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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
PubMed1994

Expression of adhesion molecules in endothelial cells during allogeneic bone marrow transplantation.

Endothelial cell activation during allogeneic bone marrow transplantation, mainly in acute graft-versus-host disease (aGvHD) was studied in 23 recipients and 5 controls using anti-von Willebrand factor (vWF) antibody, antibodies to endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), and anti-HLA-DQ antibody, by immunohistological staining of skin. vWF extravasation, ELAM-1 and VCAM-1 expression were present in most recipients with a cutaneous rash which was confirmed as an aGvHD by histological examination (documented aGvHD) (p = 0.005 for vWF extravasation and ELAM-1 expression and p = 0.03 for VCAM-1 expression in comparison with the controls). In recipients with a rash, the cases displaying vWF extravasation and ELAM-1 expression were significantly more numerous in those with a documented aGvHD than in those without histological features of aGvHD (p = 0.01). vWF extravasation and ELAM-1 occurred concomitantly (p < 0.01). This study demonstrates that, during the course of skin aGvHD following bone marrow transplantation, there is transient expression of ELAM-1 and VCAM-1 by endothelial cells and simultaneous vWF extravasation, indicating an intense inflammation with endothelial cell participation.

Acute Disease↗
PubMed1993

Increased thrombin generation in a child with a combined factor IX and protein C deficiency.

We report a quantitative protein C deficiency combined with a factor IX deficiency in a one-year-old boy. The inheritance of the two deficiency states was independent, the factor IX defect coming from the mother and the protein C defect from the father. Both factor IX activity and antigen were below 1%, and protein C activity as well as antigen were close to 27% of normal values. This association raises a real therapeutic and prognostic question. Protein C deficiency is indeed associated with a significant thrombotic risk and some factor IX concentrates seem to carry a potential thrombogenicity, particularly following infusion of repeated doses. We evaluated in this patient the potential activation of the coagulation system by measuring the levels of prothrombin fragment F1 + 2 at the basal state and after a single administration of 20 U/kg of a high purity factor IX concentrate. We found an unexpected basal activation of the hemostatic system before infusion (F1 + 2 = 1.6 nmol/L), which further increased during 8 hours. Despite the clinical predominant expression of the hemophilic trait, our results seem to assess the biologic prevalence of the protein C deficiency. This emphasizes the need for a careful follow-up after infusions of repeated doses of factor IX, as used during a surgical procedure. Furthermore, this raises the question of the prognosis because the risk of thrombotic manifestations associated with a protein C deficiency increases with age. Finally, these results highlight a part of the in vivo activation process of prothrombin in case of failure of the intrinsic pathway of coagulation. The protein C defect seems to be responsible for an upregulation of the prothrombin activation through the extrinsic pathway.

Factor IX↗
PubMed1993

Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease.

Type IIA is a variant form of von Willebrand disease (vWD) characterized by the absence of von Willebrand factor (vWF) high molecular weight multimers in plasma. Most of the candidate missense mutations potentially responsible for type IIA vWD have been found clustered within a short segment of vWF, lying between Gly742 and Glu875 of the mature subunit. The present work reports a single heterozygous T-->G transversion in eight patients from a large type IIA vWD family, resulting in the substitution Phe751-->Cys. The absence of this mutation in 100 normal vWF genes as well as the lack, in these patients, of any other abnormality within the whole exon 28 encoding amino acids 463-921 of mature vWF, provide a strong support that this non-conservative mutation may be at the origin of the disease in this family. The presence of an additional cysteine at position 751 may induce a conformational change of the vWF subunit affecting either its 'in vivo' sensitivity to proteolytic cleavage or, more likely, its intracellular transport as suggested by the abnormal multimeric pattern of platelet vWF observed in these patients.

Cysteine↗
PubMed1993

Results of splenectomy for idiopathic thrombocytopenic purpura. Review of 72 cases.

Seventy-two patients underwent splenectomy for idiopathic thrombocytopenic purpura between 1979 and 1990. Mean age at splenectomy was 36.4 years (range 11-73). Indications for splenectomy were corticodependence in 21 cases and resistance to steroids in 44 cases. Thirty-five patients had platelet kinetic studies by 51Cr alloplatelets; 22 of them had splenic sequestration. Hematologic results were evaluated on discharge, at 3 months and in the long term (median follow-up 5.4 years). We had no mortality, morbidity was seen in 7% of the cases. None of the patients suffered from secondary infectious complications. 89% had good results on discharge (> 120 x 10(9)/l), 72.6% at 3 months and 90% on long-term follow-up. Factors associated with good response to splenectomy included a high postoperative platelet count (more than 120 x 10(9)/l on discharge), younger age at the time of surgery, preoperative corticodependence and predominantly splenic sequestration.

Adolescent↗
PubMed1993

Thrombomodulin is synthesized by osteoblasts, stimulated by 1,25-(OH)2D3 and activates protein C at their cell membrane.

We have previously shown that protein S, a vitamin K-dependent protein, is a bone matrix component synthesized and secreted by osteoblasts. Because protein S is a cofactor of protein C in inhibiting factor Va and VIIIa, we have looked for the presence of the proteins related to the anticoagulant protein C system in human MG 63 osteosarcoma cells and in human adult osteoblast-like cells. Using immunoblotting, we have shown that protein C, factor V, and C4b binding protein are not secreted by these cells. We have shown by enzyme-linked immunoassay, immunocytochemistry, and immunoprecipitation of labeled proteins that thrombomodulin, a transmembrane glycoprotein involved with thrombin in the activation of protein C, is present at the cell surface of osteoblasts. Moreover, using a protein C activation system where thrombin and protein C are added to the cells, we have shown that protein C could be activated at the osteoblast cell surface. This activation of exogenous protein C, reflecting the activity of thrombomodulin, as well as the expression of the thrombomodulin antigen, is regulated by some bone resorption-enhancing factors. 1,25-dihydroxyvitamin D3 and retinoic acid increase thrombomodulin expression and activity in a dose-dependent manner whereas tumor necrosis factor alpha and interleukin 1 decrease these parameters. Because thrombomodulin is known to inhibit single-chain urokinase-type plasminogen activator, a molecule present in the osteoblast microenvironment, these findings suggest that thrombomodulin could play a role in the regulation of bone resorption by modulating the plasmin system.

Calcitriol↗
PubMed1993

Immunization by bovine thrombin used with fibrin glue during cardiovascular operations. Development of thrombin and factor V inhibitors.

Brief case histories of three patients aged 58, 38, and 44 years are reported. All underwent cardiovascular operations. Subsequently hemostasis test abnormalities developed between the seventh and eighth postoperative days after exposure to bovine thrombin used with fibrin glue. These were characterized by an increased activated partial thromboplastin time (64 to 147 seconds), prothrombin time (19 to 24 seconds), bovine thrombin time (> 120 seconds) and a markedly reduced factor V level (< 10% in two patients and 16% in the third patient). A patient plasma dilution of 1 in 200 with a normal plasma pool was necessary to correct bovine thrombin time. No fast-acting or progressive inhibitor against factor V could be detected by coagulation tests, and fresh frozen plasma perfusion had no effect. Plasmapheresis was performed preventatively to avoid bleeding, and factor V levels stabilized at around 50% after two to four exchanges. Immunologic studies showed that the inhibitors were directed not only against bovine factors but also against human ones. Therefore factor V decrease could have been the result of rapid clearance from the circulation of complexes formed with a nonneutralizing inhibitor that is not detected by clotting tests. These antibodies were purified by standard methods and immunoaffinity. Fast immunization could be explained by a prior sensitization to bovine thrombin exposure during previous operations. It is suggested that bovine thrombin used with fibrin glue contains small amounts of factor V and may be responsible for these abnormalities. This is in agreement with previous literature reports. However, these described neutralizing factor V inhibitors, which were easily detected.

Adult↗
PubMed1992

Priming effect of adrenic acid (22:4(n-6)) on tissue factor activity expressed by thrombin-stimulated endothelial cells.

Tissue factor (TF) which initiates clotting process can be expressed by stimulated endothelial cells (EC). TF is an apolipoprotein requiring an association with phospholipids (PL) in order to become active. Also PL constitute an important storage pool of polyunsaturated fatty acids (PUFAs) in EC which can be modulated by diet or cell medium supplementation. In order to test the effect of such manipulation upon TF activity, we have pre-enriched human EC cultures with different fatty acids of nutritional interest. TF was evaluated after 4 h of thrombin stimulation by using a chromogenic method. Without additional stimulating agents, these acids have no effect on the basal level of TF. Eicosapentaenoic and docosapentaenoic acids appeared to be ineffective at the stimulated TF level. Only adrenic acid (22:4(n-6)) has been found to significantly enhance TF activity of thrombin-stimulated endothelial cells. Other TF inducers were also tested after 22:4(n-6) enrichment. An increase tendency of TF expression was found only with tumor necrosis factor, whereas interleukin-1 beta, lipopolysaccharide and especially phorbol myristate acetate stimulations were not significantly modified. The priming effect of adrenic acid on thrombin stimulated TF expression might involve alterations of signal transduction pathways rather than modifications of apolipoprotein III environment. Adrenic acid, which is a prostacyclin inhibitor, appears to be potential prothrombotic agent.

Cells, Cultured↗
PubMed1992

Protein-S, a vitamin K-dependent protein, is a bone matrix component synthesized and secreted by osteoblasts.

Protein-S is a vitamin K (Vit K)-dependent protein synthesized by hepatocytes, megakaryocytes, and endothelial cells and plays an important role in the regulation of hemostasis. Two cases of free protein-S congenital deficiency were recently reported to be associated with osteopenia. We hypothesized that this osteopenia could be the result of a bone deficit of protein-S synthesized by bone cells. Using enzyme-linked immunoassay, immunocytochemistry, immunoblotting, and immunoprecipitation after labeling with [35S]methionine, we have shown that this protein is secreted by three human osteosarcoma cell lines and by human adult osteoblast-like cells. In addition, protein-S was present in protein extracts of human bone matrix. Protein-S secreted by MG 63 cells increased linearly from 1-7 days of culture, was biologically active, and was regulated by warfarin, as previously described for the other cell types secreting protein-S. Vit K had no direct effect on protein-S secretion or activity, but could overcome the effects of warfarin. In conclusion, in addition to osteocalcin and matrix gamma-carboxyglutamic acid (Gla) protein, osteoblasts secrete another Vit K-dependent protein, which is a constituent of the bone matrix. Our data suggest that osteopenia occurring in patients with congenital protein-S deficiency might be related to a deficiency of protein-S secretion by the osteoblasts. This finding raises the intriguing possibility that protein-S might play a role in bone turnover and bone mass.

Bone Neoplasms↗
PubMed1992

Acquired protein S deficiency: correlation with advanced disease in HIV-1-infected patients.

A plasma free protein S deficiency was detected in 41 of 63 patients infected with the human immunodeficiency virus type I (HIV-1). This study consisted in a prospective analysis of blood samples from 26 patients with confirmed diagnosis of AIDS, two with AIDS-related complex, 10 with polyadenopathy, and 25 who were asymptomatic. Protein S levels were compared to a matched control group of 24 healthy subjects. A deep venous thrombosis occurred in three AIDS patients with free protein S deficiency. A significant decrease in plasma free protein S levels was observed in HIV-1-seropositive patients (mean +/- SD, 56.5 +/- 23.3%) as compared with control subjects (105.3 +/- 18%, p = 0.0001). Free protein S levels were significantly lower in patients with full-blown AIDS (37.6 +/- 12.3%) than in patients without AIDS (69.8 +/- 19.9%, p = 0.0001). Low plasma free protein S levels correlated with high beta 2-microglobulin values (p = 0.0001), low CD4+ T-cell counts (p = 0.0002) and elevated urinary neopterin concentrations (p = 0.005). According to a multiple regression analysis, the progression to stages IVB, IVC1 or IVD of the Centers for Disease Control (CDC) appeared to be the main explanatory variable in free protein S-deficient patients. Such results suggest that free protein S deficiency may coincide with the development of AIDS. This could contribute to hypercoagulability and, in some instances, thromboembolic complications in AIDS patients.

Acquired Immunodeficiency Syndrome↗
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↗