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Biomedical subjects

G Reber

Publications and source records attributed to G Reber.

At least 91 records · Page 5Linked to original sources

[Acquired hemophilia. Apropos of a case report with a fatal course].

We report the case of an 86-year-old female with an unremarkable past history who suddenly developed severe and generalized bleeding. Laboratory work-up revealed prolonged aPTT, a factor VIII level of 7% and the presence of a factor VIII inhibitor. In spite of whole blood, factor VIII concentrates and immunoglobulin administration, the patient died of multiple hemorrhages on the third day after admission. At autopsy no causal or associated pathology could be found. Chromatographic separation of plasma immunoglobulins showed that the anti-factor VIII activity was associated with the patient's IgG. This inhibition was partially corrected in vitro by injectable immunoglobulin preparation. The case report stresses the discrepancy between the measured levels of inhibitor and the severity of the bleeding; our in vitro results may shed light on the mode of action of intravenous immunoglobulins.

Aged↗

Acute effects of retinoids on fibrinolysis before and after venous occlusion in healthy humans.

The effects of acitretin and etretinate on the fibrinolytic system have been investigated in a double-blind, placebo-controlled cross-over study in twelve healthy volunteers. Euglobulin fibrinolytic activity, euglobulin clot lysis time, tissue-type plasminogen activator (t-PA) activity and antigen concentration in plasma were measured before and after 10 min of venous occlusion (VO), three hours after ingestion of the compounds. The plasminogen activator inhibitor (PAI) activity was also measured in each session before fibrinolysis stimulation. None of the parameters studied was significantly affected by the two retinoids in comparison with placebo. Our study demonstrates that a single oral dose of 100 mg of etretinate or acitretin, investigated 3 hours after drug administration does not significantly influence the fibrinolytic system in vivo in humans. This observation does not exclude an effect of retinoids after prolonged intake.

Adult↗

Comparison between a low molecular weight and standard heparin for anticoagulation during extracorporeal CO2 removal in the dog.

Anticoagulant properties towards an artificial surface of a chemically depolymerized low molecular weight heparin (LMWH) have been compared to those of a standard heparin (SH). The experimental model consisted in a seven hours extracorporeal veno-venous bypass for CO2 removal (EC-CO2R) using a membrane lung. Four animals received 150 anti-FXa U/kg followed by 40 anti-FXa U/kg/h of LMWH or 300 IU/kg followed by 100 IU/kg/h of SH. Mean Factor Xa inhibition was 49% in LMWH group and 28.5% in SH group. Mean Factor IIa inhibition was 31% and 49% respectively. After three hours of bypass fibrin deposition occurred in the reservoir in three out of four dogs receiving LMWH while none was observed under SH. No statistically significant difference between the two groups was found for any of the coagulation parameters tested (fibrinogen, factor V, antithrombin III, plasminogen, alpha 2-antiplasmin, platelet counts). At the end of bypass 5000 U protamine abolished both anti-FXa and anti-FIIa activities in the SH group but failed to neutralize more than half of the anti-FXa activity in the LMWH group. These results suggest that high anti-FIIa activities are required to prevent fibrin formation induced by artificial surfaces and that equivalent amounts of anti-FXa activities are ineffective for this purpose. In addition the use of LMWH may raise problems when emergency neutralization procedures are required.

Animals↗

Antithrombin III Geneva: a hereditary abnormal AT III with defective heparin cofactor activity.

A 43-year-old man presented a pulmonary embolism. The unusual circumstances of apparition, the age and the increased heparin requirements suggested an antithrombin III (AT III) deficiency. AT III activity was low in the propositus and seven other members of his family (mean 55%), but immunologic levels were normal (mean 110%). Crossed immunoelectrophoresis in absence of heparin showed a normal pattern, but in presence of heparin showed an abnormal peak as compared with controls. Kinetics experiments showed a normal inhibition of thrombin and Xa in absence of heparin, but abnormal in presence of heparin. Affinity chromatography on heparin-Sepharose revealed two populations of AT III, one of which was devoid of heparin cofactor activity. The toponym AT III Geneva is proposed for this new familial abnormal AT III with defective heparin cofactor activity.

Antithrombin III↗

Acute influence of cigarette smoke in platelets, catecholamines and neurophysins in the normal conditions of daily life.

Cigarette smoking is firmly linked to the occurrence of acute coronary events. In twenty-two healthy volunteers in normal conditions of daily life we studied the acute influence of smoking on the following parameters: beta-thromboglobulin, thromboxane B2, epinephrine, norepinephrine, estrogen-stimulated neurophysin, and nicotine-stimulated-neurophysin. Our results show that in our population and following our protocol, smoking did not induce platelet activation, thromboxane formation, catecholamine release or estrogen-stimulated-neurophysin secretion. However, smoking did provoke a significant increase of nicotine-stimulated-neurophysin (p less than 0.05) which reflects vasopressin increase and which might explain the high incidence of ischaemic accidents in cigarette smoking via the vasoactive properties of vasopressin.

Adolescent↗

[Endogenous prostacycline and coronaropathy. Plasma levels of 6-keto-PGF1 alpha].

Prostacycline may play a preventive role in the development of ischaemic complications of coronary atherosclerosis through its vasodilatory and platelet antiaggregant properties. Its biological instability makes it difficult to measure in the plasma; however, it is possible to determine plasma concentrations by radioimmune assay of one of its stable derivatives, 6-Keto-prostaglandin F1 alpha (6KPGF1 alpha). Systemic plasma concentrations at rest of 30 patients with severe atherosclerosis were not significantly different from those of healthy control subjects (7.5 +/- 6.5 vs 10 +/- 5 pg/ml). In addition ischaemia during exercise is not associated with significant variations; at rest 7.1 +/- 6 pg/ml in the "ischaemic" group (n = 20) compared to 7.6 +/- 6.4 pg/ml in the "non-ischaemic" group (n = 10); on effort: 9 +/- 10 pg/ml compared to 13.3 +/- 14 pg/ml. These results show that measuring the plasma 6KPGF1 alpha by peripheral vein blood sampling is of no use in the diagnosis of coronary atherosclerosis or of myocardial ischaemia on effort.

6-Ketoprostaglandin F1 alpha↗

[Platelet function and coronary disease: demonstration of a so-called unstable platelet syndrome].

Radio-immunological assay of specific platelet substances in the serum allows assessment of in vivo platelet function at a given moment. Plasma levels of beta thromboglobulin (beta TG) platelet factor 4 (PF4) and thromboxane B2 (TXB2) were measured at rest and during exercise stress testing in 39 patients with known coronary artery disease with stable effort angina. The patients were divided into two groups according to the results of exercise ECG and thallium 201 myocardial scintigraphy: ischaemic (n = 28) and non-ischaemic (n = 11). Resting and exercise levels of the three platelet substances were compared with a group of normal controls (n = 14). The average control values at rest and on exercise were, respectively: PF4: 8.5 +/- 5 and 22 +/- 14 ng/ml; beta TG: 36 +/- 17 and 68 +/- 36 ng/ml and TXB2: 112 +/- 41 and 201 +/- 81 pg/ml. The average values of the non-ischaemic patients did not differ significantly, either at rest or during exercise. The variation of pathological values was higher in the ischaemic group. This seems to reflect the absence of univocal platelet behaviour and does not allow statistical comparison of mean values. Our results suggest the existence of an "unstable platelet syndrome", which seems to be associated with poor effort tolerance especially when present under resting conditions. There would seem to be a causal relationship between platelet instability and myocardial ischaemia, which would justify anti-platelet aggregation therapy in primary and secondary prophylaxis of myocardial infarction.

Adult↗

Anticoagulant properties of three mucopolysaccharides used in rheumatology.

Three mucopolysaccharides (MPS) used in the treatment of degenerative joint disease were compared to heparin to establish their relative potencies on 3 coagulation tests, the aPTT, the antifactor Xa activity and the dilute thrombin time. One of the compounds, Arteparon, was one fourth as potent as heparin on the aPTT, but had little or no influence on the 2 other tests. Further in vitro studies suggested that Arteparon acted at a higher level than factor Xa generation in the intrinsic amplification system and that its effect was independent of antithrombin III. In vivo administration of Arteparon confirmed its anticoagulant properties, which raises the question of the clinical use of this MPS.

Anti-Inflammatory Agents↗

Pregnancy-associated plasma protein-A (PAPP-A) inhibits thrombin-induced coagulation of plasma.

Concentrations of immunoreactive PAPP-A have been found significantly lower in the serum as compared to heparin or EDTA plasma from the same patients. After coagulation significant amounts of PAPP-A remain associated with the clot. Purified PAPP-A inhibits thrombin induced coagulation of plasma. This inhibition cannot be attributed to a direct effect of PAPP-A on thrombin. It is exerted via an activation of endogenous antithrombin III since the inhibitory effect of PAPP-A on thrombin induced coagulation in a euglobulin system can be observed only if antithrombin III is added. The fact that protamine sulphate is capable of neutralizing the inhibitory effects of PAPP-A made us postulate that PAPP-A, like heparin, possesses strongly acidic residues which bind to protamine.

Animals↗

Labelling of the cyclitol permease in Klebsiella aerogenes.

The protein component(s) of the cyclitol-transport system in Klebsiella aerogenes has been labelled by using three different procedures. One method is based on differential alkylation with N-ethylmaleimide, and another on incorporation of amino acids during the induction process. A protein of mol.wt. 34 000 was labelled by both procedures; by alkylation with N-ethylmaleimide two other proteins of mol.wts. 55 000 and 67 000 were also labelled. The third uses diazotized [35S]sulphanilic acid after protection by substrate and the comparison of labelling of induced cells with non-induced cells; the label was also concentrated in a mol.wt.-33 000 peak. The labelled protein is, from the evidence, the cyclitol carrier.

Amino Acids↗

Transport of cyclitols by a proton symport in Klebsiella aerogenes.

The respiration and the ATP content of Klebsiella aerogenes in the presence of various inhibitors were compared to the transport of scyllo-inositol. The ATPase was found to be inhibited by dicyclohexyl carbodiimide. The transport has been tested in anaerobiosis and aerobiosis. From the results obtained it is concluded that either ATP or respiration can sustain the transport activity in independent manner. 2. The energy derived from the respiratory chain reactions or the ATP hydrolysis results in electrogenic extrusion of protons. The electrochemical potential created drives the accumulation of scyllo-inositol, as shown by an increase of pH of the medium on addition of the substrate to cells in anaerobiosis. With non-induced cells no change in pH occurs, which demonstrates that proton flow is really linked to the transport. No H+/Na+ or K+ exchange is observed and the proton conductor carbonylcyanide m-chlorophenylhydrazone abolishes the pH shift caused by substrate addition. The stoichiometry of the symport H+/cyclitol is 1 and the half-maximum value of the pH variation as a function of the amount of scyllo-inositol added corresponds to a concentration of scyllo-inositol very close to the KT of influx.

Adenosine Triphosphatases↗

Assymetry of the myo-inositol transport system in Klebsiella aerogenes. Energy is necessary to create the assymetry of the transport system.

1. In Klebsiella aerogenes the influx of myo-inositol proceeds during the steady state at a rate equal to that of efflux. 2. The kinetic parameters of influx during the steady state are similar to those observed at the initial time of uptake. 3. Efflux and influx processes share the same transport system. 4. The ability of other cyclitols to chase the accumulated scyllo-inositol is dependent on their affinity for the transport system. 5. A counter transport can be observed in preloaded cells only in poisoned cells and under anaerobiosis. 6. The efflux process is not temperature-dependent. 7. The KT of influx in poisoned cells is larger than that in normal cells. 8. Although no saturation kinetics of efflux could be observed, it can be inferred that the KT of efflux is at least 50-fold larger than the KT of influx; 9. The results suggest that in the transport of myo-inositol by K. aerogenes energy coupling enhances the affinity of the carrier for the substrate at the outer side of the cytolplasmic membrane by lowering the KT.

Aerobiosis↗