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PubMed | Brest University Hospital Center, Unite de consultations externes, Nancy University Hospital Center, Institute Federatif Of Biologie and 20 more.
Type: Journal Article | Journal: European journal of human genetics : EJHG | Year: 2016

Heterozygous COL2A1 variants cause a wide spectrum of skeletal dysplasia termed type II collagenopathies. We assessed the impact of this gene in our French series. A decision tree was applied to select 136 probands (71 Stickler cases, 21 Spondyloepiphyseal dysplasia congenita cases, 11 Kniest dysplasia cases, and 34 other dysplasia cases) before molecular diagnosis by Sanger sequencing. We identified 66 different variants among the 71 positive patients. Among those patients, 18 belonged to multiplex families and 53 were sporadic. Most variants (38/44, 86%) were located in the triple helical domain of the collagen chain and glycine substitutions were mainly observed in severe phenotypes, whereas arginine to cysteine changes were more often encountered in moderate phenotypes. This series of skeletal dysplasia is one of the largest reported so far, adding 44 novel variants (15%) to published data. We have confirmed that about half of our Stickler patients (46%) carried a COL2A1 variant, and that the molecular spectrum was different across the phenotypes. To further address the question of genotype-phenotype correlation, we plan to screen our patients for other candidate genes using a targeted next-generation sequencing approach.


Cescutti P.,University of Trieste | Cuzzi B.,University of Trieste | Liut G.,University of Trieste | Segonds C.,Institute Federatif Of Biologie | And 2 more authors.
Carbohydrate Research | Year: 2011

Stenotrophomonas maltophilia is a non-fermenting Gram-negative microorganism capable of causing chronic pulmonary infection in cystic fibrosis patients and its ability to form biofilms on polystyrene and glass surfaces, as well as on cystic fibrosis-derived bronchial epithelial IB3-I cells was recently demonstrated. The latter evidence might explain the power of S. maltophilia to produce persistent lung infections, despite intensive antibiotic treatment. In addition to being important components of the extracellular biofilm matrix, polysaccharides are involved in virulence, as they contribute to bacterial survival in a hostile environment. With the aim of contributing to the elucidation of S. maltophilia virulence factors, the exopolysaccharides produced by two mucoid clinical isolates of S. maltophilia obtained from two cystic fibrosis patients were completely characterised, mainly by means of ESI-MS and NMR spectroscopy. The results showed that, although the two isolates were recovered from two different patients living in different countries (Italy and France), the exopolysaccharides produced have an identical primary structure, with the following repeating unit: {equation presented} The exopolysaccharide is highly negatively charged for the presence of three uronic acids on four residues in the repeating unit. Moreover, an ether-linked D-lactate substituent is located on C-3 and one Oacetyl group on C-4 of the galacturonic acid side chain. Another O-acetyl group substitutes C-2 of the galacturonic acid in the backbone, making this primary structure unique. © 2011 Elsevier Ltd. All rights reserved.


Robert J.,University Pierre and Marie Curie | Tristan A.,University of Lyon | Cavalie L.,Institute Federatif Of Biologie | Decousser J.-W.,Bacteriologie Hygiene | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

The epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) differs from country to country. We assess the features of the ST80 European clone, which is the most prevalent PVL-positive CA-MRSA clone in Europe, and the TSST-1 ST5 clone that was recently described in France. In 2008, all MRSA strains susceptible to fluoroquinolones and gentamicin and resistant to fusidic acid that were isolated in 104 French laboratories were characterized using agr alleles, spa typing, and the staphylococcal cassette chromosome mec element and PCR profiling of 21 toxin genes. Three phenotypes were defined: (i) kanamycin resistant, associated with the ST80 clone; (ii) kanamycin and tobramycin resistant, associated with the ST5 clone; and (iii) aminoglycoside susceptible, which was less frequently associated with the ST5 clone. Among the 7,253 MRSA strains isolated, 91 (1.3%) were ST80 CA-MRSA (89 phenotype 1) and 190 (2.6%) were ST5 CA-MRSA (146 phenotype 2, 42 phenotype 3). Compared to the latter, ST80 CA-MRSAs were more likely to be community acquired (80% versus 46%) and found in young patients (median age, 26.0 years versus 49.5 years) with deep cutaneous infections (48% versus 6%). They were less likely to be tetracycline susceptible (22% versus 85%) and to be isolated from respiratory infections (6% versus 27%). The TSST-1 ST5 clone has rapidly emerged in France and has become even more prevalent than the ST80 European clone, whose prevalence has remained stable. The epidemiological and clinical patterns of the two clones differ drastically. Given the low prevalence of both among all staphylococcal infections, no modification of antibiotic recommendations is required yet. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Formosa C.,French National Center for Scientific Research | Formosa C.,Toulouse 1 University Capitole | Grare M.,Institute Federatif Of Biologie | Duval R.E.,University of Lorraine | And 2 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2012

Studying living bacteria at the nanoscale in their native liquid environment opens an unexplored landscape. We focus on Pseudomonas aeruginosa and demonstrate how the cell wall is biophysically affected at the nanoscale by two reference antibiotics (ticarcillin and tobramycin). The elasticity of the cells drops dramatically after treatment (from 263 ± 70 kPa to 50 ± 18 and 24 ± 4 kPa, respectively on ticarcillin- and tobramycin-treated bacteria) and major micro- and nano-morphological modifications are observed (the surface roughness of native, ticarcillin- and tobramycin-treated bacteria are respectively 2.5, 0.8, and 4.4 nm for a surface area of 40,000 nm2). Thus the nanoscale approach in liquid is valid and can be extended. From the Clinical Editor: Pseudomonas aeruginosa cell wall was demonstrated to be biophysically affected at the nanoscale by two reference antibiotics, ticarcillin, and tobramycin, with the elasticity dropping dramatically after treatment. © 2012 Elsevier Inc.


Feigerlova E.,Toulouse University Hospital Center | Diene G.,Toulouse University Hospital Center | Oliver I.,Toulouse University Hospital Center | Gennero I.,Institute Federatif Of Biologie | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Background: Children with Prader-Willi syndrome (PWS) are routinely treated with GH and have a response comparable with that observed in children with GH deficiency (GHD). Objective: The objective of the study was to compare changes in serum IGF-I, IGF binding protein 3 (IGFBP-3), IGF-I to IGFBP-3 molar ratio, and growth velocity during the first 2 yr of GH therapy in PWS and GHD children. Subjects and Methods: Thirty-three children with PWS (14 boys, 4.9 ± 3.8 yr) and 591 with GHD (351 boys, 9.6 ± 3.6 yr), all naive to GH treatment, were included in this study. Serum IGF-I and IGFBP-3 were measured at 0, 6, 12, and 24 months of GH therapy. The mean initial dose of GH was 0.9 and 1 mg/m2·d in the PWS and GHD groups, respectively. Results: Mean ± SD IGF-I SDscore (SDS) and IGFBP-3 SDS were significantly higher in PWS compared with GHD. The IGF-I to IGFBP-3 molar ratio was significantly lower at baseline and subsequently not different. Despite significantly lower GH doses in PWS children at 6, 12, and 24 months (P = 0.021, P = 0.021, P = 0.001), IGF-I reached 2.8 ± 1.2 SDS at 24 months (72% of values > 2 SDS), and remained at 0.7 ± 1.6 SDS in GHD children (17% of values > 2 SDS). IGFBP-3 did not exceed 2 SDS in either group. There was no significant change in the IGF-I to IGFBP-3 molar ratio. Conclusions: IGF-I SDS increases to a greater extent in PWS than GHD. Bioavailable IGF-I is apparently not different, suggesting that any possible safety issues related to elevated IGF-I are similar in both groups. Copyright © 2010 by The Endocrine Society.


Gallian P.,EHESP School of Public Health | Lhomme S.,Institute National Of La Sante Et Of La Recherche Medicale Unite 1043 | Lhomme S.,University Paul Sabatier | Lhomme S.,Institute Federatif Of Biologie | And 13 more authors.
Emerging Infectious Diseases | Year: 2014

We screened plasma samples (minipools of 96 samples, corresponding to 53,234 blood donations) from France that had been processed with solvent–detergent for hepatitis E virus RNA. The detection rate was 1 HEV-positive sample/2,218 blood donations. Most samples (22/24) from viremic donors were negative for IgG and IgM against HEV. © 2014, Centers for Disease Control and Prevention (CDC). All Rights Reserved.


Arellano C.,Institute Claudius Regaud | Gandia P.,Institute Federatif Of Biologie | Gandia P.,Institute Claudius Regaud | Bettuing L.,University Paul Sabatier | And 2 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2010

Topetecan is an important anti-cancer drug that has recently become available as an oral formulation. In order to study its intestinal absorption in vitro and a potential drug-drug interaction with the anti-emetic ondansetron, a sensitive and accurate method for the analysis of topotecan in biological media was required. We developed a liquid-liquid extraction method at pH 7.0-7.5 with a recovery of 85% and which took into account the complex chemical behaviour of topotecan related to the lactone opening and the keto-enol tautomerism. This enabled us to validate a new specific and sensitive LC-MS method of analysis, with satisfactory inter- and intra-day repeatability and accuracy. The method was applied to a study of topotecan uptake in rat everted gut sacs that showed that, despite being a P-glycoprotein substrate like topotecan, ondansetron did not interfere with topotecan uptake. © 2010 Elsevier B.V. All rights reserved.


Bedia C.,French Institute of Health and Medical Research | Bedia C.,University Paul Sabatier | Camacho L.,CSIC - Institute of Advanced Chemistry of Catalonia | Abad J.L.,CSIC - Institute of Advanced Chemistry of Catalonia | And 4 more authors.
Journal of Lipid Research | Year: 2010

Acid ceramidase (aCDase) is one of several enzymes responsible for ceramide degradation within mammalian cells. As such, aCDase regulates the intracellular levels of the bioactive lipid ceramide. An inherited deficiency of aCDase activity results in Farber disease (FD), also called lipogranulomatosis, which is characterized by ceramide accumulation in the tissues of patients. Diagnosis of FD is confirmed by demonstration of a deficient aCDase activity and the subsequent storage of ceramide. Existing methods include extremely complex assays, many of them using radiolabeled compounds. Therefore, the aCDase assay and the in vitro enzymatic diagnosis of FD are still performed in only a very limited number of specialized laboratories. Here, the new fluorogenic substrate Rbm14-12 was synthesized and characterized as a new tool to determine aCDase activity. The resulting optimized assay was performed in 96-well plates, and different fibroblast and lymphoid cell lines derived from FD patients and controls were tested to measure aCDase activity. As a result, the activity in cells of FD patients was found to be very low or even null. This new fluorogenic method offers a very easy and rapid way for specific and accurate determination of aCDase activity and, consequently, for diagnosis of FD. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.


Miedouge M.,Institute Federatif Of Biologie | Izopet J.,Institute Federatif Of Biologie
Revue Francophone des Laboratoires | Year: 2010

An accreditation experiency in virology The laboratory of virology from Toulouse University Hospital decided in 2003 to reach the accreditation with reference to the ISO 15 189 norm « Medical laboratories - Particular requirements for quality and competence ». A first step of optimization in the organization and processes leads to up-date the document management under the coordination of the quality assurance manager, the referents and all the biologists. An electronic quality management system was installed to facilitate and achieved the project. Methods validation data were sent to the Cofrac in July 2006 and a preliminary audit was performed (quality and technical aspects) in December 2006. Cofrac audit was realised in February 2007 and the laboratory was accredited in April 2007. Apart the document management, the most critical points were : human resources management, continue quality improvement, metrological follow up, sampling manual, validation of methods, quality control assessment and determination of uncertainty. © 2010 - Elsevier Masson SAS - Tous droits réservés.


Izopet J.,Institute Federatif Of Biologie
Revue Francophone des Laboratoires | Year: 2010

Hepatitis E virus (HEV) is an agent responsible for waterborne acute hepatitis in tropical and subtropical areas. Epidemiological and molecular data indicate zoonotic transmission of HEV in industrialized countries. HEV infections can lead to fulminant hepatitis in pregnant women and patients with chronic liver diseases. The virus can persist in immunocompromised patients and lead to chronic hepatitis and cirrhosis. Among mammalian strains, genotypes 1 and 2 HEV are found only in humans. By contrast, genotype 3 and 4 have been characterized both in humans and several animal species (pigs, wild-boars and deers). Avian strains have also been described but they are not transmissible to humans. Further studies are needed to improve our knowledge on the size of animal reservoir and molecular and cellular determinants of viral tropism.. © 2010 - Elsevier Masson SAS - Tous droits réservés.

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