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1
SPENTCHIAN, MARC. "Interaction aspergillus fumigatus - laminine : etude preliminaire." Nantes, 1990. http://www.theses.fr/1990NANT016M.
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Allegra, Maryline. "Étude fonctionnelle de la laminine-5." Nice, 2001. http://www.theses.fr/2001NICE5643.
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Les épidermolyses bulleuses jonctionnelles (EBJ) sont des génodermatoses caractérisées par des décollements de l’épiderme à la jonction dermo-épidermique. Elles sont associées à des mutations dans les gènes codant pour les protéines des structures d’ancrage des kératinocytes à la membrane basale, les hémidesmosomes. La laminine-5, protéine hétérotrimérique α6β4 est une protéine essentielle pour la structuration des hémidesmosomes. La laminine-5, protéine α3β3γ2 de la matrice extracellulaire, est le ligand de l’intégrine α6β4. Nous avons identifié le défaut génétique présent chez deux patients atteints d’EBJ. Le premier patient atteint d’EBJ avec atrésie pylorique présentait un défaut d’expression de l’intégrine α6, dû à une mutation ponctuelle entraînant une dégradation massive de la protéine. Le deuxième patient présentait à la naissance une EBJ létale de type Herlitz, qui a évolué progressivement bers une forme non létale. Nous avons identifié les deux mutations sur le gène codant pour la chaîne β3 de la laminine-5 qui expliquent l’évolution progressive de la maladie. Puis nous avons étudié la fonction du clivage protéolytique de la chaîne γ2 de la laminine-5. Dans la matrice extracellulaire secrétée par les kératinocytes basaux la laminie-5 est présente sous une forme minoritaire de 440 kDa et une forme majoritaire de 400 kDa résultant du clivage protéolytique de la chaîne γ2. Le rôle respectif de ces deux formes de la laminine-5 dans l’adhésion kératinocytaire n’est pas déterminé. Nous avons transfecté une lignée de kératinocytes qui n’expriment pas la chaîne γ2 avec des plasmides codant pour des chaines γ2 mutées. Nous avons démontré le rôle essentiel des domaines N-terminaux de la chaîne γ2 pour l’intégration de la laminine-5 à la matrice extracellulaire et le rôle actif de la forme de 440 kDa de la laminine-5 dans l’adhésion kératinocytaireJunctional epidermolysis bullosa (JEB) are characterized by blistering within the dermoepidermal junction. These diseases are associated with mutations in the genes encoding the proteins of the anchoring devices developed by keratinocytes for adhering to the basement membrane, the hemidesmosomes. Integrin α6β4 is crucial for the nucleation of hemidesmosomes. Laminin-5, a heterotrimerique protein α3β3γ2 of the extracellular matrix, is the ligand of α6β4 integrin. We identified the genetic mutations underlying two cases of JEB. The first patient suffering of JEB with pyloric atresia did not express α6 subunit, because of a punctual mutation triggering high protein instability. The second patient was suffering of Herlitz type JEB, but later the disease evolved toward a mild form. We identified the two mutations within the lamini-5 β3 chain gene responsible for this evolution. Then we studied the function of the proteolytic cleavage of the laminin-5 γ2 chain. In the extracellular matrix secreted by the basal keratinocytes malinin-5 is present as a minor from of 440 kDa and a major form of 400 kDa, resulting from the cleavage of the γ2 chain. The function of these two forms is unknown. We transfected a keratinocyte cell line which does not express the γ2 chain, with mutant γ2 chains. We demonstrated the critical role of the N-terminal domains of the γ2 chain for the integration of laminin-5 into the extracellular matrix and that the 440 kDa form of laminin-5 functions as an adhesion ligand for keratinocytes
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GALLIANO, M. FLORENCE. "Implication de la laminine-5 dans les epidermolyses bulleuses jonctionnelles. Identification des isoformes alpha3 de la laminine." Nice, 1996. http://www.theses.fr/1996NICE5009.
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La laminine-5 est une proteine d'adhesion presente dans la peau. Cette molecule heterotrimerique est constituee par les chaines alpha3, beta3 et gamma2. La laminine-5 est un constituant des filaments d'ancrage qui connectent les hemidesmosomes des keratinocytes de l'epiderme a la lamina densa de la jonction derm-epidermique. Des defauts d'expression de cette proteine sont observes dans l'epidermolyse bulleuse jonctionnelle gravis, ou syndrome d'herlitz, qui est une genodermatose autosomique recessive caracterisee par un decollement de l'epiderme du derme. Dans le but d'impliquer la laminine-5 dans le syndrome d'herlitz, nous avons procede a une etude genetique de familles atteintes par la maladie. La caracterisation d'un microsatellite associe au gene lamc2 codant pour la chaine gamma2 de la laminine-5 a permis d'etablir une liaison genetique entre ce gene et la pathologie. Cette etude genetique a permis par la suite d'identifier des mutations portees par les genes codant pour la laminine-5 chez des patients atteints du syndrome d'herlitz. Afin d'etudier l'expression de la laminine-5 au cours de l'embryogenese, nous avons entrepris une etude complete de l'expression de chacune des chaines de la proteine au cours du developpement embryonnaire et ftal de la souris. Le clonage et le sequencage complet de la chaine alpha3 murine revele l'existence de deux isoformes issues d'epissages alternatifs, alpha3a, et alpha3b, qui divergent dans leur partie n-terminale. L'analyse de la distribution tissulaire des isoformes alpha3 revele une expression differentielle des deux proteines
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Orian-Rousseau, Véronique. "Expression et role de la laminine-2 et de la laminine-5 dans la morphogenese et la differenciation de l'intestin." Université Louis Pasteur (Strasbourg) (1971-2008), 1997. http://www.theses.fr/1997STR13084.
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Nous avons analyse l'expression et tente de determiner le role physiologique dans l'intestin de deux isoformes de laminines, constituants de la lame basale. La laminine-2 est exprimee de facon restrictive dans les cryptes intestinales (compartiment proliferatif) chez l'homme comme chez la souris ; son origine cellulaire est exclusivement mesenchymateuse. L'absence de cette glycoproteine dans l'intestin de souris mutante dy n'a pas affecte la morphogenese des cryptes ni la differenciation des cellules de paneth. La laminine-5, dont l'apparition est precoce, presente un gradient d'expression qui est parallele a l'etat de differenciation des cellules epitheliales le long de la villosite. L'utilisation de cellules cancereuses coliques humaines plus ou moins differenciees ne nous a pas permis de conclure a une relation directe entre l'expression de la laminine-5 et la differenciation. Les resultats sont plutot en accord avec ceux obtenus grace au modele des intestins hybrides montrant un relai pour le depot de la chaine 2 de la laminine-5 par les cellules epitheliales indifferenciees aux stades precoces puis par les cellules mesenchymateuses aux stades tardifs de developpement. Contrairement aux keratinocytes, les cellules coliques secretent majoritairement une laminine-5 comprenant le precurseur de la chaine 2, et de la laminine-6/7. Des etudes d'adhesion cellulaire couplees a des tests de denaturation ont permis de montrer pour la premiere fois que l'integrine 21 portee par les cellules cancereuses coliques est un recepteur potentiel majeur a la laminine-5. L'analyse en microscopie confocale de l'integrine 21 montre une segregation sur laminine-5 de ce recepteur au pole basal des cellules. Les integrines 31, 61 et 64 sont egalement impliquees dans l'adhesion a ce substrat.
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Basora, Nuria. "Involvement of laminin binding integrins in human intestinal epithelial cell functions." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape10/PQDD_0006/NQ40509.pdf.
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Al, safadi Rim. "Impact d'éléments génétiques variables sur l'expression de quatre gènes de virulence chez streptococcus agalactiae." Thesis, Tours, 2010. http://www.theses.fr/2010TOUR4015/document.
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Nous avons étudié l’impact d’éléments génétiques variables sur l’expression de quatre gènes de virulence, lmb, scpB, fbsA et fbsB, permettant respectivement l’attachement à la laminine, à la fibronectine et au fibrinogène humain, chez Streptococcus agalactiae, première cause d’infections néonatales. L’étude de l’impact de la séquence d’insertion IS1548 et de l’intron de groupe II GBSi1, insérés dans la région intergénique scpB-lmb en amont du gène lmb, sur l’expression des gènes lmb et scpB, montre que i) la structure de la région intergenique scpB-lmb corrèle avec les lignées phylogénétiques constituant l’espèce; ii) la présence d’IS1548 ou de GBSi1 n'a aucune influence sur l'expression du gène scpB; iii) l’expression du gène lmb est significativement plus élevée chez les souches possédant IS1548; et iv) IS1548 active directement le gène lmb. L’étude des propriétés de liaison au fibrinogène des souches du clone invasif CC17 par rapport aux souches des autres lignées phylogénétiques montre que i) des combinaisons spécifiques de gènes fbs et de leur gènes régulateurs corrèlent avec les lignées; ii) le système à deux composants RgfA/C inhibe le gène fbsA et active le gène fbsB; et iii) la protéine FbsB joue un rôle majeur dans la capacité de liaison au fibrinogène des souches de CC17We studied the impact of variable genetic elements on the expression of four virulence genes, lmb, scpB, fbsA, and fbsB that allow attachment to human laminin, fibronectin and fibrinogen, respectively, in Streptococcus agalactiae, the leading cause of neonatal infections. The study of the impact of the insertion sequence IS1548 and of the group II intron GBSi1, integrated in the scpB-lmb intergenic region upstream of the lmb gene, on the expression of scpB and lmb genes, showed that i) the structure of the scpB-lmb intergenic region correlated with the phylogenetic lineages constituting the species; ii) the presence of IS1548 or GBSi1 had no impact on the expression of the scpB gene; iii) the lmb gene expression was significantly higher in strains with IS1548; and iv) IS1548 directly activates the lmb gene. The study of the fibrinogen binding properties of strains of the invasive clone CC17, as compared with strains of other lineages showed that i) specific combinations of fbs genes and fbs regulator genes correlated with genetic lineages ii) the two-component system RgfA/C inhibited the fbsA gene and activated the fbsB gene; and iii) FbsB plays the major role in the fibrinogen binding ability of CC17strains
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Florea, Florina [Verfasser], and Cassian [Akademischer Betreuer] Sitaru. "Pathogenic autoimmunity against skin laminins = Pathogene Autoimunität gegen Laminine der Haut." Freiburg : Universität, 2012. http://d-nb.info/1123474478/34.
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Souza, Adriana Helena de [UNESP]. "Tamponamento cecal: aspectos clínico, fisiopatológico e terapêutico na laminite experimental em eqüinos." Universidade Estadual Paulista (UNESP), 2007. http://hdl.handle.net/11449/101104.
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Inúmeros estudos vêm sendo realizados objetivando esclarecer os mecanismos da laminite aguda em eqüinos. Muitos destes esclarecendo ou suscitando dúvidas sobre teorias já descritas; outros sugerindo novos mecanismos cruciais no desenvolvimento da laminite. Modelos in vitro e in vivo, focados na inflamação, distúrbios hemodinâmicos, ativação enzimática no dígito e eventos gastrintestinais somam-se para explicar sinais clínicos observados na laminite. Apesar da existência de dados correlacionando alterações metabólicas, mudanças da microflora e do pH cecal com a fisiopatologia da laminite poucas são as medidas profiláticas ou terapêuticas que visam restabelecer ou manter a função cecal. O objetivo deste estudo foi avaliar os efeitos da administração intracecal de solução tampão contendo hidróxido de alumínio e hidróxido de magnésio (Al(OH)3 e Mg(OH)2) na evolução da laminite induzida por sobrecarga de CHO balizado em parâmetros clínicos e laboratoriais; quantificando e qualificando aminas bioativas do conteúdo cecal; comparando número, tipo, localização e distribuição de células apoptóticas epidermais laminares e comparando a expressão gênica de MMP-2 e MMP-9 em tecido laminar digital. Os animais que desenvolveram laminite tiveram sinais de claudicação de ocorrência mais tardia no grupo que recebeu solução tampão, porém, ambos os grupos expostos ao CHO exibiram alterações laboratoriais características deste modelo experimental. As concentrações cecais da putrescina e cadaverina, o número de células epidérmicas laminares apoptóticas e a expressão gênica das MMP-2 e MMP-9 apresentaram-se elevadas nos eqüinos expostos à sobrecarga de CHO em relação aos do grupo controle, no entanto, foram menos evidentes no grupo tratado com solução tampão...
A large number of studies have been undertaken aimed at furthering our understanding of the complex mechanisms of acute laminitis in the horse. Many of these studies have either reinforced or cast doubt on previously theories on the pathogenesis of this disease, while others have suggested new mechanisms which may play a key role in its development. Studies utilising in vitro and in vivo models of the disease, particularly addressing the areas of inflammation, haemodynamic disturbances and enzyme activation in the hoof, as well as the events occurring in the hindgut, have helped to explain many clinical observations of the disease. Instead of the existence of results linking the metabolic alterations, microflora and cecal pH changes with laminitis physiopatology there are no effective therapies and means of prevention to reestablish or maintain the cecal function. The aim of this study was evaluate the effects of an intracecal buffer solution composed of aluminum and magnesium hydroxide on the development of carbohydrate overload (CHO)-induced laminitis by characterization and comparison of clinical parameters, bioactives amines in cecal content, apoptotic epidermal cells and gene expression of MMP-2 e MMP-9 in digital laminar tissues. All CHO-treated horses developed lamenees, but it was significantly delayed in group that received buffering treatment. However, both CHO-treated group presented similar laboratorial changes which are particular to this experimental model. The cecal putrescine and cadaverine level, the number of laminar apoptotic epidermal cells, and gene expression of MMP-2 and MMP-9 were increased in CHO-treated horses compared to control group, but it was less in the buffer-treated group...(Complete abstract, access undermentioned eletronic address)
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Souza, Adriana Helena de. "Tamponamento cecal : aspectos clínico, fisiopatológico e terapêutico na laminite experimental em eqüinos /." Jaboticabal : [s.n.], 2007. http://hdl.handle.net/11449/101104.
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Orientador: Carlos Augusto Araújo ValadãoBanca: José Correa de Lacerda Neto
Banca: Luiz Cláudio Nogueira Mendes
Banca: Rafael Resende Faleiros
Banca: Rita de Cássia Campebell
Resumo: Inúmeros estudos vêm sendo realizados objetivando esclarecer os mecanismos da laminite aguda em eqüinos. Muitos destes esclarecendo ou suscitando dúvidas sobre teorias já descritas; outros sugerindo novos mecanismos cruciais no desenvolvimento da laminite. Modelos in vitro e in vivo, focados na inflamação, distúrbios hemodinâmicos, ativação enzimática no dígito e eventos gastrintestinais somam-se para explicar sinais clínicos observados na laminite. Apesar da existência de dados correlacionando alterações metabólicas, mudanças da microflora e do pH cecal com a fisiopatologia da laminite poucas são as medidas profiláticas ou terapêuticas que visam restabelecer ou manter a função cecal. O objetivo deste estudo foi avaliar os efeitos da administração intracecal de solução tampão contendo hidróxido de alumínio e hidróxido de magnésio (Al(OH)3 e Mg(OH)2) na evolução da laminite induzida por sobrecarga de CHO balizado em parâmetros clínicos e laboratoriais; quantificando e qualificando aminas bioativas do conteúdo cecal; comparando número, tipo, localização e distribuição de células apoptóticas epidermais laminares e comparando a expressão gênica de MMP-2 e MMP-9 em tecido laminar digital. Os animais que desenvolveram laminite tiveram sinais de claudicação de ocorrência mais tardia no grupo que recebeu solução tampão, porém, ambos os grupos expostos ao CHO exibiram alterações laboratoriais características deste modelo experimental. As concentrações cecais da putrescina e cadaverina, o número de células epidérmicas laminares apoptóticas e a expressão gênica das MMP-2 e MMP-9 apresentaram-se elevadas nos eqüinos expostos à sobrecarga de CHO em relação aos do grupo controle, no entanto, foram menos evidentes no grupo tratado com solução tampão...(Resumo completo, clicar acesso eletrônico abaixo)
Abstract: A large number of studies have been undertaken aimed at furthering our understanding of the complex mechanisms of acute laminitis in the horse. Many of these studies have either reinforced or cast doubt on previously theories on the pathogenesis of this disease, while others have suggested new mechanisms which may play a key role in its development. Studies utilising in vitro and in vivo models of the disease, particularly addressing the areas of inflammation, haemodynamic disturbances and enzyme activation in the hoof, as well as the events occurring in the hindgut, have helped to explain many clinical observations of the disease. Instead of the existence of results linking the metabolic alterations, microflora and cecal pH changes with laminitis physiopatology there are no effective therapies and means of prevention to reestablish or maintain the cecal function. The aim of this study was evaluate the effects of an intracecal buffer solution composed of aluminum and magnesium hydroxide on the development of carbohydrate overload (CHO)-induced laminitis by characterization and comparison of clinical parameters, bioactives amines in cecal content, apoptotic epidermal cells and gene expression of MMP-2 e MMP-9 in digital laminar tissues. All CHO-treated horses developed lamenees, but it was significantly delayed in group that received buffering treatment. However, both CHO-treated group presented similar laboratorial changes which are particular to this experimental model. The cecal putrescine and cadaverine level, the number of laminar apoptotic epidermal cells, and gene expression of MMP-2 and MMP-9 were increased in CHO-treated horses compared to control group, but it was less in the buffer-treated group...(Complete abstract, access undermentioned eletronic address)
Doutor
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Bach, Elmina. "Implication de la chaîne α1 de laminine dans l’angiogenèse physiologique et tumorale." Thesis, Strasbourg, 2012. http://www.theses.fr/2012STRAJ110/document.
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Les laminines, composants majeurs des lames basales, sont des hétérodimères glycosylés formés de trois chaînes α, β et γ. La chaîne α1 de laminine (LMα1), caractéristique du trimère LM111 est indispensable au développement de la membrane limitante interne de la rétine, sa perte de fonction et mutation impactant négativement l’angiogenèse physiologique, tandis que sa surexpression stimule l’incidence de la tumorigenèse colique, la maturation des vaisseaux sanguins et l’expansion des fibroblastes. La LMα1 favorise la prolifération des cellules cancéreuses coliques et stimule l’expression du VEGFA, des composants de la voie Notch, de Dll4 et de ses cibles Hey1 et Hey2 dans le stroma tumoral. Inversement, la perte de fonction et la mutation de la LMα1 diminuent l’expression de Dll4, Hey1 et Hey2 dans la rétine. L’action de la LMα1 sur l’expression de ces facteurs proangiogéniques est sélective, car en étant une molécule chémoattractante pour les fibroblastes associés au cancer elle y stimule l’expression de VEGFA et de Dll4. Tandis que dans les cellules endothéliales, son action stimulatrice sur Dll4 s’accompagne de l’activation de la voie Notch. Chez l’homme, dans le contexte de tumorigenèse colique, la LMα1 est fortement exprimée. Cette surexpression s’accompagne d’une augmentation de l’expression du VEGFA et de Dll4. A la lumière de ces résultats, LMα1 pourrait constituer une cible potentielle dans les thérapies anti-anticancéreusesLaminins, major components of basement membrane are glycosylated heterodimers composed of three chains α, β and γ. Laminin α1 chain (LMα1), specific to LM111 trimer is essential in development of retinal inner limiting membrane. Loss of function and mutation of LMα1 negatively impact physiological angiogenesis, whereas its overexpression promotes colon cancer incidence, tumor cell proliferation, blood vessel maturation and fibroblast expansion. LMα1 stimulates VEGFA, Notch pathway components Dll4 and its targets Hey1 and Hey2 in tumor stroma. Contrarily, mutation and loss of function of LMα1 decrease Dll4, Hey1 and Hey2 expression in retina. LMα1 differentially regulates the expression of pro-angiogenic factors. As a chemoattractive molecule for cancer associated fibroblasts, LMα1 stimulates VEGFA and Dll4 expression in these stromal cells, while in endothelial cells, LMα1 stimulated Dll4 triggers Notch pathway activation. LMα1 is overexpressed in human cancer, which associated with increased expression of VEGFA and Dll4. In settings of these data, LMα1 could be a potential target in anticancer therapies
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Gimond, Clotilde. "Signaux intracellulaires induits par une glycoprotéine spécifique des membranes basales, la laminine." Lyon 1, 1994. http://www.theses.fr/1994LYO10159.
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Le comportement cellulaire peut être régulé par des glycoprotéines de la matrice extracellulaire telles que la laminine, spécifique des membranes basales, ou la fibronectine, abondante dans le tissu conjonctif intersticiel. L'étude des réorganisations des protéines du cytosquelette a montré que la vinculine est absente des structures d'adhésion formées sur la laminine tandis qu'elle colocalise avec l'extrémité des filaments d'actine développés par des cellules étalées sur la fibronectine. Le rôle de différentes protéines kinases dans l'adhésion cellulaire a été abordé grâce à l'utilisation d'un ensemble d'inhibiteurs de kinases. Les inhibiteurs des kinases dépendantes de la calmoduline entraînent une inhibition de l'adhésion cellulaire à la laminine et à la fibronectine, tandis que les inhibiteurs de la protéine kinase C activent l'adhésion et l'étalement cellulaire sur la laminine mais pas sur la fibronectine. De plus, l'activation de la protéine kinase C conduit à une désorganisation du cytosquelette et un arrondissement de cellules préalablement étalées sur la laminine, tandis que la morphologie des cellules sur la fibronectine n'est pas modifiée. L'activation de la protéine kinase C s'accompagne de modifications du contenu cellulaire en protéines phosphorylées sur résidus tyrosine et de la phosphorylation du domaine cytoplasmique de la sous-unité d'intégrine alpha 6a. Des expériences de phosphorylation ont montré que ce domaine était un substrat in vitro pour la protéine kinase C et la proteine kinase A mais pas pour la MAP kinase. Cette étude suggère que la laminine induit des signaux intracellulaires divers, différents de ceux induits par la fibronectine, et qui comprennent des réorganisations des protéines du cytosquelette et la régulation de l'activité de certaines protéines kinases
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Abou, Farha Khalid Mohamed Mohamed. "Diagnostic and prognostic value of laminin as a biochemical and a histological marker in human bladder carcinoma." Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1992. http://arno.unimaas.nl/show.cgi?fid=6506.
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Sabes, Amanda Festa. "Estresse oxidativo e expressão das metaloproteinases 2 e 9 e seus inibidores em ovinos com acidose ruminal subaguda /." Jaboticabal, 2019. http://hdl.handle.net/11449/183495.
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Orientador: Luiz Carlos MarquesResumo: A produção de ovinos no Brasil está em constante ascensão e tal fato leva ao aumento do número de animais confinados, visando maior ganho de peso em curto período de tempo. Essa situação predispõe os animais a desordens como acidose ruminal subaguda (ARS) e, consequentemente, laminite, gerando perdas econômicas pela diminuição da produtividade do rebanho e, em casos graves, descarte de animais. Com o objetivo de avaliar a ocorrência de estresse oxidativo, a expressão das metaloproteinases (MMPs) 2 e 9 e seus inibidores (TIMPs) 1 e 2 e também a termografia infravermelha podal (TIV) oito ovelhas adultas foram utilizadas, sendo as mesmas divididas entre os grupos controle (GC) contendo três animais e o grupo indução (GI) contendo cinco animais. Para indução da ARS os animais do GI receberam dieta com alto teor de alimento concentrado durante 30 dias. Todos os animais do GI apresentaram diminuição do pH ruminal, indicando a ocorrência de ARS, e também sinais clínicos de laminite em diversos momentos ao longo do período. Somente foi expressa a forma pró ativa da MMP 2, com valores aumentados nos dias 6 e 11, além da detecção dos TIMPs 1 e 2 ao longo de todo o período. Com relação ao estresse oxidativo, as variáveis relacionadas com a liberação de fatores oxidantes como a capacidade oxidante total (TOC), a peroxidação lipídica (LPO) e o índice de estresse oxidativo (IEO) encontram-se elevadas nos animais do GI, notadamente a partir do dia 20. A região da banda coronária e pele adja... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The production of sheep in Brazil is constantly rising and this fact leads to an increase in the number of confined animals, aiming to have a greater weight gain in a short period of time. This situation predisposes the animals to disorders such as subacute ruminal acidosis (SARA) and, consequently, laminitis, generating economic losses by decreasing the productivity of the herd and, in severe cases, disposal of animals. With the objective of evaluating the occurrence of oxidative stress, the expression of metalloproteinases (MMPs) 2 and 9 and their inhibitors (TIMPs) 1 and 2 and also the infrared thermography (IT) eight adult ewes were used, divided among control group (CG) containing three animals and the induction group (IG) with five animals. For the induction of SARA, GI animals received a diet with high content of concentrated food during 30 days. All animals from IG group showed a decrease in ruminal pH, indicating the occurrence of SARA, as well as clinical signs of laminitis at various times during the period. Only the pro-active form of MMP 2 was expressed, with values increased on days 6 and 11, besides the detection of TIMPs 1 and 2 all long the period. Regarding oxidative stress, the variables related to the release of oxidant factors such as total oxidant capacity (TOC), lipid peroxidation (LPO) and oxidative stress index (OSI) are high in IG animals, mainly from day 20. The region of the coronary band and adjacent skin was evaluated through the IT. All IG anima... (Complete abstract click electronic access below)
Doutor
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Perrin, Arnaud. "Augmentation de l'expression de la chaine α1 de la laminine 111, un potentiel traitement pour la Dystrophie musculaire de Duchenne." Master's thesis, Université Laval, 2016. http://hdl.handle.net/20.500.11794/27259.
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La protéine hétérotrimérique laminine-111 permet le lien entre la matrice-extracellulaire et l’intégrine α7β1 du sarcolemme, remplaçant ainsi dans les muscles dystrophiques, des liens normalement assurés par le complexe de la dystrophine. L’injection de laminine-111 dans des souris mdx a permis, entre autre, l’augmentation de l'expression de l'intégrine α7β1, d’empêcher les bris du sarcolemme lors de la contraction musculaire, de restaurer un niveau normal de la créatine kinase sérique, ainsi que d’augmenter la résistance et la force dans les muscles déficients en dystrophine. Ces résultats suggèrent que l'augmentation de la laminine-111 est un potentiel traitement pour la DMD. Les chaines β1 et γ1 de la laminine sont déjà exprimées dans le muscle humain adulte, mais la chaine α1 de la laminine (Lamα1) est exprimée uniquement pendant le stade très précoce 16 cellules de l'embryogenèse. Nous avons donc développé une méthode alternative à l’injection répétée de Laminine-111 en induisant l'expression endogène du gène LAMA1, afin de reformer le complexe trimérique α1β1γ1, la laminine 111. Ceci a été réalisé avec une technologie récente, le système CRISPR/Cas9, dont la Cas9 a été désactivée (dCas9) puis couplée à un domaine d’activation de la transcription, le VP160 (dCas9-VP160). L’utilisation d’un ou plusieurs ARN guides (ARNg) a permis de cibler le promoteur du gène LAMA1. L’ARNm de Lamα1 (qRT-PCR) ainsi que la protéine (immunohistochimie et immunobuvardage) n’ont pas été détecté dans le contrôle négatif, des myoblastes murins (C2C12). Cependant, une expression significative a été observée dans ces myoblastes transfectés avec des plasmides codant pour dCas9-VP160 et un ARNg. L’analyse protéique in vivo, dans des muscles de souris électroporés avec le même plasmide, a démontré une forte augmentation de la chaine α1 de la laminine. Des augmentations plus importantes de l’ARNm de Lamα1 ont été observées en utilisant 2 ARNg, suggérant un effet synergique. L’augmentation de l’expression de Lamα1 par le système de CRISPR/Cas9 devrait être étudiée d’avantage afin de vérifier si cette stratégie pourrait s’avérer efficace dans des cas de myopathies.Laminin-111 protein complex links the extra-cellular matrix to integrin α7β1 in sarcolemma, thus replacing in dystrophic muscles links normally insured by dystrophin complex. Laminin-111 injection in mdx mouse increased expression of integrin α7β1, stabilized sarcolemma, restored serum creatine kinase to wild-type levels, and protected muscles from exercised-induced damages. These results suggested that increased Laminin-111 is a potential therapy for DMD. Laminin β1 and γ1 chains are expressed in adult human muscle but laminin α1 (LAMA1) gene is expressed only during embryogenesis. We thus developed an alternative method to Laminin-111 protein repeated administration by inducing expression of the endogenous LAMA1 gene. This was done with the CRSPR/Cas9 system, i.e., by targeting the LAMA1 promoter with one or several gRNAs and a dCas9 coupled with the VP160 transcription activation domain. LAMA1 mRNA (qRT-PCR) and proteins (immunohistochemistry and western blot) were not detected in the control C2C12 myoblasts. However, significant expression was observed in cells transfected and in mouse muscles electroporated with plasmids coding for dCas9-VP160 a gRNA. Larger synergic increases were observed by using 2 or 3 gRNAs. Increased expression of LAMA1 by the CRISPR/Cas9 system will have to be further investigated to verify whether this could be a treatment for several myopathies.
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Spenlé, Caroline. "La laminine-511, acteur de l’inflammation et de la progression tumorale dans l’intestin?" Strasbourg, 2010. https://publication-theses.unistra.fr/public/theses_doctorat/2010/SPENLE_Caroline_2010.pdf.
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La laminine-511 (α5β1y1), élément de la matrice extracellulaire, fait partie des molécules médiatrices des interactions épithélio-mésenchymateuses qui contrôlent le développement intestinal puis le renouvellement cellulaire dans l’organe mature. Une rupture de l’homéostasie de l’ensemble de ces mécanismes est centrale dans les maladies inflammatoires chroniques de l’intestin (MICI) qui, dans une certaine proportion, peuvent dégénérer en cancer colorectal. Ce travail de thèse a permis de démontrer que la chaîne α5 de laminine, caractéristique de la laminine-511, pouvait d’une part réguler l’expression de gènes cibles importants dans les fonctions biologiques majeures des cellules intestinales et d’autre part était capable de réprimer ou d’activer deux voies de signalisation, Wnt et PI3K/Akt, suivant le contexte physiologique. Dans le contexte pathologique particulier des MICI, j’ai pu définir la composition en laminines de la lame basale dans des segments pathologiques issus d’exérèses chirurgicales de côlons de patients atteints de maladie de Crohn ou de rectocolite hémorragique. De façon très intéressante, des glandes atypiques y ont été trouvées, délimitées par une lame basale enrichie en chaînes α1 et α5 de laminines et caractérisées par une accumulation nucléaire de la protéine p53, suppresseur de tumeur. J’ai pu définir, par des expériences in vitro, une chronologie d’activation montrant que la protéine p53 était capable de stimuler l’expression endogène de la chaîne α1 de laminine. J’ai également pu modéliser les résultats obtenus chez l’humain par des inductions chimiques d’inflammation et de tumorigenèse associée grâce à des modèles de souris transgéniques sur-exprimant soit la chaîne α1 soit la chaîne α5 dans l’épithélium intestinal, modèles établis par l’équipe. Les dérégulations des laminines qui ont été observées peuvent jouer un rôle important dans la rupture de l’épithélium, l’inflammation et les mécanismes de réparation qui leur sont inhérents ou dans la progression des MICI en cancerThe laminin-511 (α5β1y1), key element of the extracellular matrix, mediates the epithelialmesenchymal interactions controlling the intestinal development and the cell renewal in the mature organ. A deregulation of the mechanisms implied in the homeostasis is obvious in inflammatory bowel diseases (IBD). IBD can in some cases degenerate into colorectal cancer. My present work demonstrates that the α5 chain, characteristic of the laminin-511 molecule, regulates the expression of target genes important for major biological functions of the intestinal cells as well as is able to repress or activate two signaling pathways, Wnt and PI3K/Akt, according to the physiological context. In the particular context of IBD, I could define the laminin composition of the basement membrane in pathological samples from surgical resection of colon from patients with Crohn’s disease or Ulcerative colitis. Interestingly, atypical glands are also found in these samples. These glands are encircled with a basement membrane enriched in laminin α1 and α5 chains and are characterized by a nuclear accumulation of p53, a tumor suppressor. By in vitro experiments, I have defined a chronology of activation showing that the p53 protein is able to stimulate the endogenous expression of the laminin α1 chain. I could mimic the results obtained in humans by triggering inflammation and inflammation-associated tumorigenesis chemically to transgenic murine models overexpressing either the laminin α1 or α5 chain, models that were previously established in the team. The laminin-observed deregulations could play an important role in the epithelium rupture, the inflammation and the inherent repair mechanisms, as well as in the progression of IBD into cancer
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Moutsita, Richard. "Proprietes d'un recepteur de la laminine isole a partir de fibroblastes de poulet." Paris 5, 1992. http://www.theses.fr/1992PA05S016.
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L'etude des mecanismes intervenant dans l'une des phases avancees de l'adherence cellulaire, c'est-a-dire l'etalement, de fibroblastes d'embryon de poulet de 8 jours (8-cef) sur la laminine et la fibronectine, glycoproteines de la matrice extracellulaire, a ete entreprise en utilisant une lectine vegetale la concanavaline a (cona) comme sonde. En effet, cette lectine inhibe l'etalement des cef sur la laminine mais pas sur la fibronectine et n'a aucun effet sur l'attachement cellulaire sur ces matrices. Les glycoproteines interagissant avec la cona representent une population heterogene de masse moleculaire comprise entre 30 kd et 72 kd. Parmi ces glycoproteines, seule la glycoproteine de masse moleculaire 72 kd (cbg72) est reconnue par la laminine immobilisee. De plus, cette glycoproteine inhibe specifiquement l'etalement des cef sur la laminine mais pas sur le fibronectine. L'utilisation du triton x-114 et l'incorporation de la cbg72 dans les liposomes ont permis de mettre en evidence la nature transmembranaire de cette glycoproteine. L'isolement des glycoproteines des cef ayant adhere sur la laminine en utilisant le triton x-100 nous a permis d'etablir la relation de la cbg72 avec le cytosquelette. Par ailleurs, la cbg72 n'a aucune parente antigenique avec certains recepteurs connus de la laminine (5'-nucleotidase, recepteur 69 kd, integrines de la famille 1#1). Enfin a l'aide des fragments fab anti-cbg72, nous avons mis en evidence que le fragment e8 de la laminine est responsable de la reconnaissance de cette glycoproteine.
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Loureiro, Marcos Gomes. "Estudo da técnica de venografia dos dígotos de vacas /." Botucatu, 2013. http://hdl.handle.net/11449/101095.
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Orientador: Celso Antonio RodriguesBanca: Marcos Jun Watanabe
Banca: Delphim da Graça Macoris
Banca: Luis Cláudio Lopes Correia da Silva
Banca: Caio Biasi Mauro
Resumo: Em bovinos a venografia retrógrada podal é pouco descrita, quando comparada com a espécie equina. O objetivo deste estudo foi descrever a técnica de venografia retrógrada podal em vacas, comparando os acessos da veia digital dorsal comum III com a digital comum II ou IV, nos membros torácicos e pélvicos mediante a administração de dois diferentes volumes de contraste. Foram utilizados 53 membros torácicos e pélvicos de 14 vacas, contidas em decúbito lateral no tronco com o torniquete de borracha posicionado a 5 cm do paradígito. Administrou-se 10 mL do diatrizoato de meglumine em 24 membros (grupo 1), sendo 13 na veia digital dorsal comum III pelo acesso 1 (A1) e 11 na digital II ou IV no acesso 2 (A2). No grupo 2, administrou-se 20 mL em 29 membros, sendo 15 pelo A1 e 19 no A2. Após a administração do contraste, as radiografias foram repetidas a cada 20 segundos até 120 segundos, na projeção dorso palmar/plantar 0°. O grau de preenchimento vascular foi maior no grupo 2, independente do acesso venoso, do membro ou momento. Não houve diferença significativa no grau de radiopacidade das imagens radiográficas quando comparado o acesso venoso, momento e membro de ambos os grupos. Conclui-se que a administração de 20 ml de contraste apresentou melhor preenchimento e radiopacidade, não havendo diferença entre 20 e 120 segundos após a administração do contraste na qualidade radiográfica independente do acesso venoso
Abstract: In cattle the foot retrograde venography is rarely described, compared with the equine species. The aim of this study was to describe the technique of retrograde venography foot in cows, comparing the approaches of the dorsal common digital vein III with the digital commons II or IV, thoracic and pelvic by administering two different volumes of contrast members. Were used fifty tree fore and hindlimbs of 14 cows, contained in the lateral position on the trunk with rubber tourniquet placed at 5 cm from paradígito were used. Was administered 10 mL of diatrizoate meglumine 24 members (group 1), 13 dorsal common digital vein III for access 1 (A1) and 11 digital II or IV access 2 (A2). In group 2 was administered 20 mL 29 members, 15 by 19 in A1 and A2. After contrast administration, the radiographs were repeated every 20 seconds until 120 seconds, back projection on the palmar/plantar 0°. The degree of vascular filling was greater in group 2, independent of venous access, member or moment. There was no significant difference in the degree of radiopacity of radiographic images when compared to the venous access, time and a member of both groups. We conclude that administration of 20 ml of contrast showed better filling and radiopacity, with no difference between 20 and 120 seconds after contrast administration in independent radiographic quality venous access
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Esnault, Karine. "Expression et identification de molecules participant a l'adherence et a la germination des conidies d'aspergillus fumigatus (doctorat : microbiologie et biologie cellulaire)." Angers, 1999. http://www.theses.fr/1999ANGE0504.
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Le, Bars Pierre. "Etude histo-immunologique de la stomatite prothetique." Nantes, 2000. http://www.theses.fr/2000NANT23VS.
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Pommeret, Olivier. "Etude fonctionnelle in vivo et in vitro des différentes formes de la Laminine-5." Paris 7, 2003. http://www.theses.fr/2003PA077232.
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Ritié-Pertusa, Léa. "Recherche du rôle de la chaîne α5 de laminine dans l’intestin normal et pathologique." Université Louis Pasteur (Strasbourg) (1971-2008), 2008. https://publication-theses.unistra.fr/public/theses_doctorat/2008/RITIE-PERTUSA_Lea_2008.pdf.
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La chaîne α5 de laminine, représentante majeure des lames basales, est médiatrice des interactions épithélio-mésenchymateuses indispensables à la morphogenèse et à l’homéostasie de l’intestin. Ce travail de thèse a révélé que les souris mutantes pour le gène Lama5 présentent une altération d’expression de gènes de différenciation épithéliale et musculaire, de molécules d'adhésion et de 2 voies de signalisation, la voie de la PI3Kinase/Akt et la voie Wnt. Cette étude a permis de démontrer que la chaîne α5 est une molécule signal capable de réguler l’expression de gènes cibles lui conférant un rôle dans plusieurs fonctions biologiques dans les cellules intestinales - prolifération, survie, migration et différenciation. La chaîne α5 favorise notamment la survie cellulaire en induisant l’activation d'Akt via la PI3K. L’invalidation génique d’un des récepteurs de la chaîne α5, le Luthéran, a révélé l’importance de la signalisation laminine α5/Luthéran pour l’intégrité tissulaire du rein et du muscle intestinal. Cette signalisation est essentielle à une organisation normale des lames basales dans ces deux tissus. Enfin, j’ai montré que la chaîne α5 de laminines est dérégulée dans deux pathologies intestinales : la maladie de Hirschsprung et le cancer colorectal. Les intestins atteints de maladie de Hirschsprung présentent une accumulation de chaîne α5 dans le muscle qui pourrait partiellement être à l’origine de l’aganglionose intestinale caractéristique de cette maladie. Par cette étude, nous avons mis en évidence une nouvelle caractéristique des cas d’aganglionose qui est la présence anormale de cellules de Schwann au sein des plexus entériques et révélé une modification du profil d’expression de plusieurs laminines qui pourra être utilisé comme marqueur diagnostique des cas d’aganglionose. Ce travail a par ailleurs montré une dérégulation de la chaîne α5 dans les cancers colorectaux. La chaîne α5 est en effet trouvée sur-exprimée dans les zones tumorales encore bien différenciées où elle pourrait contribuer aux phases précoces de la tumorigenèse. En revanche, son expression chute dans les zones plus altérées permettant certainement l’invasion tumorale. En conclusion, ce travail de thèse a montré que la chaîne α5 de laminine est une molécule signal du microenvironnement cellulaire qui influence le devenir des cellules intestinales en régulant de nombreux processus cellulaires essentiels au développement et à l’homéostasie intestinaleThe laminin α5 chain, a major component of the basement membrane, plays an essential role in intestinal morphogenesis and homeostasis by driving epithelial-mesenchymal interactions. The present work demonstrated, in intestines lacking the laminin α5 chain, an alteration of genes implied in epithelial and muscle differentiation, of some adhesion receptors and a deregulation of Wnt and PI3K/Akt signaling pathways. We identified the laminin α5 chain as a signaling molecule able to induce expression of specific genes that will trigger various cellular processes including proliferation, survival, migration and differentiation of intestinal cells. The α5 chain has notably an anti-apoptotic effect by inducing the PI3K-dependent activation of Akt. We also studied the role of Lutheran, an exclusive receptor for the α5 chain by gene invalidation in mice. We showed that the laminin α5 chain/Lutheran signaling is essential for renal and intestinal muscle integrity and is required for a normal organization of basement membranes. Finally, I have shown the deregulation of laminin α5 chain in two intestinal diseases: Hirschsprung disease and colorectal cancer. First, we found an accumulation of α5 chain in intestinal muscle of patients with Hirschsprung disease which could be implied in the pathogenesis. We identified the abnormal presence of Schwann cells and found modifications in the expression profile of several laminin chains in aganglionic plexuses that could be new markers of intestinal aganglionosis. Second, we hightlighted the deregulation of laminin α5 chain in colorectal tumors. Indeed, α5 chain is overexpressed in still differentiated tumor areas where it could participate in onset of tumorigenesis. With increasing grade of the tumors, the α5 chain expression becomes downregulated to permit tumoral cell invasion. In conclusion, this work identified the laminin α5 chain as a signal molecule of the cell microenvironment which determines intestinal cell fate during intestinal development and homeostasis
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Girardi, Annita Morais. "Acidose ruminal subaguda em ovinos Santa Inês : estudo clínico, laboratorial e avaliação da laminite por termografia infravermelha e radiologia digital /." Jaboticabal, 2016. http://hdl.handle.net/11449/134272.
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Orientador: Luiz Carlos MarquesBanca: Thaís Helena Constantino Patelli
Banca: Lúcia Helena Rodrigues
Banca: Daniela Gomes da Silva
Banca: Luís Guilherme de Oliveira
Resumo: Este estudo avaliou o uso da termografia infravermelha e do exame radiológico digital como ferramentas de diagnóstico precoce da laminite em ovinos com acidose ruminal subaguda induzida experimentalmente e os efeitos da ingestão prolongada de alta proporção de alimento concentrado sobre as variáveis clínicas e laboratoriais. Foram utilizadas sete ovelhas adultas, com cânulas ruminais permanentes, que não tiveram prévio contato com alimento concentrado. Para a indução da acidose ruminal, incluiu-se ao volumoso, diariamente, 10% de alimento concentrado até atingir 80%, porcentagem mantida até completarem 19 semanas. A observação dos sinais de diarreia deu-se do quarto ao 22º dia e de laminite do quinto ao 24º dia. O fluido ruminal foi predominantemente líquido, de odor ácido e coloração amarelada. Observou-se elevação inicial nos valores da frequência cardíaca, tempo de sedimentação e flotação no fluido ruminal, plaquetas, neutrófilos segmentados, AST, FA, GGT, cálcio ionizado, magnésio, glicose, ureia, triglicérides e bilirrubinas indireta e total. No início do experimento, notou-se redução da frequência respiratória, linfocitopenia, monocitopenia, hipocalcemia, hipofosfatemia, hiponatremia, hipoproteinemia e hipocolesterolemia. A frequência de movimentos ruminais, o tempo de redução do azul de metileno, os níveis sanguíneos de creatinina, bilirrubina direta, lactato e CK foram reduzidos, enquanto as médias de temperatura, peso e escore corporal, eosinófilos, albumina, cloretos e potássio no sangue aumentaram durante todo o período de observação. Redução do pH ruminal ocorreu nos primeiros dias, a despeito de sua manutenção acima de 5,5 durante as 19 semanas de observação. Mecanismos compensatórios respiratórios e metabólicos, principalmente a acidificação da urina, mantiveram o pH sanguíneo dentro dos limites fisiológicos considerados...
Abstract: This study evaluated the use of infrared termography and digital radiologic examination as early diagnostic tools for laminitis in sheep with experimentally induced subacute ruminal acidosis, and the effects of long-term ingestion of a high concentrate diet on clinical and laboratory variables. Seven adult ewes with permanent rumen cannula were used, which did not have any previous ingestion of concentrate feed. For the induction of ruminal acidosis, it was added to the roughage, 10% of concentrate feed until reach 80%, percentage held to the end of the 19-week experiment. Diarrhea signs were observed from fourth to 22nd day and laminitis from fifth to 24th day. Ruminal fluid was predominantly liquid, sour-smelling and yellowish. Initial increases of heart rate, sedimentation and flotation time, platelets, segmented neutrophils, AST, ALP, GGT, ionized calcium, magnesium, glucose, urea, triglycerides, indirect and total bilirubin were noted. At the beginning of the experiment, there was reduction of respiratory rate, lymphocytopenia, monocytopenia, hypocalcemia, hypophosphatemia, hyponatremia, hypoproteinemia, and hypocholesterolemia. Ruminal movement rate, methylene blue reduction time, creatinine, direct bilirubin, lactate and CK blood levels decreased, while body temperature, weight and score, eosinophils, albumin, chloride and potassium blood levels increase throughout the period. Ruminal pH reduction occurred within the first days, despite its maintenance above 5.5 during the 19 weeks. Respiratory and metabolic mechanisms, mainly urine acidification, remained the blood pH between physiologic limits for sheep. Sixteen protein fractions were separated by electrophoresis, among them eight proteins of unknown functions, identified by their molecular weights. Most acute phase proteins and the immunoglobulins identified in the electrophoretic fractionation varied throughout the observation ...
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Cagnet, Stéphanie. "Etude du rôle des intégrines liant la laminine dans le développement et la tumorigenèse mammaires." Thesis, Paris 11, 2013. http://www.theses.fr/2013PA11T079/document.
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Le développement de traitements thérapeutiques du cancer du sein reste limité par le niveau de connaissance des mécanismes moléculaires et cellulaires impliqués lors du développement normal et tumoral de la glande mammaire. L’épithélium mammaire est entouré d’une matrice extracellulaire (MEC) organisée, la membrane basale, dont le constituant principal est la laminine. Des études ont montré que les interactions entre les cellules mammaires et la MEC, dépendantes des intégrines, jouent un rôle majeur dans le développement et la tumorigenèse mammaires. Ces études n’ont cependant pas permis de déterminer les hétérodimères d’intégrine spécifiquement impliqués. Dans ce contexte, mon projet de thèse a visé à définir le rôle joué par les intégrines liant la laminine (dimères contenant les sous-unités 3 et/ou 6) dans le développement mammaire, dans le maintien de cellules souches mammaires fonctionnelles dans la glande adulte et dans le développement tumoral. Les résultats de mon travail suggèrent que :(i) l’intégrine 31 présente une fonction unique au cours de la lactation. Les mécanismes moléculaires impliqués en aval de 31 font intervenir la voie FAK/Rac1/PAK1 menant à l’inhibition de la MLCK, nécessaire à la relaxation des cellules myoépithéliales mammaires et permettant de nouveaux cycles de contraction. (ii) les interactions régulées par les intégrines entre les cellules basales mammaires et la laminine sont essentielles pour régénérer l’épithélium mammaire. Cependant, les intégrines 3 et 6 présentent des fonctions redondantes dans les cellules souches mammaires. (iii) l’intégrine 31 joue un rôle clef dans le développement tumoral mammaire. L’intégrine 31 active des voies de signalisation intracellulaires FAK/Rac1/PAK1, MAPK et JNK qui favorisent la survie et la prolifération des cellules tumorales. Ensembles, ces données permettent une meilleure compréhension des mécanismes moléculaires impliqués dans le développement mammaire, la fonction de la glande adulte et la tumorigenèseThe improvement of breast cancer therapy requires thorough analysis of the pathways leading to tumorigenesis and clear understanding of the molecular and cellular mechanisms involved in normal mammary gland development. Mammary epithelium is surrounded by a specifically organized extracellular matrix (ECM), basement membrane, and secreted glycoproteins, laminins, are among its major constituents. Integrin-mediated interactions between mammary epithelial cells and ECM have been shown to play an essential role in the control of mammary development and tumorigenesis. However, specific roles played by distinct integrin heterodimers are yet poorly understood. My thesis project aimed to define the functions of laminin-binding integrins, i.e., heterodimers, containing 3 or 6 subunits, in normal mammary gland development, in control of mammary stem and progenitor cell functions in adult gland, and in mammary tumorigenesis. The results of my work suggest that: (i31 integrin has a unique function in the control of the myoepithelial cell contractile activity during lactation; it contributes to the activation of the FAK/Rac1/PAK1 pathway leading to MLCK inhibition required for myoepithelial cell relaxation, thereby, permitting further contractile cycles. (ii) integrin-mediated interactions of mammary basal cells with laminins are essential for the regeneration of the mammary epithelium. However, 31 and 6-contaning integrins have redundant functions in mammary stem cells.(iii) 31 integrin plays a major role in mammary tumorigenesis, it promotes survival and proliferation of tumor cells activating intracellular signaling pathways involving FAK/Rac1/PAK1, MAPK and JNK pathways. Altogether, these data provide new insights into the molecular mechanisms of mammary development, adult gland function and tumorigenesis
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Noronha, Filho Antônio Dionísio Feitosa. "Indução experimental de acidose ruminal e laminite em bezerros mestiços pela administração intrarruminal de oligofrutose." Universidade Federal de Goiás, 2017. http://repositorio.bc.ufg.br/tede/handle/tede/7877.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq
Among diseases that can affect cattle in intensive production systems are rumen acidosis laminitis. It was produced initially a literature review about experimental induction of rumen acidosis and after this, was evaluated rumen acidosis and initial phase of laminitis in calves, both induced by intrarruminal administration of oligofructose. In the different protocols, in both acute and subacute forms of acidosis, are usually evaluated fermentative and clinical aspects. In the study was used six crossbred male calves (Bos taurus X Bos indicus) aging one year and weighting 175 ± 22,6 kg. Initially were used three animals in a pilot group (GP), receiving oligofructose in the dose of 13g/kg and after this, three animals were used as experimental group (GE) receiving oligofructose in the dose of 17 g/kg. Were evaluated parameters from clinical exam, hematocrite, plasmatic protein, blood gas analysis and histology of hoof samples. Oligofructose overload induced rumen acidosis in both groups. It was also observed metabolic acidosis with reduction of blood pH, PCO2, bicarbonate and base excess. Was observed neither elevation in hoof sensibility nor lameness. Despite this, many animals presented apathy and slower gait, possibly due to metabolic acidosis. In histologic evaluation, were observed circulatory changes and inflammatory infiltrate in dermis, irregularities in basement membrane and morphologic changes in basal epidermis. Protocol for laminitis induction with intrarruminal administration of oligofructose in crossbred calves was well succeeded. In the initial phase, laminitis was characterized by clinical signs of the primary disease, in this case rumen acidosis, and histologic lesions indicative of acute inflammation and compromise of basement membrane and basal epidermis.
Entre as doenças que acometem bovinos em sistemas de alta produtividade estão a acidose ruminal e a laminite. Objetivou-se inicialmente realizar revisão de literatura sobre indução experimental de acidose ruminal em bovinos e, posteriormente, avaliar o quadro de acidose ruminal e da fase inicial de laminite induzidas pela administração de oligofrutose em bezerros. Nos diferentes protocolos de indução podem ser avaliados aspectos fermentativos e clínicos da acidose ruminal, nas formas aguda e subaguda. Para o estudo, utilizaram-se seis bezerros mestiços (Bos taurus X Bos indicus) de um ano de idade. Inicialmente usaram-se três animais em um grupo piloto (GP) recebendo oligofrutose na dose de 13 g/kg e em seguida um grupo experimental (GE) recebendo na dose de 17 g/kg. Avaliaram-se alterações clínicas, laboratoriais e histológicas do casco. A sobrecarga de oligofrutose provocou acidose ruminal caracterizada por baixo pH em ambos os grupos. Observou-se também acidose metabólica com redução de pH, PCO2, bicarbonato e excesso de base. Não se observou aumento da sensibilidade dos cascos ou claudicação. Apesar disso, muitos animais apresentaram apatia e marcha mais lenta, possivelmente devido a acidose metabólica. Histologicamente observaram-se alterações circulatórias e infiltrado inflamatório na derme, irregularidades de membrana basal e alterações morfológicas na camada basal da epiderme. O protocolo de indução de laminite com administração intrarruminal de oligofrutose se mostrou eficaz em bezerros mestiços de um ano. Na fase inicial a laminite se caracterizou por sinais clínicos da enfermidade primária, no caso acidose ruminal, e por alterações histológicas indicativas de inflamação aguda e comprometimento de membrana basal e epiderme.
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Madeleine, Noelly. "Recherche d'inhibiteurs de l'interaction Lutheran-Laminine par des techniques de modélisation et de simulation moléculaires." Thesis, La Réunion, 2017. http://www.theses.fr/2017LARE0054/document.
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La drépanocytose est une maladie génétique qui se caractérise par des globules rouges en forme de faucille. Chez les personnes atteintes de drépanocytose, ces globules rouges (GR) adhèrent à l’endothélium vasculaire et provoquent ainsi une vaso-occlusion. Ce phénomène s’explique par la surexpression de la protéine Lutheran (Lu) à la surface des globules rouges falciformes qui se lie fortement à la Laminine (Ln) 511/521 exprimée par l’endothélium vasculaire enflammé. Le but de cette étude est d’identifier un inhibiteur d’interaction protéine-protéine (PPI) qui possède une forte probabilité de liaison à Lu afin d’inhiber l’interaction Lu-Ln 511/521. Un criblage virtuel de 1 295 678 composés ciblant la protéine Lu a été réalisé. La validation préalable d’un protocole de scoring a été envisagée sur la protéine CD80 qui présente un site de liaison avec des caractéristiquestopologiques et physico-chimiques similaires au site de liaison prédit sur Lu ainsi que plusieurs ligands avec des constantes d’affinité connues. Ce protocole contient différentes étapes de sélection basées sur les affinités calculées (scores), des simulations de dynamique moléculaire et les propriétés moléculaires. Un protocole de scoring fiable a été validé sur CD80 avec le programme de docking DOCK6 et les fonctions de scoring XSCORE et MM-PBSA ainsi qu’avec la méthode decalcul FMO. L’application de ce protocole sur Lu a permis d’obtenir deux ligands validés par des tests in vitro qui font l’objet d’un dépôt de brevet. La fonction de scoring XSCORE a permis d’identifier neuf autres ligands qui semblent aussi être des candidats prometteurs pour inhiber l’interaction Lu-Ln 511/521Drepanocytosis is a genetic blood disorder characterized by red blood cells that assume an abnormal sickle shape. In the pathogenesis of vaso-occlusive crises of sickle cell disease, red blood cells bind to the vascular endothelium and promote vaso-occlusion. At the surface of these sickle red blood cells, the overexpressed protein Lutheran (Lu) strongly interacts with the Laminin (Ln) 511/521.The aim of this study was to identify a protein-protein interaction (PPI) inhibitor with a highprobability of binding to Lu for the inhibition of the Lu-Ln 511/521 interaction. A virtual screening was performed with 1 295 678 compounds that target Lu. Prior validation of a robust scoring protocol was considered on the protein CD80 because this protein has a binding site with similar topological and physico-chemical characteristics and it also has a series of ligands with known affinity constants. This protocol consisted of multiple filtering steps based on calculated affinities (scores), molecular dynamics simulations and molecular properties. A robust scoring protocol was validated on the protein CD80 with the docking program DOCK6 and the scoring functions XSCORE and MM-PBSA and also with the FMO method. This protocol was applied to the protein Lu and we found two compounds that were validated by in vitro studies. The protection of these ligands by a patent is under process. Nine other compounds were identified by the scoring functionXSCORE and seem to be promising candidates for inhibiting the Lu-Ln 511/521 interaction
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Péterszegi, Gabriella. "Expression du récepteur de l'élastine-laminine sur les lymphocytes humains activés. Rôle possible dans l'athérogenèse." Paris 7, 1997. http://www.theses.fr/1997PA077064.
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Nos expériences mettent en évidence la présence du récepteur de l'élastine-laminine sur les lymphocytes humains activés in vitro, ainsi qu'in vivo sur les lymphocytes dans les plaques d'athérome. La démonstration de ce récepteur sur les lymphocytes présents dans les plaques ouvre de nouvelles perspectives quant à la compréhension du rôle de ces cellules dans le processus athéromateux. Notre travail a également montré que les lymphocytes humains activés synthétisent et libèrent deux sérine protéases particulièrement impliquées dans l'athérogenèse, l'élastase et la cathepsine G. Le récepteur de l'élastine-laminine est activé lorsque les produits de dégradation de l'élastine, les peptides d'élastine se fixent sur sa sous-unité de 67 kD. La prolifération des lymphocytes, ainsi que l'activité de ces deux enzymes, sont significativement augmentées quand des peptides d'élastine sont ajoutés, à faible concentration, au milieu de culture. Il paraît donc probable que le gène codant la PMN-élastase soit exprimé dans les lymphocytes et que cette expression soit sous le contrôle du récepteur de l'élastine. Nos expériences montrent également que l'âge et certaines pathologies peuvent influencer ces phénomènes. Il paraît probable que l'immunosénescence, concernant surtout la capacité de prolifération des lymphocytes T après stimulation spécifique ou non-spécifique, ainsi que des défauts de la maturation lymphocytaire influencent la synthèse et la libération de l'élastase et de la cathepsine G. Vu le rôle important des lymphocytes dans les phénomènes pathologiques et en particulier dans le développement de la plaque d'athérosclérose, l'activation de leur potentiel protéolytique par le récepteur de l'élastine et leurs modifications au cours du vieillissement, pourraient jouer un rôle important dans l'athérogenèse ainsi que dans d'autres pathologies où intervient le système immunitaire.
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Cadalbert, Laurence. "Etude de la fonction de la laminine-8 au cours de l'embryogénèse chez la souris." Université Louis Pasteur (Strasbourg) (1971-2008), 2001. http://www.theses.fr/2001STR13175.
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Mollo, Neto Mario. "Desenvolvimento de um sistema para diagnostico preventivo de laminite em bovinos de leite utilizando logica Fuzzy." [s.n.], 2007. http://repositorio.unicamp.br/jspui/handle/REPOSIP/257064.
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Orientador: Irenilza de Alencar NaasTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Agricola
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Resumo: A partir de meados do século XX, geneticistas e produtores intensificaram os trabalhos de melhoramento de bovinos leiteiros. Progressos surgiram, mas estes resultados não foram acompanhados pelo melhoramento de patas e cascos. Foram realizadas modificações das instalações visando adequá-las às necessidades de intensificação dos rebanhos e torná-los mais produtivos, culminando em uma maior concentração de animais por área, resultando em um maior volume de dejetos, maior umidade, menor higiene e dificuldades de manejo. Para solucionar estes problemas iniciou-se um processo de impermeabilização dos pisos destas construções para diminuir a umidade e facilitar a higiene. Isto foi reforçado com as construções dos sistemas ¿free-stall¿, nos quais as vacas freqüentemente passam a maioria do tempo em pé sobre o piso de concreto. Este quadro propicia o surgimento de patologias de casco. Este trabalho propôs o desenvolvimento de um sistema computacional para o diagnóstico preventivo da patologia de casco em gado de leite confinado em modalidade freestall, a pododermatite asséptica difusa, também conhecida por laminite e tem como público alvo os veterinários, os proprietários de plantéis, tratadores, consultores, fabricantes de ração, projetistas e construtores de galpões para alojamento do plantel. Clinicamente, a diagnose da laminite só é possível mediante a observação de deficiências de locomoção, porém quando este sintoma se revela, a patologia apresenta-se já em avançado grau, o que exige a imediata intervenção de um veterinário, incorrendo em perdas econômicas e prejudicando o bem estar animal. Uma correlação com os fatores nutricionais do arraçoamento, a presença de pisos mais abrasivos, variáveis climáticas e condições de manejo dos cascos permitiram a conversão destes dados para termos lingüísticos, as quais, por apresentar vantagens do uso de conceitos subjetivos que provêem um alto grau de certeza, aplicou-se a Lógica Fuzzy para o desenvolvimento de um algoritmo motor de inferência baseado em regras como base para o processo de suporte a decisão. Os resultados mostraram que o sistema especialista gera informações de possível acréscimo ou decréscimo nas chances do desenvolvimento da laminite e ainda fornece recomendações para ações dos criadores por meio de modificações em parâmetros referentes às condições de ambiência, arraçoamento e manejo. A tecnologia gerada contribui na redução das perdas econômicas e melhorando o bem estar animal
Abstract: From the middle of the 20th century experts on genetics and producers had intensified the work to improve dairy production. Advances have appeared, however these results have not been followed by the improvement of cows legs and hooves. The intensification of herd¿s needs have been carried through housing modifications aiming at to adjust them as well as to become them more productive, leading into a larger concentration of animals per floor area, resulting in a higher volume of dejects, higher humidity, less hygiene, and difficulties of handling. In order to solve these problems a process of waterproofing for these constructions floors was started in order to reduce the humidity and to make easier the hygiene process. This are reinforced whith the free-stall housing systems constructions, where the dairy cows often stay most of the time standing on the concrete floor. This scenario results in the sprouting of hoof pathologies. This research considered the development of a computational system for preventive diagnosis of confined dairy cattle hoof pathologies in free-stall housing, for estimating the presence of diffuse aseptic pododermatitis, also known as laminitis, and has as target the public such as: veterinarians, producers, handlers, consultants, ration manufacturers, breeding lodging¿s designers and constructors. Clinical diagnosis of the laminitis is only possible by observing faulty locomotion; however when the symptoms are apparent, the pathology is already in an advanced stage demanding the immediate intervention of a veterinarian, incurring into economic losses and animal welfare restrains. A correlation with the nutritional factors of feed intake, the presence of more abrasive pavements, climatic changes and handling conditions has allowed the conversion of these data into linguistic terms, due to its advantages of using subjective concepts that provides a high degree certainty, and the application of Fuzzy Logic for the development of a inference algorithm based on a rule database to be used as the decision support process. The results showed that the expert system generates information of possible increase or decrease in the laminitis development possibilities and also supplies recommendations for producers¿ actions by making modifications in parameters regarding environmental conditions, feeding and handling management. The technology generated contributes for the reduction of the economic losses and leads to improvement in dairy cattle welfare
Doutorado
Construções Rurais e Ambiencia
Doutor em Engenharia Agrícola
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SANTOS, Carlos Anselmo dos. "Alterações placentárias associadas à hipertensão arterial em éguas com laminite crônica no terço final da gestação." Universidade Federal de Pelotas, 2013. http://repositorio.ufpel.edu.br/handle/ri/2506.
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Previous issue date: 2013-01-17The cardiovascular changes in horses with laminitis are described since the 70's, however few studies have been conducted to demonstrate such changes in pregnant mares with chronic laminitis. The present study aims to evaluate blood pressure, heart rate, serum cortisol levels, gestational age and placental changes of pregnant mares with chronic laminitis and its consequences for fetal morphometry. A prospective longitudinal case-control was conducted in 6 Thoroughbred horse farms in southern Rio Grande do Sul - Brazil. Were used a total of 20 multiparous mares (10 control animals and 10 animals with chronic laminitis). The selected animals were subjected to clinical examination, blood sample collection and blood pressure measurement on alternate days in the last month of pregnancy. Serum levels of cortisol were obtained by chemiluminescence, and blood pressure measurement by indirect method and apparatus for noninvasive oscillometric sphygmomanometer at the base of the tail. Assessment of placental was effected by using the histological method of Schlafer (2004) and morphometric using ImageJ® software. Mean control group regarding measurements of systolic blood pressure were 98,3 ± 1,41 mmHg. The average diastolic blood pressure was 62,2 ± 1,14 mmHg. The mean heart rate was 44 ± 0,53 bpm and the mean serum cortisol levels were 5,06 ± 0,14 μg/dL. The group of pregnant mares with chronic laminitis kept the mean systolic blood pressure and heart rate higher than the control group, being respectively 116 ± 6,73 mmHg and 52 ± 4 bpm. The average values of diastolic blood pressure was 70 ± 7,3 mmHg and mean serum cortisol was 5,07 ± 0,19 μg/dL with no difference compared to the control group. The placentas of pregnant mares with laminitis had higher number of chronic histological changes and higher wall thickness / lumen than the control group (p <0,05). The foals born from mares of the control group had higher birth weight than foals born from chronic laminitis s group mares (p <0,05).
As alterações cardiovasculares em cavalos com laminite são descritas desde a década de 70, porem poucos estudos foram realizados para demonstrar tais alterações em éguas gestantes com laminite crônica. O presente estudo tem como objetivo avaliar a pressão arterial, frequência cardíaca, níveis de cortisol séricos, tempo gestacional e alterações placentárias de éguas gestantes com laminite crônica e suas consequências sobre a morfometria fetal. Foi realizado um estudo prospectivo longitudinal de caso controle em 6 criatórios de equinos Puro Sangue Inglês na região sul do Rio Grande do Sul Brasil. Foram utilizados um total de 20 éguas multíparas (10 animais do grupo controle e 10 animais com laminite crônica). Os animais selecionados foram submetidos ao exame clínico, coletas de sangue e mensurações da pressão arterial em dias alternados no último mês de gestação. Os níveis séricos de cortisol foram obtidos pelo método de quimiluminescência, e a aferição da pressão arterial através do método indireto e não invasivo por aparelho de esfigmomanômetro oscilométrico na base da cauda. A avaliação placentária foi efetuada por meio histológico utilizando o método de Schlafer (2004) e morfométrico utilizando o programa de domínio público ImageJ. Os valores médios do grupo controle referentes às aferições da pressão arterial sistólica foram de 98,3 ±1,41mmHg. O valor médio da pressão arterial diastólica foi de 62,2 ±1,14mmHg. A frequência cardíaca média foi de 44 ±0,53 bpm e as médias dos níveis séricos de cortisol foram de 5,06 ±0,14 μg/dL. O grupo de éguas gestantes com laminite crônica manteve as médias de pressão arterial sistólica e frequência cardíaca mais altas que ao grupo controle, sendo respectivamente, 116 ±6,73 mmHg e 52 ±4 bpm. Os valores médios obtidos da pressão arterial diastólica foi de 70 ±7,3 mmHg e a media dos níveis séricos de cortisol foi de 5,07± 0,19 μg/dL não havendo diferença em relação ao grupo controle. As placentas do grupo de éguas gestantes com laminite crônica obtiveram maior número de alterações histológicas e maior relação de espessura parede/luz arterial que o grupo controle (p<0,05). Os potros provenientes das gestações de éguas do grupo controle obtiveram peso ao nascimento superior aos potros nascidos do grupo de éguas com laminite crônica (p<0,05).
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Gagnoux, Laurent. "Reversion phenotypique de keratinocytes de patients atteints d'epidermolyse bulleuse jonctionnelle. Etude fonctionnelle de la laminine-5." Nice, 1997. http://www.theses.fr/1997NICE5100.
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Des formes cliniques graves d'epidermolyse bulleuse jonctionnelle (ebj), une genodermatose caracterisee par des decollements de l'epiderme a la jonction dermo-epidermique, sont dues a des mutations genetiques de la laminine-5 ; d'autres formes d'ebj ont ete associees a des mutations dans les composants de l'hemidesmosome (bp180, l'integrine 64 et la plectine). Le but de mon travail a ete tout d'abord d'identifier le defaut genetique chez deux patients atteints d'une forme ebj associee a un defaut d'expression de l'integrine 64. Dans un deuxieme temps, j'ai mis au point un modele d'etude de l'adhesion keratinocytaire et de therapie genique par l'utilisation de keratinocytes immortalises issus d'un patient ebj deficient dans l'expression de la chaine 2. La reexpression dans ces cellules d'une chaine 2 recombinante, par transfert d'un adnc codant pour cette proteine, a permis de restaurer la capacite d'adhesion des keratinocytes ebj. Par l'emploi d'adnc mutants, j'ai notamment demontre que le bras court de la chaine 2 est implique dans la polarisation et la stabilisation de la laminine-5 a la matrice extracellulaire. Nous avons donc transduit des keratinocytes ebj secondaires, deficients dans l'expression de la chaine 3 de la laminine-5, avec un transgene codant pour ce polypeptide. Nous avons ainsi demontre que les keratinocytes modifies restructurent des hds dans des epidermes artificiels. Par une approche analogue, nous avons montre que les defauts genetiques bloquant la synthese des constituants de l'hd peuvent etre complementes par transfert d'adnc dans des keratinocytes ebj presentant une alteration de l'integrine 64 et de bp180. L'ensemble de ce travail a abouti a la validation d'un modele d'etude structure/fonction de la laminine-5 et des composants des hds (l'integrine 4, bp180 et la plectine/hd1) d'un modele de therapie genique dans certaines formes d'ebj non letales.
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Piccinni, Silvia Angela. "Etude de la régulation de l'expression du gène LAMA1 codant pour la chaîne α1 de laminine." Université Louis Pasteur (Strasbourg) (1971-2008), 2003. http://www.theses.fr/2003STR13004.
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Les interactions épithélio-mésenchymateuses dans l'intestin sont médiées par les molécules de la lame basale (LB) dont les laminines (glycoprotéines hétérotrimériques constituées de chaînes a, b et g) sont des constituants ubiquitaires. Des travaux antérieurs associent la chaîne a1 de laminine (codée par le gène LAMA1) à la différenciation épithéliale mais aussi à la croissance tumorale. Durant le développement intestinal, la chaîne a1 est localisée à l'interface mésenchyme/endoderme, puis le long des villosités naissantes; dans l'organe mature, elle est restreinte à la LB sous-épithéliale du compartiment prolifératif des cryptes. L'objectif de ce travail était de caractériser le promoteur du gène LAMA1 murin et de déterminer les éléments de régulation intervenant dans le contrôle de son expression. Nous avons cloné et caractérisé 2kb en 5' du premier ATG de ce gène dépourvu de boîte TATA, localisé le site +1 de la transcription ainsi que des sites potentiels de régulation. L'analyse du promoteur dans les cellules intestinales Caco-2/TC7 a montré que (i) 90% de l'activité basale dépendent d'un site SP1 proximal sur lequel nous avons montré la fixation du facteur ubiquitaire SP1, (ii) un élément KLF fixant des facteurs de la famille Krüppel joue un rôle clef dans l'expression de LAMA1; en effet, deux facteurs intestin-spécifiques de cette famille (KLF-4/-5) ont des effets opposés (inhibition/activation) sur l'activité du promoteur, corrélant leur expression respective (villosité/crypte) à celle de la chaîne a1 dans l'épithélium intestinal. Nous avons de plus montré que l'activité du promoteur est stimulée par les glucocorticoi͏̈des et l'acide rétinoi͏̈que, facteurs différenciant et morphogène de l'intestin. Enfin, le TPA joue un rôle inhibiteur. Ainsi, l'activité transcriptionnelle du gène LAMA1 dépend d'un facteur ubiquitaire mais est modulable par des facteurs de transcription tissu-spécifiques ainsi que par des facteurs impliqués dans la différenciation intestinaleEpithelial-mesenchymal interactions in the intestine are mediated by molecules of the basement membrane (BM), of which laminins, trimeric glycoproteins constituted of one a, b and g chain are ubiquituous components. Previous work pointed to a role of the laminin a1 chain (encoded by the LAMA1 gene) in epithelial differentiation but also in tumour growth in the intestinal tissue. During intestinal development, this chain is expressed at the interface of mesenchymal and endodermal layers, then in the BM of the developing villi. In the adult mouse intestine, its expression is restricted to the BM underlying the proliferative crypts. Our aim was to characterise the LAMA1 gene promoter and to determine regulatory elements responsible for its expression. We cloned and analysed a 2kb region upstream of the first ATG of this TATA-less gene, localised the transcription-start site as well as some potentially interesting regulatory elements. The analysis of this promoter in intestinal epithelial cells (Caco-2/TC7) allowed us to show that (i) 90% of its basal activity depend on a proximal SP1-site on which we demonstrated the fixation of the ubiquituous transcription factor SP1, (ii) a KLF element recognised by Krüppel-like factors plays an important part in the regulation of LAMA1 expression; indeed, two factors of the Krüppel family (KLF-4/-5) showing an intestine-specific expression (villus/crypt) play opposite roles on the promoter activity (inh/act), correlating their respective expression pattern to that of the a1-chain within the intestinal epithelium. We further showed that the LAMA1 promoter activity is stimulated by glucocorticoids and retinoic acid (differentiating and morphogenic factors of the intestine). Finally, we showed that TPA plays an inhibitory role. Our results underline that transcription of the LAMA1 gene depends on an ubiquituous transcription factor and is modulated by tissue-specific factors and factors involved in intestinal differentiation
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Loureiro, Marcos Gomes [UNESP]. "Estudo da técnica de venografia dos dígotos de vacas." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/101095.
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000740527.pdf: 2750453 bytes, checksum: 84b108cb780a8a07dcbb67e643bf2540 (MD5)Em bovinos a venografia retrógrada podal é pouco descrita, quando comparada com a espécie equina. O objetivo deste estudo foi descrever a técnica de venografia retrógrada podal em vacas, comparando os acessos da veia digital dorsal comum III com a digital comum II ou IV, nos membros torácicos e pélvicos mediante a administração de dois diferentes volumes de contraste. Foram utilizados 53 membros torácicos e pélvicos de 14 vacas, contidas em decúbito lateral no tronco com o torniquete de borracha posicionado a 5 cm do paradígito. Administrou-se 10 mL do diatrizoato de meglumine em 24 membros (grupo 1), sendo 13 na veia digital dorsal comum III pelo acesso 1 (A1) e 11 na digital II ou IV no acesso 2 (A2). No grupo 2, administrou-se 20 mL em 29 membros, sendo 15 pelo A1 e 19 no A2. Após a administração do contraste, as radiografias foram repetidas a cada 20 segundos até 120 segundos, na projeção dorso palmar/plantar 0°. O grau de preenchimento vascular foi maior no grupo 2, independente do acesso venoso, do membro ou momento. Não houve diferença significativa no grau de radiopacidade das imagens radiográficas quando comparado o acesso venoso, momento e membro de ambos os grupos. Conclui-se que a administração de 20 ml de contraste apresentou melhor preenchimento e radiopacidade, não havendo diferença entre 20 e 120 segundos após a administração do contraste na qualidade radiográfica independente do acesso venoso
In cattle the foot retrograde venography is rarely described, compared with the equine species. The aim of this study was to describe the technique of retrograde venography foot in cows, comparing the approaches of the dorsal common digital vein III with the digital commons II or IV, thoracic and pelvic by administering two different volumes of contrast members. Were used fifty tree fore and hindlimbs of 14 cows, contained in the lateral position on the trunk with rubber tourniquet placed at 5 cm from paradígito were used. Was administered 10 mL of diatrizoate meglumine 24 members (group 1), 13 dorsal common digital vein III for access 1 (A1) and 11 digital II or IV access 2 (A2). In group 2 was administered 20 mL 29 members, 15 by 19 in A1 and A2. After contrast administration, the radiographs were repeated every 20 seconds until 120 seconds, back projection on the palmar/plantar 0°. The degree of vascular filling was greater in group 2, independent of venous access, member or moment. There was no significant difference in the degree of radiopacity of radiographic images when compared to the venous access, time and a member of both groups. We conclude that administration of 20 ml of contrast showed better filling and radiopacity, with no difference between 20 and 120 seconds after contrast administration in independent radiographic quality venous access
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Gravena, Kamila [UNESP]. "Respostas inflamatórias sistêmica, do casco e do cólon menor submetido à distensão em equinos." Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/121867.
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000814302.pdf: 1407031 bytes, checksum: 9de8d1bc0d71b1356605f4186396018e (MD5)A relação entre a ocorrência de cólica e a manifestação da laminite tem sido estudada por inúmeros pesquisadores. Alguns trabalhos com indução experimental de laminite demonstram a participação da resposta inflamatória na origem da afecção. Devido a isso, buscou-se entender a resposta inflamatória de equinos tanto em nível sistêmico, como local, no intestino e no tecido dérmico/epidérmico podal, assim como determinar possíveis alterações clínicas e laboratoriais após obstrução intraluminal do cólon menor. Para isso, foram utilizados oito equinos adultos, hígidos, com idade entre oito e 14 anos. Estes foram submetidos a celiotomia associada a dilatação intraluminal do cólon menor, simulando o abdômen agudo por enterólito. Biópsias de casco e cólon menor foram efetuadas neste momento e, também, foram colhidas amostras de sangue e líquido peritoneal. Após quatro horas de obstrução intraluminal, o balão foi desinflado e realizou-se novas biópsias de casco e cólon menor e colheu-se novamente amostras de sangue e líquido peritoneal. Durante o pós-cirúrgico, os animais foram monitorados por meio de exames físicos em intervalos de 12 horas. Após 72 horas da desobstrução foram efetuadas as últimas coletas de casco, cólon, sangue e líquido peritoneal. As amostras de sangue e líquido peritoneal foram utilizadas para avaliação hematológicas e para a determinação da expressão gênica das IL-1β, IL-6, IL-8, IL-10 e TNF-α por meio da PCR em tempo real e para quantificar as IL-1β, IL-6 e TNF-α por ELISA sanduiche. Os tecidos obtidos nas biópsias foram processados para avaliação histológica e determinação das IL-1β, IL-6, IL-8, IL-10 e TNF-α pela técnica da PCR em tempo real. Os valores obtidos nas avaliações hematológicas diferiram (p<0,05) dos valores basais, principalmente após quatro horas de obstrução (M4) e após 12 horas de pós-cirúrgico (M12). As citocinas avaliadas por ...
Numerous researchers have studied the relationship between colic and laminitis manifestation. Some studies with experimentally induced laminitis demonstrated involvement of the inflammatory response in the development of the disease. Therefore, the aim of this study was to investigate systemic and local inflammatory response, in intestines and hoof dermal and epidermal tissues, as well as to determine clinical and laboratory changes after intraluminal obstruction in small colon. For this purpose, eight healthy adult horses were submitted to a celiotomy to induce intraluminal distension of the small colon simulating acute abdomen by enterolith. Hoof and small colon biopsies were made at this time, and samples of blood and peritoneal fluid were collected. After four hours of intraluminal obstruction, the ball was deflated and new biopsies of hoof and small colon collected and blood and peritoneal fluid sampled. During the postoperative, animals were monitored by physical examinations every 12 hours. After 72 hours of ball removal, the last biopsies of hoof, colon, blood and peritoneal fluid were collected. The samples of blood and peritoneal fluid were used for hematological evaluation, for determining gene expression of IL- 1β, IL-6, IL-8, IL-10 and TNF-α by real-time PCR and to quantify IL-1β , IL- 6 and TNF-α by sandwich ELISA. Tissues obtained from biopsies were processed for histological evaluation and determination of IL-1β, IL-6, IL-8, IL- 10 and TNF-α by real time PCR. The values obtained in hematological evaluation differ (p<0.05) from baseline, especially four hours after obstruction (M4) and after 12 hours of postoperative (M12). Cytokines concentrations in peritoneal fluid increased in M4, returned to baseline within M72 and remained unchanged in serum samples. Regarding gene expression in blood, there was no significant difference. In peritoneal fluid, all cytokines differed from baseline. Concerning the colon, the ...
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Gravena, Kamila. "Respostas inflamatórias sistêmica, do casco e do cólon menor submetido à distensão em equinos /." Jaboticabal, 2014. http://hdl.handle.net/11449/121867.
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Orientador: José Corrêa de Lacerda NetoCoorientador: Juliana Regina Peiró
Banca: Antonio Carlos Alessi
Banca: Paulo Alescio Canola
Banca: Rafael Resende Faleiros
Banca: Luiz Claudio Nogueira Mendes
Resumo: A relação entre a ocorrência de cólica e a manifestação da laminite tem sido estudada por inúmeros pesquisadores. Alguns trabalhos com indução experimental de laminite demonstram a participação da resposta inflamatória na origem da afecção. Devido a isso, buscou-se entender a resposta inflamatória de equinos tanto em nível sistêmico, como local, no intestino e no tecido dérmico/epidérmico podal, assim como determinar possíveis alterações clínicas e laboratoriais após obstrução intraluminal do cólon menor. Para isso, foram utilizados oito equinos adultos, hígidos, com idade entre oito e 14 anos. Estes foram submetidos a celiotomia associada a dilatação intraluminal do cólon menor, simulando o abdômen agudo por enterólito. Biópsias de casco e cólon menor foram efetuadas neste momento e, também, foram colhidas amostras de sangue e líquido peritoneal. Após quatro horas de obstrução intraluminal, o balão foi desinflado e realizou-se novas biópsias de casco e cólon menor e colheu-se novamente amostras de sangue e líquido peritoneal. Durante o pós-cirúrgico, os animais foram monitorados por meio de exames físicos em intervalos de 12 horas. Após 72 horas da desobstrução foram efetuadas as últimas coletas de casco, cólon, sangue e líquido peritoneal. As amostras de sangue e líquido peritoneal foram utilizadas para avaliação hematológicas e para a determinação da expressão gênica das IL-1β, IL-6, IL-8, IL-10 e TNF-α por meio da PCR em tempo real e para quantificar as IL-1β, IL-6 e TNF-α por ELISA sanduiche. Os tecidos obtidos nas biópsias foram processados para avaliação histológica e determinação das IL-1β, IL-6, IL-8, IL-10 e TNF-α pela técnica da PCR em tempo real. Os valores obtidos nas avaliações hematológicas diferiram (p<0,05) dos valores basais, principalmente após quatro horas de obstrução (M4) e após 12 horas de pós-cirúrgico (M12). As citocinas avaliadas por ...
Abstract: Numerous researchers have studied the relationship between colic and laminitis manifestation. Some studies with experimentally induced laminitis demonstrated involvement of the inflammatory response in the development of the disease. Therefore, the aim of this study was to investigate systemic and local inflammatory response, in intestines and hoof dermal and epidermal tissues, as well as to determine clinical and laboratory changes after intraluminal obstruction in small colon. For this purpose, eight healthy adult horses were submitted to a celiotomy to induce intraluminal distension of the small colon simulating acute abdomen by enterolith. Hoof and small colon biopsies were made at this time, and samples of blood and peritoneal fluid were collected. After four hours of intraluminal obstruction, the ball was deflated and new biopsies of hoof and small colon collected and blood and peritoneal fluid sampled. During the postoperative, animals were monitored by physical examinations every 12 hours. After 72 hours of ball removal, the last biopsies of hoof, colon, blood and peritoneal fluid were collected. The samples of blood and peritoneal fluid were used for hematological evaluation, for determining gene expression of IL- 1β, IL-6, IL-8, IL-10 and TNF-α by real-time PCR and to quantify IL-1β , IL- 6 and TNF-α by sandwich ELISA. Tissues obtained from biopsies were processed for histological evaluation and determination of IL-1β, IL-6, IL-8, IL- 10 and TNF-α by real time PCR. The values obtained in hematological evaluation differ (p<0.05) from baseline, especially four hours after obstruction (M4) and after 12 hours of postoperative (M12). Cytokines concentrations in peritoneal fluid increased in M4, returned to baseline within M72 and remained unchanged in serum samples. Regarding gene expression in blood, there was no significant difference. In peritoneal fluid, all cytokines differed from baseline. Concerning the colon, the ...
Doutor
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Pfeifer, João Pedro Hübbe. "Padronização da cultura de queratinócitos lamelares de casco equino." Botucatu, 2017. http://hdl.handle.net/11449/150969.
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Orientador: Ana Liz Garcia AlvesResumo: Os queratinócitos são células presentes na epiderme, constituída pelo epitélio estratificado pavimentoso queratinizado. Estas células organizam-se em camadas de diferentes estágios de maturação celular (camada basal ou germinativa, espinhosa, granulosa, lúcida e córnea) e tem a função de revestimento desses tecidos. Diversos estudos buscam elucidar e caracterizar tecidos hígidos de origem epitelial, como pele, olhos e casco, para que possam identificar os mecanismos de desenvolvimento de enfermidades nesses tecidos. O casco equino é formado por epiderme em diferentes estágios de queratinização, subdivididos em estrato externo ou parede do casco, estrato médio e estrato interno, nesse último estão localizadas as lâminas epidermais primárias (LEP) e secundárias (LES) onde os queratinócitos estão presentes junto a membrana basal (transição de epiderme e derme, junção que faz a adesão do casco com a falange distal). É notória a importância do casco na saúde dos equinos, mas o conhecimento em nível celular é pouco entendido. Estudos envolvendo o cultivo de queratinócitos equinos são escassos. Sabe-se que o desenvolvimento de cultivos de queratinócitos in vitro é uma condição para estudos sobre a biologia molecular, crescimento e diferenciação celular. Alguns métodos já estão estabelecidos, como para cultivo de queratinócitos de pele, mas poucas metodologias são encontradas para queratinócitos lamelares. O objetivo desse estudo, foi padronizar o cultivo de queratinócitos provenient... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The keratinocytes are cells presented in the epidermis, constituted by the stratified keratinized squamous epithelium. These cells organized in layers of different stages of cell maturation (basal or germinative, prickly, granular, lucid and corneal layers) and have a tissue coating function. Several studies seek to elucidate and characterize healthy tissues of epithelial origin, such as skin, eyes and hoof, so that they can identify the mechanisms of development of diseases in these tissues. The equine hoof is composed of epidermis at different stages of keratinization, subdivided into external stratum, middle stratum and internal stratum, in which the primary epidermal lamellae (PEL) and secondary epidermal (SEL) are located and where keratinocytes are present along the basement membrane (Transition of the epidermis and dermis, which joins the hoof to the distal phalanx). It is evident the importance of the hoof health of horses, but the knowledge at the cellular level is poorly understood. Studies involving the culture of equine keratinocytes are scarce. The development of keratinocyte cultures in vitro is a condition for studies on molecular biology, cell growth and differentiation. Some methods are already established, such as for culture of skin keratinocytes, but few methodologies are found for lamellar keratinocytes. The aim of this study was to standardize the cultivation of keratinocytes from equine hoof, aiming future associate with the study of regenerative medici... (Complete abstract click electronic access below)
Mestre
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Karam, Jean-Pierre. "Développement de microcarriers pharmacologiquement actifs transportant des cellules souches et libérant des facteurs de croissance pour l’ingénierie tissulaire cardiaque." Angers, 2012. http://tel.archives-ouvertes.fr/tel-00991568.
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La thérapie cellulaire constitue une stratégie prometteuse dans le traitement de l'infarctus du myocarde. Afin de mieux contrôler la survie, la différenciation et l'intégration des cellules greffées, nous avons tenté une approche d'ingénierie tissulaire en associant les cellules à un microvecteur comportant une surface biomimétique et pouvant libérer un facteur de croissance (FC), les microcarriers pharmacologiquement actifs (MPA). Parmi les cellules utilisées dans une telle approche, les cellules souches adultes dérivées du tissu adipeux (ADSC) ne soulèvent pas de problèmes d'ordre éthique et permettent de réaliser des greffes autologues. Ces cellules sont largement étudiées pour la régénération de nombreux tissus en vertu de leurs propriétés immuno-modulatrices, de leur capacité à sécréter des FC et chémokines, mais également de leur large potentiel de différenciation. Dans une première étape, nous avons étudié l'effet des molécules de la matrice extracellulaire et des MPA sur la différentiation en cardiomyocytes des ADSC en présence d'un cocktail de FC. Nous avons ainsi pu observer que l'apport du cocktail de FC permettait aux cellules de s'engager dans la voie de différentiation cardiaque après 2 semaines. En comparant l'effet de la laminine (LM) et de la fibronectine sur cette différentiation, nous avons pu observer que la LM permettait d'induire une différentiation dans une cellule plus mature et que ceci était potentialisée par un enrichissement du milieu en TGF!1. Finalement, l'apport de MPA recouverts de LM favorisait une différentiation plus rapide des cellules en présence du cocktail. Les MPA peuvent également libérer un facteur de croissance de manière prolongée au cours du temps. Par conséquent, nous avons encapsulé 3 protéines, le VEGF, le HGF et l'IGF-1, et d'étudier leur effet sur les comportement des ADSC. Nous avons ainsi pu observer que des MPA libérant du HGF et de l'IGF-1 induisaient une différenciation de ADSC dans la voie cardiaque et que cette différentiation était également observée lorsque les complexes ADSCMPA étaient intégrés dans un hydrogel thermosensible. Cependant, nous avons aussi observé que la quantité de protéines libérées à partir des MPA était plus faible dans le gel. Nous avons donc cherché dans une dernière partie à améliorer le profile de libération des protéines à partir des MPA en changeant la composition du polymère. Nous avons ainsi utilisé différents copolymères triblock PLGA-PEG-PLGA pour formuler des microsphères et évaluer leur rôle sur la libération de la protéine mais aussi sur la stabilité de celle-ci durant la dégradation du polymèreCell therapy constitutes a promising strategy for the treatment of myocardial infarction. To better control the survival, the differentiation and the integration of the grafted cells, we have used a tissue-engineering approach associating the cells with a microvector comprising a biomimetic surface and able to release a growth factor (GF), the pharmacologically active microcarriers (PAM). Among the cell used for such approach, adipose-derived stem cells (ADSC) do not raise ethical concerns/issues and allow autologous transplantation. These cells are widely studied for the regeneration of various tissues due to their immunoregulatory properties, their potential to secrete GFs and chemokines but also their large potential of differentiation. In a first step, we have investigated the effect of extracellular matrix molecules and PAMs on ADSCs differentiation into cardiomyocytes in combination with a GF cocktail. We have thus observed that the GFs cocktail allowed cell commitment into the cardiac lineage after 2 weeks. Comparing the effects of the laminin (LM) and fibronectin (FN) on this differentiation, we found that LM allowed ADSCs differentiation into a more mature phenotype. Moreover, the enrichment of the GF cocktail with TGF!1 potentiated the LM effect. Finally, providing PAM covered with LM allowed an earlier differentiation into cardiac lineage in combination with the cocktail. PAMs can release a GF in a prolonged manner. Consequently, we encapsulated 3 proteins, the VEGF, the HGF and the IGF-1, and assessed their effect on ADSCs behavior. We observed that PAMs releasing HGF and IGF-1 induced ADSCs cardiomyogenic differentiation. Moreover, we also observed ADSCs cardiac differentiation markers expression, when ADSCPAMs complexes are integrated within a thermosensitive hydrogel. However, we also found that the amount of protein released from PAMs decreased within the gel. In a last part we have sought to improve protein release profile from PAMs changing polymer composition. So, we used various triblock copolymers of PLGA-PEG-PLGA to formulate microspheres and then evaluated their role on protein release but also on protein stability during polymer degradation
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Ringeard, Sophie. "Role des integrines dans la reaction stromale des tumeurs coliques." Nantes, 1995. http://www.theses.fr/1995NANT02VS.
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Loréal, Olivier. "Effets de la surcharge en fer sur la fibrogenese hepatique." Rennes 1, 1993. http://www.theses.fr/1993REN1B007.
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Ould, Abeih Mohamed Barikalla. "Etude de la protéine ribosomale SA humaine : un récepteur membranaire de la laminine, d'anticancéreux et d'agents infectieux." Paris 7, 2012. http://www.theses.fr/2012PA077115.
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La Protéine Ribosomale SA humaine (RPSA ou LamRl) est une protéine multifonctionnelle qui appartient au ribosome mais est aussi récepteur membranaire pour la laminine, des facteurs de croissance, le prion, des microorganismes pathogènes, des toxines et l'anticancéreux épigallocatechin gallate (EGCG). Elle est utilisée comme marqueur des métastases. RPSA inclut un domaine N-terminal, qui est homologue aux Protéines Ribosomales S2 procaryotes, et une extension C-terminale, qui est conservée chez les vertébrés. La structure de son domaine-N a été résolue à partir de cristaux obtenus à 17 °C, celle de son domaine-C restait inconnue. Nous avons produit chez Escherichia coli et purifié la protéine RPSA complète et ses domaines-N et -C. Nous avons caractérisé les états de repliement de ces protéines recombinantes par spectrométries de fluorescence et de dichroïsme circulaire, en association avec des analyses quantitatives de leurs équilibres de dépliement, induits par l'urée ou la chaleur. Les résultats ont montré que le domaine-N se dépliait suivant un équilibre à trois états. L'intermédiaire monomérique était prédominant à la température corporelle de 37 °C. Il existait aussi pour la protéine RPSA complète et fixait TANS, une petite molécule fluorescente. Le domaine-C était dans un état intrinsèquement désordonné. Nous avons montré par des méthodes immunochimiques et spectrofluorimétriques que les domaines-N et -C interagissaient faiblement entre eux, que les deux domaines fixaient la laminine avec les mêmes affinités mais que seul le domaine-N fixait l'EGCG. La plasticité structurale de RPSA pourrait être importante pour ses fonctions multiplesThe human Ribosomal Protein SA (RPSA or LamRl) is a multilocus protein, present in most cellular compartments. It is a multifunctional protein, which belongs to the ribosome but is also a membrane receptor for laminin, growth factors, prion, microorganisms, toxins and the anticarcinogen epigallocatechin-gallate (EGCG). It contributes to the crossing of the blood-brain barrier by pathogens, and is used as a marker of metastasis. RPSA includes an N-terminal domain, which is homologous to the prokaryotic Ribosomal Proteins S2, and a C-terminal extension, which is conserved in vertebrates. The structure of its N-domain has been solved from crystals grown at 17 °C whereas that of the C-domain remained unknown. We produced in Escherichia coli and purified the full-length RPSA and its N- and C-domains. We characterized the folding states of these recombinant proteins by methods of fluorescence and circular dichroism spectrometry, in association with quantitative analyses of their unfolding equilibria, induced with heat or urea. The necessary equations were derived from first principles. The results showed that the N-domain unfolded according to a three state equilibrium. The monomeric intermediate was predominant at the body temperature of 37 °C. It also existed in the full-length RPSA and bound ANS, a small fluorescent molecule. The C-domain was in an intrinsically disordered state. We showed by immunochemical and spectrofluorimetric methods that the recombinant N- and C-domains weakly interacted together, that both domains bound laminin with similar affinities whereas only the N-domain bound EGCG. The structural plasticity of RPSA could be important for its multiple functions
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BAUDOIN, CHRISTIAN. "La laminine-5 : une nouvelle proteine d'adhesion impliquee dans les epidermolyses bulleuses jonctionnelles. caracterisation genetique et fonctionnelle." Nice, 1994. http://www.theses.fr/1994NICE4784.
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Nous avons identifie une nouvelle proteine d'adhesion specifique des systemes epitheliaux qui n'est pas detectee dans la peau de la plupart des patients atteints d'epidermolyse bulleuse jonctionnelle gravis (ebj herlitz), une genodermatose caracterisee par le decollement de l'epiderme et du derme. Cette sialoglycoproteine d'environ 400 kda est constituee de 3 sous-unites de 105 kda (gamma 2), 140 (beta3) et 165 kda (alpha3). L'isolement et la caracterisation de clones codant pour les sous-unites gamma2 et alpha3 nous ont revele que cette proteine est une isolaminine avec des domaines n- et c-terminaux tronques et une sequence en acides amines tres divergente de celles des laminines isolees a ce jour. Dans le but de mettre en evidence un lien entre l'expression alteree de la laminine-5 et les ebj herlitz, une analyse systematique du taux d'expression des genes codant pour les trois sous-unites de la proteine a ete entreprise. Dans tous les cas etudies, un defaut d'expression d'au moins une des trois sous-unites est mis en evidence, suggerant que chez les patients ebj herlitz les genes codants pour la laminine-5 sont porteurs d'alterations genetiques. Le sequencage des adnc de la sous-unite gamma2 obtenue d'un patient atteint d'ebj herlitz nous a permis la detection d'une mutation non-sens sur le gene correspondant lamc2. Une expression forte et transitoire de la chaine alpha3 dans le plancher du tube neural, lorsque les neurones moteurs migrent et se polarisent, nous revele que la laminine-5 pourrait avoir d'autres roles que l'adhesion cellulaire et la cohesion des systemes epitheliaux
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Le, Bellego Frédérique. "Rôle de la laminine dans le contrôle des fonctions des cellules de granulosa dans l'ovaire de brebis." Tours, 2002. http://www.theses.fr/2002TOUR4007.
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In vivo dans les follicules ovariens de brebis, la laminine (LN) est localisée au niveau de la lame basale et l'intégrine α6β1 dans les cellules de granulosa (CG). In vitro, des cultures de CG sur LN améliorent la survie, stimulent la prolifération, diminuent la sécrétion d'oestradiol (E2) et augmentent celle de progestérone (P4). L'intégrine α6β1 serait le médiateur essentiel des actions de la LN. L'ajout d'anticorps (Ac) anti-α6 dans ces cultures modifie la forme des CG, réduit la prolifération et la survie, augmente la sécrétion d'E2 et diminue celle de P4. L'arrondissement des CG par la cytochalasine D reproduit les effets de l'Ac anti-α6. Des cultures de CG sur mélange LN/peptides RGD avec l'Ac anti-α6 montrent que la prolifération et la survie sont liées à la forme des CG alors qu'il semble y avoir un découplage entre forme cellulaire et stéroi͏̈dogénèse. L'action de la LN sur les CG, via α6β1, met en jeu différentes voies de signalisation dont celle, entre autres, du cytosquelette.
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Bignon, Christophe. "Contribution à l'étude du gène d'une protéine intervenant dans un mécanisme d'adhésion des cellules à la laminine." Aix-Marseille 2, 1991. http://www.theses.fr/1991AIX22014.
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La laminine est un composant majeur des membranes basales. Cette glycoproteine de haut poids moleculaire (pm) joue un role important dans certains evenements cellulaires incluant la metastase des cellules cancereuses. Parmi les proteines fixant specifiquement la laminine a la surface des cellules, un recepteur (rl) de soixante-sept kilo-dalton (kd) a ete associe a un potentiel metastatique plus eleve des cellules cancereuses. Dans une premiere partie, nous avons etudie le bien-fonde de cette hypothese. Nous avons trouve que des lignees b non malignes presentaient un niveau de mrna de rl plus eleve que les cellules b normales. Les cellules malignes du sang presentent ce meme caractere. Il semble donc que c'est plutot l'immortalisation et/ou la proliferation cellulaire non controlee qui soit associee a la derepression du gene que l'acquisition du phenotype malin. La seule proteine membranaire specifiquement reconnue par nos anticorps anti-rl a un pm de quarante-cinq kd et non soixante-sept. Elle intervient aussi dans l'attachement des cellules a la fibronectine. Cette intervention pourrait n'etre pas directe, et ce dans les deux cas. Le rl forme une famille de retroposons chez les mammiferes. Nous avons isole un nouveau mrna dont le gene suit la meme conservation phylogenique que le rl
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Jivkov, Ivo. "La chaîne de laminine α1 dans la différenciation cellulaire et son rôle activateur dans la tumorigenèse intestinale." Strasbourg 1, 2008. http://www.theses.fr/2008STR13113.
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Canello, Vinícius Athaydes. "Expressão das metaloproteinases e morfologia do tecido laminar do casco de equinos submetidos à obstrução intra-luminal do cólon menor /." Jaboticabal, 2013. http://hdl.handle.net/11449/89175.
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Orientador: José Corrêa de Lacerda NetoCoorientador: Rita de Cássia de Lima Sampaio
Banca: Lina Maria Wehrle Gomide
Banca: Deborah Penteado Martins Dias
Resumo: Diferentes estudos foram realizados buscando relacionar a ocorrência de distúrbios gastrointestinais e a manifestação da laminite. Neste contexto, destacou-se a participação de processos inflamatórios e sua relação com a expressão de metaloproteinases (MMP), que sabidamente promovem a degradação da membrana basal no tecido laminar do casco. O presente estudo objetivou avaliar a expressão das MMP-2 e MMP-9 no tecido laminar, bem como sua integridade celular por avaliação histológica, em equinos submetidos à obstrução intraluminal do cólon menor. Oito equinos adultos hígidos foram avaliados. Realizou-se laparotomia e obteve-se obstrução do cólon menor utilizando-se balão de vinil inserido no lúmem intestinal. O balão foi inflado à pressão de 80 mmHg e a obstrução foi mantida por 4 horas, simulando a presença de um enterólito. Foram realizadas biópsias pelo acesso transmural-dorsal para obtenção de tecido laminar podal em três momentos (T): antes da obstrução (T0), imediatamente após desobstrução (T4) e após 72 horas da desobstrução (T72). As amostras foram submetidas à análise zimográfica e histológica. Segundo a zimografia, não observou-se alterações nos valores de MMP-2 e MMP-9 em T4 e T72. Entretanto, observou-se o surgimento de lesões no tecido laminar analisado microscopicamente (T4 e T72). Concluiu-se que as alterações inflamatórias decorrentes da obstrução do cólon menor levaram ao surgimento de lesões no tecido laminar podal. Porém, a inflamação promovida não foi suficiente para ocasionar alteração na expressão das MMP-2 e MMP-9 no tecido avaliado
Abstract: A number of studies have been conducted in order to relate gastrointestinal disorders and laminitis occurrence in horses. In this issue, special attention has been given to the role of inflammatory process and its relation with metalloproteinase (MMP) expression, which may lead to basement membrane degradation in the hoof laminar tissue. The purpose of the present study was to investigate MMP-2 and MMP-9 expression in the laminar tissue, as well as its cellular integrity assessed histologically, in horses subjected to intraluminal obstruction of the small colon. Eight healthy horses were evaluated. A laparotomy was performed and the small colon obstruction was achieved by the use of a vinyl ball inserted into the intestinal lumen. The ball was insufflated at 80 mmHg and the obstruction was sustained for 4 hours, mimicking an enterolithiasis. Through a dorsal-transmural access, podal laminar tissue samples were biopsied at three time-points: before obstruction (T0), immediately after desobstruction (T4) and after 72 hours from desobstruction. Samples were subjected to zymographic and histological analysis. The zymography did not reveal changes in MMP-2 and MMP-9 values at T4 and T72. However, microscopic evaluation showed laminar tissue lesions (T4 and T72). In conclusion, the inflammatory changes followed by the small colon obstruction led to podal laminar tissue damage. However, the inflammation was not sufficient to induce changes in MMP-2 and MMP-9 expression in the evaluated tissue
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Canello, Vinícius Athaydes [UNESP]. "Expressão das metaloproteinases e morfologia do tecido laminar do casco de equinos submetidos à obstrução intra-luminal do cólon menor." Universidade Estadual Paulista (UNESP), 2013. http://hdl.handle.net/11449/89175.
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canello_va_me_jabo.pdf: 467302 bytes, checksum: dd80810c8be22a5e0ad8934c12d77552 (MD5)Diferentes estudos foram realizados buscando relacionar a ocorrência de distúrbios gastrointestinais e a manifestação da laminite. Neste contexto, destacou-se a participação de processos inflamatórios e sua relação com a expressão de metaloproteinases (MMP), que sabidamente promovem a degradação da membrana basal no tecido laminar do casco. O presente estudo objetivou avaliar a expressão das MMP-2 e MMP-9 no tecido laminar, bem como sua integridade celular por avaliação histológica, em equinos submetidos à obstrução intraluminal do cólon menor. Oito equinos adultos hígidos foram avaliados. Realizou-se laparotomia e obteve-se obstrução do cólon menor utilizando-se balão de vinil inserido no lúmem intestinal. O balão foi inflado à pressão de 80 mmHg e a obstrução foi mantida por 4 horas, simulando a presença de um enterólito. Foram realizadas biópsias pelo acesso transmural-dorsal para obtenção de tecido laminar podal em três momentos (T): antes da obstrução (T0), imediatamente após desobstrução (T4) e após 72 horas da desobstrução (T72). As amostras foram submetidas à análise zimográfica e histológica. Segundo a zimografia, não observou-se alterações nos valores de MMP-2 e MMP-9 em T4 e T72. Entretanto, observou-se o surgimento de lesões no tecido laminar analisado microscopicamente (T4 e T72). Concluiu-se que as alterações inflamatórias decorrentes da obstrução do cólon menor levaram ao surgimento de lesões no tecido laminar podal. Porém, a inflamação promovida não foi suficiente para ocasionar alteração na expressão das MMP-2 e MMP-9 no tecido avaliado
A number of studies have been conducted in order to relate gastrointestinal disorders and laminitis occurrence in horses. In this issue, special attention has been given to the role of inflammatory process and its relation with metalloproteinase (MMP) expression, which may lead to basement membrane degradation in the hoof laminar tissue. The purpose of the present study was to investigate MMP-2 and MMP-9 expression in the laminar tissue, as well as its cellular integrity assessed histologically, in horses subjected to intraluminal obstruction of the small colon. Eight healthy horses were evaluated. A laparotomy was performed and the small colon obstruction was achieved by the use of a vinyl ball inserted into the intestinal lumen. The ball was insufflated at 80 mmHg and the obstruction was sustained for 4 hours, mimicking an enterolithiasis. Through a dorsal-transmural access, podal laminar tissue samples were biopsied at three time-points: before obstruction (T0), immediately after desobstruction (T4) and after 72 hours from desobstruction. Samples were subjected to zymographic and histological analysis. The zymography did not reveal changes in MMP-2 and MMP-9 values at T4 and T72. However, microscopic evaluation showed laminar tissue lesions (T4 and T72). In conclusion, the inflammatory changes followed by the small colon obstruction led to podal laminar tissue damage. However, the inflammation was not sufficient to induce changes in MMP-2 and MMP-9 expression in the evaluated tissue
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Bouzon, Madeleine. "Contribution à l'étude des mécanismes cellulaires d'adhésion et de migration sur la laminine : une protéine des membranes basales." Aix-Marseille 2, 1990. http://www.theses.fr/1990AIX22021.
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La laminine, glycoproteine des membranes basales, constitue un substrat d'adhesion et de migration cellulaire. Pour etudier les relations structure-activite de la laminine, deux fragments distincts p1 et e8 ont ete prepares par proteolyse enzymatique. Leurs proprietes d'adhesion et de migration ont ete etudiees. Les resultats suggerent que: i) les fragments e8 et p1 interagissent avec des recepteurs membranaires differents; ii) l'expression et/ou la fonctionnalite de ces recepteurs est variable d'une lignee a l'autre; iii) la stimulation de la mobilite cellulaire resulte d'une interaction specifique substrat/cellule; iv) les cellules interagissent principalement avec le domaine e8 sur la laminine native. Le capping de la laminine liee et le maintien d'un pool de recepteurs libres, caracterises a la surface des rms s4 par une technique de double marquage en immunofluorescence, permettent de proposer un modele de recirculation des sites recepteurs de la laminine necessaire a la migration de ces cellules. Les cellules b16 f1 acquierent des morphologies distinctes sur la laminine, e8 et p1, definies par les parametres de forme et de surface quantifies par traitement d'images. La lectine wga appliquee au substrat inhibe totalement l'etalement des cellules b16f1 sur la laminine et partiellement sur le fragment e8. La deglycosylation par l'endoglycosidase f de la laminine et du e8 n'a pas d'effet sur l'etalement. En revanche, les carbohydrates du p1 semblent impliques dans ce processus. Les recepteurs membranaires induisant l'etalement cellulaire sur la laminine sont donc distincts de ceux impliques dans l'attachement; l'effet inhibiteur de la wga sur l'etalement semble du a un encombrement sterique et non a un effet direct. Les developpements ulterieurs de ce travail pourront s'orienter vers la caracterisation des recepteurs specifiques des deux etapes de l'adhesion, attachement et etalement, et vers l'etud
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André, Frédéric. "Expression d'isoformes de la laminine en relation avec la polarisation et la differenciation de cellules epitheliales en culture." Aix-Marseille 3, 1995. http://www.theses.fr/1995AIX30052.
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Le travail presente ici est une contribution a l'etude des relations entre l'expression d'isoformes de laminine et le degre de differenciation et de polarisation des cellules epitheliales en culture (culture primaire de cellules thyroidiennes, lignees d'origine hepatique). Il a permis d'etablir les points suivants. (1) les thyreocytes en culture synthetisent et deposent la laminine-2. Nous montrons pour la premiere fois la chaine alpha2 sous sa forme integrale de 380 kda. Elle represente la forme mature de la molecule dans la thyroide. (2) l'analyse du metabolisme de la laminine-2 demontre clairement que dans ce systeme cellulaire la laminine-2 est degradee. Les mecanismes responsables de sa degradation sont dependants de l'organisation cellulaire. L'inhibition de la degradation de laminine-2 par la leupeptine dans les structures folliculaires indique qu'une protease a cysteine participe a cette degradation. (3) toutes les lignees d'origine hepatique etudiees, quel que soit leur degre de differenciation et de polarite synthetisent les laminines-2 et -4, formes moleculaires trouvees dans le foie in vivo. (4) l'analyse des messagers suggere pour la chaine alpha2 la presence d'un epissage alternatif ce qui n'a encore jamais ete montre pour les chaines de laminine. Ceci laisse presager une microheterogeneite au niveau de la proteine. (5) dans les deux modeles etudies il n'existe pas de relation nette entre l'expression d'isoformes de laminine et le degre de differentiation et de polarite des cellules en culture
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Schminke, Boris [Verfasser]. "Laminine während der Knorpelentwicklung, im gesunden Knorpel und deren Bedeutung für die Pathogenese der Osteoarthritis des Menschen / Boris Schminke." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/1231076232/34.
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Bernard-Jaoul, Adrien. "Identification et caractérisation de l'intéraction du Pigment Epithelium-Derived Factor (PEDF) avec le récepteur de la laminine 37LRP/67LR." Paris 6, 2009. http://www.theses.fr/2009PA066726.
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DE, ARCANGELIS DIEBOLD ADELE. "Definition du role de la chaine 1 de la laminine-1 dans la differenciation intestinale et la cancerogenese colique." Université Louis Pasteur (Strasbourg) (1971-2008), 1997. http://www.theses.fr/1997STR13252.
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Le developpement et la differenciation intestinale dependent d'interactions etroites entre cellules epitheliales et mesenchymateuses (stromales) mediees par les elements de la lame basale. Cette structure hautement organisee est constituee essentiellement de collagene de type iv, de laminine-1, de nidogene et de perlecan. Dans le present travail, l'implication de la laminine-1 et plus particulierement de la chaine 1 constitutive a ete analysee afin de determiner son role dans la differenciation et dans la tumorigenese intestinale. Les points essentiels qui se degagent de ce travail sont les suivants : 1) l'expression de la chaine 1 est determinante pour la production endogene de laminine-1 et la formation d'une lame basale. Ces donnees sont issues de l'analyse : a) de lignees cancereuses coliques humaines presentant des caracteres phenotypiques differents en coculture, et b) de cellules epitheliales caco-2 dans lesquelles la chaine 1 a ete inhibee de maniere endogene par une strategie antisens. 2) l'absence de toute structure organisee de type lame basale suite a l'inhibition specifique de la chaine 1 conduit a des alterations de certains aspects de la differenciation epitheliale (desorganisation structurale des microvillosites, absence d'une enzyme digestive : la saccharase). 3) l'absence de chaine 1 dans les cellules cancereuses coliques entraine une diminution de la tumorigenicite des cellules apres injection sous-cutanee a la souris nude. Parallelement, la lame basale a l'interface cellules cancereuses/stroma est fortement perturbee conjointement a des modifications des recepteurs de type integrine (64 essentiellement). Les caracteres d'agressivite de ces cellules testes par greffe orthotopique ne sont, par contre, que faiblement modifies. 4) l'utilisation d'une autre lignee cellulaire, les cellules ht29, suggere une regulation propre a chaque modele liee vraisemblablement a l'existence d'isoformes de laminine. En effet, la reintroduction de la chaine 1 de la laminine dans ces cellules n'a pas permis a elle seule de modifier ni la synthese globale de laminine ni la differenciation epitheliale.