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Biomedical subjects

C Caranobe

Publications and source records attributed to C Caranobe.

At least 55 records · Page 3Linked to original sources

Abnormal platelet serotonin uptake and binding sites in myeloproliferative disorders.

A simultaneous investigation of the kinetics of serotonin (5 HT) uptake and of binding sites was carried out in the platelets of normal subjects and of 10 patients affected with various types of myeloproliferative disorders (MD). The 5 HT uptake was analysed according to the Lineweaver-Burk and the Eadie-Hofstee methods. With the two methods, the patient's platelets exhibited a dramatic reduction of the Vi max and of the Km; in some patients the Eadie-Hofstee analysis revealed that a passive diffusion phenomenon is superimposed on the active 5 HT uptake at least for the higher concentration used. The binding data were analysed with the Scatchard method. Two classes of binding sites (high affinity - low capacity, low affinity - high capacity) were found in normal subjects and patients. Pharmacological studies with imipramine, a specific inhibitor of 5 HT uptake, suggested that both the sites are involved in 5 HT uptake. The number of both binding sites was significantly decreased in patient's platelets while the affinity constants of these binding sites were not significantly reduced in comparison with those of the control subjects. No correlations were found between Vi max, Km and the number of binding sites. These results suggest that a reduction in the number of platelet membrane acceptors for 5 HT commonly occurs in myeloproliferative disorders but does not provide a full explanation of the uptake defect.

Blood Platelets↗

Platelet density analysis: a tool for the detection of acquired storage pool disease in man.

This study was designed to evaluate the usefulness of platelet density analysis in the detection of acquired storage pool defects in human patients. Two groups of patients were investigated: 19 subjects affected with a myeloproliferative disorder (group I) where abnormal platelets are released from the megakaryocytes and 11 patients hospitalized in an intensive care unit (Group II) where normal platelets are injured in the circulation. Platelet density distribution after isopycnic centrifugation on a discontinuous stractan density gradient, dense granule markers (serotonin, ATP and ADP) and alpha granule markers (intraplatelet beta-thromboglobulin and platelet factor 4) were simultaneously determined. An increased proportion of the percentage of light platelets was observed in 16 patients of group I and nine of group II; an increased ATP/ADP ratio was observed in 12 patients of group I and 10 of group II. Both the tests were abnormal in 11 patients of group I and nine of group II. In group I, the level of serotonin was low and was related to the percentage of light platelets. The alpha granule specific proteins were normal in the two groups. These results indicate that platelet density analysis may serve as a screening test to detect exhausted platelets in human diseases.

Adenosine Diphosphate↗

[A study of antithrombin systems during heparin therapy].

Plasma levels of three thrombin inhibitors (antithrombin III--AT-III-, alpha 2 macroglobulin - alpha 2M -; alpha 1 antitrypsin - alpha 1 AT-) were measured, together with total plasma antithrombin activity (Howie's method), in 19 hospital patients with venous thromboembolic disease before and during heparin therapy. A decrease in AT III levels was observed during treatment and found to correlate significantly with heparin plasma levels, but there were no significant changes in alpha 2M and alpha 1 AT levels. Variations in total plasma antithrombin activity were not significant. In 9 patients whose AT III levels were under 60% a significant increase in alpha 2M level was noted. The therapeutic problems associated with this category of patients are discussed.

Antithrombin III↗

Factor II related antigen and antithrombin III levels as indicators of liver failure in consumption coagulopathy.

In order to detect impaired synthesis of blood coagulation factors associated to consumption coagulopathy, a simultaneous evaluation of factor II-related antigen (II rAg) and of antithrombin III (AT III) was carried out in 16 patients affected with severe defibrination. An in vitro preliminary study on plasma and serum demonstrated that the levels of II rAg and of AT III, assessed by the Laurell technique with Behring antisera, were not reduced by the coagulation process. The patients were, a posteriori, classified into two groups according to the absence (group A) or the presence (group B) of factors predisposing to liver failure such as metastasis, cirrhosis, and prolonged shock. II rAg and AT III levels are significantly correlated; they are in the normal range in group A but reduced in group B. Thus II rAg or AT III level determinations are useful markers in the detection of liver failure associated to the consumption phenomenon. These results also suggest that part of the decreased AT III levels reported in severe cases of disseminated intravascular coagulation may be the consequence of an associated liver failure.

Antigens↗

Further studies on the relationship between platelet buoyant density and platelet age.

The relationship between platelet buoyant density and platelet age was investigated in eight human subjects submitted to an autologous chromium labeled platelet survival study. Platelets were isolated after isopycnic centrifugation using eight discontinuous isoosmotic stractan gradients (five subjects), or various continuous and linear isoosmolar gradients (three subjects). A paradoxical radioactivity enrichment of the dense platelets and a premature loss of radioactivity in the light platelets were observed. These results are explained by a shift of the radioactivity distribution curve toward higher densities during the 3-4 days after platelet injection, while the standard deviation of the distribution was conserved throughout the platelet life span. These results suggest that young platelets are heterogeneous and slightly less dense than the total platelet population.

Blood Platelets↗

Serotonin uptake and storage in human platelet density subpopulations.

Serotonin uptake and storage were studied in human platelet density subpopulations which were isolated after isopycnic centrifugation on a discontinuous iso-osmolar stractan gradient. Kinetic parameters of the serotonin uptake were calculated (Km, Vi max) and the granular storage capacity was determined by comparing the total amount taken up in the presence or absence of reserpine, a specific inhibitor of the uptake at the granular level. Mean platelet volume and the number of mepacrine-labelled dense bodies were also determined. The results show that the active metabolic process of serotonin uptake is identical whatever the platelet subpopulation but the storage capacity is greater in the densest fraction which contains more dense bodies than the lightest one. Thus active serotonin uptake appears as another well-defined platelet metabolic process which is independent of platelet density; this argues against the conception that light platelets could be old platelets with reduced functional capacities.

Blood Platelets↗

Coulter Counter studies of hypotonic-induced macrothrombocytosis in normal subjects and in idiopathic thrombocytopenic purpura patients.

The addition of distilled water to platelet rich plasma converts the platelets into large spherocytes without lysis. This phenomenon implies an evagination of the platelet membrane which participates in the surface connecting system. An adaptation of the direct microscopic method (Milton & Frojmovic, 1979) to the Coulter Counter is reported. The maximum increase in platelet volume without platelet lysis was obtained for 120 mOsm. These volume changes are a consequence of a shift in the platelet volume distribution curve towards higher values without loss of log normality, while the volume dispersion is only slightly modified. This suggests that the amount of evaginable platelet membrane is correlated to the size of the platelet. The size parameters (volume, surface, diameter) of hypotonic-induced spherocytes closely agree with those reported in the original microscopic method. Application of this technique to ITP-platelets suggests a reduced evaginable platelet membrane; this fact probably reflects the abnormal demarcation of platelet territories at the megakaryocytic level.

Blood Platelets↗

Evaluation of some platelet parameters in a group of elderly people.

Platelet production time (PPT), plasmatic beta-thromboglobulin (beta-TG), platelet density distribution, and mepacrine labelled granular content of the platelets were simultaneously determined in a group of elderly subjects. Vascular deterioration, assessed by the history and clinical examination, was variable in extension and severity. PPT was slightly but not significantly shortened, whereas the raised beta-TG level and diminished platelet density and granular content suggested an in vivo release reaction process. The results are not correlated with the apparent severity of vascular deterioration, and the release reaction may not be solely related to enhanced platelet-vessel wall interactions.

Adult↗

Platelets in myeloproliferative disorders. III: Glycoprotein profile in relation to platelet function and platelet density.

Membrane glycoproteins (GP) are implicated in platelet functions. In myeloproliferative diseases (MD), some of these functions are known to be perturbed. 16 patients with various MD were investigated for platelet functions (retention to glass beads, epinephrine- and ristocetin-induced aggregation), platelet density distribution and PAS-staining glycoprotein profile on SDS-polyacrylamide-gel-electrophoresis. An abnormal GP pattern (moderate reduction of GP (Ib + Is) and GP IIb with corresponding increase in GP IIIb) was demonstrated but no relation to platelet dysfunction or density distribution was observed. No differences between the various types of MD were noticed although the group of polycythaemia vera was the less perturbed for platelet function, platelet density and also GP profile.

Blood Platelets↗

Comparison of progressive antithrombin activity and the concentration of three thrombin inhibitors in nephrotic syndrome.

In order to compare the plasmatic progressive antithrombin activity to the concentration of three thrombin inhibitors, antithrombin III (AT III), alpha 2 macroglobulin (alpha 2 M), alpha 1 anti-trypsin (alpha 1, AT) in nephrotic syndrome, a prospective study was carried out on a group of 28 children affected with the disease. A dramatic reduction of the level of AT III and of alpha 1 AT, two inhibitors of molecular weight close to that of albumin, was observed. The decreased level of AT III was counterbalanced by an increase in alpha 2 M. This phenomenon accounts for the increased progressive antithrombin activity observed in all the affected children. It is suggested that the above compensatory mechanism explains the absence of thrombotic accidents in this series and that the benefit of heparin therapy is doubtful in these conditions.

Adolescent↗

[Limits of platelet aggregation tests for investigating thromboses (author's transl)].

Three methods--spontaneous aggregation, ADP-induced aggregation and levels of circulating platelet aggregates--were used to test for platelet hyperaggregation in 87 adult patients divided into three groups. Group A comprised 26 patients with severe arterial diseases, including cerebral vascular accidents (16) and peripheral thrombosis (10) ; group B consisted of 31 patients with venous conditions, including deep phlebitis (22) and recurrent thrombo-embolic disease (9) ; group C, which served as control, comprised 30 patients with various non-vascular disorders. Spontaneous aggregation and enhanced reactivity to ADP correlated well with each other and were more frequent in patients with vascular diseases. However, one-third of patients in group C had pathological results, while one-third of patients in groups A and B had normal results, independently of any clinical particularity or therapeutic regimen. There were no significant differences between the three groups with regard to circulating platelet aggregates. These tests, therefore, appear to be of statistical and epidemiological interest, but of questionable practical value.

Adenosine Diphosphate↗

Platelets in myeloproliferative disorders. II. Serotonin uptake and storage: correlations with mepacrine labelled dense bodies and with platelet density.

Platelet serotonin (5-HT) uptake and storage in the presence and absence of reserpine were studied simultaneously with platelet volume, density and dense bodies content (mepacrine test) in 33 patients affected with myeloproliferative disorders (MD): 12 chronic myeloid leukaemia (CML), 9 polycythaemia vera (PV), 6 essential thrombocythaemia (ET) and 9 agnogenic myeloid metaplasia (AMM). Observations were (1) a dramatic reduction of the initial velocity (Vi) uptake and of the granular pool of 5-HT; (2) a slight reduction of the number of platelet dense bodies which, in many cases, were less fluorescent than in controls; (3) an increase of the percentage of light platelets while platelet volume was mostly normal; (4) a significant correlation between the number of dense bodies per platelet volume unit and either the percentage of light platelets (r = 0.76) or the size of the granular pool of 5-HT (r = 0.81). These results support evidence of a quantitative and qualitative acquired storage pool syndrome in these patients. In addition, the Vi studies demonstrate that the serotonin uptake across the plasmatic membrane is abnormal.

Blood Platelets↗

Platelets in myeloproliferative disorders. I. A comparative evaluation with certain platelet function tests.

Certain platelet functions were evaluated in 24 patients with secondary polycythaemia (SP) and in a large number of patients suffering from myeloproliferative disorders (MD'S): 89 patients with chronic myeloid leukaemia (CML) at different stages of development, 58 with polycythaemia vera (PV), 23 with essential thrombocythaemia (ET), and 25 with agnogenic myeloid metaplasia (AMM). Bleeding time, epinephrine-induced platelet aggregation and adhesiveness agreed with those generally reported in the literature; they are independent of thrombocytosis, the haemoglobin level and the leucocyte count. Macrothrombocytosis, evaluated by an electronic method, was only found in CML, mainly during acute blast crisis. An increased percentage of light platelets was a constant feature in all groups except in the SP and in 20% of the PV. The most severe abnormalities were observed in AMM and CML in the acute stage; in the chronic phase of CML there is no correlation between the severity of platelet abnormalities and the survival of the patients.

Blood Platelets↗

Platelet volume, density and 5 HT organelles (mepacrine test) in acute leukaemia.

Qualitative platelet parameters (volume, 5 hydroxy-tryptamine (5 HT) organelles studied by the mepacrine test, and density) were evaluated in 31 patients with acute leukaemia: 11 myelomonocytic (AML), 8 lymphoblastic (ALL), 12 granulocytic (AGL). Macrothrombocytosis was observed in most of the cases of AML, was rare in AGL and was never found in ALL. The 5 HT organelles/volume ratio was normal in AGL and ALL but was significantly decreased in AML. In contrast, platelet density distribution was always abnormal whatever the platelet volume and 5 HT organelle concentration. Thus, using simple new methods, convenient even in cases of thrombocytopenia, we demonstrate that qualitative platelet abnormalities are a constant feature in acue leukaemia and that they are more severe in AML.

Blood Cell Count↗