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Biomedical subjects

G Tobelem

Publications and source records attributed to G Tobelem.

At least 163 records · Page 9Linked to original sources
PubMed1981

Monoclonal antibody to human platelet glycoprotein I. I. Immunological studies.

A monoclonal hybridoma antibody specific for platelet glycoprotein I complex is described. The nature od the antigen was determined by demonstration that it was chymotrypsin sensitive and gave a peak at 150 000 daltons on SDS-PAGE after immunoprecipitation. The expression of the antigen is restricted to platelets and megakaryocytes with at least 1.6 x 10(4) molecules of antigen per platelet. The antibody failed to bind to platelets from patients with Bernard Soulier syndrome, where there is known to be a deficiency of glycoprotein Ib/Is expression. Binding to platelets from patients with Glanzmann's thrombasthenia was normal.

Animals↗
PubMed1981

Monoclonal antibody to human platelet glycoprotein I. II. Effects on human platelet function.

The effect on platelet function of a monoclonal platelet antibody to platelet membrane glycoprotein I was tested. This antibody, AN51, inhibited ristocetin or bovine factor VIII-induced aggregation but did not modify ADP, collagen type I or type III, thrombin or arachidonic acid induced aggregations. Furthermore, the adhesion-aggregation of platelets induced by microfibrils was also inhibited by the antibody. Platelet adhesion to rabbit aorta subendothelium was impaired by the antibody. The persistent adhesion of platelets to collagenase-treated subendothelium was also inhibited. These findings strongly suggested that platelet membrane glycoprotein I could interact with a non-collagenic microfibrillar component of subendothelium. The binding of factor VIII/von Willebrand factor to platelet membrane in the presence of ristocetin was decreased in the binding site for factor VIII/von Willebrand factor to allow platelet adhesion to subendothelium.

Antibodies, Monoclonal↗
PubMed1981

[Binding of factor VIII/Willebrand to Bernard-Soulier and thrombasthenic platelets (author's transl)].

We have studied the binding of Factor VIII/Willebrand factor (FVIII/WF) to the platelets of ten normal donors, five patients with Bernard-Soulier syndrome (BSS), three clinically normal patients heterozygous for BSS (BSS hetero), and three with Glanzmann's thrombasthenia (GT). The amount of 125I-FVIII/WF bound to the platelets was measured in the presence or absence of ristocetin, the results expressed as percentage of total radioactivity added. The time course of 125I-FVIII/WF showed that maximum binding to the platelets was observed at 30 min, and then a plateau was reached. The binding was ristocetin-dependent and was relative to the concentration of ristocetin added. At a final concentration of 0.5 mg/ml of ristocetin, specific binding to the normal platelets was 30.9 +/- 2.5 %; at 1.0 mg/Ml, specific binding was 34.7 +/- 3.2% in the normal donors. In the five BSS patients lacking platelet membrane Glycoprotein 1 (GPI), reduced binding of 125I-FVII/WF was observed. At a final concentration of 1 mg/ml of ristocetin, the mean value of the binding was 13.7 % (11.5 % -14.8 %); at a final concentration of 0.5 mg/ml of ristocetin, the mean value decreased to 5.6 % (2.9 %-7.2 %). In the three BSS hetero patients, binding was near normal, although there were reduced amounts of platelet membrane GPI. Binding was slightly decreased in the three thrombasthenic patients lacking GP IIb/IIIa.

Binding Sites↗
PubMed1980

[Acute monoblastic leukaemia. Clinical data and therapeutic results in 74 patients (author's transl)].

Seventy-four patients with acute pure monoblastic leukaemia treated between 1970 and 1978 were studied retrospectively. The disease was usually hyperleucocytic and tumoral in character. It occurred with equal frequency in subjects of both sexes and at all ages, with peaks at the two extremes of life. Rubidazone gave a high percentage (75%) of complete remissions, but the prognosis remained sombre, with a mean survival time of 200 days. The incidence of meningeal relapses was reduced by prophylactic measures at central nervous system level, but gingival and cutaneous relapses were frequent. The possibility of bettering the present modest therapeutic results by more intensive chemotherapy is discussed.

Adolescent↗
PubMed1980

High risk acute lymphocytic leukemia: a study of 141 cases with initial white blood cell counts over 100,000/cu mm.

The cases of one hundred and forty-one patients (85 males, 56 females) treated for hyperleucocytic acute lymphocytic leukemia (H-ALL) were reviewed. In all cases the initial white blood cell count was over 100,000/cu mm. One hundred patients (71%) attained complete remission (CR). The median duration of CR was six months and the median survival was nine months for all patients and 11 months for those who attained CR. Age, initial hemoglobin, and the height of initial white blood cell count over 100,000 had no significant prognostic value. Relapses occurred earlier in patients with a mediastinal mass. The results depended on the treatment used. With modern treatment, including more intensive chemotherapy and central nervous system prophylaxis, CR rate increased from 65% to 81% and median duration of CR improved from four months to ten months. The most important prognostic difference was related to the sex: CR rate was higher (78.5% vs. 66%) and median duration of CR and hematological remission was longer for females (nine months vs. six months and ten months vs. 6.5 months, respectively). This difference only appeared with modern treatments, however: before 1972 the median duration of CR was four months for both sexes, and after 1972, it was eight months for males and 17 months for females. This difference could be explained by the site of the first relapse, which was testicular in only 2% of cases before 1972 and 27% (47% of the males who relapsed) after 1972.

Adolescent↗
PubMed1980

[Myeloma together with acute myeloblastic leukaemia in an untreated patient (author's transl)].

In a 66-year old man without previous major disease the unexpected finding of pancytopenia on routine blood count during an acute respiratory infection led to the diagnosis of IgG-producing myeloma without radiological bone lesions, associated with partial blastocytosis and abnormalities in granulocyte maturation. No treatment was given. Within 15 days, the circulating blastocytes became more numerous and type M1 acute myeloblastic leukaemia was diagnosed. A combined rubidazone and cytosine arabinoside treatment failed, and the patient died rapidly.

Aged↗
PubMed1980

[Interaction between the platelets and the vessel wall. Part 3: Investigation].

Numerous techniques are now suggested for the investigation of interactions between the platelets and the vessel wall. These techniques offer the possibility of precise diagnosis of the majority of haemorrhagic diseases of primary haemostasis. A critical study nevertheless shows that few tests of haemostasis are of use in defining a state predisposing to thrombosis and amongst others, biological study of the vessel remains very limited.

Animals↗
PubMed1980

[Interactions between the platelets and the vessel wall. Part 2: physiopathology (author's transl)].

The role of the blood platelets in the aetiogenesis of arterial lesions has been underlined in recent years by studies of platelet elastase and above all the mitogenic factor of smooth muscle cells. A truly thrombogenic theory of atherosclerosis can now be envisaged. In the context of arterial thromboses, it is interaction between the damaged vessel wall, the lesion most often being atherosclerosis, and blood platelets which gives rise to the thrombus. In certain conditions such as diabetes abnormalities in the interaction between platelets and vessel walls may favour the development of vascular lesions and thromboses. With regard to venous thrombosis, the participation of the vessel and/or platelets is less clear. However, recently described platelet procoagulant activities could activate coagulation mechanisms. Knowledge of diseases of primary haemostasis has benefited from studies of platelet-vessel interaction. Whilst the spontaneous haemorrhagic syndrome of major thrombocytopaenia remains mysterious, platelet membrane molecular abnormalities in thrombopathies such as Bernard Soulier syndrome or thrombasthenia offer an explanation for their mechanisms. By their interaction with the vessel, platelets finally participate in mechanisms of inflammation, immunological conflicts, disseminated intravascular coagulation and metastatic dissemination.

Arteries↗
PubMed1980

[Interactions between the platelets and the vessel wall. Part 1: Physiology (author's transl)].

The vessel wall plays an important role in the maintenance of balance between haemorrhage and thrombosis. The endothelial lining of a normal vessel wall is thrombo-resistant, in particular by virtue of prostacyclin, whilst the sub-endothelium with its collagen is thrombogenic. If the endothelium is pathologically or experimentally damaged, adhesion of the blood platelets becomes possible. This mechanism, presently studied at a molecular level itself, involves the Willebrand factor, the glycoproteins of the platelet membrane and constituents of the sub-endothelium which remain poorly defined. Platelet adhesion is responsible for cellular activation with the liberation of numerous intraplatelet constituents and synthesis of prostaglandins. Agregation between platelets involves complex biochemical phenomena which concern the platelet membrane and fibrinogen, contractile proteins and the cyclic AMP system, prostaglandins and ADP. The role of calcium in these different phenomena is very important.

Adenosine Diphosphate↗
PubMed1980

Acute monoblastic leukemia: a clinical and biologic study of 74 cases.

Seventy-four cases of pure acute monoblastic leukemia (AMol) have been retrospectively studied. All patients were treated at Hospital Saint-Louis between 1970 and 1978. Diagnosis was based on morphological and cytochemical features according to the FAB classification. This type of leukemia occurred at any age and in both sexes, with a high frequency of extramedullary involvements. Hyperleukocytosis was very frequent and was significantly correlated with increased blood and urine levels of lysozyme, with renal failure and hypokalemia, and with coagulation abnormalities. AMol still has a poor prognosis, despite a best remission rate (75%) obtained with rubidazone, since the duration of complete remission was short. Central nervous irradiation prolonged remission and prevented meningeal relapses, while 6 meningeal relapses occurred in the patients not irradiated. The high frequency of the extramedullary relapses, including gum and skin, emphasized the question of persistant blast cell sanctuaries after achievement of bone marrow remissions. A more intensive induction with several drugs active against monoblasts could be more efficient and prolong the duration of complete remissions.

Adolescent↗
PubMed1979

[Thrombocytopenic purpura during heparinotherapy. Two cases (author's transl)].

In two patients treated by heparin for thrombosis, thrombocytopenia under 10 000/cumm occured accompanied with bleeding cud recurrent thrombosis. The demonstration in the patients' serum of a factor inducing platelet aggregation and serotonin release in the presence of heparin suggests that the thrombocytopenia could be of immuno-allergic origin. In both cases, the discontinuation of heparin resulted in clinical and biological improvement. The rare cases of heparin-induced thrombocytopenia reported in the literature are discussed.

Aged↗
PubMed1979

[Acute lymphoblastic leukemia with hyperleucocytosis: an urgent problem during initial treatment (author's transl)].

The frequency and the severity of disseminated intravascular coagulation (DIC) and of metabolic complications during the induction treatment were studied in 62 cases of acute lymphocytic leukemia with initial white blood cell count over 100 000/cu mm. Transient DIC were noted in 20,5% of cases. Metabolic complications were frequent: hyper-uricemia noted in 62% of cases was not the chief problem. Hyperazotemia was noted in 33% of cases and hyperkaliemia in 26% of cases. Hypocalcemia, noted in 34% of cases, was always associated with hyperphosphoremia. Blood glucose was low in 4 cases and increased in 7 cases out of 39.

Adolescent↗
PubMed1979

Further studies on a specific platelet antibody found in Bernard-Soulier syndrome and its effects on normal platelet function.

An IgG antiplatelet antibody found in a multitransfused patient with Bernard-Soulier syndrome (BSS), reacted with a normal platelet surface antigen of 150 000 daltons which was similar to the glycoprotein missing from BSS platelets. The BSS platelet antibody (BSS-Pab) aggregated all control platelets which then released ADP and 5-HT and synthesized thromboxane. When mixed with the antibody, BSS platelets did not aggregate, did not release ADP and 5-HT and failed to synthesize thromboxane. The BSS-Pab was not inactivated by incubation with BSS platelet stroma. While the antibody did not aggregate thrombasthenic platelets, its aggregating activity was lost after incubation with their stroma. The BSS-Pab did not provoke ADP or 5-HT release or thromboxane synthesis in thrombasthenic platelets or in the platelets of a patient with platelet cyclooxygenase deficiency or in normal platelets treated with indomethacin. The aggregating, release and synthetic responses of platelets after binding of BSS-Pab to its membrane antigen (probably glycoprotein I) requires the presence of glycoprotein IIb and/or IIa and the normal metabolism of arachidonic acid.

Antibodies↗
PubMed1979

[The platelet membrane: some aspects of the pathophysiology of haemostasis].

Platelet membranes play a key role in all stages of the haemostatic mechanism. Four of these in particular are considered here: adhesion to subendothelium, which involves an interaction between the glycoprotein I complex in the platelet membrane (deficient in the Bernard-Soulier syndrome) and plasma factor VIII; aggregation, involving the membrane glycoprotein IIb/IIIa complex (deficient in thrombasthenia), plasma fibrinogen and divalent cations; platelet factor 3 availability, a function of surface membrane phospholipids; and thromboxane synthesis, a function of the phospholipids of the membrane of the dense tubular system. The glycoprotein I complex also carries binding sites for thrombin and for drug-dependent antibodies, and glycoprotein IIb/IIIa is the site of the P1A1 antigen and of alpha-actinin.

Blood Platelet Disorders↗
PubMed1979

Clinical activity of detorubicin: a new anthracycline derivative.

The anthracycline derivatives are intercalating drugs which are of major importance in the treatment of leukemias and in the management of solid tumors. Structural analogs have been prepared by semisynthetic modifications in an attempt to extend the spectrum of antitumor activity and to reduce toxicity (acute myelosuppression and cardiotoxicity). This report concerns our preliminary clinical experience in 111 patients who received detorubicin. Two dose schedules were used in acute leukemia patients. Sequential doses were active in acute leukemia relapses but the mucous membrane toxicity was excessive; more recently, intermittent doses proved active in acute leukemia relapses (one 6-mg/kg dose) and in a patient with resistant Burkitt's lymphoma. In non-Hodgkin's lymphomas, a complete response rate of 71% was achieved with an intermittent schedule (3 mg/kg/day X 3 weeks). A remarkable shrinkage of skin involvement was also observed. Detorubicin showed a high activity in mycosis fungoides (five regressions among six patients) and some activity in soft tissue sarcomas, osteosarcomas, and various solid tumors.

Acute Disease↗