949 results on '"Reynier, Pascal"'
Search Results
152. Thanatobiochemistry: its contribution to the diagnosis of hypothermia fatalities
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Rousseau, Guillaume, additional, Rougé-Maillart, Clotilde, additional, Alarcan, Hugo, additional, Drevin, Guillaume, additional, Gaconnet, Alexia, additional, Reynier, Pascal, additional, Saint-Martin, Pauline, additional, and Rérolle, Camille, additional
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- 2019
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153. Metabolomics shows no impairment of the microenvironment of the cumulus–oocyte complex in women with isolated endometriosis
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Bouet, Pierre-Emmanuel, primary, Chao de la Barca, Juan Manuel, additional, El Hachem, Hady, additional, Descamps, Philippe, additional, Legendre, Guillaume, additional, Reynier, Pascal, additional, and May-Panloup, Pascale, additional
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- 2019
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154. Papilloedema and MRI enhancement of the prechiasmal optic nerve at the acute stage of Leber hereditary optic neuropathy
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Lamirel, Cédric, Cassereau, Julien, Cochereau, Isabelle, Vignal-Clermont, Catherine, Pajot, Olivier, Tanguy, Jean-Yves, Zanlonghi, Xavier, Reynier, Pascal, Amati-Bonneau, Patrizia, Dubas, Frédéric, Bonneau, Dominique, and Verny, Christophe
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- 2010
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155. Mitochondrial bioenergetic background confers a survival advantage to HepG2 cells in response to chemotherapy
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Loiseau, Dominique, Morvan, Daniel, Chevrollier, Arnaud, Demidem, Aicha, Douay, Olivier, Reynier, Pascal, and Stepien, Georges
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- 2009
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156. Molecular Screening of 980 Cases of Suspected Hereditary Optic Neuropathy with a Report on 77 Novel OPA1 Mutations
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Ferré, Marc, Bonneau, Dominique, Milea, Dan, Chevrollier, Arnaud, Verny, Christophe, Dollfus, Hélène, Ayuso, Carmen, Defoort, Sabine, Vignal, Catherine, Zanlonghi, Xavier, Charlin, Jean-Francois, Kaplan, Josseline, Odent, Sylvie, Hamel, Christian P., Procaccio, Vincent, Reynier, Pascal, and Amati-Bonneau, Patrizia
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- 2009
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157. Late‐onset argininosuccinic aciduria in a 72‐year‐old man presenting with fatal hyperammonemia.
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Leuger, Laurent, Dieu, Xavier, Chao de la Barca, Juan Manuel, Moriconi, Mikael, Halley, Guillaume, Donin de Rosière, Xavier, Reynier, Pascal, Mirebeau‐Prunier, Delphine, and Homedan, Chadi
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- 2021
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158. Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance
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Hudson, Gavin, Amati-Bonneau, Patrizia, Blakely, Emma L., Stewart, Joanna D., He, Langping, Schaefer, Andrew M., Griffiths, Philip G., Ahlqvist, Kati, Suomalainen, Anu, Reynier, Pascal, McFarland, Robert, Turnbull, Douglass M., Chinnery, Patrick F., and Taylor, Robert W.
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- 2008
159. OPA1 mutations induce mitochondrial DNA instability and optic atrophy ‘plus’ phenotypes
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Amati-Bonneau, Patrizia, Valentino, Maria Lucia, Reynier, Pascal, Gallardo, Maria Esther, Bornstein, Belén, Boissière, Anne, Campos, Yolanda, Rivera, Henry, de la Aleja, Jesús González, Carroccia, Rosanna, Iommarini, Luisa, Labauge, Pierre, Figarella-Branger, Dominique, Marcorelles, Pascale, Furby, Alain, Beauvais, Katell, Letournel, Franck, Liguori, Rocco, La Morgia, Chiara, Montagna, Pasquale, Liguori, Maria, Zanna, Claudia, Rugolo, Michela, Cossarizza, Andrea, Wissinger, Bernd, Verny, Christophe, Schwarzenbacher, Robert, Martín, Miguel Ángel, Arenas, Joaqun, Ayuso, Carmen, Garesse, Rafael, Lenaers, Guy, Bonneau, Dominique, and Carelli, Valerio
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- 2008
160. Is multidetector CT-scan able to detect T3a renal tumor before surgery?
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Caillaud, Marie, Laisney, Mickaël, Bejanin, Alexandre, Scherer-Gagou, Clarisse, Duclos, Harmony, Eustache, Francis, Desgranges, Béatrice, Allain, Philippe, Cassereau, Julien, Chevrollier, Arnaud, Codron, Philippe, Goizet, Cyril, Gueguen, Naïg, Verny, Christophe, Chabrun, Floris, Dieu, Xavier, Rousseau, Guillaume, Chupin, Stéphanie, Letournel, Franck, Procaccio, Vincent, Bonneau, Dominique, Lenaers, Guy, Simard, Gilles, Mirebeau-Prunier, Delphine, Chao de La Barca, Juan Manuel, Reynier, Pascal, Renard, Anne Sophie, Nedelcu, Cosmina, Paisant, Anita, Saulnier, Patrick, Le Bigot, Jérôme, Azzouzi, Abdel Rahmene, Bigot, Pierre, Aubé, Christophe, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Adult ,Male ,medicine.medical_specialty ,Urology ,[SDV]Life Sciences [q-bio] ,030232 urology & nephrology ,030204 cardiovascular system & hematology ,Multidetector ct ,Sensitivity and Specificity ,Adipose capsule of kidney ,03 medical and health sciences ,0302 clinical medicine ,Renal cell carcinoma ,Predictive Value of Tests ,Multidetector computed tomography ,Multidetector Computed Tomography ,medicine ,Humans ,Venous Invasion ,Carcinoma, Renal Cell ,Sinus (anatomy) ,ComputingMilieux_MISCELLANEOUS ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Reproducibility of Results ,Renal tumor ,Middle Aged ,medicine.disease ,Kidney Neoplasms ,medicine.anatomical_structure ,Nephrology ,Preoperative Period ,Female ,Radiology ,Renal vein ,business - Abstract
Objective: To evaluate the diagnostic accuracy of multidetector Computed Tomography (MDCT) in predicting T3a renal cell carcinoma (RCC).Materials and methods: Preoperative MDCT of 96 patients with 100 pathologically proven RCC were assessed by two radiologists focusing on the presence of peritumoral fat, sinus fat or venous invasion for cT3a staging. Nature of tumor margins and the presence of peritumoral neovessels were also evaluated, as the influence of perinephric soft-tissue stranding in the interpretation of peritumoral fat.Results: Sensitivity for the identification of peritumoral fat, sinus fat or renal vein invasion was 77%, 86% and 86%, and specificity was 72%, 88% and 97%, respectively. Sensitivity and specificity in the prediction of T3a tumors were 72% and 70% respectively (κ score = 0.38 (0.29-0.47)). Among the 38 pT3 tumors, 6 (16%) were under-staged, and the neovessels and irregular tumor edge as secondary CT signs did not significantly increase the accuracy of the prediction of local invasion. Among the 62 confined tumors, 17 (27%) were over-staged as cT3 and among these 17 false positives cases, perinephric soft-tissue stranding was present in 14 cases.Conclusion: MDCT provides good results in detecting sinus fat, venous invasion and kidney-confined tumors, but evaluation of perinephric fat remains a difficult task, leading to reduced accuracy in T3a staging.
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- 2019
161. Nicotinamide Deficiency in Primary Open-Angle Glaucoma
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Kouassi Nzoughet, Judith, Chao de La Barca, Juan Manuel, Guehlouz, Khadidja, Coulbault, Laurent, Allouche, Stéphane, Bocca, Cinzia, Muller, Jeanne, Gohier, Philippe, Simard, Gilles, Milea, Dan, Desquiret-Dumas, Valérie, Leman, Géraldine, Wetterwald, Celine, Chupin, Stéphanie, Lebert, Anaïs, Khiati, Salim, Le Mao, Morgane, Geffroy, Guillaume, Kane, Mariame Selma, Chevrollier, Arnaud, Goudenège, David, Gadras, Cédric, Tessier, Lydie, Barth, Magalie, Leruez, Stéphanie, Amati-Bonneau, Patrizia, Henrion, Daniel, Bonneau, Dominique, Procaccio, Vincent, Reynier, Pascal, Lenaers, Guy, Gueguen, Naïg, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de biochimie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Singapore Eye Research Institute, Singapore National Eye Centre, ARN : régulations naturelle et artificielle, Université Bordeaux Segalen - Bordeaux 2-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Biochimie et Génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Réseau Maladies Métaboliques, Hôpitaux Universitaires du Grand Ouest, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA)
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0301 basic medicine ,Adult ,Male ,Niacinamide ,Intraocular pressure ,Spectrometry, Mass, Electrospray Ionization ,medicine.medical_specialty ,Open angle glaucoma ,[SDV]Life Sciences [q-bio] ,Urology ,Glaucoma ,Cohort Studies ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Intraocular Pressure ,ComputingMilieux_MISCELLANEOUS ,Aged ,030304 developmental biology ,Therapeutic strategy ,Aged, 80 and over ,0303 health sciences ,Nicotinamide ,Case-control study ,Nicotinamide deficiency ,Middle Aged ,medicine.disease ,3. Good health ,030104 developmental biology ,Endocrinology ,chemistry ,Case-Control Studies ,Plasma concentration ,Cohort ,030221 ophthalmology & optometry ,Female ,030217 neurology & neurosurgery ,Glaucoma, Open-Angle ,Cohort study ,Chromatography, Liquid - Abstract
PurposeTo investigate the plasma concentration of nicotinamide in primary open-angle glaucoma (POAG).MethodsPlasma of 34 POAG individuals were compared to that of 30 age-and sex-matched controls using a semi-quantitative method based on liquid chromatography coupled to high-resolution mass spectrometry. Subsequently, an independent quantitative method, based on liquid chromatography coupled to mass spectrometry, was used to assess nicotinamide concentration in the plasma from the same initial cohort and from a replicative cohort of 20 POAG individuals and 15 controls.ResultsUsing the semi-quantitative method, the plasma nicotinamide concentration was significantly lower in the initial cohort of POAG individuals compared to and further confirmed in the same cohort, using the targeted quantitative method, with mean concentrations of 0.14 µM (median: 0.12 µM; range: 0.06-0.28 µM) in the POAG group (−30 %;p= 0.022), and 0.19 µM (median: 0.18 µM; range: 0.08-0.47 µM) in the control group. The quantitative dosage also disclosed a significantly lower plasma nicotinamide concentration (−33 %;p= 0.011) in the replicative cohort with mean concentrations of 0.14 µM (median: 0.14 µM; range: 0.09-0.25 µM) in the POAG group, and 0.19 µM (median: 0.21 µM; range: 0.09-0.26 µM) in the control group.ConclusionsGlaucoma is associated with lower plasmatic nicotinamide levels, compared to controls, suggesting that nicotinamide supplementation might become a future therapeutic strategy. Further studies are needed, in larger cohorts, to confirm these preliminary findings.
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- 2019
162. Additional file 1: of OPA1: 516 unique variants and 831 patients registered in an updated centralized Variome database
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Roux, Bastien, Lenaers, Guy, Zanlonghi, Xavier, Amati-Bonneau, Patrizia, Chabrun, Floris, Foulonneau, Thomas, AngĂŠlique Caignard, StĂŠphanie Leruez, Gohier, Philippe, Procaccio, Vincent, Milea, Dan, Dunnen, Johan, Reynier, Pascal, and FerrĂŠ, Marc
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Variants listed in the OPA1 database that are unpublished in the literature (count: 149). (PDF 133 kb)
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- 2019
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163. mtDNA controls expression of the Death Associated Protein 3
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Jacques, Caroline, Chevrollier, Arnaud, Loiseau, Dominique, Lagoutte, Laetitia, Savagner, Frédérique, Malthièry, Yves, and Reynier, Pascal
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- 2006
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164. Two-Step Differential Expression Analysis Reveals a New Set of Genes Involved in Thyroid Oncocytic Tumors
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Jacques, Caroline, Baris, Olivier, Prunier-Mirebeau, Delphine, Savagner, Frédérique, Rodien, Patrice, Rohmer, Vincent, Franc, Brigitte, Guyetant, Serge, Malthiery, Yves, and Reynier, Pascal
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- 2005
165. The Metabolomic Signature of Opa1 Deficiency in Rat Primary Cortical Neurons Shows Aspartate/Glutamate Depletion and Phospholipids Remodeling
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de la Barca, Juan Manuel Chao, Arrázola, Macarena S, Bocca, Cinzia, Arnauné-Pelloquin, Laetitia, Iuliano, Olga, Tcherkez, Guillaume, Lenaers, Guy, Simard, Gilles, Belenguer, Pascale, Reynier, Pascal, de la Barca, Juan Manuel Chao, Arrázola, Macarena S, Bocca, Cinzia, Arnauné-Pelloquin, Laetitia, Iuliano, Olga, Tcherkez, Guillaume, Lenaers, Guy, Simard, Gilles, Belenguer, Pascale, and Reynier, Pascal
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Pathogenic variants of OPA1, which encodes a dynamin GTPase involved in mitochondrial fusion, are responsible for a spectrum of neurological disorders sharing optic nerve atrophy and visual impairment. To gain insight on OPA1 neuronal specificity, we performed targeted metabolomics on rat cortical neurons with OPA1 expression inhibited by RNA interference. Of the 103 metabolites accurately measured, univariate analysis including the Benjamini-Hochberg correction revealed 6 significantly different metabolites in OPA1 down-regulated neurons, with aspartate being the most significant (p < 0.001). Supervised multivariate analysis by OPLS-DA yielded a model with good predictive capability (Q(cum)(2) = 0.65) and a low risk of over-fitting (permQ2 = -0.16, CV-ANOVA p-value 0.036). Amongst the 46 metabolites contributing the most to the metabolic signature were aspartate, glutamate and threonine, which all decreased in OPA1 down-regulated neurons, and lysine, 4 sphingomyelins, 4 lysophosphatidylcholines and 32 phosphatidylcholines which were increased. The phospholipid signature may reflect intracellular membrane remodeling due to loss of mitochondrial fusion and/or lipid droplet accumulation. Aspartate and glutamate deficiency, also found in the plasma of OPA1 patients, is likely the consequence of respiratory chain deficiency, whereas the glutamate decrease could contribute to the synaptic dysfunction that we previously identified in this model.
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- 2019
166. Transcriptional Profiling Reveals Coordinated Up-Regulation of Oxidative Metabolism Genes in Thyroid Oncocytic Tumors
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Baris, Olivier, Savagner, Frédérique, Nasser, Valéry, Loriod, Béatrice, Granjeaud, Samuel, Guyetant, Serge, Franc, Brigitte, Rodien, Patrice, Rohmer, Vincent, Bertucci, François, Birnbaum, Daniel, Malthièry, Yves, Reynier, Pascal, and Houlgatte, Rémi
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- 2004
167. Dominant optic atrophy
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Lenaers Guy, Hamel Christian, Delettre Cécile, Amati-Bonneau Patrizia, Procaccio Vincent, Bonneau Dominique, Reynier Pascal, and Milea Dan
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Medicine - Abstract
Abstract Definition of the disease Dominant Optic Atrophy (DOA) is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC) and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3) encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8) are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7) are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of bilateral, mild, otherwise unexplained visual loss related to optic discs pallor or atrophy, and typically occurring in the context of a family history of DOA. Optical Coherence Tomography further discloses non-specific thinning of retinal nerve fiber layer, but a normal morphology of the photoreceptors layers. Abnormal visual evoked potentials and pattern ERG may also reflect the dysfunction of the RGCs and their axons. Molecular diagnosis is provided by the identification of a mutation in the OPA1 gene (75% of DOA patients) or in the OPA3 gene (1% of patients). Prognosis Visual loss in DOA may progress during puberty until adulthood, with very slow subsequent chronic progression in most of the cases. On the opposite, in DOA patients with associated extra-ocular features, the visual loss may be more severe over time. Management To date, there is no preventative or curative treatment in DOA; severely visually impaired patients may benefit from low vision aids. Genetic counseling is commonly offered and patients are advised to avoid alcohol and tobacco consumption, as well as the use of medications that may interfere with mitochondrial metabolism. Gene and pharmacological therapies for DOA are currently under investigation.
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- 2012
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168. Lopinavir/ritonavir Induces Mitochondrial Toxicity in HIV-exposed Uninfected Children
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Monnin, Audrey, Nagot, Nicolas, Peries, Marianne, Vallo, Roselyne, Meda, Nicolas, Singata-Madliki, Mandisa, Tumwine, James, Kankasa, Chipepo, Reynier, Pascal, Tylleskär, Thorkild, van de Perre, Philippe, Molès, Jean-Pierre, and Vallo, Roselyne
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[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology - Published
- 2018
169. How Can a Ketogenic Diet Improve Motor Function?
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Veyrat-Durebex, Charlotte, Reynier, Pascal, Procaccio, Vincent, Hergesheimer, Rudolf, Corcia, Philippe, Andres, Christian R, Blasco, Hélène, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; A ketogenic diet (KD) is a normocaloric diet composed by high fat (80-90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and spinal cord injury. These studies have proposed that KD may induce a modification in synaptic morphology and function, involving ionic channels, glutamatergic transmission, or synaptic vesicular cycling machinery. However, little is understood about the molecular mechanisms underlying the impact of KD on motor function and the perspectives of its use to acquire the neuromuscular effects. The aim of this review is to explore the conditions through which KD might improve motor function. First, we will describe the main consequences of KD exposure in tissues involved in motor function. Second, we will report and discuss the relevance of KD in pre-clinical and clinical trials in the major diseases presenting motor dysfunction.
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- 2018
170. Mutations in MTHFR and POLG impaired activity of the mitochondrial respiratory chain in 46-year-old twins with spastic paraparesis
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Wiedemann, Arnaud, primary, Chery, Céline, additional, Coelho, David, additional, Flayac, Justine, additional, Gueguen, Naïg, additional, Desquiret-Dumas, Valérie, additional, Feillet, François, additional, Lavigne, Christian, additional, Neau, Jean-Philippe, additional, Fowler, Brian, additional, Baumgartner, Matthias R., additional, Reynier, Pascal, additional, Guéant, Jean-Louis, additional, and Oussalah, Abderrahim, additional
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- 2019
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171. A 3.2–3.6GHz SOI-LDMOS Dual-Input Doherty Power Amplifier
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Boutayeb, Saad, primary, Serhan, Ayssar, additional, Reynier, Pascal, additional, Parat, Damien, additional, Divay, Alexis, additional, Arnould, Jean-Daniel, additional, Lauga-Larroze, Estelle, additional, and Giry, Alexandre, additional
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- 2019
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172. Lipidomics Reveals Triacylglycerol Accumulation Due to Impaired Fatty Acid Flux in Opa1-Disrupted Fibroblasts
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Bocca, Cinzia, primary, Kane, Mariame Selma, additional, Veyrat-Durebex, Charlotte, additional, Nzoughet, Judith Kouassi, additional, Chao de la Barca, Juan Manuel, additional, Chupin, Stephanie, additional, Alban, Jennifer, additional, Procaccio, Vincent, additional, Bonneau, Dominique, additional, Simard, Gilles, additional, Lenaers, Guy, additional, Reynier, Pascal, additional, and Chevrollier, Arnaud, additional
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- 2019
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173. Nicotinamide Deficiency in Primary Open-Angle Glaucoma
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Nzoughet, Judith Kouassi, primary, de la Barca, Juan Manuel Chao, additional, Guehlouz, Khadidja, additional, Leruez, Stéphanie, additional, Coulbault, Laurent, additional, Allouche, Stéphane, additional, Bocca, Cinzia, additional, Muller, Jeanne, additional, Amati-Bonneau, Patrizia, additional, Gohier, Philippe, additional, Bonneau, Dominique, additional, Simard, Gilles, additional, Milea, Dan, additional, Lenaers, Guy, additional, Procaccio, Vincent, additional, and Reynier, Pascal, additional
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- 2019
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174. Retinal Neuronal Loss in Visually Asymptomatic Patients With Myoclonic Epilepsy With Ragged-Red Fibers
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Najjar, Raymond P., primary, Reynier, Pascal, additional, Caignard, Angélique, additional, Procaccio, Vincent, additional, Amati-Bonneau, Patrizia, additional, Mack, Heather, additional, and Milea, Dan, additional
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- 2019
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175. Metabolomics signatures of a subset of RET variants according to their oncogenic risk level
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Veyrat-Durebex, Charlotte, primary, Bouzamondo, Nathalie, additional, Le Mao, Morgane, additional, Chao de la Barca, Juan Manuel, additional, Bris, Céline, additional, Dieu, Xavier, additional, Simard, Gilles, additional, Gadras, Cédric, additional, Tessier, Lydie, additional, Drui, Delphine, additional, Borson-Chazot, Françoise, additional, Barlier, Anne, additional, Reynier, Pascal, additional, and Prunier-Mirebeau, Delphine, additional
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- 2019
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176. Metabolomic Profiling of Aqueous Humor in Glaucoma Points to Taurine and Spermine Deficiency: Findings from the Eye-D Study
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Buisset, Adrien, primary, Gohier, Philippe, additional, Leruez, Stéphanie, additional, Muller, Jeanne, additional, Amati-Bonneau, Patrizia, additional, Lenaers, Guy, additional, Bonneau, Dominique, additional, Simard, Gilles, additional, Procaccio, Vincent, additional, Annweiler, Cédric, additional, Milea, Dan, additional, Reynier, Pascal, additional, and Chao de la Barca, Juan Manuel, additional
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- 2019
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177. Metabolomic Approach in STEMI-Patients Undergoing Left Ventricular Remodeling
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Garcia, Gabriel, primary, Chao de la Barca, Juan, additional, Mirebeau-Prunier, Delphine, additional, Reynier, Pascal, additional, Furber, Alain, additional, Prunier, Fabrice, additional, and Bière, Loïc, additional
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- 2019
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178. Liquid chromatography-tandem mass spectrometry for monitoring vitamin D hydroxymetabolites in human aqueous humor
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Fabregat-Cabello, Neus, primary, Darimont, Pierre, additional, Huyghebaert, Loreen, additional, Reynier, Pascal, additional, Annweiler, Cédric, additional, Milea, Dan, additional, Le Goff, Caroline, additional, and Cavalier, Étienne, additional
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- 2019
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179. Next generation sequencing in family with MNGIE syndrome associated to optic atrophy: Novel homozygous POLG mutation in the C-terminal sub-domain leading to mtDNA depletion
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Felhi, Rahma, primary, Sfaihi, Lamia, additional, Charif, Majida, additional, Desquiret-Dumas, Valerie, additional, Bris, Céline, additional, Goudenège, David, additional, Ammar-Keskes, Leila, additional, Hachicha, Mongia, additional, Bonneau, Dominique, additional, Procaccio, Vincent, additional, Reynier, Pascal, additional, Amati-Bonneau, Patrizia, additional, Lenaers, Guy, additional, and Fakhfakh, Faiza, additional
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- 2019
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180. A locus-specific database for mutations in GDAP1 allows analysis of genotype-phenotype correlations in Charcot-Marie-Tooth diseases type 4A and 2K
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Cassereau Julien, Chevrollier Arnaud, Bonneau Dominique, Verny Christophe, Procaccio Vincent, Reynier Pascal, and Ferré Marc
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inherited peripheral neuropathy ,Charcot-Marie-Tooth disease (CMT) ,ganglioside-induced differentiation-associated protein 1 (GDAP1) ,locus-specific database (LSDB) ,Medicine - Abstract
Abstract Background The ganglioside-induced differentiation-associated protein 1 gene (GDAP1), which is involved in the Charcot-Marie-Tooth disease (CMT), the most commonly inherited peripheral neuropathy, encodes a protein anchored to the mitochondrial outer membrane. The phenotypic presentations of patients carrying GDAP1 mutations are heterogeneous, making it difficult to determine genotype-phenotype correlations, since the majority of the mutations have been found in only a few unrelated patients. Locus-specific databases (LSDB) established in the framework of the Human Variome Project provide powerful tools for the investigation of such rare diseases. Methods and Results We report the development of a publicly accessible LSDB for the GDAP1 gene. The GDAP1 LSDB has adopted the Leiden Open-source Variation Database (LOVD) software platform. This database, which now contains 57 unique variants reported in 179 cases of CMT, offers a detailed description of the molecular, clinical and electrophysiological data of the patients. The usefulness of the GDAP1 database is illustrated by the finding that GDAP1 mutations lead to primary axonal damage in CMT, with secondary demyelination in the more severe cases of the disease. Conclusion Findings of this nature should lead to a better understanding of the pathophysiology of CMT. Finally, the GDAP1 LSDB, which is part of the mitodyn.org portal of databases of genes incriminated in disorders involving mitochondrial dynamics and bioenergetics, should yield new insights into mitochondrial diseases.
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- 2011
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181. Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration
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Angebault Claire, Gueguen Naïg, Desquiret-Dumas Valérie, Chevrollier Arnaud, Guillet Virginie, Verny Christophe, Cassereau Julien, Ferre Marc, Milea Dan, Amati-Bonneau Patrizia, Bonneau Dominique, Procaccio Vincent, Reynier Pascal, and Loiseau Dominique
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Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Background Leber's hereditary optic neuropathy (LHON) is caused by mutations in the complex I subunits of the respiratory chain. Although patients have been treated with idebenone since 1992, the efficacy of the drug is still a matter of debate. Methods We evaluated the effect of idebenone in fibroblasts from LHON patients using enzymatic and polarographic measurements. Results Complex I activity was 42% greater in treated fibroblasts compared to controls (p = 0.002). Despite this complex I activity improvement, the effects on mitochondrial respiration were contradictory, leading to impairment in some cases and stimulation in others. Conclusion These results indicate that idebenone is able to compensate the complex I deficiency in LHON patient cells with variable effects on respiration, indicating that the patients might not be equally likely to benefit from the treatment.
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- 2011
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182. Bioinformatics Tools and Databases to Assess the Pathogenicity of Mitochondrial DNA Variants in the Field of Next Generation Sequencing
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Bris, Céline, primary, Goudenege, David, additional, Desquiret-Dumas, Valérie, additional, Charif, Majida, additional, Colin, Estelle, additional, Bonneau, Dominique, additional, Amati-Bonneau, Patrizia, additional, Lenaers, Guy, additional, Reynier, Pascal, additional, and Procaccio, Vincent, additional
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- 2018
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183. Alagille syndrome: a case report
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Benabed, Yacine, additional, Chaillou, Emilie, additional, Denis, Marie-Christine, additional, Simard, Gilles, additional, Reynier, Pascal, additional, and Homedan, Chadi, additional
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- 2018
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184. OPA1-related dominant optic atrophy is not strongly influenced by mitochondrial DNA background
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Amati-Bonneau Patrizia, Thoraval Didier, Murail Pascal, Chevrollier Arnaud, Rocher Christophe, Ferré Marc, Pierron Denis, Reynier Pascal, and Letellier Thierry
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Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA) are the most frequent forms of hereditary optic neuropathies. LHON is associated with mitochondrial DNA (mtDNA) mutations whereas ADOA is mainly due to mutations in the OPA1 gene that encodes a mitochondrial protein involved in the mitochondrial inner membrane remodeling. A striking influence of mtDNA haplogroup J on LHON expression has been demonstrated and it has been recently suggested that this haplogroup could also influence ADOA expression. In this study, we have tested the influence of mtDNA backgrounds on OPA1 mutations. Methods To define the relationships between OPA1 mutations and mtDNA backgrounds, we determined the haplogroup affiliation of 41 French patients affected by OPA1-related ADOA by control-region sequencing and RFLP survey of their mtDNAs. Results The comparison between patient and reference populations did not revealed any significant difference. Conclusion Our results argue against a strong influence of mtDNA background on ADOA expression. These data allow to conclude that OPA1 could be considered as a "severe mutation", directly responsible of the optic atrophy, whereas OPA1-negative ADOA and LHON mutations need an external factor(s) to express the pathology (i.e. synergistic interaction with mitochondrial background).
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- 2009
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185. Impact of various handling and storage conditions on quantitative detection of hepatitis C virus RNA
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Halfon, Philippe, Khiri, Hacène, Gerolami, Victoria, Bourliere, Marc, Feryn, Jean M., Reynier, Pascal, Gauthier, André, and Cartouzou, Guy
- Published
- 1996
186. New evidence of a mitochondrial genetic background paradox: Impact of the J haplogroup on the A3243G mutation
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Pennarun Erwann, Arveiler Benoit, Bellanne-Chantelot Christine, Feldmann Delphine, Rotig Agnes, Godinot Catherine, de Camaret Benedicte, Batandier Cécile, Allouche Stéphane, Martin-Négrier Marie-Laure, Reynier Pascal, Amati-Bonneau Patricia, Rocher Christophe, Pierron Denis, Rossignol Rodrigue, Crouzet Marc, Murail Pascal, Thoraval Didier, and Letellier Thierry
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Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background The A3243G mutation in the tRNALeu gene (UUR), is one of the most common pathogenic mitochondrial DNA (mtDNA) mutations in France, and is associated with highly variable and heterogeneous disease phenotypes. To define the relationships between the A3243G mutation and mtDNA backgrounds, we determined the haplogroup affiliation of 142 unrelated French patients – diagnosed as carriers of the A3243G mutation – by control-region sequencing and RFLP survey of their mtDNAs. Results The analysis revealed 111 different haplotypes encompassing all European haplogroups, indicating that the 3243 site might be a mutational hot spot. However, contrary to previous findings, we observed a statistically significant underepresentation of the A3243G mutation on haplogroup J in patients (p = 0.01, OR = 0.26, C.I. 95%: 0.08–0.83), suggesting that might be due to a strong negative selection at the embryo or germ line stages. Conclusion Thus, our study supports the existence of mutational hotspot on mtDNA and a "haplogroup J paradox," a haplogroup that may increase the expression of mtDNA pathogenic mutations, but also be beneficial in certain environmental contexts.
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- 2008
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187. Obesity-induced metabolic disturbance drives oxidative stress and complement activation in the retinal environment
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Natoli, Riccardo, Fernando, Nilisha, Dahlenburg, Tess, Jiao, Haihan, Aggio-Bruce, Riemke, Barnett, Nigel L., Chao De La Barca, Juan, Tcherkez, Guillaume, Reynier, Pascal, Chu-Tan, Joshua, Valter, Krisztina, Provis, Jan, Rutar, Matthew, Natoli, Riccardo, Fernando, Nilisha, Dahlenburg, Tess, Jiao, Haihan, Aggio-Bruce, Riemke, Barnett, Nigel L., Chao De La Barca, Juan, Tcherkez, Guillaume, Reynier, Pascal, Chu-Tan, Joshua, Valter, Krisztina, Provis, Jan, and Rutar, Matthew
- Abstract
Purpose Systemic increases in reactive oxygen species, and their association with inflammation, have been proposed as an underlying mechanism linking obesity and age-related macular degeneration (AMD). Studies have found increased levels of oxidative stress biomarkers and inflammatory cytokines in obese individuals; however, the correlation between obesity and retinal inflammation has yet to be assessed. We used the leptin-deficient (ob/ob) mouse to further our understanding of the contribution of obesity to retinal oxidative stress and inflammation.
- Published
- 2018
188. Neurologic phenotypes associated with mutations in RTN4IP1 (OPA10) in children and young adults
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Charif, M, Nasca, A, Thompson, K, Gerber, S, Makowski, C, Mazaheri, N, Bris, C, Goudenège, D, Legati, A, Maroofian, R, Shariati, G, Lamantea, E, Hopton, S, Ardissone, A, Moroni, I, Giannotta, M, Siegel, C, Strom, T, Prokisch, H, Vignal-Clermont, C, Derrien, S, Zanlonghi, X, Kaplan, J, Hamel, C, Leruez, S, Procaccio, V, Bonneau, D, Reynier, P, White, F, Hardy, S, Barbosa, I, Simpson, M, Vara, R, Trujillo, Y, Galehdari, H, Deshpande, C, Haack, T, Rozet, J, Taylor, R, Ghezzi, D, Amati-Bonneau, P, Lenaers, G, Charif, Majida, Nasca, Alessia, Thompson, Kyle, Gerber, Sylvie, Makowski, Christine, Mazaheri, Neda, Bris, Céline, Goudenège, David, Legati, Andrea, Maroofian, Reza, Shariati, Gholamreza, Lamantea, Eleonora, Hopton, Sila, Ardissone, Anna, Moroni, Isabella, Giannotta, Melania, Siegel, Corinna, Strom, Tim M., Prokisch, Holger, Vignal-Clermont, Catherine, Derrien, Sabine, Zanlonghi, Xavier, Kaplan, Josseline, Hamel, Christian P., Leruez, Stephanie, Procaccio, Vincent, Bonneau, Dominique, Reynier, Pascal, White, Frances E., Hardy, Steven A., Barbosa, Inês A., Simpson, Michael A., Vara, Roshni, Trujillo, Yaumara Perdomo, Galehdari, Hamind, Deshpande, Charu, Haack, Tobias B., Rozet, Jean-Michel, Taylor, Robert W., Ghezzi, Daniele, Amati-Bonneau, Patrizia, Lenaers, Guy, Charif, M, Nasca, A, Thompson, K, Gerber, S, Makowski, C, Mazaheri, N, Bris, C, Goudenège, D, Legati, A, Maroofian, R, Shariati, G, Lamantea, E, Hopton, S, Ardissone, A, Moroni, I, Giannotta, M, Siegel, C, Strom, T, Prokisch, H, Vignal-Clermont, C, Derrien, S, Zanlonghi, X, Kaplan, J, Hamel, C, Leruez, S, Procaccio, V, Bonneau, D, Reynier, P, White, F, Hardy, S, Barbosa, I, Simpson, M, Vara, R, Trujillo, Y, Galehdari, H, Deshpande, C, Haack, T, Rozet, J, Taylor, R, Ghezzi, D, Amati-Bonneau, P, Lenaers, G, Charif, Majida, Nasca, Alessia, Thompson, Kyle, Gerber, Sylvie, Makowski, Christine, Mazaheri, Neda, Bris, Céline, Goudenège, David, Legati, Andrea, Maroofian, Reza, Shariati, Gholamreza, Lamantea, Eleonora, Hopton, Sila, Ardissone, Anna, Moroni, Isabella, Giannotta, Melania, Siegel, Corinna, Strom, Tim M., Prokisch, Holger, Vignal-Clermont, Catherine, Derrien, Sabine, Zanlonghi, Xavier, Kaplan, Josseline, Hamel, Christian P., Leruez, Stephanie, Procaccio, Vincent, Bonneau, Dominique, Reynier, Pascal, White, Frances E., Hardy, Steven A., Barbosa, Inês A., Simpson, Michael A., Vara, Roshni, Trujillo, Yaumara Perdomo, Galehdari, Hamind, Deshpande, Charu, Haack, Tobias B., Rozet, Jean-Michel, Taylor, Robert W., Ghezzi, Daniele, Amati-Bonneau, Patrizia, and Lenaers, Guy
- Abstract
Importance: Neurologic disorders with isolated symptoms or complex syndromes are relatively frequent among mitochondrial inherited diseases. Recessive RTN4IP1 gene mutations have been shown to cause isolated and syndromic optic neuropathies. Objective: To define the spectrum of clinical phenotypes associated with mutations in RTN4IP1 encoding a mitochondrial quinone oxidoreductase. Design, Setting, and Participants: This study involved 12 individuals from 11 families with severe central nervous system diseases and optic atrophy. Targeted and whole-exome sequencing were performed-at Hospital Angers (France), Institute of Neurology Milan (Italy), Imagine Institute Paris (France), Helmoltz Zentrum of Munich (Germany), and Beijing Genomics Institute (China)-to clarify the molecular diagnosis of patients. Each patient's neurologic, ophthalmologic, magnetic resonance imaging, and biochemical features were investigated. This study was conducted from May 1, 2014, to June 30, 2016. Main Outcomes and Measures: Recessive mutations in RTN4IP1 were identified. Clinical presentations ranged from isolated optic atrophy to severe encephalopathies. Results: Of the 12 individuals in the study, 6 (50%) were male and 6 (50%) were female. They ranged in age from 5 months to 32 years. Of the 11 families, 6 (5 of whom were consanguineous) had a member or members who presented isolated optic atrophy with the already reported p.Arg103His or the novel p.Ile362Phe, p.Met43Ile, and p.Tyr51Cys amino acid changes. The 5 other families had a member or members who presented severe neurologic syndromes with a common core of symptoms, including optic atrophy, seizure, intellectual disability, growth retardation, and elevated lactate levels. Additional clinical features of those affected were deafness, abnormalities onmagnetic resonance images of the brain, stridor, and abnormal electroencephalographic patterns, all of which eventually led to death before age 3 years. In these patients, novel and ver
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- 2018
189. Deep learning shows nomorphological abnormalities in neutrophils in Alzheimer’s disease.
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Chabrun, Floris, Dieu, Xavier, Doudeau, Nicolas, Gautier, Jennifer, Luque-Paz, Damien, Geneviève, Franck, Ferré, Marc, Mirebeau-Prunier, Delphine, Annweiler, Cédric, and Reynier, Pascal
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PATHOLOGICAL physiology ,ALZHEIMER'S disease ,NEUTROPHILS ,DEEP learning ,LEUCOCYTES ,ARTIFICIAL intelligence - Abstract
Introduction: Several studies have provided evidence of the key role of neutrophils in the pathophysiology of Alzheimer’s disease (AD). Yet, no study to date has investigated the potential link between AD and morphologically abnormal neutrophils on blood smears. Methods: Due to the complexity and subjectivity of the task by human analysis, deep learning models were trained to predict AD from neutrophil images. Control models were trained for a known feasible task (leukocyte subtype classification) and for detecting potential biases of overfitting (patient prediction). Results: Deep learning models achieved state-of-the-art results for leukocyte subtype classification but could not accurately predict AD. Discussion: We found no evidence of morphological abnormalities of neutrophils in AD. Our results show that a solid deep learning pipeline with positive and bias control models with visualization techniques are helpful to support deep learning model results. [ABSTRACT FROM AUTHOR]
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- 2021
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190. Increase of mitochondrial DNA content and transcripts in early bovine embryogenesis associated with upregulation of mtTFA and NRF1 transcription factors
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Heyman Yvan, Chrétien Marie-Françoise, Vignon Xavier, May-Panloup Pascale, Tamassia Manoel, Malthièry Yves, and Reynier Pascal
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Gynecology and obstetrics ,RG1-991 ,Reproduction ,QH471-489 - Abstract
Abstract Background Recent work has shown that mitochondrial biogenesis and mitochondrial functions are critical determinants of embryonic development. However, the expression of the factors controlling mitochondrial biogenesis in early embryogenesis has received little attention so far. Methods We used real-time quantitative PCR to quantify mitochondrial DNA (mtDNA) in bovine oocytes and in various stages of in vitro produced embryos. To investigate the molecular mechanisms responsible for the replication and the transcriptional activation of mtDNA, we quantified the mRNA corresponding to the mtDNA-encoded cytochrome oxidase 1 (COX1), and two nuclear-encoded factors, i.e. the Nuclear Respiratory Factor 1 (NRF1), and the nuclear-encoded Mitochondrial Transcription Factor A (mtTFA). Results Unlike findings reported in mouse embryos, the mtDNA content was not constant during early bovine embryogenesis. We found a sharp, 60% decrease in mtDNA content between the 2-cell and the 4/8-cell stages. COX1 mRNA was constant until the morula stage after which it increased dramatically. mtTFA mRNA was undetectable in oocytes and remained so until the 8/16-cell stage; it began to appear only at the morula stage, suggesting de novo synthesis. In contrast, NRF1 mRNA was detectable in oocytes and the quantity remained constant until the morula stage. Conclusion Our results revealed a reduction of mtDNA content in early bovine embryos suggesting an active process of mitochondrial DNA degradation. In addition, de novo mtTFA expression associated with mitochondrial biogenesis activation and high levels of NRF1 mRNA from the oocyte stage onwards argue for the essential function of these factors during the first steps of bovine embryogenesis.
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- 2005
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191. Novel gene mutation in an atypical late-onset mitochondrial form of multifocal dystonia
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Bris, Céline, Rouaud, Tiphaine, Desquiret-Dumas, Valérie, Gueguen, Naïg, Goudenège, David, Barth, Magalie, Bonneau, Dominique, Amati-Bonneau, Patrizia, Lenaers, Guy, Reynier, Pascal, Lebre, Anne-Sophie, Procaccio, Vincent, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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NDUFS4 mitochondria dystonia ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics - Abstract
International audience; Mitochondrial complex I, the largest component of the mitochondrial respiratory chain, comprises 44 subunits of which 7 are encoded by the mitochondrial genome and the remainder by the nuclear genome. Isolated complex I deficiencies represent a major contribution within the group of respiratory chain defects. We report an atypical case carrying a homozygous NDUFS4 missense mutation, with late-onset multifocal dystonia, in contrast to expected clinical phenotypes due to other NDUFS4 mutations, which have been constantly reported to be responsible for Leigh syndrome of early onset and death.
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- 2017
192. Lipidomics Reveals Cerebrospinal-Fluid Signatures of ALS
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Blasco, Hélène, Veyrat-Durebex, Charlotte, Bocca, Cinzia, Patin, Franck, Vourc'H, Patrick, Kouassi Nzoughet, Judith, Lenaers, Guy, Andres, Christian R, Simard, Gilles, Corcia, Philippe, Reynier, Pascal, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Stress Oxydant et Pathologies Métaboliques (SOPAM), and Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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lcsh:R ,lcsh:Medicine ,lcsh:Q ,lcsh:Science ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
International audience; Amyotrophic lateral sclerosis (ALS), the commonest adult-onset motor neuron disorder, is characterized by a survival span of only 2-5 years after onset. Relevant biomarkers or specific metabolic signatures would provide powerful tools for the management of ALS. The main objective of this study was to investigate the cerebrospinal fluid (CSF) lipidomic signature of ALS patients by mass spectrometry to evaluate the diagnostic and predictive values of the profile. We showed that ALS patients (n = 40) displayed a highly significant specific CSF lipidomic signature compared to controls (n = 45). Phosphatidylcholine PC(36:4), higher in ALS patients (p = 0.0003) was the most discriminant molecule, and ceramides and glucosylceramides were also highly relevant. Analysis of targeted lipids in the brain cortex of ALS model mice confirmed the role of some discriminant lipids such as PC. We also obtained good models for predicting the variation of the ALSFRS-r score from the lipidome baseline, with an accuracy of 71% in an independent set of patients. Significant predictions of clinical evolution were found to be correlated to sphingomyelins and triglycerides with long-chain fatty acids. Our study, which shows extensive lipid remodelling in the CSF of ALS patients, provides a new metabolic signature of the disease and its evolution with good predictive performance.
- Published
- 2017
193. A randomized, double-blind, placebo-controlled trial evaluating cysteamine in Huntington's disease
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Verny, Christophe, Bachoud-Lévi, Anne-Catherine, Dürr, Alexandra, Goizet, Cyril, Azulay, Jean-Philippe, Simonin, Clémence, Tranchant, Christine, Calvas, Fabienne, Krystkowiak, Pierre, Charles, Perrine, Youssov, Katia, Scherer, Clarisse, Prundean, Adriana, Olivier, Audrey, Reynier, Pascal, Saudou, Frédéric, Maison, Patrick, Allain, Philippe, von Studnitz, Erica, Bonneau, Dominique, Group, CYST-HD, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA)
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Adult ,Male ,Cysteamine ,Huntington disease ,Middle Aged ,Treatment Outcome ,Double-Blind Method ,Delayed-Action Preparations ,Humans ,Female ,Cystine Depleting Agents ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Aged ,Follow-Up Studies - Abstract
International audience; BACKGROUND: Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington's disease.METHODS: Ninety-six patients with early-stage Huntington's disease were randomized to 1200 mg delayed-release cysteamine bitartrate or placebo daily for 18 months. The primary end point was the change from baseline in the UHDRS Total Motor Score. A linear mixed-effects model for repeated measures was used to assess treatment effect, expressed as the least-squares mean difference of cysteamine minus placebo, with negative values indicating less deterioration relative to placebo.RESULTS: At 18 months, the treatment effect was not statistically significant - least-squares mean difference, -1.5 ± 1.71 (P = 0.385) - although this did represent less mean deterioration from baseline for the treated group relative to placebo. Treatment with cysteamine was safe and well tolerated.CONCLUSIONS: Efficacy of cysteamine was not demonstrated in this study population of patients with Huntington's disease. Post hoc analyses indicate the need for definitive future studies. © 2017 International Parkinson and Movement Disorder Society.
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- 2017
194. Sexual Dimorphism of Metabolomic Profile in Arterial Hypertension.
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Goïta, Yaya, Chao de la Barca, Juan Manuel, Keïta, Asmaou, Diarra, Mamadou Bocary, Dembélé, Klétigui Casimir, Chabrun, Floris, Dramé, Boubacar Sidiki Ibrahim, Kassogué, Yaya, Diakité, Mahamadou, Mirebeau-Prunier, Delphine, Cissé, Bakary Mamadou, Simard, Gilles, and Reynier, Pascal
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HYPERTENSION ,SEXUAL dimorphism ,METABOLOMICS ,LECITHIN ,INSULIN resistance ,NITRIC oxide - Abstract
Metabolomic studies have demonstrated the existence of biological signatures in blood of patients with arterial hypertension, but no study has hitherto reported the sexual dimorphism of these signatures. We compared the plasma metabolomic profiles of 28 individuals (13 women and 15 men) with essential arterial hypertension with those of a healthy control group (18 women and 18 men), using targeted metabolomics. Among the 188 metabolites explored, 152 were accurately measured. Supervised OPLS-DA (orthogonal partial least squares-discriminant analysis) showed good predictive performance for hypertension in both sexes (Q
2 cum = 0.59 in women and 0.60 in men) with low risk of overfitting (p-value-CV ANOVA = 0.004 in women and men). Seventy-five and 65 discriminant metabolites with a VIP (variable importance for the projection) greater than 1 were evidenced in women and men, respectively. Both sexes showed a considerable increase in phosphatidylcholines, a decrease in C16:0 with an increase in C28:1 lysophosphatidylcholines, an increase in sphingomyelins, as well as an increase of symmetric dimethylarginine (SDMA), acetyl-ornithine and hydroxyproline. Twenty-nine metabolites, involved in phospholipidic and cardiac remodeling, arginine/nitric oxide pathway and antihypertensive and insulin resistance mechanisms, discriminated the metabolic sexual dimorphism of hypertension. Our results highlight the importance of sexual dimorphism in arterial hypertension. [ABSTRACT FROM AUTHOR]- Published
- 2020
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195. Mutations in aARS genes revealed by targeted next-generation sequencing in patients with mitochondrial diseases.
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Felhi, Rahma, Charif, Majida, Sfaihi, Lamia, Mkaouar-Rebai, Emna, Desquiret-Dumas, Valerie, Kallel, Rim, Bris, Céline, Goudenège, David, Guichet, Agnès, Bonneau, Dominique, Procaccio, Vincent, Reynier, Pascal, Amati-Bonneau, Patrizia, Hachicha, Mongia, Fakhfakh, Faiza, and Lenaers, Guy
- Abstract
Mitochondrial diseases are a clinically heterogeneous group of multisystemic disorders that arise as a result of various mitochondrial dysfunctions. Autosomal recessive aARS deficiencies represent a rapidly growing group of severe rare inherited mitochondrial diseases, involving multiple organs, and currently without curative option. They might be related to defects of mitochondrial aminoacyl t-RNA synthetases (mtARS) that are ubiquitous enzymes involved in mitochondrial aminoacylation and the translation process. Here, using NGS analysis of 281 nuclear genes encoding mitochondrial proteins, we identified 4 variants in different mtARS in three patients from unrelated Tunisian families, with clinical features of mitochondrial disorders. Two homozygous variants were found in KARS (c.683C>T) and AARS2 (c.1150-4C>G), respectively in two patients, while two heterozygous variants in EARS2 (c.486-7C>G) and DARS2 (c.1456C>T) were concomitantly found in the third patient. Bio-informatics investigations predicted their pathogenicity and deleterious effects on pre-mRNA splicing and on protein stability. Thus, our results suggest that mtARS mutations are common in Tunisian patients with mitochondrial diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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196. Metabolomics hallmarks OPA1 variants correlating with their in vitro phenotype and predicting clinical severity.
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Barca, Juan Manuel Chao de la, Fogazza, Mario, Rugolo, Michela, Chupin, Stéphanie, Dotto, Valentina Del, Ghelli, Anna Maria, Carelli, Valerio, Simard, Gilles, Procaccio, Vincent, Bonneau, Dominique, Lenaers, Guy, Reynier, Pascal, and Zanna, Claudia
- Published
- 2020
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197. Tryptophane–kynurenine pathway in the remote ischemic conditioning mechanism.
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Bakhta, Oussama, Pascaud, Adrien, Dieu, Xavier, Beaumont, Justine, Kouassi Nzoughet, Judith, Kamel, Rima, Croyal, Mikaël, Tamareille, Sophie, Simard, Gilles, Chao de la Barca, Juan Manuel, Reynier, Pascal, Prunier, Fabrice, and Mirebeau-Prunier, Delphine
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TRYPTOPHAN ,LIQUID chromatography-mass spectrometry ,NIACIN ,KYNURENINE ,SIRTUINS ,ISCHEMIC conditioning - Abstract
The actual protective mechanisms underlying cardioprotection with remote ischemic conditioning (RIC) remain unclear. Recent data suggest that RIC induces kynurenine (KYN) and kynurenic acid synthesis, two metabolites derived from tryptophan (TRP), yet a causal relation between TRP pathway and RIC remains to be established. We sought to study the impact of RIC on the levels of TRP and its main metabolites within tissues, and to assess whether blocking kynurenine (KYN) synthesis from TRP would inhibit RIC-induced cardioprotection. In rats exposed to 40-min coronary occlusion and 2-h reperfusion, infarct size was significantly smaller in RIC-treated animals (35.7 ± 3.0% vs. 46.5 ± 2.2%, p = 0.01). This protection was lost in rats that received 1-methyl-tryptophan (1-MT) pretreatment, an inhibitor of KYN synthesis from TRP (infarct size = 46.2 ± 5.0%). Levels of TRP and nine compounds spanning its metabolism through the serotonin and KYN pathways were measured by reversed-phase liquid chromatography–tandem mass spectrometry in the liver, heart, and limb skeletal muscle, either exposed or not to RIC. In the liver, RIC induced a significant increase in xanthurenic acid, nicotinic acid, and TRP. Likewise, RIC increased NAD-dependent deacetylase sirtuin activity in the liver. Pretreatment with 1-MT suppressed the RIC-induced increases in NAD-dependent deacetylase sirtuin activity. Altogether, these findings indicate that RIC mechanism is dependent on TRP–KYN pathway activation. [ABSTRACT FROM AUTHOR]
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- 2020
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198. Second report of RING finger protein 113A (RNF113A) involvement in a Mendelian disorder.
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Tessarech, Marine, Gorce, Magali, Boussion, Françoise, Bault, Jean‐Philippe, Triau, Stéphane, Charif, Majida, Khiaty, Salim, Delorme, Benoit, Guichet, Agnès, Ziegler, Alban, Bris, Céline, Laquerrière, Annie, Fallet‐Bianco, Catherine, Jacquette, Aurélia, Salhi, Houria, Héron, Delphine, Reynier, Pascal, Procaccio, Vincent, Bonneau, Dominique, and Colin, Estelle
- Abstract
RING Finger Protein 113 A (RNF113A, MIM 300951) is a highly conserved gene located on chromosome Xq24‐q25, encoding a protein containing two conserved zinc finger domains involved in DNA alkylation repair and premessenger RNA splicing. To date, only one pathogenic variant of RNF113A, namely c.901C>T; p.Gln301Ter, has been reported in humans by Tarpey et al. in 2009. Thereafter, Corbett et al. stated that this variant was responsible for an X‐linked form of nonphotosensitive trichothiodystrophy associated with profound intellectual disability, microcephaly, partial corpus callosum agenesis, microphallus, and absent or rudimentary testes. This variant was then shown to alter DNA alkylation repair, providing an additional argument supporting its pathogenicity and important clues about the underlying pathophysiology of nonphotosensitive trichothiodystrophy. Using exome sequencing, we identified exactly the same RNF113A variant in two fetuses affected with abnormalities similar to those previously reported by Corbett et al. To our knowledge, this is the second report of a RNF113A pathogenic variant in humans. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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199. Biochimie thanatologique : ses apports au diagnostic de décès par hypothermie.
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Rousseau, Guillaume, Rougé-Maillart, Clotilde, Alarcan, Hugo, Drevin, Guillaume, Gaconnet, Alexia, Reynier, Pascal, Saint-Martin, Pauline, and Rérolle, Camille
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- 2019
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200. Updated review of postmortem biochemical exploration of hypothermia with a presentation of standard strategy of sampling and analyses
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Rousseau, Guillaume, primary, Reynier, Pascal, additional, Jousset, Nathalie, additional, Rougé-Maillart, Clotilde, additional, and Palmiere, Cristian, additional
- Published
- 2018
- Full Text
- View/download PDF
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