[The clinical significance of protein C].
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Biomedical subjects
Publications and source records attributed to P Kubisz.
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A 63-year-old woman presented with a massive proliferative growth in the urethral region. Fine needle aspiration and biopsy revealed nonHodgkin's lymphoma. No other tumor localization was found and complete remission occurred after 3 courses of chemotherapy. Primary localization of a lymphoma to the urethra is rare.
From January 1980 to September 1985, 82 patients with IA to IIIB clinical stage (CS) Hodgkin's disease were treated by three MOPP chemotherapy (CT) cycles followed by extended field radiotherapy (RT) including the spleen (30-40 Gy). 2 patients died during the treatment (medullary aplasia, pulmonary edema). 6 were in failure after three MOPP cycles; they received other CT; 3 died and 3 are alive in remission (survival: 2.5 to 3.5 yr). 74 were in complete remission (CR) after completion of treatment. 4 patients relapsed (all alive after re-treatment) and 4 died in first CR (tuberculosis, hepatitis, myeloma, unknown cause). At 6 yr, actuarial survival and relapse-free survival are respectively 89.8% for the 82 patients and 93% for those in CR. These good results are due to: the administration of CT before RT, limited to three cycles; identification of failures after CT; inclusion of the spleen in RT ports in all cases; and a short lumbo-aortic port in CS I and II.
The effect of lomustin on platelet functions was investigated in vitro using a wide battery of tests. Lomustin was found to act as a specific inhibitor of platelet aggregation, release reaction and clot retraction and to induce acquired thrombocytopathy. Thus, impairment of platelet functions might play a role in hemorrhagic complications accompanying lomustin therapy in some cases.
Between 1967 and 1978, 152 Algerian patients (31 children and 121 adults) with Hodgkin's disease were treated with the mechlorethamine, vincristine, procarbazine, prednisone combination (MOPP) alone and without radiotherapy. They were separated without lymphography into limited stage (n = 37) and extensive (n = 115) stage. The high initial failure rate (54%) was principally due to inadequate symptomatic treatment and to the patients' low socio-economic status. The complete remission rate was 45% (54% for limited stages; 42% for extensive stages) and significantly higher in women (58%) than in men (37%). In 20/23 cases relapses occurred during the first 4 years of complete remission; however, the final relapse was observed during the 12th year of complete remission. The actuarial relapse rate at 15 years was 48%. The long-term (10-15 years) life expectancy was 31% overall and 70% in cases with complete remission. Prognosis was significantly better in patients with limited forms and/or without systemic symptoms.
The oocyte nucleus of Pleurodeles waltlii contains a major 32,000-mol-wt acidic protein which is called nucleoplasmin. Rabbit antibodies were raised against total nuclear proteins from Pleurodeles oocytes. Affinity-purified antibodies directed against nucleoplasmin were prepared using antigens bound to nitrocellulose paper. The specificity of the antibody was controlled on two-dimensional electrophoretic gels of nuclear proteins. The intranuclear distribution of nucleoplasmin was analyzed by indirect immunofluorescence and the immunogold technique in light and electron microscopy. The antibody was tested on a spread of the nuclear content prepared in the presence of calcium, on the nuclear content spread in the presence of phalloidin so that an actin network appeared, and on a spread of nuclei from oocytes previously treated by actinomycin D. In all cases, nucleoplasmin appeared to be localized on the lampbrush loops, i.e., on the sites of transcription and, more specifically, on the ribonucleoprotein (RNP) particles; this protein was also associated with the RNP particles of the nuclear sap (free or inserted in the actin network). Nucleoplasmin was localized on large RNP particles that appeared when transcription was blocked. We never found this protein on the chromosome axis. These results suggest that nucleoplasmin may play a role in transcriptional activity.
Serum levels of apolipoprotein B were measured, and investigations of the platelet function were carried out in 32 patients with insulin-dependent diabetes and in 34 healthy controls similar in age. Mean serum levels of apolipoprotein B were 1.51 g/l in the diabetic patients and 1.18 g/l in the control group, and this difference was significant. In the diabetic patients a secondary wave of aggregation was more easily induced by low concentrations of adenosine diphosphate or adrenaline. It was also possible to induce 50% of maximal aggregation by lower concentrations of adenosine diphosphate or arachidonic acid in these patients, and their number of circulating platelet aggregates increased. Plasma levels of beta-thromboglobulin and platelet factor 4 were raised and, in the presence of N-ethyl maleimide, platelets from diabetic patients produced significantly more malondialdehyde than those from normal controls. The relationship between increased serum levels of apolipoprotein B and platelet hyperreactivity may be more than accidental and should be studied further to elucidate its possible implication with platelet function and atherogenesis.
The incidence of second wave of platelet aggregation induced by a small dose of ADP (1 mumol/l) was compared with plasma levels of beta-thromboglobulin in 81 normal individuals, 34 patients with acute myocardial infarction, 11 patients with acute cerebrovascular disease and 26 patients with renal disease. Platelet hyperaggregability was observed in 7% of normal individuals. Plasma levels of beta-thromboglobulin were higher in normal individuals over 60 years of age (48 vs. 32 micrograms/l). In contrast, hyperaggregability was observed in 79% of patients with acute myocardial infarction and in 64% of those with acute cerebrovascular disease. Median plasma levels of beta-thromboglobulin were also significantly elevated in patients with acute myocardial infarction (82 micrograms/ml) or acute cerebrovascular disease (99 micrograms/l). Levels of beta-thromboglobulin in plasma were significantly higher in those patients who demonstrated hyperaggregability. In patients with renal disease only 12% had signs of hyperaggregability. Nevertheless their plasma levels of beta-thromboglobulin were elevated (76 micrograms/l) and correlated with the serum creatinine values. These investigations indicate that patients with acute myocardial infarction or stroke have hyperreactive platelets and evidence of increased platelet inactivation in the circulation. However, evaluation of increased levels of beta-thromboglobulin requires consideration of renal function.
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A group of 53 healthy donors has been compared with another group of patients suffering from lipid metabolic disorders of Fredrickson type IIa (n = 14), IIb (n = 11) and IV (n = 21). In the course of three weeks the determinations have been carried out of lipid mechanism parameters, of Apoprotein B, of aggregation response upon ADP and adrenaline++ induction, of beta thromboglobulin, of heparin neutralizing activity, of malonyldialdehyde production upon N-ethylmaleimide stimulation and of the amount of circulating aggregates. In patients with HLP of IIa and IIb type a significant increase of plasmic beta thromboglobulin level was noted as well as shifts of other thrombocytic parameters towards higher platelet reactivity. The correlation between individual platelet parameters and parameters of lipid metabolism was statistically significant only in the case of cholesterol and malonyldialdehyde. A positive correlation of Apo B with BTG and with the aggregation response together with the observation of an increased Apo B concentration in normolipemic subjects with changed platelet reactivity, are indicative of an important role of Apo B during platelet activation in vivo.
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Platelet count was 225 X 10(9)/l in 225 healthy male Algerians and 263 X 10(9)/l in 208 females. The mean platelet volume was 9.15 fl in the males and 9.30 in the females. The figures agree with those obtained in a British and an American population, but differed from those of an Australian population of immigrants from Mediterranean countries, essentially Italy and Greece. The prevalence of Mediterranean thrombocytopenia must therefore be low in Algeria.
Investigations on the platelet function in diabetes mellitus were performed on 28 patients with insulin-dependent diabetes and in 33 healthy controls of similar age. In the diabetic patients it was possible to induce 50% of maximal aggregation by lower concentrations of adenosine diphosphate or arachidonic acid than in the controls. In the presence of N-ethyl maleimide, platelets from diabetic patients produced significantly more malondialdehyde than those from normal controls. After addition of arachidonic acid the platelets from the diabetic patients also synthesized more thromboxane B2. This synthesis of thromboxane was inversely correlated to the minimal concentration of arachidonic acid necessary to induce 50% platelet aggregation. Circulating platelet aggregates were more common in the diabetic patients than in the controls. Plasma levels of beta-thromboglobulin and platelet factor 4 were raised in parallel in the diabetic patients and correlated with the increased production of thromboxane B2 by the platelets from the same patients. Platelets from patients with diabetes thus demonstrated signs of hyperreactivity both in vivo and in vitro. This may be of clinical importance for the development of vascular complications in this disease.
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The inhibition of glycolysis by an inhibitor of glucose utilization isolated from urine of the uremic subjects reflects in: (1) decreased platelet aggregation induced by adenosine diphosphate, adrenaline, or collagen, respectively; (2) decreased platelet factor 4 release induced by the same inductors; (3) decreased availability of platelet factor 3, and (4) inhibition of retraction of reptilase clot. It is concluded that the inhibition of glycolysis by 'inhibitor of glucose utilization' contributes to the functional changes of platelets and thus to the alteration of hemostasis in uremic patients.
Cis-platinum added to citrated platelet rich plasma in vitro did not influence the aggregation of the platelets, their adhesion to glass, their release of platelet factor 4 or availability of platelet factor 3 and acid phosphatase. Neither any effect on the uptake of 14C-serotonin, the reptilase clot retraction or the coagulation system has been observed.
Platelet-rich plasma was incubated with dianhydrogalactitol (DAG) in vitro. This moderately diminished platelet aggregation induced by adrenaline and to a smaller degree by adenosine diphosphate /ADP) or collagen. The availability of platelet factor 3 induced by ADP, adrenaline or collagen was decreased irrespective of the inducer. The release of platelet factor 4 was unaffected. Reptilase clot retraction induced by ADP or collagen was slightly inhibited. Uptake of 14C-serotonin was slightly decreased. Uptake of 14C-adenine was normal. Platelet adhesion onto glass was not depressed. DAG did not release lactic dehydrogenase from the cytoplasm of the platelets. Coagulation factors were not affected.