Professeur des universités en sciences de gestion
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Churg-Strauss syndrome: retrospective study in Burgundian population in France in past 10 years
- Type de publi. : Article dans une revue
- Date de publi. : 29/12/2009
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Auteurs :
Julien VinitGéraldine MullerPhilip BielefeldPierre PfitzenmeyerPhilippe BonniaudBernard LorcerieJean-François Besancenot
Fiche détaillée
Churg-Strauss syndrome: retrospective study in Burgundian population in France in past 10 years
- Type de publi. : Article dans une revue
- Date de publi. : 29/12/2009
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Auteurs :
Julien VinitGéraldine MullerPhilip BielefeldPierre PfitzenmeyerPhilippe BonniaudBernard LorcerieJean-François Besancenot
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Organismes :
Service de médecine interne et des maladies sytémiques (hôpital général, CHU Dijon)
Service de médecine interne et des maladies sytémiques (hôpital général, CHU Dijon)
Service de médecine interne et des maladies sytémiques (hôpital général, CHU Dijon)
Service de médecine gériatrique (CHU de Dijon - Centre gériatrique de Champmaillot - EHPAD)
Service des maladies respiratoires [CHU de Dijon]
Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon]
Service de médecine interne et des maladies sytémiques (hôpital général, CHU Dijon)
- Publié dans Rheumatology International le 29/10/2020
Résumé : Churg-Strauss Syndrome (SCS) is a systemic vasculitis associated with asthma and eosinophilia. The aim of our work is to describe this pathology in the Burgundian population in France. We counted from the hospitalisation data-processing summaries, the whole of the SCS hospitalised in Burgundy between 1998 and 2008. During the follow-up, the clinical and paraclinical characteristics of every patient were collected. The average prevalence is of 11.3 per million inhabitants and the incidence is of 1.2 new cases per million inhabitants per annum. There exists however, a great prevalence disparity and incidence amongst the various departments of the area. The patient's average follow-up is of 7.7 years. In 23% of the cases one finds a starting factor for vasculitis. The delay between the first signs and the diagnostic is an average of 61 months. The ANCA are positive in 26% of cases and of anti-myeloperoxidase specificity in 83% of cases ( < 0.001). The most profitable biopsies are essentially cutaneous and neuromuscular. At the diagnostic, two-third of the patients have had a treatment adapted according to the current recommendations based on the Five Factor Score. The remission rate within a 1-year period is of 77%. The remission is strongly correlated to the therapeutic protocol associating corticoids and cyclophosphamide ( < 0.05). In conclusion, the prevalence of SCS in our area is similar to that observed in other European regions. However, this vasculitis remains a difficult and often a tardive diagnostic pathology.
Fichiers liés :
PEER_stage2_10.1007%2Fs00296-009-1275-y.pdf
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Bistability between a stationary and an oscillatory dynamo in a turbulent flow of liquid sodium
- Type de publi. : Article dans une revue
- Date de publi. : 25/12/2009
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Auteurs :
Mickaël BourgoinMichael BerhanuBasile GalletRomain MonchauxPhilippe OdierJean-François PintonNicolas PlihonRomain VolkStéphan FauveNicolas MordantFrançois PétrélisSébastien AumaîtreArnaud ChiffaudelFrançois DaviaudBérengère DubrulleFlorent Ravelet
Fiche détaillée
Bistability between a stationary and an oscillatory dynamo in a turbulent flow of liquid sodium
- Type de publi. : Article dans une revue
- Date de publi. : 25/12/2009
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Auteurs :
Mickaël BourgoinMichael BerhanuBasile GalletRomain MonchauxPhilippe OdierJean-François PintonNicolas PlihonRomain VolkStéphan FauveNicolas MordantFrançois PétrélisSébastien AumaîtreArnaud ChiffaudelFrançois DaviaudBérengère DubrulleFlorent Ravelet
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Organismes :
Laboratoire des Écoulements Géophysiques et Industriels [Grenoble]
Laboratoire de Physique Statistique de l'ENS
Laboratoire de Physique Statistique de l'ENS
Service de physique de l'état condensé
Laboratoire de Physique de l'ENS Lyon
Laboratoire de Physique de l'ENS Lyon
Laboratoire de Physique de l'ENS Lyon
Laboratoire de Physique de l'ENS Lyon
Laboratoire de Physique Statistique de l'ENS
Laboratoire de Physique Statistique de l'ENS
Laboratoire de Physique Statistique de l'ENS
Service de physique de l'état condensé
Service de physique de l'état condensé
Service de physique de l'état condensé
Service de physique de l'état condensé
Service de physique de l'état condensé
Laboratoire de Dynamique des Fluides
- Publié dans Journal of Fluid Mechanics le 26/10/2020
Résumé : We report the first experimental observation of a bistable dynamo regime. A turbulent flow of liquid sodium is generated between two disks ill the von karman geometry (VKS experiment). When one disk is kept at rest, bistability is observed between a stationary and an oscillatory magnetic field. The stationary and oscillatory branches occur in the vicinity of a codimension-two bifurcation that results from the coupling between two modes of magnetic field. We present an experimental study or the two regimes and study in detail the region of bistability that we understand ill terms of dynamical system theory. Despite the very turbulent nature of the flow, the bifurcations of the magnetic field are correctly described by a low-dimensional model. In addition, the different regimes are robust; i.e. turbulent fluctuations do not drive any transition between the oscillatory and stationary states in the region of bistability.
Fichiers liés :
Berhanu2009_JFM.pdf
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Eye-centered vs body-centered reaching control: A robotics insight into the neuroscience debate
- Type de publi. : Communication dans un congrès
- Date de publi. : 19/12/2009
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Auteurs :
Minh Tuan TranPhilippe SouèresMichel TaïxBenoît Girard
Fiche détaillée
Eye-centered vs body-centered reaching control: A robotics insight into the neuroscience debate
- Type de publi. : Communication dans un congrès
- Date de publi. : 19/12/2009
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Auteurs :
Minh Tuan TranPhilippe SouèresMichel TaïxBenoît Girard
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Organismes :
Équipe Mouvement des Systèmes Anthropomorphes
Équipe Mouvement des Systèmes Anthropomorphes
Équipe Mouvement des Systèmes Anthropomorphes
Institut des Systèmes Intelligents et de Robotique
Résumé : Whether the central nervous system of primates uses a body-centered or an eye-centered frame for reaching is still a controversial debate in neurosciences. Does the proprioceptive information allow to represent the visual information with respect to the body or inversely, does it transform the hand position in retinal coordinates? In this paper, we implement and test two control schemes associated to each of these two hypotheses by using a computational approach from robotics. To this end, biological models of motor control are applied to a realistic dynamic model of upper body including a 4 DOF eye-neck kinematic chain and a 6DOF arm. Important characteristics, such as proprioceptive biases and sensory delay, are considered. Simulation results allow to compare the geometry of trajectories and illustrate the better robustness of the eye-centered control scheme with respect to biases and sensory delay. Applications to the control of the humanoid robot HRP2 are finally presented.
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Carbon monoxide transport in the Arctic: A joint study using IASI satellite and aircraft data in spring and summer 2008
- Type de publi. : Communication dans un congrès
- Date de publi. : 14/12/2009
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Auteurs :
Matthieu PommierKathy S. LawCathy ClerbauxSolène TurquetyJuliette Hadji-LazaroDaniel HurtmansPierre-François CoheurH. SchlagerGérard AncelletJean-Daniel ParisPhilippe NédelecGlenn S. DiskinJames R. PodolskePeter Bernath
Fiche détaillée
Carbon monoxide transport in the Arctic: A joint study using IASI satellite and aircraft data in spring and summer 2008
- Type de publi. : Communication dans un congrès
- Date de publi. : 14/12/2009
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Auteurs :
Matthieu PommierKathy S. LawCathy ClerbauxSolène TurquetyJuliette Hadji-LazaroDaniel HurtmansPierre-François CoheurH. SchlagerGérard AncelletJean-Daniel ParisPhilippe NédelecGlenn S. DiskinJames R. PodolskePeter Bernath
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Organismes :
TROPO - LATMOS
TROPO - LATMOS
TROPO - LATMOS
Laboratoire de Météorologie Dynamique (UMR 8539)
TROPO - LATMOS
Spectroscopie de l'atmosphère, Service de Chimie Quantique et Photophysique
Spectroscopie de l'atmosphère, Service de Chimie Quantique et Photophysique
DLR Institut für Physik der Atmosphäre = DLR Institute of Atmospheric Physics
TROPO - LATMOS
Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette]
Laboratoire d'aérologie
NASA Langley Research Center [Hampton]
NASA Ames Research Center
Department of Chemistry [Waterloo]
Résumé : Carbon monoxide (CO) is a reactive toxic gas, mainly produced by the combustion of fossil fuels and vegetation burning. It also plays an important role in the budget of tropospheric ozone and can be used a tracer for transport of sources of different origin. The impact of the transport of such pollutants on climate change in the Arctic still remains to be quantified with global models often failing to reproduce seasonal cycles especially in summertime. One possible explanation is the underestimation of modelled ozone production in forest fires plumes. This study focuses on the analysis of the POLARCAT/IPY spring and summer campaigns which took place, in Kiruna, Sweden in April 2008 and in Kangerlussuaq, Greenland in July 2008. During the campaigns different air masses were sampled including clean air, polluted plumes originating from anthropogenic sources in Europe and North America, and forest fire plumes from Siberia and Canada. These different transport pathways were well observed by the IASI (Infrared Atmospheric Sounding Interferometer) interferometer, onboard the METOP-A satellite. Measurements of CO collected by the ATR-42 aircraft as part of POLARCAT-France have been used to validate the satellite measurements. Furthermore, a more general validation procedure was developed to compare IASI with ATR-42, DLR-Falcon, NASA DC-8 and NOAA P3-B CO data. YAK summer flights in Siberia are also available for these comparisons. Both in-situ and satellite data are also compared to simulations from the LMDz-INCA global chemistry model. We will discuss how the good global coverage of IASI and regional flights allow can be used improve estimates of CO emissions and to evaluate the impact of forest fires on CO and O
3 (ozone) distributions.
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Analysis of PTEN, BRAF, and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer
- Type de publi. : Article dans une revue
- Date de publi. : 10/12/2009
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Auteurs :
Pierre Laurent-PuigAnne CayreGilles ManceauEmmanuel BucJean-Baptiste BachetThierry LecomtePhilippe RougierAstrid LievreBruno LandiValerie BoigeMichel DucreuxMarc YchouFrederic BibeauOlivier BoucheJulia ReidSteven StoneFrédérique Penault-Llorca
Fiche détaillée
Analysis of PTEN, BRAF, and EGFR Status in Determining Benefit From Cetuximab Therapy in Wild-Type KRAS Metastatic Colon Cancer
- Type de publi. : Article dans une revue
- Date de publi. : 10/12/2009
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Auteurs :
Pierre Laurent-PuigAnne CayreGilles ManceauEmmanuel BucJean-Baptiste BachetThierry LecomtePhilippe RougierAstrid LievreBruno LandiValerie BoigeMichel DucreuxMarc YchouFrederic BibeauOlivier BoucheJulia ReidSteven StoneFrédérique Penault-Llorca
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Organismes :
Bases moléculaires de la réponse aux xénobiotiques
Génétique, immunothérapie, chimie et cancer
- Publié dans Journal of Clinical Oncology le 01/11/2020
Résumé : Purpose The occurrence of KRAS mutation is predictive of nonresponse and shorter survival in patients treated by anti-epidermal growth factor receptor (anti-EGFR) antibody for metastatic colorectal cancer (mCRC), leading the European Medicine Agency to limit its use to patients with wild-type KRAS tumors. However, only half of these patients will benefit from treatment, suggesting the need to identify additional biomarkers for cetuximab-based treatment efficacy. Patients and Methods We retrospectively collected tumors from 173 patients with mCRC. All but one patient received a cetuximab-based regimen as second-line or greater therapy. KRAS and BRAF status were assessed by allelic discrimination. EGFR amplification was assessed by chromogenic in situ hybridization and fluorescent in situ hybridization, and the expression of PTEN was assessed by immunochemistry. Results In patients with KRAS wild-type tumors (n = 116), BRAF mutations (n = 5) were weakly associated with lack of response (P = .063) but were strongly associated with shorter progression-free survival (P < .001) and shorter overall survival (OS; P < .001). A high EGFR polysomy or an EGFR amplification was found in 17.7% of the patients and was associated with response (P = .015). PTEN null expression was found in 19.9% of the patients and was associated with shorter OS (P = .013). In multivariate analysis, BRAF mutation and PTEN expression status were associated with OS. Conclusion BRAF status, EGFR amplification, and cytoplasmic expression of PTEN wereassociated with outcome measures in KRAS wild-type patients treated with a cetuximab-based regimen. Subsequent studies in clinical trial cohorts will be required to confirm the clinical utility of these markers.
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Le non-recours aux soins des actifs précaires - bilan de la recherche
- Type de publi. : Communication dans un congrès
- Date de publi. : 09/12/2009
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Auteurs :
Philippe WarinCarine ChatainCatherine ChauveaudStéphanie GuttonJean-Jacques MoulinAntoine RodeCatherine SassEmilie Labbe
Fiche détaillée
Le non-recours aux soins des actifs précaires - bilan de la recherche
- Type de publi. : Communication dans un congrès
- Date de publi. : 09/12/2009
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Auteurs :
Philippe WarinCarine ChatainCatherine ChauveaudStéphanie GuttonJean-Jacques MoulinAntoine RodeCatherine SassEmilie Labbe
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Organismes :
Pacte, Laboratoire de sciences sociales
Centre technique, d'appui et de formation des centres d'examens de santé de l'Assurrance maladie
Pacte, Laboratoire de sciences sociales
Centre technique, d'appui et de formation des centres d'examens de santé de l'Assurrance maladie
Pacte, Laboratoire de sciences sociales
Centre technique, d'appui et de formation des centres d'examens de santé de l'Assurrance maladie
Centre technique, d'appui et de formation des centres d'examens de santé de l'Assurrance maladie
Pacte, Laboratoire de sciences sociales
Centre technique, d'appui et de formation des centres d'examens de santé de l'Assurrance maladie
Pacte, Laboratoire de sciences sociales
Centre technique, d'appui et de formation des centres d'examens de santé de l'Assurrance maladie
Résumé : Présentation synthétique de la recherche "Le non-recours aux soins des actifs précaires" réalisée dans le cadre du programme Santé Environnement / Santé Travail de l'ANR.
Fichiers liés :
COM_Colloque_SEST_ANR_decembre_2009.pdf
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L1506: a prestellar core in the making
- Type de publi. : Pré-publication, Document de travail
- Date de publi. : 02/12/2009
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Auteurs :
Pagani L.Isabelle RistorcelliNathalie BoudetMartin GiardAlain AbergelJean-Philippe Bernard
Fiche détaillée
L1506: a prestellar core in the making
- Type de publi. : Pré-publication, Document de travail
- Date de publi. : 02/12/2009
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Auteurs :
Pagani L.Isabelle RistorcelliNathalie BoudetMartin GiardAlain AbergelJean-Philippe Bernard
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Organismes :
Laboratoire d'Etude du Rayonnement et de la Matière en Astrophysique
Centre d'étude spatiale des rayonnements
Centre d'étude spatiale des rayonnements
Centre d'étude spatiale des rayonnements
Institut d'astrophysique spatiale
Centre d'étude spatiale des rayonnements
Résumé : Exploring the structure and dynamics of cold starless clouds is necessary to understand the different steps leading to the formation of protostars. Because clouds evolve slowly, many of them must be studied in detail to pick up different moments of a cloud's lifetime. We study here L1506C in the Taurus region, a core with interesting dust properties which have been evidenced with the PRONAOS balloon-borne telescope. To trace the mass content of L1506C and its kinematics, we mapped the dust emission, and the line emission of two key species, C18O and N2H+ (plus 13CO and C17O). This cloud shows peculiar features: i) a large envelope traced solely by 13CO holding a much smaller core with a strong C18O depletion in its center despite a low maximum opacity (Av~20 mag), ii) extremely narrow C18O lines indicating a low, non-measurable turbulence, iii) contraction traced by C18O itself (plus rotation), iv) unexpectedly, the kinematical signature from the external envelope is opposite to the core one: the 13CO and C18O velocity gradients have opposite directions and opposite profiles (C18O blue peaked, 13CO red peaked). The core is large (r = 3E4 AU) and not very dense (n(H2) ≤ 5E4 cm-3 or less). This core is therefore not prestellar yet. All these facts suggest that the core is kinematically detached from its envelope and in the process of forming a prestellar core. This is the first time that the dynamical formation of a prestellar core is witnessed. The extremely low turbulence could be the reason for the strong depletion of this core despite its relatively low density and opacity in contrast with undepleted cores such as L1521E which shows a turbulence at least 4 times as high.
Fichiers liés :
article.pdf
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Évolution de l'architecture de messagerie d'Osiris
- Type de publi. : Communication dans un congrès
- Date de publi. : 01/12/2009
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Auteurs :
Pierre DavidAlain ZamboniPhilippe PegonJean Benoit
Fiche détaillée
Évolution de l'architecture de messagerie d'Osiris
- Type de publi. : Communication dans un congrès
- Date de publi. : 01/12/2009
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Auteurs :
Pierre DavidAlain ZamboniPhilippe PegonJean Benoit
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Organismes :
Université de Strasbourg
Université de Strasbourg
Université de Strasbourg
Université de Strasbourg
Résumé : La messagerie proposée par l'université de Strasbourg aux établissements membres du réseau métropolitain Osiris satisfait à la contrainte de disponibilité de 99,9 % fixée par les instances politiques du réseau, pour une volumétrie d'environ 100 000 boîtes aux lettres. Pour cela, l'architecture tant matérielle que logicielle a considérablement évolué ces dernières années : mise en place d'un SAN, séparation des tâches de dépôt et de lecture déportée, consolidation à travers un cluster de serveurs, équilibrage de charge basé d'abord sur le protocole CARP et un mécanisme de « round-robin DNS » puis sur un « load balancer » permettant une répartition de charge « active-active » et une augmentation facile de la capacité. Hormis le SAN, l'ensemble est entièrement basé sur des logiciels libres. La dernière évolution majeure consiste en la migration du campus strasbourgeois vers SMTP authentifié, ce qui a eu pour effet d'apporter une réelle transparence pour les utilisateurs nomades et de couper net les émissions de spam sortant de notre réseau .
Fichiers liés :
author_124.pdf
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Polymer Multilayer Films Obtained by Electrochemically Catalyzed Click Chemistry
- Type de publi. : Article dans une revue
- Date de publi. : 01/12/2009
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Auteurs :
Gaulthier RydzekJean-Sébastien ThomannNejla Ben AmeurLoïc JierryPhilippe MésiniArnaud PoncheChristophe ContalAlae El HaitamiJean-Claude VoegelBernard SengerPierre SchaafBenoit FrischFouzia Boulmedais
Fiche détaillée
Polymer Multilayer Films Obtained by Electrochemically Catalyzed Click Chemistry
- Type de publi. : Article dans une revue
- Date de publi. : 01/12/2009
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Auteurs :
Gaulthier RydzekJean-Sébastien ThomannNejla Ben AmeurLoïc JierryPhilippe MésiniArnaud PoncheChristophe ContalAlae El HaitamiJean-Claude VoegelBernard SengerPierre SchaafBenoit FrischFouzia Boulmedais
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Organismes :
Institut Charles Sadron
Conception et application de molécules bioactives
Conception et application de molécules bioactives
Institut Charles Sadron
Institut Charles Sadron
Institut de Science des Matériaux de Mulhouse
Institut Charles Sadron
Biomatériaux et ingénierie tissulaire
Biomatériaux et ingénierie tissulaire
Biomatériaux et ingénierie tissulaire
Institut Charles Sadron
Conception et application de molécules bioactives
Institut Charles Sadron
- Publié dans Langmuir le 27/10/2020
Résumé : We report the covalent layer-by-layer construction of polyelectrolyte multilayer (PEM) films by using an efficient electrochemically triggered Sharpless click reaction. The click reaction is catalyzed by Cu(I) which is generated in situ from Cu(II) (originating from the dissolution of CuSO(4)) at the electrode constituting the substrate of the film. The film buildup can be controlled by the application of a mild potential inducing the reduction of Cu(II) to Cu(I) in the absence of any reducing agent or any ligand. The experiments were carried out in an electrochemical quartz crystal microbalance cell which allows both to apply a controlled potential on a gold electrode and to follow the mass deposited on the electrode through the quartz crystal microbalance. Poly(acrylic acid) (PAA) modified with either alkyne (PAA(Alk)) or azide (PAA(Az)) functions grafted onto the PAA backbone through ethylene glycol arms were used to build the PEM films. Construction takes place on gold electrodes whose potentials are more negative than a critical value, which lies between -70 and -150 mV vs Ag/AgCl (KCl sat.) reference electrode. The film thickness increment per bilayer appears independent of the applied voltage as long as it is more negative than the critical potential, but it depends upon Cu(II) and polyelectrolyte concentrations in solution and upon the reduction time of Cu(II) during each deposition step. An increase of any of these latter parameters leads to an increase of the mass deposited per layer. For given buildup conditions, the construction levels off after a given number of deposition steps which increases with the Cu(II) concentration and/or the Cu(II) reduction time. A model based on the diffusion of Cu(II) and Cu(I) ions through the film and the dynamics of the polyelectrolyte anchoring on the film, during the reduction period of Cu(II), is proposed to explain the major buildup features.
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Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Type 2 Caused by Mitofusin 2 Mutations
- Type de publi. : Article dans une revue
- Date de publi. : 01/12/2009
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Auteurs :
Judith CalvoBenoit FunalotRobert A. OuvrierLeila LazaroA ToutainPhilippe de MasPierre BoucheBrigitte Gilbert-DussardierMarie-Christine Arné-BesJean-Pierre CarrièreHubert JournelMarie-Christine Minot-MyhieClaire GuillouKarima GhorabLaurent MagyFranck SturtzJean-Michel VallatCorinne Magdelaine
Fiche détaillée
Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Type 2 Caused by Mitofusin 2 Mutations
- Type de publi. : Article dans une revue
- Date de publi. : 01/12/2009
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Auteurs :
Judith CalvoBenoit FunalotRobert A. OuvrierLeila LazaroA ToutainPhilippe de MasPierre BoucheBrigitte Gilbert-DussardierMarie-Christine Arné-BesJean-Pierre CarrièreHubert JournelMarie-Christine Minot-MyhieClaire GuillouKarima GhorabLaurent MagyFranck SturtzJean-Michel VallatCorinne Magdelaine
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Organismes :
Service de Neurologie [CHU Limoges]
Centre de référence national neuropathies périphériques rares [CHU Limoges]
Intituto de neurologia
Centre de référence national neuropathies périphériques rares [CHU Limoges]
Biomolécules Thérapies anti-tumorales
Service de Biochimie et Génétique Moléculaire [CHU Limoges]
Westmead Hospital [Sydney]
Département de médecine de l'enfant et de l'adolescent
Service de génétique [CHRU Tours]
Consultation de génétique
AP-HP - Hôpital de la Pitié Salpêtrière
Service de Génétique Médicale [CHU Poitiers]
Neurologie et Explorations Fonctionnelles du Système Nerveux [Toulouse]
Service Neurologie Pédiatrique [CHU Toulouse]
Génétique Médicale
Service de rééducation fonctionnelle
Service de Neurologie [CHU Limoges]
Centre de référence national neuropathies périphériques rares [CHU Limoges]
Service de Neurologie [CHU Limoges]
Centre de référence national neuropathies périphériques rares [CHU Limoges]
Biomolécules Thérapies anti-tumorales
Biomolécules Thérapies anti-tumorales
Service de Biochimie et Génétique Moléculaire [CHU Limoges]
Service de Neurologie [CHU Limoges]
Centre de référence national neuropathies périphériques rares [CHU Limoges]
Biomolécules Thérapies anti-tumorales
Biomolécules Thérapies anti-tumorales
Service de Biochimie et Génétique Moléculaire [CHU Limoges]
- Publié dans Archives of Neurology -Chigago- le 27/10/2020
Résumé : Background: Mutations in the gene encoding mito- fusin 2 (MFN2) cause Charcot-Marie-Tooth disease type 2 (CMT2), with heterogeneity concerning severity and associated clinical features. Objective: To describe MFN2 mutations and associ- ated phenotypes in patients with hereditary motor and sensory neuropathy (HMSN). Design: Direct sequencing of the MFN2 gene and clini- cal investigations of patients with MFN2 mutations. Setting: Molecular genetics laboratory of a university hospital and the LimogesNational Referral Center for Rare Peripheral Neuropathies. Patients: One hundred fifty index patients with HMSN and amedianmotor nerve conduction velocity of 25m/s or greater and without mutations in the genes encoding connexin 32 and myelin protein zero. Main Outcome Measures: Results of genetic analy- ses and phenotypic observations. Results: Twenty different missense mutations were identified in 20 index patients. Mutation frequency was 19 of 107 (17.8%) in patients with CMT2 and 1 of 43 (2.3%) in patients with a median motor nerve conduc- tion velocity less than 38 m/s. Four patients had proven de novo mutations, 8 families had autosomal dominant inheritance, and 3 had autosomal recessive inheritance. The remaining 5 patients were sporadic cases with het- erozygous mutations. Phenotypes varied from mild forms to early-onset severe forms. Additional features were encountered in 8 patients (32%). Six patients un- derwent sural nerve biopsy: electronic microscopy showed prominent mitochondrial abnormalities on longitudinal sections. Conclusions: MFN2 mutations are a frequent cause of CMT2, with variable severity and either dominant or recessive inheritance. MFN2 gene testing must be a first-line analysis in axonal HMSN irrespective of the mode of inheritance or the severity of the peripheral neuropathy.
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