Manioc : Portail | resultats 41 - 60 pour la recherche: Chartier, Anne-Marie

Éditeur(s) : HAL CCSD American Society for Biochemistry and Molecular Biology
Résumé : International audience
Background: We used evolutionary analysis of alkaline phosphatase (tissue nonspecific alkaline phosphatase, TNSALP) to predict missense mutations leading to hypophosphatasia. Results: We found 469 sensitive positions and validated 99% of the 204 known mutations. Conclusion: It is a more powerful method than in silico models to validate missense mutations in TNSALP. Significance: Such an approach should be widely used to support genetic diagnostics. ALPL encodes the tissue nonspecific alkaline phosphatase (TNSALP), which removes phosphate groups from various substrates. Its function is essential for bone and tooth mineralization. In humans, ALPL mutations lead to hypophosphatasia, a genetic disorder characterized by defective bone and/or tooth mineralization. To date, 275 ALPL mutations have been reported to cause hypophosphatasia, of which 204 were simple missense mutations. Molecular evolutionary analysis has proved to be an efficient method to highlight residues important for the protein function and to predict or validate sensitive positions for genetic disease. Here we analyzed 58 mammalian TNSALP to identify amino acids unchanged, or only substituted by residues sharing similar properties, through 220 millions years of mammalian evolution. We found 469 sensitive positions of the 524 residues of human TNSALP, which indicates a highly constrained protein. Any substitution occurring at one of these positions is predicted to lead to hypophosphatasia. We tested the 204 missense mutations resulting in hypophosphatasia against our predictive chart, and validated 99% of them. Most sensitive positions were located in functionally important regions of TNSALP (active site, homodimeric interface, crown domain, calcium site, ...). However, some important positions are located in regions, the structure and/or biological function of which are still unknown. Our chart of sensitive positions in human TNSALP (i) enables to validate or invalidate at low cost any ALPL mutation, which would be suspected to be responsible for hypophosphatasia, by contrast with time consuming and expensive functional tests, and (ii) displays higher predictive power than in silico models of prediction.
ISSN: 0021-9258

hal-01545479
https://hal.archives-ouvertes.fr/hal-01545479
DOI : 10.1074/jbc.M114.576843

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Les amours de Zémédare et Carina, et description de l'île de la Martinique
Auteur(s) : Prévost de Sansac de Traversay, Auguste (1762-1849)
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Débats entre les accusateurs et les accusés, dans l'affaire des colonies, imprimés en exécution de la loi du 4 pluviose. Tome II
Auteur(s) : France. Convention nationale
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La France moderne et le problème colonial.[1], Les traditions et les idées nouvelles, la réorganisation administrative, la reprise de l'expansion : 1815-1830
Auteur(s) : Schefer, Christian (1866-1944)
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Unmet needs in the treatment of idiopathic pulmonary fibrosis-insights from patient chart review in five European countries
Auteur(s) : Maher, Toby M. Molina-Molina, Maria Russell, Anne-Marie Bonella, Francesco Jouneau, Stéphane Ripamonti, Elena Axmann, Judit Vancheri, Carlo
Auteurs secondaires : Imperial College London Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL) Institut de recherche, santé, environnement et travail [Rennes] (Irset) ; Université d'Angers (UA) - Université des Antilles et de la Guyane (UAG) - Université de Rennes 1 (UR1) - École des Hautes Études en Santé Publique [EHESP] (EHESP) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) F. Hoffmann-La Roche [Basel] Università degli studi di Catania [Catania] F. Hoffmann-La Roche Ltd

Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
Background: Two antifibrotic drugs, pirfenidone and nintedanib, are approved by the European Medicines Agency and the US Food and Drug Administration for the treatment of idiopathic pulmonary fibrosis (IPF). In this analysis, treatment patterns of European patients with IPF were investigated to understand antifibrotic prescribing and identify unmet needs in IPF treatment practice. Methods: Between February and March 2016, respiratory physicians from France, Germany, Italy, Spain, and the UK participated in an online questionnaire designed to collect information on IPF treatment patterns in patients under their care. Patients were categorized as treated (received approved antifibrotics) or untreated (did not receive approved antifibrotics, but may have received other unapproved therapies). Classification of IPF diagnosis (confirmed/suspected) and severity ('mild'/'moderate'/'severe') for each patient was based on the individual physician's report. Patients' perspectives were not recorded in this study. Results: In total, 290 physicians responded to the questionnaire. Overall, 54% of patients with IPF did not receive treatment with an approved antifibrotic. More patients had a confirmed IPF diagnosis in the treated (84%) versus the untreated (51%) population. Of patients with a confirmed diagnosis, 40% did not receive treatment. The treated population was younger than the untreated population (67 vs 70 years, respectively; p = 0.01), with more frequent multidisciplinary team evaluation (83% vs 57%, respectively; p = 0.01). A higher proportion of untreated patients had forced vital capacity > 80% at diagnosis versus treated patients. Of patients with 'mild' IPF, 71% did not receive an approved antifibrotic versus 41% and 60% of patients with 'moderate' and 'severe' IPF, respectively. Conclusions: Despite the availability of antifibrotic therapies, many European patients with confirmed IPF do not receive approved antifibrotic treatment. Importantly, there appears to be a reluctance to treat patients with 'mild' or 'stable' disease, and instead adopt a 'watch and wait' approach. More education is required to address diagnostic uncertainty, poor understanding of IPF and its treatments, and issues of treatment access. There is a need to increase physician awareness of the benefits associated with antifibrotic treatment across the spectrum of IPF severity.
ISSN: 1471-2466

hal-01616061
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01616061
DOI : 10.1186/s12890-017-0468-5
PUBMED : 28915874

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Histoire générale des Antilles T.4
Auteur(s) : Dessalles, Adrien (1809-1870)
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Histoire des colonies françaises : ouvrage illustré de gravures hors texte
Auteur(s) : Besson, Maurice (1885-1946)
Auteurs secondaires : Joseph, Gaston (1884-1977)
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La R. M. Javouhey, fondatrice de la Congrégation de Saint-Joseph de Cluny : histoire de sa vie, des oeuvres et missions de la congrégation. Tome II
Auteur(s) : Delaplace, François (1825-1911)
Auteurs secondaires : Buland, Jean-Marie (18..?-18..? ; graveur)
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Bulletin officiel de la Guyane française
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