Biomedical subjects
G Tobelem
Publications and source records attributed to G Tobelem.
Hypercalcemia in chronic myelogenous leukemia: evidence for excessive parathyroid hormone secretion.
Hypercalcemia was associated with osteolytic bone lesions in a 60-year-old woman with chronic myelogenous leukemia in the accelerated phase. Using highly specific antisera to parathyroid hormone, radioimmunoassays disclosed elevated levels of carboxyl-terminal (53-84) and intermediate (44-68) fragments. In addition, concomitant variations of serum calcium level and leukocyte counts, increased urinary c-AMP excretion, morphological integrity of parathyroid glands, and absence of bone resorbing activity in myeloblast culture supernatants are consistent with the hypothesis that the humoral hypercalcemia was due to the excessive production of PTH. This production may have been ectopic, although no PTH secretion was demonstrated in myeloblast culture supernatants.
Importance of the interaction between plasminogen and fibrin for plasminogen activation by tissue-type plasminogen activator.
The potentiating effect of fibrin monomer on plasminogen activation by tissue-type plasminogen activator is much more important with lys-plasminogen than with mini-plasminogen (which lacks the high affinity lysine-binding site important for binding to fibrin). Furthermore, this potentiating effect is totally abolished when lys-plasminogen is eluted from fibrin by the addition of 1 mM epsilon-amino caproic acid. Binding does however not seem to be the only condition required since it was found that fragment D is a much stronger potentiator of the activation of plasminogen by tissue-type plasminogen activator than fragment E although plasminogen binds to both fragment D and fragment E. Furthermore, fragment E has the same effect on the activation of lys-and mini-plasminogen by tissue-type plasminogen activator. Therefore, it is suggested that binding of plasminogen to fibrin involves a conformational change in the plasminogen molecule, facilitating its activation by tissue-type plasminogen activator.
[Urethral stricture: one-stage urethroplasty using a free skin flap].
We report our experience of one-stage free skin graft urethroplasty in 18 patients, most of whom had iatrogenic stricture of the urethral bulb. Our results were similar to those reported in the literature, being satisfactory in about 80% of the cases, and were further improved by adjuvant procedures, such as urethrotomy. We consider that free skin graft urethroplasty is the most reliable method to treat strictures of the urethral bulb after failure of urethrotomy.
Acute monoblastic leukaemia. Clinical, biological data and survival in 45 cases.
Between 1978 and 1980, 45 cases of acute monoblastic leukaemia have been diagnosed, treated and followed in our institute. Morphological diagnosis was performed according to the French-American-British classification. Tumoral syndrome (particularly extra-medullary) and hyperleucocytosis were the most striking findings at the time of diagnosis. Cytogenetic analysis performed in 31 cases before treatment has showed that abnormality of the long arm of chromosome 11 seemed to be more frequently associated with the poorly differentiated cytological subtype M5 (a). Intensive chemotherapy with zorubicin and cytosine arabinoside led to complete remission in 75% of the cases. Central nervous system prophylaxis appeared definitively useful in preventing meningeal relapse. Despite a prolongation of the median duration of complete remission which now reaches 12 months, the prognostic is still poor.
Interactions of platelets with standard heparin and low molecular weight fractions.
The availability of fibrinogen receptors on platelets after ADP stimulation, was investigated in order to analyze platelet hyperaggregability induced by heparin. Unfractionated heparin increased the binding of fibrinogen on ADP-treated platelets. The results varied according to both the donor platelets and the kind of heparin preparation used. Beef lung heparin was more active than porcine intestinal mucosa heparin (P less than 0.001). Low molecular weight (LMW) heparin fractions however did not significantly increase the binding of fibrinogen to ADP-treated platelets. The effect of standard heparin and LMW heparin on the aggregation of normal platelets induced by the addition of plasma from patients with heparin-induced immune thrombocytopenia was also studied. Concerning heparin-induced immune thrombocytopenia we have shown that the plasma cofactor present in some patient plasma may induce platelet aggregation both in the presence of standard-heparin and in the presence of LMW heparin fractions. Therefore, one has to be careful when replacing standard heparin by LMW heparin or heparinoids since each patient may react differently.
[Glycoproteins and platelet function].
Interactions between platelets and blood vessels are very important to maintain the equilibrium between haemorrhagy and thrombosis. Plasmatic membrane of platelets, with its external surface rich in carbon hydrates, contains specific glycoproteins the role of which is essential in adhesive mechanisms and platelet aggregation. This cellular surface also carry numerous receptors for many agents. New progresses will allow a better physiopharmacological approach of platelet inhibition, adhesion and aggregation.
[Willebrand syndrome acquired during an amylosis of primitive appearance].
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[1-step urethroplasty using Devine's technic. Its use in 18 cases of urethral stricture].
A one stage procedure using a free patch graft of skin for correcting of the urethral strictures was executed in 18 patients. In our series the strictures were mainly located in the region of the bulbar urethra. Good results have been obtained in 14 (80%) of 18 cases with a follow up of up to two years. It is a simple and effective method of treatment. It has given us a more consistent satisfactory result than any other methods described until now. The good results obtained by us with this method results substantiated by the other series, we advocate this on stage urethroplasty for repair of selected bulbar urethral strictures.
Binding of heparin and low molecular weight heparin fragments to human vascular endothelial cells in culture.
The interaction of standard heparin and some low molecular weight heparin fragments (CY 222, mw 1,500-8,000 daltons) with human vascular endothelium in culture was studied using both 125I and 3H labeled ligands. A specific and saturable binding was shown for both labeled standard heparins. Two populations of binding sites for 3H-standard heparin could be distinguished: one of high affinity (KD = 0.12 microM), and another of lower affinity (KD = 1.37 microM). Total binding capacity was in the order of 10(7) molecules per cell. The same high level of affinity was calculated for unlabeled compounds from competition experiments with 125I-standard heparin. No other glycosaminoglycans, except a highly sulfated heparan (fraction IIA) could compete for heparin binding sites. A specific binding was also shown for 125I-CY 222. The affinity of unlabeled CY 222 was approximately ten times lower than that of unfractionated heparin. However, CY 222 could compete for approximatively 30% of standard heparin binding. Binding was not completely reversible. Even in the presence of a large excess of unlabeled compounds, a fraction of 25% of radioactive heparins remained bound to the endothelium. This fraction was three times lower if incubation was carried out at +4 degrees C, suggesting a possible incorporation of heparin into the endothelial cells.
[Use of Ommaya reservoirs in the treatment of meningeal relapse of acute lymphoblastic leukemia].
We report our experience in the treatment of meningeal relapses in acute lymphoblastic leukemia (ALL) with intraventricular chemotherapy via an Ommaya reservoir. We treated 5 children in this way with some complications secondary to the use of the reservoir: methotrexate leukoencephalopathy, bacterial meningitis, reservoir malfunction. But patient comfort homogeneous drug distribution when injected via the Ommaya reservoir and the possibility of long term meningeal remission justify the discussion of the use of an Ommaya reservoir use in meningeal relapses in ALL.
[Evaluation of hemostasis in thrombotic pathology? A critical study apropos of 200 records].
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Fibrinogen binding on human platelets. Influence of different heparins and of pentosane polysulfate.
Unfractionated heparin increased the binding of fibrinogen on ADP-treated platelets. The results varied according to both, the platelets of the donor and the kind of heparin preparation used. Beef lung heparin was more active than porcine intestinal mucosa heparin (p less than 0.02). A fraction of low molecular weight low sulfated heparin, did not significantly increase the binding of fibrinogen, except in one case for which the binding of fibrinogen to platelets was largely increased by standard heparin. On the contrary, pentosane polysulfate, a sulfated polysaccharide (of low molecular weight) significantly increased the binding of fibrinogen (p less than 0.01).
[Pure defibrination after timber rattlesnake bite].
The only disorder of coagulation observed after a timber rattlesnake (Crotalus horridus) bite was a total absence of fibrinogen which lasted 64 hours despite hourly administration of cryoprecipitates. The pure defibrination experimentally obtained with this particular species of crotalid snakes underlines the specificity of the coagulation disorder and the impossibility of identifying the coagulopathy induced by venom poisoning without laboratory examination.
[Molecular abnormalities in recurrent thromboembolic disease].
The diagnosis and treatment of apparently idiopathic recurrent thromboembolic disease (RTED) still raise difficult problems. However, recent data suggest that abnormalities of coagulation and fibrinolysis factors are important. Hereditary antithrombin III (AT III) deficiency or abnormal AT III, and hereditary protein C deficiency with autosomal dominant transmission have been associated with severe familiar RTED. More recently, we described a dysfibrinogenemia characterized by abnormal fibrin polymerization and abnormal plasminogen binding to the fibrin clot, responsible for familial RTED. Disorders of fibrinolytic activity in RTED are represented, in 70% of the cases, by reduced release or lack of production by endothelial cells of a vascular plasminogen activator. Hereditary plasminogen deficiency or abnormal plasminogen, although rare, are regularly responsible for RTED.
[Parameters of hemostasis in Behçet's disease].
Venous thrombosis occurred frequently in Behçet's disease. In 12 patients with Behçet's disease of whom 6 have had leg venous thrombosis, some parameters of hemostasis or fibrinolysis have been studied. Platelet count, fibrinogen level, factor VIII coagulant activity, factor VIII antigen, plasminogen and antithrombin III level were in the normal range. Fibrinolytic capacity in response to venous occlusion of the arms was the same in patients and in healthy subjects, in the patients, there was no difference in regard to the occurrence of venous thrombosis. These parameters seemed therefore not able to detect the thrombotic tendency in this disease. These results are discussed with the other reports of the literature.
Interaction of blood platelets with a microfibrillar extract from adult bovine aorta: requirement for von Willebrand factor.
Adult bovine aortic tissue was treated with 6 M guanidinium chloride in the presence of proteinase inhibitors to obtain an extract that was essentially devoid of collagenous components and appeared homogeneous by electron microscopy. When this extract was dispersed by sonication it was found to be a very potent inducer of human platelet aggregation. This interaction required the presence of von Willebrand factor and of its receptor (glycoprotein Ib) on platelet membrane. This was demonstrated by the fact that the aggregation of normal blood platelets resuspended in plasmas deficient in von Willebrand factor was significantly diminished as compared to aggregation in control plasma. Moreover, this aggregation was inhibited by a monoclonal antibody, IgG AN51, to platelet glycoprotein Ib. These studies provide direct biochemical evidence for the existence of a thrombogenic constituent of the vessel wall that is noncollagenous and von Willebrand factor-dependent.
The domain of platelet glycoprotein I as recognized by various antibodies, both monoclonal and polyspecific.
Platelet membrane glycoprotein Ib plays a major role in the binding of factor VIII/von Willebrand factor to allow platelet adhesion to subendothelium. We have used polyspecific and monoclonal antibodies to glycoprotein Ib and have demonstrated that both antibodies were directed to glycoprotein Is, a soluble fragment of glycoprotein Ib. By showing an inhibition of the binding of factor VIII/von Willebrand factor to control platelets in presence of the antibodies, it can be concluded that glycoprotein Is is involved in these binding sites.