80 results on '"Derambure, P."'
Search Results
2. Assessment of parental mosaicism rates in neurodevelopmental disorders caused by apparent de novo pathogenic variants using deep sequencing
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Lecoquierre, François, Cassinari, Kévin, Drouot, Nathalie, May, Angèle, Fourneaux, Steeve, Charbonnier, Francoise, Derambure, Celine, Coutant, Sophie, Saugier-Veber, Pascale, Hoischen, Alexander, Charbonnier, Camille, and Nicolas, Gaël
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- 2024
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3. Glucocorticoids paradoxically promote steroid resistance in B cell acute lymphoblastic leukemia through CXCR4/PLC signaling
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Souleymane Abdoul-Azize, Rihab Hami, Gaetan Riou, Céline Derambure, Camille Charbonnier, Jean-Pierre Vannier, Monica L. Guzman, Pascale Schneider, and Olivier Boyer
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Science - Abstract
Abstract Glucocorticoid (GC) resistance in childhood relapsed B-cell acute lymphoblastic leukemia (B-ALL) represents an important challenge. Despite decades of clinical use, the mechanisms underlying resistance remain poorly understood. Here, we report that in B-ALL, GC paradoxically induce their own resistance by activating a phospholipase C (PLC)-mediated cell survival pathway through the chemokine receptor, CXCR4. We identify PLC as aberrantly activated in GC-resistant B-ALL and its inhibition is able to induce cell death by compromising several transcriptional programs. Mechanistically, dexamethasone (Dex) provokes CXCR4 signaling, resulting in the activation of PLC-dependent Ca2+ and protein kinase C signaling pathways, which curtail anticancer activity. Treatment with a CXCR4 antagonist or a PLC inhibitor improves survival of Dex-treated NSG mice in vivo. CXCR4/PLC axis inhibition significantly reverses Dex resistance in B-ALL cell lines (in vitro and in vivo) and cells from Dex resistant ALL patients. Our study identifies how activation of the PLC signalosome in B-ALL by Dex limits the upfront efficacy of this chemotherapeutic agent.
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- 2024
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4. Genome-wide expression analysis in a Fabry disease human podocyte cell line
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Sarah Snanoudj, Céline Derambure, Cheng Zhang, Nguyen Thi Hai Yen, Céline Lesueur, Sophie Coutant, Lénaïg Abily-Donval, Stéphane Marret, Hong Yang, Adil Mardinoglu, Soumeya Bekri, and Abdellah Tebani
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Fabry disease ,RNAseq ,Transcriptomics ,Metabolic modeling ,Systems biology ,Podocyte ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Fabry disease (FD) is an X-linked lysosomal disease caused by an enzyme deficiency of alpha-galactosidase A (α-gal A). This deficiency leads to the accumulation of glycosphingolipids in lysosomes, resulting in a range of clinical symptoms. The complex pathogenesis of FD involves lysosomal dysfunction, altered autophagy, and mitochondrial abnormalities. Omics sciences, particularly transcriptomic analysis, comprehensively understand molecular mechanisms underlying diseases. This study focuses on genome-wide expression analysis in an FD human podocyte model to gain insights into the underlying mechanisms of podocyte dysfunction. Human control and GLA-edited podocytes were used. Gene expression data was generated using RNA-seq analysis, and differentially expressed genes were identified using DESeq2. Principal component analysis and Spearman correlation have explored gene expression trends. Functional enrichment and Reporter metabolite analyses were conducted to identify significantly affected metabolites and metabolic pathways. Differential expression analysis revealed 247 genes with altered expression levels in GLA-edited podocytes compared to control podocytes. Among these genes, 136 were underexpressed, and 111 were overexpressed in GLA-edited cells. Functional analysis of differentially expressed genes showed their involvement in various pathways related to oxidative stress, inflammation, fatty acid metabolism, collagen and extracellular matrix homeostasis, kidney injury, apoptosis, autophagy, and cellular stress response. The study provides insights into molecular mechanisms underlying Fabry podocyte dysfunction. Integrating transcriptomics data with genome-scale metabolic modeling further unveiled metabolic alterations in GLA-edited podocytes. This comprehensive approach contributes to a better understanding of Fabry disease and may lead to identifying new biomarkers and therapeutic targets for this rare lysosomal disorder.
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- 2024
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5. Assessment of parental mosaicism rates in neurodevelopmental disorders caused by apparent de novo pathogenic variants using deep sequencing
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François Lecoquierre, Kévin Cassinari, Nathalie Drouot, Angèle May, Steeve Fourneaux, Francoise Charbonnier, Celine Derambure, Sophie Coutant, Pascale Saugier-Veber, Alexander Hoischen, Camille Charbonnier, and Gaël Nicolas
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Medicine ,Science - Abstract
Abstract While de novo variants (DNV) are overall at low risk of recurrence in subsequent pregnancies, a subset is at high risk due to parental mosaicism. Accurately identifying cases of parental mosaicism is therefore important for genetic counseling in clinical care. Some studies have investigated the rate of parental mosaics, but most were either limited by the sensitivity of the techniques (i.e. exome or genome sequencing), or focused on specific types of disease such as epileptic syndromes. This study aimed to determine the proportion of parental mosaicism among the DNV causing neurodevelopmental disorders (NDDs) in a series not enriched in epilepsy syndromes. We collected 189 patients with NDD-associated DNV. We applied a smMIP enrichment method and sequenced parental blood DNA samples to an average depth of 7000x. Power simulation indicated that mosaicism with an allelic fraction of 0.5% would have been detected for 87% of positions with 90% power. We observed seven parental mosaic variants (3.7% of families), of which four (2.1% of families) had an allelic fraction of less than 1%. In total, our study identifies a relatively low proportion of parental mosaicism in NDD-associated DNVs and raises the question of a biological mechanism behind the higher rates of parental mosaicism detected in other studies, particularly those focusing on epileptic syndromes.
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- 2024
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6. Tri-axial rubidium and helium optically pumped magnetometers for on-scalp magnetoencephalography recording of interictal epileptiform discharges: a case study
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Odile Feys, Pierre Corvilain, Etienne Labyt, Mahdi Mahmoudzadeh, Laura Routier, Claudine Sculier, Niall Holmes, Matthew Brookes, Serge Goldman, Rudy Romain, Sergey Mitryukovskiy, Agustin Palacios-Laloy, Denis Schwartz, Nacim Betrouni, Philippe Derambure, Fabrice Wallois, Vincent Wens, and Xavier De Tiège
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magnetoencephalography ,optically pumped magnetometers ,on-scalp magnetoencephalography ,refractory epilepsy ,focal epilepsy ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Cryogenic magnetoencephalography (MEG) enhances the presurgical assessment of refractory focal epilepsy (RFE). Optically pumped magnetometers (OPMs) are cryogen-free sensors that enable on-scalp MEG recordings. Here, we investigate the application of tri-axial OPMs [87Rb (Rb-OPM) and 4He gas (He-OPM)] for the detection of interictal epileptiform discharges (IEDs). IEDs were recorded simultaneously with 4 tri-axial Rb- and 4 tri-axial He-OPMs in a child with RFE. IEDs were identified visually, isolated from magnetic background noise using independent component analysis (ICA) and were studied following their optimal magnetic field orientation thanks to virtual sensors. Most IEDs (>1,000) were detectable by both He- and Rb-OPM recordings. IEDs were isolated by ICA and the resulting magnetic field oriented mostly tangential to the scalp in Rb-OPMs and radial in He-OPMs. Likely due to differences in sensor locations, the IED amplitude was higher with Rb-OPMs. This case study shows comparable ability of Rb-OPMs and He-OPMs to detect IEDs and the substantial benefits of triaxial OPMs to detect IEDs from different sensor locations. Tri-axial OPMs allow to maximize spatial brain sampling for IEDs detection with a limited number of sensors.
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- 2023
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7. Prenatal Alcohol Exposure Impairs the Placenta–Cortex Transcriptomic Signature, Leading to Dysregulation of Angiogenic Pathways
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Camille Sautreuil, Maryline Lecointre, Céline Derambure, Carole Brasse-Lagnel, Philippe Leroux, Annie Laquerrière, Gaël Nicolas, Sophie Gil, Daniel D. Savage, Stéphane Marret, Florent Marguet, Anthony Falluel-Morel, and Bruno J. Gonzalez
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FASD ,neuroplacentology ,neurovascular ,neurodevelopment ,diagnosis ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Although alcohol consumption during pregnancy is a major cause of behavioral and learning disabilities, most FASD infants are late- or even misdiagnosed due to clinician’s difficulties achieving early detection of alcohol-induced neurodevelopmental impairments. Neuroplacentology has emerged as a new field of research focusing on the role of the placenta in fetal brain development. Several studies have reported that prenatal alcohol exposure (PAE) dysregulates a functional placenta–cortex axis, which is involved in the control of angiogenesis and leads to neurovascular-related defects. However, these studies were focused on PlGF, a pro-angiogenic factor. The aim of the present study is to provide the first transcriptomic “placenta–cortex” signature of the effects of PAE on fetal angiogenesis. Whole mouse genome microarrays of paired placentas and cortices were performed to establish the transcriptomic inter-organ “placenta–cortex” signature in control and PAE groups at gestational day 20. Genespring comparison of the control and PAE signatures revealed that 895 and 1501 genes were only detected in one of two placenta–cortex expression profiles, respectively. Gene ontology analysis indicated that 107 of these genes were associated with vascular development, and String protein–protein interaction analysis showed that they were associated with three functional clusters. PANTHER functional classification analysis indicated that “intercellular communication” was a significantly enriched biological process, and 27 genes were encoded for neuroactive ligand/receptors interactors. Protein validation experiments involving Western blot for one ligand–receptor couple (Agt/AGTR1/2) confirmed the transcriptomic data, and Pearson statistical analysis of paired placentas and fetal cortices revealed a negative correlation between placental Atg and cortical AGTR1, which was significantly impacted by PAE. In humans, a comparison of a 38WG control placenta with a 36WG alcohol-exposed placenta revealed low Agt immunolabeling in the syncytiotrophoblast layer of the alcohol case. In conclusion, this study establishes the first transcriptomic placenta–cortex signature of a developing mouse. The data show that PAE markedly unbalances this inter-organ signature; in particular, several ligands and/or receptors involved in the control of angiogenesis. These data support that PAE modifies the existing communication between the two organs and opens new research avenues regarding the impact of placental dysfunction on the neurovascular development of fetuses. Such a signature would present a clinical value for early diagnosis of brain defects in FASD.
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- 2023
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8. Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants
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Raphaël Leman, Hélène Tubeuf, Sabine Raad, Isabelle Tournier, Céline Derambure, Raphaël Lanos, Pascaline Gaildrat, Gaia Castelain, Julie Hauchard, Audrey Killian, Stéphanie Baert-Desurmont, Angelina Legros, Nicolas Goardon, Céline Quesnelle, Agathe Ricou, Laurent Castera, Dominique Vaur, Gérald Le Gac, Chandran Ka, Yann Fichou, Françoise Bonnet-Dorion, Nicolas Sevenet, Marine Guillaud-Bataille, Nadia Boutry-Kryza, Inès Schultz, Virginie Caux-Moncoutier, Maria Rossing, Logan C. Walker, Amanda B. Spurdle, Claude Houdayer, Alexandra Martins, and Sophie Krieger
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Branch point ,Prediction ,RNA ,Benchmark ,HSF ,SVM-BPfinder ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Branch points (BPs) map within short motifs upstream of acceptor splice sites (3’ss) and are essential for splicing of pre-mature mRNA. Several BP-dedicated bioinformatics tools, including HSF, SVM-BPfinder, BPP, Branchpointer, LaBranchoR and RNABPS were developed during the last decade. Here, we evaluated their capability to detect the position of BPs, and also to predict the impact on splicing of variants occurring upstream of 3’ss. Results We used a large set of constitutive and alternative human 3’ss collected from Ensembl (n = 264,787 3’ss) and from in-house RNAseq experiments (n = 51,986 3’ss). We also gathered an unprecedented collection of functional splicing data for 120 variants (62 unpublished) occurring in BP areas of disease-causing genes. Branchpointer showed the best performance to detect the relevant BPs upstream of constitutive and alternative 3’ss (99.48 and 65.84% accuracies, respectively). For variants occurring in a BP area, BPP emerged as having the best performance to predict effects on mRNA splicing, with an accuracy of 89.17%. Conclusions Our investigations revealed that Branchpointer was optimal to detect BPs upstream of 3’ss, and that BPP was most relevant to predict splicing alteration due to variants in the BP area.
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- 2020
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9. Bacterial Aspiration Pneumonia in Generalized Convulsive Status Epilepticus: Incidence, Associated Factors and Outcome
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Romain Tortuyaux, Frédéric Wallet, Philippe Derambure, and Saad Nseir
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status epilepticus ,intensive care unit ,bacterial aspiration pneumonia ,3-month outcome ,Medicine - Abstract
Suspicion of bacterial aspiration pneumonia (BAP) is frequent during generalized convulsive status epilepticus (GCSE). Early identification of BAP is required in order to avoid useless antibiotic therapy. In this retrospective monocentric study, we aimed to determine the incidence of aspiration syndrome and BAP in GCSE requiring mechanical ventilation (MV) and factors associated with the occurrence of BAP. Patients were older than 18 years and had GCSE requiring MV. To distinguish BAP from pneumonitis, tracheal aspirate and quantitative microbiological criterion were used. Out of 226 consecutive patients, 103 patients (46%) had an aspiration syndrome, including 54 (52%) with a BAP. Staphylococcus aureus represented 33% of bacterial strains. No relevant baseline characteristics differed, including serum levels of CRP, PCT, and albumin. The median duration of treatment for BAP was 7 days (5–7). Patients with BAP did not have a longer duration of MV (p = 0.18) and ICU stay (p = 0.18) than those with pneumonitis. At 3 months, 24 patients (44%) with BAP and 10 (27%) with pneumonitis had a poor functional outcome (p = 0.06). In conclusion, among patients with GCSE, half of the patients had an aspiration syndrome and one-quarter suffered from BAP. Clinical characteristics and biomarkers were not useful for differentiating BAP from pneumonitis. These results highlight the need for a method to rapidly differentiate BAP from pneumonitis, such as polymerase-chain-reaction-based techniques.
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- 2022
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10. Performance Analysis of Optically Pumped 4He Magnetometers vs. Conventional SQUIDs: From Adult to Infant Head Models
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Saeed Zahran, Mahdi Mahmoudzadeh, Fabrice Wallois, Nacim Betrouni, Philippe Derambure, Matthieu Le Prado, Agustin Palacios-Laloy, and Etienne Labyt
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optically pumped 4He magnetometer ,SQUID ,forward and inverse models ,Chemical technology ,TP1-1185 - Abstract
Optically pumped magnetometers (OPMs) are new, room-temperature alternatives to superconducting quantum interference devices (SQUIDs) for measuring the brain’s magnetic fields. The most used OPM in MagnetoEncephaloGraphy (MEG) are based on alkali atoms operating in the spin-exchange relaxation-free (SERF) regime. These sensors do not require cooling but have to be heated. Another kind of OPM, based on the parametric resonance of 4He atoms are operated at room temperature, suppressing the heat dissipation issue. They also have an advantageous bandwidth and dynamic range more suitable for MEG recordings. We quantitatively assessed the improvement (relative to a SQUID magnetometers array) in recording the magnetic field with a wearable 4He OPM-MEG system through data simulations. The OPM array and magnetoencephalography forward models were based on anatomical MRI data from an adult, a nine-year-old child, and 10 infants aged between one month and two years. Our simulations showed that a 4He OPMs array offers markedly better spatial specificity than a SQUID magnetometers array in various key performance areas (e.g., signal power, information content, and spatial resolution). Our results are also discussed regarding previous simulation results obtained for alkali OPM.
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- 2022
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11. Chest physiotherapy enhances detection of Pseudomonas aeruginosa in nonexpectorating children with cystic fibrosis
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Christophe Marguet, Véronique Houdouin, Isabelle Pin, Philippe Reix, Frédéric Huet, Marie Mittaine, Sophie Ramel, Nathalie Wizla-Derambure, Michel Abely, Marie-Laure Dalphin, Michael Fayon, Tiphaine Bihouée, Muriel Le Bourgeois, Eric Deneuville, Harriet Corvol, Muriel Laurans, Laure Couderc, Evelyne Leroux, and Ludovic Lémée
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Medicine - Abstract
Lung damage in cystic fibrosis (CF) is strongly associated with lower airway infections. Early treatment of Pseudomonas aeruginosa is recommended. Pathogen detection requires sampling of lower airway secretions, which remains a challenge in nonexpectorating patients. Our hypothesis was that chest physiotherapy would improve the quality of airway secretion samples and increase the rates of pathogens detected in nonexpectorating patients. This prospective multicentre study compared three successive methods for sampling airway secretions applied through the same session: 1) an oropharyngeal swab (OP), 2) a chest physiotherapy session followed by a provoked cough to obtain sputum (CP-SP) and 3) a second oropharyngeal swab collected after chest physiotherapy (CP-OP). Haemophilus influenzae, Staphylococcus aureus and P. aeruginosa growth cultures were assessed. Accuracy tests and an equivalence test were performed to compare the three successive methods of collection. 300 nonexpectorating children with CF were included. P. aeruginosa was detected cumulatively in 56 (18.9%) children, and according to the different collection methods in 28 (9.8%), 37 (12.4%) and 44 (14.7%) children by using OP, CP-OP and CP-SP, respectively. Compared with OP, the increased detection rate was +22% for CP-OP (p=0.029) and +57% for CP-SP (p=0.003). CP-SP had the best positive predictive value (86.3%) and negative predictive value (96.0%) for P. aeruginosa compared with the overall detection. The results of this adequately powered study show differences in the rates of pathogens detected according to the sampling method used. Chest physiotherapy enhanced detection of P. aeruginosa in nonexpectorating children with CF.
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- 2021
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12. Hypoxia-Ischemia Induced Age-Dependent Gene Transcription Effects at Two Development Stages in the Neonate Mouse Brain
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Nicolas Dupré, Céline Derambure, Bérénice Le Dieu-Lugon, Michelle Hauchecorne, Yannick Detroussel, Bruno J. Gonzalez, Stéphane Marret, and Philippe Leroux
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brain-development ,cholesterol-biosynthesis ,encephalopathy ,hypoxia-ischemia ,inflammation ,mouse ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Human brain lesions in the perinatal period result in life-long neuro-disabilities impairing sensory-motor, cognitive, and behavior functions for years. Topographical aspects of brain lesions depend on gestational age at the time of insult in preterm or term infants and impaired subsequent steps of brain development and maturation. In mice, the Rice-Vannucci procedure of neonate hypoxia-ischemia (HI) was used at 5 days (P5) or P10, mimicking the development of 30 week-gestation fetus/preterm newborn, or full-term infant, respectively. Transcription response to HI was assessed at 3, 6, 12, and 24 h after insult, using micro-array technology. Statistical Pathway and Gene Ontology terms enrichments were investigated using DAVID®, Revigo® and Ingenuity Pathway Analysis (IPA®) to identify a core of transcription response to HI, age-specific regulations, and interactions with spontaneous development. Investigations were based on direction, amplitude, and duration of responses, basal expression, and annotation. Five major points deserve attention; (i) inductions exceeded repressions (60/40%) at both ages, (ii) only 20.3% (393/1938 records) were common to P5 and P10 mice, (iii) at P5, HI effects occurred early and decreased 24 h after insult whereas they were delayed at P10 and increased 24 h after insult, (iv) common responses at P5 and P10 involved inflammation, immunity, apoptosis, and angiogenesis. (v) age-specific effects occurred with higher statistical significance at P5 than at P10. Transient repression of 12 genes encoding cholesterol biosynthesis enzymes was transiently observed 12 h after HI at P5. Synaptogenesis appeared inhibited at P5 while induced at P10, showing reciprocal effects on glutamate receptors. Specific involvement of Il-1 (interleukin-1) implicated in the firing of inflammation was observed at P10. This study pointed out age-differences in HI responses kinetics, e.g., a long-lasting inflammatory response at P10 compared to P5. Whether the specific strong depression of cholesterol biosynthesis genes that could account for white matter-specific vulnerability at P5 or prevent delayed inflammation needs further investigation. Determination of putative involvement of Il-1 and the identification of upstream regulators involved in the delayed inflammation firing at P10 appears promising routes of research in the understandings of age-dependent vulnerabilities in the neonatal brain.
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- 2020
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13. CD11c+ B Cells Are Mainly Memory Cells, Precursors of Antibody Secreting Cells in Healthy Donors
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Marie-Laure Golinski, Mélanie Demeules, Céline Derambure, Gaetan Riou, Maud Maho-Vaillant, Olivier Boyer, Pascal Joly, and Sébastien Calbo
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human ,CD11c ,B cells ,microarray ,plasma cells ,pemphigus ,Immunologic diseases. Allergy ,RC581-607 - Abstract
CD11c+ B cells have been reported to be increased in autoimmune diseases, but they are detected in the blood of healthy individuals as well. We aimed to characterize CD11c+ B cells from healthy donors by flow cytometry, microarray analysis, and in vitro functional assays. Here, we report that CD11c+ B cells are a distinct subpopulation of B cells, enriched in the memory subpopulation even if their phenotype is heterogeneous, with overexpression of genes involved in B-cell activation and differentiation as well as in antigen presentation. Upon activation, CD11c+ B cells can differentiate into antibody-secreting cells, and CD11c could be upregulated in CD11c− B cells by B-cell receptor activation. Finally, we show that patients with pemphigus, an autoimmune disease mediated by B cells, have a decreased frequency of CD11c+ B cell after treatment, relative to baseline. Our findings show that CD11c+ B cells are mainly memory B cells prone to differentiate into antibody secreting cells that accumulate with age, independently of gender.
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- 2020
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14. Gene expression regulated by abatacept associated with methotrexate and correlation with disease activity in rheumatoid arthritis.
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Céline Derambure, Gaelle Dzangue-Tchoupou, Maria Antonietta D'Agostino, Thierry Lequerré, and Olivier Vittecoq
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Medicine ,Science - Abstract
ObjectivesAbatacept acts as a competitive inhibitor of the CD28/(CD80/86) costimulation signal required for T cell activation. Mechanisms of action of abatacept have not been fully investigated. The objective of this study was to provide detailed insight into the mode of action of Abatacept based on gene expression data.MethodsIn this ancillary study from the APPRAISE trial, we investigated the global molecular effects of Abatacept in whole blood samples collected prospectively in biologic naive rheumatoid arthritis patients (n = 19) at baseline and 6 months after the initiation of Abatacept therapy concomitant with methotrexate. Whole human genome microarrays (4x44K) were performed on both baseline and 6-month samples from responders and non-responders patients categorized according to EULAR criteria. T-test with Benjamini-Hochberg correction was performed to identify significant gene expression changes. Gene Ontology and Single Experiment Analysis tools allowed us to highlight specific biological mechanisms involved in methotrexate/Abatacept.ResultsIn methotrexate/Abatacept responders, 672 genes were significantly (q
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- 2020
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15. Assessment of branch point prediction tools to predict physiological branch points and their alteration by variants
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Leman, Raphaël, Tubeuf, Hélène, Raad, Sabine, Tournier, Isabelle, Derambure, Céline, Lanos, Raphaël, Gaildrat, Pascaline, Castelain, Gaia, Hauchard, Julie, Killian, Audrey, Baert-Desurmont, Stéphanie, Legros, Angelina, Goardon, Nicolas, Quesnelle, Céline, Ricou, Agathe, Castera, Laurent, Vaur, Dominique, Le Gac, Gérald, Ka, Chandran, Fichou, Yann, Bonnet-Dorion, Françoise, Sevenet, Nicolas, Guillaud-Bataille, Marine, Boutry-Kryza, Nadia, Schultz, Inès, Caux-Moncoutier, Virginie, Rossing, Maria, Walker, Logan C., Spurdle, Amanda B., Houdayer, Claude, Martins, Alexandra, and Krieger, Sophie
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- 2020
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16. Effect of Neuroprotective Magnesium Sulfate Treatment on Brain Transcription Response to Hypoxia Ischemia in Neonate Mice
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Bérénice Le Dieu-Lugon, Nicolas Dupré, Céline Derambure, François Janin, Bruno J. Gonzalez, Stéphane Marret, Arnaud Arabo, and Philippe Leroux
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neonate brain ,hypoxia–ischemia ,magnesium ,transcriptome ,neuroprotection ,preterm ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
MgSO4 is widely used in the prevention of preterm neurological disabilities but its modes of action remain poorly established. We used a co-hybridization approach using the transcriptome in 5-day old mice treated with a single dose of MgSO4 (600 mg/kg), and/or exposed to hypoxia-ischemia (HI). The transcription of hundreds of genes was altered in all the groups. MgSO4 mainly produced repressions culminating 6 h after injection. Bio-statistical analysis revealed the repression of synaptogenesis and axonal development. The putative targets of MgSO4 were Mnk1 and Frm1. A behavioral study of adults did not detect lasting effects of neonatal MgSO4 and precluded NMDA-receptor-mediated side effects. The effects of MgSO4 plus HI exceeded the sum of the effects of separate treatments. MgSO4 prior to HI reduced inflammation and the innate immune response probably as a result of cytokine inhibition (Ccl2, Ifng, interleukins). Conversely, MgSO4 had little effect on HI-induced transcription by RNA-polymerase II. De novo MgSO4-HI affected mitochondrial function through the repression of genes of oxidative phosphorylation and many NAD-dehydrogenases. It also likely reduced protein translation by the repression of many ribosomal proteins, essentially located in synapses. All these effects appeared under the putative regulatory MgSO4 induction of the mTORC2 Rictor coding gene. Lasting effects through Sirt1 and Frm1 could account for this epigenetic footprint.
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- 2021
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17. Pre-silencing of genes involved in the electron transport chain (ETC) pathway is associated with responsiveness to abatacept in rheumatoid arthritis
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C. Derambure, G. Dzangue-Tchoupou, C. Berard, N. Vergne, M. Hiron, M. A. D’Agostino, P. Musette, O. Vittecoq, and T. Lequerré
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Biomarkers ,Rheumatoid arthritis ,Abatacept ,Microarray ,Abatacept response ,Oxydative stress ,Diseases of the musculoskeletal system ,RC925-935 - Abstract
Abstract Background In the current context of personalized medicine, one of the major challenges in the management of rheumatoid arthritis (RA) is to identify biomarkers that predict drug responsiveness. From the European APPRAISE trial, our main objective was to identify a gene expression profile associated with responsiveness to abatacept (ABA) + methotrexate (MTX) and to understand the involvement of this signature in the pathophysiology of RA. Methods Whole human genome microarrays (4 × 44 K) were performed from a first subset of 36 patients with RA. Data validation by quantitative reverse-transcription (qRT)-PCR was performed from a second independent subset of 32 patients with RA. Gene Ontology and WikiPathways database allowed us to highlight the specific biological mechanisms involved in predicting response to ABA/MTX. Results From the first subset of 36 patients with RA, a combination including 87 transcripts allowed almost perfect separation between responders and non-responders to ABA/MTX. Next, the second subset of patients 32 with RA allowed validation by qRT-PCR of a minimal signature with only four genes. This latter signature categorized 81% of patients with RA with 75% sensitivity, 85% specificity and 85% negative predictive value. This combination showed a significant enrichment of genes involved in electron transport chain (ETC) pathways. Seven transcripts from ETC pathways (NDUFA6, NDUFA4, UQCRQ, ATP5J, COX7A2, COX7B, COX6A1) were significantly downregulated in responders versus non-responders to ABA/MTX. Moreover, dysregulation of these genes was independent of inflammation and was specific to ABA response. Conclusion Pre-silencing of ETC genes is associated with future response to ABA/MTX and might be a crucial key to susceptibility to ABA response.
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- 2017
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18. Functional connectivity disruptions correlate with cognitive phenotypes in Parkinson's disease
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M. Hassan, L. Chaton, P. Benquet, A. Delval, C. Leroy, L. Plomhause, A.J.H. Moonen, A.A. Duits, A.F.G. Leentjens, V. van Kranen-Mastenbroek, L. Defebvre, P. Derambure, F. Wendling, and K. Dujardin
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Parkinson's disease ,Cognitive deficits ,Dense electroencephalography ,Brain connectivity ,Network measures ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Cognitive deficits in Parkinson's disease are thought to be related to altered functional brain connectivity. To date, cognitive-related changes in Parkinson's disease have never been explored with dense-EEG with the aim of establishing a relationship between the degree of cognitive impairment, on the one hand, and alterations in the functional connectivity of brain networks, on the other hand. This study was aimed at identifying altered brain networks associated with cognitive phenotypes in Parkinson's disease using dense-EEG data recorded during rest with eyes closed. Three groups of Parkinson's disease patients (N = 124) with different cognitive phenotypes coming from a data-driven cluster analysis, were studied: G1) cognitively intact patients (63), G2) patients with mild cognitive deficits (46) and G3) patients with severe cognitive deficits (15). Functional brain networks were identified using a dense-EEG source connectivity method. Pairwise functional connectivity was computed for 68 brain regions in different EEG frequency bands. Network statistics were assessed at both global (network topology) and local (inter-regional connections) level. Results revealed progressive disruptions in functional connectivity between the three patient groups, typically in the alpha band. Differences between G1 and G2 (p
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- 2017
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19. Modifications of the Transcriptomic Profile of Autoreactive B Cells From Pemphigus Patients After Treatment With Rituximab or a Standard Corticosteroid Regimen
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Vivien Hébert, Marie Petit, Maud Maho-Vaillant, Marie-Laure Golinski, Gaëtan Riou, Céline Derambure, Olivier Boyer, Pascal Joly, and Sébastien Calbo
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pemphigus ,rituximab ,corticosteriods ,autoreactive B cell ,transcriptomic analysis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Pemphigus Vulgaris is an autoimmune disease of the skin and mucous membranes, which is due to the production of pathogenic autoantibodies targeting desmoglein (DSG) 1 and 3, which are adhesion proteins of the keratinocytes. Rituximab is an anti-CD20 mAb which induces a prolonged depletion of blood B cells. We recently showed that rituximab was more effective than a standard oral corticosteroid (CS) treatment, allowing 90% of patients to achieve complete remission (CR). Additionally, we showed that DSG-specific-B (DSG positive) cells were still detectable during the B cell recovery which follows the initial rituximab-induced B cell depletion, even in patients in CR. In order to characterize DSG positive B cells in patients in CR after rituximab or CS treatment relative to those detectable at baseline in patients with an active pemphigus, we studied the expression profile of 31 genes of interest related to inflammatory cytokines, TNF receptors and activation markers. Using quantitative Polymerase Chain Reaction performed on one cell with a microfluidic technique, we found that patients' autoreactive B cells collected at baseline had a significantly higher expression of genes encoding for IL-1β, IL-23p19, and IL-12p35 pro-inflammatory cytokines and the IRF5 transcription factor, than non-autoreactive B cells. Surprisingly, the gene expression profile of DSG positive B cells collected after rituximab treatment in patients in CR was close to that of DSG positive B cells at baseline in patients with active pemphigus, except for the IL-1β and the CD27 memory marker genes, which were under-expressed after rituximab compared to baseline. Conversely, we observed a decreased expression of genes encoding for IL-1β and IL-23p19 in patients treated with CS relative to baseline. This study showed that: (i) DSG positive autoreactive B cells have a different gene expression profile than non-autoreactive B cells; (ii) rituximab and CS have different effects on the genes' expression in autoreactive DSG positive B cells from pemphigus patients.
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- 2019
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20. New Insights into Plant Extracellular DNA. A Study in Soybean Root Extracellular Trap
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Marie Chambard, Carole Plasson, Céline Derambure, Sophie Coutant, Isabelle Tournier, Benjamin Lefranc, Jérôme Leprince, Marie-Christine Kiefer-Meyer, Azeddine Driouich, Marie-Laure Follet-Gueye, and Isabelle Boulogne
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plant exDNA ,root extracellular trap (RET) ,high-throughput DNA sequencing ,PEP-13 ,Glycine max (L.) Merr ,Cytology ,QH573-671 - Abstract
exDNA is found in various organisms, including plants. However, plant exDNA has thus far received little attention related to its origin and role in the RET (root extracellular trap). In this study, we performed the first high-throughput genomic sequencing of plant exDNA from a Fabaceae with worldwide interest: soybean (Glycine max (L.) Merr.). The origin of this exDNA was first investigated in control condition, and the results show high-coverage on organelles (mitochondria/plastid) DNA relative to nuclear DNA, as well as a mix of coding and non-coding sequences. In the second part of this study, we investigated if exDNA release was modified during an elicitation with PEP-13 (a peptide elicitor from oomycete genus Phytophthora). Our results show that treatment of roots with PEP-13 does not affect the composition of exDNA.
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- 2021
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21. Proteomic and transcriptomic study of brain microvessels in neonatal and adult mice.
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Baptiste Porte, Clémence Chatelain, Julie Hardouin, Céline Derambure, Yasmine Zerdoumi, Michèle Hauchecorne, Nicolas Dupré, Soumeya Bekri, Bruno Gonzalez, Stéphane Marret, Pascal Cosette, and Philippe Leroux
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Medicine ,Science - Abstract
Infants born before 29 weeks gestation incur a major risk of preterm encephalopathy and subependymal/intracerebral/intraventricular haemorrhage. In mice, an ontogenic window of haemorrhage risk was recorded up to 5 days after birth in serpine1 knock-out animals. Using proteome and transcriptome approaches in mouse forebrain microvessels, we previously described the remodelling of extracellular matrix and integrins likely strengthening the vascular wall between postnatal day 5 (P5) and P10. Haemorrhage is the ultimate outcome of vessel damage (i.e., during ischaemia), although discreet vessel insults may be involved in the aetiology of preterm encephalopathy. In this study, we examined proteins identified by mass spectrometry and segregating in gene ontology pathways in forebrain microvessels in P5, P10, and adult wild type mice. In parallel, comparative transcript levels were obtained using RNA hybridization microarrays and enriched biological pathways were extracted from genes exhibiting at least a two-fold change in expression. Five major biological functions were observed in those genes detected both as proteins and mRNA expression undergoing at least a two-fold change in expression in one or more age comparisons: energy metabolism, protein metabolism, antioxidant function, ion exchanges, and transport. Adult microvessels exhibited the highest protein and mRNA expression levels for a majority of genes. Energy metabolism-enriched gene ontology pathways pointed to the preferential occurrence of glycolysis in P5 microvessels cells versus P10 and adult preparations enriched in aerobic oxidative enzymes. Age-dependent levels of RNA coding transport proteins at the plasma membrane and mitochondria strengthened our findings based on protein data. The data suggest that immature microvessels have fewer energy supply alternatives to glycolysis than mature structures. In the context of high energy demand, this constraint might account for vascular damage and maintenance of the high bleeding occurrence in specific areas in immature brain.
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- 2017
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22. BTS Tourisme. Réceptif / Émetteur. Incoming / Outgoing : Entraînement intensif aux épreuves écrites et orales Ed. 3
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Derambure-Degraeve, Christine and Derambure-Degraeve, Christine
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Ouvrages complets avec des fiches de révisions, des exercices d’application et des sujets d’annales corrigés pour chaque matière de l’examen final. Toutes les matières et tous les entraînements en un seul volume pour avoir en mains les clés de la réussite a` l’examen ! Le contenu : 30 % de cours et 70 % d’entraînements : Présentation de chaque épreuve avec des conseils, trucs et astuces, Fiches de révisions, Exercices ciblés et corrigés, Annales corrigées. L’objectif : Avoir en un seul volume un outil complet et pratique pour réviser les matières de l’examen final de BTS.
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- 2022
23. Subthalamic Nucleus Stimulation Modulates Motor Cortex Oscillatory Activity in Parkinson's Disease
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Devos, D., Labyt, E., and Derambure, P.
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In Parkinson's disease, impaired motor preparation has been related to an increased latency in the appearance of movement-related desynchronization (MRD) throughout the contralateral primary sensorimotor (PSM) cortex. Internal globus pallidus (GPi) stimulation improved movement desynchronization over the PSM cortex during movement execution but failed to improve impaired motor preparation. PET studies indicate that subthalamic nucleus (STN) stimulation partly reverses the abnormal premotor pattern of brain activation during movement. By monitoring MRD, we aimed to assess changes in premotor and PSM cortex oscillatory activity induced by bilateral STN stimulation and to compare these changes with those induced by L-dopa. Ten Parkinson's disease patients and a group of healthy, age-matched controls performed self-paced wrist flexions in each of four conditions: without either stimulation or L-dopa (the "off" condition), with stimulation and without L-dopa (On Stim), with L-dopa and without stimulation ("on drug"), and with both stimulation and L-dopa (On Both). Compared with the Off condition, in both the On Stim and the On Drug condition the Unified Parkinson's Disease Rating Scale (UPDRS) III score decreased by about 60% and in the On Both condition it decreased by 80%. The desynchronization latency over central regions contralateral to movement and the movement desynchronization over bilateral central regions were significantly increased by stimulation and by L-dopa, with a maximal effect when the two were associated. Furthermore, desynchronization latency significantly decreased over bilateral frontocentral regions in the three treatment conditions compared with the Off condition. In Parkinson's disease, STN stimulation may induce a change in abnormal cortical oscillatory activity patterns (similar to that produced by L-dopa) by decreasing the abnormal spreading of desynchronization over frontocentral regions and increasing PSM cortex activity during movement preparation and execution, with a correlated improvement in bradykinesia. Parkinsonians under treatment displayed a desynchronization pattern close to that seen in healthy, age-matched controls, although central latencies remained shorter. The study indicates that it is possible to influence cortical reactivity related to the planning and execution of voluntary movement through the basal ganglia, and furthermore that the oscillatory activity of the PSM cortex (in addition to that of premotor areas) could be of major importance in the control of movement-associated, neural activity in Parkinson's disease.
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- 2004
24. Effects of stimulus-driven and goal-directed attention on prepulse inhibition of brain oscillations
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Agnes Annic, Jean-Louis Bourriez, Arnaud Delval, Perrine Bocquillon, Claire Trubert, Philippe Derambure, and Kathy Dujardin
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Attention ,brain oscillations ,prepulse inhibition ,Continuous Performance Test (CPT) ,Time frequency analysis ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Objective: Prepulse inhibition (PPI) is an operational measure of sensory gating. PPI of cortical response to a startling pulse is known to be modulated by attention. With a time-frequency analysis, we sought to determine whether goal-directed and stimulus-driven attention differentially modulate inhibition of cortical oscillations elicited by a startling pulse. Methods: An electroencephalogram was recorded in 26 healthy controls performing an active acoustic PPI paradigm. Startling stimuli were presented alone or either 400 or 1000 ms after one of three types of visual prepulse: to-be-attended (goal-directed attention), unexpected (stimulus-driven attention) or to-be-ignored (non-focused attention). We calculated the percentage PPI for the auditory event-related spectral perturbation (ERSP) of theta (4-7 Hz), alpha (8-12 Hz), beta1 (13-20 Hz) and beta2 (20-30 Hz) oscillations and changes in inter-trial coherence (ITC), a measure of phase synchronization of electroencephalographic activity.Results: At 400 ms, (i) PPI of the ERSP of alpha, theta and beta1 oscillation was greater after an unexpected and a to-be-attended prepulse than after a to-be-ignored prepulse, and (ii) PPI of beta2 oscillations was greater after a to-be-attended than a to-be-ignored prepulse. At 1000 ms, (i) PPI of alpha oscillations was greater after an unexpected and a to-be-attended prepulse than after a to-be-ignored prepulse, and (ii) PPI of beta1 oscillations was greater after a to-be-attended than a to-be-ignored prepulse. The ITC values did not vary according to the type of prepulse.Conclusions: In an active PPI paradigm, stimulus-driven and goal-directed attention each have differential effects on the modulation of cortical oscillations.
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- 2016
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25. Impaired Early Attentional Processes in Parkinson's Disease: A High-Resolution Event-Related Potentials Study.
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Perrine Bocquillon, Jean-Louis Bourriez, Ernesto Palmero-Soler, Luc Defebvre, Philippe Derambure, and Kathy Dujardin
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Medicine ,Science - Abstract
The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. A previous study using the P3 component of the event-related potentials suggested that a reduced ability to resist interference could be responsible for attention disorders at early stages of Parkinson's disease (PD), with a possible role of the dorsolateral prefrontal cortex (DLPFC).Our objective was to better determine the origin of this impairment, by studying an earlier ERP component, the N2, and its subcomponents, as they reflect early inhibition processes and as they are known to have sources in the anterior cingulate cortex (ACC), which is involved together with the DLPFC in inhibition processes. Fifteen early-stage PD patients and 15 healthy controls (HCs) performed a three-stimulus visual oddball paradigm, consisting in detecting target inputs amongst standard stimuli, while resisting interference from distracter ones. A 128-channel electroencephalogram was recorded during this task and the generators of the N2 subcomponents were identified using standardized weighted low-resolution electromagnetic tomography (swLORETA).PD patients displayed fewer N2 generators than HCs in both the DLPFC and the ACC, for all types of stimuli. In contrast to controls, PD patients did not show any differences between their generators for different N2 subcomponents.Our data suggest that impaired inhibition in PD results from dysfunction of the DLPFC and the ACC during the early stages of attentional processes.
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- 2015
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26. Prophylactic Injection of Recombinant Alpha-Enolase Reduces Arthritis Severity in the Collagen-Induced Arthritis Mice Model.
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Clément Guillou, Céline Derambure, Manuel Fréret, Mathieu Verdet, Gilles Avenel, Marie-Laure Golinski, Jean-Christophe Sabourin, François Le Loarer, Sahil Adriouch, Olivier Boyer, Thierry Lequerré, and Olivier Vittecoq
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Medicine ,Science - Abstract
To evaluate the ability of the glycolytic enzyme alpha-enolase (ENO1) or its immunodominant peptide (pEP1) to reduce the severity of CIA in DBA/1 mice when injected in a prophylactic way.Mice were treated with mouse ENO1 or pEP1 one day prior to collagen II immunization. Clinical assessment was evaluated using 4 parameters (global and articular scores, ankle thickness and weight). Titers of serum anti-ENO1, anti-cyclic citrullinated peptides (anti-CCP) and anti-CII (total IgG and IgG1/IgG2a isotypes) antibodies were measured by ELISA at different time-points. Disease activity was assessed by histological analysis of both anterior and hind paws at the end of experimentation.Prophylactic injection of 100 μg of ENO1 reduced severity of CIA. Serum levels of anti-CII antibodies were reduced in ENO1-treated mice. Concordantly, ENO1-treated mice joints presented less severe histological signs of arthritis. ENO1 did not induce a shift toward a Th2 response since IgG1/IgG2a ratio of anti-CII antibodies remained unchanged and IL-4 serum levels were similar to those measured in the control group.Pre-immunization with ENO1 or its immunodominant peptide pEP1 reduces CIA severity at the clinical, immunological and histological levels. Effects of pEP1 were less pronounced. This immunomodulatory effect is associated with a reduction in anti-CII antibodies production but is not due to a Th1/Th2 shift.
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- 2015
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27. Sleep disorders in aging and dementia
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Bombois, S., Derambure, P., Pasquier, F., and Monaca, C.
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- 2010
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28. Role of basal ganglia circuits in resisting interference by distracters: a swLORETA study.
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Perrine Bocquillon, Jean-Louis Bourriez, Ernesto Palmero-Soler, Alain Destée, Luc Defebvre, Philippe Derambure, and Kathy Dujardin
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Medicine ,Science - Abstract
BACKGROUND: The selection of task-relevant information requires both the focalization of attention on the task and resistance to interference from irrelevant stimuli. Both mechanisms rely on a dorsal frontoparietal network, while focalization additionally involves a ventral frontoparietal network. The role of subcortical structures in attention is less clear, despite the fact that the striatum interacts significantly with the frontal cortex via frontostriatal loops. One means of investigating the basal ganglia's contributions to attention is to examine the features of P300 components (i.e. amplitude, latency, and generators) in patients with basal ganglia damage (such as in Parkinson's disease (PD), in which attention is often impaired). Three-stimulus oddball paradigms can be used to study distracter-elicited and target-elicited P300 subcomponents. METHODOLOGY/PRINCIPAL FINDINGS: In order to compare distracter- and target-elicited P300 components, high-density (128-channel) electroencephalograms were recorded during a three-stimulus visual oddball paradigm in 15 patients with early PD and 15 matched healthy controls. For each subject, the P300 sources were localized using standardized weighted low-resolution electromagnetic tomography (swLORETA). Comparative analyses (one-sample and two-sample t-tests) were performed using SPM5® software. The swLORETA analyses showed that PD patients displayed fewer dorsolateral prefrontal (DLPF) distracter-P300 generators but no significant differences in target-elicited P300 sources; this suggests dysfunction of the DLPF cortex when the executive frontostriatal loop is disrupted by basal ganglia damage. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the cortical attention frontoparietal networks (mainly the dorsal one) are modulated by the basal ganglia. Disruption of this network in PD impairs resistance to distracters, which results in attention disorders.
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- 2012
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29. Perceiving what is reachable depends on motor representations: evidence from a transcranial magnetic stimulation study.
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Yann Coello, Angela Bartolo, Bastien Amiri, Hervé Devanne, Elise Houdayer, and Philippe Derambure
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Medicine ,Science - Abstract
BackgroundVisually determining what is reachable in peripersonal space requires information about the egocentric location of objects but also information about the possibilities of action with the body, which are context dependent. The aim of the present study was to test the role of motor representations in the visual perception of peripersonal space.MethodologySeven healthy participants underwent a TMS study while performing a right-left decision (control) task or perceptually judging whether a visual target was reachable or not with their right hand. An actual grasping movement task was also included. Single pulse TMS was delivered 80% of the trials on the left motor and premotor cortex and on a control site (the temporo-occipital area), at 90% of the resting motor threshold and at different SOA conditions (50ms, 100ms, 200ms or 300ms).Principal findingsResults showed a facilitation effect of the TMS on reaction times in all tasks, whatever the site stimulated and until 200ms after stimulus presentation. However, the facilitation effect was on average 34ms lower when stimulating the motor cortex in the perceptual judgement task, especially for stimuli located at the boundary of peripersonal space.ConclusionThis study provides the first evidence that brain motor area participate in the visual determination of what is reachable. We discuss how motor representations may feed the perceptual system with information about possible interactions with nearby objects and thus may contribute to the perception of the boundary of peripersonal space.
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- 2008
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30. Subthalamic nucleus stimulation modulates motor cortex oscillatory activity in Parkinsonʼs disease
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Devos, D., Labyt, E., Derambure, P., Bourriez, J. L., Cassim, F., Reyns, N., Blond, S., Guieu, J. D., Destée, A., and Defebvre, L.
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- 2004
31. Abnormal Cortical Activation During Planning of Voluntary Movement in Patients with Epilepsy with Focal Motor Seizures: Event-Related Desynchronization Study of Electroencephalographic mu Rhythm
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Derambure, P., Bourriez, J. L., Defebvre, L., Cassim, F., Josien, E., Duhamel, A., Destée, A., and Guieu, J. D.
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- 1997
32. Functional connectivity disruptions correlate with cognitive phenotypes in Parkinson's disease
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Hassan, M., Chaton, L., Benquet, P., Delval, A., Leroy, C., Plomhause, L., Moonen, A.J.H., Duits, A.A., Leentjens, A.F.G., van Kranen-Mastenbroek, V., Defebvre, L., Derambure, P., Wendling, F., Dujardin, K., RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Psychiatrie & Neuropsychologie, MUMC+: MA Med Staf Spec Psychiatrie (9), MUMC+: HZC Med Staf Spec Klinische Neurofys (9), Laboratoire Traitement du Signal et de l'Image (LTSI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Troubles cognitifs vasculaires et dégénératifs, Université de Lille, Sciences et Technologies, Michael J. Fox Foundation for Parkinson's Research, ANR-10-LABX-07-01, Agence Nationale de la Recherche, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,CORTICAL NETWORKS ,Parkinson's disease ,Statistics as Topic ,Neuropsychological Tests ,lcsh:Computer applications to medicine. Medical informatics ,lcsh:RC346-429 ,QUANTITATIVE EEG ,Network measures ,Neural Pathways ,Humans ,Brain connectivity ,RATING-SCALE ,SMALL-WORLD ,lcsh:Neurology. Diseases of the nervous system ,Aged ,Analysis of Variance ,Brain Mapping ,MEG ,Spectrum Analysis ,Cognitive deficits ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Brain ,Electroencephalography ,Parkinson Disease ,Regular Article ,FRONTOTEMPORAL DEMENTIA ,Middle Aged ,LEWY BODIES ,ALZHEIMERS-DISEASE ,BRAIN NETWORKS ,Cross-Sectional Studies ,GRAPH-THEORETICAL ANALYSIS ,Disease Progression ,lcsh:R858-859.7 ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Female ,Cognition Disorders ,Dense electroencephalography ,[SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing - Abstract
Cognitive deficits in Parkinson's disease are thought to be related to altered functional brain connectivity. To date, cognitive-related changes in Parkinson's disease have never been explored with dense-EEG with the aim of establishing a relationship between the degree of cognitive impairment, on the one hand, and alterations in the functional connectivity of brain networks, on the other hand. This study was aimed at identifying altered brain networks associated with cognitive phenotypes in Parkinson's disease using dense-EEG data recorded during rest with eyes closed. Three groups of Parkinson's disease patients (N = 124) with different cognitive phenotypes coming from a data-driven cluster analysis, were studied: G1) cognitively intact patients (63), G2) patients with mild cognitive deficits (46) and G3) patients with severe cognitive deficits (15). Functional brain networks were identified using a dense-EEG source connectivity method. Pairwise functional connectivity was computed for 68 brain regions in different EEG frequency bands. Network statistics were assessed at both global (network topology) and local (inter-regional connections) level. Results revealed progressive disruptions in functional connectivity between the three patient groups, typically in the alpha band. Differences between G1 and G2 (p, Highlights • We test the use of dense-EEG to identify altered brain networks associated with cognitive phenotypes in Parkinson's disease. • The functional connectivity decreases with the worsening of cognitive performance • The loss of frontotemporal connectivity may be a promising neuromarker of cognitive impairment in Parkinson's disease.
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- 2016
33. Blood functional assay for rapid clinical interpretation of germline TP53variants
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Raad, Sabine, Rolain, Marion, Coutant, Sophie, Derambure, Céline, Lanos, Raphael, Charbonnier, Francoise, Bou, Jacqueline, Bouvignies, Emilie, Lienard, Gwendoline, Vasseur, Stéphanie, Farrell, Michael, Ingster, Olivier, Baert Desurmont, Stéphanie, Kasper, Edwige, Bougeard, Gae¨lle, Frébourg, Thierry, and Tournier, Isabelle
- Abstract
BackgroundThe interpretation of germline TP53variants is critical to ensure appropriate medical management of patients with cancer and follow-up of variant carriers. This interpretation remains complex and is becoming a growing challenge considering the exponential increase in TP53tests. We developed a functional assay directly performed on patients’ blood.MethodsPeripheral blood mononuclear cells were cultured, activated, exposed to doxorubicin and the p53-mediated transcriptional response was quantified using reverse transcription–multiplex ligation probe amplification and RT-QMPSF assays, including 10 p53 targets selected from transcriptome analysis, and two amplicons to measure p53 mRNA levels. We applied this blood functional assay to 77 patients addressed for TP53analysis.ResultsIn 51 wild-type TP53individuals, the mean p53 functionality score was 12.7 (range 7.5–22.8). Among eight individuals harbouring likely pathogenic or pathogenic variants, the scores were reduced (mean 4.8, range 3.1–7.1), and p53 mRNA levels were reduced in patients harbouring truncating variants. We tested 14 rare unclassified variants (p.(Pro72His), p.(Gly105Asp), p.(Arg110His), p.(Phe134Leu), p.(Arg158Cys), p.(Pro191Arg), p.(Pro278Arg), p.(Arg283Cys), p.(Leu348Ser), p.(Asp352Tyr), p.(Gly108_Phe109delinsVal), p.(Asn131del), p.(Leu265del), c.-117G>T) and 12 yielded functionally abnormal scores. Remarkably, the assay revealed that the c.*1175A>C polymorphic variant within TP53poly-adenylation site can impact p53 function with the same magnitude as a null variant, when present on both alleles, and may act as a modifying factor in pathogenic variant carriers.ConclusionThis blood p53 assay should therefore be a useful tool for the rapid clinical classification of germline TP53variants and detection of non-coding functional variants.
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- 2021
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34. Functional connectivity disruptions correlate with cognitive phenotypes in Parkinson's disease
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Hassan, M., primary, Chaton, L., additional, Benquet, P., additional, Delval, A., additional, Leroy, C., additional, Plomhause, L., additional, Moonen, A.J.H., additional, Duits, A.A., additional, Leentjens, A.F.G., additional, van Kranen-Mastenbroek, V., additional, Defebvre, L., additional, Derambure, P., additional, Wendling, F., additional, and Dujardin, K., additional
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- 2017
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35. Usefulness of head-up tilt test combined with video electroencephalogram to investigate recurrent unexplained atypical transient loss of consciousness.
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Ninni, Sandro, Kouakam, Claude, Szurhaj, William, Baille, Guillaume, Klug, Didier, Lacroix, Dominique, and Derambure, Philippe
- Abstract
Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2019
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36. Nutritional Status in the First 2 Years of Life in Cystic Fibrosis Diagnosed by Newborn Screening
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Munck, Anne, Boulkedid, Rym, Weiss, Laurence, Foucaud, Pierre, Wizla-Derambure, Nathalie, Reix, Philippe, Bremont, François, Derelle, Jocelyne, Schroedt, Julien, and Alberti, Corinne
- Abstract
Supplemental Digital Content is available in the text
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- 2018
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37. Pre-silencing of genes involved in the electron transport chain (ETC) pathway is associated with responsiveness to abatacept in rheumatoid arthritis
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Derambure, C., Dzangue-Tchoupou, G., Berard, C., Vergne, N., Hiron, M., D’Agostino, M., Musette, P., Vittecoq, O., and Lequerré, T.
- Abstract
In the current context of personalized medicine, one of the major challenges in the management of rheumatoid arthritis (RA) is to identify biomarkers that predict drug responsiveness. From the European APPRAISE trial, our main objective was to identify a gene expression profile associated with responsiveness to abatacept (ABA) + methotrexate (MTX) and to understand the involvement of this signature in the pathophysiology of RA. Whole human genome microarrays (4 × 44 K) were performed from a first subset of 36 patients with RA. Data validation by quantitative reverse-transcription (qRT)-PCR was performed from a second independent subset of 32 patients with RA. Gene Ontology and WikiPathways database allowed us to highlight the specific biological mechanisms involved in predicting response to ABA/MTX. From the first subset of 36 patients with RA, a combination including 87 transcripts allowed almost perfect separation between responders and non-responders to ABA/MTX. Next, the second subset of patients 32 with RA allowed validation by qRT-PCR of a minimal signature with only four genes. This latter signature categorized 81% of patients with RA with 75% sensitivity, 85% specificity and 85% negative predictive value. This combination showed a significant enrichment of genes involved in electron transport chain (ETC) pathways. Seven transcripts from ETC pathways (NDUFA6, NDUFA4, UQCRQ, ATP5J, COX7A2, COX7B, COX6A1) were significantly downregulated in responders versus non-responders to ABA/MTX. Moreover, dysregulation of these genes was independent of inflammation and was specific to ABA response. Pre-silencing of ETC genes is associated with future response to ABA/MTX and might be a crucial key to susceptibility to ABA response.
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- 2017
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38. Long-Term Increase of Kcnn4 Potassium Channel Surface Expression on B Cells in Pemphigus Patients after Rituximab Treatment
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Caillot, Frédérique, Derambure, Céline, Berkani, Nicolas, Riou, Gaëtan, Maho-Vaillant, Maud, Calbo, Sébastien, Joly, Pascal, and Musette, Philippe
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- 2018
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39. 531 Arrhythmogenic epilepsy: an unusual presentation of recurrent unexplained syncope
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Kouakam, C., primary, Daems-Monpeurt, C., additional, Gu don-Moreau, L., additional, Lacroix, D., additional, Derambure, P., additional, and Kacet, S., additional
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- 2005
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40. Dysregulation of RasGRP1 in rheumatoid arthritis and modulation of RasGRP3 as a biomarker of TNFa inhibitors
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Golinski, Marie-Laure, Vandhuick, Thibault, Derambure, Céline, Fréret, Manuel, Lecuyer, Matthieu, Guillou, Clément, Hiron, Martine, Boyer, Olivier, Le Loët, Xavier, Vittecoq, Olivier, and Lequerré, Thierry
- Abstract
B and T cells play a key role in rheumatoid arthritis (RA) pathophysiology. RasGRP1 and RasGRP3 are involved in T and B cell receptors signaling, and belong to gene combination able to predict infliximab responsiveness, leading to the question of RasGRP1 and RasGRP3 involvement in RA. RasGRP1 and RasGRP3 expression levels were measured by qRT-PCR and/or western-blot in peripheral blood mononuclear cells (PBMCs), in T and B cells from untreated RA patients and in RA patients treated by TNFa inhibitors. T and B cells from healthy controls (HC) were cultured with TNFa, and TNFa receptors neutralizing antibodies to highlight the TNFa effects on RasGRP1 and RasGRP3 pathways. MAPK pathways and apoptosis were respectively analyzed using the Proteome Profiler arrays and flow cytometry. In PBMCs from RA patients, gene expression levels of RasGRP1were invariant while RasGRP3was downregulated under TNFa inhibitors and upregulated under TNFa. In T cells from RA patients, RasGRP1 was decreased and its gene expression level was correlated with disease activity. In T cells from HC, TNFa stimulation increased RasGRP1gene expression level while it reduced RasGRP1 protein expression level. Bryostatin-1 experiments have confirmed that the TNFa effect observed on T cells proliferation was due to the decrease of RasGRP1 expression. Besides, RasGRP3expression level increased in PBMCs from RA patients under TNFa and in B cells from HC leading us to conclude that RasGRP3 in B cells was modulated by TNFa. This study demonstrates RasGRP1 dysregulation in RA patients while RasGRP3 is characterized as a biomarker linked to TNFa inhibitors. After binding to TNFR1, TNFa reduced RasGRP1 protein expression resulting in inhibition of T cell activation. Clinicaltrials.gov NCT00234234, registered 04 November 2008; NCT00767325, registered 05 October 2005.
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- 2015
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41. Usefulness of video-EEG monitoring in children.
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Riquet, Audrey, Lamblin, Marie-Dominique, Bastos, Maria, Bulteau, Christine, Derambure, Philippe, Vallée, Louis, and Auvin, Stéphane
- Abstract
Abstract: Video-EEG monitoring (v-EEG) was originally restricted to the evaluation for epilepsy surgery. It is now widely available and often utilized to clarify the nature of paroxysmal events or to identify the epileptic syndrome. It is important to define carefully the diagnostic value of this high-cost and time-consuming procedure. Few data on children are available. In this study, we have evaluated the utility of this procedure and the factors leading to a successful recording in children. We retrospectively reviewed 380 v-EEG done in 320 children. The rate of event detection was 59%. The v-EEG recorded a seizure in 40% (n =150), a non-epileptic event in 19% (n =73), and both seizure and non-epileptic events in 3% (n =11). Only 9% remained without diagnosis after v-EEG. The frequency of the usual events was the only factor contributing to a successful recording. This procedure confirmed the diagnosis of epilepsy in 43% of patients but excluded it in 25% of them. In children with epilepsy, the v-EEG allowed to define a new syndrome (30% of patients) or to improve clinical description and to identify the origin of the seizures (30%). The treatments were modified in 66% of patients following the v-EEG. Continuous video-EEG monitoring is an efficient and valuable procedure in the diagnosis and management of epilepsy and paroxysmal disorders in children. [ABSTRACT FROM AUTHOR]
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- 2011
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42. Recurrent unexplained syncope may have a cerebral origin: Report of 10 cases of arrhythmogenic epilepsy.
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Kouakam, Claude, Daems, Christine, Guédon-Moreau, Laurence, Delval, Arnaud, Lacroix, Dominique, Derambure, Philippe, and Kacet, Salem
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SYNCOPE ,TOMOGRAPHY ,STANDARD deviations ,BRAIN diseases - Abstract
Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2009
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43. Impact of Intravenous Antibiotic Therapy on Total Daily Energy Expenditure and Physical Activity in Cystic Fibrosis Children with Pseudomonas aeruginosaPulmonary Exacerbation
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BÉGHIN, LAURENT, GOTTRAND, FRÉDÉRIC, MICHAUD, LAURENT, LOEUILLE, GUY-ANDRÉ, WIZLA-DERAMBURE, NATHALIE, SARDET, ANNE, GUIMBER, DOMINIQUE, DESCHILDRE, ANTOINE, AND, and TURCK, DOMINIQUE
- Abstract
Resting energy expenditure (REE) increases during pulmonary exacerbation by Pseudomonas aeruginosain cystic fibrosis (CF) patients, and decreases after i.v. anti-Pseudomonas aeruginosaantibiotic therapy (IVAT). However, the impact of IVAT on total energy expenditure (TEE) is unknown. The aim of this study was to assess the changes in TEE and its main components after IVAT administered at home. Body composition measured by skinfold thickness and bio-impedance analysis, energy intake (EI) assessed by a weekly diary, REE measured by indirect calorimetry (IC), TEE assessed by a technique using 24-h heart-rate monitoring method and physical activity (PA) monitored using an activity diary (AD) were assessed in 16 patients (9 boys and 7 girls) aged 12.1 ± 2.3 y (range, 7.1–14.6 y), before and after 28 ± 4 d including a 14-d IVAT course. After IVAT, weight increased significantly by 1.9 (32.1 ± 7.5 versus32.7 ± 7.6 kg; p< 0.05), while fat mass and fat free mass increased non significantly. EI increased by 4.6 (10,797 ± 3,039 versus11,320 ± 3,074 kJ/d; p< 0.05). TEE was not affected by IVAT (7,014 ± 1,929 versus7,081 ± 1,478 kJ/d) whereas REE decreased by 4.1 (5,295 ± 909 versus5,093 ± 837 kJ/d; p< 0.05), resulting in 9.3 increase in PA assessed by AD converted to metabolic equivalent tasks (MET) (37.0 ± 3.1 versus40.7 ± 4.5 MET; p< 0.05). The improvement in nutritional status after IVAT is not related to a decrease in TEE, but probably to an increase in EI and a decrease of REE after IVAT. After IVAT, the reduction in REE is probably compensated by an increase in PA in CF patients.
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- 2003
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44. Impact of Intravenous Antibiotic Therapy on Total Daily Energy Expenditure and Physical Activity in Cystic Fibrosis Children with Pseudomonas aeruginosa Pulmonary Exacerbation
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Béghin, Laurent, Gottrand, Frédéric, Michaud, Laurent, Loeuille, Guy-André, Wizla-Derambure, Nathalie, Sardet, Anne, Guimber, Dominique, Deschildre, Antoine, and Turck, Dominique
- Abstract
Resting energy expenditure (REE) increases during pulmonary exacerbation by Pseudomonas aeruginosa in cystic fibrosis (CF) patients, and decreases after i.v. anti-Pseudomonas aeruginosa antibiotic therapy (IVAT). However, the impact of IVAT on total energy expenditure (TEE) is unknown. The aim of this study was to assess the changes in TEE and its main components after IVAT administered at home. Body composition measured by skinfold thickness and bio-impedance analysis, energy intake (EI) assessed by a weekly diary, REE measured by indirect calorimetry (IC), TEE assessed by a technique using 24-h heart-rate monitoring method and physical activity (PA) monitored using an activity diary (AD) were assessed in 16 patients (9 boys and 7 girls) aged 12.1 ± 2.3 y (range, 7.1–14.6 y), before and after 28 ± 4 d including a 14-d IVAT course. After IVAT, weight increased significantly by 1.9% (32.1 ± 7.5 versus 32.7 ± 7.6 kg; p < 0.05), while fat mass and fat free mass increased non significantly. EI increased by 4.6% (10,797 ± 3,039 versus 11,320 ± 3,074 kJ/d; p < 0.05). TEE was not affected by IVAT (7,014 ± 1,929 versus 7,081 ± 1,478 kJ/d) whereas REE decreased by 4.1% (5,295 ± 909 versus 5,093 ± 837 kJ/d; p < 0.05), resulting in 9.3% increase in PA assessed by AD converted to metabolic equivalent tasks (MET) (37.0 ± 3.1 versus 40.7 ± 4.5 MET; p < 0.05). The improvement in nutritional status after IVAT is not related to a decrease in TEE, but probably to an increase in EI and a decrease of REE after IVAT. After IVAT, the reduction in REE is probably compensated by an increase in PA in CF patients.
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- 2003
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45. Familial and Community Environmental Risk Factors for Helicobacter pyloriInfection in Children and Adolescents
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Wizla-Derambure, Nathalie, Michaud, Laurent, Ategbo, Simon, Vincent, Pascal, Ganga-Zandzou, Serge, Turck, Dominique, and Gottrand, Frédéric
- Abstract
The aim of the study was to identify familial and community environmental risk factors associated with Helicobacter pyloriinfection in a pediatric population.
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- 2001
46. 0444: Usefulness of combined head-up tilt testing with video-EEG monitoring in the evaluation of patients with atypical seizure-like unexplained loss of consciousness.
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Kouakam, Claude, Szurhaj, William, Guédon-Moreau, Laurence, Monpeurt, Christine, Lacroix, Dominique, Derambure, Philippe, and Kacet, Salem
- Abstract
Background It is well established that tonic-clonic seizure-like activity can be part of a syncope yet many patients with these clinical features are misdiagnosed with seizures and often referred to epilepsy centers. Head-up tilt test (HUT) is the gold standard for diagnosing vasovagal syncope, but it can fail to provide clinical details that help distinguish convulsive syncope from epileptic seizures. We aimed to evaluate the diagnostic yield of a combined HUT and video-EEG monitoring strategy in patients with atypical episodes of unexplained loss of consciousness (LOC). Methods and results A total of 87 patients (mean age 32±15 years, 71% women) who underwent HUT with concomitant video-EEG between March 2007 and August 2013 were retrospectively analyzed. Events were classified as vasovagal syncope, epilepsy or psychogenic. Median number of episodes of LOC was 6 [range 1 - 30]. 45% of patients had prolonged LOC (>1 min), 75% had myoclonic jerks and 52% abnormal standard EEG. Antiepileptic drugs (AEDs) were prescribed in 38 patients (43%). The majority of patients (78/87) had undergone prior neurological and cardiac evaluation with routine EEG, neuroimaging and/or Holter ECG, and HUT (n=30). HUT combined with video-EEG was diagnostic in 67/87 (77%) of patients. Vasovagal syncope was seen in 62/87 (71%), 31 of which had associated myoclonic jerks, especially dose with severe bradycardia <40 bpm (n=26) or asystole (n=5). Five patients (6%) experienced psychogenic non-epileptic events. Epilepsy was diagnosed in only 8 patients (9%), and LOC remained unexplained in 12 (14%). AEDs were discontinued in non-epileptic patients as a result of the testing. Conclusions Patients with convulsive syncope are often misdiagnosed and treated with AEDs. Combined HUT and video-EEG monitoring is a useful diagnostic test in patients with atypical episodes of unexplained LOC and can avoid expensive non-diagnostic evaluations as well as ongoing treatment with unnecessary AEDs. [ABSTRACT FROM AUTHOR]
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- 2015
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47. 362 B-cells transcriptome analysis in pemphigus patients after anti-CD20 treatment
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Caillot, F., Derambure, C., Berkani, N., Riou, G., Maho Vaillant, M., Calbo, S., Joly, P., and Musette, P.
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- 2016
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48. Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia
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Lequerré, Thierry, Bansard, Carine, Vittecoq, Olivier, Derambure, Céline, Hiron, Martine, Daveau, Maryvonne, Tron, François, Ayral, Xavier, Biga, Norman, Auquit-Auckbur, Isabelle, Chiocchia, Gilles, Le Loët, Xavier, and Salier, Jean-Philippe
- Abstract
Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia.
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- 2009
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49. Gene profiling in white blood cells predicts infliximab responsiveness in rheumatoid arthritis
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Lequerré, Thierry, Gauthier-Jauneau, Anne-Christine, Bansard, Carine, Derambure, Céline, Hiron, Martine, Vittecoq, Olivier, Daveau, Maryvonne, Mejjad, Othmane, Daragon, Alain, Tron, François, Le Loët, Xavier, and Salier, Jean-Philippe
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- 2006
50. NUTRITIONAL IMPACT OF RECOMBINANT HUMAN DEOXYRIBONUCLEASE (rhDNase) IN CYSTIC FIBROSIS (CF) PATIENTS
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Wizla‐Derambure, N., Michaud, L., Sardet, A., Deschildre, A., Loeuille, G A., Tassin, E., Loire, N., Buisine, C., Boutry, E., Gottrand, F., and Turck, D.
- Published
- 1998
- Full Text
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