Monospecific anti-GPIIIb antibodies interfered with the expression of endogenous thrombospondin on thrombin-activated platelets and partially inhibited collagen- and thrombin-induced platelet aggregation without a significant effect on platelet secretion. Glycoprotein IIIb, by interacting with thrombospondin on the activated platelet surface, may play an important role in the platelet aggregation process.

Blood Platelets↗
PubMed1989

Increased in vivo biosynthesis of prostacyclin and thromboxane A2 in chronic idiopathic thrombocytopenic purpura.

The production of thromboxane A2 (TxA2) and prostacyclin (PGI2) was studied in patients with chronic idiopathic thrombocytopenic purpura (10 patients) compared to central thrombocytopenia (five patients) and healthy subjects (10 subjects). This production was monitored by the assay of urinary 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha as respective breakdown products of TxA2 and PGI2 by stable isotope dilution assays employing negative ion-chemical gas-chromatography-mass-spectrometry. Evidence is presented for the existence of an enhanced PGI2 and TxA2 urinary excretion in the group of idiopathic thrombocytopenic purpura (ITP) patients. Moreover, production of serum TxB2 per platelet was decreased in ITP group. These results provide arguments for an in vivo platelet cyclooxygenase hyperactivity during chronic ITP.

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Randomized trial of a low-molecular-weight heparin (Kabi 2165) versus adjusted-dose subcutaneous standard heparin in the prophylaxis of deep-vein thrombosis after elective hip surgery.

124 patients undergoing total hip replacement were randomly allocated to receive Kabi 2165, 2,500 anti-Xa units twice a day (group A); Kabi 2165, 2,500 anti-Xa units twice a day during the first 48 h postoperatively and then 5,000 anti-Xa units once a day (group B), or adjusted-dose standard heparin, monitored by activated partial thromboplastin time (group C). The first dose was given 2 h before surgery in the three groups. Deep-vein thrombosis (DVT) was detected by radiolabelled fibrinogen uptake and bilateral venography was performed in patients who had a positive scan. In patients who had a negative scan, bilateral venography was performed routinely the day before discharge from hospital. The frequency of DVT demonstrated by venography was 4.9% in group A, 7.3% in group B and 10% in group C. The difference between the three groups was not statistically significant. The incidence of proximal DVT was 2.4, 2.4 and 7.5%, respectively, for the three groups. There was no significant difference between the three groups with respect to mean estimated blood loss, the number of blood units transfused, wound hematoma formation, or hemoglobin and hematocrit levels.

Drug Evaluation↗
PubMed1989

[IgM kappa gastric plasmacytoma].

A case of gastric plasmacytoma in a 50-year old woman was reported. Immunofluorescent and immunoperoxidase studies were performed. Polyclonal antibodies reactive with immunoglobulin chains and a panel of 14 monoclonal antibodies reactive with B and T cells, and epithelial cells were used. These studies showed that the tumor cells produced IgM Kappa molecules whereas no monotypic immunoglobulin could be detected in the serum and urine. On the other hand the tumor cells had the immunologic phenotype of plasma cells. This helps diagnosis: some lymphomas with plasmocytic differentiation could also produce a monotypic immunoglobulin. Treatment using a combination of surgery, radio and polychimiotherapy was effective, leading to complete remission.

Female↗
PubMed1988

Complex formation of human thrombospondin with osteonectin.

Human thrombospondin, a 450-kDa glycoprotein isolated from platelets and endothelial cells, specifically interacts with osteonectin, a protein of 30 kDa isolated from bovine bones and human platelets. Using ELISA, purified osteonectin binds to solid-phase-adsorbed thrombospondin with a dissociation constant (Kd) of 0.7 nM. Binding of thrombospondin to solid-phase-adsorbed osteonectin was also observed (Kd = 0.86 nM). The interaction of thrombospondin with solid-phase-adsorbed osteonectin was significantly decreased (81% inhibition) when using an excess of fluid-phase osteonectin. Thrombospondin-osteonectin complex formation was calcium-dependent as shown by a 50-80% inhibition in the presence of EDTA. None of the proteins known to interact with thrombospondin (fibrinogen, fibronectin, collagen, plasminogen) had a significant inhibitory effect on thrombospondin-osteonectin complex formation. This selective interaction was confirmed by affinity chromatography. Iodinated osteonectin, previously incubated with purified thrombospondin, specifically bound to an anti-thrombospondin monoclonal antibody (P10) linked to protein-A--Sepharose 4B. Elution of the anti-thrombospondin antibody from protein A allowed the recovery of the thrombospondin-osteonectin complex in the eluate, as judged by SDS/polyacrylamide gel electrophoresis and autoradiography. Blotting of purified thrombospondin to osteonectin adsorbed onto nitrocellulose further confirmed complex formation. In addition, when released from thrombin-stimulated platelets, thrombospondin and osteonectin bound to anti-thrombospondin IgG-coated plates indicating that osteonectin was complexed to thrombospondin once the platelet-release reaction has occurred.

Animals↗
PubMed1988

Platelets and aging. I--Aggregation, arachidonate metabolism and antioxidant status.

Platelet functions were investigated in sixteen old (78-94 years) and eight young (25-35 years) subjects. Whole blood platelet aggregation induced by collagen was higher in the elderly. Similarly, aggregation of platelet rich plasma and plasma-free platelets induced by various agents was increased but the collagen-induced release of ATP was reduced. In agreement with the enhanced platelet aggregability, the increase of thromboxane formation (under thrombin stimulation) was also noted in platelets from elderly people. To further assess platelet and vascular function in vivo, we measured the excretion of urinary TXB2, 2,3-dinor TXB2, 6-keto-PGF1 alpha and 2,3-dinor-6-keto-PGF1 alpha. The four metabolites were all increased in the elder population. In addition, a significant reduction of platelet vitamin E was observed in the elderly people, although the plasma content was normal. These results indicate numerous modifications of platelet behaviour with aging. They include the increased platelet susceptibility to aggregation, and the depletion of ATP granule content, which could reflect an activation in vivo in agreement with the enhanced urinary excretion of thromboxane and prostacyclin metabolites. We hypothesize that platelet hyperactivity associated with the enhanced oxygenated metabolism of arachidonic acid could be linked to vitamin E depletion. These changes may reveal a prethrombotic state in the elderly population.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Acute myocardial infarction: measurement of arachidonate end-products in whole blood as an index of platelet cyclo-oxygenase activity in vivo.

The endogenous arachidonic acid metabolism was investigated ex vivo, in separated serum from clotted whole blood, soon after the onset of acute myocardial infarction (3.3 +/- 0.7 hr). A group of eight consecutive male patients was selected, since no evidence was obtained of any associated disease known to increase platelet activity or any recent exposure to cyclo-oxygenase inhibitors. This group of patients compared to an age and sex matched control group showed a large decrease in the platelet cyclo-oxygenase end-products in whole blood: thromboxane B2 (TXB2), 12-hydroxy-5-cis, 8-cis, 10-trans-heptadecatrienoic acid (HHT) and 6-keto-PGF1 alpha (p less than .01). In addition, platelet lipoxygenase produced an increased amount of 12-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) as measured by its reduced metabolite 12-HETE (p less than .05). Furthermore, the TXB2 plasma concentration was significantly elevated in patients (p less than .01), confirming the enhanced platelet reactivity during the early stages of acute myocardial infarction. These results point out that a decreased level of cyclo-oxygenase end-products and an increased level of lipoxygenase end-product in serum is consistent with a previous in vivo cyclo-oxygenase hyperactivity.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Intravenous high-dose IgG therapy induced alterations of spleen lymphocyte IgM secretion and T cell subsets in patients with idiopathic thrombocytopenic purpura.

High-dose intravenous (IV) IgG therapy is an effective possible means of raising platelet counts in patients with idiopathic thrombocytopenic purpura (ITP). In order to elucidate further the mechanism of action of such treatment we comparatively studied spleen mononuclear cells (SMC) from two groups of ITP patients. Group I consisted of 9 patients who had not received any recent treatment before splenectomy. The 8 patients in group II had received IV IgG infusions 1-5 days before splenectomy. The SMC were cultured either unstimulated or stimulated by pokeweed-mitogen (PWM), and proliferation (as assessed by 3H-thymidine uptake), and IgG and IgM secretion were measured. In addition T lymphocyte subsets were determined in the SMC by indirect immunofluorescence using monoclonal antibodies (OKT3,4,8). By comparison with group I SMC, our results in group II SMC mainly showed a significant decrease in proliferation and IgM secretion, in both unstimulated and PWM stimulated cultures. In addition, a significant decrease in the proportion of T helper-inducer lymphocytes (OKT4+ cells) was also found in group II SMC, as compared to group I SMC. However, these immunological alterations in group II SMC were paradoxically more pronounced in those patients who failed to respond to IV IgG infusions. Thus, these results suggest that, although immune suppression takes place in the SMC of ITP patients following IV IgG therapy, it has not a pronounced effect on the increase of platelet.

Adolescent↗