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1. L’étude de la cristallurie améliore le diagnostic et la prise en charge thérapeutique de la lithiase rénale

Author

Vincent Frochot, Paul Jungers, Dominique Bazin, Michel Daudon, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and d'Eggis, Gilles

Subjects
Crystalluria, medicine.medical_specialty, Chemistry(all), Global crystal volume, General Chemical Engineering, 030232 urology & nephrology, Calcium oxalate, Urology, Renal function, Uric acids, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Primary hyperoxaluria, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cristallurie, Oxalates de calcium, medicine, Hypercalciuria, 030212 general & internal medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Crystalluria index, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Pathological, Index cristallurique, business.industry, Dihydroxyadenine, Acides uriques, General Chemistry, Cystinuria, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Dihydroxyadénine, 3. Good health, Volume cristallin global, chemistry, Hereditary Diseases, Chemical Engineering(all), Cystine, medicine.symptom, business, Calcium oxalates
Abstract

The search for crystalluria and morphologic analysis of urinary crystals is of interest in the diagnostic evaluation and assessment of efficacy of therapeutic strategies in stone formers. In common calcium oxalate (CaOx) nephrolithiasis, identification of the monohydrate or dihydrate form of CaOx orients toward hyperoxaluria or hypercalciuria as the main lithogenic mechanism, respectively. An unusual high abundance of crystals exclusively made of CaOx monohydrate is highly suggestive of primary hyperoxaluria, the most severe of all types of renal stone diseases. The identification of crystal species such as struvite, cystine, 2,8-dihydroxyadenine, which are not found in normal urine, is indicative of specific pathological conditions, namely, infection stones and hereditary diseases such as cystinuria and dihydroxyadeninuria. Such diseases expose to progressive loss of renal function unless they are prevented by specific therapeutic measures. The presence of crystals made of drugs may entail the risk of kidney dysfunction because of crystallization of the drug or its metabolites.Serial determination of crystalluria, which reflects the activity of stone disease and its response to therapeutic measures, is of major interest in the follow-up of patients suffering from nephrolithiasis. It should be more largely used in clinical practice in most stone formers, still more for the surveillance of patients affected by severe, hereditary renal stone diseases such as primary hyperoxaluria, cystinuria, and dihydroxyadeninuria, where determination of the global crystal volume allows assessing the efficacy of therapeutic measures and optimizing the medical management of the patients., L’étude de la cristallurie et de ses caractéristiques qualitatives et quantitatives est d'un intérêt clinique majeur pour le diagnostic de la maladie lithiasique et l’évaluation de l'efficacité des mesures thérapeutiques proposées aux patients. Dans la lithiase oxalocalcique commune, la forme cristalline, whewellite ou weddellite, oriente respectivement vers une hyperoxalurie ou une hypercalciurie. Une quantité élevée de cristaux de whewellite traduit une forte hyperoxalurie et doit faire rechercher une hyperoxalurie primaire. L'identification de cristaux particuliers tels que la struvite, la cystine, la dihydroxy-2,8-adénine permet le diagnostic de pathologies spécifiques qui exposent à une altération progressive de la fonction rénale lorsqu'elles ne sont pas traitées précocement par des mesures adaptées. La présence de cristaux médicamenteux peut expliquer l'origine d'une insuffisance rénale aiguë développée sous traitement.Au cours du suivi des patients souffrant de lithiase, la détermination de la cristallurie sur des prélèvements sériés est d'un grand intérêt pour la prévention du risque de récidive de calculscar elle reflète l'activité de la maladie lithiasique et sa réponse aux mesures diététiques et thérapeutiques. Elle peut donc bénéficier à la plupart des patients lithiasiques. Elle se doit d’être réalisée chez tout patient souffrant d'une forme héréditaire sévère de lithiase telle que cystinurie, hyperoxalurie primaire ou dihydroxyadéninurie pour en optimiser la prise en charge thérapeutique, la détermination du volume cristallin global dans ces pathologies cristallines sévères permettant d'adapter le traitement médical, d’évaluer l'efficacité des mesures thérapeutiques proposées et de modifier celles-ci en fonction des résultats obtenus.

Published
2016
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2. Rapid and reliable diagnosis of Wilson disease using X‐ray fluorescence

Author

Jean-Charles Duclos-Vallée, Françoise Schmitt, Catherine Guettier, Slavka Kascakova, Tuan Huy Nguyen, Andrea Somogyi, Cameron M. Kewish, Christophe Sandt, Didier Samuel, Joël Poupon, Emmanuel Jacquemin, Dominique Bazin, Bruno Francou, François Le Naour, Stéphan Rouzière, Rodolphe Sobesky, Anne Dubart-Kupperschmitt, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hepatinov (DHU), Université Paris-Sud - Paris 11 (UP11)-Centre Hépato-Biliaire Paul Brousse, Ligne de lumière NANOSCOPIUM, Synchrotron SOLEIL, Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence pour la maladie de Wilson (CNR wilson), CNR Wilson, Service de Neurologie, Hôpital Lariboisière, Laboratoire de toxicologie biologique [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ligne de lumière SMIS, Service de Génétique Moléculaire Pharmacogénétique et Hormonologie, Hôpital Bicêtre, Service d’Hépatologie et de Transplantation Hépatique Pédiatriques, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Service d’Anatomo-Pathologie [AP-HP], Hôpital Paul Brousse, d'Eggis, Gilles, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Pathology, medicine.medical_specialty, Cirrhosis, diagnosis, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, chemistry.chemical_element, X-ray fluorescence, Zinc, X‐ray fluorescence spectroscopy, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Cholestasis, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Wilson disease, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Elemental composition, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Original Articles, Long evans, medicine.disease, Copper, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Paraffin embedded, 3. Good health, X-ray fluorescence spectroscopy, 030104 developmental biology, chemistry, copper, Original Article, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 030217 neurology & neurosurgery
Abstract

International audience; Wilson's disease (WD) is a rare autosomal recessive disease due to mutations of the gene encoding the copper-transporter ATP7B. The diagnosis is hampered by the variability of symptoms induced by copper accumulation , the inconstancy of the pathognomonic signs and the absence of a reliable diagnostic test. We investigated the diagnostic potential of X-ray fluorescence (XRF) that allows quantitative analysis of multiple elements. Studies were performed on animal models using Wistar rats (n = 10) and Long Evans Cinnamon (LEC) rats (n = 11), and on human samples including normal livers (n = 10), alcohol cirrhosis (n = 8), haemo-chromatosis (n = 10), cholestasis (n = 6) and WD (n = 22). XRF experiments were first performed using synchrotron radiation to address the elemental composition at the cellular level. High-resolution mapping of tissue sections allowed measurement of the intensity and the distribution of copper, iron and zinc while preserving the morphology. Investigations were further conducted using a laboratory X-ray source for irradiating whole pieces of tissue. The sensitivity of XRF was highlighted by the discrimination of LEC rats from wild type even under a regimen using copper deficient food. XRF on whole formalin-fixed paraffin embedded needle biopsies allowed profiling of the elements in a few minutes. The intensity of copper related to iron and zinc significantly discriminated WD from other genetic or chronic liver diseases with 97.6% specificity and 100% sensitivity. This study established a definite diagnosis of Wilson's disease based on XRF. This rapid and versatile method can be easily implemented in a clinical setting.

Published
2016
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3. Effects of a Single Escape Mutation on T Cell and HIV-1 Co-adaptation

Author

Masafumi Takiguchi, Mamoru Fujiwara, Christian Schönbach, Tomohiro Akahoshi, George F. Gao, Victor Appay, Nozomi Kuse, Hiroyuki Gatanaga, Shinichi Oka, Yi Shi, Xiaoming Sun, Center for AIDS Research, Kumamoto University, Research Network of Immunity and Health (RNIH), Chinese Academy of Sciences [Beijing] (CAS), AIDS Clinical Center, National Center for Global Health and Medicine [Japan] (NCGM), School of Science and Technology [Kazakhstan], Nazarbayev University [Kazakhstan], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology, International Research Center of Medical Sciences (IRCMS), and d'Eggis, Gilles

Subjects
0301 basic medicine, Models, Molecular, [SDV.IMM] Life Sciences [q-bio]/Immunology, Protein Conformation, T cell, T-Lymphocytes, Mutant, Population, Receptors, Antigen, T-Cell, Human leukocyte antigen, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Epitope, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, education, lcsh:QH301-705.5, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Genetics, Mutation, education.field_of_study, HLA-A Antigens, T-cell receptor, Water, Adaptation, Physiological, 3. Good health, Clone Cells, 030104 developmental biology, medicine.anatomical_structure, lcsh:Biology (General), HIV-1, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Peptides, CD8, Protein Binding, T-Lymphocytes, Cytotoxic
Abstract

International audience; The mechanistic basis for the progressive accumulation of Y135F Nef mutant viruses in the HIV-1-infected population remains poorly understood. Y135F viruses carry the 2F mutation within RW8 and RF10, which are two HLA-A∗24:02-restricted superimposed Nef epitopes recognized by distinct and adaptable CD8+ T cell responses. We combined comprehensive analysis of the T cell receptor repertoire and cross-reactive potential of wild-type or 2F RW8- and RF10-specific CD8+ T cells with peptide-MHC complex stability and crystal structure studies. We find that, by affecting direct and water-mediated hydrogen bond networks within the peptide-MHC complex, the 2F mutation reduces both TCR and HLA binding. This suggests an advantage underlying the evolution of the 2F variant with decreased CD8+ T cell efficacy. Our study provides a refined understanding of HIV-1 and CD8+ T cell co-adaptation at the population level.

Published
2016
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4. Hippocampal volume predicts antidepressant efficacy in depressed patients without incomplete hippocampal inversion

Author

Bruno Falissard, Denis Ducreux, Emmanuelle Corruble, Ghaidaa Nasser, Romain Colle, Claire Cury, Eric Deflesselle, Olivier Colliot, Marie Chupin, Patrick Hardy, d'Eggis, Gilles, Santé mentale et santé publique (SMSP - U1178), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de psychiatrie [Le Kremlin-Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Algorithms, models and methods for images and signals of the human brain (ARAMIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Santé mentale et santé publique ( SMSP - U1178 ), Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ), Algorithms, models and methods for images and signals of the human brain ( ARAMIS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Inria de Paris, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute ( ICM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Imagerie par Résonance Magnétique Médicale et Multi-Modalités ( IR4M ), Université Paris-Sud - Paris 11 ( UP11 ) -Hôpital Bicêtre-Centre National de la Recherche Scientifique ( CNRS ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Sud - Paris 11 (UP11), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Inria de Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Inria de Paris

Subjects
Male, [ SDV.MHEP.PSM ] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, [SDV.MHEP.PSM] Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Antidepressant, Hippocampus, lcsh:RC346-429, 0302 clinical medicine, Image Processing, Computer-Assisted, Hippocampus (mythology), Prospective Studies, Young adult, Major depressive episode, Prospective cohort study, Response, Middle Aged, Magnetic Resonance Imaging, Antidepressive Agents, Neurology, Predictive value of tests, Cardiology, lcsh:R858-859.7, Major depressive disorder, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, medicine.symptom, Psychology, Adult, medicine.medical_specialty, Adolescent, Major Depressive Disorder, Remission, Cognitive Neuroscience, Context (language use), IHI, Incomplete Hippocampal Inversion, lcsh:Computer applications to medicine. Medical informatics, Article, 03 medical and health sciences, Young Adult, Predictive Value of Tests, Internal medicine, medicine, Humans, Incomplete Hippocampal Inversion, Radiology, Nuclear Medicine and imaging, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Psychiatry, lcsh:Neurology. Diseases of the nervous system, Aged, Psychiatric Status Rating Scales, Depressive Disorder, Major, medicine.disease, MDD, Major Depressive Disorder, Hippocampal volume, 030227 psychiatry, ROC Curve, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health, Case-Control Studies, Neurology (clinical), HV, hippocampal volume, MDE, Major Depressive Episode, 030217 neurology & neurosurgery
Abstract

Background Incomplete hippocampal inversion (IHI), also called malrotation, is a frequent atypical anatomical pattern of the hippocampus. Because of the crucial implication of the hippocampus in Major Depressive Disorder (MDD) and the neurodevelopmental hypothesis of MDD, we aimed to assess the prevalence of IHI in patients with MDD, the link of IHI with hippocampal volume (HV) and the impact of IHI on the predictive value of HV for response and remission after antidepressant treatment. Methods IHI (right and left, partial and total and IHI scores) and HV were assessed in 60 patients with a current Major Depressive Episode (MDE) in a context of MDD and 60 matched controls. Patients were prospectively assessed at baseline and after one, three and six months of antidepressant treatment for response and remission. Results The prevalence of IHI did not significantly differ between MDD patients (right = 23.3%; left = 38.3%) and controls (right = 16.7%; left = 33.3%). IHI was not significantly associated with MDD clinical characteristics. IHI alone did not predict response and remission after antidepressant treatment. However, an interaction between left HV and left IHI predicted six-month response (p = 0.04), HDRS score decrease (p = 0.02) and both three-month (p = 0.04) and six-month (p = 0.03) remission. A case-control design in 30 matched patients with or without left IHI confirmed that interaction. In patients without left IHI, left HV at baseline were smaller in six-month non-remitters as compared to remitters (2.2(± 0.43) cm3 vs 2.97(± 0.5) cm3 p = 0.02), and in six-month non-responders as compared to responders (2.18(± 0.42) cm3 vs 2.86(± 0.54) cm3, p = 0.03). In patients with left IHI, no association was found between left HV at baseline and antidepressant response and remission. Conclusion IHI is not more frequent in MDD patients than in controls, is not associated with HV, but is a confounder that decreases the predictive value of hippocampal volume to predict response or remission after antidepressant treatment. IHI should be systematically assessed in future research studies assessing hippocampal volume in MDD., Highlights • Incomplete hippocampal inversion (IHI) is not significantly more frequent in MDD than in controls. • IHI is not significantly associated with MDD clinical characteristics. • Hippocampal volume predicts antidepressant efficacy in MDD patients without IHI. • Hippocampal volume does not predict antidepressant efficacy in patients with IHI.

Published
2016
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5. Novel CXCL13 transgenic mouse: inflammation drives pathogenic effect of CXCL13 in experimental myasthenia gravis

Author

Weiss, Julia Miriam, Robinet, Marieke, Aricha, Revital, Cufi, Perrine, Villeret, Bérengère, Lantner, Frida, Shachar, Idit, Fuchs, Sara, Souroujon, Miriam C, Berrih-Aknin, Sonia, Le Panse, Rozen, Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Weizmann Institute of Science [Rehovot, Israël], Open University of Israël, Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Immunology, The Weizmann Institute, and d'Eggis, Gilles

Subjects
0301 basic medicine, Male, Immunoenzyme Techniques, Mice, 0302 clinical medicine, thymus, Cells, Cultured, CXCL13-CXCR5, B-Lymphocytes, Reverse Transcriptase Polymerase Chain Reaction, autoimmunity, Research Paper: Immunology, Flow Cytometry, 3. Good health, Lymphatic system, Oncology, Immunology and Microbiology Section, Female, medicine.symptom, Genetically modified mouse, [SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Inflammation, Mice, Transgenic, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Real-Time Polymerase Chain Reaction, 03 medical and health sciences, medicine, [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Humans, RNA, Messenger, CXCL13, Immune response, B cells, chemokine, Autoantibody, Immunity, Germinal center, Epithelial Cells, medicine.disease, Germinal Center, Chemokine CXCL13, Myasthenia gravis, Myasthenia Gravis, Autoimmune, Experimental, Keratin 5, Mice, Inbred C57BL, 030104 developmental biology, Immunology, Thymus Hyperplasia, 030217 neurology & neurosurgery
Abstract

International audience; Abnormal overexpression of CXCL13 is observed in many inflamed tissues and in particular in autoimmune diseases. Myasthenia gravis (MG) is a neuromuscular disease mainly mediated by anti-acetylcholine receptor autoantibodies. Thymic hyperplasia characterized by ectopic germinal centers (GCs) is a common feature in MG and is correlated with high levels of anti-AChR antibodies. We previously showed that the B-cell chemoattractant, CXCL13 is overexpressed by thymic epithelial cells in MG patients. We hypothesized that abnormal CXCL13 expression by the thymic epithelium triggered B-cell recruitment in MG. We therefore created a novel transgenic (Tg) mouse with a keratin 5 driven CXCL13 expression. The thymus of Tg mice overexpressed CXCL13 but did not trigger B-cell recruitment. However, in inflammatory conditions, induced by Poly(I:C), B cells strongly migrated to the thymus. Tg mice were also more susceptible to experimental autoimmune MG (EAMG) with stronger clinical signs, higher titers of anti-AChR antibodies, increased thymic B cells, and the development of germinal center-like structures. Consequently, this mouse model finally mimics the thymic pathology observed in human MG. Our data also demonstrated that inflammation is mandatory to reveal CXCL13 ability to recruit B cells and to induce tertiary lymphoid organ development.

Published
2016
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6. Optimization of brain PET imaging for a multicentre trial: the French CATI experience

Author

Sullivan Marie, Jean-Baptiste Martini, Mamadou Hassimiou Diallo, Marie-Odile Habert, Aurélie Kas, Hugo Bertin, Regine Trebossen, Moana Reynal, Laboratoire d'Imagerie Biomédicale (LIB), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre pour l'Acquisition et le Traitement des Images (CATI), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and d'Eggis, Gilles

Subjects
medicine.medical_specialty, PET/CT, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, Biomedical Engineering, Imaging phantom, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Radiology, Nuclear Medicine and imaging, Medical physics, Instrumentation, Original Research, PET-CT, Radiation, business.industry, Multicentre trials, Pet imaging, Quality assurance, Standardization, Large cohort, Neurology, Cohort, Test protocol, business, 030217 neurology & neurosurgery
Abstract

International audience; BackgroundCATI is a French initiative launched in 2010 to handle the neuroimaging of a large cohort of subjects recruited for an Alzheimer’s research program called MEMENTO. This paper presents our test protocol and results obtained for the 22 PET centres (overall 13 different scanners) involved in the MEMENTO cohort. We determined acquisition parameters using phantom experiments prior to patient studies, with the aim of optimizing PET quantitative values to the highest possible per site, while reducing, if possible, variability across centres.MethodsJaszczak’s and 3D-Hoffman’s phantom measurements were used to assess image spatial resolution (ISR), recovery coefficients (RC) in hot and cold spheres, and signal-to-noise ratio (SNR). For each centre, the optimal reconstruction parameters were chosen as those maximizing ISR and RC without a noticeable decrease in SNR. Point-spread-function (PSF) modelling reconstructions were discarded. The three figures of merit extracted from the images reconstructed with optimized parameters and routine schemes were compared, as were volumes of interest ratios extracted from Hoffman acquisitions. The net effect of the 3D-OSEM reconstruction parameter optimization was investigated on a subset of 18 scanners without PSF modelling reconstruction.ResultsCompared to the routine parameters of the 22 PET centres, average RC in the two smallest hot and cold spheres and average ISR remained stable or were improved with the optimized reconstruction, at the expense of slight SNR degradation, while the dispersion of values was reduced.For the subset of scanners without PSF modelling, the mean RC of the smallest hot sphere obtained with the optimized reconstruction was significantly higher than with routine reconstruction. The putamen and caudate-to-white matter ratios measured on 3D-Hoffman acquisitions of all centres were also significantly improved by the optimization, while the variance was reduced.ConclusionsThis study provides guidelines for optimizing quantitative results for multicentric PET neuroimaging trials.

Published
2015
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7. p53 downregulates the Fanconi anaemia DNA repair pathway

Author

Vincent Lejour, Sara Jaber, Eléonore Toufektchan, Boris Bardot, Franck Toledo, d'Eggis, Gilles, Dynamique de l'information génétique : bases fondamentales et cancer (DIG CANCER), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), and Université Paris sciences et lettres (PSL)

Subjects
0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, DNA Repair, DNA repair, Molecular biology, Science, General Physics and Astronomy, Down-Regulation, E2F4 Transcription Factor, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Transcriptome, 03 medical and health sciences, chemistry.chemical_compound, Mice, Germline mutation, hemic and lymphatic diseases, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, Cells, Cultured, Multidisciplinary, Fanconi Anemia Complementation Group D2 Protein, General Chemistry, DNA Repair Pathway, medicine.disease, 3. Good health, Telomere, Biological sciences, 030104 developmental biology, Fanconi Anemia, chemistry, Cancer research, NIH 3T3 Cells, Tumor Suppressor Protein p53, Dyskeratosis congenita, DNA
Abstract

Germline mutations affecting telomere maintenance or DNA repair may, respectively, cause dyskeratosis congenita or Fanconi anaemia, two clinically related bone marrow failure syndromes. Mice expressing p53Δ31, a mutant p53 lacking the C terminus, model dyskeratosis congenita. Accordingly, the increased p53 activity in p53Δ31/Δ31 fibroblasts correlated with a decreased expression of 4 genes implicated in telomere syndromes. Here we show that these cells exhibit decreased mRNA levels for additional genes contributing to telomere metabolism, but also, surprisingly, for 12 genes mutated in Fanconi anaemia. Furthermore, p53Δ31/Δ31 fibroblasts exhibit a reduced capacity to repair DNA interstrand crosslinks, a typical feature of Fanconi anaemia cells. Importantly, the p53-dependent downregulation of Fanc genes is largely conserved in human cells. Defective DNA repair is known to activate p53, but our results indicate that, conversely, an increased p53 activity may attenuate the Fanconi anaemia DNA repair pathway, defining a positive regulatory feedback loop., P53 is regarded as the guardian of the genome, however it is known that mice with increased p53 activity display characteristics of dyskeratosis congenita. Here the authors show that increased p53 activity leads to the repression of telomere maintenance and DNA repair genes.

Published
2015
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8. SPIRONOLACTONE FOR NONRESOLVING CENTRAL SEROUS CHORIORETINOPATHY: A RANDOMIZED CONTROLLED CROSSOVER STUDY

Author

Benedicte Couraud, Rui Batista, Nicolette Farman, Alain Gaudric, Elodie Bousquet, Talal Beydoun, Francine Behar-Cohen, Pierre-Raphaël Rothschild, Marie-Laure Brandely, Ciara Bergin, Min Zhao, François Chast, Immunologie et Cancérologie Intégratives ( CRC - Inserm U1138 ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Departement d'ophthalmologie, Assistance publique - Hôpitaux de Paris (AP-HP), Department of Ophthalmology, Université de Lausanne ( UNIL ), Department of Pharmacy, Departement d'Ophthalmologie, Hôpital Lariboisière, Immunologie et Cancérologie Intégratives (CRC - Inserm U1138), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Lausanne (UNIL), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), d'Eggis, Gilles, Université de Lausanne = University of Lausanne (UNIL), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)

Subjects
Male, choroidal thickness, Visual acuity, genetic structures, Visual Acuity, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Original Study, Prospective Studies, Prospective cohort study, Mineralocorticoid Receptor Antagonists, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Cross-Over Studies, treatment, Subretinal Fluid, General Medicine, Middle Aged, 3. Good health, Serous fluid, spironolactone, Adult, Aged, Central Serous Chorioretinopathy/drug therapy, Central Serous Chorioretinopathy/metabolism, Double-Blind Method, Female, Humans, Mineralocorticoid Receptor Antagonists/therapeutic use, Spironolactone/therapeutic use, Subretinal Fluid/metabolism, Tomography, Optical Coherence, Young Adult, medicine.symptom, medicine.medical_specialty, choroidal vessels, Placebo, Serous Retinal Detachment, 03 medical and health sciences, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Ophthalmology, medicine, central serous chorioretinopathy, mineralocorticoid receptor, business.industry, Crossover study, eye diseases, Surgery, chemistry, 030221 ophthalmology & optometry, Spironolactone, sense organs, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

This study is a randomized controlled crossover study evaluating the effect of spironolactone, a mineralocorticoid receptor antagonist for the treatment of nonresolving central serous chorioretinopathy. Spironolactone significantly reduced both serous retinal detachment and choroidal thickness as compared with placebo. Larger clinical trials are needed to confirm these promising results., Purpose: To evaluate the effect of spironolactone, a mineralocorticoid receptor antagonist, for nonresolving central serous chorioretinopathy. Methods: This is a prospective, randomized, double-blinded, placebo-controlled crossover study. Sixteen eyes of 16 patients with central serous chorioretinopathy and persistent subretinal fluid (SRF) for at least 3 months were enrolled. Patients were randomized to receive either spironolactone 50 mg or placebo once a day for 30 days, followed by a washout period of 1 week and then crossed over to either placebo or spironolactone for another 30 days. The primary outcome measure was the changes from baseline in SRF thickness at the apex of the serous retinal detachment. Secondary outcomes included subfoveal choroidal thickness and the ETDRS best-corrected visual acuity. Results: The mean duration of central serous chorioretinopathy before enrollment in study eyes was 10 ± 16.9 months. Crossover data analysis showed a statistically significant reduction in SRF in spironolactone treated eyes as compared with the same eyes under placebo (P = 0.04). Secondary analysis on the first period (Day 0–Day 30) showed a significant reduction in subfoveal choroidal thickness in treated eyes as compared with placebo (P = 0.02). No significant changes were observed in the best-corrected visual acuity. There were no complications related to treatment observed. Conclusion: In eyes with persistent SRF due to central serous chorioretinopathy, spironolactone significantly reduced both the SRF and the subfoveal choroidal thickness as compared with placebo.

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