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Mahoney, Brian. "Examination of platelet adhesion by Streptococcus sanguinis." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/1978.
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Streptococcus sanguinis is a leading cause of infective endocarditis. Bacterial adhesion to platelets is likely important in the pathogenesis of infective endocarditis. Bacterial cell wall-anchored (Cwa) proteins may mediate this adhesion. To begin to test this hypothesis, S. sanguinis adhesion to platelets was examined in vitro. The requirement of 12 Cwa proteins for S. sanguinis-platelet adhesion was individually assessed, measuring adhesion of purified platelets to polystyrene wells coated with S. sanguinis strain SK36 or 12 isogenic Cwa protein mutants. Significantly fewer platelets adhered to wells coated with one mutant strain, VT1614. However, results of a whole-cell enzyme-linked immunosorbent assay (ELISA) showed that 8 mutants, including VT1614, adhered in significantly lower numbers to wells than did SK36. After accounting for unequal bacterial numbers, we determined there was no significant difference in platelet adhesion among the strains. This suggests that none of the Cwa proteins examined were required for S. sanguinis-platelet adhesion.
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Atia, Sawsan. "SYSTEMATIC ANALYSIS OF ABC TRANSPORTERS IN STREPTOCOCCUS SANGUINIS." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3054.
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The bacterium Streptococcus sanguinis is a primary member of the human oral microflora and also has been recognized as a key player in the bacterial colonization of the mouth. It is considered the most common viridians streptococcal species implicated in infective endocarditis. In all kingdoms of life, ATP binding cassette (ABC) transporters are essential to many cellular functions. Sequencing of the SK36 genome provided the opportunity to study ABC transporter mutants and their relationship with acidity of the oral environment. Despite numerous studies that have focused on carbohydrate uptake systems in closely related streptococcal species such as S. mutans, S. pneumonia and S. pyogenes, the mechanism of the response of these ABC transporters to acidic conditions in S. sanguinis is still unknown. The capability of S. sanguinis to adapt in these harsh environments suggests this bacterium is capable of responding to various environmental stimuli. The purpose of this study was to examine ABC mutants to identify functions that contribute to acid tolerance in S. sanguinis. This study demonstrates that two acid-sensitive mutant genes, SSA_1507 and SSA_1508, identify genes involved in acid tolerance. The two mutants grew on different sugars and none of them showed a defect in sugar utilization at acid pH. We couldn’t recognize any significant differences in sugar uptake for the two acid sensitive mutants or in mutants of their neighboring genes. Thus, the observed acid sensitivity is not due to a failure to take up any of the common sugars tested. The cytoplasmic pH of S. sanguinis was studied with the fluorescent pH indicator (BCECF) and SK36 was observed to have a wider pH range than either of the two acid-sensitive mutants SSA_1507 or SSA_1508. In these two mutants, intracellular pH was not as well maintained. At all pH values tested, the mutants displayed a lower intracellular pH than the wild type. These observations indicate that the cell membrane of these two mutants is unable to protect the interior components from adverse effects of higher pH values and lower pH values, and prove that these two mutant genes SSA_1507 and SSA_1508 are unable to grow in lower pH values. These results support a role for these ABC transporters in proton pump or export and indicate that the mutants are less able to pump out protons.
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Callahan, Jill. "Functional Characterization of the Streptococcus sanguinis com Regulon." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/252.
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Streptococcus sanguinis is an important component of the dental plaque biofilm and is believed to play a beneficial role in the oral cavity. S. sanguinis is also a leading cause of infective endocarditis (IE), a potentially lethal infection of the cardiac valves. S. sanguinis possesses genetic competence, the ability to acquire exogenous DNA into its genome. In the well characterized system of S. pneumoniae, genetic competence requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternate sigma factor, ComX. Previous studies in other streptococcal species have suggested functions for the com regulon apart from DNA uptake. Here we characterized functions of the S. sanguinis com regulon genes in genetic competence, IE virulence, and biofilm formation. Our findings indicated that the early regulatory genes and those under the control of ComX in S. sanguinis play similar roles in genetic competence as their orthologs in other competent streptococci; however the sequence and mechanism of processing of the quorum sensing signal, competence-stimulating peptide, CSP, were determined to be unique. Using a rabbit endocarditis model, we determined that the comCDE and comX genes were not required for virulence, bacteremia, or pathology under a variety of infection conditions. In contrast, examination of biofilms by microscopy and crystal violet staining indicated that S. sanguinis CSP enhanced biofilm formation in a comDE-dependent manner. Deletion of the early com gene SSA_0195 eliminated this effect, while expression of the gene from an inducible promoter increased biofilm formation in the absence of CSP. Deletion of the comX gene resulted in biofilms with increased staining, cell death, and profoundly altered structure. Treatment with DNase I reduced biofilm formation in a com-independent manner. Taken together, these results suggest that expression of SSA_0195 is both necessary and sufficient for CSP-dependent biofilm enhancement, and that the late gene activator, ComX, is required to maintain normal biofilm architecture. Our findings suggest the com regulon of S. sanguinis may be an important determinant of competitiveness in the mouth, where native CSP production may occur at levels sufficient to influence biofilm formation.
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Patel, Jenishkumar. "ENVIRONMENTAL RESPONSES OF TWO-COMPONENT SYSTEMS IN STREPTOCOCCUS SANGUINIS." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2270.
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The gram-positive bacterium Streptococcus sanguinis is a member of human indigenous oral microbialflora and has long been recognized as a key player in the bacterial colonization of the mouth. S. sanguinis is also the most common viridians streptococcal species implicated in infective endocarditis. Although many studies have focused on two-component systems in closely related Streptococcus species such as S. mutans, S. pneumoniae and S. gordonii; the mechanism of the response regulator in S. sanguinis is still unknown. The ability of S. sanguinis to adapt and thrive in hostile environments suggests this bacterium is capable of sensing and responding to various environmental stimuli. The present study clearly demonstrates that a number of RR genes, SSA_0204, SSA_0217, SSA_1810, SSA_1794, and SSA_1842, in S. sanguinis are essential to the recognition and response to various environmental stresses. Results from this study also identified genes SSA_0260, SSA_0261, and SSA-0262, involved in acidic tolerance and suppressed by SSA_0204 response regulator.
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Turner, Lauren. "Identification of Virulence Determinants for Streptococcus sanguinis Infective Endocarditis." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1560.
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Streptococcus sanguinis is the second most common causative agent of bacterial infective endocarditis (IE). Risk of S. sanguinis IE is dependent on pre-disposing damage to the heart valve endothelium, which results in deposition of clotting factors for formation of a sterile thrombus (referred to as vegetation). Despite medical advances, high mortality and morbidity rates persist. Molecular characterization of S. sanguinis virulence determinants may enable development of prevention methods. In a previous screen for S. sanguinis virulence determinants by signature-tagged mutagenesis (STM) an attenuated mutant was identified with a transposon insertion in the nrdD gene, encoding an anaerobic ribonucleotide reductase. Evaluation of this mutant, as well as an nrdD in-frame deletion mutant, JFP27, by a soft-agar growth assay confirmed the anaerobic growth sensitivity of these strains. These studies suggest that an oxygen gradient occurs at the site of infection which selects for expression of anaerobic-specific genes at the nexus of the vegetation. The random STM screen failed to identify any favorable streptococcal surface-exposed prophylactic candidates. It was also apparent that additional genetic tools were required to facilitate the in vivo analyses of mutant strains. As it was desirable to insert antibiotic resistance markers into the chromosome, we identified a chromosomal site for ectopic expression of foreign genes. In vitro and in vivo analyses verified that insertion into this site did not affect important cellular phenotypes. The genetic tools developed facilitated further in vivo screening of S. sanguinis cell wall-associated (Cwa) protein mutants. A directed application of STM was employed for a comprehensive analysis of this surface protein class in the rabbit model of IE. Putative sortases, upon which Cwa proteins are dependent for cell surface localization, were also evaluated. No single S. sanguinis Cwa protein was determined essential for IE by STM screening; however competitiveness for colonization of the infection site was reduced for the mutant lacking expression of sortase A. The studies described here present a progressive picture of S. sanguinis IE, beginning with surface protein-dependent colonization of the vegetation in early IE, that later shifts to a bacterial persistence in situ dependent on condition-specific housekeeping genes, including nrdD.
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Turner, Lauren Senty. "Identification of virulence determinants for streptococcus sanguinis infective endocarditis /." Online version not available until 8/4/2013, 2008. http://hdl.handle.net/10156/2243.
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Al, Moussawi Ali. "Reconstruction 3D de vaisseaux sanguins." Thesis, Toulon, 2014. http://www.theses.fr/2014TOUL0014/document.
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Ce travail concerne la reconstruction 3D de vaisseaux sanguins à partir de coupes transversales en nombre éventuellement réduit. Si des données sont manquantes, une reconstruction cohérente avec un réseau de vaisseaux est obtenue. Cette approche permet en outre de limiter les interventions humaines lors du traitement des images des coupes transversales 2D. Sachant que les images utilisées sont obtenues par scanner,la difficulté est de connecter les vaisseaux sanguins entre deux coupes espacées pour obtenir un graphe qui correspond au cœur des vaisseaux. En associant les vaisseaux sanguins sur les coupes à des masses à transporter, on construit un graphe solution d’un problème de transport ramifié. La reconstruction 3D de la géométrie résulte des données 2D d’imagerie issues des différentes coupes transversales et du graphe. La géométrie 3D des vaisseaux sanguins est représentée par la donnée d’une fonction Level Set définie en tout point de l’espace dont l’iso-valeur zéro correspond aux parois des vaisseaux. On s’intéresse ensuite à résoudre numériquement le modèle de Navier-Stokes en écoulement incompressible sur un maillage cartésien inclus dans la géométrie reconstruite. Ce choix est motivé par la rapidité d’assemblage du maillage et des opérateurs discrets de dérivation, en vue d’éventuelles déformation des vaisseaux. L’inadaptation du maillage avec l’interface de la géométrie amène à considérer une condition limite modifiée permettant un calcul consistant des contraintes aux paroisThis work concerns the 3D reconstruction of blood vessels from a limited number of 2D transversal cuts obtained from scanners. If data are missing, a coherentreconstruction with a vessel network is obtained. This approach allows to limit human interventions in processing images of 2D transversal cuts. Knowing that the images used are obtained by scanner, the difficulty is to connect the blood vessels between some widely spaced cuts in order to produce the graph corresponding to the network of vessels. We identify the vessels on each trnasversal cut as a mass to be transported, we construct a graph solution of a branched transport problem. At this stage, we are able to reconstruct the 3D geometry by using the 2D Level Set Functions given by the transversal cuts and the graph information. The 3D geometry of blood vessels is represented by the data of the Level Set function defined at any point of the space whose 0-level corresponds to the vessel walls. The resulting geometry is usually integrated in a fluid mechanic code solving the incompressible Navier-Stokes equations on a Cartesian grid strictly included in a reconstructed geometry. The inadequacy of the mesh with the interface of the geometry is overcomed thanks to a modified boundary condition leading to an accurate computation of the constraints to the walls
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Xikota, João Carlos. "Contribuição ao estudo do comportamento da arteria cerebelar caudal no cão (CANIS FAMILIARIS - Linnaeus, 1758)." reponame:Repositório Institucional da UFSC, 1996. http://repositorio.ufsc.br/xmlui/handle/123456789/76540.
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Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciencias BiologicasMade available in DSpace on 2012-10-16T11:17:26Z (GMT). No. of bitstreams: 0Bitstream added on 2016-01-08T20:51:05Z : No. of bitstreams: 1 105627.pdf: 3171900 bytes, checksum: 5058f3926f899d9cd5c6ba0660b79c5c (MD5)
O estudo da origem, trajeto e ramificação da artéria cerebelar caudal, em 40 cães, injetados com solução de Schlesinger. Resultados: em 58,75% das observações, encontramos a artéria cerebelar caudal única e em 41,25% dupla. Em 5,00% dos lados observamos a presença de uma artéria cerebelar caudal acessória. A artéria cerebelar caudal originou-se da artéria basilar em 70,80% dos casos, da artéria vertebral em 26,55% ou de um tronco vértebro-basilar em 2,65%. Correlacionando origem e número da artéria cerebelar caudal verificamos que, quando única, esta teve origem na artéria basilar em 37,50% dos lados, na vertebral em 17,50%, e no tronco vértebro-basilar em 3,75%. Quando dupla, originou-se na artéria basilar em 21,25% e em 20,00% um ramo teve origem na artéria basilar e o outro na artéria vertebral.
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Jittapalapong, Sathaporn. "Immune resistance to Rhipicephalus Sanguineus in dogs /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488191124572314.
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Runnels, Cora. "Phylogeography and Species Status of Ramphogordius sanguineus." VCU Scholars Compass, 2013. http://scholarscompass.vcu.edu/etd/3165.
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Ramphogordius sanguineus (Rathke 1799) is a gregarious nemertean with a worldwide distribution and found mainly on hard substrates associated with mussels, oysters and other organisms of the fouling community. Asexual reproduction occurs by spontaneous fragmentation and only anecdotal accounts of sexual reproduction exist. This is the first phylogeographic study of R. sanguineus as well as the first species delimitation analyses employing DNA markers. Analysis of the mitochondrial gene nad6 and nuclear ISSR markers showed little diversity among geographically widespread populations, but AMOVA analyses of both markers revealed moderate to high genetic differentiation. Populations from Maine and Massachusetts exhibited the highest level of differentiation. These findings are consistent with predictions for invertebrates lacking a planktonic larval stage. Results of the nad6 tree-based delimitation analysis were in agreement with modern morphological and histocompatibility observations, suggesting that R. sanguineus is a single species and that a former division into four separate species was solely based on geographic location.
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Rodriguez, Alejandro. "Physiological and Molecular Characterization of Genetic Competence in Streptococcus sanguinis." VCU Scholars Compass, 2008. http://scholarscompass.vcu.edu/etd/1570.
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The ability of bacteria to assimilate free DNA from the environment is known as competence. Though many studies have focused on competence regulation in Streptococcus pneumoniae and Streptococcus gordonii, Streptococcus sanguinis has yet to be examined. Physiological characterization of competence in S. sanguinis strain SK36 and its comC mutant, JFP41, led to the genome-wide transcriptional analysis of cells induced to competence via addition of competence-stimulating peptide (CSP). A total of 128 genes were induced at least 2-fold, 74 of which were classified as either “early” or “late” based on their induction patterns. Expression patterns were verified using qRT-PCR. This study identified genes not up-regulated in S. pneumoniae or S. gordonii and lays the foundation for bioinformatic studies to identify conserved binding sites upstream from CSP-regulated genes. These results also shed light on the possible existence and identity of expected CSP exporters in S. sanguinis, which have so far eluded discovery.
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Aynapudi, Jessica. "Involvement of Signal Peptidase I in Streptococcus sanguinis Biofilm Formation." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4451.
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Biofilm accounts for 65%-80% of microbial infections in humans. Considerable evidence links biofilm formation to oral disease and consequently systemic infections. Eradication of biofilm-associated infections is important. Streptococcus sanguinis, a Gram-positive bacterium, is one of the most abundant species in oral biofilm. It contributes to biofilm development in oral cavities and is one of the recognized causes of infective endocarditis. To study and identify biofilm genes in S. sanguinis, biofilm formation of 51 mutants was compared with the wild type SK36 strain using crystal violet (CV) staining in a microtiter plate. Confocal laser scanning microscopy (CLSM) and image analysis was done to compare biofilm formation by the mutant to the wild type SK36 strain. A biofilm mutant XG2_0351, encoding a type I signal peptidase (SPase I), was further investigated. SPase I cleaves proteins that are transported through secretory machinery and is necessary for the release of translocated preproteins from a cytoplasmic site of synthesis to extracytoplasmic/membrane destinations. S. sanguinis, like many Gram-positive bacteria, has multiple SPases I. The objective of this project is to investigate the distinctive role that SPase I plays in biofilm formation in S. sanguinis. Using a plate reader, the growth curves of the wild type strain SK36 and XG2_0351 were compared. The scanning electron microscope (SEM) was utilized to compare the cell surface morphologies. Coomassie staining was done to narrow the list of potential substrates of XG2_0351. CV staining and CLSM images indicated phenotypic differences between the SPase I mutant and SK36. The growth curves of XG2_0351 and SK36 showed no significant difference although SEM illustrated a difference in the cell surface morphologies. Coomassie staining illustrated a number of substrates that were present in SK36 but not XG2_0351. In addition bioinformatics was used to understand the gene function. In conclusion, XG2_0351 reduces biofilm formation in S. sanguinis but further research is necessary to elucidate the specific proteins that are involved. Clarifying the vii role that SPase I plays in reduced biofilm formation in S. sanguinis will give a better understanding of the biofilm formation mechanism.
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Sollier, Elodie. "Microsystèmes pour la préparation d'échantillons sanguins." Phd thesis, Université Joseph Fourier (Grenoble), 2009. http://tel.archives-ouvertes.fr/tel-00434954.
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Beaucoup de tests de diagnostic médical sont réalisés sur le sang, qui est un échantillon représentatif d'états pathologiques complexes. La séparation des différents constituants du sang est surtout réalisée par centrifugation ; son passage en microsystème reste l'obstacle principal en vue de l'intégration complète de l'analyse sanguine. Notre but est donc de développer une technique simple et rapide, permettant de séparer les éléments sanguins de façon continue et efficace, et intégrable dans un laboratoire sur puce. Tout d'abord, des dispositifs microfluidiques innovants sont proposés pour l'extraction du plasma, fondés sur le couplage de différents phénomènes microfluidiques passifs. En particulier, ces dispositifs exploitent la couche appauvrie dans un écoulement en canal et l'amplifient par l'effet restriction ainsi que par des singularités géométriques. Un rendement d'extraction maximal de 17% est obtenu à partir de sang dilué au 1:20 et injecté à 100µL/min, soit une amélioration d'un facteur 4 par rapport au dispositif de référence. L'influence de la dilution de l'échantillon est analysée, et le plasma extrait est biologiquement validé. En parallèle, des méthodes de tri cellulaire par capture spécifique sont développées, fondées sur la fonctionnalisation de surface et le greffage d'anticorps. Une accroche spécifique et proportionnelle est mise au point et optimisée, à partir de sang total, pour chaque type cellulaire. Des solutions ont été proposées pour l'intégration de ces deux opérations unitaires, séparation microfluidique et tri cellulaire.
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Chabannes, Vincent. "Vers la simulation des écoulements sanguins." Phd thesis, Université de Grenoble, 2013. http://tel.archives-ouvertes.fr/tel-00923731.
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Contrairement aux liquides ordinaires, les fluides complexes comme le sang exhibent des comportements étranges qui dépendent essentiellement des structures sous-jacentes qui les composent. La simulation des écoulements sanguins continue de poser un formidable défi pour les modélisations théoriques et numériques dont l'intérêt est de développer des méthodes et des outils de simulation pour la communauté médicale. Nous proposons dans cette thèse une contribution à ce projet qui sera majoritairement centré sur les aspects numériques et informatiques. Nous nous sommes particulièrement intéressés à l'interaction entre le sang et la paroi vasculaire, qui joue un rôle important dans les grandes artères comme l'aorte. Nous nous sommes aussi investis dans la simulation du transport des cellules sanguines dans le sang. Pour la résolution des équations aux dérivées partielles décrivant nos modèles d'hémodynamique, nous avons choisi d'utiliser des méthodes numériques dont la précision pourra être accrue de manière arbitraire. Dans ce but, les principaux ingrédients qui ont été mis en oeuvre sont (i) la méthode des éléments finis basée sur des approximations de Galerkin d'ordre arbitraire en espace et géométrie, (ii) la méthode ALE pour la prise en compte de la mobilité des domaines pour des déplacements d'ordre arbitraire, (iii) les couplages implicites et semi-implicites pour l'interaction fluide-structure. Nous proposons également une nouvelle formulation de la méthode de la frontière élargie visant à modéliser le transport de particules déformables immergées dans un fluide. Nos simulations numériques se sont appuyées sur la librairie de calcul Feel++, spécialisée dans la résolution d'EDP. Outre l'implémentation des modèles physiques, nous y avons développé diverses fonctionnalités nécessaires à la mise en oeuvre de nos méthodes : interpolation, méthode de Galerkin non standard, méthode ALE, environnement pour l'interaction fluide-structure. De plus, de par la taille des géométries et la complexité des modèles mis en jeu, le passage au calcul parallèle a été indispensable pour pouvoir réaliser nos simulations. Ainsi, nous avons décrit le développement qui a été effectué dans cette librairie pour permettre le déploiement de nos programmes sur des architectures parallèles.
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Boileau, Adeline. "Biomarqueurs transcriptomiques sanguins des maladies cardiovasculaires." Thesis, Université de Lorraine, 2018. http://www.theses.fr/2018LORR0186/document.
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Les maladies cardiovasculaires (MCV) représentent la première cause de mortalité dans le Monde et en Europe. Le diagnostic et la prédiction de l’évolution des MCV reposent actuellement sur l’utilisation de biomarqueurs protéiques, mais doivent être améliorés pour optimiser la prise en charge des patients. Le transcriptome sanguin comprend l’ensemble des molécules ARN circulantes, qui sont présentes dans les cellules sanguines et libres dans le sang. Parmi elles, les ARN messagers (ARNm) codent pour des protéines alors que de petits ARN non codants, les microARNs (miARNs), répriment l’expression de leurs gènes cibles. Nous avons émis l’hypothèse que le transcriptome sanguin, et en particulier les ARNm et les miARNs, avaient un potentiel de biomarqueur, diagnostique ou pronostique, dans les MCV. En premier lieu, nous avons montré que l’héparine endogène pouvait induire une inhibition de la transcription inverse couplée à la PCR quantitative lors de la mesure des miARNs circulants et que ce paramètre devait être pris en compte lors de l’étude du transcriptome sanguin. Nous avons ensuite montré que 3 transcrits (codants pour les gènes LMNB1, LTBP4, TGFBR1) exprimés dans le sang total, étaient des prédicteurs indépendants de l’altération de la fonction cardiaque à 4 mois post-IM. De plus, l’ajout de ces 3 transcrits dans un modèle de prédiction contenant des variables cliniques augmente la valeur prédictive de ce modèle. Dans une troisième étude, nous avons montré que les niveaux circulants de miR-574-5p étaient capables de discriminer les patients porteurs d’un AAT des personnes saines. De plus, le miR-574-5p est encapsulé dans des vésicules extracellulaires dans le sang, suggérant un rôle paracrine. Au cours des quatrième et cinquième études, nous avons montré que les niveaux circulants de miR-122-5p étaient des prédicteurs indépendants de l’évolution neurologique et de la survie à moyen terme post-AC, et capable d’améliorer les modèles de prédiction existants. Nous avons également identifié le miR-574-5p comme prédicteur indépendant de l’évolution neurologique post-AC, spécifiquement chez les femmes. En conclusion, ce travail de thèse a permis la découverte ou la confirmation de la valeur de biomarqueurs potentiels de transcrits et miARNs dans différentes MCV. Cependant, leur capacité de biomarqueur devra être validée dans d’autres études à grande échelle et à l’aide d’autres techniques avant d’envisager leur utilisation en cliniqueCardiovascular disease (CVD) is the main cause of mortality in the World and in Europe. Diagnosis and prediction of outcome of CVD currently rely on the use of protein biomarkers, but should be improved to optimize patient healthcare. Blood transcriptome contains all RNA molecules present in blood cells and in the acellular compartment. Among them, messenger RNA (mRNA) code for proteins whereas small non coding RNA, microRNA (miRNA), have a regulatory function by repressing the expression of their target genes. We hypothesized that blood transcriptome, mRNA and miRNA in particular, had a potential as biomarker, diagnostic or prognostic, in CVD. In a first study, we showed that endogenous heparin could lead to an inhibition of reverse transcription and quantitative PCR reaction used to measure miRNAs expressed in the blood, and that this parameter should be considered for studies on blood transcriptome. Secondly, we showed that 3 transcripts (coding for genes LMNB1, LTBP4, TGFBR1) expressed in whole blood, were independent predictors of cardiac function alteration at 4 months post-MI. Furthermore, the inclusion of these 3 transcripts in a prediction model containing clinical variables had an incremental predictive value. In a third study, we showed that circulating levels of miR-574-5p were able to discriminate patients with TAA from healthy controls. Furthermore, miR-574-5p was encapsulated in extracellular vesicles in the blood, suggesting a paracrine role. In the fourth and fifth studies, we showed that circulating levels of miR-122-5p were independent predictors of neurological outcome and survival at middle term post-CA, and were able to increase the prediction value of existing models. We also identified miR-574-5p as an independent predictor of neurological outcome post-CA, specifically in women. To conclude, this work allowed the discovery or the confirmation of the potential biomarker value of transcripts and miRNAs in different CVD. However, their biomarker value should be validated in other large scale studies and with other methods of measurement before foreseeing their clinical utilization
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Dupire, Jules. "Dynamique de cellules sanguines dans des microécoulements." Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM4090/document.
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Cette thèse traite de la dynamique de cellules sanguines dans la microcirculation. Cette appellation regroupe les deux thématiques de mon travail. La première est l'étude du mouvement de globules rouges soumis à un écoulement de cisaillement. Prenant la suite des travaux réalisés par Manouk Abkarian, Magalie Faivre et Annie Viallat, nous avons étudié le mouvement de cellules dans un flux oscillant et mis en évidence l'apparition de chaos (Dupire J. et al, PRL 104,168101 (2010)). Nous avons ensuite repris l'étude sous écoulement constant pour comprendre les régimes de mouvement encore non étudiés (article accepté à PNAS). Tous ces travaux se basent sur un modèle à forme ellipsoïdale constante (type Keller & Skalak) auquel a été rajouté un terme tenant compte de l'élasticité de la membrane. Pour mieux modéliser la mémoire de forme, nous avons recalculé les équations du modèle en tenant compte d'une nouvelle forme non contrainte du cytosquelette élastique. Elle nous permet entre autres d'ajuster le modèle aux données expérimentales en utilisant des valeurs de viscosité et de module élastique de cisaillement compatibles avec la littérature. Le deuxième partie traite de l'étude du mouvement de globules blancs dans un réseau de canaux microfluidiques. Ce réseau est régulier et possède des dimensions biomimétiques. Nous étudions comment la rhéologie des cellules influe sur leur mouvement à travers le dispositif. Nous montrons que l'entrée des cellules, et donc leur première déformation, peut être utilisée pour obtenir des informations sur leur rhéologie (viscosité, élasticité, tension)This thesis deals with dynamics of blood cells in microflow. This title regroups two aspects of my work. The first one studies the movement of red blood cells (RBC) under flow. Continuing the work done by M. Abkarian, M. Faivre and A. Viallat, we looked at RBCs in an oscillating shear flow and showed the presence of chaos in the motion (Dupire J. et al, PRL 104,168101 (2010) ). Then we continued the study of RBC under constant flow to understand the regime of motion that were still to elucidate (PNAS, accepted for publication). These works use a ellipsoidal fixed shape model (based on Keller and Skalak's) to which we add an elastic membrane term. To take into account the shape memory, we calculated again the equations of motion considering a new stress-free shape of the elastic cytoskeleton. It allows us to fit the model on the experimental data using viscosity and elasticity coefficient compatible with the litterature. The second part deals with the motion of white blood cell (WBC) in a microfluidic channel network. The device has a regular geometry and has biomimetic shape characteristics matching the human lung mean values. We aim to study how the cell's rheology is related to their motion through the device. We show how the entry of the cell, and thus their first deformation, can be used to obtain information about a single cell rheology (viscosity, elasticity, tension). The motion is then decomposed in 2 phases : a transient regime right after the entrance and a final stationary regime. We study these regimes in terms of cellular deformation and wall friction
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Piranda, Eliane Mattos. "Estudos biol?gicos de Rhipicephalus sanguineus e intera??o Rickettsia rickettsii, R. sanguineus e c?es em condi??es laboratoriais." Universidade Federal Rural do Rio de Janeiro, 2008. https://tede.ufrrj.br/jspui/handle/tede/827.
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Previous issue date: 2008-02-29Funda??o de Amparo a Pesquisa do Estado de S?o Paulo
The bacterium Rickettsia rickettsii is the etiological agent of an acute, severe human disease called Rocky Mountain Spotted Fever in the United States or Brazilian Spotted Fever in Brazil. The infection occurs through the tick bite. Reports of clinical illness on dogs due to this agent have been restricted to the United States. The brown dog tick or kennel tick, Rhipicephalus sanguineus (Latreille, 1806) is the most widespread tick species throughout the tropics and subtropics. Biological studies on ticks are very important to the tick-borne pathogens transmission knowledge. For this purpose, the present study evaluated experimental infection of dogs with a Itaia?u (Mogi das Cruzes/ S?o Paulo, Brasil) strain of R. rickettsii and some biological aspects of Rhipicephalus sanguineus. Initially, dogs were infected with R. rickettsii its susceptibility and the role of R. sanguineus as a vector was verified. In the second part the viability of adults ticks (R. sanguineus) on three different temperatures were tested. Ticks were maintained under the controlled conditions of 18 ? 1◦C, 27 ? 1◦C e 32 ? 1◦C e 80 ? 5% (temperature ? humidity) for different times without feed. The dogs were susceptible to R. rickettsii infection. R. sanguineus was able to acquire the pathogen and to transmit R. rickettsii to guinea pigs. Based on the second part s results, R. sanguineus viability is affected by both, temperature and unfed time.
A bact?ria Rickettsia rickettsii ? o agente etiol?gico de uma doen?a aguda e severa em humanos denominada Rocky Mountain Spotted Fever nos Estados Unidos e Febre Maculosa Brasileira no Brasil. A infec??o se d? pela picada de carrapatos. Relatos da doen?a cl?nica nos c?es s?o restritos aos EUA. O carrapato marrom do c?o ou carrapato dos canis, Rhipicephalus sanguineus (Latreille, 1806), ? a esp?cie de carrapato mais freq?ente nos tr?picos e subtr?picos. Estudos da biologia de carrapatos s?o de grande import?ncia para o entendimento da transmiss?o de biogentes. O objetivo do presente trabalho ? avaliar experimentalmente a infec??o nos c?es com R. rickettsii cepa Itaia?u (Mogi das Cruzes/ S?o Paulo, Brasil) e aspectos da biologia de Rhipicephalus sanguineus. Na primeira etapa, c?es foram infectados com R. rickettsii e avaliou-se a susceptibilidade dos animais a infec??o e o comportamento de R. sanguineus como vetor. No segundo experimento, adultos de R. sanguineus tiveram a viabilidade de infestar novos hospedeiros analisada. Os carrapatos foram mantidos a18 ? 1◦C, 27 ? 1◦C e 32 ? 1◦C e 80 ? 5% UR por tr?s per?odos de jejum. Observou-se que os c?es s?o suscept?veis a infec??o por R. rickettsii cepa Itaia?u. Foi verificado que R. sanguineus se infectam com R. rickettsii e s?o capazes de transmitir o agente a cobaias. Baseado nos resultados do segundo experimento, concluem-se que R. sanguineus tem a viabilidade influenciada pela temperatura e tempo de jejum.
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Baker, Shannon. "Examination of Strain-Dependent Differences in S. sanguinis Virulence and Growth." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5707.
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Streptococcus sanguinis, an abundant and benign inhabitant of the oral cavity, is an important etiologic agent of infective endocarditis, particularly in people with pre-disposing cardiac valvular damage. Although commonly isolated from patients with IE, little is known about the factors that make any particular S. sanguinis isolate more virulent than another or, indeed, whether significant differences in virulence exist among isolates. To investigate the virulence of multiple isolates, a variation of the Bar-seq (barcode sequencing) method was employed. A conserved chromosomal site was identified for subsequent insertion of a barcode identifier, unique for each strain. Barcode insertion did not affect growth in vitro or in a rabbit model of endocarditis. Pooling of these strains and inoculation into rabbits demonstrated that all strains were capable of causing disease; however, virulence varied widely among strains. Genomic comparisons of the more virulent strains versus less virulent strains failed to conclusively identify any single gene responsible for virulence. Given this result, we continued our examination of the manganese transport system SsaACB, which is present in every strain of S. sanguinis examined. Although its contribution to virulence has not been confirmed in any strain other than SK36, it has been shown to be required for virulence in multiple species of streptococci, making it a candidate for emerging targeted therapies. In S. sanguinis strain SK36, previous studies have confirmed that loss of the manganese transport protein SsaB is tantamount to loss of virulence. Moreover, ssaB-deficient mutants are deficient for serum growth—a phenotype we have previously found to be associated with virulence. Our in vitro studies of manganese transporter-deficient strain SK36 supported this, but also revealed the emergence of suppressor mutants. In each suppressor mutant that was isolated, mutations were identified that mapped to a common gene, SSA_0696. Deletion of SSA_0696 resulted in restored in vitro growth in the ssaACB-deficient background, unearthing a novel mechanism for bacterial growth under manganese limitation. Fortunately, the suppressor mutant phenotype was not maintained in vivo; however, the combined results of these experiments suggest the efficacy of future therapeutics may require consideration of virulence at the species level and the incorporation of multiple targets.
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Garcia, Telma Alves. "Purificação e caracterização das lacases de Pycnoporus sanguineus." reponame:Repositório Institucional da UnB, 2006. http://repositorio.unb.br/handle/10482/2253.
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Tese (doutorado)—Universidade de Brasília, Instituto de Ciências Biológicas, Departamento de Biologia Celular, 2006.Submitted by wesley oliveira leite (leite.wesley@yahoo.com.br) on 2009-11-21T11:39:00Z No. of bitstreams: 1 Telma Alves Garcia.PDF: 1041199 bytes, checksum: f43838dc7fc3e11fe66d87f8ec48892f (MD5)
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O fungo Pycnoporus sanguineus foi eficiente na descoloração de alguns corantes empregados na indústria farmacêutica. Os resultados obtidos indicam que o P. sanguineus e principalmente as lacases produzidas por este fungo apresentam grande potencial para aplicações biotecnológicas. Para a produção de lacase (EC 1.10.3.2, p-difenol:dioxigênio oxidoredutase) o fungo foi cultivado em meio contendo 2,5- xilidina e cobre como indutores. Duas isoformas da enzima (Lac 1 e Lac 2) foram identificadas e separadas através de cromatografia de interação hidrofóbica. As enzimas Lac 1 e Lac 2 apresentaram uma massa molecular de 79,7 kDa e 68,1 kDa, respectivamente. As duas isoformas apresentaram características bioquímicas diferentes. A enzima Lac 1, contendo menor atividade especifica, foi parcialmente purificada. Usando seringaldazina como substrato a enzima apresentou um pH ótimo de 4,8, temperatura ótima de 25-30 °C e Km de 10,3 μmol.L-1. A enzima mostrou baixa estabilidade à temperatura de 50 °C, mantendo apenas 10% da atividade após 5 horas de incubação. A enzima Lac 2, contendo maior atividade especifica, foi purificada com um rendimento final de 13,9 %. Usando seringaldazina como substrato a enzima apresentou um pH ótimo de 4,2, temperatura ótima de 50 °C e Km de 8,3 μmol.L-1. A enzima mostrou alta estabilidade a temperatura de 50 °C, mantendo 100 % da atividade após 5 horas de incubação. Ambas as enzimas foram inibidas por azida sódica e fluoreto de sódio. _________________________________________________________________________________ ABSTRACT
Fungus Pycnoporus sanguineus was efficient in the discoloration of some dyes used in the pharmaceutical industry. Ours results indicated that the P. sanguineus and mainly laccases produced by this fungus presents great potential for biotechnological applications. For the production of laccase (EC 1.10.3.2, p-diphenol:dioxigen oxidoreductase) this fungus was cultivated in medium containing 2,5- xylidine and copper as inducer. Two isoforms of the enzyme (Lac 1 and Lac 2) had been identified and separated through chromatography on hydrophobic interaction. The enzymes Lac 1 and Lac 2 had presented a molecular mass of 68.1 kDa and 79.7 kDa, respectively. The two isoforms presented different biochemical characteristics. The enzyme Lac 1, with lower specific activity, was partially purified. Using syringaldazine as substrate the enzyme showed pH optima of 4.8, temperature optima of 25-30 °C and Km of 10.3 μmol.L-1. The enzyme showed low stability at temperature of 50 °C, keeping only 10% of the activity, after 5 hours of incubation. The enzyme Lac 2, with higher specific activity, was purified with a final yield of 13.9 %. Using syringaldazine as substrate the enzyme presented one pH optima of 4.2, temperature optima of 50 °C and Km of 8.3 μmol.L-1. The enzyme showed high stability at temperature of 50 °C, keeping 100% of the activity even after 5 hours of incubation. Both enzymes were inhibited by sodium azide and sodium fluoride.
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Tazi, Myriem. "Modélisations d'écoulements sanguins au passage de bifurcations." Toulouse, INPT, 1991. http://www.theses.fr/1991INPT056H.
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Les singularites du systeme vasculaire telles que les bifurcations, constituent des sites privilegies tant en microcirculation pour la repartition du flux sanguin qu'en macrocirculation pour la genese du phenomene d'atherosclerose. Il est donc necessaire d'etudier la structure de l'ecoulement du sang au passage de ces bifurcations et en particulier, d'analyser l'influence des facteurs hemodynamiques et geometriques sur la deformation des champs de vitesse et de pression. Un modele numerique aux elements finis est mis en uvre afin de determiner le champ hydrodynamique, en regime permanent, dans un domaine geometrique constitue d'une bifurcation symetrique, bidimensionnelle, pour des fluides a comportement newtonien et non-newtonien suivant la loi d'ostwald. Une etude experimentale, utilisant la velocimetrie laser, permet de caracteriser les profils de vitesse axiale dans le plan de la bifurcation a partir de modeles en verre de section circulaire. Les mesures sont effectuees pour deux types de fluide: une solution de glycerine a comportement newtonien et une solution de carboxymethylcellulose de sodium a comportement pseudoplastique. Les resultats d'origines diverses mettent en evidence l'influence primordiale du nombre de reynolds sur la forme et la longueur de retablissement de l'ecoulement apres l'embranchement
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CRESPEAU, HERVE. "Idiotypie des groupes sanguins du systeme ABO." Paris 6, 1992. http://www.theses.fr/1992PA066101.
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L'idiotypie des anticorps diriges contre les epitopes oligosidiques definissant les groupes sanguins du systeme abo humain, a ete etudiee a travers une cascade immune. Un anticorps antiidiotypique xenogenique (ab2) developpe chez le lapin contre un anticorps monoclonal (acm) murin anti-a61 (ab1), a ete purifie, et sa reactivite vis-a-vis de nombreux acm anti-abh d'origine murine ou humaine, et vis-a-vis d'un anticorps polyclonal anti-a humain, a ete testee. Trois acm anti-a et trois anti-a, b provenant de souris de meme souche que celle qui a produit l'ab1, ainsi qu'un anticorps polyclonal anti-a humain, ont presente des idiotopes ayant des reactions croisees avec l'ab1. Cette reactivite croisee semble due a un idiotope recurrent biozzi, reagissant avec des anticorps antiidiotypiques a la oudin presents dans l'ab2 polyclonal. La reactivite croisee avec des anticorps anti-a d'une autre espece (humaine) suggere quant a elle la presence d'anticorps antiparatopiques. L'inhibition par l'ab2, de l'hemagglutination de globules rouges a, b ou o humains par plusieurs acm murins anti-abh, et par des acm ou par l'anticorps polyclonal anti-a humains suggere fortement la presence d'un ab2 mimant un epitope appartenant aux determinants abh de type 2. Enfin, un lapin immunise par l'ab2 a produit une reponse ab3 caracterisee par une specificite anti-a et anti-h de type 2. Ces resultats sont la premiere description de la production d'un ab2 mimant la configuration tridimensionnelle d'un epitope de nature strictement glucidique, et suscitant la synthese d'un ab3 hemagglutinant
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Kurbatova, Polina. "Modélisation hybride de l'érythropoïèse et des maladies sanguines." Phd thesis, Université Claude Bernard - Lyon I, 2011. http://tel.archives-ouvertes.fr/tel-00752835.
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La thèse est consacrée au développement de nouvelles méthodes de modélisations mathématiques en biologie et en médecine, du type "off-lattice" modèles hybrides discret-continus, et de leurs applications à l'hématopoïèse et aux maladies sanguines telles la leucémie et l'anémie. Dans cette approche, les cellules biologiques sont considérées comme des objets discrets alors que les réseaux intracellulaire et extracellulaire sont décrits avec des modèles continus régis par des équations aux dérivées partielles et des équations différentielles ordinaires. Les cellules interagissent mécaniquement et biochimiquement entre elles et avec le milieu environnant. Elles peuvent se diviser, mourir par apoptose ou se différencier. Le comportement des cellules est déterminé par le réseau de régulation intracellulaire et influencé par le contrôle local des cellules voisines ou par la régulation globale d'autres organes. Dans la première partie de la thèse, les modèles hybrides du type "off-lattice" dynamiques sont introduits. Des exemples de modèles, spécifiques aux processus biologiques, qui décrivent au sein de chaque cellule la concurrence entre la prolifération et l'apoptose, la prolifération et la différenciation et entre le cycle cellulaire et de l'état de repos sont étudiés. L'émergence des structures biologiques est étudiée avec les modèles hybrides. L'application à la modélisation des filamente de bactéries est illustrée. Dans le chapitre suivant, les modèle hybrides sont appliqués afin de modéliser l'érythropoïèse ou production de globules rouges dans la moelle osseuse. Le modèle inclut des cellules sanguines immatures appelées progéniteurs érythroïdes, qui peuvent s'auto-renouveler, se différencier ou mourir par apoptose, des cellules plus matures appelées les réticulocytes, qui influent les progéniteurs érythroïdes par le facteur de croissance Fas-ligand, et des macrophages, qui sont présents dans les îlots érythroblastiques in vivo. Les régulations intracellulaire et extracellulaire par les protéines et les facteurs de croissance sont précisées et les rétrocontrôles par les hormones érythropoïétine et glucocorticoïdes sont pris en compte. Le rôle des macrophages pour stabiliser les îlots érythroblastiques est montré. La comparaison des résultats de modélisation avec les expériences sur l'anémie chez les souris est effectuée. Le quatrième chapitre est consacré à la modélisation et au traitement de la leucémie. L'érythroleucémie, un sous-type de leucémie myéloblastique aigüe (LAM), se développe à cause de la différenciation insuffisante des progéniteurs érythroïdes et de leur auto-renouvellement excessif. Un modèle de type "Physiologically Based Pharmacokinetics-Pharmacodynamic" du traitement de la leucémie par AraC et un modèle de traitement chronothérapeutique de la leucémie sont examinés. La comparaison avec les données cliniques sur le nombre de blast dans le sang est effectuée. Le dernier chapitre traite du passage d'un modèle hybride à un modèle continu dans le cas 1D. Un théorème de convergence est prouvé. Les simulations numériques confirment un bon accord entre ces deux approches.
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Peyre, Thi Kim Anh. "Rôle inflammatoire des plaquettes sanguines : application en transfusion." Phd thesis, Université Jean Monnet - Saint-Etienne, 2013. http://tel.archives-ouvertes.fr/tel-01058759.
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Les plaquettes sanguines sont des cellules qui ont un rôle majeur au cours des processus de l'hémostase primaire et jouent un rôle primordial dans l'immunité innée mais aussi adaptative. Ces cellules anucléées ont une capacité sécrétoire très importante de facteurs solubles notamment de cytokines, de chimiokines (CK/CH) et de facteurs immunomodulateurs. L'émergence du rôle inflammatoire des plaquettes sanguines dans la communauté scientifique a soulevé de nombreuses questions auxquelles nous essayons de répondre dans ce manuscrit. La majorité de ces questions repose sur la capacité de ces cellules anucléées à répondre de manière régulée à des stimuli complexes. Nos investigations pour répondre à ces questions ont été réalisées dans un contexte transfusion sanguine. Au cours de nos travaux, nous avons mis en évidence la corrélation des profils de sécrétion plaquettaire avec les récepteurs membranaires et les voies de signalisations intraplaquettaires engagées. Les plaquettes expriment plusieurs récepteurs immunitaires sur leur surface notamment les " Pattern recognition receptors " (PRR) et des récepteurs aux CK/CH. Nous avons démontré et caractérisé la fonction d'un nouveau récepteur plaquettaire, le Siglec-7. Ce récepteur est localisé dans les granules a ; son expression sur la membrane est corrélée avec l'état d'activation plaquettaire. Le Siglec-7 a une avidité élevée avec les molécules composées d'α2,8-disialyl (NeuAcα2,8NeuAcα2,3Gal) et de α2,6-sialyl (Gal-b1,3[NeuAcα2,6]HexNAc) (comme les gangliosides GD2, GD3 et GT1b). L'engagement de ce récepteur peut induire l'apoptose plaquettaire par la voie intrinsèque et extramitochondriale. Ce processus nécessite l'engagement du récepteur GPIIbIIIa et P2Y1 et la signalisation de la voie de PI3k. Nous avons également étudié et mis en évidence une composante inflammatoire multifactorielle dans les effets indésirables des receveurs (EIR) et trouvé dans les concentrés plaquettaires (CP), plusieurs facteurs solubles ayant une valeur prédictive élevée pour la survenue des EIR, notamment le sCD40L et l'IL-13. Nous avons confirmé que la concentration de ces facteurs augmente au cours de temps de stockage des CP, étant, en partie, responsable du taux élevé de l'EIR des CP âgés. Enfin, en plus de la conservation, les processus de préparation des CP peuvent aussi avoir des impacts sur les propriétés inflammatoires des plaquettes. Ces travaux montrent que la réponse inflammatoire plaquettaire est régulée en fonction du stimulus, permettant d'argumenter sur le rôle présumé de sentinelle des plaquettes sanguines humaines. Ainsi, mes travaux s'inscrivent dans la ré-exploration de la fonction inflammatoire des plaquettes sanguines et l'étude du rôle des plaquettes comme cellules de l'immunité à composante inflammatoire
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Demin, Ivan. "Modélisations mathématiques de l'hématopoïèse et des maladies sanguines." Phd thesis, Université Claude Bernard - Lyon I, 2009. http://tel.archives-ouvertes.fr/tel-00653348.
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Cette thèse est consacrée à la modélisation mathématique de l'hématopoïèse et des maladies sanguines. Plusieurs modèles traitant d'aspects différents et complémentaires de l'hématopoïèse y sont étudiés.Tout d'abord, un modèle multi-échelle de l'érythropoïèse est analysé, dans lequel sont décrits à la fois le réseau intracellulaire, qui détermine le comportement individuel des cellules, et la dynamique des populations de cellules. En utilisant des données expérimentales sur les souris, nous évaluons les rôles des divers mécanismes de retro-contrôle en réponse aux situations de stress.Ensuite, nous tenons compte de la distribution spatiale des cellules dans la moelle osseuse, question qui n'avait pas été étudiée auparavant. Nous décrivons l'hématopoïèse normale à l'aide d'un système d'équations de réaction-diffusion-convection et nous démontrons l'existence d'une distribution stationnaire des cellules. Puis, nous introduisons dans le modèle les cellules malignes. Pour certaines valeurs des paramètres, la solution "disease-free" devient instable et une autre solution, qui correspond à la leucémie, apparaît. Cela mène à la formation d'une tumeur qui se propage dans la moelle osseuse comme une onde progressive. La vitesse de cette propagation est étudiée analytiquement et numériquement. Les cellules de la moelle osseuse échangent des signaux qui régulent le comportement cellulaire. Nous étudions ensuite une équation integro-différentielle qui décrit la communication cellulaire et nous prouvons l'existence d'une solution du type onde progressive en utilisant la théorie du degré topologique et la méthode de Leray et Schauder. L'approche multi-agent est utilisée afin d'étudier la distribution des différents types de cellules dans la moelle osseuse.Finalement, nous étudions un modèle de type "Physiologically Based Pharmacokinetics-Pharmacodynamics" du traitement de la leucémie par l'AraC. L'AraC agit comme chimiothérapie et induit l'apoptose de toutes les cellules proliférantes, saines et malignes. La pharmacocinétique donne accès à la concentration intracellulaire d'AraC. Cette dernière, à son tour, détermine la dynamique des populations cellulaires et, par conséquent, l'efficacité de différents protocoles de traitement.
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Chabert, Adrien. "Rôle inflammatoire des plaquettes sanguines lors du sepsis." Thesis, Lyon, 2017. http://www.theses.fr/2017LYSES024/document.
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Depuis quelques années, les plaquettes sanguines sont reconnues comme un véritable élément de l’immunité. En effet, de nombreux rôles clés lors du processus inflammatoire sont attribués aux plaquettes, tels que la détection d’un signal, la libération de nombreux immunomodulateurs ou une forte interaction avec les autres cellules immunitaires. Le constat clinique d’une corrélation entre le taux plaquettaire et la mortalité du sepsis permet de relever l’importance de cette cellule dans la physiopathologie du sepsis. Ainsi ce travail doctoral a eu pour objectif de mettre en relief la part inflammatoire des plaquettes lors des interactions entre les facteurs de virulence de Staphylococcus aureus (S.aureus) que sont différentes exotoxines ou de souches de S. aureus issues de bactériémies de patients septiques. Un modèle expérimental de sepsis murin nous a permis de comprendre la composante inflammatoire jouée par les plaquettes ainsi que leurs implications dans la dysfonction pulmonaire issue lors du sepsis. Enfin, nous avons évalué la modulation de molécules antiplaquettaires, et particulièrement de l’acide acétylsalicylique, sur les nombreux rôles pathogéniques des plaquettes durant cette pathologieDuring some years, platelets are recognized as an key element of immunity. In fact, platelets play several roles, as signal detection, immunomodulator release and interaction with other immunity cells. The clinical significance of a correlation between platelet rate and sepsis mortality reveals the importance of this cell in the pathophysiology of sepsis. Thus, the purpose of this doctoral work was to highlight the inflammatory role of platelets in the interactions between the virulence factors of Staphylococcus aureus (S. aureus) that are different exotoxins or strains of S. aureus from bacteremia of septic patients. An experimental model of murine sepsis allowed us to understand the inflammatory component played by platelets as well as their implications in pulmonary dysfunction resulting from sepsis. Finally, we evaluated the modulation of antiplatelet molecules, particularly acetylsalicylic acid, on the numerous pathogenic roles of platelets during this pathology
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Demin, Ivan. "Modélisations mathématiques de l’hématopoïèse et des maladies sanguines." Thesis, Lyon 1, 2009. http://www.theses.fr/2009LYO10333/document.
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Cette thèse est consacrée à la modélisation mathématique de l'hématopoïèse et des maladies sanguines. Plusieurs modèles traitant d'aspects différents et complémentaires de l'hématopoïèse y sont étudiés.Tout d'abord, un modèle multi-échelle de l'érythropoïèse est analysé, dans lequel sont décrits à la fois le réseau intracellulaire, qui détermine le comportement individuel des cellules, et la dynamique des populations de cellules. En utilisant des données expérimentales sur les souris, nous évaluons les rôles des divers mécanismes de retro-contrôle en réponse aux situations de stress.Ensuite, nous tenons compte de la distribution spatiale des cellules dans la moelle osseuse, question qui n'avait pas été étudiée auparavant. Nous décrivons l'hématopoïèse normale à l'aide d'un système d'équations de réaction-diffusion-convection et nous démontrons l'existence d'une distribution stationnaire des cellules. Puis, nous introduisons dans le modèle les cellules malignes. Pour certaines valeurs des paramètres, la solution "disease-free" devient instable et une autre solution, qui correspond à la leucémie, apparaît. Cela mène à la formation d'une tumeur qui se propage dans la moelle osseuse comme une onde progressive. La vitesse de cette propagation est étudiée analytiquement et numériquement. Les cellules de la moelle osseuse échangent des signaux qui régulent le comportement cellulaire. Nous étudions ensuite une équation integro-différentielle qui décrit la communication cellulaire et nous prouvons l'existence d'une solution du type onde progressive en utilisant la théorie du degré topologique et la méthode de Leray et Schauder. L'approche multi-agent est utilisée afin d'étudier la distribution des différents types de cellules dans la moelle osseuse.Finalement, nous étudions un modèle de type "Physiologically Based Pharmacokinetics-Pharmacodynamics" du traitement de la leucémie par l'AraC. L'AraC agit comme chimiothérapie et induit l'apoptose de toutes les cellules proliférantes, saines et malignes. La pharmacocinétique donne accès à la concentration intracellulaire d'AraC. Cette dernière, à son tour, détermine la dynamique des populations cellulaires et, par conséquent, l'efficacité de différents protocoles de traitementThis PhD thesis is devoted to mathematical modelling of haematopoiesis and blood diseases. We investigate several models, which deal with different and complementary aspects of haematopoiesis.The first part of the thesis concerns a multi-scale model of erythropoiesis where intracellular regulatory networks, which determine cell choice between self-renewal, differentiation and apoptosis, are coupled with dynamics of cell populations. Using experimental data on anemia in mice, we evaluate the roles of different feedback mechanisms in response to stress situations. At the next stage of modelling, spatial cell distribution in the bone marrow is taken into account, the question which has not been studied before. We describe normal haematopoiesis with a system of reaction-diffusion-convection equations and prove existence of a stationary cell distribution. We then introduce malignant cells into the model. For some parameter values the disease free solution becomes unstable and another one, which corresponds to leukaemia, appears. This leads to the formation of tumour which spreads in the bone marrow as a travelling wave. The speed of its propagation is studied analytically and numerically. Bone marrow cells exchange different signals that regulate cell behaviour. We study, next, an integro-differential equation which describes cell communication and prove the existence of travelling wave solutions using topological degree and the Leray-Schauder method. Individual based approach is used to study distribution of different cell types in the bone marrow. Finally, we investigate a Physiologically Based Pharmacokinetics-Pharmacodynamics model of leukaemia treatment with AraC drug. AraC acts as chemotherapy, inducing apoptosis of all proliferating cells, normal and malignant. Pharmacokinetics provides the evolution of intracellular AraC. This, in turn, determines cell population dynamics and, consequently, efficacy of treatment with different protocols
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Kurbatova, Polina. "Modélisation hybride de l’érythropoïèse et des maladies sanguines." Thesis, Lyon 1, 2011. http://www.theses.fr/2011LYO10258/document.
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La thèse est consacrée au développement de nouvelles méthodes de modélisations mathématiques en biologie et en médecine, du type “off-lattice" modèles hybrides discret-continus, et de leurs applications à l’hématopoïèse et aux maladies sanguines telles la leucémie et l’anémie. Dans cette approche, les cellules biologiques sont considérées comme des objets discrets alors que les réseaux intracellulaire et extracellulaire sont décrits avec des modèles continus régis par des équations aux dérivées partielles et des équations différentielles ordinaires. Les cellules interagissent mécaniquement et biochimiquement entre elles et avec le milieu environnant. Elles peuvent se diviser, mourir par apoptose ou se différencier. Le comportement des cellules est déterminé par le réseau de régulation intracellulaire et influencé par le contrôle local des cellules voisines ou par la régulation globale d’autres organes. Dans la première partie de la thèse, les modèles hybrides du type “off-lattice" dynamiques sont introduits. Des exemples de modèles, spécifiques aux processus biologiques, qui décrivent au sein de chaque cellule la concurrence entre la prolifération et l’apoptose, la prolifération et la différenciation et entre le cycle cellulaire et de l’état de repos sont étudiés. L’émergence des structures biologiques est étudiée avec les modèles hybrides. L’application à la modélisation des filamente de bactéries est illustrée. Dans le chapitre suivant, les modèle hybrides sont appliqués afin de modéliser l’érythropoïèse ou production de globules rouges dans la moelle osseuse. Le modèle inclut des cellules sanguines immatures appelées progéniteurs érythroïdes, qui peuvent s’auto-renouveler, se différencier ou mourir par apoptose, des cellules plus matures appelées les réticulocytes, qui influent les progéniteurs érythroïdes par le facteur de croissance Fas-ligand, et des macrophages, qui sont présents dans les îlots érythroblastiques in vivo. Les régulations intracellulaire et extracellulaire par les protéines et les facteurs de croissance sont précisées et les rétrocontrôles par les hormones érythropoïétine et glucocorticoïdes sont pris en compte. Le rôle des macrophages pour stabiliser les îlots érythroblastiques est montré. La comparaison des résultats de modélisation avec les expériences sur l’anémie chez les souris est effectuée. Le quatrième chapitre est consacré à la modélisation et au traitement de la leucémie. L’érythroleucémie, un sous-type de leucémie myéloblastique aigüe (LAM), se développe à cause de la différenciation insuffisante des progéniteurs érythroïdes et de leur auto-renouvellement excessif. Un modèle de type “Physiologically Based Pharmacokinetics-Pharmacodynamic” du traitement de la leucémie par AraC et un modèle de traitement chronothérapeutique de la leucémie sont examinés. La comparaison avec les données cliniques sur le nombre de blast dans le sang est effectuée. Le dernier chapitre traite du passage d’un modèle hybride à un modèle continu dans le cas 1D. Un théorème de convergence est prouvé. Les simulations numériques confirment un bon accord entre ces deux approchesThis dissertation is devoted to the development of new methods of mathematical modeling in biology and medicine, off-lattice discrete-continuous hybrid models, and their applications to modelling of hematopoiesis and blood disorders, such as leukemia and anemia. In this approach, biological cells are considered as discrete objects while intracellular and extracellular networks are described with continuous models, ordinary or partial differential equations. Cells interact mechanically and biochemically between each other and with the surrounding medium. They can divide, die by apoptosis or differentiate. Their fate is determined by intracellular regulation and influenced by local control from the surrounding cells or by global regulation from other organs. In the first part of the thesis, hybrid models with off-lattice cell dynamics are introduced. Model examples specific for biological processes and describing competition between cell proliferation and apoptosis, proliferation and differentiation and between cell cycling and quiescent state are investigated. Biological pattern formation with hybrid models is discussed. Application to bacteria filament is illustrated. In the next chapter, hybrid model are applied in order to model erythropoiesis, red blood cell production in the bone marrow. The model includes immature blood cells, erythroid progenitors, which can self-renew, differentiate or die by apoptosis, more mature cells, reticulocytes, which influence erythroid progenitors by means of growth factor Fas-ligand, and macrophages, which are present in erythroblastic islands in vivo. Intracellular and extracellular regulation by proteins and growth factors are specified and the feedback by the hormones erythropoietin and glucocorticoids is taken into account. The role of macrophages to stabilize erythroblastic islands is shown. Comparison of modelling with experiments on anemia in mice is carried out. The following chapter is devoted to leukemia modelling and treatment. Erythroleukemia, a subtype of Acute Myeloblastic Leukemia (AML), develops due to insufficient differentiation of erythroid progenitors and their excessive slef-renewal. A Physiologically Based Pharmacokinetics-Pharmacodynamics (PBPKPD) model of leukemia treatment with AraC drug and chronotherapeutic treatments of leukemia are examined. Comparison with clinical data on blast count in blood is carried out. The last chapter deals with the passage from a hybrid model to a continuous model in the 1D case. A convergence theorem is proved. Numerical simulations confirm a good agreement between these approaches
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Eymard, Nathalie. "Modélisation hybride de l’hématopoïèse et de maladies sanguines." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10340/document.
Full textAbstract:
Cette thèse est consacrée au développement de modèles mathématiques de l'hématopoïèse et de maladies du sang. Elle traite du développement de modèles hybrides discrets continus et de leurs applications à la production de cellules sanguines (l'hématopoïèse) et de maladies sanguines telles que le lymphome et le myélome. La première partie de ce travail est consacrée à la formation de cellules sanguines à partir des cellules souches de la moelle osseuse. Nous allons principalement étudier la production des globules rouges, les érythrocytes. Chez les mammifères, l'érythropoïèse se produit dans des structures particulières, les îlots érythroblastiques. Leur fonctionnement est régi par de complexes régulations intra et extracellulaire mettant en jeux différents types de cellules, d'hormones et de facteurs de croissance. Les résultats ainsi obtenus sont comparés avec des données expérimentales biologiques ou médicales chez l'humain et la souris. Le propos de la deuxième partie de cette thèse est de modéliser deux maladies du sang, le lymphome lymphoblastique à cellules T (T-LBL) et le myélome multiple (MM), ainsi que leur traitement. Le T-LBL se développe dans le thymus et affecte la production des cellules du système immunitaire. Dans le MM, les cellules malignes envahissent la moelle osseuse et détruisent les îlots érythroblastiques empêchant l'érythropoïèse. Nous développons des modèles multi-échelles de ces maladies prenant en compte la régulation intracellulaire, le niveau cellulaire et la régulation extracellulaire. La réponse au traitement dépend des caractéristiques propres à chaque patient. Plusieurs scénarios de traitements efficaces, de rechutes et une résistance au traitement sont considérés. La dernière partie porte sur un modèle d'équation de réaction diffusion qui peut être utilisé pour décrire l'évolution darwinienne des cellules cancéreuses. L'existence de “pulse solutions”, pouvant décrire localement les populations de cellules et leurs évolutions, est prouvéeThe thesis is devoted to mathematical modeling of hematopoiesis and blood diseases. It is based on the development of hybrid discrete continuous models and to their applications to investigate production of blood cell (hematopoiesis) and blood diseases such as lymphoma and myeloma. The first part of the thesis concerns production of blood cells in the bone marrow. We will mainly study production of red blood cells, erythropoiesis. In mammals erythropoiesis occurs in special structures, erythroblastic islands. Their functioning is determined by complex intracellular and extracellular regulations which include various cell types, hormones and growth factors. The results of modeling are compared with biological and medical data for humans and mice. The purpose of the second part of the thesis is to model some blood diseases, T cell Lymphoblastic lymphoma (T-LBL) and multiple myeloma (MM) and their treatment. TLBL develops in the thymus and it affects the immune system. In MM malignant cells invade the bone marrow and destroy erythroblastic islands preventing normal functioning of erythropoiesis. We developed multi-scale models of these diseases in order to take into account intracellular molecular regulation, cellular level and extracellular regulation. The response to treatment depends on the individual characteristics of the patients. Various scenarios are considered including successful treatment, relapse and development of the resistance to treatment. The last part of the thesis is devoted to a reaction-diffusion model which can be used to describe Darwinian evolution of cancer cells. Existence of pulse solutions, which can describe localized cell populations and their evolution, is proved
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Nguyen, Thi Kim Anh. "Rôle inflammatoire des plaquettes sanguines : application en transfusion." Thesis, Saint-Etienne, 2013. http://www.theses.fr/2013STET014T/document.
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Les plaquettes sanguines sont des cellules qui ont un rôle majeur au cours des processus de l’hémostase primaire et jouent un rôle primordial dans l’immunité innée mais aussi adaptative. Ces cellules anucléées ont une capacité sécrétoire très importante de facteurs solubles notamment de cytokines, de chimiokines (CK/CH) et de facteurs immunomodulateurs. L’émergence du rôle inflammatoire des plaquettes sanguines dans la communauté scientifique a soulevé de nombreuses questions auxquelles nous essayons de répondre dans ce manuscrit. La majorité de ces questions repose sur la capacité de ces cellules anucléées à répondre de manière régulée à des stimuli complexes. Nos investigations pour répondre à ces questions ont été réalisées dans un contexte transfusion sanguine. Au cours de nos travaux, nous avons mis en évidence la corrélation des profils de sécrétion plaquettaire avec les récepteurs membranaires et les voies de signalisations intraplaquettaires engagées. Les plaquettes expriment plusieurs récepteurs immunitaires sur leur surface notamment les « Pattern recognition receptors » (PRR) et des récepteurs aux CK/CH. Nous avons démontré et caractérisé la fonction d’un nouveau récepteur plaquettaire, le Siglec-7. Ce récepteur est localisé dans les granules a ; son expression sur la membrane est corrélée avec l’état d’activation plaquettaire. Le Siglec-7 a une avidité élevée avec les molécules composées d’α2,8-disialyl (NeuAcα2,8NeuAcα2,3Gal) et de α2,6-sialyl (Gal-b1,3[NeuAcα2,6]HexNAc) (comme les gangliosides GD2, GD3 et GT1b). L’engagement de ce récepteur peut induire l’apoptose plaquettaire par la voie intrinsèque et extramitochondriale. Ce processus nécessite l’engagement du récepteur GPIIbIIIa et P2Y1 et la signalisation de la voie de PI3k. Nous avons également étudié et mis en évidence une composante inflammatoire multifactorielle dans les effets indésirables des receveurs (EIR) et trouvé dans les concentrés plaquettaires (CP), plusieurs facteurs solubles ayant une valeur prédictive élevée pour la survenue des EIR, notamment le sCD40L et l’IL-13. Nous avons confirmé que la concentration de ces facteurs augmente au cours de temps de stockage des CP, étant, en partie, responsable du taux élevé de l’EIR des CP âgés. Enfin, en plus de la conservation, les processus de préparation des CP peuvent aussi avoir des impacts sur les propriétés inflammatoires des plaquettes. Ces travaux montrent que la réponse inflammatoire plaquettaire est régulée en fonction du stimulus, permettant d’argumenter sur le rôle présumé de sentinelle des plaquettes sanguines humaines. Ainsi, mes travaux s’inscrivent dans la ré-exploration de la fonction inflammatoire des plaquettes sanguines et l’étude du rôle des plaquettes comme cellules de l’immunité à composante inflammatoireBlood platelets are non-nucleated cells and play a major role in primary hemostasis and a key role in inflammation, innate and adaptive immunity. They secrete a large variety of soluble factors including cytokines/chemokines (CK/CH) and immunomodulator factors. The emergence of their inflammatory role has raised numerous questions based on the ability of platelets to respond to complex stimuli. Our investigations to answer these questions were realized in the context of platelet component transfusion. In our study, we demonstrated the correlation between the platelet secretion of soluble factors with their membrane receptors and the signaling pathways involved. Platelets express many immune receptors on their surface, including "Pattern recognition receptors" (PRRs) and receptor for CK/CH. We discovered and characterized the function of a new platelet receptor, the Siglec-7. This receptor is located in the granules a and its expression is correlated to the platelet activation level. The Siglec -7 has a high avidity with the molecules composed of α2,8-disialyl (NeuAcα2,8NeuAcα2,3Gal) and of α2,6-sialyl (Gal-b1,3[NeuAcα2,6]HexNAc) (ganglioside GD2 , GD3 and GT1b). Stimulation of this platelet receptor may induce platelet apoptosis by the intrinsic and extramitochondrial pathway. This process requires the engagement of GPIIbIIIa and P2Y1 receptor and the PI3K pathway. We also demonstrated a multifactorial inflammatory component in adverse effects issuing from platelets transfusion, and identified many soluble factors which have a high predictive value of Acute Transfusion Reactions (ATR) occurrence, such as sCD40L and IL- 13. We confirmed that the concentration of these factors increases during storage time of platelet component (PC), being partly responsible for the high rate of ATR by old PC. Finally, in addition to the PC conservation, the process of PC preparation may also have impacts on the inflammatory properties of platelets. These studies showed that the platelet inflammatory response is regulated by the stimulus, explaining the sentinel role of human blood platelets. Therefore, my work contributes to the re-exploration of inflammatory function of these cells and studies their role as an immune cell with an inflammatory component
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Damien, Pauline. "Plaquettes sanguines et entretien de l’inflammation post-infectieuse." Thesis, Saint-Etienne, 2013. http://www.theses.fr/2013STET018T/document.
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Les plaquettes sanguines sont des cellules anucléées qui jouent un rôle majeur dans l’hémostase. Au-delà de cette fonction, elles possèdent une composante inflammatoire multifacette ; recouvrant la détection du signal de danger, la libération de cytokines et la migration leucocytaire. Dans ce contexte, la première partie de ces travaux met en avant la capacité des plaquettes à mettre en place une activation de type inflammatoire en réponse à un pathogène. En effet, lors de l’infection à HIV les plaquettes sont dans un état d’hyperréactivité et libèrent des facteurs immunomodulateurs pouvant participer à l’inflammation observée chez les patients infectées. D’une manière parallèle, les plaquettes présentent une sensibilité aux bactéries, faisant intervenir les TLR2 et 4 mais aussi les exotoxines, voire les bactéries entières. Le profil de la réponse inflammatoire induite est assez conséquent et diversifié pour participer à la physiopathologie du sepsis. La participation des plaquettes à l’inflammation concerne également leur interconnexion avec les neutrophiles. La seconde partie des travaux traite d’ailleurs de cette coopération qui ne semble pas s’arrêter à la barrière endothéliale, car lors de leur extravasation les neutrophiles transportent avec eux les plaquettes ; qui sont encore capables d’entretenir l’inflammation au niveau du site inflammatoire (ici, modèle de l’alvéole pulmonaire). La diversité du répertoire moléculaire plaquettaire, mis en avant au cours de cette thèse, qui participe à l’inflammation ouvre plusieurs possibilités quant à l’élaboration d’anti-plaquettaires qui pourraient moduler une réponse inflammatoire exacerbéeBlood platelets are anucleate cells which play an key role in haemostasis. In addition to this function, they participate in a number of other functions related to the inflammatory response including danger detection, cytokine release, and leukocyte transmigration. In the first part of the study, we highlight the ability of platelets to undergo an inflammatory activation response to a pathogen. Indeed during HIV infection, platelets are hyperresponsive and release immunomodulatory factors that can be involved in the inflammatory state seen in the patients. In a parallel way, platelets are also sensitive to bacteria, involving TLRs 2 and 4, exotoxins, as well as whole live bacteria. The inflammatory profile induced is sufficient, and quite diversified to participate in sepsis physiopathology. Platelet inflammatory functions also apply to their ability to crosstalk with neutrophils. Thus in the second part of our study, we focus on this interconnection, which does not appear to be stopping at the endothelial barrier, and can be seen during extravasation where neutrophils carry surface bound platelets in order to maintain inflammation directly onsite (alveolar inflammation model here).The diversity of platelet inflammatory activities highlighted in our work leads to several possibilities for the development of an antiplatelet therapeutic target which could modulate an exacerbated inflammatory response
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Evans, Karra. "SYSTEMATIC STUDY OF GENE FUNCTIONS FOR MORPHOLOGICAL CHAIN FORMATION IN STREPTOCOCCUS SANGUINIS." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/2514.
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Streptococcus sanguinis is a gram-positive facultative anaerobe that is indigenous to the oral cavity and a primary colonizer of the oral cavity. It serves as a tether for the attachment of several oral bacteria that colonize the tooth surface, form dental plaque, and cause periodontal disease. Previous experiments with streptococcal strains have suggested that cellular chain morphology of streptococci may influence the competitiveness, susceptibility to phagocytosis, acidurance, and aggregation of the bacterium. The purpose of this study was to systematically determine gene functions that contribute to cellular chain length morphology in the SK36 strain of S. sanguinis. Gene functions for 2048 mutants were elucidated along with Clusters of Orthologous Groups (COG) functions that may be related to or regulate chain formation and morphology. The COG functions with high ratios of genes involved with chain length morphology per number of total non-essential mutant COG functions were in the following order: Cell division and Chromosome Separation, Defense Mechanisms, and Signal Transduction Mechanisms, and Cell Motility and Secretion. Examination of gene annotations of the 326 mutants involved with chain morphology suggests that cellular chain length is dependent on cell wall division and septation, peptidoglycan synthesis, and cell wall mobility. Some of the genes that contribute to chain length properties may be co-regulated which may suggest that chain length phenotypes are a transcriptionally regulated property that further studies may confirm.
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Dvergsten, Erik C. "A Weighted Gene Co-expression Network Analysis for Streptococcus sanguinis Microarray Experiments." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4430.
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Streptococcus sanguinis is a gram-positive, non-motile bacterium native to human mouths. It is the primary cause of endocarditis and is also responsible for tooth decay. Two-component systems (TCSs) are commonly found in bacteria. In response to environmental signals, TCSs may regulate the expression of virulence factor genes.
Gene co-expression networks are exploratory tools used to analyze system-level gene functionality. A gene co-expression network consists of gene expression profiles represented as nodes and gene connections, which occur if two genes are significantly co-expressed. An adjacency function transforms the similarity matrix containing co-expression similarities into the adjacency matrix containing connection strengths. Gene modules were determined from the connection strengths, and various network connectivity measures were calculated.
S. sanguinis gene expression profile data was loaded for 2272 genes and 14 samples with 3 replicates each. The soft thresholding power β=6 was chosen to maximize R2 while maintaining a high mean number of connections. Nine modules were found. Possible meta-modules were found to be: Module 1: Blue & Green, Module 2: Pink, Module 3: Yellow, Brown & Red, Module 4: Black, Module 5: Magenta & Turquoise. The absolute value of module membership was found to be highly positively correlated with intramodular connectivity. Each of the nine modules were examined. Two methods (intramodular connectivity and TOM-based connectivity followed by network mapping) for identifying candidate hub genes were performed. Most modules provided similar results between the two methods. Similar rankings between the two methods can be considered equivalent and both can be used to detect candidate hub genes. Gene ontology information was unavailable to help select a module of interest. This network analysis would help researchers create new research hypotheses and design experiments for validation of candidate hub genes in biologically important modules.
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McGregor, John. "Étude structurale et fonctionnelle des glycoprotéines membranaires plaquettaires humaines : applications en pathologie." Lyon 1, 1987. http://www.theses.fr/1987LYO1T066.
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Pellegrino, Junior Jordão 1953. "Biologia molecular de grupos sanguineos aplicada a medicina transfusional." [s.n.], 2001. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308637.
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Orientador: Carmino Antonio de SouzaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-07-29T01:38:00Z (GMT). No. of bitstreams: 1 PellegrinoJunior_Jordao_D.pdf: 19309699 bytes, checksum: 1f1f8e41e2e7506cbc57707ef2e868a6 (MD5) Previous issue date: 2001
Resumo: Com a finalidade de avaliarmos se as técnicas moleculares, atualmente utilizadas na genotipagem de grupos sanguíneos, poderiam ser utilizadas com segurança em uma população com antecedentes étnicos diversos, foram estudadas 250 amostras de DNA de doadores voluntários de sangue, atendidos no Centro de Hematologia e Hemoterapia da Unicamp, previamente fenotipadas para os sistemas Rh, Kell, Duffy e Kidd. Nossos resultados demonstraram concordância entre o fenótipo e o genótipo, indicando que os primers utilizados e que foram desenhados de acordo com as sequências genômicas obtidas de indivíduos com ancestrais caucasianos, podem ser empregados na determinação dos genótipos de grupos sanguíneos em populações com antecedentes étnicos diversos. No sistema Duffy, 66% das amostras genotipadas como FY B foram fenotipadas como Fy(b-), devido à mutação no promotor eritróide GATA, o que demonstra que estes indivíduos são de fato FY B e, expressam a proteína Fyb em outros tecidos. Com o objetivo ainda de correlacionar os resultados dos fenótipos e genótipos dos sistemas Rh, Kell, Duffy e Kidd, em pacientes politransfundidos, e pelo fato de acreditarmos que a genotipagem molecular pode ser uma alternativa importante na determinação do perfil antigênico de pacientes portadores de anemias, em esquema de transfusão de sangue fenotipado, selecionamos dez pacientes portadores de 'beta' talassemia homozigótica e quarenta pacientes portadores de anemia falciforme. A fenotipagem eritrocitária foi realizada por testes de hemaglutinação em gel, enquanto que a genotipagem foi realizada pelas técnicas de AS-PCR e PCR-RFLP. Discrepâncias entre o fenótipo e o genótipo foram encontradas em nove dos dez pacientes portadores de 'beta' talassemia (90%) e, em seis dos quarenta pacientes portadores de anemia falciforme (15%). Para uma maior segurança de nossos resultados, em todos os pacientes que apresentaram resultados discrepantes entre a fenotipagem e a genotipagem, novas análises foram realizadas empregando-se DNA extraído de células do epitélio bucal e, todas confirmaram os resultados previamente obtidos em DNA extraído de leucócitos de sangue periférico. Nestes casos, tivemos a oportunidade de realizar nova determinação do fenótipo nas amostras das unidades de sangue transfundidas e pudemos verificar que os fenótipos pertenciam aos doadores e não aos receptores. Nossos resultados sugerem que a genotipagem de grupos sanguíneos contribui, substancialmente,na qualidade da transfusão de sangue fenotipado, sobretudo em pacientes que necessitam de transfusões de repetição, como por exemplo, pacientes portadores de anemia falciforme ou thalassemia. Nos casos onde a discrepância de resultados foi identificada, a nova conduta hemoterápica possibilitou um aumento na sobrevida das hemácias transfundidas e um aumento nos níveis de hemoglobina dos pacientes. Em conclusão, a genotipagem de grupos sanguíneos deve ser recomendada em pacientes dependentes de transfusão pois permite a seleção correta do sangue a ser transfundido. Auxilia portanto, na prevenção da aloimunização podendo diminuir os efeitos de potenciais reações hemolíticas
Abstract: Accurate phenotyping of red blood cells (RBCs) can be difficult in transfusiondependent patients such as those with thalassemia and sickle celIs anemia because of the presence of previously transfused RBCs in the patient's circulation. Recently,the molecular basis associated with the expression of many blood group antigens was established. This allowed the development of a plethora of polymerase chain reaction (PCR)-based tests for identification of the blood group antigens by testing DNA. These new technologies complement phenotyping by overcoming some of the limitations of hemagglutination assays. These molecular assays were developed on the basis of DNA sequences of individuals of Caucasian ancestry. The present study addresses the concern that these genotyping assays may not be suitable to populations of highly diverse ancestry because of variability in intronic regions or because of unrecognized alleles. We determined both, phenotype and genotype for RHD, RH C/c, RH E/e, KEL 1/KEL 2, JK A/JK B, FY A/ FY B (nt -33) in 250 normal blood donors using PCR. Phenotype and genotype results agreed in 100% of the cases, indicating that molecular genotyping protocols can be effectively applied to populations with a highly diverse genetic background. Furthermore" genotyping for Duffy antigens provided information that could not be obtained by phenotyping. Essentially, 30.5 % ofthe donors with the FY B gene typed as Fy(b-) due to mutation in the GATA box. This information is very useful for the management of transfusion dependent patients. We also evaluated the usefulness of DNA genotyping for red blood cell antigens as a tool for the management of polytransfused patients with 'beta' thalassemia and Sickle Cell disease (SCD) to overcome the limitations of hemagglutination assays. We studied blood samples ftom 10 patients with 'beta' thalassemia and 40 SCD patients by hemagglutination and by Polymerase Chain Reaction/Restriction Fragment Length Polymorphism (pCR-RFLP) for the Rh (D, C/c, E/e), Kell, Kidd and Duffy systems. We found discrepancies between hemagglutination and DNA typing test results in nine of the ten patients with 'beta' thalassemia (90%) and in six of the forty SCD patients (15%). In these 15 patients, DNA typing results by PCR-RFLP from buccal cells were identical with those from peripheral blood leukocytes, ruling out a potential role for microchimerism due to contaminating donor leukocytes. DNA typing of samples from segments of transfused units confinned the blood group phenotype of blood donors to these patients. In conclusion, DNA typing of blood groups by PCR-RFLP in peripheral blood leukocytes contributes to the man~gement of transfusions in patients with 'beta' thalassemia and in SCD patients by allowing more accurate selection of donor units with consequent prevention of alloimmunizationand potential hemolytic reactions
Doutorado
Clinica Medica
Doutor em Clínica Médica
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Stephenson, Elizabeth. "Possible Limits to Range Expansion for Non-native Asian Shore Crabs in Maine: A Biogeographic-thermogeographic Approach." Fogler Library, University of Maine, 2007. http://www.library.umaine.edu/theses/pdf/StephensonE2007.pdf.
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Donnet, Thibault. "Développement d'une nouvelle méthode de déshydratation des plaquettes sanguines par zéodratation." Paris 6, 2013. http://www.theses.fr/2013PA066033.
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Les plaquettes sanguines sont conservées dans les centres de transfusion pendant 5 jours, à température ambiante et sous agitation constante. Ces conditions ne permettent pas leur stockage à long terme ni leur transport, pourtant nécessaire afin de répondre aux besoins de la médecine de catastrophe. Les méthodes de stockage à long terme développées jusqu’ici n’ont pas apporté satisfaction puisque l’exposition au froid altère la recirculation et la fonctionnalité des plaquettes. Dans ce contexte, nous avons adapté un procédé innovant de déshydratation à température ambiante : la zéodratation. Les objectifs de cette thèse ont été (i) de concevoir un zéodrateur à l’échelle pilote, (ii) d’identifier les conditions de zéodratation adaptées au stockage des plaquettes sanguines, (iii) de caractériser les plaquettes zéodratées/réhydratées in vitro (iv) puis d’évaluer leur capacité hémostatique in vivo. Cette étude a mis en évidence la faisabilité de la méthode de zéodratation pour le stockage à long terme des plaquettes. Malgré leur morphologie altérée, les plaquettes zéodratées sont capables de corriger l’hémostase dans un modèle murin de saignement. Des recherches concernant l’amélioration de la fonctionnalité des plaquettes zéodratées, ainsi que l’évaluation du risque qu’elles représentent pour le receveur seront à fournir afin de déboucher sur un produit transfusionnel
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Gurung, Ishwori. "Deciphering type IV pilus biology in the Gram-positive opportunistic pathogen Streptococcus sanguinis." Thesis, Imperial College London, 2017. http://hdl.handle.net/10044/1/55879.
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Type IV pili (Tfp) are the paradigm of a large group of diverse and functionally versatile nanomachines, intensively studied in Gram-negative bacteria. However, details regarding the molecular mechanisms of Tfp biogenesis and/or mediated functions are still unclear. Thus, owing to the inherent lack of outer cell wall in Gram-positive bacteria, my PhD has focused on molecular characterisation of Tfp in a simpler such bacterium Streptococcus sanguinis. My work has shown that the naturally competent S. sanguinis produces bona fide retractable Tfp enabling twitching motility, but dispensable for competence. Unlike Gram-negative Tfp, we show that S. sanguinis Tfp are unusual since they are composed of two pilin proteins, a feature likely to be shared by other Gram-positive Tfp-expressing species. All the genes involved in Tfp biology in S. sanguinis are found within a pil locus encoding 21 proteins. A systematic genetic study highlighted that 10 proteins only are required for Tfp biogenesis, whilst another four modulate twitching motility. To enhance genetic manipulation of S. sanguinis, a markerless mutagenesis strategy was devised enabling us to make various mutations in situ, which helped us characterise some of these proteins further. Via this methodology, the last six genes of the pil locus were found to be completely dispensable for Tfp biology. To get an overall structural picture of Tfp in S. sanguinis, the structure of one of the major pilins (PilE1) was determined by NMR. Moreover, three pilin-like proteins within the pil locus were found to be minor Tfp components. Collectively, my work has established S. sanguinis as a robust Gram-positive model organism for studying Tfp, which paves way for interesting future studies.
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Medina, Flores Dyanne Adenea, Urizar Gabriela Ulloa, Colarossi Rosella Camere, García Stefany Caballero, Tovalino Frank Mayta, and Valle Mendoza Juana Del. "Antibacterial activity of Bixa orellana L. (achiote) against Streptococcus mutans and Streptococcus sanguinis." Universidad Peruana de Ciencias Aplicadas (UPC), 2016. http://hdl.handle.net/10757/604437.
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Objective To evaluate the cytotoxic and antibacterial effect of Bixa orellana L. (B. orellana) (achiote) methanol extract against Streptococcus mutans (ATCC 25175) (S. mutans) and Streptococcus sanguinis (ATCC 10556) (S. sanguinis). Methods Two methanol extracts of B. orellana were prepared in vitro, from the seeds and leaves. The antibacterial activity of extracts against S. mutans and S. sanguinis was evaluated using the cup-plate agar diffusion method. The minimum inhibitory concentration (MIC) was determined using the microdilution method and the cytotoxic activity was determinated by using the cell line MDCK. Results A stronger antibacterial effect was observed with the leaves methanolic extract with an inhibition zone of (19.97 ± 1.31) mm against S. mutans and (19.97 ± 1.26) mm against S. sanguinis. The methanolic extract of the seeds had an activity of (15.11 ± 1.03) mm and (16.15 ± 2.15) mm against S. mutans and S. sanguinis, respectively. The MIC of the leaf and the seed extracts against S. sanguinis was 62.5 and 125 μg/mL, respectively, and the MIC of the leaf extract against S. mutans was 62.5 μg/mL, and for the seed extract it was 31.25 μg/mL. The 50% cytotoxic concentration was 366.45 and 325.05 μg/mL for the leaves and seeds extracts, respectively. Conclusions The experimental findings demonstrated the antibacterial effect of the methanolic extract of B. orellana (achiote) on S. mutans and S. sanguinis. The extract of this plant is cytotoxic at high concentrations.Peer review
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Camere, Colarossi Rosella, Urizar Gabriela Ulloa, Flores Dyanne Medina, García Stefany Caballero, Tovalino Frank Mayta, and Valle Mendoza Juana Mercedes Del. "Antibacterial activity of Myrciaria dubia (Camu camu) against Streptococcus mutans and Streptococcus sanguinis." Elsevier B.V, 2016. http://hdl.handle.net/10757/620656.
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Objective: To evaluate the antibacterial and cytotoxic effect of Myrciaria dubia (Camu camu) (M. dubia) methanol extract, against Streptococcus mutans (ATCC 25175) (S. mutans) and Streptococcus sanguinis (ATCC 10556) (S. sanguinis). Methods: Two methanol extracts of M. dubia were prepared in vitro, from the seeds and pulp. Ten independent tests were prepared for each type of extract, using 0.12% chlorhexidine solution as positive control. Agar diffusion test was used by preparing wells with the experimental solutions cultivated in anaerobic conditions for 48 h at 37 °C. Meanwhile, the minimum inhibitory concentration and the cytotoxic effect over MDCK cell line was found. Results: A higher antibacterial effect was observed with the methanol seed extract with an inhibitory halo of (21.36 ± 6.35) mm and (19.21 ± 5.18) mm against S. mutans and S. sanguinis, respectively. The methanol extract of the pulp had an effect of (16.20 ± 2.08) mm and (19.34 ± 2.90) mm, respectively. The minimum inhibitory concentration of the pulp extract was 62.5 µg/mL for both strains, whereas for the seed antibacterial activity was observed even at low concentrations. The CC50 of the seeds extract was at a higher concentration than 800 µg/mL and 524.37 µg/mL for the pulp extract.This study was supported by Universidad Peruana de Ciencias Aplicadas (UPC) Lima-Peru with Grant No. MANUSCRIPT ACCEPTED ACCEPTED MANUSCRIPT UPC-501-2015
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Oliveira, Eduardo Soares de. "SEMEN SANGUINIS CRISTIANORUM: A CONSTRUÇÃO DE UM PROJETO DE IDENTIDADE CRISTÃ EM TERTULIANO." Pontifícia Universidade Católica de Goiás, 2014. http://localhost:8080/tede/handle/tede/771.
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EDUARDO SOARES DE OLIVEIRA.pdf: 1633591 bytes, checksum: 2e1f5e9c6dd64c889dabe214f60ee22e (MD5)
Previous issue date: 2014-12-04Esta tese apresenta o apologista Tertuliano de Cartago e seu projeto, que busca defender o cristianismo diante das arbitrariedades do Império Romano e sua consequente e injusta perseguição. O principal tema desta pesquisa é o martírio e tem como principal objeto os textos arrolados de Tertuliano. O presente trabalho tem como objetivo e problemática principal demonstrar a importância do martírio no cristianismo africano durante o período imperial romano e sua função na construção de um projeto identitário para o cristianismo. É nesse momento que se tem na região africana do Império as condições que favoreceram o crescimento do incipiente movimento cristão que buscava se afirmar na África romanizada. Dentre a vasta obra do autor, em que se apresenta o seu posicionamento político favorável aos cristãos, várias destas obras se destacam, são elas Apologeticum, Ad Martyras, Scorpiace, Ad Scapulam. Para tanto, esta pesquisa está estruturada em três capítulos. No primeiro capítulo, busca-se identificar como se apresenta o cristianismo na transição do segundo para o terceiro século d.C., destacando-se o domínio de Roma sobre a África. No segundo capítulo, analisa-se o martírio e suas características e perspectivas dentre as quais se identifica o papel das perseguições como fundamentais neste processo. Chamam a atenção para o sacrifício como representação identitária e a conformação da memória cristã martirial a partir da literatura cristã latina, enquanto ponto fundamental e simbólico do momento martirial. Já no terceiro capítulo, esta postura martirial cristã é vista como consolidadora do movimento cristão na África. Ao se ter em vista que os mártires se tornem exemplum de fé e compromisso para com o evangelho, percebe-se que o sacrifício cristão, a partir do martírio, se afirma enquanto projeto identitário deste cristianismo africano latino-romano.
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Nail, Sandrine. "L'interaction plaquettes sanguines-levures in vivo et ses conséquences." Angers, 2002. http://www.theses.fr/2002ANGE0505.
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Les mycoses systémiques sont en constante augmentation depuis deux décennies. Parmi celles-ci, les candidoses et les cryptococcoses disséminées représentent à elles seules 80% des infections fongiques nosocomiales. Lorsque la dissémination des levures, à partir d'un foyer infectieux primaire, se fait par voie hématogène, elles peuvent interagir avec les composants sanguins en particulier avec les plaquettes. Dans le but d'étudier les mécanismes et les conséquences de l'interaction plaquettes sanguines-levures in vivo, nous avons développé un modèle de levurose disséminée chez la souris. Après injection intraveineuse des levures, leur cinétique de disparition du sang périphérique est très rapide d'où l'hypothèse d'une formation d'agrégats plaquettes-levures qui seraient bloqués dans les capillaires profonds. L'étude du sang des souris inoculées avec C. Albicans, C. Glabrata, C. Tropicalis, C. Parapsilosis, C. Krusei, C. Guilliermondii et S. Cerevisiae montre que plus de 90% des blastospores sont liées à une ou plusieurs plaquettes. Pour C. Neoformans, la présence de la capsule inhibe l'interaction avec les plaquettes. Nous avons également constaté que l'interaction de C. Albicans avec les plaquettes pouvait être affectée par l'EDTA ou l'EGTA, alors que ces agents ne modifient pas l'interaction des autres espèces avec les plaquettes. Deux systèmes de fixation entre les levures et les plaquettes ont été envisagés, un calcium dépendant pour C. Albicans et un calcium non dépendant pour les autres espèces. Les résultats de la microscopie électronique montrent que la fixation des plaquettes sur C. Albicans s'accompagne d'une modification morphologique et d'une agrégation plaquettaire ce qui suggère une activation et donc une libération de composants plaquettaires dont les protéines microbicides plaquettaires (PMP). L'étude de l'action des protéines microbicides plaquettaires induite par l'action de la thrombine (tPMPs) sur différentes levures a montré que S. Cerevisiae est sensible à ces tPMPs alors que C. Albicans et C. Glabrata sont résistantes à leur action microbicide. Nous avons caractérisé comme récepteur fongique pour les plaquettes une mannoprotéine de 55kDa pour C. Albicans et 2 mannoprotéines de 45 et 55 kDa pour S. Cerevisiae. L'utilisation, in vivo, de mutants de S. Cerevisiae pour des gènes codant pour des protéines de masse moléculaire de 45 à 60 kDa a montré que comparativement à la souche sauvage S288C, la capacité des souches PCK1 et TIR4 à fixer les plaquettes est diminuée d'environ 50%. Avec la souche WSC2, cette diminution atteint les 80%. On peut donc supposer que le gène WSC2 code pour une protéine de surface de 55 kDa pouvant se lier aux plaquettes. La comparaison de la séquence d'acides nucléiques du gène WSC2 avec celle du génome de C. Albicans nous donne un pourcentage d'homologie de 63% pour une séquence située sur le contig 2519. Toutefois le gène et sa fonction ne sont pas connus chez cette levure. L'identification chez C. Albicans des gènes intervenant dans l'interaction plaquettes-levures permettra la construction de mutants qui seront ensuite testés in vivo pour l'étude de leur pouvoir pathogène.
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Essassi, Dalila. "Liaisons sanguines, transferts cérébral et hépatique de la pipequaline." Paris 12, 1991. http://www.theses.fr/1991PA120008.
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Les liaisons proteiques plasmatiques de la pipequaline sont etudiees par dialyse a l'equilibre. In vitro, son pourcentage de fixation dans le plasma est d'environ 95%, il est constant aux concentrations therapeutiques. Cette molecule se fixe avec une grande affinite a un site de l'aga et a deux sites specifiques sur la sah. Les lipoproteines presentent un profil de fixation saturable avec un nombre de sites eleve. La membrane erythrocytaire lie de maniere non saturable la piquequaline. Sur l'aga, la pipequaline partage son site avec la plupart des medicaments basiques mais egalement avec l'ans, molecule acide. Cette sonde de fluorescence a permis d'etudier les interactions ans-medicaments sur le site de l'aga par quenching de fluorescence. Chez le rat in vivo, les techniques d'oldendorf et du foie isole perfuse, ont montre que les liaisons sanguines de la pipequaline ont peu d'influence sur son transfert tissulaire. Ainsi, on constate que dans le cerveau comme dans le foie, une fraction importante de la forme liee sanguine peut diffuser. La vitesse de dissociation du complexe pipequaline-proteine par rapport a sa vitesse de transfert a travers la paroi capillaire et a son temps de transit capillaire est le parametre important dont depend la quantite de medicament extraite a partir de sa fraction initialement liee. De meme, l'effet de la fixation proteique sur l'extraction tissulaire de la pipequaline depend essentiellement de sa fraction initialement libre dans le sang arteriel. Le medicament s'incorpore dans l'hepatocyte selon un mecanisme de transport passif. En revanche, son metabolisme est dose-dependant et son elimination essentiellement biliaire
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VIAL, CATHERINE. "Les recepteurs p2 des plaquettes sanguines : identification et caracterisation." Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13223.
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De part leur interaction avec les facteurs de la coagulation et les composants de la paroi vasculaire, les plaquettes sanguines jouent un role majeur dans l'arret des hemorragies et le maintien de l'integrite vasculaire. Les plaquettes repondent a de nombreux composants solubles, comme par exemple l'adenosine 5-diphosphate (adp), qui se lient a des recepteurs de la membrane plasmique des plaquettes. L'adp est un mediateur important de l'activation plaquettaire. Nous avons identifie et caracterise deux recepteurs a l'adp sur les plaquettes sanguines humaines. Un premier recepteur p2y 1 dont nous avons montre que c'etait un recepteur a l'adp pour lequel l'atp est un antagoniste competitif. Ce recepteur est responsable de la mobilisation des stocks intracellulaires de calcium et de l'initiation de l'agregation. Un second recepteur est le recepteur p2x 1 responsable de l'entree rapide de calcium dont le role dans l'activation plaquettaire reste a determiner. D'autre part, nous avons pu mettre en evidence la presence d'un troisieme recepteur a l'adp, de nature inconnue, couple a l'inhibition de l'activite de l'adenylyl cyclase, qui est responsable de l'amplification de l'agregation initiee par l'activation du recepteur p2y 1.
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Rice, Alison Mary. "Caractérisation fonctionnelle des cellules souches sanguines mobilisées par chimiothérapie." Bordeaux 2, 1993. http://www.theses.fr/1993BOR28240.
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Randriantsoa, Mialy. "Synthèse microbiologique des antigènes glucidiques des groupes sanguins." Université Joseph Fourier (Grenoble), 2008. http://www.theses.fr/2008GRE10132.
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Les antigènes glucidiques des groupes sanguins ont été longtemps étudiés pour leur rôle crucial en matière de greffe et de transplantation. Ils ont été identifiés à la surface des globules rouges mais sont également présents dans les sécrétions et sur de nombreux tissus de l’organisme et. L’essor de la glycobiologie au cours des vingt dernières années a permis de définir leur implication dans d’autres mécanismes biologiques importants notamment l’infection, l’oncogenèse ou l’embryogenèse. De ces différentes implications découlent de nombreuses applications thérapeutiques. Les structures saccharidiques présentent un énorme potentiel pour des développements innovants dans le domaine de la santé. La fabrication de nouveaux médicaments à partir d’oligosaccharides des groupes sanguins requiert leur disponibilité en grande quantité. Les méthodes de synthèse chimique et enzymatique ont été développées, mais elles restent difficiles et donnent un rendement final assez faible. Une approche alternative est la synthèse par voie microbiologique. Elle consiste en une production par culture à haute densité de souches recombinantes d’Escherichia coli qui surexpriment des gènes codant pour des glycosyltransférases. Grâce à ce procédé, une cinquantaine d’oligosaccharides des groupes sanguins ont été obtenus à l’échelle du gramme lors de cette étude. Ces molécules appartiennent aux familles d’antigènes sanguins principales possédant de réels potentiels biologiques, en l’occurence les systèmes ABH (types 1, 2, 4, 5), Lewis et PSaccharidic blood group antigens are well known for their crucial role in blood transfusion and organe transplantation. They were first discovered more than a century ago on red cells and were later found in various tissues and secretion fluids. The rise of glycobiology during the past twenty years demonstrates their involvment in other biological mechanisms such as the binding of bacteria, toxins, or viruses to mammalian cell surface glycans or the specific role in oncogenesis and embryogenesis. From these different implications derived several therapeutic applications, the blood group antigens are very promising targets for drug development. In this perspective, large amount of these molecules is required. Chemical and enzymatic syntheses are developed but not allow the obtaining of large scale preparative samples of pure well-characterized oligosaccharides for use in biological studies. An alternative approach called “the living factory” is proposed in this study, it is based on high cell density culture of Escherichia coli strain overexpressing the glycosyltransferase genes. Through this process, some fifty oligosaccharides with biological interest belong to three systems of blood group (ABH type 1, 2, 4, 5, Lewis and P) have been synthesized in gram scale
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Souza, Filho Wanderley de. "Determinação de parametros de forma para analise de celulas sanguineas." [s.n.], 2000. http://repositorio.unicamp.br/jspui/handle/REPOSIP/276530.
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Orientadores : Neucimar Jeronimo Leite, Konradin MetzeDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Computação
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Resumo: Este traba1ho foi realizado juntamente com o Laboratório de Anatomia Patológica UNICAMP na análise de AgNORs (Regiões Organizadoras do Nuc1éolo) em células sangüíneas. Estudos anteriores demonstram que o padrão das AgNORs pode evidenciar alterações de proliferação e diferenciação celular. Assim, o estudo das AgNORs poderia dar informações adicionais sobre a cinética celular. Na grande maioria das pesquisas, a análise de AgNORs é restrita a parâmetros simples, como o número de precipitações ou a área ocupada pelas AgNORs. O objetivo deste trabalho é introduzir novos parâmetros de forma, ainda não considerados na literatura, que possam trazer informações objetivas adicionais para melhorar a classificação entre vários tipos de neoplasias e, eventualmente, trazer informações prognósticas complementares. Para tanto, foi desenvolvido um sistema ImAgNOR - com ferramentas que possibilitam tanto a segmentação semi-automática das estruturas como a extração dos parâmetros relacionados
Abstract: This work was accomplished together with the Laboratory of Pathological Anatomy UNICAMP in the analysis of AgNORs (Nucleolar Organizing Regions) in blood cells. Previous studies demonstrate that the pattem of AgNORs can evidence proliferation alterations and cellular differentiation. Thus, the study of AgNORs could give additional information on the cellular kinetics. In many researches, the analysis of AgNORs is restricted to simple parameters, as the number of precipitations or the area occupied by AgNORs. The goal ofthis work is to introduce new shape parameters, not yet considered in the literature that can bring additional objective information to improve the c1assification among several types of neoplasias and, eventually, to bring supplementary prognostic information. In this sense, a system was developed - ImAgNOR - with tools that facilitate the semiautomatic segmentation of the structures as well as the extraction of the related parameters
Mestrado
Mestre em Ciência da Computação
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Credidio, Edson Velardi. "Estudo do efeito do abacate nos lipideos sanguineos em humanos." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/256668.
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Orientador: Glaucia Maria PastoreTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia de Alimentos
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Resumo: O consumo regular de abacate Persea gratissima, tipo ¿Avocado¿, frutos que incluem as espécies Fuerte e Hass, foi avaliado em relação ao efeito sobre os lipídeos plasmáticos em humanos. Foi realizado estudo prospectivo, com intervenção. Foram selecionados voluntários militares, da ativa do Batalhão de Policia Militar de São Paulo em Campinas - Unidade de Saúde do CPI - 2 de Campinas, São Paulo. A escolha desta população alvo, foi a possíbilidade da utilização, de dieta e condicionamento físico uniformes e comparáveis. Os indivíduos selecionados, após assinatura Termo de Consentimento Livre e Esclarecido ¿ TCLE tiveram o sangue coletado para dosagem dos níveis de colesterol total e frações e de triglicérides, no início e após o consumo do abacate no término do experimento. Foram estimados os valores de Colesterol plasmático (HDL- LDL- VLDL) e Triglicérides , após a utilização da polpa da fruta do abacate por um período de dois meses tendo a finalidade de determinar o efeito do consumo do abacate nos lipídeos sanguíneos. Foi observado após o tempo de intervenção houve redução dos índices lipemicos com redução dos índices lipêmicos sanguíneos e significativo aumento do Colesterol ¿ HDL em 99% dos militares participantes. O grupo controle foi constituído pelos militares que mantiveram a mesma rotina dos voluntários, porém não ingeriram o abacate. Foram analisadas também a composição da polpa do fruto visando a melhor compreensão dos resultados obtidos na pesquisa
Abstract: The regular use of the Persea gratissima ¿Avocado¿ kind, fruits that include the Fuerte and Hass varieties, was evaluated in relation to the effects on the plasmatic lipids in human. A prospective study was realized with intervention. Soldiery volunteers in active from the battalion of São Paulo military police in Campinas ¿ CPI Health unit of Campinas, São Paulo. The choice of this specific group was the possibility to have an equal and comparable diet and physical condition. After the subscription of the informed consent ¿ IC, the select group had their blood collected for total cholesterol and fraction and triglycerides levels test, In the beginning and after the use of Avocado in the end of the experiment. The plasmatic (HDL ¿ LDL ¿ VLDL) cholesterol and triglycerides were obtained after the use of the pulp of Avocado for two months in order to determine the effect of the Avocado use in the blood lipids levels. It was observed, after intervention period, that there was a reduction of the blood lipemic levels and a significative HDL ¿ Cholesterol increase in 99% of the soldiery group. The control group was formed by soldiery that kept the same routine, but did not eat the Avocado. The nutritional composition of the Avocado pulp was also analyzed for a better understanding of the results, obtained in this work
Doutorado
Doutor em Ciência de Alimentos
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BATISTA, Francislene Lavôr. "PRODUÇÃO DE LACASE E BIOCONVERSÃO DE FLAVONÓIDES POR Pycnoporus sanguineus." Universidade Federal de Goiás, 2009. http://repositorio.bc.ufg.br/tede/handle/tde/2130.
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Previous issue date: 2009-06-30The bioconversion is an area of the biotechnology that has increased in an expansive way, and it includes enzymatic reactions by microorganisms. These microorganisms that present enzymatic systems similar to those present in mammalian systems, it s the cytochrome P450 (CYP450). That s why the biotransformation an important alternative constitute as models for drug metabolism study. The Pycnoporus sanguineus is a filamentous fungi, basidiomycete of the Polyporaceae family and laccase producer (EC 1.10.3.2), an oxidoreductase enzyme. It was evaluated the influence of flavonoids naringin, naringenin, and quercetin in the growth of P. sanguineus, production of laccase in differents culture media. It was performed various conditions of reaction, such as temperature, agitation and the time of the flavonoids addition. The bioconversion processes were carried out for 24 up to 96 hours and monitored by TLC and HPLC to confirm the existence of potential metabolites. It was used purified laccase of the Pycnoporus sanguineus to evalute the participation of laccase in metabolites of naringin production. Pycnoporus sanguineus developed in differents culture media tested. Naringenin and naringin presented the capability to induce the laccase production by P. sanguineus, whereas quercetin and rutin inhibited the laccase production. The incubation using PDSM did not producted laccase. It was detected several of metabolites, whereas the incubations using quercetin acquired fourteen differents metabolites and the incubations using naringenin producted nine metabolites and naringin producted eight metabolites. In biocatalytic assay under 28ºC and 150rpm using naringin it was not detected the presence of metabolites
A bioconversão é uma área da biotecnologia que tem crescido extensamente e inclui reações enzimáticas por meio de microrganismos. Dentre os microrganismos utilizados destacam-se os fungos filamentosos, que apresentam um sistema enzimático semelhante ao dos seres humanos, o citocromo P450 (CYP, P450), responsável pelo metabolismo dos fármacos. O Pycnoporus sanguineus é um basidiomiceto da família Polyporaceae produtor de lacase (EC 1.10.3.2), que é uma enzima da classe das oxidoredutases. Neste trabalho, foi avaliada a influência dos flavonóides naringina, naringenina e quercetina no crescimento de P. sanguineus e produção de lacase em diferentes meios de culturas. Foram utilizadas condições reacionais variadas como alteração de temperatura, agitação e o tempo de adição dos flavonóides. As reações de bioconversão de flavonóides por P. sanguineus foram realizadas por um período de 24 a 96 horas e monitoradas por CCD e CLAE para verificar a presença de possíveis metabólitos. Aplicou-se a lacase purificada do P. sanguineus para avaliar a participação desta enzima na produção dos metabólitos da naringina. O fungo cresceu nos meios de cultura testados. A naringenina e a naringina apresentaram a capacidade de induzir a produção de lacase pelo fungo, enquanto a quercetina inibiu a produção da mesma. Nas incubações com o meio PDSM não houve a produção de lacase. Nos ensaios de bioconversão foram detectados vários metabólitos nas incubações com microrganismo inteiro, sendo que nas incubações com quercetina foram obtidos catorze metabólitos diferentes. Nas incubações com naringenina foram produzidos nove metabólitos e a naringina levou à produção de oito metabólitos. No ensaio biocatalítico a 28°C e 150rpm na presença de naringina não foi evidenciada a presença de metabólitos
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Martinazzo-Portz, Tatiane. "Formulação de substrato para produção de basidiocarpos de Pycnoporus sanguineus." Universidade Estadual do Oeste do Paraná, 2011. http://tede.unioeste.br:8080/tede/handle/tede/1418.
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Previous issue date: 2011-06-28Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
The biochemical composition of fungi can vary with climatic conditions and cultivation substrate. Several species have shown biochemical activities, such as Pycnoporus sanguineus, which is highlighted by orange to red color of their basidiocarps. Although the antimicrobial activity verified in various fields such as pharmaceutical, industrial and agricultural, there is no method for growing basidiocarps described in the literature. This work aimed to develop a substrate with Eucalyptus sp. for the cultivation of P. sanguineus and production of basidiocarps. There were two assays, and in vitro and in formulated substrate, developed in the Unioeste, Campus of Marechal Cândido Rondon. We used sawdust of Eucalyptus sp. Separate in two particle sizes: less than 500 microns (G1) and between 500 and 841 microns (G2). In the in vitro assay were used four isolates of P. sanguineus (Ps04, Ps08, PS13 and PS14), grown in Petri dishes containing culture medium CBA plus sawdust in the proportions of zero, 1, 5, 10 and 15% for both sizes. In each dish was peaked a 0.5 cm disc containing mycelium and kept in dark at 25±2ºC, until the first treatment to reach the edge of the Petri dish. Was evaluated the diameter of colony, growth rate of mycelium, the fresh weight of mycelium and production of the pigment cinnabarin. The experiment was DIC in 4x2x5 factorial design, four isolates of P. sanguineus, two particle size of sawdust of Eucalyptus sp. and five concentrations of sawdust added to the culture medium, both with six repetitions. In the assay with formulated substrate, we used two isolates of P. sanguineus (Ps08 and Ps14), grown in polypropylene bags of 28x16 cm, containing sawdust of Eucalyptus sp. and rice bran. At zero, 5 and 20%, particle size in G1 and G2, with humidity of 75% and compacted to 0.5 g mL-1. The substrates remained 30 days in BOD at 25±2ºC, then taken to the greenhouse. Two havest of basidiocarps were made, at 90 and 180 days. Where were evaluated diameter, fresh and dry weight, the average number of basidiocarps and production cinnabarin. Was used experimental DIC in 2x2x3 factorial design, with two isolates of P. sanguineus, two particle size of sawdust of Eucalyptus sp. and three concentrations of rice bran added to sawdust, both with six repetitions. Was observed that the sawdust of Eucalyptus sp. is suitable for substrate for the production of basidiocarps of P. sanguineus, which is G1 showed better results only in vitro assays, while on substrate, the two particle sizes showed good results for the production isolates of P. sanguineus. The Ps08, produced more mass of basidiocarps, while the Ps14 showed higher content of cinnabarin in the basidiocarps. It can be concluded that the genetic characteristics of the biological potential of the isolates of P. sanguineus are more related to productive results that the characteristics of substrates used in this research
A composição bioquímica dos fungos pode variar com condições climáticas de cultivo e substrato. Diversas espécies têm mostrado atividades bioquímicas, como o Pycnoporus sanguineus, que se destaca pela coloração vermelho-alaranjada de seus basidiocarpos. Embora este fungo possua atividade antimicrobiana estudada em diversas áreas, como farmacêutica, industrial e agrícola, não há nenhum método para cultivo de basidiocarpos descrito na literatura. Este trabalho objetivou desenvolver substrato com resíduos madeireiros de Eucalyptus sp. para o cultivo de P. sanguineus e produção de basidiocarpos. Realizaram-se dois ensaios, in vitro e em substrato formulado, desenvolvidos na UNIOESTE, Campus de Marechal Cândido Rondon. Utilizou-se serragem de madeira de Eucalyptus sp., separada em duas granulometrias: inferior a 500 micra (G1) e entre 500 e 841 micra (G2). No ensaio in vitro utilizaram-se quatro isolados de P. sanguineus (Ps04, Ps08, Ps13 e Ps14), cultivados em placas de Petri contendo meio de cultura CBA acrescidos de serragem nas proporções de zero, 1, 5, 10 e 15%, para as duas granulometrias. Em cada placa foi repicado um disco de 0,5 cm contendo micélio e mantidos em ambiente escuro a 25±2ºC, até que o primeiro tratamento atingisse a borda da placa de Petri. Avaliou-se diâmetro de colônia, velocidade de crescimento do micélio, a massa fresca do micélio e a produção do pigmento cinabarina. O delineamento experimental foi DIC, em esquema fatorial 4x2x5, sendo quatro isolados de P. sanguineus, duas granulometrias de serragem de Eucalyptus sp. e cinco concentrações de serragem acrescidos ao meio de cultivo, ambos com seis repetições. No ensaio em substrato formulado, utilizou-se dois isolados de P. sanguineus (Ps08 e Ps14), cultivados em sacos de polipropileno de 28x16 cm, contendo serragem de Eucalyptus sp. e farelo de arroz, nas proporções de zero, 5 e 20%, nas granulometrias G1 e G2, com umidade de 75% e compactados a 0,5 g mL-1. Os substratos permaneceram 30 dias em BOD a 25±2ºC e então foram levados a casa de vegetação. Realizaram-se duas coletas de basidiocarpos, a primeira após 90 dias e a segunda após 180 dias do ensaio em casa de vegetação. A cada coleta avaliou-se o diâmetro, as massas fresca e seca, o número médio de basidiocarpos e a produção do pigmento cinabarina. Utilizou-se delineamento experimental DIC, em esquema fatorial 2x2x3, sendo dois isolados de P. sanguineus, duas granulometrias de serragem de Eucaliptus sp. e três concentrações de farelo de arroz adicionadas a serragem, ambos com seis repetições. Foi observado que a serragem de Eucalyptus sp. é apropriada para formulação de substrato para produção de basidiocarpos de P. sanguineus, sendo a que G1 mostrou melhores resultados apenas nos ensaios in vitro. Nos ensaios em substrato formulado, as duas granulometrias mostraram bons resultados produtivos para os isolados de P. sanguineus. O Ps08, nos ensaios em substrato formulado, teve produção de massa de basidiocarpos, enquanto o Ps14 mostrou maior teor de cinabarina nos basidiocarpos. Pode-se concluir que as características genéticas de potencial biológico dos isolados de P. sanguineus estão mais relacionados aos resultados produtivos que as características dos substratos utilizados nesta pesquisa
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PAIVA, JÚNIOR Sérgio de Sá Leitão. "Detecção de vasos sanguineos em imagens de fundo de olhos." Universidade Federal Rural de Pernambuco, 2006. http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/5311.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
We describe an automated method for blood vessel segmentation in two-dimensional color retinal images. This method may be used by specialized software for automated screening of diabetic rethinopaty and other eye diseases, for evaluation of treatment evolution, and clinical study. The proposed method is based on a combination of “2d matched filter” response procedure (for vessel location), and the Hoshen-Kopelman algorithm (for vessel segmentation). We compare the results obtained through this method with the results of manual segmentation of 20 imagens of the DRIVE project, where ROC(Receiver Operating Characteristic curve) analysis was used for quantitative comparison with others works published on this subject.
Descrevemos neste trabalho um método automático para localizar e segmentar vasos sanguíneos em imagens de fundo de olhos. Este método pode ser usado por um software especialista em imagens de retina para diagnosticar automaticamente doenças como retinopatia diabética entre outra s , para avaliação da evolução do tratamento, e para estudos clínicos. O método proposto é baseado na combinação do procedimento “2d matched fi l t e r” ( usado na localização dos vasos) com o algoritmo de “Hoshen-Kopelman” (usado na segmentação dos vasos). Resultados obtidos com este método foram comparados, com a segmentação manual em 20 imagens do projeto DRIVE,usando ROC(Receiver Operating Characterist i c curve) para comparação quant i t a t i v a com os resultados de outros trabalhos publicados sobre este assunto.