34 research outputs found
Las cadenillas de Hércules : stratégies discursives de l’argumentation pour convaincre, persuader et séduire (Moyen âge et Siècle d’or)
No full textS’il fallait une image pour évoquer le pouvoir du discours, ce pourrait être celle d’Hercule Ogmios entraînant à sa suite un cortège dont les oreilles sont enchaînées à sa langue. Emblème de la force de l’éloquence, c’est sous l’égide de cet Hercule gaulois que nous plaçons notre réflexion ici pour tenter de saisir la nature de ces chaînes par lesquelles l’auteur captive son auditoire : comment le texte se fait-il irrésistiblement convaincant et persuasif pour faire suivre au lecteur le chemin de l’auteur séducteur ? L’image communique clairement l’emprise que confère ce pouvoir sur les autres et rappelle la défiance qu’a pu éveiller cet art de la conviction : cet outil pourrait-il être dévoyé et, manipulant la crédulité des auditeurs, convaincre de la véracité du faux ? L’étude des procédés de l’éloquence a pris plus récemment une force nouvelle avec le linguistic turn; la force des mots, le pouvoir du langage sont à nouveau reconnus pleinement comme indissociables des contenus du discours. Les études proposées ici qui concernent l'Espagne médiévale et classique, permettront d’évaluer la diversité des éléments textuels et contextuels qui priment à chaque fois, afin de démasquer les ressorts qui ont vocation à emporter l’adhésion du lecteur et à construire l’apparence d’une vérité. Si se necesitara una imagen para evocar el poder del discurso, podría ser la de Hércules Ogmios que conduce a una procesión cuyos oídos están encadenados a su lengua. Emblema de la fuerza de la elocuencia, bajo los auspicios de este Hércules galo colocamos nuestra reflexión aquí para tratar de comprender la naturaleza de estas cadenas por las cuales el autor cautiva a su audiencia: ¿ cómo se hace el texto irresistiblemente convincente y persuasivo para que el lector siga el camino del autor seductor? La imagen comunica claramente el poder que este poder confiere sobre los demás y recuerda la desconfianza que ha despertado este arte de la convicción: ¿podría esta herramienta estar equivocada y, manipulando la credulidad de los oyentes, convencer de la veracidad de lo falso? El estudio de los procesos de elocuencia ha adquirido más recientemente una nueva fuerza con el giro lingüístico; El poder de las palabras, el poder del lenguaje son nuevamente completamente reconocidos como inseparables de los contenidos del habla. Los estudios propuestos aquí, que conciernen a la España medieval y clásica, permitirán evaluar la gran diversidad de elementos textuales y contextuales que prevalecen, para desenmascarar los resortes que tienen como objetivo ganar la adhesión del lector y construir la apariencia de la verdad If an image were needed to evoke the power of the speech, it could be that of Hercules Ogmios leading to a procession whose ears are chained to his tongue. Emblem of the force of eloquence, it is under the aegis of this Gallic Hercules that we place our reflection here to try to grasp the nature of these chains by which the author captivates his audience: how the text is made irresistibly convincing and persuasive to make the reader follow the path of the seductive author? The image clearly communicates the power that this power confers on others and recalls the distrust that this art of conviction has aroused: could this tool be misguided and, manipulating the credulity of the listeners, convince of the veracity of the wrong? The study of the processes of eloquence has more recently taken on a new force with the linguistic turn; the power of words, the power of language are again fully recognized as inseparable from the contents of speech. The studies proposed here which concern medieval and classical Spain, will make it possible to evaluate the great diversity of the textual and contextual elements which take precedence in order to unmask the springs which aim at winning the adhesion of the reader and to build the appearance of a truth
Caractéristiques et modalités évolutives de l' anémie hémolyotique auto-immune à anticorps chauds de l' adulte (série rétrospective monocentrique de 60 patients)
No full textNous avons mené une étude rétrospective monocentrique sur l anémie hémolytique auto-immune à anticorps chauds de l adulte, incluant 60 patients d âge moyen 54+-23 ans. L AHAI était considérée comme primitive dans 35% des cas. Les formes secondaires étaient le plus souvent liées à une hémopathie lymphoïde (23%) ou une autre maladie auto-immune (13%). La quasi-totalité des patients a reçu une corticothérapie avec 87% de réponse initiale mais une cortico-dépendance dans 63% des cas, nécessitant une seconde ligne de traitement chez 52% des patients. Une réponse complète à la corticothérapie était prédictive de rémission en fin de suivi. Au total, 45% ont reçu du rituximab, avec 86% de réponse initiale mais des rechutes fréquentes. La splénectomie était réalisée chez 8 patients avec dans tous les cas une réponse initiale, mais durable que chez la moitié. Au total, après un suivi de 42+-40 mois, 52% des patients étaient en rémission complète (absence d hémolyse en l absence de traitement poursuivi) et 20% en rémission partielle. Pour les 28% restants, l AHAIc était toujours active (hémolyse non compensée et/ou nécessité de poursuivre un traitement autre qu une corticothérapie inférieure à 10mg/j d équivalent prednisone). Dix patients (17%) ont présenté des manifestations thrombo-emboliques veineuses, 5 patients (8%) sont décédés. La comparaison de l ensemble des formes secondaires aux formes primaires n a pas montré de différence significative. En revanche, dans le sous-groupe des AHAIc associées à une hémopathie lymphoïde, une hypogammaglobulinémie et surtout une immunoglobuline monoclonale étaient plus fréquemment observées et la réponse à la corticothérapie était moins bonne.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF
Combinatorial Control of Th17 and Th1 Cell Functions by Genetic Variations in Genes Associated With the Interleukin‐23 Signaling Pathway in Spondyloarthritis
No full textInternational audienceRecent genome-wide association studies have revealed numerous genetic associations between specific single-nucleotide polymorphisms (SNPs) and immune-mediated inflammatory diseases. The current challenge is to identify associations of the genetic variants with effector mechanisms implicated in pathogenesis. This study was undertaken to investigate the link between genetic variation at loci associated with spondyloarthritis (SpA) and the effector function of CD4+ T lymphocyte subsets involved in chronic inflammatory disease
Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan
No full textMicroglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer’s and Parkinson’s). Taking into account the recent identification of microglia-specific markers, and the availability of compounds that target these cells selectively in vivo, we consider the prospect of disease intervention via the microglial route
Ezrin interacts with the SARS coronavirus spike protein and restrains infection at the entry stage
No full text© 2012 Millet et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: Entry of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) and its envelope fusion with host cell membrane are controlled by a series of complex molecular mechanisms, largely dependent on the viral envelope glycoprotein Spike (S). There are still many unknowns on the implication of cellular factors that regulate the entry process. Methodology/Principal Findings: We performed a yeast two-hybrid screen using as bait the carboxy-terminal endodomain of S, which faces the cytosol during and after opening of the fusion pore at early stages of the virus life cycle. Here we show that the ezrin membrane-actin linker interacts with S endodomain through the F1 lobe of its FERM domain and that both the eight carboxy-terminal amino-acids and a membrane-proximal cysteine cluster of S endodomain are important for this interaction in vitro. Interestingly, we found that ezrin is present at the site of entry of S-pseudotyped lentiviral particles in Vero E6 cells. Targeting ezrin function by small interfering RNA increased S-mediated entry of pseudotyped particles in epithelial cells. Furthermore, deletion of the eight carboxy-terminal amino acids of S enhanced S-pseudotyped particles infection. Expression of the ezrin dominant negative FERM domain enhanced cell susceptibility to infection by SARS-CoV and S pseudotyped particles and potentiated S-dependent membrane fusion. Conclusions/Significance: Ezrin interacts with SARS-CoV S endodomain and limits virus entry and fusion. Our data present a novel mechanism involving a cellular factor in the regulation of S-dependent early events of infection.This work was supported by the Research Grant Council of Hong Kong (RGC#760208)and the RESPARI project of the International Network of Pasteur Institutes
Microglia Gone Rogue: Impacts on Psychiatric Disorders across the Lifespan
No full textInternational audienceMicroglia are the predominant immune response cells and professional phagocytes of the central nervous system (CNS) that have been shown to be important for brain development and homeostasis. These cells present a broad spectrum of phenotypes across stages of the lifespan and especially in CNS diseases. Their prevalence in all neurological pathologies makes it pertinent to reexamine their distinct roles during steady-state and disease conditions. A major question in the field is determining whether the clustering and phenotypical transformation of microglial cells are leading causes of pathogenesis, or potentially neuroprotective responses to the onset of disease. The recent explosive growth in our understanding of the origin and homeostasis of microglia, uncovering their roles in shaping of the neural circuitry and synaptic plasticity, allows us to discuss their emerging functions in the contexts of cognitive control and psychiatric disorders. The distinct mesodermal origin and genetic signature of microglia in contrast to other neuroglial cells also make them an interesting target for the development of therapeutics. Here, we review the physiological roles of microglia, their contribution to the effects of environmental risk factors (e.g., maternal infection, early-life stress, dietary imbalance), and their impact on psychiatric disorders initiated during development (e.g., Nasu-Hakola disease (NHD), hereditary diffuse leukoencephaly with spheroids, Rett syndrome, autism spectrum disorders (ASDs), and obsessive-compulsive disorder (OCD)) or adulthood (e.g., alcohol and drug abuse, major depressive disorder (MDD), bipolar disorder (BD), schizophrenia, eating disorders and sleep disorders). Furthermore, we discuss the changes in microglial functions in the context of cognitive aging, and review their implication in neurodegenerative diseases of the aged adult (e.g., Alzheimer's and Parkinson's). Taking into account the recent identification of microglia-specific markers, and the availability of compounds that target these cells selectively in vivo, we consider the prospect of disease intervention via the microglial route
Acute myeloid leukemia with T-cell receptor gamma gene rearrangement occurring in a patient with chronic lymphocytic leukemia: A case report
No full textThe association of chronic lymphocytic leukemia (CLL) and acute leukemia, either lymphoid or myeloid is a rare event. Our review of the medical literature revealed only 6 cases of CLL transformation to acute myeloid leukemia (AML) (M0, M1 and M2) with no other associated malignancy. We report a similar case but with occurrence of AML-M4 associated with normal cytogenetic analysis and molecular testing but with positive T-cell receptor gamma gene rearrangement rather than the usual Vbeta rearrangement. © 2006 Wiley-Liss, Inc.Barresi GM, 2000, LEUKEMIA LYMPHOMA, V38, P621, DOI 10.3109-10428190009059282; Bellosillo B, 1999, BLOOD, V94, P2836; Boeckx N, 2002, LEUKEMIA, V16, P368, DOI 10.1038-sj-leu-2402387; BRACEY AW, 1989, AM J HEMATOL, V30, P174, DOI 10.1002-ajh.2830300310; BROUET JC, 1973, BRIT MED J, V4, P23; CATOVSKY D, 1971, LANCET, V1, P478; Cheson BD, 1999, J CLIN ONCOL, V17, P2454; ESCUDIER SM, 1993, BLOOD, V81, P2702; FRENKEL EP, 1981, AM J HEMATOL, V10, P391, DOI 10.1002-ajh.2830100409; KANTARJIAN HM, 1986, J CLIN ONCOL, V4, P1748; KEMPIN S, 1982, BLOOD, V60, P1110; Lai R, 1999, AM J CLIN PATHOL, V111, P373; Li Rong-Fu, 2002, Zhongguo Shi Yan Xue Ye Xue Za Zhi, V10, P299; MCPHEDRA.P, 1970, BLOOD-J HEMATOL, V35, P7; Morrison VA, 2002, J CLIN ONCOL, V20, P3878, DOI 10.1200-JCO.2002.08.128; ROBERTSON LE, 1994, LEUKEMIA, V8, P2047; Roumier C, 2003, BLOOD, V101, P1277, DOI 10.1182-blood-2002-05-1474; ROZMAN C, 1995, NEW ENGL J MED, V333, P1052, DOI 10.1056-NEJM199510193331606; Scrivener S, 2003, LEUKEMIA LYMPHOMA, V44, P383, DOI 10.1080-1042819021000029993; STERN N, 1981, CANCER, V47, P1849, DOI 10.1002-1097-0142(19810401)47:71849::AID-CNCR28204707223.0.CO;2-X; YANG L, 2000, ZHONGGUO SHI YAN XUE, V8, P196; ZARRABI MH, 1977, ARCH INTERN MED, V137, P1059, DOI 10.1001-archinte.137.8.105923
CCR5 Blockade in Inflammatory PML and PML-IRIS Associated With Chronic Inflammatory Diseases' Treatments
No full textInternational audienceBackground and objectives: Progressive multifocal leukoencephalopathy (PML) is a disabling neurologic disorder resulting from the infection of the CNS by JC polyomavirus in immunocompromised individuals. For the last 2 decades, increasing use of immunotherapies leads to iatrogenic PML. Iatrogenic PML is often associated with signs of inflammation at onset (inflammatory PML) and/or after treatment withdrawal immune reconstitution inflammatory syndrome (PML-IRIS). Although immune reconstitution is a key element for viral clearance, it may also be harmful and induce clinical worsening. A C-C chemokine receptor type 5 (CCR5) antagonist (maraviroc) has been proposed to prevent and/or limit the deleterious immune responses underlying PML-IRIS. However, the data to support its use remain scarce and disputed.Methods: We conducted a multicenter retrospective cohort study at 8 university hospitals in France and Switzerland by collecting clinical, biological, and radiologic data of patients who developed inflammatory PML (iPML) or PML-IRIS related to immunosuppressive therapies used for chronic inflammatory diseases between 2010 and 2020. We added to this cohort, a meta-analysis of individual case reports of patients with iPML/PML-IRIS treated with maraviroc published up to 2021.Results: Overall, 27 cases were identified in the cohort and 9 from the literature. Among them, 27 met the inclusion criteria: 16 treated with maraviroc and 11 with standard of care (including corticosteroids use). Most cases were related to MS (92.6%) and natalizumab (88%). Inflammatory features (iPML) were present at onset in 12 patients (44.4%), and most patients (92.6%) received corticosteroids within the course of PML. Aggravation due to PML-IRIS was not prevented by maraviroc compared with patients who received only corticosteroids (adjusted odds ratio: 0.408, 95% CI: 0.06-2.63). Similarly, maraviroc did not influence time to clinical worsening due to PML-IRIS (adjusted hazard ratio = 0.529, 95% CI: 0.14-2.0) or disability at the last follow-up (adjusted odds ratio: 2, 95% CI: 0.23-17.3).Discussion: The use of CCR5 blockade did not help to keep deleterious immune reconstitution in check even when associated with corticosteroids. Despite maraviroc's reassuring safety profile, this study does not support its use in iPML/PML-IRIS.Classification of evidence: This study provides Class IV evidence showing that adding maraviroc to the management of iatrogenic iPML/PML-IRIS does not improve the outcome
High dose romiplostim as a rescue therapy for adults with severe bleeding and refractory immune thrombocytopenia
No full textInternational audienc
