Etablissement francais du sang Alpes Mediterranee

Marseille, France

Etablissement francais du sang Alpes Mediterranee

Marseille, France
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Dales J.-P.,Plateforme Transcriptome | Beaufils N.,Biochemistry and Molecular Biology | Silvy M.,Etablissement Francais du Sang Alpes Mediterranee | Picard C.,Etablissement Francais du Sang Alpes Mediterranee | And 3 more authors.
BMC Medicine | Year: 2010

Background: Hypoxia-inducible factor 1 (HIF-1) is a master transcriptional regulator of genes regulating oxygen homeostasis. The HIF-1 protein is composed of two HIF-1α and HIF-1β/aryl hydrocarbon receptor nuclear translocator (ARNT) subunits. The prognostic relevance of HIF-1α protein overexpression has been shown in breast cancer. The impact of HIF-1α alternative splice variant expression on breast cancer prognosis in terms of metastasis risk is not well known.Methods: Using real-time quantitative reverse transcription PCR assays, we measured mRNA concentrations of total HIF-1α and 4 variants in breast tissue specimens in a series of 29 normal tissues or benign lesions (normal/benign) and 53 primary carcinomas. In breast cancers HIF-1α splice variant levels were compared to clinicopathological parameters including tumour microvessel density and metastasis-free survival.Results: HIF-1α isoforms containing a three base pairs TAG insertion between exon 1 and exon 2 (designated HIF-1αTAG) and HIF-1α736mRNAs were found expressed at higher levels in oestrogen receptor (OR)-negative carcinomas compared to normal/benign tissues (P = 0.009 and P = 0.004 respectively). In breast carcinoma specimens, lymph node status was significantly associated with HIF-1αTAGmRNA levels (P = 0.037). Significant statistical association was found between tumour grade and HIF-1αTAG(P = 0.048), and total HIF-1α (P = 0.048) mRNA levels. HIF-1αTAGmRNA levels were also inversely correlated with both oestrogen and progesterone receptor status (P = 0.005 and P = 0.033 respectively). Univariate analysis showed that high HIF-1αTAGmRNA levels correlated with shortened metastasis free survival (P = 0.01).Conclusions: Our results show for the first time that mRNA expression of a HIF-1αTAGsplice variant reflects a stage of breast cancer progression and is associated with a worse prognosis.See commentary: © 2010 Dales et al; licensee BioMed Central Ltd.

Colson P.,Center Hospitalo University Timone | Colson P.,Aix - Marseille University | Borentain P.,Center Hospitalo University Conception | Queyriaux B.,Institute of Veille Sanitaire | And 9 more authors.
Journal of Infectious Diseases | Year: 2010

Background: The source and route of autochthonous hepatitis E virus (HEV) infections are not clearly established in industrialized countries despite evidence that it is a zoonosis in pigs. We investigated the role of figatellu, a traditional pig liver sausage widely eaten in France and commonly consumed raw, as a source of HEV infection. Methods: A case-control study was conducted of 3 patients who presented autochthonous hepatitis E and 15 members of their 3 different families. Anti-HEV immunoglobulin G and immunoglobulin M antibody testing was performed with commercial assays. HEV RNA was detected in serum samples of patients and in pig liver sausages by means of real-time polymerase chain reaction and sequenced by means of in-house sequencing assays. Genetic links between HEV sequences were analyzed. Results: Acute or recent HEV infection, defined by detection of anti-HEV immunoglobulin M antibodies and/ or HEV RNA, was observed in 7 of 13 individuals who ate raw figatellu and 0 of 5 individuals who did not eat raw figatellu ( ). Moreover, HEV RNA of genotype Pp.041 3 was recovered from 7 of 12 figatelli purchased in supermarkets, and statistically significant genetic links were found between these sequences and those recovered from patients who ate raw figatellu. Conclusion: Our findings strongly support the hypothesis of HEV infection through ingestion of raw figatellu. © 2010 by the Infectious Diseases Society of America. All rights reserved.

Mohsen-Kanson T.,University of Nice Sophia Antipolis | Hafner A.-L.,University of Nice Sophia Antipolis | Wdziekonski B.,University of Nice Sophia Antipolis | Takashima Y.,University of Cambridge | And 10 more authors.
Stem Cells | Year: 2014

Identification of molecular mechanisms involved in generation of different types of adipocytes is progressing substantially in mice. However, much less is known regarding characterization of brown (BAP) and white adipocyte progenitors (WAPs) in humans, highlighting the need for an in vitro model of human adipocyte development. Here, we report a procedure to selectively derive BAP and WAPs from human-induced pluripotent stem cells. Molecular characterization of APs of both phenotypes revealed that BMP4, Hox8, Hoxc9, and HoxA5 genes were specifically expressed in WAPs, whereas expression of PRDM16, Dio2, and Pax3 marked BAPs. We focused on Pax3 and we showed that expression of this transcription factor was enriched in human perirenal white adipose tissue samples expressing UCP1 and in human classical brown fat. Finally, functional experiments indicated that Pax3 was a critical player of human AP fate as its ectopic expression led to convert WAPs into brown-like APs. Together, these data support a model in which Pax3 is a new marker of human BAPs and a molecular mediator of their fate. The findings of this study could lead to new anti-obesity therapies based on the recruitment of APs and constitute a platform for investigating in vitro the developmental origins of human white and brown adipocytes. Stem Cells 2014;32:1459-1467 © 2013 AlphaMed Press.

Duboz P.,French National Center for Scientific Research | Lazaygues C.,Etablissement francais du sang Alpes Mediterranee | Boetsch G.,Cheikh Anta Diop University | Chiaroni J.,Etablissement francais du sang Alpes Mediterranee
Transfusion Clinique et Biologique | Year: 2012

Aim: Blood donor retention represents a fundamental objective in public health. Comparison between the sociodemographic characteristics and motivational factors between lapsed and regular donors is then required. The objectives of this analysis were: (1) to compare the sociodemographic characteristics of lapsed donors and current donors; (2) to compare the motivations to donate blood expressed by lapsed and current donors. Patients and methods: Data from a 2008 survey, representative of the population by crossed quotas method, of 1400 individuals questioned by phone were used to reach these objectives. Chi 2 tests and binary logistic regressions were used. Results: Results show that socio-occupational categories and motivational factors are different between lapsed and regular donors. Workers, senior management and higher intellectual professions are more often lapsed than regular donors. Concerning motivations, results show that lapsed donors more frequently mention the first experience with blood donation (with colleagues, friends, and parents) than regular donors, for whom altruistic and community motivations are more frequently cited. Conclusion: Workers, senior management and higher intellectual professions should be targeted uppermost, in order to convert them in regular donors. Finally, concerning motivations, the social pressure applied to lapsed donors for their first blood donation appears crucial, whereas regular donors have internalized their motives, more often altruistic and community motivations. © 2011 Elsevier Masson SAS.

The Marseille public hospital system (APHM) has expressed its willingness to pool its services of immunohematology and delivery of labile blood products with those of the French blood institute Alps Mediterranean division (EFS AM). An agreement setting out the terms of this partnership was signed between the two parties. The users of the APHM and EFS AM blood watch wished to preserve the channels of distribution. Implementation of this reorganization has focused on ensuring transfusional safety, reinforcing harmonization of APHM practices, and finding ways to reduce costs. Despite joint information campaigns (to medical and paramedical personnel) carried out by the APHM and EFS AM blood watch, problems have arisen during start-up and adjustments have been necessary on both sides. The success of this project hinges on the involvement of the EFS AM in our transfusional practices, deployment of a system for diffusion of information, and consolidation of physical and human resources at the level of the APHM blood watch. © 2009 Elsevier Masson SAS. All rights reserved.

Granier T.,Etablissement Francais du Sang Alpes Mediterranee | Granier T.,Aix - Marseille University | Beley S.,Etablissement Francais du Sang Alpes Mediterranee | Beley S.,Aix - Marseille University | And 6 more authors.
Transfusion | Year: 2013

BACKGROUND: The RH system is one of the most polymorphic blood group systems with numerous allele variants affecting Rh polypeptides expression. This complexity is at the origin of difficulties for transfusion of African patients especially sickle cell disease patients requiring chronic transfusion therapy with high risk of immunization. As a complete survey of RH variants is lacking in African populations, we performed red blood cell genotyping to determine the type and frequency of RHD and RHCE alleles in sub-Saharan African populations. STUDY DESIGN AND METHODS: A total of 347 blood samples were collected from individuals of six nonpygmoid and three pygmoid populations. RH typing was performed using two single-tube multiplex polymerase chain reaction amplifications (BioArray Solutions, Immucor). RESULTS: All six sub-Saharan nonpygmoid populations exhibited constant variety in both type and frequency of aberrant RHD and RHCE alleles. Predicted partial RH1 (1.8%) and RH5 (0.9%) phenotypes were less than expected. Conversely, predicted partial phenotype RH2 (5.5%) was frequent. Data confirmed the high frequency of samples positive for the non-clinically significant RH10/RH20 antigens (39.5%) and revealed a high frequency of RH54 (DAK, 8.1%). The pygmoid groups showed higher percentages of predicted partial RH antigens and greater heterogeneity reflecting wide genetic differentiation. CONCLUSION: Our data show that frequencies of aberrant RHD and RHCE alleles were similar, irrespective of location and ethnicity. In view of the predicted frequencies and relative clinical significance of both private antigens and high-prevalence antigens absent, the most relevant assays for individuals of African descent in a transfusion setting are for 1) partial RH2 in the patient and 2) RH54 (DAK) in the donor.

Elkaim E.,Aix - Marseille University | Picard C.,Etablissement Francais du Sang Alpes Mediterranee | Picard C.,Aix - Marseille University | Galambrun C.,Aix - Marseille University | And 7 more authors.
British Journal of Haematology | Year: 2014

This study aimed to describe kinetics of complete donor chimerism occurrence (cDC, >99·9% donor) after unrelated cord blood transplantation (UCBT), to identify its predictive factors and its impact on post-transplant outcome. Ninety-four children who received single UCBT after a myeloablative conditioning regimen had blood chimerism evaluation at predefined post-transplant dates, using a real-time polymerase chain reaction method with 0·1% sensitivity. Cumulative incidence of cDC at 1 year post-transplantation was 61·8%. Three predictive factors were identified in multivariate analysis: history of malignant disease (P = 0·03), older age (above 2·16 years, the first quartile of age, P = 0·0055) and higher level of cord/recipient human leucocyte antigen mismatch (4/6 vs. 5-6/6, P < 0·001) increased the probability of post-transplant cDC. Although graft cell dose had a strong impact on haematological recovery, it did not apparently influence cDC occurrence. Early cDC (i.e. more than 99·9% donor chimerism on days 15-30 post-transplant) appeared useful to predict engraftment (P = 0·003) as well as acute and chronic graft-versus-host disease (GvHD). Severe acute or chronic GvHD never occurred in patients with DC ≤99·9%, suggesting than even minimal residual host haematopoiesis is associated with a very low risk of GvHD after UCBT. © 2014 John Wiley & Sons Ltd.

de Coulgeans C.D.,Etablissement Francais du Sang Alpes Mediterranee | de Coulgeans C.D.,Aix - Marseille University | Silvy M.,Etablissement Francais du Sang Alpes Mediterranee | Silvy M.,Aix - Marseille University | And 7 more authors.
British Journal of Haematology | Year: 2014

Summary: To gain further insight into ART4 (DO) gene alleles (DO*A, DO*JO1, DO*A-WL, DO*DOYA, DO*B, DO*B-WL, DO*B-SH-Q149K, DO*B-(WL)-I175N, DO*HY1, DO*HY2, DO*DOMR) and evaluate the impact of synonymous nucleotide polymorphisms on protein expression and mRNA accumulation of DO*A-HA, DO*A-SH and DO*B-SH alleles, human erythroleukaemic K562 cells were transducted with variant DO-lentiviral particles and analysed by flow cytometry and quantitative reverse transcription polymerase chain reaction. Monoclonal antibody (MoAb) detection of DO*A-HA and DO*JO1 transductants was lower than DO*A transductants, while detection of DO*A-SH, DO*A-WL and DO*DOYA transductants was higher. Variant DO*B alleles, i.e. DO*B-SH, DO*B-WL, DO*HY1, DO*HY2 and DO*DOMR, showed reduced MoAb binding. The unexpected modifications of protein expression of the DO*A-HA, DO*A-SH and DO*B-SH alleles that differ from the DO*A or DO*B alleles by a single synonymous polymorphism were abolished by reversion, thus implying involvement of these polymorphisms. Depending on the Leu208 codon used, detection level ranged from 1 to 4·14. In the variant alleles resulting from single synonymous polymorphism, mRNA accumulation correlated roughly with MoAbs detection levels, suggesting post-transcriptional regulation. Other than a few reports involving aberrant splicing, the experiments described herein provide the first evidence that synonymous nucleotide polymorphisms can influence Dombrock blood group expression. Such polymorphisms should be taken into account for molecular screening and potential impact on transfusion. © 2013 John Wiley & Sons Ltd.

Kaba M.,Center Hospitalo University Timone | Kaba M.,Aix - Marseille University | Brouqui P.,Aix - Marseille University | Richet H.,Aix - Marseille University | And 5 more authors.
Emerging Infectious Diseases | Year: 2010

To determine the prevalence of hepatitis E virus (HEV) infection among sheltered homeless persons in Marseille, France, we retrospectively tested 490 such persons. A total of 11.6% had immunoglobulin (Ig) G and 2.5% had IgM against HEV; 1 person had HEV genotype 3f. Injection drug use was associated with IgG against HEV.

Bagnis C.,Etablissement Francais du Sang Alpes Mediterranee | Bagnis C.,Aix - Marseille University
Blood Reviews | Year: 2015

In the field of transfusion, controlling expression of blood group system antigens on the surface of RBCs has been envisioned as a major research objective for five decades. With the advent of gene transfer techniques in the 1980s, genetic manipulation acquired the tools and know-how necessary to propose this goal along with other strategies. Besides the use of gene transfer to study blood group antigens and to develop tools for transfusion purposes, since the beginning of the new millennium, technological advances in combination with the recognition of the clinical potential of gene transfer have led the transfusion domain into development of cell therapy approaches for therapeutic purposes based on genetic manipulation. © 2014 Published by Elsevier Ltd.

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