PubMed Health⌕ Search

Biomedical subjects

J Delobel

Publications and source records attributed to J Delobel.

At least 19 recordsLinked to original sources
PubMed1997

Activated Stat related transcription factors in acute leukemia.

Cell proliferation and differentiation are under the control of cytokines and growth factors. Different signaling pathways are involved in the transmission of a specific signal through successive phosphorylation and dephosphorylation of proteins leading to gene transcription necessary for growth and differentiation. The cytokines and growth factors activate the Stat family of transcription factors. The Jak-Stat pathway is essential for cytokine signal transduction. Dysregulation of this cascade might lead to uncontrolled hematopoiesis. Studies have been carried out to examine the functionality of this pathway in cells from patients with acute leukemia. Members of the Stat protein family (Stat1, Stat3 and Stat5) are constitutively activated in cells collected from some acute leukemias suggesting dysregulation of the Jak-Stat pathway. Evidence of the existence of constitutively activated spliced variants of Stat3 and Stat5 proteins are described. The mechanisms of such activation remain to be clarified.

Acute Disease↗
PubMed1996

STAT-related transcription factors are constitutively activated in peripheral blood cells from acute leukemia patients.

A signal transduction pathway activated by many cytokines has recently been elaborated. The JAK kinases and the signal transducers and activators of transcription (STAT) factors have been found to be essential components. In this report, we describe the presence of constitutively activated STAT factors in peripheral blood cells from patients with acute leukemia. We used oligonucleotide probes from the beta-casein and IRF-1 gene promoters and the ISRE probe to detect STAT proteins in nuclear extracts from acute leukemia cells in bandshift assays. Specific DNA protein complex formation was observed with the probes from the beta-casein and IRF-1 gene promoters, but not with the ISRE oligonucleotide probe, when cell extracts from acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were investigated. We used nonradioactive oligonucleotides as competitors to show the specificity of the complex formation. Specific antibodies directed against the individual STAT proteins were used in supershift experiments. STAT5- and STAT1-related factors were detected in ALL and STAT1-, STAT3-, and STAT5-related proteins were present in nuclear cell extracts from AML. Since the cells were not treated with cytokines before the nuclear proteins were extracted, we conclude that these factors are constitutively activated in vivo. It is likely that the constitutive activation of STAT proteins is a part of the events of leukemogenesis.

Acute Disease↗
PubMed1994

Four cases of spuriously low WBC count due to in vitro leukocyte agglutination: contribution of the hematology analyzer Coulter STKS in detecting this clinically misleading artefact.

Four spuriously lowered WBC counts due to in vitro leukoagglutination were reported from an automated cell counter (Coulter STKS). Leukocyte aggregates (3 to 50 cells), detected in the peripheral blood smears, included different cell types, normal (neutrophils, eosinophils, monocytes, lymphocytes) or abnormal (lymphoma cells). The phenomenon was associated with either a spurious leukoneutropenia or an underestimation of hyperleucocytosis. Leukoagglutination was extensively investigated in 3 cases : as shown in several reports, leukoagglutination may occur with various features, especially due to temperature and anticoagulant dependence. Our four cases reflected this variability. Furthermore, one case was found both temperature-dependent and anticoagulant-independent, a pattern not yet described in the literature. A common STKS graphic pattern was found in our 4 cases, suggesting that hematology analyzers such as Coulter STKS may be useful to detect leukoagglutination. In conclusion, each leukoneutropenia and/or each suggestive graphic pattern must be controlled by means of a blood smear examination in order to rule out the possibility of in vitro leukoagglutination.

Aged↗
PubMed1992

Evaluation of the erythrocyte and platelet morphological analysis given by the hematology analyzer Coulter STKS.

The morphological profiles of red blood cells (RBC) and platelets (Plt) derived from the distribution analysis given by the Coulter STKS were evaluated in two groups of patients suffering from non hematological (n = 293) and hematological (n = 257) conditions. The RBC and Plt flags were studied in terms of sensitivity of the morphological analysis and specificity and significance of each flag. When all RBC and Plt flags were considered, the percentages of false negatives and false positives in our subjects were found to be 4.7% and 13.4% respectively, with a global efficiency of 81.8%. The sensitivity of the alarm system was higher than 90% for all types of abnormality, except microcytosis (81%) and Howell-Jolly bodies (57% over a limited number of 7 cases). The specificity of the STKS response was found to be low except for anisocytosis (88.5%) and macrocytosis (86.1%). It was shown that the flags microcytosis and/or hypochromia and macrocytosis were poorly significant when they appeared in isolation (false positive rates of 86.6% and 84.2% respectively). Thus, these alarms could be eliminated from the review criteria. When considering only the flags anisocytosis, NRBCs, micro RBCs/RBC fragments, dimorphic RBC pop, PLT clumps and giant Plt, the percentage of false positives was 8.1%. However, it must be kept in mind that suspect leucocyte flags remained review criteria, resulting in a final false negative rate of 2.5% for RBC and Plt morphological abnormalities.

Blood Platelets↗
PubMed1991

A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type 1.

A 36-year-old patient was investigated for a lifelong history of epistaxis and delayed bleeding after minor surgeries. Deficiencies or abnormalities of the coagulation system, of platelet function, or of factor XIII and alpha-2-antiplasmin were excluded. Consistently, however, over a period of 7 years, a high basal euglobulin fibrinolytic activity was observed that was characterized by a high tissue-type plasminogen activator (t-PA) activity, normal t-PA antigen, and undetectable plasminogen activator inhibitor type-1 (PAI-1) antigen and activity. The high specific activity of t-PA (640,000 IU/mg) and the minimal amounts of t-PA/PAI-1 complexes detected by fibrin zymography suggest that in this patient all t-PA was active. This is in striking contrast to normal plasma, where the majority of t-PA is complexed to PAI-1. Thus, in this patient, a severe deficiency of PAI-1 is associated with a delayed type bleeding tendency. Our observation underscores the importance of plasma PAI-1 for the stabilization of the hemostatic plug.

Adult↗
PubMed1990

Influence of thromboembolism prophylaxis by low molecular weight heparin CY 216 (Fraxiparine) on several parameters of haemostasis in patients under dialysis and receiving either unfractionated heparin or CY 216.

The hemorrhagic risk of an association of the low molecular weight (LMWH), Fraxiparine injected intravenously at the dose of 7.500 AXalCU or of unfractionated heparin (UFH) injected intravenously at the usual dose used during hemodialysis (3.750 +/- 1.280 IU + 1.000 IU after 2 hours of dialysis) to the subcutaneous administration once daily of a thromboembolism preventive dose of Fraxiparine (7.500 AXalCU) was evaluated on the modification of the following hemostasis parameters: thrombin time, activated partial thromboplastin time (APTT), anti Xa activity, in 13 uremic patients on hemodialysis. The association of intravenous and subcutaneous Fraxiparine prevented efficiently the clotting of the extracorporeal circulation without inducing a detectable antithrombinic activity. In contrast, the association of I.V. UFH to subcutaneous Fraxiparine induced a significant increase of the thrombin time and of the APTT, so explained by the activity of UFH. It is concluded that subcutaneous Fraxiparine at the thromboembolism preventive dose can be associated as well to I.V. Fraxiparine as to UFH without increasing the potential hemorrhagic risk. Nevertheless the association of SC and IV Fraxiparine 7.500 AXalC u seems preferable to the association of SC Fraxiparine with UFH.

Aged↗
PubMed1990

A new von Willebrand factor (vWF) defect in a patient with factor VIII (FVIII) deficiency but with normal levels and multimeric patterns of both plasma and platelet vWF. Characterization of abnormal vWF/FVIII interaction.

The patients with inherited bleeding diathesis related to quantitative, structural, and/or functional abnormalities of von Willebrand factor (vWF) are said to have von Willebrand's disease (vWD). We report here the clinical and laboratory features of a 50-year-old woman with a life-long history of excessive bleeding. Her particular laboratory data are factor VIII (FVIII) deficiency, subnormal bleeding time, and the presence of all plasma and platelet vWF multimers in normal amounts. Infused with FVIII/vWF concentrate, she showed a persistent increase in FVIII that led us to discard hemophilia A carrier or "acquired hemophilia" diagnoses. vWF devoid of FVIII purified from normal and patient's plasma by immunoaffinity on anti-vWF monoclonal antibody (MoAb) was immobilized onto polystyrene tubes that were further incubated with purified normal FVIII. The bound FVIII was evidenced using radiolabeled anti-FVIII MoAb. The data showed that the patient's vWF, in contrast to vWF purified from normal plasma, was unable to bind FVIII. Furthermore, no inhibitor of FVIII/vWF interaction was evidenced in incubating purified normal vWF with the patient's plasma before the addition of FVIII and anti-FVIII MoAb. These results support the concept that the bleeding diathesis of this patient appears to be due mainly to her abnormal vWF preventing FVIII/vWF interaction. This abnormality, which is not yet described in present classification of vWD, could be considered as a new variant of vWD.

Factor VIII↗
PubMed1990

[Parameters of hemostasis during treatments associating fractionated heparin administered subcutaneously to standard and fractionated heparin administered intravenously in the chronic hemodialysis patient].

The hemorrhagic risk of an association of fractioned heparin (Fraxiparine) injected intravenously at the dose of 7500 AXaICU or of unfractionned heparin (UFH) injected intravenously at the usual dose used for a priming dose for hemodialysis (3750 +/- 1280 IU + 1000 IU after 2 hours of dialysis) to the subcutaneous administration of a thrombo-embolism preventive dose of Fraxiparine (7500 AXaICU) was evaluated on the modifications of the following hemostasis parameters: thrombin time, Activated Partial Thrombin Time (APTT), prothrombin time, anti Xa activity in 13 uremic patients on hemodialysis. The association of intravenous and subcutaneous Fraxiparine prevents efficiently the clotting of the extracorporeal circulation without inducing a detectable antithrombinic activity. In contrast, the association of I.V. UFH to subcutaneous Fraxiparine induces a significant increase of the thrombin time and of the APTT. This latter is exclusively explained by the activity of UFH. It is concluded that subcutaneous Fraxiparine at the thromboembolism preventive dose can be associated as well to I.V. Fraxiparine as to UFH without increasing the antithrombinic activity of the plasma.

Aged↗
PubMed1989

[Mixed cryoglobulinemia].

Mixed cryoglobulinemia are divided in two types: type II is the association of polyclonal IgG and a monoclonal IgM and type III is the association of polyclonal IgG and polyclonal IgM. In 70 p. 100 of cryoglobulinemia, a cause may be found (hematologic, auto immune disorder, infections, hepatic disorders), in some cases the recognition of the cause is delayed. In 30 p. 100 of cases, no cause can be identified and the cryoglobulinemia is considered as essential. Main clinical finding are purpuric skin rash, urticaria, arthralgia, motor sensitive polyneuropathy, diffuse proliferative glomerulo nephritis. Biological signs associate anemia, rheumatoïd factor and hypocomplementemia. Mixed essential cryoglobulinemia (the Meltzer and Franklin syndrome) is characterized by a systemic vasculitis involving small and middle size vessels.

Cryoglobulinemia↗
PubMed1989

Low-molecular-weight heparin Fraxiparin in chronic hemodialysis. A dose-finding study.

A two-step dose-ranging study was undertaken with CY216 (Fraxiparin) in 8 patients on 7 sessions each. The different doses were administered each time as a single bolus injection at the start of hemodialysis without heparinized priming nor further administration during the 4-hour session. In the first step, the clinical efficacy of 4 different doses of Fraxiparin was compared with that of standard heparin on the percentage of sessions free of clot formation in the extracorporeal circulation (ECC). Safety was evaluated by the compression time for hemostasis at the puncture sites. The second step was a randomized comparison of 3 Fraxiparin dosages. In addition to the clinical assessment of efficacy, the following biological parameters were measured: fibrinopeptide A (FPA), anti-Xa (AXa) activity calibrated against Fraxiparin, thrombin time (TT), activated partial thromboplastin time, blood counts, hemoglobin, hematocrit, plasma creatinine and urea, and residual blood volume in the dialyzer. A 'standard' dosage of 10,000 AXa Institut Choay units of Fraxiparin was shown to prevent clot formation in the ECC. It resulted in a marked increase in TT, without any lengthening of the puncture site compression time. After 4 h, AXa and FPA levels in the venous line were related to the doses used (p less than 0.05). After 48 h AXa activity was very low. Dialysance and tolerance were excellent. Thus, a single dose of Fraxiparin unrelated to body weight and not determined by the measurement of the whole-blood activated clotting time appeared to be a safe and effective means for preventing fibrin formation in 4-hour dialysis sessions.

Adult↗
PubMed1988

Occurrence of hereditary spherocytosis and beta thalassaemia in the same family: globin chain synthesis and visco diffractometric studies.

Hereditary spherocytosis and beta thalassaemia are rarely inherited together. We have studied a large family of Caucasian extraction in whom these two diseases segregate independently over four generations. The diagnosis rested on specialized laboratory findings and in a number of subjects on the measurement of alpha and beta globin chain synthesis. In addition, a viscometric method (osmotic gradient ektacytometry) was used to evaluate the rheological function of the erythrocytes. In patients inheriting both diseases, the results indicate that the clinical and biological expression of hereditary spherocytosis is modulated by the degree of imbalanced globin chain synthesis. The opposite properties of spherocytes (decreased surface/volume ratio, increased haemoglobin concentration) and thalassaemic red cells (increased surface/volume ratio, decreased haemoglobin concentration) may explain the antagonistic influence of each genotype.

Adolescent↗
PubMed1987

[Anticoagulation in hemodialysis sessions with a low molecular weight heparin (CY 222, Choay). Dosage studies in chronic hemodialysis. Its use in patients at high risk of hemorrhage].

Efficacy of CY 222 for providing anticoagulation during hemodialysis was evaluated in three successive trials by rating quality of blood restitution (degree of coagulum formation in extracorporeal circulation) and by assay of fibrinopeptide A. Its safety was assessed by measurement of manual compression time necessary to ensure hemostasis of puncture points at end of session. Details of the first preliminary study were: 60 sessions in 11 chronic uremia patients; CY 222: 75, 150 and 300 A-Xa IC U/kg + 1,000 A-Xa IC U/h, then 150 and 300 A-Xa IC U/kg without continuous injection, compared with standard heparin (SH) at the usual dosage for each patient (60 +/- 13 IU/kg). Results showed CY 222 at 150 U/kg + 1,000 U/h to possess the same efficacy as SH and to give a shorter compression test time: for 150 U/kg the efficacy was satisfactory, although less than with SH, and compression times were shorter (interest in patients at risk of hemorrhage). For 300 U/kg, efficacy was superior (improved restitution and lower FPA level at end of seance: 6 ng/ml instead of 15 ng/ml.p less than 0.002) and compression times were identical. The second study to evaluate optimal dosage of CY 222 in chronic hemodialysis (CHD) involved: 10 patients; CY 222: 200 A-Xa IC U/kg and 250 A-Xa IC U/kg by single-dose injection. Results failed to demonstrate any significant difference in evolution of FPA levels, but restitution was better at 250 U/kg. In addition, investigation of the effect of rinsing of ECC with standard heparin before the session showed that its suppression did not alter effectiveness but improved tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Coagulation↗