Laboratoire MERCI

Sotteville-lès-Rouen, France

Laboratoire MERCI

Sotteville-lès-Rouen, France
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Mirshahi S.,Service dOnco Hematologie | Mirshahi S.,University Paris Diderot | Soria C.,Laboratoire dHematologie | Soria C.,Laboratoire MERCI | And 10 more authors.
PLoS ONE | Year: 2014

Aim: To establish a new and reliable assay for quantification of the soluble fibrin (SF) in combination with that of D-dimer for early diagnosis of venous thromboembolism. Methods and Samples: The SF assay is based on D-dimer generated after incubation of plasma with tissue-type plasminogen activator (t-PA). SF and standard D-dimer assays, run in blind, were used to test 119 untreated outpatients with clinically suspected deep-vein thrombosis (DVT, 49 patients) or pulmonary embolism (PE, 70 patients) consulting at the emergency unit of the hospital. Thromboses were confirmed by current imaging methods such as ultrasonography, scintigraphy, computed tomographic pulmonary angiography (CTPA) and ventilation/perfusion scan. Results: SF assay was validated in 270 healthy volunteers [51.8% males; mean age years ± SD: 41±13; age range 19 to 65]. Among these normal plasmas, SF levels were ≤200 ng/mL in 97.8% of them, and 200-250 ng/mL in the remainder [26-46 years old; 50% males]. ROC curves were used to determine the SF cut-off value for plasma SF positivity, which was found to be 300 ng/mL. In patients with suspected venous thromboembolism, SF sensitivities for DVT and PE (92% and 94%, respectively) were comparable to those of D-dimer (96% and 94%), whereas SF specificities (86% and 95%) were higher than those of D-dimer (50% and 54%). Positive-predictive values for SF (89% and 94%) were again higher than those of D-dimer (70% and 65%) in DVT and PE. The amount of circulating SF normalized rapidly after anticoagulant therapy. Conclusion: Results from this small group of patients suggest that the evaluation of plasma SF, in combination with that of D-dimer, represents a potentially useful tool for the early diagnosis of venous thromboembolism, provided that the patients have not been treated previously by anticoagulants. © 2014 Soria et al.


Costa O.,Laboratoire MERCI | Schneider P.,Laboratoire MERCI | Coquet L.,PISSARO Proteomic Facility | Coquet L.,CNRS Polymers, Biopolymer and Surfaces Laboratory | And 7 more authors.
Clinical Proteomics | Year: 2014

Background: Until now, the major prognostic factors for pediatric acute lymphoblastic leukemia (ALL), age, white blood cell count and chromosomal alterations are initially taken into account for the risk stratification of patients. In the light of protein marker studies to classify subtypes of Acute Myeloblastic Leukemia efficiently, we have compared the lymphoblastes proteome in Childhood ALL in accordance with the presence of t(12;21), indicator of good prognosis, usually.Methods: Protein expression in pre-B2 lymphoblastic cells, collected from residual bone marrow cells after diagnostic procedures, was analyzed using two dimensional gel electrophoresis protocol. Protein spots whose average normalized volumes were statistically different in the two patients groups (n = 13; student t test p < 0.01), were excised. Tryptic peptides were then analyzed using a nano-LC1200 system coupled to a 6340 Ion Trap mass spectrometer equipped with a HPLC-chip cube interface. The tandem mass spectrometry peak lists extracted using the DataAnalysis program, were compared with the protein database Mascot Daemon.Results: We focused on twelve spots corresponding to sixteen identified candidate proteins among the 26 found differentially expressed (p ≤0.05) regarding the presence of t(12;21). Among over expressed proteins, two proteins were implicated in cellular growth arrest (i.e. calponine 2, p ≤; 0.001 and phosphatidylinositol transfer protein beta, p ≤0.001) in accordance with good prognosis, while two other proteins favored cell cycle proliferation (i.e. methionine adenosyl transferase 2β, p ≤; 0.005 and heterogeneous nuclear ribonucleo-proteins A2 p ≤0.01) and could therefore be good marker candidates of aggressiveness. Level of expression of proteasome subunit beta type-2 (p ≤; 0.01) and protein casein kinase 2α (p ≤0.01) which both favored apoptosis, deubiquitinating enzyme OTUB1 (p ≤; 0.05) and MLL septin-like fusion protein MSF-B, septin 9 i4 (p ≤0.01) were in accord with a good prognosis related to t(12;21) lymphoblasts.Conclusion: By drawing up the protein map of leukemic cells, these new data identified marker candidates of leukemic aggressiveness and new t(12;21) patients subgroups. These preliminary results will be in the near future confirmed by using a larger sample of pre-B2 childhood ALLs from national lymphoblastic cell collections. © 2014 Costa et al.; licensee BioMed Central Ltd.


Varin R.,University Pierre and Marie Curie | Varin R.,Laboratoire MERCI | Mirshahi S.,Research and Development Stago | Mirshahi P.,University Pierre and Marie Curie | And 7 more authors.
Thrombosis Research | Year: 2013

Introduction Defective thrombolysis, a thrombotic risk factor, can be attributed to the formation of a compact clot poorly accessible to fibrinolytic enzymes. Venous thrombi, rich in red blood cells (RBCs), and arterial thrombi containing various amounts of RBCS, plasma and whole blood (WB) clot permeability and degradability were compared. The effect of rivaroxaban, a potent direct factor Xa inhibitor, was also evaluated. Materials and Methods Fibrin permeability was determined by flow measurement through the clot. Clot degradability was evaluated by the amount of D-dimer generated by clot perfusion with plasminogen and tissue plasminogen activator. Fibrin clot structure was assessed by confocal microscopy. Results WB clot permeability (KS) and degradability were 6.7- and 38-fold lower, respectively, compared with plasma clots. This is attributed to 1) occlusion of fibrin pores by RBCs and 2) a consistent increase in thrombin generation due to platelets and RBCs inducing formation of a tighter clot. Rivaroxaban added to plasma or WB before clotting, in reducing thrombin generation, led to the formation of a looser clot that is more degradable by fibrinolytic enzymes. Permeability and degradability of whole blood clots formed in the presence of rivaroxaban were very similar to those of plasma clots. Conclusion The resistance to fibrinolysis of WB clots was reduced considerably when clots were formed with rivaroxaban. These results may have implications for the development of antithrombotic agents. © 2012 Elsevier Ltd.


PubMed | Center Henri Becquerel, PISSARO Proteomic facility, CNRS Polymers, Biopolymer and Surfaces Laboratory and Laboratoire MERCI
Type: Journal Article | Journal: Clinical proteomics | Year: 2014

Until now, the major prognostic factors for pediatric acute lymphoblastic leukemia (ALL), age, white blood cell count and chromosomal alterations are initially taken into account for the risk stratification of patients. In the light of protein marker studies to classify subtypes of Acute Myeloblastic Leukemia efficiently, we have compared the lymphoblastes proteome in Childhood ALL in accordance with the presence of t(12;21), indicator of good prognosis, usually.Protein expression in pre-B2 lymphoblastic cells, collected from residual bone marrow cells after diagnostic procedures, was analyzed using two dimensional gel electrophoresis protocol. Protein spots whose average normalized volumes were statistically different in the two patients groups (n=13; student t test p<0.01), were excised. Tryptic peptides were then analyzed using a nano-LC1200 system coupled to a 6340 Ion Trap mass spectrometer equipped with a HPLC-chip cube interface. The tandem mass spectrometry peak lists extracted using the DataAnalysis program, were compared with the protein database Mascot Daemon.We focused on twelve spots corresponding to sixteen identified candidate proteins among the 26 found differentially expressed (p0.05) regarding the presence of t(12;21). Among over expressed proteins, two proteins were implicated in cellular growth arrest (i.e. calponine 2, p0.001 and phosphatidylinositol transfer protein beta, p0.001) in accordance with good prognosis, while two other proteins favored cell cycle proliferation (i.e. methionine adenosyl transferase 2, p0.005 and heterogeneous nuclear ribonucleo-proteins A2 p0.01) and could therefore be good marker candidates of aggressiveness. Level of expression of proteasome subunit beta type-2 (p0.01) and protein casein kinase 2 (p0.01) which both favored apoptosis, deubiquitinating enzyme OTUB1 (p0.05) and MLL septin-like fusion protein MSF-B, septin 9 i4 (p0.01) were in accord with a good prognosis related to t(12;21) lymphoblasts.By drawing up the protein map of leukemic cells, these new data identified marker candidates of leukemic aggressiveness and new t(12;21) patients subgroups. These preliminary results will be in the near future confirmed by using a larger sample of pre-B2 childhood ALLs from national lymphoblastic cell collections.

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