Descriptor: "MESH : Humans" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"MESH : Humans"' showing total 2,059 results

Start Over Descriptor "MESH : Humans"

2,059 results on '"MESH : Humans"'

151. Meningococcal Type IV Pili Recruit the Polarity Complex to Cross the Brain Endothelium

Author: Xavier Nassif, Guillaume Duménil, Florence Miller, Mathieu Coureuil, Pierre-Olivier Couraud, Babette B. Weksler, Hervé Lécuyer, Christine Bernard, Ignacio A. Romero, Sandrine Bourdoulous, René-Marc Mège, Guillain Mikaty, INSERM U1002, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Institut du Fer à Moulin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Weill Medical College of Cornell University [New York], Department of Biological Sciences, The Open University [Milton Keynes] (OU), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), The Open University [Milton Keynes] ( OU ), and Coureuil, Mathieu
Subjects: MESH : Cell Line, Delta Catenin, Cell Cycle Proteins, blood brain barrier, Neisseria meningitidis, medicine.disease_cause, Cell junction, MESH : cdc42 GTP-Binding Protein, Bacterial Adhesion, MESH: Cadherins, MESH : Blood-Brain Barrier, MESH: Blood-Brain Barrier, MESH : Cell Cycle Proteins, 0302 clinical medicine, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Cell polarity, MESH: Endothelial Cells, MESH : Adaptor Proteins, Signal Transducing, cdc42 GTP-Binding Protein, MESH: Antigens, CD, Protein Kinase C, 0303 health sciences, Multidisciplinary, Cell adhesion molecule, MESH : Fimbriae, Bacterial, Brain, Cell Polarity, meningitis, Catenins, Cadherins, endothelial cells, 3. Good health, Cell biology, Endothelial stem cell, Intercellular Junctions, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, Cdc42 GTP-Binding Protein, Blood-Brain Barrier, MESH : Intercellular Junctions, MESH: Cell Adhesion Molecules, MESH : Cadherins, MESH: Endothelium, Vascular, MESH: Membrane Proteins, MESH: Cell Polarity, MESH : Cell Polarity, MESH : Bacterial Adhesion, Biology, Blood–brain barrier, MESH: Phosphoproteins, Article, MESH: Neisseria meningitidis, MESH : Cell Adhesion Molecules, Cell Line, MESH: Fimbriae, Bacterial, MESH: Brain, 03 medical and health sciences, MESH: Cell Cycle Proteins, Antigens, CD, MESH : Antigens, CD, medicine, Humans, MESH : Protein Kinase C, MESH: Bacterial Adhesion, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Catenins, Adaptor Proteins, Signal Transducing, MESH: Adaptor Proteins, Signal Transducing, 030304 developmental biology, MESH: Humans, MESH: cdc42 GTP-Binding Protein, MESH : Endothelial Cells, MESH : Neisseria meningitidis, Cadherin, MESH : Humans, Membrane Proteins, Phosphoproteins, MESH: Protein Kinase C, MESH : Catenins, MESH: Cell Line, MESH : Brain, MESH : Endothelium, Vascular, MESH : Membrane Proteins, Fimbriae, Bacterial, Endothelium, Vascular, MESH : Phosphoproteins, Cell Adhesion Molecules, 030217 neurology & neurosurgery, MESH: Intercellular Junctions
Abstract: Breaking the Barrier Being able to deliver drugs into the brain to treat degenerative diseases such as Alzheimer's or Parkinson's requires the ability to traverse the blood-brain barrier (BBB). Understanding the formation of the very specific adherent junctions (AJ) and tight junctions present at the BBB cell junctions is a prerequisite to the design of such therapeutics. However, diminishing the expression of any one component involved in the formation of these intercellular junctions destroys them. Coureuil et al. (p. 83 , published online 11 June) exploited the specific recruitment of AJ proteins by Neisseria meningitidis to dissect this process. Adhesion of the bacteria to human brain endothelial cells recruited the polarity complex Par3/Par6/PKCζ required for the establishment of eukaryotic cell polarity and the formation of intercellular junctions. The bacterial recruitment of the polarity complex depleted junctional proteins at the cell-cell interface opening the intercellular junctions at the brainendothelial interface.
Published: 2009

152. Detection and Genomic Characterization of Aichi Viruses in Stool Samples from Children in Monastir, Tunisia

Author: Nabil Sakly, Mouna Hassine, Pierre Pothier, Mohamed Neji Guediche, Katia Ambert-Balay, Mahjoub Aouni, Khira Sdiri-Loulizi, S. Chouchane, Hakima Gharbi-Khelifi, Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), Laboratoire de sérologie-virologie (CHU de Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )
Subjects: Diarrhea, Microbiology (medical), Kobuvirus, Tunisia, MESH : Molecular Sequence Data, MESH : Prevalence, viruses, Molecular Sequence Data, MESH : Diarrhea, Genome, Viral, MESH : Child, Preschool, Biology, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH : Kobuvirus, Feces, MESH : Child, Virology, MESH : Tunisia, Prevalence, medicine, Humans, Child, Picornaviridae Infections, MESH : Picornaviridae Infections, MESH : Humans, Infant, virus diseases, MESH : Infant, Sequence Analysis, DNA, MESH : Feces, Acute gastroenteritis, biology.organism_classification, Gastroenteritis, MESH : Gastroenteritis, Child, Preschool, medicine.symptom, Aichi virus, MESH : Genome, Viral, MESH : Sequence Analysis, DNA
Abstract: Aichi virus has been associated with acute gastroenteritis in adults and children. Stool samples were collected from 788 Tunisian children suffering from diarrhea. Aichi virus was found in 4.1% of the cases. The high proportion of monoinfections and the high frequency of hospitalizations support the role of Aichi virus in pediatric gastroenteritis.
Published: 2009

153. Predominance and Circulation of Enteric Viruses in the Region of Greater Cairo, Egypt

Author: Alexis de Rougemont, Mohamed A. Ali, Gaël Belliot, Hala G. Elnady, Pierre Pothier, A.H. Kamel, Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), Laboratoire de sérologie-virologie (CHU de Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )
Subjects: Rotavirus, MESH : Molecular Sequence Data, Urban Population, viruses, MESH : Capsid Proteins, MESH : Genotype, Comorbidity, MESH : Child, Preschool, medicine.disease_cause, Feces, fluids and secretions, MESH : Child, Genotype, Cluster Analysis, MESH : Enteritis, Child, Phylogeny, MESH : Viruses, education.field_of_study, virus diseases, MESH : Infant, Enteritis, Virus Diseases, Child, Preschool, Viruses, MESH : Urban Population, MESH : Comorbidity, Egypt, MESH : Mamastrovirus, Microbiology (medical), Adolescent, MESH : Rotavirus, Molecular Sequence Data, Population, Biology, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Virus, Adenoviridae, Microbiology, Astrovirus, Virology, MESH : Adolescent, medicine, Humans, MESH : Cluster Analysis, Typing, MESH : Adenoviridae, education, MESH : Norovirus, Norovirus, MESH : Humans, Infant, MESH : Phylogeny, Sequence Analysis, DNA, MESH : Feces, MESH : Virus Diseases, medicine.disease, biology.organism_classification, MESH : Egypt, Capsid Proteins, Mamastrovirus, MESH : Sequence Analysis, DNA
Abstract: The circulation of enteric viruses among the population of Cairo, Egypt, between March 2006 and February 2007 was studied. At least one virus was detected in 50% of fecal samples, 57.4% of which were positive for rotavirus, 26% for norovirus, 10.4% for adenovirus, and 1.7% for astrovirus. Over 10% of infections were mixed infections. Rotavirus typing showed that G1P[8] and G2P[4] were predominant but that the unusual G12P[4] and G12P[6] reassortants were also present. Among the noroviruses, half belonged to the predominant GGII.4 cluster. The phylogenetic analysis of the capsid gene suggested that GGII.4 strains from Cairo were similar to those circulating elsewhere. It also showed the emergence of new GGII.4 variants that were not associated with any previously known GGII.4 isolate. Further studies are required to assess the disease burden of enteric viruses in Egypt and the impact of atypical strains.
Published: 2009

154. Age-Associated Aggravation of Clinical Disease after Primary Metapneumovirus Infection of BALB/c Mice

Author: Serge Aho, Catherine Manoha, T. Petrella, Pierre Pothier, Cécile Pitoiset, Magali Darniot, Laboratoire Interactions Muqueuses Agents Transmissibles ( LIMA ), Université de Bourgogne ( UB ), Laboratoire de sérologie-virologie (CHU de Dijon), and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon )
Subjects: CD4-Positive T-Lymphocytes, MESH : Cytokines, CD8-Positive T-Lymphocytes, Antibodies, Viral, Severity of Illness Index, Mice, MESH : Female, Lung, MESH : Body Weight, Mice, Inbred BALB C, Paramyxoviridae Infections, MESH : Bronchoalveolar Lavage Fluid, biology, Respiratory tract infections, medicine.diagnostic_test, Age Factors, MESH : Plethysmography, MESH : CD8-Positive T-Lymphocytes, Respiratory Function Tests, Plethysmography, medicine.anatomical_structure, MESH : CD4-Positive T-Lymphocytes, Models, Animal, Cytokines, Female, MESH : Severity of Illness Index, Bronchoalveolar Lavage Fluid, MESH : Antibodies, Viral, Paramyxoviridae, MESH : Lung, Immunology, MESH : Neutralization Tests, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Microbiology, BALB/c, Human metapneumovirus, Neutralization Tests, Virology, MESH : Mice, MESH : Respiratory Function Tests, medicine, Animals, Humans, MESH : Mice, Inbred BALB C, Body Weight, MESH : Humans, Bronchiolitis obliterans organizing pneumonia, MESH : Paramyxoviridae Infections, biology.organism_classification, medicine.disease, MESH : Models, Animal, respiratory tract diseases, MESH : Metapneumovirus, Bronchoalveolar lavage, Insect Science, Pathogenesis and Immunity, Metapneumovirus, MESH : Age Factors, MESH : Animals, Respiratory tract
Abstract: Human metapneumovirus (hMPV) is associated with respiratory tract infections among children and adults. Because hMPV induces significant morbidity and mortality in the elderly, a model of hMPV infection in aged BALB/c mice was established. Young (8 weeks old) and aged (18 months old) mice were intranasally inoculated with hMPV. The infected mice showed respiratory dysfunction, as measured by plethysmography, a marked loss in weight (up to 24%), and severe histopathological abnormalities including bronchiolitis obliterans organizing pneumonia. However, clinical severity was far higher in the aged mice, and none of the young infected mice died. Although virus replication in the lung was greater in the older mice, clearance of virus was not delayed compared to young mice. Production of virus-specific antibody as well as neutralizing antibody was lower. Gamma interferon and monocyte chemotactic protein-1 levels in bronchoalveolar lavage fluid were significantly lower in older mice, whereas interleukin-6 and interleukin-4 levels were significantly higher. We observed by flow cytometry a significant increase in the CD4 + T lymphocytes ( P < 0.05) of the aged mice and no difference in CD8 + T-cell recruitment to the respiratory tract between the two groups. The present study investigated the effects of aging on the immunopathogenesis of hMPV infection and suggests that CD4 + T lymphocytes, the cytokine response, or a defect in humoral response may be associated with the increased disease severity observed in the aged mice.
Published: 2009

155. Patterns of cerebral activation during olfactory and trigeminal stimulations

Author: Thierry Moulin, Gérard Brand, Alexandre Comte, Jean-Louis Millot, Laurent Tatu, Sandrine Lombion, Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire d'Astrophysique de Grenoble ( LAOG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire d'Astrophysique de Grenoble (LAOG), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Olfactory system, MESH: Olfactory Perception, MESH : Brain Mapping, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, MESH : Female, MESH : Trigeminal Nerve, Research Articles, MESH: Brain Mapping, media_common, Cerebral Cortex, Brain Mapping, Radiological and Ultrasound Technology, 05 social sciences, MESH: Trigeminal Nerve, MESH : Adult, Magnetic Resonance Imaging, medicine.anatomical_structure, Neurology, MESH : Cerebral Cortex, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Anatomy, Psychology, psychological phenomena and processes, Adult, Brain activation, media_common.quotation_subject, Central nervous system, Olfaction, Stimulus (physiology), 050105 experimental psychology, 03 medical and health sciences, MESH : Magnetic Resonance Imaging, Perception, MESH : Olfactory Perception, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Trigeminal Nerve, Trigeminal nerve, MESH: Humans, MESH : Humans, MESH: Adult, Olfactory Perception, MESH: Cerebral Cortex, Olfactory stimulus, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurology (clinical), MESH: Female, Neuroscience, 030217 neurology & neurosurgery
Abstract: It is well known that most odorants stimulate both the olfactory system and the trigeminal system. However, the overlap between the brain processes involved in each of these sensorial perceptions is still poorly documented. This study aims to compare fMRI brain activations while smelling two odorants of a similar perceived intensity and pleasantness: phenyl ethyl alcohol (a pure olfactory stimulus) and iso‐amyl‐acetate (a bimodal olfactory‐trigeminal stimulus) in a homogeneous sample of 15 healthy, right‐handed female subjects. The analysis deals with the contrasts of brain activation patterns between these two odorant conditions. The results showed a significant recruitment of the right insular cortex, and bilaterally in the cingulate in response to the trigeminal component. These findings are discussed in relation to the characteristics of these odorants compared with those tested in previous studies. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Published: 2009

156. Analytical evaluation of the PapilloCheck test, a new commercial DNA chip for detection and genotyping of human papillomavirus

Author: Véronique Dalstein, Roger Dachez, Sandra Merlin, Christophe Ronsin, Maëlle Saunier, Corinne Bali, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC )
Subjects: MESH : Retrospective Studies, MESH: Reagent Kits, Diagnostic, MESH : Genotype, Cervix Uteri, MESH: Papillomavirus Infections, Polymerase Chain Reaction, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Genotype, MESH: Papillomaviridae, Genotype, MESH : Female, MESH : DNA, Viral, MESH : Reagent Kits, Diagnostic, Papillomaviridae, MESH : Polymerase Chain Reaction, MESH : Papillomavirus Infections, 0303 health sciences, MESH: Cervix Uteri, 3. Good health, MESH: Reproducibility of Results, MESH : Vaginal Smears, Female, MESH : Sensitivity and Specificity, DNA microarray, MESH: Vaginal Smears, Concordance, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Sensitivity and Specificity, Linear array, 03 medical and health sciences, Virology, Humans, False Positive Reactions, Typing, Human papillomavirus, MESH : Papillomaviridae, Genotyping, Retrospective Studies, 030304 developmental biology, Vaginal Smears, MESH: Humans, MESH: False Positive Reactions, 030306 microbiology, MESH : Reproducibility of Results, Papillomavirus Infections, MESH : Humans, Reproducibility of Results, MESH: Retrospective Studies, MESH: Polymerase Chain Reaction, Molecular biology, MESH: Sensitivity and Specificity, MESH: DNA, Viral, MESH : Cervix Uteri, DNA, Viral, MESH : False Positive Reactions, Linear Array HPV Genotyping Test, Reagent Kits, Diagnostic, MESH: Female
Abstract: International audience; Recently, a commercially available HPV DNA chip, the PapilloCheck test, developed by Greiner Bio-One, has become available for human papillomavirus (HPV) genotyping. The PapilloCheck test is a PCR-based test using a new consensus primer set targeting the E1 HPV gene. HPV oligoprobes immobilized on a DNA chip allow for the identification of 24 HPV types from the amplified product. In the present study, the analytical performance of the PapilloCheck test is compared to the Linear Array HPV genotyping test (Roche Diagnostics). Cervical specimens collected in PreservCyt (Cytyc) solution and obtained from women who presented abnormal cytological findings were tested primarily by the Hybrid Capture 2 High-Risk assay (HC2-HR, QIAGEN). A total of 144 samples were selected according to the signal intensity obtained with the HC2-HR test, expressed as RLU/CO value, and divided into 4 groups as follows: [0-1] RLU/CO (negative HC2-HR result, 34 samples); [1-5] RLU/CO (positive HC2-HR result, 30 samples); [5-40] RLU/CO (positive HC2-HR result, 40 samples); >40 RLU/CO (positive HC2-HR result, 40 samples). The concordance levels between the HC2-HR test and each of the genotyping assays was similar (88.8%) and the crude agreement between these assays was considered as "good". The detailed analysis of the discrepant results confirmed a possibly high rate of false positive results of HC2-HR test in the 1-5 RLU/CO grey zone. Genotype-specific comparison analysis was limited to the 23 HPV types detected by both genotyping assays (HPV types 6, 11, 16, 18, 31, 33, 35, 39, 40, 42, 45, 51, 52, 53, 55, 56, 58, 59, 66, 68, 70, 73 and 82). Of the 135 samples available for comparison, 91 (67.4%) showed absolute agreement between the assays (concordant genotype-specific results), 34 (25.1%) showed correspondence for some but not all genotypes detected by both assays (compatible genotype-specific results), and the remaining 10 (7.4%) samples did not show any similarity between the tests (discordant results). The majority of discordances were found in samples containing multiple HPV types and in samples harboring low amounts of HPV. For some HPV genotypes, there were slight differences in the detection rate between the two genotyping methods. The Linear Array test seemed to be more sensitive to detect HPV type 53 whereas PapilloCheck test seemed to be more sensitive to detect HPV type 56. For the other genotypes, including HPV types 16 and 18, the results obtained by the two methods did not differ significantly. In conclusion, this study shows that the PapilloCheck test and the Linear Array test give comparable results for detecting HPV in cervical specimens. However, these results also suggest that there is a need to standardize the type-specific sensitivity of genotyping methods and to evaluate their accuracy to detect multiple HPV infections. This would be a prerequisite for the use of genotyping assays in cervical cancer screening algorithms.
Published: 2009

157. CD4-CCR5 interaction in intracellular compartments contributes to receptor expression at the cell surface

Author: Georges Bismuth, Mark G.H. Scott, Catherine Labbé-Jullié, Lamia Achour, Hamasseh Shirvani, Stefano Marullo, Alain Thuret, Marullo, Stefano, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Hela Cells, Chemokine receptor CCR5, viruses, Receptor expression, MESH: Antigens, CD4, Intracellular Space, MESH : Intracellular Space, MESH: Cricetinae, Plasma protein binding, MESH: Receptors, CCR5, Endoplasmic Reticulum, Biochemistry, MESH: Cell Compartmentation, MESH : Protein Transport, MESH: Cricetulus, Cell–cell interaction, Cricetinae, MESH : CHO Cells, MESH: Animals, Receptor, Cells, Cultured, MESH : Endoplasmic Reticulum, biology, MESH : Cricetinae, virus diseases, MESH : Protein Binding, MESH : Receptors, CCR5, Hematology, Cell biology, Protein Transport, Antigens, Surface, CD4 Antigens, MESH: Intracellular Space, MESH : Antigens, Surface, Intracellular, MESH: Cells, Cultured, Protein Binding, MESH: Protein Transport, Receptors, CCR5, MESH: Antigens, Surface, MESH : Cricetulus, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, CHO Cells, Article, Cricetulus, MESH: CHO Cells, MESH: Endoplasmic Reticulum, MESH : Cells, Cultured, MESH: Protein Binding, Animals, Humans, MESH : Cell Compartmentation, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, MESH: Humans, Endoplasmic reticulum, MESH : Humans, Cell Biology, Cell Compartmentation, MESH: Hela Cells, biology.protein, MESH : Antigens, CD4, MESH : Animals, CC chemokine receptors, HeLa Cells
Abstract: International audience; The association of CD4, a glycoprotein involved in T-cell development and antigen recognition, and CC chemokine receptor 5 (CCR5), a chemotactic G protein-coupled receptor, which regulates trafficking and effector functions of immune cells, forms the main receptor for HIV. We observed that the majority of CCR5 is maintained within the intracellular compartments of primary T lymphocytes and in a monocytic cell line, contrasting with its relatively low density at the cell surface. The CCR5-CD4 association, which occurs in the endoplasmic reticulum, enhanced CCR5 export to the plasma membrane in a concentration-dependent manner, whereas inhibition of endogenous CD4 with small interfering RNAs decreased cell-surface expression of endogenous CCR5. This effect was specific for CCR5, as CD4 did not affect cellular distribution of CXCR4, the other HIV coreceptor. These results reveal a previously unappreciated role of CD4, which contributes to regulating CCR5 export to the plasma membrane.
Published: 2009

158. IRX-2, a novel immunotherapeutic, protects human T cells from tumor-induced cell death

Author: Theresa L. Whiteside, Marta Szajnik, H Brandwein, Miroslaw J. Szczepanski, J W Hadden, J Han, K Signorelli, K Quadrini, Malgorzata Czystowska, BMC, Ed., Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche Croissance et signalisation ( UMR_S 845 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Time Factors, MESH : Cytokines, T-Lymphocytes, medicine.medical_treatment, MESH : Dose-Response Relationship, Drug, Apoptosis, CD8-Positive T-Lymphocytes, Fas ligand, MESH: Dose-Response Relationship, Drug, MESH: Janus Kinase 3, Jurkat Cells, Phosphatidylinositol 3-Kinases, MESH: Jurkat Cells, STAT5 Transcription Factor, Cytotoxic T cell, MESH : Jurkat Cells, bcl-2-Associated X Protein, MESH: Cytokines, tofacitinib, Bcl-2-Like Protein 11, MESH : STAT5 Transcription Factor, MESH : CD8-Positive T-Lymphocytes, MESH: CD8-Positive T-Lymphocytes, MESH : Antineoplastic Agents, MESH : Proto-Oncogene Proteins c-akt, Cytokine, MESH : Proto-Oncogene Proteins, Cytokines, MESH: Membrane Proteins, JAK3, MESH : Apoptosis Regulatory Proteins, MESH : Time Factors, MESH : Janus Kinase 3, Programmed cell death, MESH: Cell Line, Tumor, kidney transplantation, Antineoplastic Agents, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Article, Cell Line, Tumor, Proto-Oncogene Proteins, medicine, Humans, MESH: bcl-2-Associated X Protein, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, Protein kinase B, PI3K/AKT/mTOR pathway, MESH : T-Lymphocytes, MESH: Humans, Dose-Response Relationship, Drug, MESH : bcl-2-Associated X Protein, MESH : Cell Line, Tumor, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, MESH: Proto-Oncogene Proteins c-akt, MESH: Apoptosis Regulatory Proteins, MESH: Apoptosis, MESH: STAT5 Transcription Factor, MESH : Humans, MESH: Time Factors, MESH : Phosphatidylinositol 3-Kinases, Janus Kinase 3, Membrane Proteins, Cell Biology, Molecular biology, MESH: Proto-Oncogene Proteins, MESH: T-Lymphocytes, MESH : Membrane Proteins, MESH: Phosphatidylinositol 3-Kinases, MESH: Antineoplastic Agents, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-akt, MESH : Apoptosis, CD8
Abstract: International audience; IRX-2 is a cytokine-based biologic agent that has the potential to enhance antitumor immune responses. We investigated whether IRX-2 can protect T cells from tumor-induced apoptosis. Tumor-derived microvesicles (MV) expressing FasL were purified from supernatants of tumor cells and incubated with activated CD8(+) T cells. MV induced significant CD8(+) T-cell apoptosis, as evidenced by Annexin binding (64.4+/-6.4%), caspase activation (58.1+/-7.6%), a loss of mitochondrial membrane potential (82.9+/-3.9%) and DNA fragmentation. T-cell pretreatment with IRX-2 prevented apoptosis. IRX-2-mediated cytoprotection was dose and time dependent and was comparable to effects of IL-2, IL-7 or IL-15. IRX-2 prevented MV-induced downregulation of JAK3 and TCRzeta chain and induced STAT5 activation in T cells. IRX-2 prevented MV-induced Bax and Bim upregulation (P
Published: 2009

159. Epidemiology of ischemic stroke from atrial fibrillation in Dijon, France, from 1985 to 2006

Author: Thibault Moreau, Yves Cottin, Guy-Victor Osseby, Christine Marie, Jérôme Durier, M. Giroud, Yannick Béjot, D. Ben Salem, G. Couvreur, Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Département de radiologie [Brest] (DR - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Département de radiologie [Brest] ( DR - Brest ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] ( IBMM ), and Ecole Nationale Supérieure de Chimie de Montpellier ( ENSCM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Male, MESH : Stroke, MESH: Registries, [SDV]Life Sciences [q-bio], MESH : Aged, MESH : Prospective Studies, 030204 cardiovascular system & hematology, Rate ratio, Brain Ischemia, MESH: Aged, 80 and over, 0302 clinical medicine, MESH: Risk Factors, Risk Factors, Atrial Fibrillation, MESH: Fibrinolytic Agents, MESH : Female, Prospective Studies, Registries, Myocardial infarction, Prospective cohort study, Stroke, MESH: Aged, Aged, 80 and over, education.field_of_study, MESH: Middle Aged, Cerebral infarction, Incidence (epidemiology), MESH: Brain Ischemia, Atrial fibrillation, MESH : Adult, Middle Aged, MESH : Survival Rate, MESH : Risk Factors, 3. Good health, Survival Rate, MESH: Atrial Fibrillation, Cardiology, Female, France, Adult, medicine.medical_specialty, MESH: Survival Rate, MESH : Male, Population, MESH: Stroke, 03 medical and health sciences, Fibrinolytic Agents, Internal medicine, medicine, Humans, MESH : Middle Aged, cardiovascular diseases, MESH : Aged, 80 and over, MESH : France, education, Aged, MESH: Humans, [ SDV ] Life Sciences [q-bio], business.industry, MESH : Humans, MESH : Fibrinolytic Agents, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, MESH : Atrial Fibrillation, MESH : Brain Ischemia, Neurology (clinical), business, MESH: Female, MESH : Registries, 030217 neurology & neurosurgery
Abstract: Background: Atrial fibrillation (AF) is strongly associated with age, and epidemiologic studies are needed to evaluate the impact of both aging of the population and the use of anticoagulant therapy in patients with AF on the incidence of cardioembolic stroke with AF (CE/AF stroke). Methods: We evaluated trends in incidence rates, risk factors, prestroke therapy, and survival in CE/AF stroke from a prospective population-based registry, from 1985 to 2006. Results: A total of 3,064 ischemic strokes, including 572 (18.7%) CE/AF strokes, were recorded. Over the 22 years, a decrease in the incidence of overall CE/AF stroke was noted (incidence rate ratio 0.9858, 95% confidence interval [CI] 0.9731–0.9986; p = 0.03). We observed a higher prevalence of previous AF, previous myocardial infarction, and patients aged >70 years in CE/AF stroke ( p p = 0.003). A significant increase in the use of anticoagulants and antiplatelet agents was noted, and was particularly pronounced for CE/AF stroke with previous AF. For CE/AF stroke, survival rates were 72% at 1 month (95% CI 0.68–0.76), 52% at 1 year (95% CI 0.48–0.56), and 43% at 2 years (95% CI 0.39–0.48), and remained lower than those of other ischemic stroke. Conclusions: The decrease in the incidence of cardioembolic/atrial fibrillation stroke in our study was probably due to a slight increase in the utilization of antithrombotic therapy in patients with atrial fibrillation, but the use of such therapies will have to increase further because of the expected aging of the population in coming years. AF = atrial fibrillation; CE = cardioembolic; CI = confidence interval; IRR = incidence rate ratios.
Published: 2009

160. Transcriptional repression of microRNA genes by PML-RARA increases expression of key cancer proteins in acute promyelocytic leukemia

Author: Bernard Mari, Elodie Portales-Casamar, Bruno Cassinat, Evelyne Friederich, Christine Chomienne, Khalil Arar, Pascal Barbry, Thomas Maurin, Anne Saumet, Manuella Bouttier, Laurent Vallar, Guillaume Vetter, Charles-Henri Lecellier, Wyeth W. Wasserman, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Cytoskeleton and Cell Plasticity Lab, Université du Luxembourg (Uni.lu), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), University of British Columbia (UBC), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Public Santé, CRP-Santé Luxembourg, Sigma-Proligo, Granulopoiese et Processus Leucemiques (UMR_S_718), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Institut de génétique humaine ( IGH ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Université du Luxembourg ( Uni.lu ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), University of British Columbia ( UBC ), Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Granulopoiese et Processus Leucemiques, and Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Oncogene Proteins, Fusion, Transcription, Genetic, Retinoic acid, MESH : Leukemia, Promyelocytic, Acute, MESH : Oncogene Proteins, Fusion, Biochemistry, chemistry.chemical_compound, 0302 clinical medicine, Leukemia, Promyelocytic, Acute, MESH : Tumor Markers, Biological, MESH : Homeodomain Proteins, RNA, Neoplasm, MESH : Tretinoin, Regulation of gene expression, 0303 health sciences, Gene Expression Regulation, Leukemic, Myeloid leukemia, Hematology, MESH : Arsenic, 3. Good health, MESH : Antineoplastic Agents, Leukemia, 030220 oncology & carcinogenesis, MESH: Cell Adhesion Molecules, MESH: Gene Expression Regulation, Leukemic, medicine.drug, Acute promyelocytic leukemia, MESH: Cell Line, Tumor, Immunology, Antineoplastic Agents, Tretinoin, Biology, MESH : Cell Adhesion Molecules, Arsenic, 03 medical and health sciences, Cell Line, Tumor, MESH: Arsenic, MESH: Homeodomain Proteins, microRNA, Biomarkers, Tumor, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, Homeodomain Proteins, MESH: Tretinoin, MESH: Humans, MESH : Cell Line, Tumor, MESH: Transcription, Genetic, MESH : Humans, MESH : Transcription, Genetic, Cell Biology, MESH: RNA, Neoplasm, medicine.disease, MESH : MicroRNAs, MicroRNAs, MESH : RNA, Neoplasm, MESH : Gene Expression Regulation, Leukemic, chemistry, Retinoic acid receptor alpha, MESH: Tumor Markers, Biological, Cancer research, MESH: Antineoplastic Agents, Cell Adhesion Molecules, MESH: MicroRNAs, MESH: Leukemia, Promyelocytic, Acute, MESH: Oncogene Proteins, Fusion
Abstract: Micro(mi)RNAs are small noncoding RNAs that orchestrate many key aspects of cell physiology and their deregulation is often linked to distinct diseases including cancer. Here, we studied the contribution of miRNAs in a well-characterized human myeloid leukemia, acute promyelocytic leukemia (APL), targeted by retinoic acid and trioxide arsenic therapy. We identified several miRNAs transcriptionally repressed by the APL-associated PML-RAR oncogene which are released after treatment with all-trans retinoic acid. These coregulated miRNAs were found to control, in a coordinated manner, crucial pathways linked to leukemogenesis, such as HOX proteins and cell adhesion molecules whose expressions are thereby repressed by the chemotherapy. Thus, APL appears linked to transcriptional perturbation of miRNA genes, and clinical protocols able to successfully eradicate cancer cells may do so by restoring miRNA expression. The identification of abnormal miRNA biogenesis in cancer may therefore provide novel biomarkers and therapeutic targets in myeloid leukemias.
Published: 2009

161. Population Pharmacokinetics and Dosing Recommendations for Cisplatin during Intraperitoneal Peroperative Administration

Author: Xavier Pivot, Bruno Chauffert, Jean-Pierre Kantelip, Emmanuel Guardiola, Vincent Jullien, Bruno Heyd, Bernard Royer, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pharmacologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Service de chirurgie viscérale et digestive - Unité de transplantation hépatique, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Cochin-Saint Vincent de Paul, Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'oncologie Médicale, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) ( PCVP / CARDIO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ), and Saas, Philippe
Subjects: MESH: Combined Modality Therapy, MESH : Aged, MESH : Dose-Response Relationship, Drug, MESH : Models, Biological, MESH: Risk Assessment, 030226 pharmacology & pharmacy, MESH: Dose-Response Relationship, Drug, Intraoperative Period, MESH : Metabolic Clearance Rate, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Medicine, MESH : Female, Pharmacology (medical), MESH : Risk Assessment, Ovarian Neoplasms, MESH: Aged, Volume of distribution, education.field_of_study, MESH: Middle Aged, Middle Aged, MESH : Adult, MESH : Nonlinear Dynamics, Combined Modality Therapy, 3. Good health, MESH : Antineoplastic Agents, MESH: Nonlinear Dynamics, MESH: Ovarian Neoplasms, Area Under Curve, 030220 oncology & carcinogenesis, Toxicity, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Intraoperative Period, Risk assessment, Monte Carlo Method, Injections, Intraperitoneal, MESH: Injections, Intraperitoneal, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Metabolic Clearance Rate, MESH : Drug Administration Schedule, Population, Urology, Antineoplastic Agents, MESH: Monte Carlo Method, MESH: Drug Administration Schedule, Models, Biological, Risk Assessment, Drug Administration Schedule, MESH : Cisplatin, 03 medical and health sciences, Pharmacokinetics, Humans, MESH : Middle Aged, Dosing, education, Aged, MESH: Intraoperative Period, MESH: Metabolic Clearance Rate, Pharmacology, MESH : Injections, Intraperitoneal, MESH: Humans, Dose-Response Relationship, Drug, MESH : Ovarian Neoplasms, business.industry, MESH : Humans, MESH: Models, Biological, MESH: Adult, Nomogram, NONMEM, MESH : Monte Carlo Method, Nonlinear Dynamics, MESH: Cisplatin, MESH: Antineoplastic Agents, MESH: Area Under Curve, MESH : Area Under Curve, Cisplatin, MESH : Combined Modality Therapy, business, MESH: Female
Abstract: International audience; BACKGROUND: Ovarian cancer is the leading cause of gynaecological cancer-related death in Western countries. Intraperitoneal (IP) peroperative chemotherapy is an interesting therapeutic option. However, very few data are available regarding pharmacokinetics and especially population pharmacokinetics. PATIENTS AND METHODS: Thirty-one patients with advanced epithelial cancer classified as International Federation of Gynecology and Obstetrics stage IIIC were included in the study. Blood and IP samples were taken over a 24-hour period during and after IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentrations were analysed using a population approach with nonlinear mixed-effects modelling (NONMEM) software. Improvement of the model with covariates was performed as well as assessment of the model using bootstrap and posterior visual predictive methods. RESULTS: Both IP fluid and serum pharmacokinetics were satisfactorily described with a three-compartment model for both Uf Pt and total Pt concentrations. The covariates were bodyweight for the IP volume of distribution in the Uf Pt model, and both IP and serum protein concentrations for the clearance from the central compartment in the total Pt model. A nomogram, based on the results of the Monte Carlo simulations, displays a dose recommendation regarding both the risk of renal toxicity and the potent efficacy of the treatment. A limited sampling strategy (LSS) allowing the estimation of potential risk of renal toxicity is also described. CONCLUSION: The pharmacokinetics of cisplatin during peroperative IP chemotherapy could be successfully fitted with the present model, which allowed a dosing strategy accompanied by an LSS to facilitate the follow-up of patients.
Published: 2009

162. Bacterial epidemiology and antimicrobial resistance in ascitic fluid: A 2-year retrospective study

Author: Christian Rabaud, Lionel Piroth, Yves Hansmann, Pascal Chavanet, Isabelle Patry, Tahar Hadou, Benoît Jaulhac, Anne Minello, Catherine Neuwirth, André Pechinot, Département d'infectiologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Department of Microbiology, Service d'Hépato-Gastro-Entérologie (CHU de Dijon), UFR des Sciences de Santé (Université de Bourgogne), and Université de Bourgogne ( UB )
Subjects: Liver Cirrhosis, Microbiology (medical), Cefotaxime, MESH : Retrospective Studies, medicine.medical_treatment, Peritonitis, MESH : Peritonitis, Drug resistance, MESH : Gram-Negative Bacterial Infections, Microbial Sensitivity Tests, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH : Drug Resistance, Bacterial, Gram-Positive Bacteria, Microbiology, Antibiotic resistance, Spontaneous bacterial peritonitis, Drug Resistance, Bacterial, Gram-Negative Bacteria, medicine, MESH : Liver Cirrhosis, Ascitic Fluid, Humans, MESH : Anti-Bacterial Agents, Gram-Positive Bacterial Infections, Retrospective Studies, Antiinfective agent, General Immunology and Microbiology, business.industry, MESH : Humans, General Medicine, Amoxicillin, MESH : Gram-Negative Bacteria, medicine.disease, MESH : Gram-Positive Bacterial Infections, Anti-Bacterial Agents, Infectious Diseases, MESH : Ascitic Fluid, Beta-lactamase, MESH : Gram-Positive Bacteria, MESH : Microbial Sensitivity Tests, business, Gram-Negative Bacterial Infections, medicine.drug
Abstract: International audience; The bacterial epidemiology of bacterascites and spontaneous bacterial peritonitis is evolving. Four hundred and eleven strains isolated from ascites in cirrhotic patients from 5 French hospitals were isolated in 2006 and 2007. Of these, 114 were definitely associated with spontaneous bacterial peritonitis. The proportion of Gram-positive and Gram-negative agents was quite similar, even after excluding coagulase-negative staphylococci, or when considering only definite spontaneous bacterial peritonitis or community-acquired strains. Staphylococci and Escherichia coli were the most frequent pathogens, but enterococci were also involved in nearly 15% of the cases. Among the E. coli, 28% were intermediate or resistant to amoxicillin+clavulanate, 5.3% expressed cephalosporinases or extended beta-lactamases and 17.3% were intermediate or resistant to fluoroquinolones. Resistance to methicillin was observed in 27% of Staphylococcus aureus. Cefotaxime and amoxicillin-clavulanate remained the most effective 'single' agents, however on less than 70% of isolates. Some combinations (such as cefotaxime+amoxicillin) extended coverage to a further 15% of strains. Since inadequate empiric antibiotic therapy is associated with increased mortality, these combinations may be of great interest as first-line treatment, even though they may also lead to the development of antimicrobial resistance. Repeated epidemiological surveys and new clinical trials are thus needed.
Published: 2009

163. Multiple tumours in survival estimates

Author: Stefano Guzzinati, Florence Molinié, Rafael Marcos-Gragera, Eva Ardanaz, Tiziana Cassetti, Angel Izquierdo Font, Milena Sant, Stanislaw Gozdz, Rafael Peris-Bonet, Pascale Grosclaude, Emmanuel Desandes, Michel Coleman, Laura Ciccolallo, Lucia Mangone, Freddie Bray, Hermann Brenner, Giovanna Tagliabue, Mariano Santaquilani, Enrico Grande, Maria Zwierko, Jan Willem Coebergh, Emanuele Crocetti, Giulia Zigon, Roberta De Angelis, Stefano Ferretti, Andrea Tavilla, Gemma Gatta, Silvia Francisci, Paolo Contiero, Rosario Tumino, Laufey Tryggvadottir, Franco Berrino, Hans Storm, Paolo Baili, David Brewster, National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanita [Rome], Evaluative Epidemiology Unit, Fondazione IRCCS, Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neurology, and Public Health
Subjects: Male, Oncology, Cancer Research, Survival, MESH : Age Distribution, MESH : Aged, MESH : Neoplasms, Multiple Primary, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Neoplasms, Multiple Primary, MESH: Aged, 80 and over, 0302 clinical medicine, Multiple Primary, Prostate, Neoplasms, Epidemiology, 80 and over, Cancer registries, MESH: Neoplasms, Multiple Primary, MESH : Female, 030212 general & internal medicine, Young adult, 10. No inequality, MESH : Sex Distribution, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Relative survival, Medicine (all), MESH: Sex Distribution, Multiple tumours, Neoplasm, Adolescent, Adult, Age Distribution, Aged, Europe, Female, Humans, Middle Aged, Sex Distribution, Survival Analysis, Young Adult, Percentage point, MESH : Adult, 3. Good health, Multiple tumours - survival estimates, medicine.anatomical_structure, MESH: Young Adult, MESH: Survival Analysis, 030220 oncology & carcinogenesis, medicine.medical_specialty, MESH : Male, MESH : Europe, MESH : Young Adult, Socio-culturale, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, MESH : Adolescent, medicine, MESH : Middle Aged, MESH : Aged, 80 and over, MESH: Age Distribution, Survival analysis, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, Cancer, MESH: Adult, medicine.disease, MESH: Male, Surgery, Cancer registry, MESH: Europe, MESH : Survival Analysis, business, MESH: Female
Abstract: In international comparisons of cancer registry based survival it is common practice to restrict the analysis to first primary tumours and exclude multiple cancers. The probability of correctly detecting subsequent cancers depends on the registry's running time, which results in different proportions of excluded patients and may lead to biased comparisons. We evaluated the impact on the age-standardised relative survival estimates of also including multiple primary tumours. Data from 2,919,023 malignant cancers from 69 European cancer registries participating in the EUROCARE-4 collaborative study were used. A total of 183,683 multiple primary tumours were found, with an overall proportion of 6.3% over all the considered cancers, ranging from 0.4% (Naples, Italy) to 12.9% (Iceland). The proportion of multiple tumours varied greatly by type of tumour, being higher for those with high incidence and long survival (breast, prostate and colon-rectum). Five-year relative survival was lower when including patients with multiple cancers. For all cancers combined the average difference was -0.4 percentage points in women and -0.7 percentage points in men, and was greater for older registries. Inclusion of multiple tumours led to lower survival in 44 out of 45 cancer sites analysed, with the greatest differences found for larynx (-1.9%), oropharynx (-1.5%), and penis (-1.3%). Including multiple primary tumours in survival estimates for international comparison is advisable because it reduces the bias due to different observation periods, age, registration quality and completeness of registration. The general effect of inclusion is to reduce survival estimates by a variable amount depending on the proportion of multiple primaries and cancer site. (C) 2008 Elsevier Ltd. All rights reserved.
Published: 2009

164. Coagulase-negative staphylococcal prosthetic valve endocarditis--a contemporary update based on the International Collaboration on Endocarditis: prospective cohort study

Author: Chu, V. H., Miro, J. M., Hoen, B., Cabel, C. H., Pappa, P. A., Jones, P., Stryjewski, M. E., Anguera, I., Braun, S., Mu&#241, oz, P., Commerford, P., Tornos, P., Francis, J., Oyonarte, M., Selton-Suty, C., Morris, A. J., Habib, G., Almirante, B., Sexton, D. J., Corey, G. R., Fowler, V. G. Jr, International Collaboration on Endocarditis-Prospective Cohort Study Group Investigators: Baršić, Bruno et al., Chu, Vh, Miro, Jm, Hoen, B, Cabell, Ch, Pappas, Pa, Jones, P, Stryjewski, Me, Anguera, I, Braun, S, Muñoz, P, Commerford, P, Tornos, P, Francis, J, Oyonarte, M, Selton Suty, C, Morris, Aj, Habib, G, Almirante, B, Sexton, Dj, Corey, Gr, Fowler VG, Jr, among International Collaboration on Endocarditis Prospective Cohort Study Group, Investigator, Utili, Riccardo, Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Department of Physics [Jyväskylä Univ] (JYU), University of Jyväskylä (JYU), Service de cardiologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Department of Physics, University of Jyvaskyl ( University of Jyvaskyl ), University of Jyvaskyl, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), AII - Amsterdam institute for Infection and Immunity, Infectious diseases, and Laboratoire Chrono-environnement (UMR 6249) (LCE)
Subjects: Male, Time Factors, MESH: Drug Resistance, Microbial, MESH : Aged, MESH : Prospective Studies, MESH : Coagulase, 030204 cardiovascular system & hematology, Postoperative Complications, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Postoperative Complications, MESH: Staphylococcus aureus, MESH : Female, Hospital Mortality, Prospective Studies, 030212 general & internal medicine, MESH : Endocarditis, Bacterial, Abscess, Prospective cohort study, MESH: Aged, Cross Infection, MESH: Statistics, Nonparametric, MESH: Middle Aged, biology, MESH : Staphylococcus aureus, valvular heart disease, cons, Drug Resistance, Microbial, coagulase-negative staphylococci, endoccarditis, prosthetic valves, Middle Aged, Staphylococcal Infections, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Heart Valve Prosthesis, Infective endocarditis, Female, MESH: Coagulase, Cardiology and Cardiovascular Medicine, MESH : Cross Infection, Cohort study, MESH : Time Factors, Coagulase, Staphylococcus aureus, medicine.medical_specialty, Prosthesis-Related Infections, MESH: Heart Valve Prosthesis, MESH : Male, MESH: Staphylococcal Infections, MESH : Bioprosthesis, Statistics, Nonparametric, MESH : Prosthesis-Related Infections, MESH : Heart Valve Prosthesis, MESH : Hospital Mortality, 03 medical and health sciences, MESH : Drug Resistance, Microbial, medicine, Humans, Endocarditis, MESH : Middle Aged, MESH: Endocarditis, Bacterial, MESH: Hospital Mortality, MESH : Statistics, Nonparametric, Aged, Bioprosthesis, MESH: Humans, business.industry, MESH: Prosthesis-Related Infections, MESH : Humans, MESH: Time Factors, MESH: Cross Infection, Endocarditis, Bacterial, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, MESH: Prospective Studies, Surgery, MESH: Bioprosthesis, Viridans streptococci, MESH : Postoperative Complications, MESH : Staphylococcal Infections, business, MESH: Female
Abstract: International audience; OBJECTIVE: To describe the contemporary features of coagulase-negative staphylococcal (CoNS) prosthetic valve endocarditis (PVE). DESIGN: Observational study of prospectively collected data from a multinational cohort of patients with infective endocarditis. Patients with CoNS PVE were compared to patients with Staphylococcus aureus and viridans streptococcal (VGS) PVE. SETTING: The International Collaboration on Endocarditis-Prospective Cohort Study (ICE-PCS) is a contemporary cohort of patients with infective endocarditis from 61 centres in 28 countries. PATIENTS: Adult patients in the ICE-PCS with definite PVE and no history of injecting drug use from June 2000 to August 2005 were included. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Heart failure, intracardiac abscess, death. RESULTS: CoNS caused 16% (n = 86) of 537 cases of definite non-injecting drug use-associated PVE. Nearly one-half (n = 33/69, 48%) of patients with CoNS PVE presented between 60 days and 365 days of valve implantation. The rate of intracardiac abscess was significantly higher in patients with CoNS PVE (38%) than in patients with either S aureus (23%, p = 0.03) or VGS (20%, p = 0.05) PVE. The rate of abscess was particularly high in early (50%) and intermediate (52%) CoNS PVE. In-hospital mortality was 24% for CoNS PVE, 36% for S aureus PVE (p = 0.09) and 9.1% for VGS PVE (p = 0.08). Meticillin resistance was present in 68% of CoNS strains. CONCLUSIONS: Nearly one-half of CoNS PVE cases occur between 60 days and 365 days of prosthetic valve implantation. CoNS PVE is associated with a high rate of meticillin resistance and significant valvular complications.
Published: 2009

165. The advantage of women in cancer survival: An analysis of EUROCARE-4 data

Author: Micheli, A., Ciampichini, R., Oberaigner, W., Ciccolallo, L., de Vries, E., Izarzugaza, I., Zambon, P., Gatta, G., De Angelis, R., Hackl, M., Van Eycken, E., Verstreken, Martine, Holub, J., Jurickova, L., Storm, H. H., Engholm, G., Hakulinen, T., Belot, A., Hedelin, G., Velten, M., Tron, I., Le Gall, E., Launoy, G., Guizard, A. V., Faivre, J., Bouvier, A. M., Carli, P. M., Maynadie, M., Danzon, A., Buemi, A., Tretarre, B., Lacour, B., Desandes, E., Colonna, M., Molinie, F., Bara, S., Schvartz, C., Ganry, O., Grosclaude, P., Brenner, H., Kaatsch, P., Ziegler, H., Tryggvadottir, L., Comber, H., Berrino, F., Allemani, C., Baili, P., Sant, M., Sowe, S., Zigon, G., Tagliabue, G., Contiero, P., Bellu`, F., Giacomin, A., Ferretti, S., Serraino, D., Dal Maso, L., De Dottori, M., D. e. Paoli, A., Zanier, L., Vercelli, M., Orengo, M. A., Casella, C., Quaglia, A., Pannelli, F., Federico, M., Rashid, I., Cirilli, C., Fusco, M., Traina, A., De Lisi, V., Bozzani, F., Magnani, C., Pastore, G., Tumino, R., La Rosa, M. G., Spata, E., Sigona, A., Mangone, L., Falcini, F., Foca, F., Giorgetti, S., Senatore, G., Iannelli, A., Budroni, M., Patriarca, S., Zanetti, R., Rosso, S., Piffer, S., Franchini, S., Paci, E., Crocetti, E., La Rosa, F., Stracci, F., Cassetti, T., Guzzinati, S., Caldora, M., Capocaccia, R., Carrani, E., Francisci, S., Grande, E., Inghelmann, R., Lenz, H., Martina, L., Roazzi, P., Santaquilani, M., Simonetti, A., Tavilla, A., Verdecchia, A., Dalmas, M., Langmark, F., Bray, F., Johannesen, T. B., Rachtan, J., Gozdz, S., Siudowska, U., Mezyk, R., Bielska-Lasota, M., Zwierko, M., Pinheiro, P. S., Primic-Zakelj, M., Mateos, A., Torrella-Ramos, A., Zurriaga, Oscar, Marcos-Gragera, R., Vilardell, M. L., Izquierdo, A., Martinez-Garcia, C., Sanchez, M. J., Navarro, C., Chirlaque, M. D., Peris-Bonet, R., Ardanaz, E., Moreno, C., Galceran, J., Klint, A., Talback, M., Jundt, G., Usel, M., Frick, H., Ess, S. M., Bordoni, A., Luthi, J. C., Konzelmann, I., Probst, N., Lutz, J. M., Pury, P., Visser, O., Otter, R., Schaapveld, M., Coebergh, J. W. W., Janssen-Heijnen, M. L., Louis van der Heijden, Null, Greenberg, D. C., Coleman, M. P., Woods, Laura, Moran, T., Forman, D., Cooper, N., Roche, M., Verne, J., Mã¸ller, H., Meechan, D., Poole, J., Lawrence, G., Stiller, C., Gavin, A., Black, R. J., Brewster, D. H., Steward, J. A., Basque Country Cancer Registry, Vitoria-Gasteiz, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), and Public Health
Subjects: Oncology, Male, Pathology, Cancer Research, cancer survival - women, MESH : Age Distribution, MESH : Aged, MESH: Risk Assessment, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH: Aged, 80 and over, Residence Characteristics, Neoplasms, 80 and over, Gender differences, Sex hormones, MESH: Neoplasms, MESH : Female, MESH: Residence Characteristics, Young adult, Age of Onset, MESH : Risk Assessment, MESH : Sex Distribution, MESH: Diagnosis-Related Groups, MESH: Aged, Aged, 80 and over, 0303 health sciences, education.field_of_study, MESH: Middle Aged, Relative survival, Thyroid, MESH: Sex Distribution, Middle Aged, MESH : Adult, 3. Good health, MESH : Age of Onset, Europe, MESH : Diagnosis-Related Groups, medicine.anatomical_structure, MESH: Young Adult, 030220 oncology & carcinogenesis, MESH: Survival Analysis, MESH : Residence Characteristics, Female, EUROCARE, Adult, medicine.medical_specialty, Adolescent, MESH: Age of Onset, MESH : Male, MESH : Sex Factors, Population, MESH : Europe, MESH : Young Adult, Rectum, Socio-culturale, [SDV.CAN]Life Sciences [q-bio]/Cancer, Risk Assessment, 03 medical and health sciences, Young Adult, Age Distribution, Sex Factors, MESH: Sex Factors, SDG 3 - Good Health and Well-being, Internal medicine, MESH : Adolescent, medicine, Humans, MESH : Middle Aged, Sex Distribution, education, MESH : Aged, 80 and over, MESH: Age Distribution, Survival analysis, Diagnosis-Related Groups, 030304 developmental biology, Aged, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, Cancer, Cancer survival, Survival Analysis, MESH: Adult, medicine.disease, MESH : Neoplasms, MESH: Male, MESH: Europe, Age of onset, MESH : Survival Analysis, business, MESH: Female
Abstract: We analysed 1.6 million population-based EUROCARE-4 cancer cases (26 cancer sites, excluding sex-specific sites, and breast) from 23 countries to investigate the role of sex in cancer survival according to age at diagnosis, site, and European region. For 15 sites (salivary glands, head and neck, oesophagus, stomach, colon and rectum, pancreas, lung, pleura, bone, melanoma of skin, kidney, brain, thyroid, Hodgkin disease and non-Hodgkin's lymphoma) age- and region-adjusted relative survival was significantly higher in women than men. By multivariable analysis, women had significantly lower relative excess risk (RER) of death for the sites listed above plus multiple myeloma. Women significantly had higher RER of death for biliary tract, bladder and leukaemia. For all cancers combined women had a significant 5% lower RER of death. Age at diagnosis was the main determinant of the women's advantage, which, however, decreased with increasing age, becoming negligible in the elderly, suggesting that sex hormone patterns may have a role in women's superior ability to cope with cancer. (C) 2008 Elsevier Ltd. All rights reserved.
Published: 2009

166. Egocentric reference in bidirectional readers as measured by the straight-ahead pointing task

Author: Sylvie Chokron, Esther Gaash, Eve Dupierrix, Seta Kazandjian, Itamar Y. Love, Ari Z. Zivotofsky, Maria De Agostini, Laboratoire de Psychologie et NeuroCognition (LPNC), Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Centre de recherche en épidémiologie et santé des populations (CESP), 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), Laboratoire Psychologie de la Perception (LPP - UMR 8242), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), 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), Cannard, Christine, Laboratoire de Psychologie et NeuroCognition ( LPNC ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Université Savoie Mont Blanc ( USMB [Université de Savoie] [Université de Chambéry] ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), 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 ), Laboratoire Psychologie de la Perception ( LPP - UMR 8242 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Male, Egocentrism, MESH: Proprioception, MESH: Language Tests, First language, MESH : Photic Stimulation, [SHS.PSY]Humanities and Social Sciences/Psychology, [ SCCO.PSYC ] Cognitive science/Psychology, 050109 social psychology, MESH: Observer Variation, MESH : Learning, 0302 clinical medicine, Reading (process), MESH : Female, MESH: Arm, Spatial organization, Language, media_common, Observer Variation, Language Tests, Point (typography), General Neuroscience, 05 social sciences, MESH : Adult, MESH: Ego, MESH: Photic Stimulation, medicine.anatomical_structure, MESH : Proprioception, Motor Skills, MESH: Young Adult, MESH : Motor Skills, MESH: Language, [ SCCO.NEUR ] Cognitive science/Neuroscience, [SCCO.PSYC]Cognitive science/Psychology, Arm, Educational Status, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Space Perception, Psychology, Social psychology, MESH : Orientation, Cognitive psychology, Adult, MESH : Male, media_common.quotation_subject, MESH : Language Tests, MESH: Space Perception, MESH : Young Adult, MESH: Orientation, MESH: Psychomotor Performance, MESH : Arm, [SHS.PSY] Humanities and Social Sciences/Psychology, [ SHS.PSY ] Humanities and Social Sciences/Psychology, Young Adult, 03 medical and health sciences, MESH : Verbal Behavior, MESH : Language, Orientation, medicine, Humans, Learning, 0501 psychology and cognitive sciences, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Molecular Biology, Ego, Visual search, MESH: Verbal Behavior, MESH: Humans, Verbal Behavior, [SCCO.NEUR]Cognitive science/Neuroscience, MESH : Humans, MESH: Adult, MESH : Observer Variation, MESH : Psychomotor Performance, Spatial cognition, Proprioception, MESH: Male, Sagittal plane, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Space Perception, MESH: Learning, Neurology (clinical), MESH: Educational Status, MESH: Female, MESH : Educational Status, Photic Stimulation, Psychomotor Performance, 030217 neurology & neurosurgery, MESH : Ego, MESH: Motor Skills, Developmental Biology
Abstract: International audience; The present study aimed to show that bidirectional reading and language exposure influence the position of egocentric reference (ER), the perceived direction of the body's sagittal axis proposed to act as an anchor for movements in extracorporeal space. Directional factors (e.g., visual scanning bias and reading habits) have been proposed to influence visuospatial performance, such as in line bisection and figure drawing. In past studies, bidirectional readers have been less consistent in demonstrating a bias compared to unidirectional readers. Using a straight-ahead pointing task to assess egocentric reference, we compared 14 unidirectional left-to-right readers (Uni-LR) to three bidirectional reading groups that differed in the reading direction of their native language and/or the level of their second language literacy: 16 low-English literate, native right-to-left, bidirectional readers (Lo-Bi-RL), 13 high-English literate, native right-to-left, bidirectional readers (Hi-Bi-RL), and 15 native left-to-right, bidirectional readers (Bi-LR). Participants were asked to point straight-ahead while blindfolded using either a left-to-right or a right-to-left scanning direction to approach the subjective sagittal midline. Uni-LRs showed left-side spatial bias when scanning left-to-right and right-side bias during right-to-left scanning, Bi-LRs and Lo-Bi-RLs (i.e., intermediate level or less in their second language) demonstrated the opposite pattern, and Hi-Bi-RLs showed left-side spatial bias regardless of scanning direction. Results are discussed in terms of accuracy and spatial bias regarding the interaction between reading direction and spatial cognition based on the level of bidirectional literacy and language exposure.
Published: 2009

167. Incidence and survival of gastric non-Hodgkin's lymphoma: A population-based study from the Association of the French Cancer Registries (FRANCIM)

Author: Danzon, Arlette, Belot, Aurélien, Maynadié, Marc, Remontet, Laurent, Dupont, Anne Claire Gossart, Carbonnel, Franck, Renseigné, Non, FRANCIM, Réseau des registres français du cancer, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Biostatistique, Hospices Civils de Lyon (HCL), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Département des maladies chroniques et traumatismes, Institut de Veille Sanitaire (INVS), Registre des hémopathies malignes de Côte d'Or, Service de biostatistique, Agents pathogènes et inflammation - UFC (EA 4266) (API), Université de Franche-Comté (UFC), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Hospices Civils de Lyon ( HCL ), Laboratoire de Biométrie et Biologie Evolutive ( LBBE ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique ( Inria ) -Centre National de la Recherche Scientifique ( CNRS ), Agents pathogènes et inflammation - UFC (EA 4266) ( API ), and Université de Franche-Comté ( UFC )
Subjects: Male, Multivariate analysis, MESH: Registries, MESH : Age Distribution, MESH : Aged, 0302 clinical medicine, MESH: Lymphoma, Non-Hodgkin, Risk Factors, MESH: Risk Factors, Epidemiology, MESH : Stomach Neoplasms, MESH : Neoplasm Staging, MESH : Female, Registries, MESH: Incidence, 030212 general & internal medicine, Age of Onset, MESH : Sex Distribution, MESH: Aged, MESH : Prognosis, MESH: Middle Aged, Relative survival, Incidence, Lymphoma, Non-Hodgkin, Incidence (epidemiology), MESH: Sex Distribution, Not Otherwise Specified, MESH: Stomach Neoplasms, MESH: Neoplasm Staging, Hematology, General Medicine, Middle Aged, MESH : Adult, Prognosis, MESH : Risk Factors, MESH : Incidence, MESH : Age of Onset, 3. Good health, Oncology, MESH: Young Adult, MESH: Survival Analysis, 030220 oncology & carcinogenesis, Female, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, France, Adult, medicine.medical_specialty, Adolescent, MESH : Male, MESH: Age of Onset, MESH : Young Adult, MESH: Multivariate Analysis, MESH: Prognosis, Young Adult, 03 medical and health sciences, Age Distribution, Stomach Neoplasms, MESH : Adolescent, Internal medicine, medicine, Humans, MESH : Middle Aged, MESH : Lymphoma, Non-Hodgkin, Radiology, Nuclear Medicine and imaging, Sex Distribution, MESH : France, MESH: Age Distribution, Survival analysis, Aged, Neoplasm Staging, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, MESH : Multivariate Analysis, Cancer, MESH: Adult, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Survival Analysis, MESH: Male, MESH: France, Multivariate Analysis, Immunology, MESH : Survival Analysis, Age of onset, business, MESH: Female, MESH : Registries
Abstract: International audience; BACKGROUND: Most epidemiological studies on gastric lymphomas (GL) were carried out before changes in therapy were introduced. The aim of the study was to measure the incidence of GL and to estimate survival. MATERIAL AND METHODS: Data were provided by the Association of the French Cancer Registries database. Age-standardized incidence rates were calculated for 786 incident cases diagnosed between 1978 and 2002. Crude and relative survival were calculated for 361 cases diagnosed between 1989 and 1997. Effects specific to sex, age at diagnosis, year of diagnosis, and grade of malignancy were estimated in multivariate analysis. RESULTS: Incidence was stable during the study period. However, high-grade GL frequency increased whereas low-grade and not otherwise specified (NOS) GL frequencies were respectively stable and decreased. At 5 years, relative survival was 63% in men and 60% in women. Patients aged 75 or older had a five-year relative survival of 33%. Age at diagnosis was the only significant prognostic factor in multivariate analysis. Time trend improvement in prognosis was observed. DISCUSSION: Results in elderly patients show that therapeutic regimens should be specifically designed and assessed for them. The prognosis improvement trend is probably related to the implementation of changes in management of patients and has to be confirmed by more recent data.
Published: 2009

168. Guillain‐Barré Syndrome and Influenza Virus Infection

Author: Tarek Sharshar, Pierre Lebon, Marie-Christine Durand, Valérie Sivadon-Tardy, Christiane Caudie, Sylvie van der Werf, Vincent Enouf, Elyanne Gault, David Orlikowski, Flore Rozenberg, Djillali Annane, Jean-Claude Raphaël, Jean-Louis Gaillard, Raphaël Porcher, Laboratoire de Microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Réanimation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Département de Biostatistique et Informatique Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Sain-Louis, Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de physiologie et d'explorations fonctionnelles [CHU Raymond-Poincaré], Centre National de Référence de la Grippe (France Nord) - Centre Collaborateur de l'OMS Grippe et autres virus respiratoires (CNR - CCOMS), Institut Pasteur [Paris], Génétique Moléculaire des Virus Respiratoires, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Laboratoire de Virologie, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Fédération de Biologie, Hopital Neurologique, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Sain-Louis, Service de physiologie et d'explorations fonctionnelles, AP-HP Hôpital Raymond Poincaré [Garches]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP), Université de Versailles–St. Quentin, Faculté de Médecine Paris‐Ile‐de‐France‐Ouest, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Sain-Louis, Université Paris Diderot - Paris 7 ( UPD7 ) -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 Hôpital Raymond Poincaré [Garches]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Faculté de Médecine ( UPD5 Médecine ), and Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: Male, MESH : Guillain-Barre Syndrome, Statistics as Topic, MESH : Statistics as Topic, MESH : Aged, Antibodies, Viral, MESH: Aged, 80 and over, 0302 clinical medicine, MESH : Gangliosides, Gangliosides, MESH : Influenza B virus, Medicine, MESH : Female, MESH : Influenza, Human, MESH: Incidence, 030212 general & internal medicine, MESH: Water Supply, MESH: Influenza B virus, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, biology, Respiratory tract infections, Guillain-Barre syndrome, Viral culture, Incidence, MESH: Influenza, Human, Influenzavirus B, Incidence (epidemiology), Complement Fixation Tests, Age Factors, MESH: Guidelines as Topic, virus diseases, Middle Aged, MESH : Adult, MESH : Incidence, 3. Good health, MESH : Influenza A virus, Infectious Diseases, Influenza A virus, MESH : Legislation, Medical, MESH: Hemagglutination Inhibition Tests, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, Seasons, Adult, MESH : Antibodies, Viral, Microbiology (medical), MESH : United States, MESH : United States Food and Drug Administration, MESH : Male, MESH: Influenza A virus, Orthomyxoviridae, Guillain-Barre Syndrome, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, H5N1 genetic structure, 03 medical and health sciences, MESH : Water Supply, MESH: United States Food and Drug Administration, Influenza, Human, MESH: United States, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, MESH : France, MESH : Guidelines as Topic, MESH: Statistics as Topic, Aged, MESH: Gangliosides, MESH : Complement Fixation Tests, MESH: Guillain-Barre Syndrome, MESH: Age Factors, MESH: Humans, MESH : Seasons, business.industry, MESH : Humans, MESH: Legislation, Medical, MESH: Adult, Hemagglutination Inhibition Tests, biology.organism_classification, medicine.disease, MESH : Hemagglutination Inhibition Tests, MESH: Male, MESH: France, Influenza B virus, MESH: Complement Fixation Tests, Immunology, biology.protein, MESH : Age Factors, business, MESH: Female, MESH: Seasons, MESH: Antibodies, Viral, 030217 neurology & neurosurgery, Antiganglioside antibodies
Abstract: International audience; BACKGROUND: In Western countries, the cause of 60% of all Guillain-Barré syndrome (GBS) cases remains unidentified. The number of cases of unidentified cause peaks in winter, and these cases are commonly preceded by respiratory tract infection or influenza-like illness. We investigated the triggering role of influenza virus infection. METHODS: Of 405 patients with GBS who were admitted to a French reference center during 1996-2004, 234 had cases caused by an unidentified agent. We used time-series methods to study the correlation between the monthly incidence of such cases and influenza-like illnesses reported by the Sentinelles surveillance network. We analyzed anti-influenza antibodies using complement fixation testing and hemagglutination-inhibition assays. We studied etiological subgroups using Wilcoxon and Fisher's exact tests. RESULTS: We found a positive association between the monthly incidence of GBS caused by an unidentified agent and reported influenza-like illnesses. Of 73 patients whose cases occurred during periods in which there was a possible link to influenza, 10 (13.7%) had serological evidence of recent influenza A, and 4 (5.5%) had serological evidence of influenza B. Eight of 10 influenza A-related cases occurred during "major" influenza seasons, and antibodies specific to the current epidemic strain were found in 9 cases. Most patients with influenza A-related cases were aged < 65 years, and none had antiganglioside antibodies. Influenza-related cases differed both from Campylobacter jejuni-related cases, with regard to the lack of need for mechanical ventilation (P = .014), and from the cases caused by an unidentified agent, with regard to the presence of preceding influenza-like illness or respiratory tract infection (P = .015) and longer time from the infectious event to GBS onset (P = .04). CONCLUSIONS: Influenza viruses are infrequent triggering agents of GBS but may play a significant role during major influenza outbreaks. Influenza-related GBS displays specific features and is not associated with antiganglioside antibody response, which suggests the presence of underlying immune mechanisms.
Published: 2009

169. Murine APOBEC1 Is a Powerful Mutator of Retroviral and Cellular RNA In Vitro and In Vivo

Author: Denise Guetard, Marc Sitbon, Jean-Pierre Vartanian, Anne Keriel, Myrtille Renard, Simon Wain-Hobson, Vincent Petit, Rétrovirologie Moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), and Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: Hypoxanthine Phosphoribosyltransferase, MESH : Molecular Sequence Data, MESH : RNA, Messenger, MESH : DNA, Complementary, MESH : NIH 3T3 Cells, viruses, Muscle Proteins, MESH: Base Sequence, Nucleic Acid Denaturation, MESH : Retroviridae Infections, MESH: Animals, Newborn, Mice, chemistry.chemical_compound, MESH : Hypoxanthine Phosphoribosyltransferase, Structural Biology, Murine leukemia virus, MESH : RNA, MESH: Animals, APOBEC Deaminases, MESH : Cytidine Deaminase, Gammaretrovirus, MESH : Muscle Proteins, 0303 health sciences, biology, Nucleotides, MESH : Animals, Newborn, 030302 biochemistry & molecular biology, MESH: Leukemia Virus, Murine, Cytidine, Cytidine deaminase, MESH: Apolipoproteins B, 3. Good health, Leukemia Virus, Murine, MESH: Retroviridae Infections, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH : Mutation, MESH: Genome, Viral, MESH : Genome, Viral, MESH : Leukemia Virus, Murine, MESH : Nucleic Acid Denaturation, APOBEC, DNA, Complementary, MESH: Mutation, APOBEC-1 Deaminase, Molecular Sequence Data, MESH: Leukemia, Experimental, Genome, Viral, MESH: Nucleic Acid Denaturation, [ SDV.MP.VIR ] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Muscle Proteins, 03 medical and health sciences, MESH: RNA, Cytidine Deaminase, MESH : Mice, MESH : RNA Editing, Animals, Humans, MESH: RNA Editing, RNA, Messenger, MESH: Mice, Molecular Biology, Apolipoproteins B, MESH: RNA, Messenger, MESH: Cytidine Deaminase, 030304 developmental biology, Messenger RNA, Leukemia, Experimental, MESH: Molecular Sequence Data, MESH: Humans, Base Sequence, APOBEC1, MESH : Humans, MESH: Tumor Virus Infections, RNA, MESH : Apolipoproteins B, MESH: DNA, Complementary, biology.organism_classification, MESH: Hypoxanthine Phosphoribosyltransferase, Molecular biology, MESH: Nucleotides, Tumor Virus Infections, Animals, Newborn, chemistry, Mutation, NIH 3T3 Cells, MESH : Nucleotides, MESH : Leukemia, Experimental, MESH : Base Sequence, MESH : Animals, RNA Editing, MESH : Tumor Virus Infections, Retroviridae Infections, MESH: NIH 3T3 Cells
Abstract: International audience; Mammalian APOBEC molecules comprise a large family of cytidine deaminases with specificity for RNA and single-stranded DNA (ssDNA). APOBEC1s are invariably highly specific and edit a single residue in a cellular mRNA, while the cellular targets for APOBEC3s are not clearly established, although they may curtail the transposition of some retrotransposons. Two of the seven member human APOBEC3 enzymes strongly restrict human immunodeficiency virus type 1 in vitro and in vivo. We show here that ssDNA hyperediting of an infectious exogenous gammaretrovirus, the Friend-murine leukemia virus, by murine APOBEC1 and APOBEC3 deaminases occurs in vitro. Murine APOBEC1 was able to hyperdeaminate cytidine residues in murine leukemia virus genomic RNA as well. Analysis of the edited sites shows that the deamination in vivo was due to mouse APOBEC1 rather than APOBEC3. Furthermore, murine APOBEC1 is able to hyperedit its primary substrate in vivo, the apolipoprotein B mRNA, and a variety of heterologous RNAs. In short, murine APOBEC1 is a hypermutator of both RNA and ssDNA in vivo, which could exert occasional side effects upon overexpression.
Published: 2009

170. Can the emotional connotation of concepts modulate the lexico-semantic deficits in Alzheimer's disease? : Emotion and semantic memory in Alzheimer's disease

Author: Francis Eustache, Bénédicte Giffard, Mickaël Laisney, Béatrice Desgranges, Neuropsychologie cognitive et neuroanatomie fonctionnelles de la mémoire humaine, Université de Caen Normandie ( UNICAEN ), and Normandie Université ( NU ) -Normandie Université ( NU ) -École pratique des hautes études ( EPHE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, Emotions, MESH : Aged, MESH : Alzheimer Disease, MESH : Analysis of Variance, Neuropsychological Tests, Behavioral Neuroscience, Mental Processes, 0302 clinical medicine, Semantic memory, MESH : Female, MESH : Semantics, computer.programming_language, Aged, 80 and over, 05 social sciences, Cognition, MESH : Language Disorders, Semantics, MESH : Neuropsychological Tests, Connotation (semiotics), Female, Lexico, Psychology, Priming (psychology), Cognitive psychology, MESH : Case-Control Studies, MESH : Male, MESH : Mental Processes, Cognitive Neuroscience, Decision Making, Experimental and Cognitive Psychology, Affect (psychology), MESH : Emotions, 050105 experimental psychology, 03 medical and health sciences, Alzheimer Disease, Similarity (psychology), Lexical decision task, Humans, 0501 psychology and cognitive sciences, MESH : Aged, 80 and over, Aged, Analysis of Variance, Language Disorders, MESH : Humans, MESH : Decision Making, Case-Control Studies, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], computer, 030217 neurology & neurosurgery
Abstract: International audience; Semantic memory impairments are a common symptom of Alzheimer's disease (AD) and may occur at a relatively early stage. These disturbances can be evidenced by a hyperpriming effect (greater semantic priming in AD patients than in controls). Up till now, very few studies of semantic memory have included emotionally charged concepts. Our aim was therefore to study the semantic processing of such concepts, as opposed to neutral ones, in early AD. Given that emotional processes are relatively preserved at the beginning of the disease compared with other cognitive functions, we expected that an emotional connotation would influence the spreading activation of words and affect some of the impairments in semantic processing. We administered a semantic priming task (lexical decision task) implicitly assessing semantic memory to 26 patients with AD and 26 normal controls. Primes and targets either had a semantic relationship (e.g. tiger-lion), a semantic and emotional (positive or negative) relationship (e.g. slap-smack) or no relationship at all (e.g. chair-horse), or else belonged to a word-nonword condition (e.g. window-inuly). Compared with controls, the patients showed pathological hyperpriming effects in all conditions, especially in the emotional conditions. Hyperpriming implies a deterioration in specific attributes, as it is difficult to tell two concepts apart once their distinctive attributes have been lost. These results suggest that emotional concepts, like neutral ones, lose some of their distinctive attributes in early AD, and as the emotional processes are preserved, there is greater similarity between close emotional concepts than between close neutral concepts.
Published: 2009

171. Hospital Costs of Renal Transplant Management

Author: Hugues Bittard, A. Dussaucy, Jean-Marc Chalopin, N. Chaumard, Philippe Fagnoni, Marie-Christine Woronoff-Lemsi, Samuel Limat, Virginie Nerich, Chim Analyt Lab, Equipe Sci Separat Biol & Pharmaceut, Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Centre d'Investigation Clinique de Besançon ( CICB ), Etablissement Français du Sang Bourgogne Franche-Comté-Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Franche-Comté ( UFC ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Pathologies et épithéliums : prévention, innovation, traitements, évaluation (EA 4267) (PEPITE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: MESH : Retrospective Studies, MESH : Hospital Units, 030232 urology & nephrology, MESH: Hospitalization, MESH: Length of Stay, MESH: Kidney Transplantation, Hospitals, University, 0302 clinical medicine, MESH : Costs and Cost Analysis, 030212 general & internal medicine, MESH: Diagnosis-Related Groups, health care economics and organizations, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, University hospital, 3. Good health, Hospitalization, MESH : Diagnosis-Related Groups, MESH : Length of Stay, Renal transplant, Costs and Cost Analysis, MESH : Hospitalization, MESH: Hospital Units, France, Hospital Units, Medical costs, medicine.medical_specialty, MESH: Costs and Cost Analysis, 03 medical and health sciences, Case mix index, medicine, Humans, MESH : France, Intensive care medicine, Diagnosis-Related Groups, MESH : Hospitals, University, Retrospective Studies, MESH: Hospitals, University, Transplantation, MESH: Humans, business.industry, MESH : Humans, MESH: Retrospective Studies, Retrospective cohort study, Length of Stay, Kidney Transplantation, MESH: France, Actual cost, [ SDV.SP ] Life Sciences [q-bio]/Pharmaceutical sciences, MESH : Kidney Transplantation, Surgery, business, Hospital stay
Abstract: International audience; Renal transplantation is considered to be a cost-effective therapy, but hospital medical costs are not accurately known. The aim of this work was to evaluate the costs of hospital stay for renal transplantation. This retrospective study included all patients who underwent renal transplantation between January 1, 2004, and December 31, 2005, in our University hospital. The incurred costs were determined using our center's analytical accounting (AA). The mean local cost was then compared with the median national cost of hospitalization for renal transplantation, based on a sample of participating centers contributing to the National Cost Scale (NCS) per homogenous diagnosis-related group (DRG). These mean costs were weighed against the financing obtained by national rates of the case-mix based payment system (termed T2A). Data were collected from 77 patients. Their mean length of stay was 19.4 days. AA determined the cost of management to be euro14,100 per patient. National economic approaches were significantly higher: euro16,389 for NCS and euro17,369 for national rates. Thus, the specific DRG rate (case mix index) of renal transplantation covers the expenses incurred by our center. These results are rather interesting; however, it is unlike those obtained for the management of other diseases such as acute myeloid leukemia, where T2A underestimates the actual cost by 2-4 times. Last, the hospital budget and T2A must be considered as a whole. The fact that DRGs with favorable and unfavorable pricing balance out should be taken into account.
Published: 2008

172. Interaction of the coiled‐coil domain with glycosaminoglycans protects angiopoietin‐like 4 from proteolysis and regulates its antiangiogenic activity

Author: Sylvie Ricard-Blum, Clément Faye, Corinne Ardidie-Robouant, Clémence Chomel, Laurent Muller, Stéphane Germain, Aurélie Cazes, A. Barret, Catherine Monnot, Elisa Gomez, Marine Bignon, Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by the European Vascular Genomics Network (http://www.evgn.org) (contract LSHMCT-2003-503254), ANR-06-JCJC-0160,ANGPTL4,Role of ANGPTL4 during development and ischemic heart disease(2006), Pathologie vasculaire et endocrinologie rénale, Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Experimental Medicine Unit, Collège de France ( CdF ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Service d'hématologie A [CHU HEGP], and ANR-06-JCJC-0160,ANGPTL4,Role of ANGPTL4 during development and ischemic heart disease ( 2006 )
Subjects: MESH : Cell Line, MESH : Angiopoietins, Protein Conformation, Angiogenesis, MESH: Cricetinae, Biochemistry, Extracellular matrix, angiogenesis, MESH: Protein Structure, Tertiary, MESH: Protein Conformation, 0302 clinical medicine, MESH : Lipid Metabolism, Cricetinae, MESH: Animals, MESH : Protein Conformation, Glycosaminoglycans, MESH: Lipid Metabolism, 0303 health sciences, MESH : Neovascularization, Physiologic, medicine.diagnostic_test, Chemistry, MESH : Cricetinae, MESH : Extracellular Matrix, MESH : Protein Binding, MESH: Glycosaminoglycans, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Cell biology, Endothelial stem cell, 030220 oncology & carcinogenesis, endothelial cell, MESH : Mutation, MESH : Protein Structure, Tertiary, MESH: Neovascularization, Physiologic, Protein Binding, Biotechnology, MESH: Mutation, extracellular matrix, Proteolysis, Neovascularization, Physiologic, Angiopoietin-like 4 Protein, MESH: Extracellular Matrix, Cell Line, Angiopoietin, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Glycosaminoglycans, Genetics, medicine, Animals, Humans, MESH: Protein Binding, Molecular Biology, 030304 developmental biology, MESH: Humans, hypoxia, MESH : Humans, Lipid Metabolism, Protein Structure, Tertiary, MESH: Cell Line, Cell culture, MESH: Angiopoietins, Mutation, MESH : Animals, Proprotein Convertases, Angiopoietins
Abstract: International audience; Angiopoietin-like 4 (ANGPTL4) is involved in angiogenesis and lipid metabolism. It is secreted by liver and adipose tissues and cleaved to generate circulating coiled-coil domain (CCD) and fibrinogen-like domain (FLD) fragments. The full-length ANGPTL4 produced by hypoxic endothelial cells interacts with the extracellular matrix (ECM). The ECM-bound and soluble forms of ANGPTL4 have antiangiogenic properties. We carried out a structure-function analysis to investigate the regulation of ANGPTL4 bioactivity in endothelial cells. We found that the recombinant CCD binds to the ECM, whereas the FLD is released into the medium. The CCD, like the full-length ANGPTL4, binds to heparan and dermatan sulfates in surface plasmon resonance assays and inhibits endothelial cell adhesion, motility, and tubule-like formation. In endothelial cells, ANGPTL4 is processed in the secretion medium after release from the ECM. This processing is altered by the proprotein convertases inhibitor alpha1-PDX and abolished by the mutation of the (161)RRKR(164) cleavage site without modification of the ECM binding and release. These data suggest that the full-length form, which interacts with heparan sulfate proteoglycans via its CCD, is protected from proteolysis by proprotein convertases and constitutes the major active pool of ANGPTL4 in hypoxic endothelial cells.
Published: 2008

173. High rate of early virological failure with the once-daily tenofovir/lamivudine/nevirapine combination in naive HIV-1-infected patients

Author: Clotilde Allavena, Marie-Paule Schmitt, Bruno Hoen, Pascal Chavanet, P. Meyer, Michel Duong, J. M. Lang, David Rey, M. Diemer, Thierry May, Vincent Calvez, Bruno Spire, G. Hoizey, Gilles Peytavin, J. L. Schmit, Entente Interdépartementale pour la Démoustication, Région Rhône-Alpes, Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institut de Recherches sur les lois Fondamentales de l'Univers ( IRFU ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Laboratoire du Service d'Oncologie Médicale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Chrono-environnement (UMR 6249) (LCE), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, MESH: CD4 Lymphocyte Count, HIV Infections, MESH : Viral Load, Gastroenterology, MESH: HIV-1, MESH : Adenine, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH : Female, Pharmacology (medical), 030212 general & internal medicine, MESH: Nevirapine, MESH: Anti-HIV Agents, MESH : Viral Proteins, MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, MESH: Drug Resistance, Viral, Reverse-transcriptase inhibitor, MESH : Lamivudine, Lamivudine, MESH: HIV Infections, Middle Aged, Viral Load, MESH : Adult, Resistance mutation, MESH: Amino Acid Substitution, 3. Good health, MESH : Drug Resistance, Viral, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Treatment Outcome, Infectious Diseases, Female, Viral disease, MESH: Viral Load, MESH : Phosphonic Acids, MESH : HIV-1, MESH: Lamivudine, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, MESH: Adenine, Nevirapine, Anti-HIV Agents, MESH : Male, MESH : Nevirapine, Mutation, Missense, Organophosphonates, MESH: Phosphonic Acids, MESH : Treatment Outcome, Biology, Viral Proteins, 03 medical and health sciences, Zidovudine, MESH : Amino Acid Substitution, Internal medicine, Drug Resistance, Viral, MESH : CD4 Lymphocyte Count, MESH : HIV Infections, medicine, Humans, MESH : Middle Aged, Tenofovir, Pharmacology, MESH: Mutation, Missense, MESH: Humans, 030306 microbiology, Adenine, MESH : Anti-HIV Agents, MESH : Humans, MESH: Adult, Interim analysis, MESH: Viral Proteins, Virology, MESH: Male, CD4 Lymphocyte Count, Regimen, Amino Acid Substitution, HIV-1, MESH: Female, MESH : Mutation, Missense
Abstract: International audience; BACKGROUND: The combination of one non-nucleoside reverse transcriptase inhibitor (NNRTI) with two nucleoside reverse transcriptase inhibitors is a validated first-line antiretroviral (ARV) therapy. The once-daily combination of lamivudine, tenofovirDF and nevirapine has not been evaluated in a clinical trial. METHODS: Randomized, open-label, multicentre, non-inferiority trial comparing lamivudine, tenofovirDF and nevirapine once daily (Group 2) with zidovudine/lamivudine and nevirapine twice daily (Group 1), in naive HIV-1-infected patients with a CD4 count
Published: 2008

174. Primary cystic lung light chain deposition disease: a clinicopathologic entity derived from unmutated B cells with a stereotyped IGHV4-34/IGKV1 receptor

Author: Marc Stern, Marie-Hélène Delfau-Larue, Hervé Mal, Diane Damotte, Magali Colombat, Michel Fournier, Patrice Callard, Jacques Diebold, Jean-Pierre Farcet, Christiane Copie-Bergman, Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service de pneumologie B, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Service d'anatomie pathologique, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu, Département de pathologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Service d'anatomo-pathologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service d'immunologie biologique, Service de pneumologie, and Hôpital Foch [Suresnes]
Subjects: Lung Diseases, Pathology, MESH : Molecular Sequence Data, MESH : DNA, medicine.medical_treatment, Immunoglobulin Variable Region, Paraproteinemias, MESH : Immunoglobulin Heavy Chains, Plasma cell, Biochemistry, 0302 clinical medicine, MESH : Female, MESH : Immunoglobulin Variable Region, B-Lymphocytes, 0303 health sciences, MESH : Lung Diseases, Cysts, MESH : Amino Acid Sequence, Hematology, MESH : Adult, MESH : Immunoglobulin Light Chains, 3. Good health, medicine.anatomical_structure, MESH : Paraproteinemias, 030220 oncology & carcinogenesis, MESH : Lung Transplantation, Female, Genes, Immunoglobulin Light Chain, Immunoglobulin Heavy Chains, Lung Transplantation, Adult, medicine.medical_specialty, Genes, Immunoglobulin Heavy Chain, Molecular Sequence Data, Immunology, MESH : Genes, Immunoglobulin Heavy Chain, MESH : Cysts, Biology, Immunoglobulin light chain, Article, Light chain deposition disease, MESH : B-Lymphocytes, Lung Disorder, Immunoglobulin kappa-Chains, 03 medical and health sciences, MESH : Immunoglobulin kappa-Chains, medicine, Humans, Lung transplantation, Amino Acid Sequence, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Genes, Immunoglobulin Light Chain, 030304 developmental biology, Lung, Base Sequence, MESH : Humans, DNA, Cell Biology, medicine.disease, Immunoglobulin heavy chain, MESH : Base Sequence, Immunoglobulin Light Chains, CD5
Abstract: We have recently described a new form of light chain deposition disease (LCDD) presenting as a severe cystic lung disorder requiring lung transplantation. There was no bone marrow plasma cell proliferation. Because of the absence of disease recurrence after bilateral lung transplantation and of serum-free light chain ratio normalization after the procedure, we hypothesized that monoclonal light chain synthesis occurred within the lung. The aim of this study was to look for the monoclonal B-cell component in 3 patients with cystic lung LCDD. Histologic examination of the explanted lungs showed diffuse nonamyloid κ light chain deposits associated with a mild lymphoid infiltrate composed of aggregates of small CD20+, CD5−, CD10− B lymphocytes reminiscent of bronchus-associated lymphoid tissue. Using polymerase chain reaction (PCR), we identified a dominant B-cell clone in the lung in the 3 studied patients. The clonal expansion of each patient shared an unmutated antigen receptor variable region sequence characterized by the use of IGHV4-34 and IGKV1 subgroups with heavy and light chain CDR3 sequences of more than 80% amino acid identity, a feature evocative of an antigen-driven process. Combined with clinical and biologic data, our results strongly argue for a new antigen-driven primary pulmonary lymphoproliferative disorder.
Published: 2008

175. Serological prevalence of echinococcosis and risk factors for infection among children in rural communities of southern Ningxia, China

Author: Philip S. Craig, Ling Huang, Jing Teng, Tao Sun, Gail M. Williams, Wei Zhang, Malcolm K. Jones, Yu Rong Yang, Belgees Boufana, Dominique A. Vuitton, Patrick Giraudoux, Donald P. McManus, Yanbin Li, Tian Xi Liu, Ningxia Medical College, Biomedical Sciences Research Institute, University of Salford, WHO Collaborating Center on Prevention and Treatment of Human Echinococcosis, SERF Unit, Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ), Molecular Parasitology Unit, University of Queensland [Brisbane]-The Queensland Institute of Medical Research-Australian Centre for International and Tropical Health and Nutrition ( ACITH ), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Queensland Institute of Medical Research-University of Queensland [Brisbane]-Australian Centre for International and Tropical Health and Nutrition (ACITH)
Subjects: Prevalence, Rural Health, MESH : Echinococcus multilocularis, MESH: Epidemiologic Methods, MESH : Echinococcosis, MESH: Echinococcus granulosus, 030308 mycology & parasitology, 0302 clinical medicine, MESH : Child, Risk Factors, MESH: Risk Factors, MESH: Child, MESH : Rural Health, MESH : Socioeconomic Factors, MESH: Animals, Child, Echinococcus granulosus, 0303 health sciences, biology, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Risk Factors, Echinococcosis, MESH: China, 3. Good health, [ SDE.MCG ] Environmental Sciences/Global Changes, Infectious Diseases, China, MESH: Socioeconomic Factors, Adolescent, [SDE.MCG]Environmental Sciences/Global Changes, 030231 tropical medicine, Helminthiasis, MESH : Family Health, Echinococcus multilocularis, MESH : Epidemiologic Methods, MESH: Echinococcosis, 03 medical and health sciences, MESH : Adolescent, Environmental health, parasitic diseases, medicine, Animals, Humans, MESH : China, Seroprevalence, Risk factor, Family Health, MESH: Adolescent, MESH: Echinococcus multilocularis, MESH: Humans, MESH : Echinococcus granulosus, business.industry, MESH : Humans, Public Health, Environmental and Occupational Health, MESH: Rural Health, medicine.disease, biology.organism_classification, Echinococcus, Socioeconomic Factors, MESH: Family Health, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Parasitology, MESH : Animals, Epidemiologic Methods, business
Abstract: International audience; OBJECTIVE: To assess the usefulness of serology as an indicator of Echinococcus transmission for developing preventive measures against echinococcosis in rural communities. METHODS: Cross-sectional survey in 2002 among 861 children aged 7 to 18 years in Xiji County, Ningxia, China. Before ultrasound abdominal examination, a questionnaire was used to identify socioeconomic, sanitary and hygiene risk factors for echinococcal infection; filter paper blood samples were collected from each child for specific antibody detection using EmP (Echinococcus multilocularis) and EgB (Echinococcus granulosus) antigens. RESULTS: Transmission of both E. multilocularis and E. granulosus occur in this area. Serological prevalence was far higher than disease prevalence in this age range. We found no gender-related differences of seroprevalence among the children, suggesting an equal chance of exposure to echinococcal egg-contaminated environments. The seroprevalence distribution was associated with changes in the ecology of wild hosts for E. multilocularis contamination, and with changes in socio-geographic features of the communities for E. granulosus contamination. CONCLUSIONS: Serological data obtained for children in mass surveys of echinococcosis appear to be a comprehensive and useful tool to monitor changes of transmission dynamics in humans and provide 'warning signals' to decision makers for the instigation of specific control measures against the disease.
Published: 2008

176. CD40 Ligand Protects from TRAIL-Induced Apoptosis in Follicular Lymphomas through NF-κB Activation and Up-Regulation of c-FLIP and Bcl-xL

Author: Patricia Amé-Thomas, Thierry Lamy, Olivier Micheau, Alexandre Morizot, Marion Travert, G. Semana, Thierry Guillaudeux, Céline Pangault, Thierry Fest, Karin Tarte, Microenvironnement et cancer ( MiCa ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie, Immunologie et de Thérapie Cellulaire ( HITC ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service d'Hématologie, Immunologie et de Thérapie Cellulaire (HITC), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Le Corre, Morgane
Subjects: CD4-Positive T-Lymphocytes, MESH: Signal Transduction, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein, Palatine Tonsil, CASP8 and FADD-Like Apoptosis Regulating Protein, MESH: NF-kappa B, Apoptosis, MESH: Caspase 8, Receptors, Tumor Necrosis Factor, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, TNF-Related Apoptosis-Inducing Ligand, MESH: Recombinant Proteins, MESH : TNF-Related Apoptosis-Inducing Ligand, MESH: Lymphoma, Follicular, 0302 clinical medicine, MESH: Up-Regulation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Cytotoxic T cell, MESH : Nitriles, Sulfones, MESH : Antigens, CD40, Lymphoma, Follicular, MESH : Up-Regulation, Cells, Cultured, B-Lymphocytes, Caspase 8, 0303 health sciences, MESH : Caspase 8, biology, NF-kappa B, MESH: CD4-Positive T-Lymphocytes, MESH: Sulfones, Recombinant Proteins, MESH: Nitriles, Up-Regulation, Cell biology, medicine.anatomical_structure, MESH : CD4-Positive T-Lymphocytes, MESH : NF-kappa B, 030220 oncology & carcinogenesis, MESH: Palatine Tonsil, [SDV.IMM]Life Sciences [q-bio]/Immunology, Signal transduction, MESH: TNF-Related Apoptosis-Inducing Ligand, Signal Transduction, MESH: Cells, Cultured, MESH: Cell Line, Tumor, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Recombinant Proteins, T cell, CD40 Ligand, Immunology, bcl-X Protein, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bcl-xL, MESH: Antigens, CD40, MESH: bcl-X Protein, MESH : B-Lymphocytes, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, MESH: B-Lymphocytes, Nitriles, MESH : Cells, Cultured, medicine, Humans, CD40 Antigens, MESH: Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Receptors, TNF-Related Apoptosis-Inducing Ligand, MESH : Sulfones, MESH : Palatine Tonsil, MESH: CD40 Ligand, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, CD40, MESH : Cell Line, Tumor, MESH: Apoptosis, MESH : bcl-X Protein, MESH : Lymphoma, Follicular, MESH : Humans, Germinal center, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, MESH: Receptors, Tumor Necrosis Factor, MESH : CD40 Ligand, MESH : Receptors, Tumor Necrosis Factor, Receptors, TNF-Related Apoptosis-Inducing Ligand, biology.protein, MESH : Apoptosis
Abstract: The TNF family member TRAIL is emerging as a promising cytotoxic molecule for antitumor therapy. However, its mechanism of action and the possible modulation of its effect by the microenvironment in follicular lymphomas (FL) remain unknown. We show here that TRAIL is cytotoxic only against FL B cells and not against normal B cells, and that DR4 is the main receptor involved in the initiation of the apoptotic cascade. However, the engagement of CD40 by its ligand, mainly expressed on a specific germinal center CD4+ T cell subpopulation, counteracts TRAIL-induced apoptosis in FL B cells. CD40 induces a rapid RNA and protein up-regulation of c-FLIP and Bcl-xL. The induction of these antiapoptotic molecules as well as the inhibition of TRAIL-induced apoptosis by CD40 is partially abolished when NF-κB activity is inhibited by a selective inhibitor, BAY 117085. Thus, the antiapoptotic signaling of CD40, which interferes with TRAIL-induced apoptosis in FL B cells, involves NF-κB-mediated induction of c-FLIP and Bcl-xL which can respectively interfere with caspase 8 activation or mitochondrial-mediated apoptosis. These findings suggest that a cotreatment with TRAIL and an inhibitor of NF-κB signaling or a blocking anti-CD40 Ab could be of great interest in FL therapy.
Published: 2008

177. The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells

Author: Jean-Claude Weill, Bertrand Godeau, François Paye, Nina Arakelyan, Alain Sauvanet, Pierre Buffet, Odile Beyne-Rauzy, Bruno Varet, Sandra K. Weller, Anne Berger, Jacques-Olivier Pers, Maria Mamani-Matsuda, Claude-Agnès Reynaud, Claire Fieschi, Caroline Staib, Loïc Garçon, Marc Michel, Ahmad Faili, Olivier Hermine, Antonio Cosma, Jean-Marie Andrieu, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Clinical cooperation group 'Immune monitoring', German Research Center for Environmental Health - Helmholtz Center München (GmbH), Clinical cooperation group 'Antigen-specific immunotherapy', Institute of Molecular Virology, Institute of Virology, Technical University, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne et Immunopathologie, CHU Toulouse [Toulouse], Laboratoire d'immunologie, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Immunologie et Pathologie ( EA2216 ), Université de Brest ( UBO ) -IFR148, Service d'oncologie médicale [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Service de Chirurgie Digestive, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Médical de l'Institut Pasteur, Institut Pasteur [Paris], This work was supported by the Fondation Princesse Grace, the Agence Nationale pour la Recherche ('B cell memory', MIIM program) and the Ligue Contre le Cancer (Equipe labellisée). M.M.-M. was supported by successive fellowships from the Fondation de France, the Fondation Singer-Polignac and the Région Ile-de- France, and ANR : 'B cell memory', MIIM program,'B cell memory', MIIM program
Subjects: MESH : Spleen, MESH : Case-Control Studies, MESH : Immunoglobulin G, MESH : Immunologic Memory, Immunology, Naive B cell, Vaccinia virus, Spleen, Biochemistry, Immunoglobulin G, Virus, MESH : B-Lymphocytes, 03 medical and health sciences, 0302 clinical medicine, medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, MESH : Splenectomy, 030304 developmental biology, B-Lymphocytes, 0303 health sciences, MESH : Vaccinia virus, biology, MESH : Humans, Cell Biology, Hematology, Virology, 3. Good health, B-1 cell, medicine.anatomical_structure, Case-Control Studies, Splenectomy, biology.protein, Antibody, Million Cells, Immunologic Memory, Homeostasis, 030215 immunology
Abstract: The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG+ cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG+ cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG+ B cells in blood (ie, 50-100 000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell– depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory—long-lived memory B cells and plasma cells—have specific anatomic distributions—spleen and bone marrow—and homeostatic regulation.
Published: 2008

178. Hypoxia Down-regulates CCAAT/Enhancer Binding Protein-α Expression in Breast Cancer Cells

Author: Robert Barouki, Etienne Blanc, Nathalie M. Mazure, Fabrice Lecuru, Marie-Claude Fulchignoni-Lataud, Marie-Aude Le Frere Belda, Anne Dreiem, Thérèse Hervèe Mayi, Charbel Massaad, Vincent Favaudon, Liliane Massaad-Massade, Ramzi Seifeddine, Laboratoire de Détection et de Géophysique (CEA) (LDG), DAM Île-de-France (DAM/DIF), Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction des Applications Militaires (DAM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), IFR50, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Génotoxicologie, signalisation et radiothérapie expérimentale, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique moléculaire, Régulation de la transcription et maladies génétiques (RTMG), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Stéroïdes et système nerveux : physiopathologie moléculaire et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine Paris-Sud, Université Paris-Sud - Paris 11 (UP11), Toxicologie Moleculaire (U490), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Laboratoire de Détection et de Géophysique (CEA) ( LDG ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Faculté de Médecine Nice, Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -INSTITUT CURIE, Régulation de la transcription et maladies génétiques ( RTMG ), Centre National de la Recherche Scientifique ( CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ), Toxicologie Moleculaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Faculté de Médecine Nice, Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Curie
Subjects: Cancer Research, Hypoxia-Inducible Factor 1, MESH : Molecular Sequence Data, MESH : RNA, Messenger, Transcription, Genetic, MESH : Immunohistochemistry, MESH: Cell Hypoxia, Electrophoretic Mobility Shift Assay, MESH: Cell Cycle, RNA polymerase II, MESH : Blotting, Western, MESH : Breast Neoplasms, MESH: Base Sequence, MESH : RNA, Small Interfering, MESH: Down-Regulation, MESH : Down-Regulation, 0302 clinical medicine, Transcription (biology), MESH: Reverse Transcriptase Polymerase Chain Reaction, Enhancer binding, MESH: RNA, Small Interfering, Gene expression, MESH: CCAAT-Enhancer-Binding Protein-alpha, MESH : CCAAT-Enhancer-Binding Protein-alpha, RNA, Small Interfering, Promoter Regions, Genetic, 0303 health sciences, Gene knockdown, Reverse Transcriptase Polymerase Chain Reaction, Cell Cycle, MESH : Reverse Transcriptase Polymerase Chain Reaction, Immunohistochemistry, Cell Hypoxia, 3. Good health, MESH: Promoter Regions (Genetics), Oncology, MESH : Electrophoretic Mobility Shift Assay, 030220 oncology & carcinogenesis, MESH: Cell Growth Processes, MESH : Cell Hypoxia, MESH : Transfection, Subcellular Fractions, medicine.medical_specialty, MESH : Hypoxia-Inducible Factor 1, alpha Subunit, MESH: Cell Line, Tumor, Blotting, Western, Molecular Sequence Data, MESH : Deferoxamine, Down-Regulation, Breast Neoplasms, Cell Growth Processes, MESH : Subcellular Fractions, Deferoxamine, Biology, Transfection, MESH: Hypoxia-Inducible Factor 1, alpha Subunit, 03 medical and health sciences, Cell Line, Tumor, Internal medicine, MESH : Cell Cycle, CCAAT-Enhancer-Binding Protein-alpha, medicine, Humans, MESH: Blotting, Western, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcription factor, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Cell Line, Tumor, MESH: Transcription, Genetic, MESH: Transfection, MESH : Humans, MESH : Transcription, Genetic, MESH: Immunohistochemistry, MESH: Deferoxamine, Hypoxia-Inducible Factor 1, alpha Subunit, MESH : Promoter Regions (Genetics), Molecular biology, Endocrinology, HIF1A, MESH : Cell Growth Processes, MESH: Subcellular Fractions, MESH: Electrophoretic Mobility Shift Assay, biology.protein, MESH : Base Sequence, MESH: Breast Neoplasms
Abstract: International audience; The transcription factor CCAAT/enhancer binding protein-alpha (C/EBP alpha) is involved in the control of cell differentiation and proliferation, and has been suggested to act as a tumor suppressor in several cancers. By using microarray analysis, we have previously shown that hypoxia and estrogen down-regulate C/EBP alpha mRNA in T-47D breast cancer cells. Here, we have examined the mechanism by which the down-regulation by hypoxia takes place. Using the specific RNA polymerase II inhibitor 5,6-dichlorobenzimidazole-1-beta-D-ribofuranoside, the mRNA stability was analyzed under normoxia or hypoxia by quantitative reverse transcription-PCR. Hypoxia reduced the half-life of C/EBP alpha mRNA by approximately 30%. C/EBP alpha gene promoter studies indicated that hypoxia also repressed the transcription of the gene and identified a hypoxia-responsive element (-522; -527 bp), which binds to hypoxia-inducible factor (HIF)-1 alpha, as essential for down-regulation of C/EBP alpha transcription in hypoxia. Immunocytochemical analysis showed that C/EBP alpha was localized in the nucleus at 21% O(2), but was mostly cytoplasmic under 1% O(2). Knockdown of HIF-1 alpha by RNAi restored C/EBP alpha to normal levels under hypoxic conditions. Immunohistochemical studies of 10 tumor samples did not show any colocalization of C/EBP alpha and glucose transporter 1 (used as a marker for hypoxia). Taken together, these results show that hypoxia down-regulates C/EBP alpha expression in breast cancer cells by several mechanisms, including transcriptional and posttranscriptional effects. The down-regulation of C/EBP alpha in hypoxia is mediated by HIF-1.
Published: 2008

179. Prognostic Factors for Leukemic Induction Failure in Children With Acute Lymphoblastic Leukemia and Outcome After Salvage Therapy: The FRALLE 93 Study

Author: Claudine Schmitt, Marie-Françoise Auclerc, Jean-Michel Cayuela, Gérard Michel, André Baruchel, Guy Leverger, Marianne Debré, Yves Perel, Brigitte Pautard, Thierry Leblanc, Gérard Socié, Raphaël Porcher, Caroline Oudot, Christophe Piguet, Virginie Gandemer, Vincent Levy, Claire Berger, Christiane Vermylen, Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service d'hématologie pédiatrique, Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre d'Investigations Cliniques 9504, Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Biostatistique et Informatique Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Sain-Louis, Service d'onco-hématologie pédiatrique, hôpital Sud, Service de Pédiatrie Oncologie, Service d'immuno-hématologie pédiatrique [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), Département d'hématologie pédiatrique, Université Catholique de Louvain = Catholic University of Louvain (UCL), CHU Amiens-Picardie, Service d'Hématologie et Oncologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Unité d'hématologie et de transplantation, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -CHU Saint Louis [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Sain-Louis, Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Catholique de Louvain ( UCL ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service d'hématologie-immunologie-oncologie pédiatrique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], and De Villemeur, Hervé
Subjects: Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Oncology, MESH: Remission Induction, Cancer Research, MESH : Antineoplastic Combined Chemotherapy Protocols, MESH: Treatment Failure, Lymphoblastic Leukemia, MESH : Prospective Studies, Salvage therapy, MESH : Analysis of Variance, MESH: Logistic Models, MESH : Child, Preschool, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH : Child, Risk Factors, MESH: Risk Factors, MESH: Child, Antineoplastic Combined Chemotherapy Protocols, MESH : Precursor Cell Lymphoblastic Leukemia-Lymphoma, [ SDV.MHEP.HEM ] Life Sciences [q-bio]/Human health and pathology/Hematology, MESH : Female, Prospective Studies, Treatment Failure, Child, Prospective cohort study, 0303 health sciences, MESH : Prognosis, Remission Induction, MESH : Infant, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, MESH : Adult, Prognosis, MESH : Risk Factors, MESH: Infant, MESH: Salvage Therapy, 3. Good health, MESH: Antineoplastic Combined Chemotherapy Protocols, Child, Preschool, 030220 oncology & carcinogenesis, Female, France, Adult, medicine.medical_specialty, Adolescent, MESH : Male, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Prognosis, Risk category, 03 medical and health sciences, MESH : Treatment Failure, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Adolescent, MESH: Analysis of Variance, Internal medicine, Acute lymphocytic leukemia, medicine, Humans, MESH : France, 030304 developmental biology, Salvage Therapy, MESH: Adolescent, MESH: Precursor Cell Lymphoblastic Leukemia-Lymphoma, Analysis of Variance, MESH : Remission Induction, MESH: Humans, business.industry, MESH : Humans, MESH: Child, Preschool, Infant, Cancer, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, Surgery, MESH: France, Clinical trial, Logistic Models, Multicenter study, MESH : Salvage Therapy, business, MESH: Female, MESH : Logistic Models
Abstract: Purpose To identify prognostic factors and to evaluate the outcome of children with acute lymphoblastic leukemia (ALL) failure after induction therapy. Patients and Methods Between June 1993 and December 1999, 1,395 leukemic children were included in the French Acute Lymphoblastic Leukemia 93 study. Results Fifty-three patients (3.8%) had a leukemic induction failure (LIF) after three- or four-drug induction therapy. In univariate analysis, high WBC count (P = .001), mediastinal mass (P = .017), T-cell phenotype (T-ALL; P = .001), t(9;22) translocation (P = .001), and a slow early response (at day 8 and/or on day 21, P = .001) were predictive of LIF. The following three prognostic groups for LIF were identified by multivariate analysis: a low-risk group with B-cell progenitor (BCP) ALL without t(9;22) (odds ratio [OR] = 1), an intermediate-risk group with T-ALL and a mediastinal mass (OR = 7.4, P < .0001), and a high-risk group with BCP-ALL and t(9;22) or T-ALL without a mediastinal mass (OR = 28.4, P < .0001). Complete remission (CR) was subsequently obtained in 43 patients (81%). The 5-year overall survival (OS) rate of the 53 patients was 30% ± 6%. The 5-year OS rate among allogeneic graft recipients, autologous graft recipients, and after chemotherapy were 30.4% ± 9.6% (50% ± 26% after genoidentical transplantation), 50% ± 17.7%, and 41.7% ± 14.2%, respectively (P = .18). Fourteen patients (26%) were still in first CR after a median of 83 months (range, 53 to 117 months). Conclusion Three risk categories for LIF in children with ALL were identified. Approximately one third of patients with LIF can be successfully treated with salvage therapy overall. Subsequent CR after LIF is mandatory for cure.
Published: 2008

180. DNA polymerases in adaptive immunity. : DNA polymerases in adaptive immunity

Author: Claude-Agnès Reynaud, Jean-Claude Weill, Développement du Systeme Immunitaire, and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: History, MESH : DNA-Directed DNA Polymerase, DNA polymerase, Gene Conversion, MESH : Somatic Hypermutation, Immunoglobulin, DNA-Directed DNA Polymerase, Computational biology, diversity, MESH : B-Lymphocytes, Education, chemistry.chemical_compound, Immune system, Animals, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Immunoglobulin Class Switching, Polymerase, Genetics, B-Lymphocytes, MESH : Gene Conversion, biology, Immunoglobulin genes, MESH : Immunity, Active, MESH : Humans, repertoire, Acquired immune system, Immunoglobulin Class Switching, Computer Science Applications, polymerase, Immunity, Active, chemistry, immunoglobulin genes, biology.protein, Somatic Hypermutation, Immunoglobulin, MESH : Animals, DNA
Abstract: review article; International audience; To cope with an unpredictable variety of potential pathogenic insults, the immune system must generate an enormous diversity of recognition structures, and it does so by making stepwise modifications at key genetic loci in each lymphoid cell. These modifications proceed through the action of lymphoid-specific proteins acting together with the general DNA-repair machinery of the cell. Strikingly, these general mechanisms are usually diverted from their normal functions, being used in rather atypical ways in order to privilege diversity over accuracy. In this Review, we focus on the contribution of a set of DNA polymerases discovered in the past decade to these unique DNA transactions.
Published: 2008

181. Validation of the French version of the colorectal-specific quality-of-life questionnaires EORTC QLQ-CR38 and FACT-C

Author: Franck Bonnetain, Christine Rotonda, Joelle Miny, Francis Guillemin, Mariette Mercier, A. Adenis, P Montcuquet, L. Uwer, T. Conroy, G. Breysacher, I. Léonard, Centre Alexis Vautrin (CAV), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Oncologie Médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire ISEN (L@BISEN), Institut supérieur de l'électronique et du numérique (ISEN)-YNCREA OUEST (YO), Service d'Oncologie et de Gastro-Intestinale, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER-Centre de lutte contre le cancer (CLCC), Centre de Recherche en Automatique de Nancy (CRAN), Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Centre Alexis Vautrin ( CAV ), Maladies chroniques, santé perçue, et processus d'adaptation ( APEMAC ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Service d'oncologie médicale, Clinique Saint-Vincent, Laboratoire ISEN-Brest ( L@BISEN ), Institut supérieur de l'électronique et du nunérique (ISEN), Centre de lutte contre le cancer (CLCC)-Centre Oscar Lambret, Centre de Recherche en Automatique de Nancy ( CRAN ), Université Henri Poincaré - Nancy 1 ( UHP ) -Institut National Polytechnique de Lorraine ( INPL ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Université de Lille-UNICANCER-Université de Lille-UNICANCER-Centre de lutte contre le cancer (CLCC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Laboratoire ISEN-Brest (L@BISEN), and Institut supérieur de l'électronique et du numérique (ISEN)
Subjects: Male, Psychometrics, Colorectal cancer, MESH : Aged, MESH : Prospective Studies, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Psychological Tests, MESH: Health Surveys, 0302 clinical medicine, Quality of life, Surveys and Questionnaires, MESH : Female, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, MESH: Aged, MESH: Middle Aged, MESH : Psychometrics, MESH : Psychological Tests, MESH : Questionnaires, Middle Aged, humanities, 3. Good health, Test (assessment), MESH: Reproducibility of Results, 030220 oncology & carcinogenesis, Female, France, MESH : Colorectal Neoplasms, Colorectal Neoplasms, medicine.medical_specialty, MESH : Male, MESH : Health Surveys, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, MESH: Psychometrics, medicine, Humans, MESH : Middle Aged, Psychological testing, MESH : France, Aged, Psychological Tests, MESH: Humans, business.industry, MESH : Reproducibility of Results, MESH: Questionnaires, MESH : Humans, Public Health, Environmental and Occupational Health, Reproducibility of Results, MESH: Quality of Life, Cancer, MESH : Quality of Life, medicine.disease, Health Surveys, MESH: Male, MESH: Prospective Studies, MESH: France, Quality of Life, Physical therapy, business, MESH: Female, MESH: Colorectal Neoplasms
Abstract: International audience; BACKGROUND: The aim of this study was to test the psychometric properties of the French version of the European Organization for Research and Treatment (EORTC) quality-of-life colorectal questionnaire (QLQ-CR38) and the functional assessment of cancer therapy-colorectal version 4 (FACT-C). METHOD: This prospective study included 209 patients with colorectal cancer: 71 undergoing chemotherapy, 56 radiation, 15 surgery, and 67 survivors. Patients first completed in random order the FACT-C and the EORTC QLQ-CR38 and were asked if they had any preference for either questionnaire. The timing of administration of instruments differed according to patients' treatment to better assess psychometric properties. RESULTS: The FACT-C showed good acceptability, good reproducibility and excellent internal consistency. The QLQ-CR38 had lower internal consistency. Patients did not express a preference for one survey over another. CONCLUSION: This study confirms the value of the FACT-C and suggests some limits of the QLQ-CR38 for patients with colorectal cancer.
Published: 2008

182. Comparison of AMPLICOR® and Hybrid Capture II® assays for high risk HPV detection in normal and abnormal liquid-based cytology: Use of INNO-LiPA Genotyping assay to screen the discordant results

Author: A. Petitjean, L. Z. Mo, Jean-Luc Prétet, Bernadette Kantelip, Christiane Mougin, Sylvain Monnier-Benoit, Didier Riethmuller, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC )
Subjects: Inno lipa, MESH: Reagent Kits, Diagnostic, Bethesda system, MESH : Aged, Uterine Cervical Neoplasms, MESH : Genotype, Cervix Uteri, MESH : Cervical Intraepithelial Neoplasia, MESH: Papillomavirus Infections, Polymerase Chain Reaction, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Nucleic Acid Hybridization, MESH: Genotype, 0302 clinical medicine, MESH: Papillomaviridae, Cytology, MESH : Female, MESH : Reagent Kits, Diagnostic, Papillomaviridae, MESH : Polymerase Chain Reaction, MESH : Papillomavirus Infections, MESH: Aged, 0303 health sciences, MESH: Middle Aged, medicine.diagnostic_test, Hybrid capture, Nucleic Acid Hybridization, virus diseases, MESH: Cervix Uteri, Middle Aged, MESH : Adult, MESH : Nucleic Acid Hybridization, female genital diseases and pregnancy complications, 3. Good health, MESH: Uterine Cervical Neoplasms, Infectious Diseases, 030220 oncology & carcinogenesis, Liquid-based cytology, MESH : Vaginal Smears, Female, MESH : Sensitivity and Specificity, Nucleic Acid Amplification Techniques, Adult, Adolescent, Genotype, MESH: Vaginal Smears, MESH : Uterine Cervical Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Sensitivity and Specificity, MESH: Nucleic Acid Amplification Techniques, 03 medical and health sciences, MESH : Adolescent, Virology, medicine, Humans, MESH : Middle Aged, Human papillomavirus, MESH : Papillomaviridae, Genotyping, Aged, 030304 developmental biology, Vaginal Smears, MESH: Adolescent, MESH: Humans, Papillomavirus Infections, MESH : Humans, MESH: Adult, MESH: Polymerase Chain Reaction, MESH : Nucleic Acid Amplification Techniques, Uterine Cervical Dysplasia, MESH: Sensitivity and Specificity, High risk hpv, MESH : Cervix Uteri, Reagent Kits, Diagnostic, MESH: Cervical Intraepithelial Neoplasia, MESH: Female
Abstract: International audience; The study was aimed to evaluate the feasibility of detecting human papillomavirus (HPV) in women with normal or abnormal cervical smears using the Roche Amplicor MWP HPV Test. We compared by AMPLICOR Test and Hybrid Capture II (HCII) Test, the prevalence of HR-HPV in 470 cervical samples including 55 samples with WNL cytology, 208 ASC-US, 193 LGSIL and 14 HGSIL. Samples with discordant results were retested with INNO-LiPA Genotyping HPV Test v2. The HR-HPV positivity in WNL cytology samples was similar (21.8%) by AMPLICOR and HCII. In ASC-US, the HPV positivity was 42.3% by both tests. In LGSIL, HPV positivity was 66.3% and 66.8% by AMPLICOR and HCII, respectively. In HGSIL, 92.8% of samples were positive by AMPLICOR and 85.7% by HCII. The agreement of both tests was 96.2% with a Kappa value of 0.92. Eighteen cases were discordant: 9 HCII positive/AMPLICOR negative and 9 HCII negative/AMPLICOR positive. The INNO-LiPA test revealed HPV positivity in every case. Interestingly, all HCII+/AMPLICOR- samples were found to harbour HPV53. As for the HCII-/AMPLICOR+ samples, 8 demonstrated a multiple infection with HR 16- and/or 18- and/or 56-phylogenetically related HPV types. Moreover, two of these samples were co-infected with HPV6 and two other with HPV54. By using consensus HR-HPV as our reference HPV positivity, the sensitivity (96.6%) and specificity (100%) of AMPLICOR was similar to that of HCII Test. The AMPLICOR HPV Test is sensitive, specific, feasible and appropriate for routine HPV detection.
Published: 2008

183. Comparative analysis of oxygen uptake in elderly subjects performing two walk tests: the six-minute walk test and the 200-m fast walk test

Author: Dominic Pérennou, Vincent Gremeaux, Jean-Marie Casillas, Gaëlle Deley, Marwan Iskandar, Gaelle Kervio, Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de rééducation, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Senhadji, Lotfi, and Pôle Rééducation - Réadaptation (Médecine Physique et Réadaptation) (CHU de Dijon)
Subjects: Male, medicine.medical_specialty, SIX MINUTE WALK, MESH : Male, MESH : Aged, MESH : Walking, Physical Therapy, Sports Therapy and Rehabilitation, Walking, Oxygen Consumption, Physical medicine and rehabilitation, Heart rate, medicine, Humans, MESH : Female, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, MESH : Aged, 80 and over, MESH : Oxygen Consumption, Rehabilitation department, Aged, Aged, 80 and over, [SDV.IB] Life Sciences [q-bio]/Bioengineering, Exercise Tolerance, MESH : Humans, Rehabilitation, Cardiorespiratory fitness, University hospital, Oxygen uptake, Test (assessment), MESH : Exercise Test, Walk test, Exercise Test, Physical therapy, MESH : Exercise Tolerance, Female, Psychology, human activities
Abstract: Objective: A novel walk test is proposed to assess the ability of elderly subjects to sustain a submaximal effort in ecological surroundings. Vo2 uptake during this test was compared with that of a six-minute walk test and maximal exercise test. Design: Descriptive laboratory study. Setting: Rehabilitation department, Dijon University Hospital. Subjects: Thirty-one subjects, aged from 70 to 85 years, free from any chronic disease. Intervention: Three tests to assess physical capacities: the 200-m fast walk test (200 mFWT), the six-minute walk test (6 MWT) at self-paced speed, and one maximal cardiorespiratory exercise test on an ergocycle. Main measures: Distance walked on the 6 MWT, time to perform the 200 mFWT. Heart rate (HR) and oxygen uptake (Vo2) were measured for each test. Results: All subjects successfully completed the two walk tests without any complaints. They walked more quickly during the 200 mFWT than during the 6 MWT (mean (SD) speed respectively 1.60 (0.17) versus 1.23 (0.16) m/s, P2 uptake 86.8 (8.9)% versus 67.4 (10.7)% of peak Vo2, mean (SD) HR 89.9 (9.4) versus 76.2 (0.8)% of peak HR; P Conclusion: In healthy elderly subjects, the 200 mFWT requires a more sustained effort than the 6 MWT. This test is simple, ecological and well tolerated. In addition to the 6 MWT, the 200 mFWT could be a useful tool to build up and evaluate training or rehabilitation programmes, especially when interval training is planned
Published: 2008

184. Somatic diversification in the absence of antigen-driven responses is the hallmark of the IgM+IgD+CD27+ B cell repertoire in infants

Author: Maria Mamani-Matsuda, Frédéric Gauthier, Claude-Agnès Reynaud, Corinne Cordier, Capucine Picard, Damiana Lecoeuche, Jean-Claude Weill, Sandra K. Weller, Développement du Systeme Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de chirurgie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Ligue Nationale contre le Cancer, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, and Weller, Sandra
Subjects: MESH: Spleen, MESH: Antigens, CD27, MESH: Immunoglobulin Variable Region, Immunoglobulin D, MESH: Variation (Genetics), 0302 clinical medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Immunoglobulin Variable Region, MESH: Antigens, CD, 0303 health sciences, biology, MESH : Variation (Genetics), MESH: Immunoglobulin D, MESH : Infant, hemic and immune systems, Articles, MESH: Infant, MESH: Immunoglobulin M, somatic hypermutation, "somatic hypermutation", MESH: Immunologic Memory, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: B-Lymphocyte Subsets, MESH : Spleen, MESH: Immunoglobulin mu-Chains, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Immunologic Memory, MESH: Gene Rearrangement, MESH : Immunoglobulin M, Immunology, Somatic hypermutation, "splenic marginal zone", chemical and pharmacologic phenomena, MESH : Immunoglobulin D, Article, MESH : B-Lymphocytes, 03 medical and health sciences, Immune system, Antigen, MESH : Antigens, CD27, MESH: B-Lymphocytes, MESH : Antigens, CD, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Humans, MESH: Transcription, Genetic, MESH : Humans, Ig repertoire, Germinal center, MESH : Transcription, Genetic, Gene rearrangement, MESH : Gene Rearrangement, splenic marginal zone, B-1 cell, MESH: T-Lymphocytes, MESH : Immunoglobulin mu-Chains, Immunoglobulin M, biology.protein, 030215 immunology, MESH : B-Lymphocyte Subsets, "Ig repertoire"
Abstract: International audience; T cell-dependent immune responses develop soon after birth, whereas it takes 2 yr for humans to develop T cell-independent responses. We used this dissociation to analyze the repertoire diversification of IgM(+)IgD(+)CD27(+) B cells (also known as "IgM memory" B cells), comparing these cells with switched B cells in children
Published: 2008

185. Mechanisms of action of antithymocyte globulin: old dogs with new tricks!

Author: Béatrice Gaugler, Mohamad Mohty, Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Saas, Philippe
Subjects: Cancer Research, [SDV.IMM] Life Sciences [q-bio]/Immunology, Globulin, medicine.medical_treatment, MESH : Lymphocytes, MESH : Antilymphocyte Serum, Hematopoietic stem cell transplantation, 03 medical and health sciences, 0302 clinical medicine, MESH: Antilymphocyte Serum, Antigen, Antigens, CD, MESH : Antigens, CD, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Lymphocytes, MESH: Antigens, CD, Antilymphocyte Serum, 030304 developmental biology, Immunosuppression Therapy, 0303 health sciences, MESH: Humans, MESH: Dendritic Cells, biology, MESH : Humans, MESH: Immunosuppression, Immunosuppression, T-cell depletion, Dendritic Cells, Hematology, 3. Good health, Transplantation, Oncology, Polyclonal antibodies, MESH : Dendritic Cells, MESH : Immunosuppression, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Lymphocytes, Antithymocyte globulins, 030215 immunology
Abstract: International audience; Understanding the mechanisms underlying immunological tolerance is the key to successful transplantation. Recent findings demonstrate that polyclonal antibodies such as the antithymocyte globulins preparations can provide wide spectrum immunomodulation, suggesting that their use in the immunosuppression therapeutic armamentarium may help in reducing the incidence of organ rejection and improving patients' outcome after hematopoietic stem cell transplantation.
Published: 2008

186. Accuracy of Ultrasonography in Diagnosis of Testicular Rupture After Blunt Scrotal Trauma

Author: Damien Cellarier, Carlos Del Coro, Hugues Bittard, François Kleinclauss, G. Guichard, Eric Chabannes, Jamal El Ammari, Stéphane Bernardini, Pierre Yves Loock, Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Departement of Surgery, Hospital Auxilio Mutuo, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Saas, Philippe, Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC)
Subjects: Male, MESH: Orchiectomy, MESH: Rupture, MESH : Retrospective Studies, MESH : Hematocele, MESH : Aged, 030232 urology & nephrology, Hematocele, Wounds, Nonpenetrating, 030218 nuclear medicine & medical imaging, Avulsion, MESH: Aged, 80 and over, 0302 clinical medicine, Testis, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Wounds, Nonpenetrating, MESH : Orchiectomy, Ultrasonography, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, MESH: Testis, Ultrasound, Testicular rupture, Middle Aged, MESH : Adult, MESH: Wounds, Nonpenetrating, Testicular trauma, 3. Good health, medicine.anatomical_structure, Scrotum, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Sensitivity and Specificity, medicine.symptom, Adult, endocrine system, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, MESH : Male, Urology, MESH : Scrotum, Sensitivity and Specificity, MESH : Rupture, Lesion, MESH: Hematocele, 03 medical and health sciences, Tunica albuginea (ovaries), MESH : Adolescent, medicine, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, Aged, Retrospective Studies, Rupture, MESH : Testis, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH: Scrotum, MESH: Sensitivity and Specificity, MESH: Male, Surgery, business, Orchiectomy
Abstract: International audience; OBJECTIVES: The aim of this study is to determine the accuracy of ultrasonography for the diagnosis of testis rupture after scrotal trauma and its sensitivity and specificity for testis rupture, tunica albuginea breach, testicular hematoma, testis avulsion, epididymis injuries, and hematocele. METHODS: Between 1996 and 2006, 33 patients underwent surgical exploration for blunt scrotal trauma. All these patients had an emergency scrotal ultrasonography with the use of a 7.5 or 10 MHz linear transducer. Ultrasonographic findings were compared with surgical findings to calculate sensitivity and specificity of ultrasonography for each type of lesion. RESULTS: Of 33 patients, 16 presented a testis rupture. Testis rupture was in all cases suspected ultrasonographically by the loss of contour of the testis and heterogeneous parenchyma. Tunica albuginea breach was visualized in only 8 patients. Sensitivity and specificity of ultrasound for testis rupture were 100% and 65%, respectively. Moreover, ultrasonography allowed diagnosis of hematocele (sensitivity: 87% and specificity: 89%), testicular hematoma (sensitivity: 71%, specificity: 77%), and testis avulsion (sensitivity: 100%, specificity: 97%). Ultrasonography results for epididymis injuries were poor. On 7 patients, 3 epididymis lesions were misdiagnosed by ultrasound examination. CONCLUSIONS: Ultrasonography can distinguish various scrotal injuries. Testicular rupture is probably the most severe injury that needs early surgical treatment to improve testis salvage rate. In our work, ultrasonography is highly sensitive in the diagnosis of testis rupture and can provide information on the scrotal contents integrity that can help the physician to determine the optimal treatment.
Published: 2008

187. Chromosome 1p loss evaluation in anaplastic oligodendrogliomas

Author: Judith W. M. Jeuken, Pim J. French, Catherine Carpentier, Khê Hoang-Xuan, Jean-Yves Delattre, Ahmed Idbaih, Olivier Delattre, Johannes L. Teepen, Johan M. Kros, Thierry Gorlia, Mathilde C.M. Kouwenhoven, Martin J. van den Bent, Biologie des Interactions Neurones / Glie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-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), Department of Neurology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Department of Pathology, Radboud University Medical Center [Nijmegen], EORTC, European Organization for Research and Treatment of Cancer DataCenter, St. Elisabeth Hospital, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), UPMC - Département de neurologie 2 - Mazarin, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de neurologie 1 [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Erasmus University Medical Center [Rotterdam], Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département de neurologie 2 - Mazarin, CHU Pitié-Salpêtrière [APHP]-Assistance publique - Hôpitaux de Paris (AP-HP)-Université Pierre et Marie Curie - Paris 6 ( UPMC ), Neurology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, CCA - Cancer Treatment and quality of life, Idbaih, Ahmed, 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)-Sorbonne Université (SU), Pathology, and Neurosurgery
Subjects: Chromosomes, Artificial, Bacterial, MESH : Oligodendroglioma, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Chromosomes, Human, Pair 1, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Nucleic Acid Hybridization, 0302 clinical medicine, MESH : Tumor Markers, Biological, Oligodendroglial Tumor, MESH: In Situ Hybridization, Fluorescence, In Situ Hybridization, Fluorescence, Molecular diagnosis, prognosis and monitoring [UMCN 1.2], Genetics, MESH: Middle Aged, Brain Neoplasms, Nucleic Acid Hybridization, General Medicine, Middle Aged, MESH : Nucleic Acid Hybridization, MESH : In Situ Hybridization, Fluorescence, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, MESH: Brain Neoplasms, Biomarker (medicine), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Chromosome Deletion, MESH : Chromosomes, Artificial, Bacterial, MESH: Chromosomes, Artificial, Bacterial, MESH: Chromosomes, Human, Pair 1, MESH: Chromosome Deletion, Oligodendroglioma, Anaplastic oligodendroglioma, [SDV.CAN]Life Sciences [q-bio]/Cancer, In situ hybridization, Biology, Pathology and Forensic Medicine, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Translational research [ONCOL 3], medicine, Biomarkers, Tumor, Humans, MESH : Middle Aged, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Brain Neoplasms, MESH: Oligodendroglioma, Bacterial artificial chromosome, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH : Humans, Chromosome, medicine.disease, MESH : Chromosome Deletion, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Tumor Markers, Biological, Neurology (clinical), [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, Comparative genomic hybridization
Abstract: Contains fulltext : 69651.pdf (Publisher’s version ) (Closed access) The chromosome (chr) 1p deletion is a favorable biomarker in oligodendroglial tumors and is even more powerful a marker when combined with chr 19q loss. As a result, the 1p deletion is taken into account more and more in clinical trials and the management of patients. However, the laboratory technique implemented for detection of this biomarker has been a topic of debate. To illustrate the usefulness of evaluating multiple loci, we here report two anaplastic oligodendrogliomas that were investigated using fluorescent in situ hybridization (FISH) and bacterial artificial chromosome (BAC)-array-based comparative genomic hybridization (aCGH). Indeed, segmental analysis using FISH, limited to chr 1p36 was unable to discriminate between complete and partial deletions of chrs 1p. However, complete and partial deletions of 1p are reported to have distinct clinical outcomes. Our results illustrate that aCGH (or other multiple loci technologies) provide complementary information to single locus technologies such as FISH because multiple loci technologies can evaluate the extent of the chr 1p deletion.
Published: 2008

188. Patients With Curative Resection of cT3-4 Rectal Cancer After Preoperative Radiotherapy or Radiochemotherapy: Does Anybody Benefit From Adjuvant Fluorouracil-Based Chemotherapy? A Trial of the European Organisation for Research and Treatment of Cancer Radiation Oncology Group

Author: Collette, Laurence, Bosset, Jean-Francois, Den Dulk, Marcel, Nguyen, France, Mineur, Laurent, Maingon, Philippe, Radosevic-Jelic, Ljiljana, Piérart, Marianne, Calais, Gilles, Renseigné, Non, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Institut Sainte Catherine [Avignon], Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), and Institut Sainte Catherine
Subjects: Male, Cancer Research, Colorectal cancer, medicine.medical_treatment, MESH : Aged, MESH : Analysis of Variance, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Medicine, MESH : Female, MESH : Rectal Neoplasms, Neoadjuvant therapy, MESH: Aged, MESH: Middle Aged, MESH : Chemotherapy, Adjuvant, MESH : Adult, Middle Aged, Neoadjuvant Therapy, 3. Good health, MESH : Antineoplastic Agents, Oncology, Chemotherapy, Adjuvant, MESH: Chemotherapy, Adjuvant, Fluorouracil, MESH: Survival Analysis, 030220 oncology & carcinogenesis, MESH : Fluorouracil, Female, 030211 gastroenterology & hepatology, medicine.drug, Adult, medicine.medical_specialty, MESH : Male, MESH: Neoadjuvant Therapy, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, MESH: Analysis of Variance, Humans, MESH : Middle Aged, Aged, Analysis of Variance, MESH: Humans, Rectal Neoplasms, business.industry, MESH : Humans, MESH: Rectal Neoplasms, Cancer, MESH: Adult, medicine.disease, Survival Analysis, MESH: Male, Surgery, Radiation therapy, Clinical trial, MESH: Antineoplastic Agents, MESH : Survival Analysis, business, MESH : Neoadjuvant Therapy, MESH: Female, MESH: Fluorouracil, Chemoradiotherapy
Abstract: Purpose European Organisation for Research and Treatment of Cancer (EORTC) trial 22921 compared adjuvant fluorouracil-based chemotherapy (CT) to no adjuvant treatment in a 2 × 2 factorial trial with randomization for preoperative (chemo)radiotherapy in patients with resectable T3-4 rectal cancer. The results showed no significant impact of adjuvant CT on progression-free or overall survival, although a difference seemed to emerge at approximately, respectively, 2 and 5 years after the start of preoperative treatment. We further explored the data with the aim of refining our understanding of the long-term results. Patients and Methods Data of 785 of the 1,011 randomly assigned patients who whose disease was M0 at curative surgery were used. Using meta-analytic methods, we investigated the homogeneity of the effect of adjuvant CT on the time to relapse or death after surgery (disease-free survival [DFS]) and survival in patient subgroups. Results Although there was no statistically significant impact of adjuvant CT on DFS for the whole group (P > .5), the treatment effect differed significantly between the ypT0-2 and the ypT3-4 patients (heterogeneity P = .009): only the ypT0-2 patients seemed to benefit from adjuvant CT (P = .011). The same pattern was observed for overall survival. Conclusion Exploratory analyses suggest that only good-prognosis patients (ypT0-2) benefit from adjuvant CT. This could explain why, in the whole group, the progression-free and overall survival diverged only after the poor-prognosis patients (ypT3-4) had experienced treatment failure. Patients in whom no downstaging was achieved did not benefit. This also suggests that the same prognostic factors may drive both tumor sensitivity for the primary treatment and long-term clinical benefit from further adjuvant CT.
Published: 2007

189. Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity

Author: Sami Al-Hajjar, Carlos Rodríguez-Gallego, John I. Gallin, Toshiro Hara, Maya Chrabieh, Andrew C. Issekutz, Huey Hsuan Chang, Horst von Bernuth, Joanne Smart, Helen Chapel, Eric Vivier, László Maródi, David P. Speert, Mimi L.K. Tang, Jean-Laurent Casanova, Capucine Picard, Xiaoxia Li, Steven M. Holland, Shen-Ying Zhang, Franck J. Barrat, Stephan Ehl, Abdulaziz Al-Ghonaium, Ben Zion Garty, Chaim M. Roifman, Xavier Bossuyt, Douglas R. McDonald, Anne Puel, Hidetoshi Takada, Ofer Levy, Damien Sanlaville, Laurent Abel, Frederic Geissmann, Richard L. Miller, Cheng-Lung Ku, Kun Yang, Noorbibi K. Day-Good, Coleen K. Cunningham, Génétique Humaine des Maladies Infectieuses (Inserm U980), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Interactions cellulaires neuroendocriniennes (ICN), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Interactions cellulaires neuroendocriniennes ( ICN ), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique ( CNRS ), Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] ( LA CONCEPTION ), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and University of Groningen
Subjects: Male, Myeloid, Lipopolysaccharide, MESH : Cytokines, medicine.medical_treatment, MESH : Leukocytes, MESH : Child, Preschool, chemistry.chemical_compound, 0302 clinical medicine, MESH : Child, MESH: Child, Leukocytes, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, Myeloid Cells, MESH : Female, Child, Cells, Cultured, MESH: Cytokines, 0303 health sciences, Toll-like receptor, MESH : Gene Expression Regulation, Interleukin, Cell Differentiation, PNEUMOCOCCAL MENINGITIS, MESH : Infant, Bacterial Infections, Articles, MYELOID DIFFERENTIATION FACTOR-88, MESH : Adult, MESH: Infant, MESH: Gene Expression Regulation, C-REACTIVE PROTEIN, Pedigree, 3. Good health, MESH : Bacterial Infections, Interleukin-1 Receptor-Associated Kinases, medicine.anatomical_structure, Cytokine, Child, Preschool, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, MESH : Cell Differentiation, IRAK4 KINASE-ACTIVITY, MESH: Toll-Like Receptors, MESH: Cells, Cultured, Adult, MESH: Cell Differentiation, MESH: Mutation, Adolescent, MESH : Myeloid Cells, MESH: Pedigree, MESH: Bacterial Infections, MESH : Male, Immunology, Biology, Article, MESH: Interleukin-1 Receptor-Associated Kinases, MESH: Leukocytes, IL-1 RECEPTOR, 03 medical and health sciences, Immunity, MESH : Adolescent, MESH : Cells, Cultured, medicine, Humans, 030304 developmental biology, TOLL-LIKE RECEPTORS, MESH: Adolescent, CUTTING EDGE, MESH: Humans, Innate immune system, MESH : Humans, MESH: Child, Preschool, HERPES-SIMPLEX-VIRUS, Infant, MESH: Adult, medicine.disease, MESH: Myeloid Cells, MESH: Male, Gene Expression Regulation, chemistry, MESH : Pedigree, MESH : Toll-Like Receptors, Mutation, PLASMACYTOID DENDRITIC CELLS, INNATE IMMUNITY, Primary immunodeficiency, MESH : Interleukin-1 Receptor-Associated Kinases, MESH: Female, 030215 immunology
Abstract: Human interleukin ( IL) 1 receptor - associated kinase 4 ( IRAK- 4) deficiency is a recently discovered primary immunodefi ciency that impairs Toll/ IL- 1R immunity, except for the Toll- like receptor ( TLR) 3 - and TLR4 - interferon ( IFN)-alpha/beta pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK- 4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells ( PBMCs) did not induce the 11 non- IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly( I: C). The patients' individual cell subsets from both myeloid ( granulocytes, monocytes, monocyte- derived dendritic cells [ MDDCs], myeloid DCs [ MDCs], and plasmacytoid DCs) and lymphoid ( B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly( I: C) and lipopolysaccharide in MDCs and MDDCs. Most patients ( 22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent ( 13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease ( 9 out of 28; 32%). Almost half of the patients died ( 12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK- 4 - dependent TLRs and IL- 1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK- 4 - dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria.
Published: 2007

190. Human Subinsular Asymmetry Studied by Diffusion Tensor Imaging and Fiber Tracking

Author: Y. Cointepas, Catherine Oppenheim, J.-F. Mangin, C. Poupon, J.-F. Meder, Sebastian Rodrigo, Olivier Naggara, Narly Golestani, D. Le Bihan, service de neuroradiologie [Paris], Hôpital Sainte-Anne, Laboratoire d'Imagerie et de Spectroscopie ( LRMN ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Institut d'imagerie neurofonctionnelle ( IIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -ENST-Assistance publique - Hôpitaux de Paris (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -École des hautes études en sciences sociales ( EHESS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Traitement et Communication de l'Information ( LTCI ), Télécom ParisTech-Institut Mines-Télécom [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neuroimagerie Assistée par Ordinateur ( LNAO ), Service Hospitalier Frédéric Joliot ( SHFJ ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Center for Neuroscience and Behavioral Medicine, Children's National Medical Center, Human Brain Research Center [Kyoto] ( HBRC ), Kyoto University [Kyoto], Service NEUROSPIN ( NEUROSPIN ), National Institutes of Health [Bethesda] ( NIH ), IFR de Neuroimagerie Fonctionnelle ( IFR 49 ), DIMF, Université Paris Descartes - Paris 5 ( UPD5 ) -Centre Hospitalier Sainte-Anne, Service de neuroradiologie [Paris], Laboratoire d'Imagerie et de Spectroscopie (LRMN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut d'imagerie neurofonctionnelle (IIN), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-École des hautes études en sciences sociales (EHESS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Ecole Nationale Supérieure des Télécommunications (ENST)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement et Communication de l'Information (LTCI), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuroimagerie Assistée par Ordinateur (LNAO), Service Hospitalier Frédéric Joliot (SHFJ), 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), Human Brain Research Center [Kyoto] (HBRC), Kyoto University, Service NEUROSPIN (NEUROSPIN), National Institutes of Health [Bethesda] (NIH), IFR de Neuroimagerie Fonctionnelle (IFR 49), Université Paris Descartes - Paris 5 (UPD5)-Centre Hospitalier Sainte-Anne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure des Télécommunications (ENST)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), 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, and Institut National de la Santé et de la Recherche Médicale (INSERM)-ENST-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École des hautes études en sciences sociales (EHESS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Functional Laterality, 0302 clinical medicine, Reference Values, Arcuate fasciculus, MESH : Female, [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, media_common, Cerebral Cortex, 05 social sciences, MESH: Reference Values, Brain, Anatomy, MESH : Adult, MESH : Diffusion Magnetic Resonance Imaging, medicine.anatomical_structure, MESH : Cerebral Cortex, Female, Psychology, Adult, MESH : Male, media_common.quotation_subject, Uncinate fasciculus, MESH: Diffusion Magnetic Resonance Imaging, MESH : Reference Values, Occipitofrontal fasciculus, Asymmetry, 050105 experimental psychology, Lateralization of brain function, White matter, MESH: Brain, 03 medical and health sciences, Fractional anisotropy, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, MESH: Functional Laterality, MESH : Functional Laterality, MESH: Humans, Functional, MESH : Humans, MESH: Adult, MESH: Cerebral Cortex, MESH: Male, Diffusion Magnetic Resonance Imaging, MESH : Brain, Neurology (clinical), MESH: Female, Neuroscience, 030217 neurology & neurosurgery, Diffusion MRI
Abstract: International audience; BACKGROUND AND PURPOSE: Our aim was to improve our understanding of the subinsular white matter microstructural asymmetries in healthy right-handed subjects. Structural brain asymmetries could be related to functional asymmetries such as hemisphere language dominance or handedness. Besides the known gray matter asymmetries, white matter asymmetries could also play a key role in the understanding of hemispheric specialization, notably that of language. MATERIALS AND METHODS: White matter asymmetries were studied by diffusion tensor imaging at 1.5T (41 diffusion-gradient directions; b-value set to 700 s/mm(2); matrix, 128(2); in-plane resolution, 1.875 x 1.875 mm; section thickness, 2.0 mm) and fiber tracking (BrainVISA software). The main white matter bundles passing through the subinsular area were segmented, and fractional anisotropy (FA) was measured along each of the segmented bundles. RESULTS: In line with published results, we found an asymmetry of the arcuate fasciculus and the subinsular white matter, namely left-greater-than-right FA in right-handed controls. Furthermore, by segmenting major tracts coursing through this region, we showed that the subinsular portions of the uncinate fasciculus (UF) and the inferior occipitofrontal fasciculus (IOF) contribute to this FA asymmetry. Those tracts have been reported to be likely implicated in the language network. CONCLUSION: Because the left hemisphere hosts language functions in most right-handers, the significant leftward asymmetry observed within the arcuate fasciculus, the subinsular part of the UF and IOF may be related to the hemispheric specialization for language.
Published: 2007

191. The human papillomavirus type 18 E6 oncoprotein induces Vascular Endothelial Growth Factor 121 (VEGF121) transcription from the promoter through a p53-independent mechanism

Author: Marie-Laure Plissonnier, Nicolas Clere, Maëlle Saunier, Laurent Bermont, Isabelle Lascombe, Sylvie Fauconnet, Lucie Vettoretti, Christiane Mougin, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)
Subjects: Vascular Endothelial Growth Factor A, MESH : RNA, Messenger, MESH : Hela Cells, Angiogenesis, Uterine Cervical Neoplasms, MESH : Alternative Splicing, MESH: Protein Isoforms, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Malignant transformation, HeLa, MESH : Adenocarcinoma, chemistry.chemical_compound, 0302 clinical medicine, Protein Isoforms, MESH: Human papillomavirus 18, MESH : Female, MESH : Human papillomavirus 18, MESH: Tumor Suppressor Protein p53, 0303 health sciences, Human papillomavirus 18, MESH: Alternative Splicing, MESH: Gene Expression Regulation, Neoplastic, MESH : Oncogene Proteins, Viral, 3. Good health, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, MESH: Uterine Cervical Neoplasms, Vascular endothelial growth factor, 030220 oncology & carcinogenesis, MESH : Vascular Endothelial Growth Factor A, Female, MESH : DNA-Binding Proteins, Gene isoform, MESH : Gene Expression Regulation, Neoplastic, MESH : Uterine Cervical Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Adenocarcinoma, Biology, 03 medical and health sciences, Humans, Gene silencing, RNA, Messenger, MESH: RNA, Messenger, 030304 developmental biology, MESH: Humans, MESH: Vascular Endothelial Growth Factor A, MESH: Adenocarcinoma, MESH : Humans, Alternative splicing, MESH : Protein Isoforms, Oncogene Proteins, Viral, Cell Biology, biology.organism_classification, Molecular biology, Squamous carcinoma, MESH: Hela Cells, Alternative Splicing, MESH : Tumor Suppressor Protein p53, chemistry, MESH: Oncogene Proteins, Viral, Cancer research, Tumor Suppressor Protein p53, MESH: Female, MESH: DNA-Binding Proteins, HeLa Cells
Abstract: International audience; Altered angiogenic response is associated with high-grade cervical dysplasia and with invasive squamous carcinoma of the cervix. Vascular Endothelial Growth Factor (VEGF) is one of the most potent inducers of angiogenesis and is up-regulated in carcinoma of the cervix. Infection by high-risk human papillomavirus and persistent expression of viral oncogene E6 are etiologically linked to the development of cervical cancer. E6 is able to immortalize cells and induce malignant transformation by inactivating p53. In cervical cancer, regulation of VEGF expression is poorly described. Thus, we investigated whether E6 oncoprotein could regulate VEGF expression in HPV18-positive cervical cancer-derived HeLa cells harboring a wild-type p53. The alternative splicing of vegf mRNA renders three major isoforms of 121, 165 and 189 amino-acids in humans. We have designed isoform specific real time QRT-PCR assays to quantitate vegf transcripts and VEGF121 was the predominant isoform. Silencing HPV18 E6 mRNA with specific siRNA reduced VEGF121 expression by at least 50% whereas silencing of p53 did not alter its expression. Treatment with cycloheximide did not inhibit E6-induced VEGF121 expression. Collectively, these results suggest that HPV18 E6 oncoprotein contributes to tumor angiogenesis by inducing VEGF transcription from the promoter in a p53-independent manner.
Published: 2007

192. Host and bacterial determinants of initial severity and outcome of Escherichia coli sepsis

Author: Françoise Jauréguy, C. Clec'h, Edouard Bingen, Philippe Casassus, Xavier Nassif, O. Lortholary, E. Carbonnelle, Bertrand Picard, Stéphane Bonacorsi, UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Paris 13 (UP13), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Robert Debré, Service de Réanimation Médico-Chirurgicale [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Service d'hématologie clinique [Avicenne], Mycologie moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Vesin, Aurélien, UFR Santé, Médecine et Biologie Humaine ( UFR SMBH ), Université Paris 13 ( UP13 ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Avicenne [AP-HP], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : Virulence Factors, MESH : Escherichia coli, MESH : Host-Parasite Interactions, Antibiotics, MESH : Prospective Studies, severity, Bacteremia, sepsis, Immunopathology, Prospective Studies, MESH: Bacteremia, Prospective cohort study, MESH: Sepsis, Escherichia coli Infections, MESH : Integration Host Factors, Antibacterial agent, 0303 health sciences, MESH: Escherichia coli, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, host factors, 3. Good health, Infectious Diseases, MESH : Escherichia coli Infections, outcome, MESH : Sepsis, Integration Host Factors, Microbiology (medical), Virulence Factors, medicine.drug_class, Virulence, Biology, MESH: Host-Parasite Interactions, Host-Parasite Interactions, Microbiology, Sepsis, 03 medical and health sciences, Escherichia coli, medicine, Humans, MESH: Escherichia coli Infections, MESH: Virulence Factors, 030304 developmental biology, MESH: Humans, MESH: Integration Host Factors, 030306 microbiology, Septic shock, MESH : Humans, MESH : Bacteremia, medicine.disease, MESH: Prospective Studies, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Immunology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, virulence determinants
Abstract: International audience; A 1-year prospective cohort study of all episodes of Escherichia coli bacteraemia in two French university hospitals was conducted to assess simultaneously the influence of host and bacterial determinants on the initial severity and outcome of E. coli sepsis. Clinical data (community-acquired/nosocomial infection, immune status, underlying disease, primary source of infection, severity sepsis scoring and outcome), phylogenetic groups (A, B1, D and B2), nine virulence factors (VFs) (papC, papGII, papGIII, sfa/foc, hlyC, cnf1, iucC, fyuA and iroN) and the antibiotic susceptibility of isolates were investigated. All VFs except iucC were significantly more prevalent (p
Published: 2007

193. Human Blood-Brain Barrier Disruption by Retroviral-Infected Lymphocytes: Role of Myosin Light Chain Kinase in Endothelial Tight-Junction Disorganization

Author: Marie-Christine Prévost, Christine Schmitt, Simona Ozden, Antoine Gessain, Babette B. Weksler, Pierre-Emmanuel Ceccaldi, Philippe V. Afonso, Pierre-Olivier Couraud, Ignacio A. Romero, Danielle Seilhean, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Microscopie électronique (Plate-forme), Institut Pasteur [Paris], CHU Pitié-Salpêtrière [APHP], Weill Medical College of Cornell University [New York], Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Department of Biological Sciences, The Open University [Milton Keynes] (OU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] - Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neuropathologie, Hôpital de la Salpétrière, and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: Pathology, MESH : Cerebellum, [SDV]Life Sciences [q-bio], MESH : Lymphocytes, MESH : Herpesviridae Infections, MESH : Models, Immunological, MESH : Herpesvirus 8, Human, MESH : Blood-Brain Barrier, 0302 clinical medicine, Cerebellum, Interleukin-1alpha, Tropical spastic paraparesis, Immunology and Allergy, Lymphocytes, Transcellular, Cell Line, Transformed, MESH : Tumor Necrosis Factor-alpha, Human T-lymphotropic virus 1, 0303 health sciences, MESH : Neoplasm Recurrence, Local, Tight junction, MESH : Neurodegenerative Diseases, MESH : Cell Line, Transformed, Neurodegenerative Diseases, MESH : Human T-lymphotropic virus 1, Paraparesis, Tropical Spastic, 3. Good health, Cell biology, MESH : Pleural Effusion, Malignant, medicine.anatomical_structure, Spinal Cord, Blood-Brain Barrier, Paracellular transport, Infiltration (medical), medicine.medical_specialty, Myosin light-chain kinase, Endothelium, Immunology, MESH : Lymphoma, AIDS-Related, Biology, MESH : Myosin-Light-Chain Kinase, MESH : Lymphoma, Myosin light chain kinase activity, Tight Junctions, 03 medical and health sciences, medicine, Humans, MESH : Interleukin-1alpha, Myosin-Light-Chain Kinase, 030304 developmental biology, MESH : Tight Junctions, Tumor Necrosis Factor-alpha, MESH : Endothelial Cells, MESH : Humans, Models, Immunological, Endothelial Cells, Membrane Proteins, MESH : Spinal Cord, Phosphoproteins, medicine.disease, MESH : Paraparesis, Tropical Spastic, MESH : Endothelium, Vascular, MESH : Membrane Proteins, Zonula Occludens-1 Protein, Endothelium, Vascular, MESH : Phosphoproteins, 030217 neurology & neurosurgery
Abstract: The blood-brain barrier (BBB), which constitutes the interface between blood and cerebral parenchyma, has been shown to be disrupted during retroviral associated neuromyelopathies. Human T cell leukemia virus (HTLV-1)-associated myelopathy/tropical spastic paraparesis is a slowly progressive neurodegenerative disease, in which evidence of BBB breakdown has been demonstrated by the presence of lymphocytic infiltrates in the CNS and plasma protein leakage through cerebral endothelium. Using an in vitro human BBB model, we investigated the cellular and molecular mechanisms involved in endothelial changes induced by HTLV-1-infected lymphocytes. We demonstrate that coculture with infected lymphocytes induces an increase in paracellular endothelial permeability and transcellular migration, via IL-1α and TNF-α secretion. This disruption is associated with tight junction disorganization between endothelial cells, and alterations in the expression pattern of tight junction proteins such as zonula occludens 1. These changes could be prevented by inhibition of the NF-κB pathway or of myosin light chain kinase activity. Such disorganization was confirmed in histological sections of spinal cord from an HTLV-1-associated myelopathy/tropical spastic paraparesis patient. Based on this BBB model, the present data indicate that HTLV-1-infected lymphocytes can induce BBB breakdown and may be responsible for the CNS infiltration that occurs in the early steps of retroviral-associated neuromyelopathies.
Published: 2007

194. In primary effusion lymphoma cells, MYB transcriptional repression is associated with v-FLIP expression during latent KSHV infection while both v-FLIP and v-GPCR become involved during the lytic cycle

Author: Françoise Valensi, Antoine Gessain, Christophe Nicot, Hittu Matta, Renaud Mahieux, Preet M. Chaudhary, Vincent Lacoste, Jean Gabarre, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology, Molecular genetics and Immunology, University of Kansas Medical Center [Lawrence], Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Division of Hematology-Oncology and the Hillman Cancer Center, University of Pittsburgh Medical Center, This work was supported by a grant from l'Association de Recherche sur le Cancer (ARC) and from la Fondation de France to RM and grants from NIH (CA85177 and CA124621) to PMC. VL and CN were supported by a bourse Pasteur‐Weissman and la Ligue Nationale Contre le Cancer respectively. RM was supported by a bourse Roux, from the Institut Pasteur and by INSERM., We thank Dr D. Gonzalez‐Dunia, J.S. Seeler and C. Royer‐Leveau for their help. We are indebted to Drs P. Charneau, J. Golay, N. Rice, L. Boxer, P. Murphy and W.C. Greene for generous gifts of reagents essential to the realization of this study. We thank Pr O. Hermine for providing us with some PEL fresh samples, and Dr Timothy Stinear for his critical comments., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Kansas Medical Center [Kansas City, KS, USA], Université Paris Descartes - Paris 5 (UPD5)-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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), University of Kansas Medical Center, Laboratoire d'hématologie ( ERL 8254 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]
Subjects: non-Hodgkinlymphoma, Transcription, Genetic, Genes, myb, [SDV]Life Sciences [q-bio], viruses, CASP8 and FADD-Like Apoptosis Regulating Protein, Gene Expression, MESH : Sarcoma, Kaposi, MESH : Herpesvirus 8, Human, MESH: Virus Activation, Receptors, G-Protein-Coupled, Transduction (genetics), molecular studies, 0302 clinical medicine, MESH: Lymphoma, Non-Hodgkin/virology, Transduction, Genetic, MESH: Viral Proteins/metabolism, Virus latency, MESH : Virus Latency, MYB, MESH : Cell Transformation, Viral, Viral G-Protein Coupled Receptor, MESH : Viral Proteins, MESH: Lymphoma, AIDS-Related/metabolism, Lymphoma, AIDS-Related, Regulation of gene expression, MESH : Trans-Activators, 0303 health sciences, Lymphoma, Non-Hodgkin, MESH: Virus Latency, NF-kappa B, Hematology, Transfection, MESH : Immediate-Early Proteins, MESH: Transduction, Genetic, MESH: Gene Expression Regulation, Viral, MESH: Sarcoma, Kaposi/metabolism, MESH: Herpesvirus 8, Human/physiology, Virus Latency, 3. Good health, Lytic cycle, MESH: Cell Transformation, Viral, MESH : NF-kappa B, MESH : Genes, myb, 030220 oncology & carcinogenesis, Herpesvirus 8, Human, MESH : Virus Activation, MESH : Receptors, G-Protein-Coupled, Primary effusion lymphoma, MESH : Transfection, MESH: NF-kappa B/metabolism, Gene Expression Regulation, Viral, MESH: Cell Line, Tumor, MESH: Gene Expression, animal structures, MESH : Transduction, Genetic, MESH : Lymphoma, AIDS-Related, Biology, MESH : Gene Expression Regulation, Viral, Immediate-Early Proteins, Proto-Oncogene Proteins c-myb, Viral Proteins, 03 medical and health sciences, MESH: Receptors, G-Protein-Coupled/metabolism, MESH: Sarcoma, Kaposi/virology, MESH: Trans-Activators/metabolism, Cell Line, Tumor, medicine, nuclear factor-jB, Humans, MESH : Lymphoma, Non-Hodgkin, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism, Sarcoma, Kaposi, 030304 developmental biology, B cells, MESH: Humans, MESH : Cell Line, Tumor, herpes virus, MESH: Lymphoma, AIDS-Related/virology, MESH: Transcription, Genetic, MESH: Transfection, MESH: Immediate-Early Proteins/metabolism, MESH : Humans, MESH: Proto-Oncogene Proteins c-myb/analysis, MESH : Transcription, Genetic, Kaposi sarcoma, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, Cell Transformation, Viral, medicine.disease, MESH : Proto-Oncogene Proteins c-myb, MESH : Gene Expression, MESH: Genes, myb, Trans-Activators, Cancer research, MESH: Lymphoma, Non-Hodgkin/metabolism, Virus Activation
Abstract: International audience; Primary effusion lymphoma (PEL) is a rare, distinct subtype of non-Hodgkin lymphoma, which is associated with Kaposi sarcoma-associated herpesvirus (KSHV) infection. Although MYB levels are high in most neoplastic B cells, we found that, unexpectedly, both PEL cells and uncultured PEL patients' samples contained very low levels of MYB mRNA when compared to B-cell leukaemia samples obtained from KSHV(-) patients. These results were further confirmed at the protein level. Both latent viral FLICE inhibitory protein (v-FLIP) and early lytic viral G protein coupled receptor (v-GPCR) KSHV proteins were found to activate nuclear factor (NF)-kappaB and transrepress a MYB promoter reporter construct. In contrast, a dominant negative inhibitor of NF-kappaB (IkappaB-alpha) mutant prevented v-FLIP and v-GPCR from inhibiting MYB functions while a v-GPCR mutant that was impaired for NF-kappaB activation could not repress the MYB construct. Transduction of a v-FLIP expressing vector or stable transfection of v-GPCR both resulted in a marked downregulation of the endogenous MYB protein expression. However, MYB expression transactivated the lytic switch Replication and Transcription Activator (RTA) promoter in transient transfection assays. Taken together, our results demonstrate that, contrary to a number of other haematological malignancies, MYB expression is not required for PEL cell proliferation. Repressing MYB expression also helps in maintaining the virus in latency.
Published: 2007

195. Guidelines for target volume definition in post-operative radiotherapy for prostate cancer, on behalf of the EORTC Radiation Oncology Group

Author: Poortmans , Philip, Bossi , Alberto, Vandeputte , Katia, Bosset , Mathieu, Miralbell , Raymond, Maingon , Philippe, Boehmer , Dirk, Budiharto , Tom, Symon , Zvi, Van Den Bergh , Alfons C M, Scrase , Christopher, Van Poppel , Hendrik, Bolla , Michel, Renseigné , Non, Radiotherapy, Bernard Verbeeten Institute for Radiotherapy, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Katholieke Universiteit Leuven ( KU Leuven ), Département de cancérologie et radiothérapie, CHU Grenoble, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), and Guided Treatment in Optimal Selected Cancer Patients (GUTS)
Subjects: Male, Oncology, PELVIC LYMPHADENECTOMY, medicine.medical_treatment, Planning target volume, THERAPY, DISEASE, 030218 nuclear medicine & medical imaging, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Imaging, Prostate cancer, 0302 clinical medicine, MESH: Postoperative Period, Postoperative Period, guidelines, ADJUVANT RADIOTHERAPY, MESH : Neoplasm Recurrence, Local, Prostatectomy, MESH: Guidelines as Topic, RADICAL PROSTATECTOMY, Hematology, prostate cancer, 3. Good health, 030220 oncology & carcinogenesis, MESH: Neoplasm Recurrence, Local, MESH : Prostatic Neoplasms, medicine.medical_specialty, MESH : Prostatectomy, MESH : Male, Guidelines as Topic, [SDV.CAN]Life Sciences [q-bio]/Cancer, LOCAL RECURRENCE, organ at risk definition, 03 medical and health sciences, MESH: Prostatectomy, Internal medicine, Radiation oncology, medicine, Humans, EXTRACAPSULAR EXTENSION, Radiology, Nuclear Medicine and imaging, Medical physics, MESH : Guidelines as Topic, MESH : Postoperative Period, MESH: Humans, prostatectomy, business.industry, MESH : Humans, Prostatic Neoplasms, Cancer, BLADDER, medicine.disease, MESH: Male, Post operative radiotherapy, Radiation therapy, EMISSION-TOMOGRAPHY, HIGH-RISK, Prostate Bed, MESH: Prostatic Neoplasms, target definition, Neoplasm Recurrence, Local, business
Abstract: The appropriate application of 3-D conformal radiotherapy, intensity modulated radiotherapy or image guided radiotherapy for patients undergoing post-operative radiotherapy for prostate cancer requires a standardisation of the target volume definition and delineation as well as stanclardisation of the clinical quality assurance procedures. Recommendations for this are presented on behalf of the European Organisation for Research and Treatment of Cancer (EORTC) Radiation Oncology Group and in addition to the already published guidelines for radiotherapy as the primary treatment. (c) 2007 Elsevier Ireland Ltd. All rights reserved.
Published: 2007

196. Synthesis and Biological Evaluation of 1-Amino-2-Phosphonomethylcyclopropanecarboxylic Acids, New Group III Metabotropic Glutamate Receptor Agonists

Author: Cyril Goudet, Hugues-Olivier Bertrand, Isabelle Brabet, Michael J. Marino, Pauline Sibille, Florence Gaven, Sébastien Lopez, Jacques Neyton, Jean-Philippe Pin, Ornella Valenti, Francine Acher, Nadia Oueslati, Marianne Amalric, Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques (LCBPT - UMR 8601), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Neurology, Merck Research Laboratories, Accelrys, Laboratoire de Neurobiologie (UMR 8544) (NEURO), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants from the Fondation de France (Parkinson committee), RETINA-France, the french National Research Agency (ANR-05-NEUR-021-01), the french ministry of Education and Research and the Centre National de la Recherche Scientifique., ANR-05-NEUR-0021,MGluRs Park,Cible thérapeutique potentielle de nouveaux ligands des récepteurs métabotropiques du glutamate du groupe III dans le traitement de la maladie de Parkinson : de la conception à l'évaluation préclinique(2005), Laboratoire de Chimie et de Biochimie Pharmacologiques et Toxicologiques ( LCBPT - UMR 8601 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Neurosciences Cognitives [Marseille] ( LNC ), Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Laboratoire de Neurobiologie (UMR 8544) ( NEURO ), École normale supérieure - Paris ( ENS Paris ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), ANR PARK, ANR-05-NEUR-021-01,ANR PARK, ANR-05-NEUR-021-01, Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS-PSL), Goudet, Cyril, and Neurosciences, neurologie et psychiatrie - Cible thérapeutique potentielle de nouveaux ligands des récepteurs métabotropiques du glutamate du groupe III dans le traitement de la maladie de Parkinson : de la conception à l'évaluation préclinique - - MGluRs Park2005 - ANR-05-NEUR-0021 - NEURO - VALID
Subjects: Male, Models, Molecular, MESH : Cell Line, Patch-Clamp Techniques, MESH: Amino Acids, MESH: Antiparkinson Agents, Molecular Conformation, MESH: Catalepsy, MESH: Rats, Sprague-Dawley, Pharmacology, Receptors, Metabotropic Glutamate, Synaptic Transmission, Basal Ganglia, Antiparkinson Agents, Rats, Sprague-Dawley, MESH: Basal Ganglia, MESH: Structure-Activity Relationship, 0302 clinical medicine, MESH : Structure-Activity Relationship, Drug Discovery, MESH: Animals, Amino Acids, MESH : Patch-Clamp Techniques, MESH : Haloperidol, Receptor, MESH : Synaptic Transmission, 0303 health sciences, MESH : Rats, Chemistry, Metabotropic glutamate receptor 4, MESH : Receptors, Metabotropic Glutamate, Metabotropic glutamate receptor 6, Stereoisomerism, MESH : Antiparkinson Agents, 3. Good health, HYDIA, MESH : Stereoisomerism, Biochemistry, Molecular Medicine, Metabotropic glutamate receptor 1, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Phosphonic Acids, MESH: Models, Molecular, Agonist, MESH: Rats, MESH : Models, Molecular, medicine.drug_class, MESH : Male, Organophosphonates, MESH: Phosphonic Acids, In Vitro Techniques, Catalepsy, MESH : Rats, Wistar, Receptors, N-Methyl-D-Aspartate, Cell Line, Injections, Structure-Activity Relationship, 03 medical and health sciences, MESH: Patch-Clamp Techniques, MESH: Synaptic Transmission, medicine, Animals, Humans, MESH: Injections, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Rats, Wistar, MESH: Receptors, Metabotropic Glutamate, MESH : Basal Ganglia, 030304 developmental biology, MESH: Receptors, N-Methyl-D-Aspartate, MESH: Molecular Conformation, MESH: Humans, MESH : Catalepsy, MESH : Humans, MESH: Rats, Wistar, medicine.disease, MESH : Injections, MESH: Stereoisomerism, MESH : Rats, Sprague-Dawley, MESH: Male, Rats, MESH: Cell Line, MESH: Haloperidol, MESH : Molecular Conformation, Metabotropic glutamate receptor, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Haloperidol, MESH : Amino Acids, MESH : Animals, MESH : Receptors, N-Methyl-D-Aspartate, 030217 neurology & neurosurgery
Abstract: International audience; Stereoisomers of 1-amino-2-phosphonomethylcyclopropanecarboxylic acid (APCPr), conformationally restricted analogues of L-AP4 (2-amino-4-phosphonobutyric acid), have been prepared and evaluated at recombinant group III metabotropic glutamate receptors. They activate these receptors over a broad range of potencies. The most potent isomer (1S,2R)-APCPr displays a similar pharmacological profile as that of L-AP4 (EC50 0.72, 1.95, >500, 0.34 microM at mGlu4, 6, 7, 8 receptors, respectively, and no effect at group I/II mGluRs). It was characterized on native receptors located in the basal ganglia (BG) where it induced a robust and reversible inhibition of synaptic transmission. It was tested in vivo in haloperidol-induced catalepsy, a model of Parkinsonian akinesia, by direct infusion in the globus pallidus of the BG. At a dose of 0.5 nmol/microL, catalepsy was significantly antagonized. This study reveals that (1S,2R)-APCPr is a potent group III mGluR agonist and confirms that these receptors may be considered as a therapeutic target in the Parkinson's disease.
Published: 2007

197. The Influence of Timing of Administration on the Analgesic Efficacy of Parecoxib in Orthopedic Surgery

Author: Daniel I. Sessler, Marcel Chauvin, K. Cherif, Adel Jamal, Valeria Martinez, Aithem Jaber, Anissa Belbachir, Dominique Fletcher, Yves Ozier, Hoch, Martine, Service d'anesthésie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], Service de réanimation médicale polyvalente [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of OUTCOMES RESEARCH, University of Louisville-OUTCOMES RESEARCH Institute, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP Hôpital Raymond Poincaré [Garches], and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]
Subjects: Male, Time Factors, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Arthroplasty, Replacement, Hip, medicine.medical_treatment, MESH : Aged, MESH : Arthroplasty, Replacement, Hip, MESH : Orthopedic Procedures, law.invention, 0302 clinical medicine, Randomized controlled trial, 030202 anesthesiology, law, MESH: Arthroplasty, Replacement, Hip, Orthopedic Procedures, MESH : Female, MESH: Pain, Postoperative, MESH: Aged, Pain, Postoperative, MESH: Middle Aged, MESH : Pain, Postoperative, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Middle Aged, 3. Good health, Anesthesia, Female, MESH : Time Factors, medicine.drug, medicine.medical_specialty, Visual analogue scale, MESH : Male, MESH : Isoxazoles, Analgesic, Placebo, Article, MESH: Orthopedic Procedures, 03 medical and health sciences, Parecoxib, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, MESH : Middle Aged, Aged, MESH: Humans, business.industry, MESH : Humans, MESH: Time Factors, Isoxazoles, Perioperative, Arthroplasty, MESH: Male, Surgery, MESH: Analgesia, Anesthesiology and Pain Medicine, MESH: Isoxazoles, MESH : Analgesia, Morphine, Analgesia, business, MESH: Female, 030217 neurology & neurosurgery
Abstract: International audience; BACKGROUND: Parecoxib, a selective cyclooxygenase-2 inhibitor, may reduce postoperative pain without increasing bleeding when administered before surgery. METHODS: We randomly assigned 62 patients scheduled for total hip arthroplasty to the following IV dosing schedule: 1) placebo at induction, at wound closure, and 12 h after induction (control); 2) parecoxib 40 mg at induction, placebo at wound closure, and parecoxib 40 mg 12 h after induction (pre); or, 3) placebo at induction, parecoxib 40 mg at wound closure, and parecoxib 40 mg 12 h after induction (post). Pain scores at rest and with movement were recorded every 4 h for 24 h using a visual analog scale. Treatment side effects were recorded every 4 h. Red cell loss for 5 days after surgery was calculated. RESULTS: Postoperative pain scores were less in the pre and post groups than in the control group. Postoperative bleeding was similar in the three groups. There were no significant differences between the pre and post groups, nor was their any trend suggesting a preemptive analgesic efficacy from preincision administration of parecoxib. Morphine use in the Postanesthesia Care Unit was reduced in the pre and post groups compared with the control group (14.2 +/- 2.0, and 15.7 +/- 2.0, vs 20.4 +/- 2.3 mg), although the trend was only significant (P < 0.05) in the pre group. The first pain score was also reduced in the pre and post groups compared to the control group (56.1 +/- 7.5 and 64.2 +/- 7.0 vs 78.3 +/- 5), but this was also only significant for the pre group (P = 0.001). The delay for first analgesic demand was increased for both the pre and post group compared to the control group (38 +/- 9 and 28.2 +/- 6.6 vs 18 +/- 6 min) but, again, this was only significant for the pre group (P = 0.05). Twenty-four hour consumption of morphine was similar in the pre (26 +/- 12 mg) and post groups (25 +/- 13 mg); both were significantly less than in the control group (47 +/- 27 mg, P < 0.001). CONCLUSIONS: Administration of parecoxib before hip arthroplasty did not provide preemptive analgesia. There was a trend towards improved analgesia immediately after surgery with preincision administration, consistent with the expected time course of nonsteroidal antiinflammatory drug's effect. Perioperative parecoxib administration, consisting of two injections spaced 12 h apart, improved postoperative analgesia over the first 24 h without increasing bleeding.
Published: 2007

198. Matthew-Wood Syndrome Is Caused by Truncating Mutations in the Retinol-Binding Protein Receptor Gene STRA6

Author: Michel Vekemans, Christelle Golzio, Bettina Grattagliano-Bessières, Jelena Martinovic-Bouriel, Arnold Munnich, Sophie Delahaye, Tania Attié-Bitach, Stanislas Lyonnet, Heather C. Etchevers, Soumaya Mougou-Zrelli, Maryse Bonnière, Férechté Encha-Razavi, Sophie Thomas, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Institut de Puériculture de Paris (IPP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Puériculture de Paris ( IPP ), and Assistance publique - Hôpitaux de Paris (AP-HP)
Subjects: Lung Diseases, MESH: Sequence Analysis, DNA, Vitamin A transport, MESH : Polymorphism, Genetic, MESH : Receptors, Cell Surface, MESH : Gene Deletion, MESH: Genetic Markers, MESH : Syndrome, MESH : Frameshift Mutation, MESH : Microphthalmos, Consanguinity, MESH: Lung Diseases, Exon, MESH : Exons, 0302 clinical medicine, Microphthalmos, MESH : Genetic Markers, MESH: Syndrome, Genetics(clinical), Frameshift Mutation, Genetics (clinical), MESH: Receptors, Cell Surface, 0303 health sciences, Fetal Growth Retardation, MESH : Lung Diseases, Homozygote, MESH: Frameshift Mutation, Exons, Syndrome, Pedigree, MESH: Membrane Proteins, MESH : Mutation, MESH: Homozygote, Genetic Markers, MESH: Abnormalities, Multiple, MESH: Mutation, MESH: Pedigree, MESH: Microphthalmos, MESH: Fetal Growth Retardation, Receptors, Cell Surface, Biology, Frameshift mutation, 03 medical and health sciences, Pulmonary hypoplasia, MESH : Homozygote, Report, MESH : Consanguinity, MESH: Polymorphism, Genetic, Genetics, medicine, Humans, Abnormalities, Multiple, MESH : Fetal Growth Retardation, MESH : Haplotypes, 030304 developmental biology, MESH: Consanguinity, MESH : Mutagenesis, Insertional, Polymorphism, Genetic, MESH: Humans, Anophthalmia, MESH : Abnormalities, Multiple, Genetic heterogeneity, MESH : Humans, Pulmonary Agenesis, Membrane Proteins, Sequence Analysis, DNA, MESH: Haplotypes, medicine.disease, Molecular biology, Mutagenesis, Insertional, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Haplotypes, MESH: Mutagenesis, Insertional, MESH : Membrane Proteins, MESH: Gene Deletion, MESH : Pedigree, [ SDV.BDD.EO ] Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Mutation, MESH: Exons, Matthew Wood syndrome, Gene Deletion, 030217 neurology & neurosurgery, MESH : Sequence Analysis, DNA
Abstract: International audience; Retinoic acid (RA) is a potent teratogen in all vertebrates when tight homeostatic controls on its endogenous dose, location, or timing are perturbed during early embryogenesis. STRA6 encodes an integral cell-membrane protein that favors RA uptake from soluble retinol-binding protein; its transcription is directly regulated by RA levels. Molecular analysis of STRA6 was undertaken in two human fetuses from consanguineous families we previously described with Matthew-Wood syndrome in a context of severe microphthalmia, pulmonary agenesis, bilateral diaphragmatic eventration, duodenal stenosis, pancreatic malformations, and intrauterine growth retardation. The fetuses had either a homozygous insertion/deletion in exon 2 or a homozygous insertion in exon 7 predicting a premature stop codon in STRA6 transcripts. Five other fetuses presenting at least one of the two major signs of clinical anophthalmia or pulmonary hypoplasia with at least one of the two associated signs of diaphragmatic closure defect or cardiopathy had no STRA6 mutations. These findings suggest a molecular basis for the prenatal manifestations of Matthew-Wood syndrome and suggest that phenotypic overlap with other associations may be due to genetic heterogeneity of elements common to the RA- and fibroblast growth factor-signaling cascades.
Published: 2007

199. Standards and standardization in mastocytosis: Consensus Statements on Diagnostics, Treatment Recommendations and Response Criteria

Author: Cem Akin, Peter Valent, N. A. T. Hamdy, Mariana Castells, Dean D. Metcalfe, A. Orfao, Jamie Robyn, Olivier Hermine, Lawrence B. Schwartz, Michel Arock, Hanneke C. Kluin-Nelemans, Alexander W. Hauswirth, J. J. Van Doormaal, Hans-Peter Horny, Karl Sotlar, Andrzej Hellmann, Knut Brockow, Wolfgang R. Sperr, Massimo Triggiani, Olivier Lortholary, Marek Niedoszytko, Luis Escribano, Manuela Födinger, Karin Hartmann, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pathologie et virologie moléculaire (PVM (UMR_7151)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Service d'immuno-hématologie pédiatrique [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), Division of Clinical Immunology and Allergy, Università degli studi di Napoli Federico II, Laboratoire Analyse, Géométrie et Applications (LAGA), Université Paris 8 Vincennes-Saint-Denis (UP8)-Centre National de la Recherche Scientifique (CNRS)-Institut Galilée-Université Paris 13 (UP13), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Slama, Catherine, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Pathologie et virologie moléculaire ( PVM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Analyse, Géométrie et Applications ( LAGA ), Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut Galilée-Centre National de la Recherche Scientifique ( CNRS ), Pathologie et virologie moléculaire (PVM), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris 13 (UP13)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS)
Subjects: Standardization, targeted drugs, Clinical Biochemistry, BLOOD MONONUCLEAR-CELLS, Biochemistry, 0302 clinical medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Systemic mastocytosis, ComputingMilieux_MISCELLANEOUS, URINARY N-METHYLHISTAMINE, ORAL DISODIUM-CROMOGLYCATE, Clinical Trials as Topic, mastocytosis, GASTROINTESTINAL STROMAL TUMORS, General Medicine, MESH : Diagnosis, Differential, 3. Good health, OF-THE-LITERATURE, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, medicine.medical_specialty, MESH: Clinical Trials as Topic, Diffuse cutaneous mastocytosis, MEDLINE, MESH : Mastocytosis, Mast cell activation syndrome, ACUTE MYELOID-LEUKEMIA, Diagnosis, Differential, 03 medical and health sciences, MESH: Diagnosis, Differential, AGGRESSIVE SYSTEMIC MASTOCYTOSIS, medicine, Humans, MESH: Patient Selection, MAST-CELL DISEASE, Intensive care medicine, Selection (genetic algorithm), standardization, MESH: Humans, criteria, business.industry, Cutaneous Mastocytosis, MESH : Humans, MESH : Patient Selection, C-KIT MUTATION, medicine.disease, MESH : Clinical Trials as Topic, Clinical trial, Immunology, MESH: Mastocytosis, BONE-MARROW MASTOCYTOSIS, business, patient selection, 030215 immunology
Abstract: Although a classification for mastocytosis and diagnostic criteria are available, there remains a need to define standards for the application of diagnostic tests, clinical evaluations, and treatment responses. To address these demands, leading experts discussed current issues and standards in mastocytosis in a Working Conference. The present article provides the resulting outcome with consensus statements, which focus on the appropriate application of clinical and laboratory tests, patient selection for interventional therapy, and the selection of appropriate drugs. In addition, treatment response criteria for the various clinical conditions, disease-specific symptoms, and specific pathologies are provided. Resulting recommendations and algorithms should greatly facilitate the management of patients with mastocytosis in clinical practice, selection of patients for therapies, and the conduct of clinical trials.
Published: 2007

200. Novel 1,4-benzodiazepine derivatives with antiproliferative properties on tumor cell lines

Author: Nohad Gresh, Jennifer Dourlat, Wang-Qing Liu, Christiane Garbay, Pharmacochimie Moléculaire et Cellulaire (PMC - UMR_S 648), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Hombrados, Elisabeth
Subjects: MESH : Models, Chemical, MESH : Drug Design, Chemistry, Pharmaceutical, MESH : Chemistry, Pharmaceutical, medicine.medical_treatment, Clinical Biochemistry, Molecular Conformation, Pharmaceutical Science, MESH: Drug Design, Biochemistry, Chemical synthesis, MESH: Benzodiazepinones, Benzodiazepines, Drug Discovery, MESH : Cell Proliferation, Melanoma, MESH: Inhibitory Concentration 50, Benzodiazepinones, MESH : Benzodiazepinones, MESH : Drug Screening Assays, Antitumor, Chemistry, MESH: Models, Chemical, MESH: Drug Screening Assays, Antitumor, General Medicine, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Drug Resistance, Neoplasm, [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH : Antineoplastic Agents, MESH : Drug Resistance, Neoplasm, medicine.anatomical_structure, MESH : Inhibitory Concentration 50, Melanoma cell line, Molecular Medicine, MESH: Cell Line, Tumor, medicine.drug_class, MESH: Melanoma, Ratón, MESH : Melanoma, Antineoplastic Agents, Tumor cells, Inhibitory Concentration 50, MESH: Chemistry, Pharmaceutical, Cell Line, Tumor, MESH: Cell Proliferation, medicine, Humans, Fibroblast, Molecular Biology, Cell Proliferation, MESH : Benzodiazepines, Benzodiazepine, MESH: Molecular Conformation, Chemotherapy, MESH: Humans, MESH : Cell Line, Tumor, Cell growth, MESH : Humans, Organic Chemistry, Cancer, medicine.disease, Models, Chemical, Drug Resistance, Neoplasm, MESH : Molecular Conformation, Cell culture, Drug Design, MESH: Benzodiazepines, Cancer research, MESH: Antineoplastic Agents, Drug Screening Assays, Antitumor
Abstract: International audience; Novel 1,4-benzodiazepine compounds were synthesized and evaluated for their ability to inhibit the proliferation of tumor cells. Some compounds revealed activities in the micromolar range and were more efficient than reference compound Ro 5-4864. Preliminary SAR helped to identify critical motifs for antiproliferative activity and led to the discovery of a compound selective for a melanoma cell line, known for its resistance to chemotherapy.
Published: 2007

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

2,059 results on '"MESH : Humans"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources