WorldCat Identities

École doctorale Biologie-Santé Nantes-Angers

Overview
Works: 637 works in 859 publications in 1 language and 963 library holdings
Roles: Other, 996, Degree grantor
Publication Timeline
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Most widely held works by École doctorale Biologie-Santé Nantes-Angers
Étude du trans-épissage comme outil de thérapie génique dans le modèle canin de la mucopolysaccharidose de type VII by Sylvain Sachot( )

3 editions published in 2009 in French and held by 4 WorldCat member libraries worldwide

Parmi les stratégies correctives en thérapie génique, le trans-épissage permet de remplacer, au niveau de l'ARN pré-messager, une séquence mutante par une séquence normale exogène portée par un « PTM » dans une réaction contrôlée par le spliceosome. Dans cette étude, nous avons évalué la faisabilité du trans-épissage dans le modèle canin de la mucopolysaccharidose de type VII. Nous avons testé différents PTM, de même que différentes molécules adjuvantes, le snRNAU7 et les ARN bifonctionnels. Nos résultats montrent que dans un système minigène, le trans-épissage permet la reprogrammation de l'ARN pré-messager ß-glucuronidase, détectable au niveau moléculaire comme au niveau protéique. Cependant, les choses sont beaucoup plus compliquées dans un environnement naturel. Les PTM sont ici capables d'interagir avec leur cible, mais l'efficacité de la réaction est le facteur limitant le plus critique. Ainsi, s'il a pu être possible de détecter des ARN messagers « trans-épissés », notamment en présence du snRNA U7 et des ARN bifonctionnels, nous n'avons jamais été en mesure de détecter de protéine issue de la réaction de trans-épissage dans cet environnement. Cette étude, ainsi que d'autres, pointent la difficulté de manipulation du trans-épissage dans les protocoles de thérapie génique
Optimisation des méthodes de sélection et de stimulation des lymphocytes T CD8 spécifiques de mélanome by Régis Bouquié( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Metastatic melanoma is a very aggressive cancer, and unfortunately, conventional treatments are inefficient. The existence of spontaneous regressions due to the presence of cytotoxic T lymphocytes has been described. Thus, adoptive immunotherapy could be an interesting therapeutic strategy. In the first part of this document, we describe a new immunomagnetic reagent to sort melanoma specific CD8 T lymphocytes, based on multimeric MHC/peptide complexes. All the components of this new multimer can be obtained in clinical grade. This new reagent can quickly sort pure and functional specific T cells after a single peptide stimulation of melanoma patients' PBMCs. In addition, this new multimer induces very little apoptosis or activation after binding specific T lymphocytes. Therefore, it should facilitate the development of adoptive cell therapy protocols in cancer patients. In a second part, we studied the effects of two co-stimulation molecules (CD28 and 4-1BBL) on Melan-A specific CD8 T cells. These ligands are crucial for efficient stimulation and play a key role in the generation and maintenance of CD8 memory T cells. We show that CD28 is more efficient to expand CD28+ specific T cells, both from healthy donors and melanoma patients. The co-stimulatory effect of 4-1BBL, which concerns mainly CD28- T cells, was more pronounced in specific T cells from melanoma patients than from heathy donors
Rôle des lymphocytes LAG-3 positifs en transplantation by Thomas Haudebourg( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Les traitements immunosuppresseurs ont des effets secondaires important et n'inhibent que partiellement le rejet chronique en transplantation. Il est donc important de continuer à chercher de nouvelles voies thérapeutiques pouvant améliorer l'immunosuppression et induire la tolérance immunitaire. L'utilisation d'un anticorps déplétant sélectivement les lymphocytes T lors de leur activation pourrait constituer un réactif capable d'induire la survie à long terme de greffons allogéniques et le développement de mécanismes régulateurs. LAG-3 est une protéine exprimée spécifiquement sur les lymphocytes T et NK activés. Son rôle physiologique est complexe car elle intervient dans la maturation des cellules dendritiques et à la fois transmet un signal inhibiteur au lymphocyte T. Lors de ce travail de thèse, nous avons voulu explorer les effets immunomodulateurs d'anticorps anti-LAG-3. Dans une première étude nous avons établi la présence de cette molécule au niveau du greffon au moment du rejet dans un modèle de transplantation cardiaque chez le rat. L'administration d'un anticorps cytotoxique anti LAG-3 en traitement d'induction a engendré une déplétion des cellules T activés et une prolongation significative de survie du greffon (J32 contre J5 sans traitement). L'utilisation de cet anticorps a aussi permis de retarder le rejet avec une administration tardive (J4 post greffe). Cependant, nous avons aussi constaté que cet anticorps bloquait l'induction et le maintien d'un état de tolérance immunologique dépendant des Treg, confirmant ainsi le rôle immunorégulateur essentiel des Treg LAG-3 positifs. En parallèle à cette étude, nous avons développé un modèle pré clinique d'hypersensibilité cutanée retardée chez le primate et avons étudié l'effet d'anticorps anti LAG-3. Le traitement a fortement diminué la réponse érythémateuse et a bloqué l'infiltration par des cellules T au niveau de la zone d'injection. En conclusion, ces données indiquent le potentiel mais aussi les limitations de l'utilisation thérapeutique d'anticorps anti-LAG-3
Impact de la nutrition périnatale sur la programmation du comportement alimentaire : de l'ontogenèse des réseaux hypothalamiques à la régulation de la prise alimentaire by Bérengère Coupé( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

En néonatalogie, les enfants nés avec un petit poids à la naissance (petit pour l'âge gestationnel) qui ont subi un retard de croissance intra-utérin (RCIU), sont alimentés avec des laits enrichis en protéines afin d'assurer un bon développement staturo-pondéral et cognitif. Cependant, un rattrapage de croissance après un RCIU est corrélé avec l'apparition de pathologies associées au syndrome métabolique et à un déséquilibre de la balance énergétique à l'âge adulte. Cette observation est connue sous le terme de “programmation fœtale”. Les mécanismes à l'origine de cette programmation sont encore inconnus. Nous avons émis l'hypothèse qu'une dérégulation de la prise alimentaire accompagnerait l'apparition des désordres métaboliques et trouverait son origine en période périnatale lors de l'ontogenèse de l'hypothalamus. Notre objectif a été de déterminer, chez le rat ayant subi un RCIU induit par restriction des apports en protéines in utero, l'effet d'un rattrapage de croissance précoce (les rats RCIU sont nourris par des rattes ad-libitum ou avec un lait enrichi en protéines) sur la mise en place et la régulation des réseaux hypothalamiques contrôlant la prise alimentaire. Nous avons démontré un effet bénéfique d'un rattrapage de croissance précoce après un RCIU sur l'établissement des circuits hypothalamiques et sur la régulation de la prise alimentaire à court terme. Le comportement alimentaire et la réponse métabolique après un repas sont altérés chez des rats adultes RCIU. Ces paramètres semblent être programmés in utero. Nos résultats indiquent une altération du comportement alimentaire qui peut être une cause majeure de l'apparition des désordres métaboliques
Immunothérapie des cancers : tentative de mise en évidence d'un nouvel antigène tumoral chez l'homme et développement préclinique d'un agent thérapeutique by Laure-Hélène Ouisse( Book )

2 editions published in 2011 in French and held by 3 WorldCat member libraries worldwide

The development of cancer immunotherapy treatment requires the discovery of new tumor antigens. The first part of my thesis was to determine the antigen recognized by a specific T cell clone derived from human colon tumor. This study did not lead to the discovery of a new antigen but to emphasize the importance of ICAM-1 in the costimulation of this T cell clone CD4 + CD8 +. This clone recognizes an antigen shared by a large number of cell types and may have a regulatory rôle . One obstacle to immunotherapy treatments is the development of regulatory immune responses, and the second part of my work was to study the mechanisms involved in the functional inactivition of murine T regulatory cells (Tregs) by the bacteria E.coli expressing the Listeriolysin-O (LLO). In mice, injection of these bacteria induces a strong anti-tumor response in preventive of curative protocols that has been correlated with a strong cytotoxic response, favored by a loss of Tregs function. Dendritic cells (DC) are the mediators of this inhibition. In addition, the data demonstrate the essential role of the inhibition of IL-10 secretion in DC infected with E. coli/LLO and the rôle of this inhibition in Tregs function. Infection experiments on human DC show a similar effect on the expression of IL-10 suggesting the possibility of the utilisation of these recombinant bacteria in humans immunotherapy protocols
Transports intracellulaires ciblés de macromolécules biologiques by Émilie Letrou-Bonneval( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Targeted gene transfer is a promising approach to treat various acquired or hereditary diseases. Numerous synthetic cationic vectors have been synthetized and are successfully used for in vitro gene transfer but an excess of positive charges lead to cytotoxicity and does not enable specific transfection. Therefore, we decided to design alternative molecular gene delivery systems to target cellular internalization through the receptor-mediated endocytosis pathway instead of the regular non-specific electrostatic interactions with cell membranes. This alternative system corresponds to a new neutral supramolecular assembly of lipoplexes equipped with galactose residues to specific target asialoglycoprotein receptors located on hepatocytes. The presence of galactose residues on this alternative molecular system led to specific transfection of primary hepatocytes through a specific endocytosis whereas ungalactosylated multimodular system did not transfect at all. Then, a novel class of galactosylated amphiphilic block copolymers were developed for pulmonary gene transfer as an essential alternativ to cationic lipids which lead to an important inflammation in the airways. The grafting of glycosyl residues onto the distal ends of block copolymers led to a significantly higher transfection efficiency in the lungs than unsubstituted block copolymers. Indeed, galactosylated block copolymers allows transgene expression in more epithelial pulmonary cells
Analyse de l'implantation de la stratégie de prise en charge à domicile du paludisme chez les enfants de 0 à 5 ans au Rwanda by Manassé Nzayirambaho( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Au Rwanda, la mortalité et la morbidité palustres sont particulièrement élevées chez les enfants âgés de moins de cinq ans, et la plupart décèdent avant d'arriver dans un établissement de santé. Les représentations de la population vis-à-vis de la fièvre, l'éloignement des formations sanitaires et la pauvreté sont probablement quelques uns des facteurs qui amènent les communautés à fréquenter moins les établissements de santé et à recourir plutôt au secteur privé ou informel dont les médicaments sont inadaptés et de qualité médiocre. Pour tenter de résoudre ce problème, le Ministère de la santé a introduit en 2004 une stratégie de prise en charge à domicile du paludisme connue sous le nom de « Home - Based Management for Malaria » (HBM) dans certaines zones pilotes du pays. Cette stratégie consiste à mettre des antipaludiques dans la communauté, chez un agent de santé communautaire qui les donne aux enfants fébriles. L'objectif étant d'augmenter le nombre d'enfants qui accèdent à un traitement antipaludique dans un délai de 24 heures après l'apparition des symptômes. Deux ans et demi après l'introduction de cette stratégie de HBM, nous avons mesuré son niveau de mise en œuvre et ses effets. Nous avons aussi analysé l'influence du contexte politique et structurel sur le niveau de mise en œuvre et sur les effets cette stratégie. Il s'agit d'une recherche évaluative de type « avant - après avec site contrôle contemporain de l'intervention ». Les résultats suggèrent que grâce à un bon niveau de mise en œuvre et un contexte d'implantation favorable, le HBM améliore l'accessibilité des soins et leur utilisation, et diminue la morbidité palustre
Analyse de la contribution des réponses lymphocytaires T spécifiques d'herpesvirus au répertoire alloréactif par criblage de lymphocytes T CD4+ ou CD8+ spécifiques du cytomégalovirus ou du virus d'Epstein-Barr by Alexis Morice( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

T lymphocytes expressing ab T cell antigen receptors are selected in the thymus, and are thus restricted to recognize self Major Histocompatibility Complex (MHC) molecules loaded with peptides. Yet, T lymphocytes frequently cross-react with allogeneic MHC molecules. Though association between persistent viral infection and allograft rejection is well admitted, few examples of T-cell cross-reactivity between self-MHC/viral and allogeneic HLA molecules have been documented so far. We appraised in this study the alloreactive potential of CD8+ or CD4+ T cell populations, specific for immunodominant epitopes derived from cytomegalovirus (HCMV) or Epstein-Barr virus (EBV), two herpesviruses that infect a large fraction of the human population. Most T cell lines that were screened were obtained by immunomagnetic sorting, using beads covered with recombinant peptide/MHC multimeric complexes. Our results show that herpesvirus-specific T cells frequently cross-react with allogeneic MHC molecules, exhibiting vigorous cytotoxicity toward different types of target cells. Thus, virus-specific T cells recognizing allo-MHC alleles may play an essential role in solid organ rejection. On the other hand, we bring evidence that CD8+ T lymphocytes can mediate alloresponses through an activating NKR receptor (Natural Killer cell receptor) of the LIR/ILT family, supporting the notion that activating NKR contribute to alloreactivity
Étude d'association cas-témoins pour l'identification de gènes de prédisposition au cancer colorectal sporadique by Sébastien Robiou du Pont( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Colorectal cancers (CRC) constitute the third most frequent cancer in France. Two distinct forms of CRC can be distinguished: the family forms (25%), due to deleterious mutations in known high-risk genes, and sporadic forms (75%), induced by the combined effect of both genetic and environmental risk factors not identified yet. In order to determine the genetic component of sporadic CRC, we conducted a case-control association study using low-penetrance genetic variants. By a “candidate gene approach”, we demonstrated the CRC-predisposing effect of 5 SNPs (Single Nucleotide Polymorphism) located genes PTGS1, IL8, MTHFR, PLA2G2A, PPARG, almost all involved in procarcinogenetic inflammatory events. By focusing on metabolic pathway,we highlighted a gene-environment interaction between cytochromes P450 SNPs and great red meat consumption. By a genome-wide association study based on DNA pools, we eventually showed, in our population, the involvement of two others SNPs located in CDH13 and UTP6, the predisposing effect of the CDH13 SNP being strengthened by a genotype-mRNA expression rate correlation. The fact that CDH13 belongs to the cadherin superfamily, whose members have a clear role in cancer, leads us to continue our investigations by analyzing the involvement of other SNPs of cadherin genes in CRC
Étude des modifications fonctionnelles et épigénétiques induites par la dénutrition périnatale sur les circuits cérébraux de régulation de la prise alimentaire by David Ricardo Orozco-Solis( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

The main objective of the present work was to determine the influence of the early nutritional environment on the functioning of the hypothalamic neuronal networks regulating food intake and energy homeostasis. The conceptual framework for this research is the thrifty phenotype hypothesis which postulates that in response to nutrient restriction during perinatal development an organism makes metabolic adaptations to survive optimally in a poor nutrient environment. However, when nutrition is adequate or overabundant, the conflict between the metabolic programming and the new nutritional conditions leads to obesity, insulin resistance and hypertension. More precisely, the aims of the present work were: 1) to identify and characterize the effects of protein restriction during gestation and lactation on feeding behavior; 2) to determine if these alterations are associated to epigenetic modifications. The results of the first part of our work indicate that: 1) perinatal protein-restriction leads to increased food intake in relation to body weight during the first six weeks after weaning and accelerates body weight gain; 2) the hyperphagia exhibited by young undernourished animals is characterized by a delayed appearance of satiety, an increase in meal size and reduced latency to eat as well as by an enhanced hypothalamic expression of the orexigenic peptides AgRP and NPY and a reduction in the expression levels of the mRNA coding for the anorexigenic peptide POMC; 3) protein restriction during perinatal development attenuates the inhibitory action of serotonin on food intake via a reduced sensitivity of 5-HT1B Collectively, these results indicate that the higher food intake of young undernourished rats relative to control animals is the result of both a decreased action of negative feedback signals critical to meal termination and an enhanced function of the positive signals than initiate and maintain eating. However, the fact that under conditions of exposure to standard chow, old animals exposed to protein-restriction during perinatal development consume daily the same amount of food than control offspring but exhibit body composition and metabolic disturbances indicative of obesity, suggests that perinatal malnutrition programmes obesity through a mechanism independent of its effects on feeding behaviour. This hypothesis is further sustained by the analysis of the hypothalamus transcriptome in 180 days-old rats which indicate that the programming of the hypothalamic circuits regulating energy homeostasis rather than food intake is a key step in the development of obesity associated with malnutrition in early life. Our receptors; 4) feeding a low-protein diet during gestation and lactation induces a long-lasting disruption of the diurnal expression pattern of the canonical circadian clock genes CLOCK, BMAL1 and Period1 as well as that of several genes involved in the regulation food intake. These effects persist long time after weaning and are associated with hyperphagia; 5) in spite of the fact that since the age of 2 months the offspring of protein-restricted dams consume the same quantity of food by day than their control counterparts, at 8 months, perinatal-undernourished rats show metabolic and body composition disturbances indicative of obesity including elevated levels of triglycerides and fatty acids in serum along with increased visceral fat; 6) a comparative genome wide analysis of the transcriptome in the hypothalamus of metabolic programmed rats versus controls, showed that that perinatal undernutrition induces permanent changes in the transcriptional profile of two gene clusters. The first one is constituted by several genes of the insulin and leptin signaling pathway which, additionally, act as gate keeper genes for regulation of nutrient sensing. The second cluster encompasses a functional network of nuclear receptors and co-regulators of transcription involved in the detection and use of lipid nutrients as fuel which, in addition, link temporal and nutritional cues to metabolism trough their tight interaction with the circadian clock. 12 observations constitute also the first direct evidence that the circadian clock is submitted to metabolic programming. Concerning the second part, as a first attempt to delineate the epigenetic changes induced by early malnutrition on the neuronal circuits regulating food intake, we analyzed the epigenetic status of Histone 3 (H3) and Histone 4 (H4) in several brain regions of 35 days-old offspring born to Spraguey-Dawley rats fed either a control (20%) or a low (8%) protein diet from the day of conception throughout gestation and lactation. Miniaturized protein arrays of histones from the hypothalamus, brain stem, hippocampus, and cerebral cortex of both control and undernourished animals were constructed and screened with anti-H3 or anti-H4 antibodies recognizing epigenetic modifications associated either with increased or with decreased gene transcription. The results of these experiments indicate that perinatal protein-restriction induced significant changes in the acetylated and methylated status of both H3 and H4 that differed from one brain region to another. Interestingly, the epigenetic modifications observed in the hypothalamus of malnourished animals are globally related to active gene transcription. In line with the results of the transcriptome analysis, the genome-wide high throughput study of DNA methylation in the hypothalamus using the methodology of ChIP on chip, indicated that perinatal undernutrition alters essentially the methylation levels of the promoter regions of the genes involved in the regulation of metabolic process
Effet de la supplémentation par la L-Arginine chez la femme enceinte sur le retard de croissance intra utérin vasculaire by Norbert Winer( Book )

2 editions published in 2008 in French and held by 3 WorldCat member libraries worldwide

Intra uterine growth retardation (IUGR) greatly increases neonatal morbidity and mortality, and has long term implications on the health of future adults. IUGR is frequently linked to impaired utero-placental circulation. Nitric oxide (NO) is a powerful endogenous vasodilator, produced exclusively from an amino acid, L-Arginine. In addition, the relationship observed between small- for-gestational age (SGA) and reduced amino acid concentrations in the fetal circulation, argues for a role of amino acid deficiency in the pathophysiology of IUGR. Without treatment validated so far, supplementation with L-arginine could be relevant to restore the production of NO in patients suffering from IUGR with endothelial dysfunction, as has already been shown for other vascular diseases. Our goal was to assess the effect of an exogenous supply of L Arginine in pregnant women whose fetus was suffering from a severe IUGR (<3rd percentile) with pathologic uterine dopplers, which have physiological similarities with pre-eclampsia. We included 44 patients between 24 and 32 WG, in a prospective, randomized multicenter study against placebo, arginine supplementation (14g / d). Our study, the first performed in this type of population, showed no benefit in term of weight gain or neonatal prognosis (CRIB Scoring). Our study suggests that other precursors that are metabolized less extensively such as citrulline, or modulators of placental transport, should be tested. Key words: L Arginine- NO pathway- intra uterine vascular fetal growth restriction- clinical randomised trial
Étude des mécanismes de la récidive du syndrome néphrotique idiopathique après transplantation rénale by Sarah Bruneau( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Idiopathic Nephrotic Syndrome (INS) is a glomerulopathy of unknown origin that evolves in 10 to 20% of cases toward end-stage renal failure, thus requiring long-term hemodialysis and/or kidney transplantation. However, 30 to 50% of transplant patients will develop an immediate recurrence of their initial disease, suggesting the involvement of one or several circulating factor(s) capable of injuring the glomerular filtration barrier. During this work, we tried to identify circulating permeability factors that could take part to the development of INS and its recurrence. We have shown that the sST2 protein, a potential permeability factor, is overexpressed in the serum of patients with INS recurrence after transplantation. However, this protein does not seem to be involved in the pathogenesis of recurrent INS. The potential presence of immunoglobulins which could target renal antigens has also been analyzed by the SEREX technique. This work led to the identification of three renal proteins potentially targeted by immunoglobulins in patients with INS recurrence, although these results have to be confirmed in more patients
Contribution à l'étude de la nutrition entérale et de la prévention des pneumopathies nosocomiales en milieu de réanimation by Jean Reignier( Book )

2 editions published in 2008 in French and held by 3 WorldCat member libraries worldwide

Early enteral feeding is a key component of the management of critically ill patients receiving mechanical ventilation. Compared to intravenous nutrition, enteral feeding has been associated with fewer infections and increased survival. However, many critically ill patients experience poor tolerance of early enteral nutrition because of impaired gastric motility with delayed gastric emptying. The resulting high residual gastric volumes increase the risk of gastroesophageal reflux, vomiting, aspiration, and ventilation-associated pneumonia. Moreover, the practice of enteral feeding at the bedside has never been standardized. In this thesis, we reported studies aimed to improve enteral feeding delivery and control of nosocomial pneumonia risk in patients receiving invasive mechanical ventilation. We demonstrated that erythromycin improves tolerance to early enteral feeding, that early enteral feeding is associated with higher rate of vomiting and subsequent underfeeding in patients turned in the prone position, that an intervention including prone positioning with 25° elevation and prophylactic erythromycin improves enteral nutrition delivery without increasing rates of vomiting or nosocomial pneumonia in patients turned in the prone position, and that patients without residual gastric volume monitoring during early enteral feeding receive more enteral nutrition without experiencing increased rates of vomiting or mechanical ventilation associated pneumonia
Influence de la taille sur la fonction colique et la tolérance digestive chez le chien by Joana Nery( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Le dioxyde de titane, connu pour ses applications dans les domaines de la photoactivité et du photovoltaïque, est aussi un candidat d'électrode négative pour batteries lithium-ion. Les variétés anatase et TiO2(B) sont les plus prometteuses. Leurs capacités sont respectivement de 0,50 et 0,75 Li+ par motif de TiO2. Sous forme nanométrique, elles présentent des densités d'énergie et de puissance accrues. L'objet de ce travail de thèse concerne la synthèse par chimie douce de dioxydes de titane nanométriques selon la méthode développée initialement par Kasuga et al. et leur caractérisation. La méthode en trois étapes génère successivement deux intermédiaires tels que (i) le titanate (NaOH)xTiO2(H2O)y (x = 0,3-0,5 et y = 0,4-0,7) par reflux, et (ii) l'acide titanique TiO2(H2O)z (z = 0,7-0,8) après échange ionique, et finalement, après recuit, (iii) le TiO2 de morphologie proche de celle du titanate précurseur. Quatre titanates de sodium ont été identifiés, trois structures lamellaires, se différenciant par leur morphologie (nanotubes, semi-nanotubes et nanorubans) et une structure amorphe s'apparentant à des nanosphères. Après échange ionique et recuit, les nanotubes et les nanosphères se transforment en anatase, les semi-nanotubes en un mélange d'anatase et de TiO2(B), et les nanorubans en TiO2(B) exclusivement. La quantification par spectroscopie Raman du ratio anatase/TiO2(B) a été développée en calibrant les intensités avec les résultats d'électrochimie. Enfin, les nanorubans de TiO2(B) ont été testés au sein de demi-batterie lithium métal. Les performances sont prometteuses avec une capacité réversible de 200 mAh.g-1 à C/3 (soit 0,6 Li+ par TiO2) et de 100 mAh.g-1 à C/15
Création et développement d'outils d'identification et d'évaluation de la pharmacodépendance médicamenteuse by Caroline Victorri-Vigneau( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

In order to evaluate pharmacodependence, one of its missions, the Health Products Safety Agency (AFSSAPS) monitors a network of dedicated bodies, the CEIP's (Centre for Evaluation and Information on Pharmacodependence), headed by pharmacology experts. Pharmacodependence, a complex behaviour, is a latent variable which can only be identified and characterized through its consequences. CEIP's have therefore implemented original tools evidencing medical drugs whose consumption ends up generating behaviours specifically suggesting pharmacodependence cases. As part of our aim to better identify and evaluate pharmodependence, our work led us to practice CEIP's tools, critically analyse them, and develop novel complementary tools. Our first approach consisted in using the pharmacodependence items as defined by DSM IV, in a move to creating a pharmacology seriousness score in cases of medical or street drug pharmacodependence. We then ran data bases of the French Health Insurance System, using over consumption and fraud, as patient selection criteria, to develop epidemiology tools which can properly (i) identify drugs liable to result in a pharmacodependence behaviour, and (ii) quantify the impact of measures aiming at minimizing risk. The standardized assessments of pharmacodependence cases through our score, and the development and validation of epidemiology tools, represent high performance diagnosis tools in the pharmacodependence evaluation process in France
Études structurales et fonctionnelles de trois alpha2-fucosyltransférases de rat by Valérie Bureau( )

2 editions published in 2000 in French and held by 3 WorldCat member libraries worldwide

Étude de la voie de présentation de l'antigène MMP-2 par les cellules tumorales by Virginie Renaud( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

From a patient still melanoma free after TIL injection, we characterized a new tumor antigen, MMP-2, recognized by a CD8 T cell clone in HLA-A*0201 context. Surprisingly melanoma cell lines present this tumor antigen by the cross presentation pathway (Godefroy & al., 2005). In the first part, we wondered if disulfide bonds present in MMP-2 were not responsible for its absence of presentation by the endogenous pathway. By mutagenesis, we replaced a cystein by an alanine in the cDNA coding for MMP-2, in order to induce a disulfide bond deletion and then we transfected these cDNA mutants in COS-7 and human tumor cell lines. We showed that MMP-2 deletion of one disulfide bond induce its presentation by the endogenous pathway. By pulse chase experiments we also demonstrated that MMP-2 mutated form is more rapidly degraded than the wild form. MMP-2 folding and consequently conformation seems to play an important role in the absence of its presentation by the classical pathway. In the second part, we try to determine intracellular pathway implicated in MMP-2 cross-presentation in melanoma cells. Indeed, after secretion, MMP-2 is internalized by melanoma cells in an v3 dependent manner and by an unknown pathway. MMP-2 is finally processed by the proteasome and loaded on MHC class I molecule (Godefroy & al., 2005). By using drugs, we determined that MMP-2 cross-presentation involves the retrotranslocation machinery, the proteasome and TAP, all implicated in the endogenous pathway. To determine compartments necessary to MMP-2 cross-presentation we tested Organelles lights (Invitrogen). These reagents provide a method for targeted specific subcellular structures within living cells
Optimisation de l'immunoscintigraphie tumorale par de nouvelles approches méthodologiques utilisant l'anti-antigène carcinoembryonnaire by Alain Chetanneau( )

1 edition published in 1992 in French and held by 3 WorldCat member libraries worldwide

Mécanismes moléculaires d'activation de la protéine G monomérique RhoA par l'angiotensine II : relation avec l'hypertension artérielle by Jérémy Brégeon( Book )

2 editions published in 2010 in French and held by 3 WorldCat member libraries worldwide

L'hypertension artérielle (HTA), définie par une élévation anormale de la pression artérielle (PA), est associée à des altérations structurales et fonctionnelles de la paroi artérielle, impliquant en particulier une contractilité et une prolifération excessives des cellules musculaires lisses vasculaires (CMLV). La protéine G monomérique RhoA est une protéine de signalisation connue pour son rôle dans la régulation du cytosquelette d'actine, de la contraction et de la prolifération des CMLV. Chez l'homme, ainsi que dans tous les modèles animaux d'HTA, une composante majeure du développement de l'HTA est l'activation massive de RhoA, sans que l'on connaisse son origine. Le but de ce travail a été (i) d'identifier les mécanismes de régulation de l'activité de RhoA en réponse à l'angiotensine II (AngII) jouant un rôle majeur dans le contrôle de la PA, et (ii) de valider leur intérêt thérapeutique. Dans un premier temps, nous avons montré que l'AngII inhibe un répresseur de RhoA, p190A, pour induire l'activation transitoire de la voie RhoA/ROCK. Nous avons ensuite montré que l'activation maintenue de RhoA par l'AngII nécessite le facteur d'échange Arhgef1, et que l'activité d'Arhgef1 est augmentée dans les CMLV de modèles animaux d'HTA. Après avoir généré une lignée murine qui n'exprime pas Arhgef1 spécifiquement dans les CML, nous avons montré que ces souris sont résistantes à une HTA dépendante de l'AngII. Ces souris sont également résistantes à l'HTA et aux atteintes rénales associées au diabète de type 1. L'ensemble de ces travaux a permis d'identifier de nouveaux mécanismes d'activation de RhoA dans la CML et de valider leur contribution dans le développement de l'HTA
 
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Alternative Names
BS 502

BS502

Ecole doctorale 502

ED 502

ED502

Languages
French (39)