[Heparin induced autoimmune thrombocytopenia: assessment of a rapid functional assay].

Heparin-induced thrombocytopenia (HIT) diagnosis is often difficult. Depending on the patients, the thrombocytopenia could be due to various causes. Despite their poor sensitivity and specificity, biological tests are necessary to clarify the diagnosis.

CD40lbase: a database of CD40L gene mutations causing X-linked hyper-IgM syndrome.

X-linked hyper-IgM syndrome (X-HIM) is an immunodeficiency caused by mutations in the gene encoding the CD40 ligand (CD40L). A database (CD40Lbase) of CD40L mutations has now been established, and the resultant information, together with other mutations reported elsewhere in the literature, is presented here.

Association of the protein tyrosine phosphatase PTP1C with the protein tyrosine kinase c-Src in human platelets.

Protein tyrosine phosphatase 1C (PTP1C), highly expressed in hematopoietic cells, is a soluble protein tyrosine phosphatase containing two Src homology 2 (SH2) domains at the N-terminus and two putative sites of tyrosine phosphorylation at the C-terminus. This paper reports that PTP1C and c-Src could be coimmunoprecipitated during thrombin-induced platelet activation. Moreover, association between the two signalling proteins occurred only after PTP1C had been tyrosine phosphorylated.

Association of phosphatidylinositol 3-kinase, via the SH2 domains of p85, with focal adhesion kinase in polyoma middle t-transformed fibroblasts.

Focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase, becomes activated and phosphorylated on tyrosine in cells transformed with v-src. By cytoimmunofluorescence a sub-fraction of the p85 subunit of phosphoinositide 3-kinase (PI 3-kinase) localized in focal adhesion plaques. We examined the possibility that FAK associates with PI 3-kinase.

Phosphorylation of the platelet p47 phosphoprotein is mediated by the lipid products of phosphoinositide 3-kinase.

Platelet stimulation by thrombin or the thrombin receptor activating peptide (TRAP) results in the activation of phosphoinositide 3-kinase and the production of the novel polyphosphoinositides phosphatidylinositol 3,4-bisphosphate (PtdIns-3,4-P2) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns-3,4,5-P3). We have shown previously that these lipids activate calcium-independent protein kinase C (PKC) isoforms in vitro (Toker, A., Meyer, M.

Role of Fc gamma RIIA gene polymorphism in human platelet activation by monoclonal antibodies.

The aim of this study was to determine if there is a correlation between the activity of a MoAb as an agonist and its ability to bind to the Fc platelet receptor, Fc gamma RIIa. A polymorphism at amino acid 131 [arginine (Arg) or histidine (His)] of Fc gamma RIIa was first shown to be determinant for MoAb-IgG1 binding on monocytes. To clarify the role of this polymorphism in platelet activation by MoAb-IgG1 we (i) established the Fc gamma RIIa polymorphism at the gene level by adapting the denaturating gradient gel electrophoresis method, (ii) analyzed the binding affinity of the MoAbs to Fc gamma RIIa on platelets from homozygous Arg, homozygous His, and heterozygous Arg/His donors, and (iii) characterized the different reactivities of platelets according to the Fc gamma RIIA polymorphism.

Phosphoinositide 3-kinase inhibition spares actin assembly in activating platelets but reverses platelet aggregation.

Platelet stimulation by thrombin leads to the activation of phosphoinositide 3-kinase (PI 3K) and to the production of the D3 phosphoinositides, phosphatidylinositol 3,4-bisphosphate (PdtIns-3,4P2) and 3,4,5-trisphosphate (PdtIns-3,4,5-P3). Because changes in the levels of these phosphoinositides correlate with the kinetics of actin assembly, they have been proposed to mediate actin assembly, causing cell shape changes. Wortmannin and LY294002, two unrelated inhibitors of PI 3-K, were used to investigate the role of PI 3-K in platelet actin assembly and aggregation.

[Antiplatelet glycoprotein monoclonal antibodies: properties and practical value].

The aim of this review is (i) to classify the different monoclonal antibodies against platelet glycoproteins according to their properties and (ii) to take stock of their many diagnostic and therapeutic uses. Most of these antibodies recognize antigens on resting platelets without inducing activation, sometimes however they inhibit platelet function. Some of these antibodies, especially those against specific antigens (GPIIb/IIIa, CD9, CD36), have the capacity to activate platelets in vitro, either by direct binding of antibodies on the antigen or through the Fc domain binding to its platelet receptor Fc gamma RII.

Leukemic ophthalmopathy: a report of 21 pediatric cases.

A multicentric retrospective study on leukemic ophthalmopathy (LO) is reported. It includes 21 patients, 16 males and 5 females, with acute leukemia (AL) observed in 10 SIOP centers. LO developed in three patients at the time of diagnosis of AL; five patients were in first complete remission (three off therapy); four patients were in second or third remission; and nine were in combined relapse.

[Microangiopathic anemia following thrombopenic purpura].

Background: Chronic relapsing microangiopathic hemolytic anemia is rare in children. This report describes a case associated with thrombocytopenia following idiopathic thrombocytopenic purpura.

Case Report: A 4 year-old girl was admitted for acute idiopathic thrombocytopenic purpura (platelet count: 12,000/mm3) without anemia or fragmented red cells.

Indapamide inhibits human platelet aggregation in vitro: comparison with hydrochlorothiazide.

Among antihypertensive drugs with diuretic properties, indapamide was shown to inhibit platelet growth factors production in diabetic hypertensive patients, suggesting an antiplatelet activity. The present study aimed to demonstrate the antiaggregating properties of indapamide. The effect of indapamide on platelet function was compared in vitro to that of hydrochlorothiazide.

Inhibition of platelet activation by tyrosine kinase inhibitors.

Protein tyrosine kinase (PTK) blockers (tyrphostins) inhibit in a dose-dependent fashion thrombin-induced aggregation and serotonin release with IC50 values in the 10-35 microM concentration range. The inhibition of thrombin-induced aggregation correlates with their potency in inhibiting phosphorylation of proteins on tyrosine residues. Using metabolically 32P-labelled human platelets, it was found that the tyrphostins have no effect on the decrease in [32P]phosphatidylinositol bisphosphate but prevent the replenishment of [32P]polyphosphoinositide.

Functional implications of tyrosine protein phosphorylation in platelets. Simultaneous studies with different agonists and inhibitors.

During activation of platelets by agonists, a number of proteins become phosphorylated at tyrosine residues. Using immunoblotting with a monoclonal anti-phosphotyrosine antibody, we have compared the different phosphotyrosine-protein (PTP) profiles of platelets stimulated with thrombin, collagen, ADP, arachidonic acid, phorbol myristate acetate and P256, an anti-glycoprotein-IIb-IIIa (GPIIb-IIIa) monoclonal antibody (mAb). Only a few PTPs were observed in resting platelets, of molecular masses 130, 64, 56-60 and 36 kDa.

[Parameningeal cervical rhabdomyosarcoma in the neonatal period].

A case of parameningeal cervical rhabdomyosarcoma with severe bone destruction is reported in a 3 month-old infant; symptoms were present at birth. The treatment consisted of exclusive intensive chemotherapy. The outcome was favourable with complete tumor regression and vertebral bone reconstruction.

Involvement of platelet glycoprotein IIb-IIIa (alpha IIb-beta 3 integrin) in thrombin-induced synthesis of phosphatidylinositol 3',4'-bisphosphate.

32P-Labeled human platelets were incubated with thrombin (1 unit/ml) for 5 min at 37 degrees C under conditions allowing maximal synthesis of [32P]phosphatidylinositol 3',4'-bisphosphate (PtdIns(3,4)P2). Incorporation of 32P into the latter phosphoinositide was dose-dependently reduced (to a maximal level averaging 60%) by the tetrapeptide RGDS, an inhibitor of fibrinogen binding to activated glycoprotein IIb-IIIa (alpha IIb-beta 3 integrin). Identical results were obtained with the fibrinogen gamma-chain dodecapeptide HHLGGAKQAGDV, whereas the tripeptide RGD and the tetrapeptide RGES displayed reduced or undetectable effects on 32P labeling of PtdIns(3,4)P2, respectively, in good correlation with their ability to inhibit platelet aggregation and fibrinogen binding to activated alpha IIb-beta 3 integrin.

[Primary germinal tumors of the central nervous system].

Primary intra-cranial germ-cell tumors are a rare and heterogeneous group of neoplasms, identical to germ-cell tumors of gonads and other organs. These tumors arise along the midline, from the supra-sellar cistern to the pineal gland, and have neurological, ophthalmological, and endocrinological expression. The diagnosis is established by detection of increased levels of tumoral markers and/or by histological examination.

[Brain stem tumors in children].

Gliomas involving the brain stem represent 10% of pediatric central nervous system neoplasms. They result in multiple cranial nerve involvement, long tracts signs, cerebellar signs, usually with no evidence of raising in intracranial pressure. The diagnosis is established by computed tomographic scan and magnetic resonance imaging.

Mechanisms involved in platelet activation induced by a monoclonal antibody anti glycoprotein IIb-IIIa: inositol phosphate production is not the primary event.

The mechanisms involved in platelet aggregation by a monoclonal antibody (mAb) P256 specific for the GPIIb-IIIa complex was investigated following metabolic 32P labelling of platelets. When compared with thrombin, inositol phosphates (InsP) production during P256-induced activation was delayed and no apparent peak, but a small and sustained production of [32P]-Ins(1,4,5)P3 and [32P]-Ins(1,3,4,5)P4, was observed between 20 and 90 s. [32P]-Ins(1,3,4)P3 was also produced with a maximum after 90 s.

Activation of platelets induced by mAb P256 specific for glycoprotein IIb-IIIa. Possible evidence for a role for IIb-IIIa in membrane signal transduction.

Monoclonal antibody P256, which is specific for glycoprotein IIb-IIIa complex, was found to induce aggregation of normal platelets in plasma. The mechanism of platelet activation induced by this monoclonal antibody was thoroughly studied. The divalent binding to the IIb-IIIa molecule was necessary for triggering aggregation since Fab' fragments did not induce aggregation as did IgG and F(ab')2 fragments; however, F(ab')2 did not induce the release as did the whole IgG.

[Intravenous administration of deferoxamine in over-night hospitalization: efficacy and good psychological tolerance in thalassemic children].

Daily subcutaneous infusion of deferoxamine in thalassemia and other transfusion dependent-patients can successfully treat iron overload, but most patients, mainly young children and teenagers may not comply with this method. Experience with nightly intravenous infusion of deferoxamine (8 g) through a subcutaneous-port over 5 out of 21 days, is reported in 4 children with dramatic improvement in clinical status, ferritin levels and quality of life.

Ifosfamide is an active drug in Wilms' tumor: a phase II study conducted by the French Society of Pediatric Oncology.

Twenty-one patients with advanced Wilms' tumor entered a phase II study with high-dose ifosfamide (3 g/m2 over two days every 15 days). Mesna and hyperhydration were associated with minimal bladder toxicity. After two courses, five partial responses and six complete responses were observed.

[Pulmonary and cerebral aspergillosis in Burkitt's lymphoma].

Multiple intracerebral aspergillus abscesses in a 5 year old boy with a Burkitt's lymphoma are described. The disease was fatal despite antifungal treatment. The diagnostic and therapeutic problems, the risk factors and preventive care are discussed.