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1
Planello, Aline Cristiane 1980. "Analise de polimorfismos no promotor dos genes MMP1, MMP3 e MMP9 na desordem da articulação temporomandibular." [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288534.
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Orientador: Ana Paula de Souza PardoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Objetivo: As Metaloproteinases da Matriz ( MMPs) são enzimas que degradam a matriz extracelular (MEC) e tem sido associadas às desordens temporomandibulares (DTM). Nós investigamos a freqüência dos -1607 1G/2G MMP1 polimorfismo (rs1799750), -1171 6A/5A MMP3 polimorfismo (rs3025058) e -1562 C/T MMP9 polimorfismo (rs3918242) em indivíduos com sinais de degeneração da ATM, diagnosticados por exame de imagem, a fim de analisar a associação desses polimorfismos e a DTM. Métodos: A população estudada foi composta por 115 indivíduos diagnosticados por exame de imagem (grupo DTM) e 117 controles. Os polimorfismos genéticos foram determinados por PCR/RFLP. Resultados: A freqüência do genótipo 2G/2G no gene MMP1 foi significantemente mais alta no grupo DTM do que no grupo Controle (p = 0.008). O genótipo 2G/2G no grupo DTM mostrou um risco aumentado para a DTM com um OR = 2.25 ( 95% IC = 1.26 - 3.99) quando comparado com os genótipo 1G/2G e 1G/1G. A freqüência dos alelos do gene MMP1 não mostrou diferença significativa entre os grupos (p > 0.05). A distribuição dos genótipos e alelos dos genes MMP3 e MMP9 não mostrou diferença significativa (p > 0.05). Conclusão: Nossos resultados mostram a associação entre o polimorfismo -1607 MMP1 e a suscetibilidade à DTM
Abstract: Objective. Matrix metalloproteinases (MMPs) degrade extracellular matrix components and have been implicated to play an important role in temporomandibular joint disorder (TMD). We investigated the frequency of -1607 1G/2G MMP1 polymorphism (rs1799750), -1171 6A/5A MMP3 polymorphism (rs3025058) and -1562 C/T MMP9 polymorphism (rs3918242) in individuals with TMJ degeneration diagnosed by image exam in order to analyze the association of these MMPs polymorphisms and TMD. Methods. The studied population comprised 115 TMD individuals diagnosed by image exam and 117 healthy controls. Genotypes were determined using polymerase chain reaction/Restriction fragment length polymorphism PCR/RFLP. Results. The MMP1 2G/2G genotype was significantly higher in the TMD group than in the Control group (p = 0.008). The genotype 2G/2G in the TMD group showed an increased risk to TMD with an OR = 2.25 (95% CI = 1.26 - 3.99) when compared with 1G/2G and 1G/1G genotypes. Analysis of MMP1 allele frequencies showed no significant difference (p > 0.05). The MMP3 and MMP9 genotypes distribution and alleles frequency did not differ between the groups (p > 0.05). Conclusion. Our results report the association of -1607 MMP1 gene polymorphism and increased risk to TMD
Mestrado
Histologia e Embriologia
Mestre em Biologia Buco-Dental
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Mendes, Odete Rodrigues. "Role of MMP2, MMP3 and MMP9 in the development of breast cancer brain and lung metastasis in a syngeneic rat model." Texas A&M University, 2005. http://hdl.handle.net/1969.1/2645.
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In order to study the expression of MMP2, MMP 3 and MMP9 in breast cancer
brain and lung metastasis, we used a syngeneic rat model of distant metastasis of
ENU1564, a carcinogen-induced mammary adenocarcinoma cell line. At six weeks post
inoculation we observed development of micro-metastasis in the brain and lung.
Immunohistochemistry and Western blotting analyses showed that MMP 2, -3 and -9
protein expression is consistently significantly higher in neoplastic brain tissue compared
to normal brain tissue. Lung metastases express abundant MMP2, -3 and -9 in neoplastic
cell cytoplasm. In situ zymography revealed gelatinase activity within the brain
metastasis. Gel zymography showed an increase in MMP2 and MMP3 activity in brain
metastasis. Furthermore, we were able to significantly decrease the development of breast
cancer brain and lung metastasis in animals by treatment with PD 166793, a selective
synthetic MMP inhibitor. In addition, PD 166793 decreased the in vitro invasive cell
behavior of ENU1546. TIMP2 overexpression also decreased the development of breast
cancer lung metastasis in our model. Our results suggest that MMP2, -3 and -9 may be involved in the process of metastasis of breast cancer to the brain and lung.
Because astrocytes have been associated with breast cancer brain metastasis we
evaluated the role of astrocytes and ERK2 pathway in MMP2 up-regulation in BC brain
metastasis. A significant decrease in brain metastases development, and orthotopic tumor
size and weight were observed in animals inoculated with ENU1564-TIMP2 cells. These
were associated with decreased MMP2 activity, as demonstrated by gel zymography. Rat
astrocyte-conditioned media increased expression of MMP2 in ENU15645 cells and
increased in vitro cell invasion of ENU1564 and ENU1564-TIMP2 cells. Blockage of
ERK1/2 phosphorylation by treatment with PD98059 decreased the expression of MMP2
in cancer cells grown in rat astrocyte-conditioned media. We determine that MMP2 plays
a role in in vivo development of breast cancer brain metastases. Additionally, we conclude
that astrocytes are associated with expression of MMP2 in cancer cells via ERK1/2
signaling pathway.
3
Santos, Raphaela Paulo dos. "Análise de polimorfismos nos genes HSD17B1, MMP2 e MMP9 em pacientes com endometriose." Niterói, 2013. https://app.uff.br/riuff/handle/1/4736.
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Universidade Federal Fluminense. Hospital Universitário Antonio Pedro. Centro de Ciências Médicas
A endometriose é definida pela presença de tecido endometrial (glândula e/ou estroma) fora da cavidade uterina, a patologia afeta 10-15% das mulheres em idade reprodutiva, além disso, os sintomas álgicos da doença implicam em impactos econômicos e sociais. A doença apresenta diagnóstico tardio e sua etiologia ainda não foi completamente elucidada, porém, sabe-se que a endometriose possui caráter poligênico e multifatorial. O objetivo do estudo foi avaliar se os polimorfismos no gene HSD17β1 (rs605059), envolvido na síntese de estrogênio, e nos genes MMP2 (rs243865) e MMP9 (rs17576), que atuam no remodelamento da matriz extracelular, estão associados com a endometriose quanto ao risco e o grau de severidade da doença. O estudo do tipo caso-controle foi composto por 231 mulheres, sendo 97 casos e 134 controles. Todas as pacientes do grupo caso possuíam diagnóstico histopatológico para a endometriose. O DNA genômico foi extraído a partir de saliva, e o polimorfismo no gene HSD17β1 foi detectado pela técnica de PCR- Nested seguido de digestão do produto de PCR pela enzima BstUI, os genes MMP2 e MMP9 foram genotipados pela técnica de PCR em Tempo Real. Não foi encontrada diferença estatisticamente significante entre as distribuições genotípicas e alélicas dos genes analisados entre os grupos estudados (p>0,05). Do mesmo modo não foi observada diferença significativa na frequência dos genótipos e alelos entre os diferentes estágios da doença (p>0,05). Os resultados do presente estudo sugerem que os polimorfismos nos genes HSD17β1 (rs605059), MMP2 (rs243865) e MMP9 (rs17576), não estão associado com a endometriose em pacientes brasileiras, mesmo quando avaliado as relações entre graus de severidade variados
Endometriosis is defined by the presence of endometrial tissue (glands and / or stroma) outside the uterine cavity, this condition affects 10-15% of women of reproductive age, in addition, the pain symptoms of the disease involves economic and social impacts. The disease presents late diagnosis and its etiology has not been fully elucidated, but it is known that endometriosis has multifactorial and polygenic character. The aim of the study was to assess whether the polymorphisms in the HSD17β1 (rs605059), involved in estrogen synthesis, and MMP2 genes (rs243865) and MMP9 (rs17576), which act in extracellular matrix remodeling are associated with endometriosis as the risk and severity of the disease. The case-control study consisted of 231 women, with 97 cases and 134 controls. All patients in the case group had histopathological diagnosis for endometriosis. Genomic DNA was extracted from saliva, and HSD17β1 gene polymorphism was detected by Nested-PCR followed by digestion of the PCR product by the enzyme BstUI, MMP2 and MMP9 genes were genotyped by Real Time-PCR. There was no statistically significant difference between the genotypic and allelic distributions of genes analyzed between groups (p> .05). Similarly there was no significant difference in the frequency of genotypes and alleles between different stages of the disease (p> .05). The results of this study suggest that polymorphisms in genes HSD17β1 (rs605059), MMP2 (rs243865) and MMP9 (rs17576), are not associated with endometriosis in Brazilian patients, even when the relations between different degrees of severity were evaluated
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Peres, Juliana Alves. "Avaliação histométrica do reparo de defeito ósseo em calvária de rato após implante de rhMMP-2 ligada à monoleína." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/58/58137/tde-18092012-154340/.
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As metaloproteinases da matriz (MMPs) são enzimas proteolíticas dependentes de zinco que degradam componentes da matriz extracelular, facilitando a remodelação tecidual e a migração celular. MMPs secretadas por osteoclastos exercem papel central na absorção óssea fisiológica e estão também associadas a processos de degradação patológica do osso. No entanto, o papel essencialmente degradador de osso das MMPs, particularmente da MMP-2, vem sendo questionado em anos recentes por estudos que evidenciam sua importância na diferenciação de células da linhagem osteoblástica e na formação de tecido ósseo em cultura. Neste sentido, é possível que a MMP-2 exerça um papel importante na formação de tecido ósseo em processo de reparação. O objetivo do presente trabalho foi investigar a pretensa ação osteo-estimulatória da rhMMP-2 ligada à monoleína (usada como carreador) implantada em defeito confeccionado na calvária de ratos. Foram confeccionados defeitos ósseos unilaterais de 4 mm de diâmetro na calvária de ratos adultos; nos animais controles o defeito ósseo foi mantido com o preenchimento natural de coágulo sanguíneo e nos animais implantados o defeito foi preenchido com monoleína ou com rhMMP-2 ligada à monoleína. Os animais foram eutanasiados após 2 e 4 semanas e a taxa de neoformação óssea foi estimada em cortes histológicos por um método histométrico de contagem diferencial de pontos. A taxa de neoformação óssea foi semelhante nos animais dos grupos controle e monoleína e significativamente maior nos animais do grupo MMP-2, em ambos os períodos analisados. Os resultados permitem concluir que a monoleína não interferiu com o processo reparacional e pareceu eficaz como carreador da rhMMP-2, e adicionam evidências á hipótese da importância da atividade da MMP-2 para a formação óssea, em um modelo experimental in vivo de reparo ósseo.Matrix metalloproteinases (MMPs) are zinc-dependent proteolytic enzymes that degrade extracellular matrix components, facilitating cell migration and tissue remodeling. MMPs secreted by osteclasts are important in the physiological bone resorption as in pathological bone degradation. However, the essentially bone absorbing hole of MMPs, particularly of the MMP-2, has been questioned in recent years by studies that show its importance in osteoblastic cells differentiation and in vitro bone formation. Therefore, the MMP-2 may have also an important hole in reparational bone formation. The purpose of the present study was to investigate the pretense osteostimulatory effect of the rhMMP-2 linked to monoolein (used as a carrier) implanted into rat calvarial defects. Bone defects of 4mm in diameter were created unilaterally in rats calvaria and filled with natural blood clot (control), monoolein or rhMMP-2 linked to monoolein. The animals were killed 2 and 4 weeks postoperatively and the rate of new bone formation was estimated in histological sections by a histometric differential point-counting method. The rate of reparational bone formation was similar in the animals from control and monoolein groups and was significantly greater in the MMP-2 group, in both periods. From the results it may be concluded that monoolein did not interfere with the reparacional process and seemed effective as a rhMMP-2 carrier. In addition, the results add evidence to the importance of MMP-2 activity for bone formation, in an in vivo bone healing experimental model.
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Khvaramze, Shaverdashvili. "MT1-MMP REGULATES MELANOMA METASTASIS THROUGH ACTIVATION OF MMP2/RAC1 AXIS AND INHIBITION OF TUMOR SUPPRESSOR GENE SPRY4." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1438809026.
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Meffert-Laschinski, Philipp [Verfasser], Fabian Alexander [Akademischer Betreuer] Kari, and Matthias [Akademischer Betreuer] Siepe. "Die Charakterisierung von MMP2- und MMP9- Serumspiegeln als prognostische Biomarker bei Aneurysmen der Aorta ascendens." Freiburg : Universität, 2016. http://d-nb.info/1136862838/34.
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Meffert-Laschinski, Philipp [Verfasser], Matthias [Akademischer Betreuer] Siepe, and Fabian Alexander [Akademischer Betreuer] Kari. "Die Charakterisierung von MMP2- und MMP9- Serumspiegeln als prognostische Biomarker bei Aneurysmen der Aorta ascendens." Freiburg : Universität, 2016. http://d-nb.info/1122743033/34.
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Stott, Holly Rosannah. "MMP-12 activity during vascular remodelling." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/23609.
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Matrix metalloproteinases (MMPs) are required for tissue remodelling processes, including angiogenesis. MMP activity is generally proangiogenic but MMP-12 is suggested to be antiangiogenic and its precise role is still unclear. The work in this thesis describes the synthesis of an MMP-12 inhibitor and activity probe to address the hypothesis that MMP-12 inhibits angiogenesis. An inhibitor, synthesised in-house, selectively inhibited MMP-12 in in vitro recombinant enzyme assays. An activity probe, also synthesised in-house, was selective for MMP-12 in in vitro recombinant enzyme assays. The function of MMP-12 during angiogenesis was assessed using murine models of angiogenesis; the in vivo sponge implantation, and the ex vivo aortic ring assays. Angiogenesis and MMP activity were imaged in vivo in sponges in C57Bl6/J mice over 7 − 21 days (D) using commercial probes (MMPSense™ and AngioSense™). MMP-12 protein concentration and activity were higher in sponges during early angiogenesis (D 3 − 7) when gene expression of vascular endothelial growth factor (a proangiogenic marker) was also high. Gene expression for MMP-12 and platelet-derived growth factor receptor (a marker of vascular maturation) were both higher on D 21 as angiogenesis started to stabilise. The MMP-12 activity probe was unsuccessful in selectively detecting MMP-12 activity in sponge lysate mixtures from D 7 − 21. Administration of an MMP-12 inhibitor did not increase angiogenesis in the sponges in vivo. Additionally, sponges implanted in MMP-12-/- mice did not exhibit significant changes in angiogenesis or MMP activity when imaged in vivo using commercial probes (MMPSense™ and AngioSense™) on D 7. Supporting this, histological analysis of the sponges (removed on D 21) showed that deletion of MMP-12 also did not increase angiogenesis within the sponges.
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Segarra, Blasco Marta. "Regulació de la Producció de Gelatinases (MMP2 i MMP9) pels Limfòcits. Implicació en Malalties Inflamatòries i Síndromes Limfoproliferatives." Doctoral thesis, Universitat de Barcelona, 2006. http://hdl.handle.net/10803/2200.
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Les metal·loproteïnases de matriu (MMPs) són uns enzims de gran rellevància biològica en totes les accions relacionades amb la reorganització de la matriu extracel·lular i també en la regulació de molts processos cel·lulars. Els limfòcits produeixen petites quantitats de gelatinases (MMP2 i MMP9) que són essencials en la migració a través dels teixits, tant en situacions fisiològiques com en els fenòmens patològics d'inflamació i disseminació tumoral.
Prèviament vam demostrar que la interacció amb proteïnes de la matriu extracel·lular a través de receptors integrina era un dels mecanismes més efectius no només en la producció sinó també en l'activació de gelatinases en cèl·lules limfoïdes T. No obstant, els mecanismes que modulen la producció de MMPs a través d'integrines en els limfòcits no estaven identificats. En el conjunt d'aquests treballs hem volgut aprofundir en diferents aspectes de la producció de gelatinases pels limfòcits derivada del contacte cel·lular. Primerament hem estudiat les vies de transducció de senyals involucrades en aquest procés i després hem analitzat les seves implicacions en dos processos fisiopatològics que tenen un vincle important amb el microentorn matricial: una malaltia inflamatòria invasiva (arteritis de cèl·lules gegants) i una patologia neoplàsica (síndromes limfoproliferatives).
Els resultats obtinguts en aquests treballs ens han permès arribar a les següents conclusions:
1. La senyalització a través d'integrines en resposta a estímuls del microentorn (proteïnes de la matriu extracel·lular, concretament fibronectina) és un mecanisme molt eficient per a la producció i activació de gelatinases (MMP2 i MMP9) i MMP14 pels limfòcits T i B.
2. La unió a fibronectina provoca un alliberament post-transcripcional ràpid de gelatinases en aquestes cèl·lules. La secreció d'aquests enzims és necessària per al procés d'invasió.
3. Els mecanismes de senyalització integrina estan modulats per FAK i la seva interacció amb Src. FAK, a través de l'acoblament de senyals duals, coordina l'alliberament de gelatinases i els processos d'adhesió cíclica necessaris per a la migració, suggerint que FAK adaptaria la secreció pulsàtil de gelatinases als canvis del citoesquelet en el procés invasiu limfocitari.
4. La inflamació de les artèries de pacients d'arteritis de cèl·lules gegants s'acompanya d'un increment en l'expressió i activació de gelatinases i es troba en relació topogràfica amb l'expressió d'integrines leucocitàries. Aquest fet suggereix que la progressió de l'infiltrat limfocitari està relacionat amb l'expressió i l'activació de les gelatinases, les quals a més contribuirien a la destrucció de l'estructura arterial. El tractament amb corticoids s'acompanya d'una disminució en l'expressió de MMPs.
5. La talidomida redueix la producció de gelatinases induïda per fibronectina en cèl·lules limfoïdes B interferint amb diferents vies de senyalització mitjançada per integrines. Aquest podria ser un dels mecanismes d'acció d'aquest fàrmac que explicaria la seva eficàcia en el tractament del mieloma múltiple en el microentorn medul·lar.
Com a conclusió general, les integrines leucocitàries poden coordinar la producció de gelatinases amb els mecanismes de migració cel·lular, afavorint el procés d'invasió cel·lular. Els processos inflamatoris i tumorals utilitzen aquest mecanisme, i la seva disrupció podria beneficiar l'evolució terapèutica d'aquestes patologies.
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Barreiros, Driely. "Aspectos moleculares da gênese e progressão de lesões periapicais induzidas experimentalmente em camundongos." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/58/58135/tde-01092017-093300/.
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O conhecimento dos eventos biológicos que ocorrem no periápice dos dentes com necrose pulpar se torna importante para compreender o desenvolvimento das lesões periapicais. Muitas são as moléculas e mediadores que participam na instalação da lesão periapical, a partir da infecção bacteriana que ocorre no interior dos canais radiculares. Assim, o objetivo do presente trabalho foi avaliar moléculas do sistema imune inato, da osteoclastogênese e metaloproteinases em lesões periapicais (LP) induzidas experimentalmente em camundongos knockout e wild type. Para esse objetivo, o presente estudo foi dividido em dois trabalhos distintos. O primeiro teve como objetivo avaliar a expressão de metaloproteinase 2 (MMP2) e metaloproteinase 9 (MMP9) durante a progressão da LP em camundongos knockout para TLR2 (TLR2 KO) e MyD88 (MyD88 KO), em comparação com camundongos wild type (WT). O segundo estudo avaliou a correlação da expressão gênica e imunomarcação de RANK, RANKL, OPG, TLR2 e MyD88 durante a progressão da LP em camundongos WT. No primeiro estudo lesões periapicais foram induzidas em molares inferiores de 54 camundongos TLR2 KO, MyD88 KO e WT (n=18/grupo). Após 7, 21 e 42 dias, os animais foram eutanaziados e as mandíbulas foram dissecadas e submetidas a processamento histotécnico. Os cortes histológicos foram submetidos a imunohistoquímica e posteriormente foi avaliada presença ou ausência de MMP2 e MMP9 nos diferentes grupos. No segundo estudo, 35 camundongos WT foram utilizados. As lesões periapicais foram induzidas nos primeiros molares inferiores de ambos os lados. Após 0 (G0), 7 (G7), 21 (G21) e 42 (G42) dias, os animais foram anestesiados e eutanasiados para que as mandíbulas fossem dissecadas e divididas ao meio.O lado direito das mandíbulas foi para o processamento histotécnico, para posterior marcação de RANK, RANKL, OPG, TLR2 e MyD88, por meio da imuno-histoquímica do lado esquerdo da mandíbula foi utilizado para a extração de RNA, para a determinação da expressão gênica de RANK (Tnfrsf11a), RANKL (Tnfrsf11), OPG (Tnfrsf11b), TLR2 (Tlr2) e MyD88 (Myd88) utilizando quantificação em Tempo Real da Reação da Polimerase em Cadeia (qRT-PCR). Para ambos os estudos, testes paramétricos e não paramétricos foram realizados com nível de significância de 5%. Foi possível observar, no primeiro estudo, que nos períodos iniciais da progressão da lesão periapical, houve um aumento na imunomarcação de MMP9 nos camundongos TLR2 KO e MyD88 KO, quando comparados aos WT, diferente da MMP2 que não se observou nenhum aumento na imunomarcação. No entanto, aos 42 dias observou-se uma redução da imunomarcação de MMP2 e um aumento da MMP9 nos camundongos TLR2 KO. Adicionalmente, no segundo estudo, foi possível observar um aumento da imunomarcação para RANK, RANKL, OPG, TLR2 e MyD88 durante a progressão da lesão periapical (p<0,05). O aumento da expressão de Tnfrsf11 foi diferente entre os grupos G0 e G42, e G21 e G42 (p=0,006). No entanto, a expressão de Tnfrsf11b foi diferente entre os grupos G0 e G7, G7, G21 e G42, sendo possível observar uma diminuição dessa expressão ao longo do tempo (p<0,001). Tlr2 foi mais expresso entre os grupos G0 e G42 (p=0,03). E a expressão da molécula Myd88 foi estatisticamente significante entre os grupos G0 e G7, G21 e G42 (p=0,01). A razão Tnfrsf11/Tnfrsf11b aumentou durante a progressão da lesão periapical (p=0,002). Também foi possível observar uma correlação moderada entre Myd88 e Rankl (r=0,42; p=0,03) e entre Myd88 e Tlr2 (r=0,48; p<0,0001). Após as metodologias empregadas e os dados analisados, concluímos que a produção de MMP2 e MMP9 foi modulada por TLR2 e Myd88 durante a progressão da lesão periapical. Alem disso, podemos sugerir que existe uma correlação positiva entre o sistema RANK/RANKL/OPG e as proteínas do sistema imune inato, TLR2 e MyD88, durante a perda óssea decorrente da infecção bacteriana dos canais radiculares e posterior progressão da lesão periapical.Knowledge of the biological events occurring inteeth apex with pulp necrosis becomes important to understand the development of periapical lesions. There are manymolecules and mediators that participate in the installation of the periapical lesion, from the bacterial infection that occurs inside the root canals. Thus, the aim of the present study was to evaluate molecules of the innate immune system, osteoclastogenesis and metalloproteinases in experimentally apical periodontitis (AP) induced in knockout and wild type mice. For this purpose, the present study was divided into two distinct studies. The first one aimed to evaluate the expression of metalloproteinases 2 (MMP2) and metalloproteinases 9 (MMP9) during the progression of AP in TLR2 knockout mice (TLR2 KO) and MyD88 knockout mice (MyD88 KO), compared to wild type mice (WT). The second study evaluated the correlation of gene expression and immunostaining of RANK, RANKL, OPG, TLR2 and MyD88 during LP progression in WT mice. In the first study AP were induced in lower molars of 54 TLR2 KO, MyD88 KO and WT mice (n = 18 / group). After 7, 21 and 42 days, the animals were euthanized and the jaws were dissected and submitted to histotechnical processing. The histological sections were submitted to immunohistochemistry and subsequently the presence or absence of MMP2 and MMP9 in the different groups was evaluated. In the second study, 35 WT mice were used. Periapical lesions were induced in the lower first molars on both sides. After 0 (G0) to 7 (G7), 21 (G21) and 42 (G42) days, the animals were anesthetized and euthanized so that the jaws were dissected and divided in half. The right side of the jaws was for the histotechnic processing, for subsequent imunostaining of RANK, RANKL, OPG, TLR2 and MyD88, through immunohistochemistry and the left side of the jaws was used for the extraction of RNA, for the determination of expression of RANK (Tnfrsf11a), RANKL (Tnfrsf11), OPG (Tnfrsf11b), TLR2 (Tlr2) and MyD88 (Myd88) using Quantification Real Time of Polymerase Chain Reaction (qRT-PCR). For both studies, parametric and non-parametric tests were performed with significance level of 5%. It was possible to observe in the first study that in the initial periods of AP progression there was an increase in MMP9 immunostaining in TLR2 KO and MyD88 KO mice when compared to WT, different from MMP2 that no increase in immunostaining was observed. However, at 42 days there was a reduction in MMP2 immunostaining and an increase of MMP9 in TLR2 KO mice was observed. Additionally, in the second study, it was possible to observe an increase in the immunostaining for RANK, RANKL, OPG, TLR2 and MyD88 during periapical lesion progression (p <0.05). The increase in Tnfrsf11 expression was different between groups G0 and G42, and G21 and G42 (p = 0.006). However, the expression of Tnfrsf11b was different between the G0 and G7, G7, G21 and G42 groups, and a decrease in expression over time (p <0.001) was observed. Tlr2 was more expressed between the G0 and G42 groups (p = 0.03). And the expression of the Myd88 molecule was statistically significant between the G0 and G7, G21 and G42 groups (p = 0.01). The Tnfrsf11 / Tnfrsf11b ratio increased during the AP progression (p = 0.002). It was also possible to observe a moderate correlation between Myd88 and Rankl (r = 0.42, p = 0.03) and between Myd88 and Tlr2 (r = 0.48, p <0.0001). After the methodologies used and the data analyzed, we conclude that the production of MMP2 and MMP9 was modulated by TLR2 and Myd88 during the AP progression. In addition, we can suggest that there is a positive correlation between the RANK / RANKL / OPG system and the proteins of the innate immune system, TLR2 and MyD88, during bone loss due to bacterial infection of the root canals and subsequent progression of the apical periodontitis.
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Badoual, Cécile. "Rôle pronostique des lymphocytes T CD4+CD25+ intratumoraux et analyse des mécanismes de production du CD25 soluble dans les tumeurs des voies aéro-digestives supérieures." Paris 6, 2005. http://www.theses.fr/2005PA066467.
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Hannas, Angélica Reis. "Determinação da expressão de MMP-2 e MMP-9 na saliva de pacientes portadores de lesões cervicais não cariosas e da influência das MMPs sobre lesões radiculares artificiais através de EDX." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/25/25131/tde-30032009-155558/.
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As metaloproteinases da matriz (MMPs) foram identificadas na saliva, na placa dental, na dentina e no cemento. Este trabalho teve como objetivos: Estudo I (I) - avaliar a expressão de MMP-2 e MMP-9 presentes na saliva total e parotidiana e no fluido gengival crevicular (FGC) de pacientes portadores e não portadores de lesões cervicais não cariosas (LCNC); Estudo II (II) - investigar se a presença de MMP-8 e -9/TIMPs poderia influenciar a remineralização de lesões artificialmente criadas na superfície radicular, com ou sem desgaste por abrasão. Os métodos utilizados foram: (I) Coleta de amostras de saliva e do FGC de 32 pacientes, com (n=16) e sem LCNC (n=16). A atividade gelatinolítica das MMPs foi avaliada através de análise zimográfica e Western Blot. (II): Espécimes de dentina humana radicular foram obtidos. O grupo controle G1(10) não sofreu nenhum tratamento. Os demais segmentos radiculares foram desmineralizados G2(60). O Grupo A não foi submetido à escovação e o Grupo B foi submetido à abrasão por escovação em uma máquina de escovação simulada. G2(10) foi apenas desmineralizado, G3(10) desmineralizado e remineralizado, e os Grupos G4(10), G5(10), G6(10), G7(10) foram desmineralizados e remineralizados em presença de tampão neutro, TIMP, MMP-8 e -9, MMP-8,-9 e TIMP, respectivamente. Para a análise elemental, as concentrações de Ca+2, P, Mg+2 assim como a relação molar Ca/P e Mg/Ca foram determinadas através de uma sonda eletrônica para microanálise (EPMA). A análise qualitativa por retrodispersão (BSE) foi realizada para demonstrar a distribuição global da densidade mineral. Os resultados (I) mostraram que a principal gelatinase presente, tanto na saliva total quanto no FGC, é a proMMP-9. Na saliva secretada pela glândula parótida, não foram detectadas bandas indicando a presença de gelatinases. Os resultados do estudo (II) indicaram que os espécimes escovados apresentaram maior conteúdo de Ca+2 a 20µm e maior conteúdo de Mg+2 a 30 e 50µm. Em presença de TIMPs, ocorreu uma redução do conteúdo de Ca+2 a 20µm. Para os espécimes não escovados, em todas as profundidades, as amostras incubadas com MMPs apresentaram maiores valores de Ca+2. Portanto, pode-se concluir que (I) a comparação entre pacientes com e sem LCNC mostrou não haver diferença estatisticamente significante quanto à atividade gelatinolítica; (II) quando não inibidas pelos TIMPs, as MMPs degradaram o colágeno completamente desmineralizado na superfície radicular, permitindo melhor recalcificação na superfície subjacente. Esse fenômeno foi também facilitado pela abrasão por escovação.Matrix metalloproteinases (MMPs) have been identified in saliva, plaque, gingival crevicular fluid (GCF), dentin and cementum. Study (I) aimed at evaluating the presence and quantity of gelatinases MMP-2 and MMP-9 in total and parotid saliva and in GCF (GCF) of subjects with and without NCCL. Study (II) aimed at investigating whether the presence of matrix metalloproteinase (MMP)-8 and - 9/TIMPs would influence the remineralization of artificial root lesions with and without mechanical wear. (I) Total stimulated saliva, parotid saliva, and GCF from patients with (n=16) and without NCCL (n=16) were collected and assessed for gelatin zymography and for western immunoblot analysis. (II) Human root segments from Group A (n=35) were not brushed and from Group B (n=35) were subjected to machine-controlled brushing, simulating mechanical wear. Specimens from Group 1 (control, n=10) were left untreated. Group 2 (n=10), was just demineralized; Group 3 (n=10) was demineralized and remineralized. The other samples G4 (n=10), G5 (n=10), G6 (n=10), G7 (n=10) were subjected to remineralization with HEPES buffer, tissue inhibitor of matrix metalloproteinase-2 (TIMP-2), activated MMP-8 and MMP-9 and activated MMP-8, MMP-9 and TIMP-2, respectively. Ca+2, P, Mg+2 concentrations as well as Ca/P and Mg/Ca molar ratios were determined through an Electron Probe Microanalyser (EPMA). (I) Densitometric analysis revealed that the main gelatinase was proMMP-9. No statistically significant difference was observed for MMP-2 and MMP-9 levels, separately. In parotid saliva, gelatinolytic activity was very low or absent. Western immunoblots revealed that, while little immunoreactivity was detected for MMP-2, there was positive immunoreaction for MMP-9, both in total saliva and in GCF. Gelatinases do not seem to originate from parotid gland. (II) The results indicated that the brushed specimens presented higher Ca+2 levels at 20 µm and higher Mg+2 content at 30 and 50 µm. Ca+2 content at 20 µm decreased in the presence of TIMPs. For the non-brushed specimens, in all depths, samples incubated with MMPs showed highest Ca+2 values. It can be concluded that (I) the main gelatinase present in the oral cavity is MMP-9. No significant differences were found in total gelatinolytic activity among NCCL+ and NCCL- patients. (II) When not inhibited by TIMPs, MMPs degraded the completely demineralized collagen in the root surface, allowing for better recalcification in the deeper areas. This phenomenon was also facilitated by the brushing procedure.
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Partridge, Juneth Ann Joaquin. "The role of MMPs in the intravasation of a highly disseminating HT-1080 fibrosarcoma cell variant a protective role for tumor-derived MMP-9 /." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3378523.
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Thesis (Ph. D.)--University of California, San Diego, 2009.Title from first page of PDF file (viewed October 22, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 119-134).
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Chojnacki, Joseph T. "The consistency of scores and configural patterns between the MMPI and MMPI-2 /." The Ohio State University, 1992. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487777901659682.
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Bignardi, Letícia Andreotti. "Estudo do papel do eixo IL-33/ST2 na progressão da lesão periapical experimental." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/58/58135/tde-02022015-114411/.
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A citocina IL-33 apresenta papel dual e está envolvida com a resolução ou progressão de inúmeras doenças, além disso, acredita-se que a via IL-33/ST2 esteja envolvida no equilíbrio entre a atividade de osteoclastos e osteoblastos. O objetivo deste estudo foi avaliar o papel do receptor ST2 no desenvolvimento e progressão de lesões periapicais experimentalmente induzidas em camundongos. Lesões periapicais foram induzidas em primeiros molares inferiores de camundongos WT e ST2 knockout (KO). Decorridos 7 e 14 dias, as amostras de mandíbula foram submetidas às análises: determinação da área de lesão periapical em cortes histológicos e do volume por microtomografia computadorizada (μCT); contagem de osteoclastos submetidos ao ensaio de histoenzimologia (TRAP); expressão gênica de marcadores osteogênicos e osteoclastogênicos por q-PCR; quantificação de neutrófilos por ensaio de mieloperoxidases. Os linfonodos foram submetidos à análise da expressão dos fatores transcricionais T-bet, GATA-3, RORc e Foxp-3 por q-PCR. Análise estatística utilizada foi One-way ANOVA, seguido de pós-teste de Bonferroni. Aos 14 dias, observou-se maior extensão da lesão periapical em animais WT que em ST2KO (p<0,05). O tamanho da lesão nos animais ST2KO permaneceu igual em função do tempo. Foi observada maior quantidade de neutrófilos na lesão do grupo WT aos 7 dias, em comparação aos animais ST2KO (p<0,05). Na expressão de T-bet, GATA-3, RORc e Foxp-3 não foram observadas diferenças estatisticamente significantes. O número de osteoclastos contados nos animais ST2KO foi maior que o observado em WT aos 7dias e aos 14 dias (p<0,05). A expressão de Runx2 foi maior no grupo lesão dos animais ST2KO quando comparado a seu respectivo controle. Os outros marcadores relacionados com a formação óssea não apresentaram diferenças estatisticamente significantes. Dentre os marcadores relacionados com a reabsorção óssea, a catepsina K e o MMP-9 apresentaram maior expressão aos 14 dias, na lesão dos animais WT quando comparada à expressão na lesão dos animais ST2KO (p<0,05). Com base nos resultados obtidos no presente estudo, pode-se concluir que na ausência do receptor ST2 as lesões periapicais são menos extensas e embora em maior quantidade, os osteoclastos são menos ativos. Nossos resultados sugerem um importante papel da via IL-33/ST2 na ativação dos osteoclastos e desenvolvimento da lesão periapical.The IL -33 cytokine presents a dual role and is involved either in the resolution and progression of many diseases. Furthermore, it is believed that this pathway is involved between osteoclast and osteoblast activity balance. The aim of this study was to evaluate the role of ST2 receptor in the development and progression of experimentally induced periapical lesions in mice. Periapical lesions were induced in first molars of WT and ST2 knockout (KO) mice. After 7 and 14 days, jaw samples were subjected to various analysis: determination of periapical lesions area by histology and volume by computed microtomography (μCT); osteoclasts number by TRAP histoenzymology; osteogenic and osteoclastogenic markers expression by q-PCR; neutrophil quantification by myeloperoxidase activity. The expression of transcription factors T-bet, GATA-3, RORC and Foxp-3 in lymph nodes were analysed by q-PCR. Statistical analysis was done by One-way ANOVA and Bonferroni post-test. It was observed a greater extent in periapical lesions of WT compared to ST2KO animals at 14 days (p<0.05). There is no progression in the lesion of ST2KO mice with the time. A larger number of neutrophils in WT group was observed, compared to ST2KO mice evaluated at 7 days (p<0.05). The expression of T-bet, GATA-3, RORc and Foxp-3 were not statistically significant different among the groups. The number of osteoclasts in lesions of ST2KO animals were greater than the observed in WT, at 7 and 14 days (p<0.05). Although, other osteogenic markers showed no statistically significant difference, Runx2 expression in ST2KO was higher in lesion side compared to control side at 14 days. The markers related to bone resorption, cathepsin K and MMP-9, were significantly abrogated in the lesion side of ST2KO mice, at 14 days (p<0.05). Based on the results, it can be concluded that although larger amounts of osteoclast were counted in ST2KO, the lesion was less extensive and osteoclasts less active. It all suggests that the IL-33/ST2 pathway play an important role in osteoclasts activation and periapical lesion development.
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STENGEL, CONRAD. "Mmpi et troubles fonctionnels intestinaux." Toulouse 3, 1988. http://www.theses.fr/1988TOU31151.
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Seits, Margaret M. "Identifying pedophiles with the MMPI." PDXScholar, 1988. https://pdxscholar.library.pdx.edu/open_access_etds/3850.
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The present study investigated the validity of the Pe (Toobert, Bartelme, & Jones, 1959) and Sexual Deviancy (Marsh, Hilliard, & Liechti, 1955) subscales, developed from the MMPI, to determine if the scales would discriminate convicted sexual offenders from nonsexual offenders.
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Bartholmey, Paul. "Polytopes moments des compactifications sphériques d'un groupe : application au programme des modèles minimaux." Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTS033/document.
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Le programme des modèles minimaux (MMP) est l'une des grandes théories développée en géométrie algébrique en vue de classifier les variétés algébriques complexes. Pour certaines familles d'exemples, le MMP est très bien connu. Notamment, pour les variétés toriques et horosphériques, la théorie se résume à une étude assez simple de familles de polytopes, dits polytopes moments, et elle s'étend même à des variétés plus singulières que dans le cas général. Le but de cette thèse est d'étendre ces résultats à des compactifications sphériques d'un groupe. On décrit dans un premier temps ces variétés, et on classifie tous les polytopes moments attachés à de telles compactifications. Puis on démontre que le MMP appliqué sur ces compactifications sphériques se traduit en termes de polytopes moments. Enfin on donne un programme codé en SageMath qui permet de donner les polytopes apparaissant dans le MMP d'une compactification sphérique d'un groupe simpleThe Minimal Model Program (MMP) is one of the greatest theories in Algebraic Geometry developped to classify algebraic varieties. For some families of algebraic varieties, the MMP has been studied in depth. In particular, for toric and horospherical varieties, it comes down to a quite easy study of families of polytopes, called moment polytopes, and it could be adapted to weaker hypothesis of singularities. The goal of this thesis is to show that this reduction can be extended to spherical compactifications of a group. First of all we describe these varieties and classify all moment polytopes of such compactifications. Then we prove that the MMP applied on this spherical compactifications reduces to a study of a families of this moment polytopes. Finaly we give a computer program, coded in SageMath, which gives all polytopes appearing in the MMP of a simple group's spherical compactification
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Nury, Catherine. "Développement d’une sonde de photoaffinité pour la détection sensible de formes actives de Métalloprotéases Matricielles dans des systèmes biologiques complexes." Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05P629/document.
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Le développement d’une nouvelle sonde dite « activity-based probe » pour réaliser la détection de formes actives de protéases appartenant à la famille des protéases à zinc de la matrice (MMP) a été réalisé dans ce travail, en partant d’un inhibiteur phosphinique puissant des MMP dans lequel a été introduit un groupement photoactivable de type diazérine. Ce composé se révèle un inhibiteur puissant de plusieurs MMP avec des affinités nanomolaires. Ce composé incubé avec différentes MMP est par ailleurs capables de modifier de façon covalente un grand nombre de MMP au niveau de leur site actif, avec des rendements de modification variant de plus de 50% à 11%, selon la nature des MMP. En ayant choisi comme moyen de détection la radioactivité, nous démontrons qu’avec cette nouvelle sonde qu’il est possible de détecter des formes actives de MMP avec des sensibilités de l’ordre de la femtomole dans des systèmes modèles de protéomes complexes. Appliquée à l’analyse de lavages broncho alvéolaires de souris traitées par voie pulmonaire avec des nanoparticules pour induire une réponse inflammatoire, cette nouvelle sonde permet de mettre en évidence la présence de formes actives du domaine catalytique de la MMP-12, une métalloprotéase à zinc exprimée par les macrophages, mais pas dans les animaux contrôles. En revanche l’analyse de carotides humaines de patients souffrant d’athérosclérose ne nous pas conduit avec cette sonde à la détection de formes actives de MMP. Malgré ce résultat, il est à noter que la détection de forme active de MMP dans un fluide pathologique est une première dans ce domaine. Cette sonde étant validée pour sa capacité à détecter des formes actives de MMP, elle permettra dans l’avenir de tester d’autres fluides pathologiques d’origine humaine ou bien des extraits de tissu comme des tumeurs pour lesquels les MMP pourraient être des marqueurs de ces pathologiesA new activity-based probe able to covalently modify the active site of proteases belonging to the matrix metalloprotease family (MMPs) has been developed in this thesis project. The probe was shown to behave as potent inhibitor of several MMPs, with nanomolar Ki values. This probe was also able to modify specifically only the free active site of MMPs, with particular high yields of cross-linking varying from 50 % to 11 %, depending of the MMPs tested. Using radioactivity as means of detection, this probe was able to detect active form of MMPs with a threshold of 1 femtomole. Applied to the study of bronchoalvelolar fluids (BAL) from mice exposed to nanoparticles by a lung aspiration protocol, this probe revealed the presence of the catalytic domain of MMP-12 under its active form, but not in control animals. When used to detect active form of MMPs from extracts obtained from human arteries of patient suffering from atherosclerosis, the probe was not able to detect such MMP active forms. Despite this negative result, the detection of active form of MMP in pathological fluid like BAL has never been reported before this work. Having validated this novel MMP activity-based probe, it will be possible to use it now for detecting MMPs from other pathological fluids or tissues extracts in which MMPs can be good markers of the pathology
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Reis, Sabrina Thalita dos. "Análise da expressão de MMP-2, MMP-9, MT1-MMP (MMP-14), TIMP-1, TIMP-2, RECK, TGF-Beta e interleucina-8 em câncer de próstata." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5153/tde-22092011-133255/.
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Introdução: O câncer de próstata (CaP) é o tumor mais freqüente do homem no Brasil tendo sido estimados mais de 52.350 novos casos em 2010, sendo a segunda causa de óbito por câncer em homens. O prognóstico depende fundamentalmente dos níveis séricos de Prostatic Specific Antigen (PSA) estádio tumoral (TNM) e grau de diferenciação histológica (Gleason). Porém esses têm sido insuficientes na definição do prognóstico da neoplasia. Por isso pesquisas têm sido direcionadas para a identificação de alterações moleculares que possam prever o potencial de agressividade do câncer de próstata. Metaloproteinases da matriz (MMP) são proteínas pertencentes a uma família de aproximadamente 30 enzimas proteolíticas ou endoproteinases que degradam vários componentes da matriz extracelular. A detecção de sua expressão tem sido estudada como marcador sensível e específico de vários tumores, principalmente as MMP pertencentes ao grupo das gelatinases MMP-2 e MMP-9. Objetivo: o objetivo deste nosso trabalho foi avaliarmos pela técnica de qRT-PCR e imuno-histoquímica os níveis de expressão dos genes das MMP pertencentes ao grupo das gelatinases, MMP-2 e MMP-9, bem como outros sabidamente envolvidos em suas vias de ativação (MMP-14, IL-8) e inibição (TIMP-1, TIMP-2, RECK e TGF-) no câncer localizado de próstata. Material e Métodos: O estudo consistiu na análise de espécimes de 79 pacientes com câncer da próstata submetidos a prostatectomia radical entre setembro de 1997 e fevereiro de 2000. Esses oito genes foram então testados quanto a seu valor prognóstico no câncer da próstata através da técnica de reação em cadeia da polimerase quantitativa com transcriptase reversa (qRT-PCR). Análise proteica foi feita a partir de 40 pacientes deste pool. O grupo controle foi composto de tecido de 11 pacientes com hiperplasia benigna da próstata (HPB) tratados cirurgicamente com prostatectomia retropúbica. Resultados: MMP-9 esteve superexpressa e MMP-2, TIMP-1, TIMP-2, MMP 14, IL-8, TGF- e RECK se mostraram subexpressos em tecido representativo de CaP quando comparado com HPB. A análise dos níveis de expressão dos genes com o escore de Gleason, mostrou que MMP-2 e TIMP-2 mesmo mantendo-se subexpressos, tiveram uma expressão maior entre os pacientes que apresentavam Gleason 7 (p=0,04 e p=0,02 respectivamente). De acordo com o valor de PSA préoperatório, encontramos diferenças na expressão de MMP-9. Pacientes que apresentavam um PSA pré-operatório 10 ng/mL possuíam uma mediana de expressão maior que aqueles cujo PSA pré-operatório <10 ng/mL com medianas de expressão de 5,62 e 2,76 respectivamente (p=0,033). Não encontramos diferenças estatísticas entre pacientes que apresentavam ou não recidiva bioquímica quanto a expressão dos 8 genes estudados. Porém o gene da MMP-9 apresentou uma diferença estatística marginal apresentando uma mediana de expressão de 6,29x nos pacientes que apresentaram recidiva bioquímica e de 3,25 nos pacientes que não apresentaram recidiva bioquímica (p=0,090). De acordo com a expressão proteica, encontramos uma maior positividade em MMP-9, MMP-2, TGF-, IL-8 e MMP-14. De acordo com os fatores prognósticos encontramos associação de TIMP-1 com recidiva bioquímica. Conclusão: Encontramos uma superexpressão de MMP-9 e uma subexpressão de MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, IL-8 e TGF- no CaP. Considerando os fatores prognósticos encontramos que aumentados níveis de expressão do gene da MMP-9 associou-se a aumentados níveis de PSA, e mostrou uma tendência de associação com recidiva bioquímica. De acordo com a expressão proteica encontramos que a ausência de TIMP-1 pode ser um indicativo de recidiva bioquímicaIntroduction: Currently, Prostate cancer (PCa) is the most common tumor in men in Brazil. It was estimated that more than 52,350 new cases were diagnosed in 2010, being the second cause of death by cancer in man. The prognosis depends mainly on Prostate Specific Antigen (PSA) serum levels, tumor stage (TNM) and histological grade (Gleason), but these parameters, even combined, are insufficient to define the correct prognosis of PCa. Therefore research has been directed towards the identification of molecular alterations that may predict potential aggressiveness of PCa. Matrix metalloproteinases (MMPs) are proteins that belong to a family of about 30 proteolytic enzymes that degrade various components of the extracellular matrix. The analysis of MMPs expression has been studied as a sensitive and specific marker of prognosis of several tumors, and special attention was focused in the group of gelatinases, MMP-2 and MMP-9.Objective: The aim of this study was to evaluate the expression levels of MMP-2 and MMP-9 genes and proteins by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry in localized PCa. We also evaluated the expression of genes that are involved in the control of MMP-2 and MMP as activators (MMP- 14, IL-8) or inhibitors (TIMP-1, TIMP-2, RECK and TGF-).Materials and Methods: The casuistic consisted of 79 surgical specimens from patients with localized PCa who underwent radical prostatectomy between September 1997 and February 2000. The control group was composed of specimens from 11 patients with benign prostatic hyperplasia (BPH) treated surgically with retropubic prostatectomy. The results of the 8 genes expression, through qRTPCR and immunohistochemistry, were correlated to the diagnosis and prognosis of PCa. The protein expression analysis was carried out in 40 patients of the casuistic. Results: The MMP-9 was overexpressed, while MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, IL-8, and TGF- were underexpressed in malignant prostate tissue compared to BPH. Patients with Gleason7 had higher expression of MMP-2 and TIMP-2 (p=0.04, p=0.02 respectively). According to the preoperative PSA value, we found that patients with preoperative PSA10 ng/mL had a median of expression of 5.62 compared to 2.76 when PSA<10 ng/mL (p=0.033). There were no statistical differences between expression of the eight genes and biochemical recurrence during follow up. However, the higher MMP-9 expression was marginally associated with recurrence, the median was of 6.29 in recurrence patients compared to 3.25 in those without recurrence (p=0.090). Regarding the protein expression, we found a higher positivity of MMP-9, MMP-2, TGF-, IL-8 e MMP-14 expression in PCa, and a correlation between the lack of TIMP-1 and tumor recurrence. Conclusion: MMP-9 is overexpressed while MMP-2, TIMP-1, TIMP-2, MMP-14, RECK, TGF- and IL-8 are underexpressed in CaP. According to the prognostic factors, we observed that increased level of MMP-9 was associated with pre-surgical PSA10 ng/mL. Also there was a tendency of association between higher MMP- 9 expression and biochemical recurrence. Overexpression of MMP-9 can be explained by the underexpression of their major inhibitors TIMP-1 and RECK. According to protein expression we found that absence of TIMP-1 is correlated with biochemical recurrence in the PCa
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Shah-Heydari, Shahram. "MMPP modeling of ATM multimedia traffic." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0003/MQ39477.pdf.
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Rebillet, Susan Bates. "Object Relations Correlates on the MMPI." Thesis, North Texas State University, 1987. https://digital.library.unt.edu/ark:/67531/metadc330987/.
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This study was undertaken to help determine the usefulness of the Minnesota Multiphasic Personality Inventory (MMPI) for providing information regarding a person's object relations. Subjects were 136 college students (56 males, 80 females) ranging in age from 18 to 48. Subjects were administered the Rorschach, the Self Object Scale (SOS), and the MMPI. The Rorschach was scored using Blatt, Brenneis, Schimek, and Glick's (1976a) manual for scoring the level of object relations (Developmental Analysis of the Concept of the Object Scale-DACOS), the SOS scored as Blatt, Chevron, Quinlan, and Wein's manual (1981) directs, and the MMPI scored in the standardized manner using college-age norms. MANOVA's on the SOS and the DACOS resulted in significant effects for sex on MMPI scales 6, 7, and 8. Sex differences on MMPI scales 6 and 4 were obtained for high/low level of object relations on the DACOS. Pearson correlations showed positive correlations for males between level of object relations on the SOS and MMPI scale 5, and negative correlations on MMPI scale 5 for females. For males positive correlations between the DACOS and MMPI scale 4 and negative correlations on MMPI scale 10 were noted. These results were discussed as pertaining to the socialization of males and females. The most puzzling finding was the lack of correlation between the DACOS and the SOS. This was discussed as possibly being a result of the effect of the Rorschach, which measures psychopathology, whereas the SOS may be a purer measure of object relations. The paucity and weakness of the results was attributed to the restricted variance of the population. Implications for future research included obtaining a larger sample from a normal population, establishing clear norms for object eolations measures, obtaining correlations between a measure of current functioning and the object relations measures as a step toward establishing cut-off scores for groups on the measures, and further exploration of the weights in the scoring categories "of Blatt's DACOS scale.
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Ylipalosaari, M. (Merja). "Matrix metalloproteinases (MMPs) in oral carcinomas." Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514277309.
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Abstract
Matrix metalloproteinases, MMPs, are a family of enzymes capable of modulating connective tissue components. The expression of several MMPs is increased in oral squamous cell carcinomas (OSCCs). They are assumed to have an important role in the development and progression of OSCCs. However, the exact role and mechanism of the regulation of MMPs in malignant transformation are still largely unknown.
In this study, tumour-associated trypsin-2 (TAT-2) was detected in OSCC tissue sections, and its role in MMP-2 and -9 regulation in carcinoma cells was evaluated. The TAT-2 gene was transfected into two different OSCC cell lines and one immortalized oral epithelial cell line. In TAT-2-transfected cells, MMP-9 activation increased OSCC cell invasion in chicken chorionallantoic membrane assay. Increased intravasation was prevented by tumour-associated trypsin inhibitor or specific gelatinase-inhibiting CTT-peptide. TAT-2 also converted MMP-1, -8, -13 and -3 into smaller molecular weight forms in vitro. However, TAT-2-transfected OSCC cells showed no conversion. TAT-2 was demonstrated to degrade powerfully type I collagen into small fragments in vitro. The cell surface receptor αvβ6 integrin is strongly up-regulated in OSCCs. By using β6-transfected OSCC cells, it was demonstrated that αvβ6 integrin down-regulates MMP-13 expression. However, this integrin did not regulate other collagenases or TIMP-1. β6-transfected cells invaded more efficiently through the basement membrane matrix, but their migration through type I collagen remained unchanged. MMP-8 expression was detected for the first time in head and neck squamous cell carcinoma (HNSCC) cell lines and corresponding cultured dermal and tumour fibroblasts. The localization of MMP-8 in HNSCC was determined by immunohistochemical stainings and in situ hybridization. MMP-8 production levels in carcinoma cells were faint and sporadic in HNSCCs sections. Ninety-two primary mobile tongue SCCs were subjected to MMP-8 immunohistochemical staining, and the staining results were compared to survival rates. MMP-8 was associated with improved disease-free survival in females but not in males.
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Discher, Philipp Martin [Verfasser], Matthias [Forscher] Siepe, Fabian Alexander [Forscher] Kari, Philipp [Forscher] Meffert-Laschinski, Matthias [Akademischer Betreuer] Siepe, and Fabian Alexander [Akademischer Betreuer] Kari. "Untersuchung der MMP-2 Isoformen und der aktiv-MMP-2/pro-MMP-2 Ratio im Aneurysma der Aorta ascendens." Freiburg : Universität, 2019. http://d-nb.info/1202010385/34.
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ARAÚJO, Leonardo Cordeiro de. "Avalia-MMPE : uma ferramenta para suporte a avaliações no MMPE-SI/TI (Gov) com foco no usuário." Universidade Federal de Pernambuco, 2013. https://repositorio.ufpe.br/handle/123456789/12399.
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No âmbito das avaliações, as organizações procuram investir altos valores a fim de prover ao mercado competitivo formas de reconhecimento, como certificações, comprovando o seu alto padrão, geralmente de qualidade. Existem diversos modelos de avaliação de maturidade no âmbito dos sistemas de informação/tecnologia da informação (SI/TI), onde, recentemente, foi desenvolvido um modelo para direcionar o Planejamento Estratégico de TI em organizações governamentais brasileiras, o MMPE-SI/TI (Gov), cujo foco é auxiliar as organizações a identificarem em que nível de maturidade elas se encontram e a tomarem medidas assertivas. Existem ferramentas (softwares) que, baseadas em alguns dos modelos e métodos mais conhecidos, possibilitam o apoio a avaliações de maturidade nos processos organizacionais. Todavia, essas ferramentas não se preocupam de forma clara com as necessidades do usuário, em especial na simplicidade da execução das tarefas, uma vez que não existem pesquisas que relatem isso. O intuito desta pesquisa foi desenvolver uma ferramenta para apoiar as avaliações com o uso do MMPE-SI/TI (Gov) com foco no usuário final (implementadores e avaliadores). Para isso foram analisados quatorze trabalhos advindos da literatura técnica, dois métodos de avaliação de processos de software amplamente utilizados e duas ferramentas com os mesmos propósitos. Uma vez desenvolvida, a ferramenta foi submetida a avaliações piloto, onde foram respondidos cinco questionários com cinquenta e uma questões cada, baseados em um instrumento de avaliação de qualidade de software em uso (iASUS). Com os resultados retornados, pode ser observado que a ferramenta em questão atendeu, de forma satisfatória, às principais características de qualidade de software em uso.
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Turner, Matthew. "THE USE OF THE MMPI-A SHORT FORM FOR IDENTIFYING STUDENTS WITH EMOTIONALITY IN THE SCHOOLS." UKnowledge, 2007. http://uknowledge.uky.edu/gradschool_diss/572.
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This study investigated the utility of the MMPI-A short form described by Archer, Tirrell, and Elkins (2001) for detecting the presence of emotionality in adolescents in the school setting. Students were placed in one of three groups based on their performance on an established and frequently used self-report measure of personality, the Behavior Assessment System for Children-II (BASC- 2). Subjects who had significant elevations on one or more of the scales in Internalizing Index on the BASC-2 were placed in the Clinical group and subjects who had significant elevations on one or more of the scales the School Problems Index or Personal Adjustment Index were placed in the Adjustment group. Those without significant elevations on the BASC-2 were placed in the Nonclinical group. Differences between the three groups on each of the MMPI-A short form clinical scales were reported. The results indicated that the students in the Clinical group scored higher than students in the Non-clinical group on each of the MMPI-A short form scales. Adjustment group scores tended to be higher than Non-clinical group scores but not all scales were significantly higher. Discriminant analysis correctly classified 75% of the non-clinical group, 52% of the Clinical group, but only 37% of the Adjustment group. These findings, combined with additional analysis of clinical relevant data, provided positive indicators supporting the use of the short form in clinical settings.
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Seabra, Fl?vio Roberto Guerra. "An?lise imuno-histoqu?mica das metaloproteinases da matriz ( MMP-1,MMP-2 e MMP-9) na doen?a periodontal." Universidade Federal do Rio Grande do Norte, 2006. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17147.
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Previous issue date: 2006-09-19The tissular destruction found in periodontal diseases is caused mainly by components of the host that have its production stimulated by the products of the microorganisms present on the plaque. Matrix Metalloproteinases (MMPs), a class of enzymes involved both in physiologic and pathologic extracellular matrix degradation are considered the main responsible for the characteristic tissular loss in periodontal disease, and the understanding of how this happens can have a series of beneficial implications for prevention, diagnosis and treatment of this illness. The aim of this work was to study the immunohistochemical expression of MMP-1, MMP-2, and MMP-9 in fragments of gingival biopsies with clinical diagnose of periodontal disease. MMP-1 has expressed significantly more than the others MMPs in gingivitis both in the epithelium (p=0,0008) and connective tissue (p=0,0049). In periodontitis, both MMP-1 and MMP-9 has expressed significantly more than MMP-2 in the epithelium (p<0,0001) and in the connective tissue (p=0,0002). MMP-1 and MMP-9 presented more expression in periodontitis than in gingivitis but MMP-1 only in the connective tissue (p=0,03) and MMP-9 in the epithelium (p=0,003) and in the connective tissue (p=0,04). In conclusion, these results indicate that the MMP-1 presents high expression in every stages of the periodontal diseases, and increases its expression in the connective tissue when the gingivitis evolves to periodontitis. Therefore, it may have an important role in connective tissue degradation and bone loss observed in disease, since early, in gingivitis, until late stages, in periodontitis, of the periodontal disease. MMP-9 has expressed more in periodontitis than in gingivitis, both in epithelium and in connective tissue. It means that this enzyme may have some importance in the progression of gingivitis to periodontitis by acting in bone resorption observed in this desease
A destrui??o tecidual observada na doen?a periodontal ? causada, principalmente, por componentes do hospedeiro que t?m sua produ??o estimulada pelos produtos liberados pelas bact?rias. As Metaloproteinases da Matriz ou MMPs, enzimas relacionadas ? degrada??o de matriz extracelular em processos tanto fisiol?gicos quanto patol?gicos s?o consideradas as principais respons?veis pela perda tecidual caracter?stica da doen?a periodontal, e o entendimento de como isso ocorre pode ter uma s?rie de implica??es ben?ficas em rela??o ? preven??o, ao diagn?stico e ao tratamento desta doen?a. Neste trabalho foi estudada a express?o imuno-histoqu?mica da MMP-1, da MMP-2 e da MMP-9 em gengivas clinicamente diagnosticadas com doen?a periodontal. A MMP-1 teve express?o significativamente maior que as outras duas nos casos de gengivite tanto no epit?lio (p=0,0008) quanto no tecido conjuntivo (p=0,0049). Na periodontite, a MMP-1 e MMP-9 tiveram express?es significativamente maiores que a MMP-2 tanto no epit?lio (p<0,0001) quanto no conjuntivo (p=0,0002). A MMP-1 e MMP-9 mostraram maior express?o na periodontite que na gengivite sendo a MMP-1 apenas no tecido conjuntivo (p=0,03) e a MMP-9 no epit?lio (p=0,003) e no conjuntivo (p=0,04). Concluiu-se portanto que a MMP-1 apresenta forte express?o em todos os est?gios da doen?a peridontal, aumentando no tecido conjuntivo no caso de progress?o para periodontite, podendo portanto ter um papel crucial na degrada??o de tecido conjuntivo e perda ?ssea observada na doen?a desde os est?gios iniciais de gengivite at? a progress?o para periodontite. A MMP-9, ? expressa mais na periodontite que na gengivite, tanto no epit?lio quanto no conjuntivo significando que esta enzima pode ter import?ncia na progress?o da gengivite para a periodontite atuando na reabsor??o ?ssea observada na doen?a periodontal
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Blüm, Leonid. "Expression von MMP-2 und MMP-14 in verschiedenen Tumorkomponenten des Urothelkarzinoms /." Düsseldorf, 2008. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000278418.
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Kuittinen, O. (Outi). "Matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in hematological malignancies." Doctoral thesis, University of Oulu, 2003. http://urn.fi/urn:isbn:951426942X.
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Abstract
Gelatinases (MMP-2 and MMP-9) play a key role during
invasion and metastazising of malignant cells and they have been
shown to be associated to invasive phenotype and poor prognosis in
several solid tumours. However little is known about their role in
hematological malignancies. In the present work, gelatinase
expression and its clinicopathological correlations were studied
with immunohistochemical staining in 10 cases representing normal
bone marrow aspirate smears, 123 cases representing diagnostic
bone marrow samples of patients with different leukaemias (35 AML,
7 CLL, 6 CML, 75 ALL), 67 diagnostic paraffin-embedded lymph node
biopsies from patients with Hodgkin's lymphoma and 57 biopsies
from patients with non-Hodgkin's lymphomas. The lymphoma samples
were also stained with factor VIII antibody to evaluate the extent
of new vessel formation and the non-Hodgkin's lymphoma cases also
with tissue inhibitor of metalloproteinases -1 (TIMP-1) antibody.
CLL did not express either of the MMP enzymes, while CML in the
chronic phase expressed strongly both of the enzymes. In ALL,
gelatinase expression was weak and detectable in pediatric cases
in only 12.7% and in the adults in 65% of the cases. In adult ALL,
MMP-2 expression correlated strongly with an extramedullary and
invasive pattern of disease presentation. In AML MMP-2 positivity
had markedly favorable prognostic and predictive power. In
lymphoma studies, no correlations could be detected between
gelatinase expression and the clinical parameters of invasion.
MMP-9 positivity was related to the presence of B symptoms, which
difference was statistically significant in Hodgkin's lymphoma. In
Hodgkin's lymphoma, strong MMP-9 expression also implicated
decreased neovascularization. In both lymphoma types, strong MMP-9
expression correlated with unfavorable prognosis, which difference
was statistically significant in non-Hodgkin's lymphomas and
remained as a tendency in Hodgkin's lymphoma. MMP-2 had
statistically significant association with a favorable prognosis
in Hodgkin's lymphoma. Combination of the results of both
stainings further increased prognostic power. All together these
findings implicate that gelatinases could be used as prognostic
tools in AML and lymphomas albeit this needs to be verified in
larger materials.
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Ampudia, Rueda Amada, Crespo Guadalupe Sánchez, and Gómez Fernando Jiménez. "Diagnostic accuracy of the MMPI-2 with the Mexican criminal personality: The ROC curve analysis." Pontificia Universidad Católica del Perú, 2016. http://repositorio.pucp.edu.pe/index/handle/123456789/100481.
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The objective of this study is to assess the diagnostic accuracy of the personality of the Mexican criminal with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). The inventory was administered to 1,740 Mexican participants of which 870 (728 male and 142 female) are prison inmates, processed and/or sentenced for various crimes from various prisons in Mexico City, and the other 870 participants (728 male and 142 female) are not prison inmates. The ROC (Receiver Operating Characteristic) curve analysis was used to assess the level of diagnostic accuracy through indexes of the Area below the curve (ABC), sensitivity (S) and specificity (E). The analysis was differentiated by gender and showed significant differencesEl objetivo de este estudio es poder apreciar la precisión diagnóstica de la personalidad del delincuente mexicano con la prueba del Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Se administró la prueba a un total de 1740 participantes mexicanos de los que 870 (728 varones y 142 mujeres) son reclusos, procesados y/o sentenciados por diferentes delitos, procedentes de diversas cárceles del Estado y Distrito Federal, y otros 870 (728 varones y 142 mujeres) son personas no reclusas. Se utilizó el análisis de la curva ROC (Receiver Operating Characteristic) para apreciar el nivel de precisión diagnóstica a través de sus índices del Área Bajo la Curva (ABC), su Sensibilidad (S) y Especificidad (E). El análisis, diferenciado por género, mostró notables diferencias.
O objetivo do presente estudo consiste em avaliar a precisão diagnóstica da personalidade do delinquente mexicano através da prova Minnesota Multiphasic Personality Inventory-2 (MMPI-2). A prova foi administrada a 1.740 participantes mexicanos, dos quais 870 (728 homens e 142 mulheres) são reclusos, julgados e condenados por diferentes delitos, procedentes de diferentes estabelecimentos prisionais da cidade do México, e outros 870 (728 homens e 142 mulheres) são pessoas não reclusas. Foi utilizada uma análise da curva de ROC (Receiver Operating Characteristics) para avaliar o nível de precisão diagnóstica através dos índices da Área Abaixo da Curva (ABC), sua sensibilidade (S) e Especificidade (E). A análise de diferenciação entre sexos revelou diferenças significativas.
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Bourd-Boittin, Katia. "Rôle des métalloprotéinases matricielles (MMPs) dans l'odontologie." Paris 5, 2005. http://www.theses.fr/2005PA05M001.
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La dégradation protéolytique des constituants de la matrice extracellulaire par les métalloprotéinases matricielles (MMPs) joue un rôle majeur dans l'odontogénèse. Après avoir identifié la présence et le profil d'expression des gélatinases (MMP-2 et MMP-9), de la MMP-20 et des TIMP-1 et -2 dans l'incisive de rat, nous avons cherché à mieux comprendre comment les MMPs et plus particulièrement les gélatinases et la MMP-20 pouvaient agir dans les processus d'organisation et de minéralisation des matrices dentaires. L'inhibition de leur activité par un inhibiteur synthétique des MMPs à large spectre, le Marimastat, dans un modèle des germes embryonnaires de souris en culture, a pertubé les mécanismes de nucléation dans la matrice dentinaire et a provoqué des pertubations sévères de la mise en place et par conséquent de la minéralisation de l'émail. Ces importantes altérations observées au niveau structural sont associées à des modifications au niveau moléculaire. En présence de Marimastat, deux des protéines majoritaires du tissu dentaire, la sialoprotéine dentinaire (DSP) et plus particulièrement l'amélogénine s'accumulent de manière anormale dans la matrice extracellulaire. Ces pertubations se traduisent par une modification de leurs différentes formes moléculaires. Ceci démontre la nécessité de la dégradation progressive de ces constituants matriciels. Le clivage de l'amélogénine par la MMP-20 a déjà été rapporté. En revanche, la dégradation protéolytique de la DSP par des protéases n'a jamais été décrite auparavant, nous avons pu montrer que la DSP mais aussi l'amélogénine sont clivées de manière rapide et totale par la MMP-2 recombinante. Par contre la MMP-9 n'a pas d'effet sur ces deux protéines dans les mêmes conditions expérimentales. La large distribution de la MMP-2 au sein des tissus dentaires, ainsi que sa capacité à dégrader certains constituants spécifiques des matrices dentaires permettent de lui attribuer un rôle majeur en association avec la MMP-20 dans l'établissement et la minéralisation de la dentine et de l'émailThe proteolytic degradation of the ECM components by the matrix metalloproteinases (MMPs) is thought to play a crucial role in odontogenesis. The aim of this thesis was to analyse the expression of several MMPs, namely MMP-2, MMP-9 and MMP-20, as well as of their physiological inhibitors, the TIMP-1 and TIMP-2 during tooth development and study their role in the formation and maturation of dental matrices. The two gelatinases (MMP-2 and MMP-9), enamelysin (MMP-20) and TIMP-1 and -2 have shown a developmentally regulated expression and specific localization within the developing tootth. The role of these MMPs in the processing and mineralization of the dental matrix was further studied in an organotypic culture model of developing mouse tooth germ. The inhibition of the MMPs activity in this model by a broad spectrum synthetic inhibitor, Marimastat, altered dental matrix nucleation and caused severe disruptions of enamel organisation and mineralization. These macroscopic effects was associated with significant modifications at the molecular level. MMP inhibition deregulated the molecular processing of two major dental matrix proteins, amelogenin and dental sialoprotein (DSP), coinciding with their accumulation and the loss of their normal distribution. While the cleavage of amelogenin by MMP-20 has been extensively studied, that of DSP has not been previously described. Our experiments provide evidence that MMP-2 is able to efficiently degrade DSP as well as amelogenin, while under the same conditions, MMP-9 had no effect. Based on the intense expression and large distribution of MMP-2 and its importance in the processing of the dental matrix, we suggest a major role for this enzyme, in association with MMP-20, in the maturation and mineramization of dentin and enamel
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Domeij, Helena. "Expression and regulation of MMP-1 and MMP-3 in human gingival fibroblasts /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-544-5/.
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David, Arnaud. "Protéomique fonctionnelle des Métalloprotéases Matricielles (MMPs) dédiée à la détection des formes acitves de MMPs dans des protéomes complexes." Phd thesis, Museum national d'histoire naturelle - MNHN PARIS, 2007. http://tel.archives-ouvertes.fr/tel-00555061.
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Les Métalloprotéases matricielles (MMPs) constituent une famille des métalloprotéases à zinc capables conjointement de dégrader l'ensemble des protéines de la matrice extracellulaire. Aujourd'hui, vingt-trois MMPs humaines ont été identifiées et sont caractérisées par leur séquence en aminoacides et leur structure 3D fortement conservées. Ces enzymes sont exprimées de manière constitutive au cours des processus de remodelage tissulaire. Leur surexpression dans un certain nombre de pathologies étroitement liée au phénomène d'inflammation (arthrite, emphysème, cancer) fait des MMPs des cibles thérapeutiques de choix. Cependant, le remodelage entraînant des modifications des contacts cellulaires, les MMPs apparaissent aujourd'hui comme des protéines des voies de signalisation à part entière. Les récentes découvertes de substrats des MMPs ne faisant pas partie des constituants de la matrice extracellulaire renforcent cette vision. Dans le but d'identifier le rôle particulier et le taux d'expression protéique des MMPs dans un contexte pathologique, nous avons développé une technique de protéomique fonctionnelle dédiée à la détection des formes actives des MMPs dans des échantillons tumoraux. Cette technique repose sur le développement d'une nouvelle sonde de photoaffinité, basée sur la structure d'un puissant inhibiteur des MMPs de type phosphinique, permettant de cibler les MMPs sous forme active et de les isoler par marquage par photoaffinité. Le marquage par photoaffinité nous permet ainsi grâce à un élément radioactif incorporé à la sonde de radiomarquer les protéines ciblées. Cette sonde a montré in vitro sa capacité remarquable à modifier de manière covalente la hMMP-12 avec un rendement de 42 %, affichant une sensibilité extrême de détection (2.5 fmoles de hMMP-12). En présence de protéome complexe, la sensibilité de détection de la sonde pour la hMMP-12 est tout à fait comparable (5 fmoles) ; la hMMP-12 représente une fraction de 0.001 % de la quantité totale des protéines. Cette méthode nous a permis également d'identifier de manière indirecte les formes actives des gélatinases en comparant les extraits tumoraux traités par la sonde et les extraits tumoraux analysés en zymographie. Ces études indiquent que les niveaux d'expression des formes actives de MMPs sont très faibles (fmoles) ne permettant pas une caractérisation de celles-ci par spectrométrie de masse, ce qui constitue un véritable défi pouvant être abordé avec de nouvelles sondes incorporant une biotine. Cet exemple de protéines exprimées sous forme active en très faible abondance, implique une orientation des efforts à consentir vers le développement de nouvelles stratégies de capture.
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A, David Arnaud. "Protéomique fonctionnelle des métalloprotéases naturelles (MMPs) dédiée à la détection des formes actives de MMPs dans des protéomes complexes." Phd thesis, Museum national d'histoire naturelle - MNHN PARIS, 2007. http://tel.archives-ouvertes.fr/tel-00327187.
Full textAbstract:
Les Métalloprotéases matricielles (MMPs) constituent une famille des métalloprotéases à zinc capables conjointement de dégrader l'ensemble des protéines de la matrice extracellulaire. Aujourd'hui, vingt-trois MMPs humaines ont été identifiées et sont caractérisées par leur séquence en aminoacides et leur structure 3D fortement conservées. Ces enzymes sont exprimées de manière constitutive au cours des processus de remodelage tissulaire. Leur surexpression dans un certain nombre de pathologies étroitement liée au phénomène d'inflammation (arthrite, emphysème, cancer) fait des MMPs des cibles thérapeutiques de choix. Cependant, le remodelage entraînant des modifications des contacts cellulaires, les MMPs apparaissent aujourd'hui comme des protéines des voies de signalisation à part entière. Les récentes découvertes de substrats des MMPs ne faisant pas partie des constituants de la matrice extracellulaire renforcent cette vision. Dans le but d'identifier le rôle particulier et le taux d'expression protéique des MMPs dans un contexte pathologique, nous avons développé une technique de protéomique fonctionnelle dédiée à la détection des formes actives des MMPs dans des échantillons tumoraux. Cette technique repose sur le développement d'une nouvelle sonde de photoaffinité, basée sur la structure d'un puissant inhibiteur des MMPs de type phosphinique, permettant de cibler les MMPs sous forme active et de les isoler par marquage par photoaffinité. Le marquage par photoaffinité nous permet ainsi grâce à un élément radioactif incorporé à la sonde de radiomarquer les protéines ciblées. Cette sonde a montré in vitro sa capacité remarquable à modifier de manière covalente la hMMP-12 avec un rendement de 42 %, affichant une sensibilité extrême de détection (2.5 fmoles de hMMP-12). En présence de protéome complexe, la sensibilité de détection de la sonde pour la hMMP-12 est tout à fait comparable (5 fmoles) ; la hMMP-12 représente une fraction de 0.001 % de la quantité totale des protéines. Cette méthode nous a permis également d'identifier de manière indirecte les formes actives des gélatinases en comparant les extraits tumoraux traités par la sonde et les extraits tumoraux analysés en zymographie. Ces études indiquent que les niveaux d'expression des formes actives de MMPs sont très faibles (fmoles) ne permettant pas une caractérisation de celles-ci par spectrométrie de masse, ce qui constitue un véritable défi pouvant être abordé avec de nouvelles sondes incorporant une biotine. Cet exemple de protéines exprimées sous forme active en très faible abondance, implique une orientation des efforts à consentir vers le développement de nouvelles stratégies de capture.
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Lang, Rupert. "Klonierung, Expression, Reinigung und Kristallisation von Dipeptidyl Carboxypeptidase Röntgenstrukturanalyse der katalytischen Domänen von MMP-12, MT3-MMP und MMP-13/TIMP-2 /." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963846914.
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Munhoz, Francielle Boçon de Araujo. "Associação entre polifmorfismo na MMP-13 (isolado e em Haplótipo com MMP-1 e MMP-8) e tendinopatia primária do tibial posterior." reponame:Repositório Institucional da UFPR, 2014. http://hdl.handle.net/1884/37205.
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Orientadora : Profª Drª Maria Cristina L. G. SantosCo-orientador : Prof. Dr. Ricardo Lehtonen de Souza
Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Biologia Celular e Molecular. Defesa: Curitiba, 24/09/2014
Inclui referências
Área de concentração : Biologia celular e molecular
Resumo: O tendão tibial posterior (TTP) é particularmente vulnerável e sua insuficiência é reconhecida como a principal causa do pé plano adquirido do adulto. Alguns pacientes têm uma predisposição sem causa clinicamente reconhecida, sugerindo que as características individuais, incluindo fatores genéticos, desempenham um papel importante na tendinopatia. As metaloproteinases da matriz (MMP) são enzimas responsáveis por degradar e remodelar o colágeno, principal componente dos tendões. O objetivo do presente estudo foi investigar a associação do polimorfismo -77 (rs2252070) da MMP-13 isoladamente e em haplótipo com os polimorfismos -519 (rs1144393) e -1607 (rs1799750) da MMP-1 e -799 (rs11225395) da MMP-8 e a predisposição a disfunção do TTP. A amostra de 200 pacientes selecionados foi dividida em: grupo teste com 100 pacientes submetidos à procedimentos cirúrgicos e de diagnóstico histopatológico de lesão degenerativa do tendão tibial posterior e grupo controle com 100 pacientes com tendão do tibial posterior intacto e sem sinais de degeneração. O DNA dos voluntários foi obtido a partir de células epiteliais da mucosa bucal, por extração com acetato de amônio. A identificação dos genótipos foi realizada por PCR e RFLP. A análise estatística dos resultados foi realizada pelos testes de Mann-Whitney U (idade), Exato de Fisher (IMC), Regressão logística múltipla, Análise por combinação, Chi-quadrado (frequências alélicas e genotípicas) e SNPstats (haplótipos), todos com nível de significância de 5%. Houve uma diferença significativa nas frequências alélicas e genotípicas entre os grupos teste e controle para os polimorfismos -77 da MMP-13, -519 e -1607 da MMP-1 e -799 da MMP-8. Análise de haplótipo indicou diferença significativa entre os dois grupos estudados. De acordo com nossos resultados o polimorfismo -77 da MMP-13 isoladamente e em haplótipo com polimorfismos -519 e -1607 da MMP-1 e -799 da MMP-8 está associado à tendinopatia no tendão do tibial posterior. Palavras-chave: MMPs, MMP-1, MMP-8, MMP-13, Metaloproteinases, Polimorfismos em MMPs, Tendinopatia do Tibial Posterior.
Abstract: Posterior tibial tendon (PTT) is particularly vulnerable and its insufficiency is recognized as the main cause of adult acquired flatfoot. Some patients have a predisposition without clinically recognized cause, suggesting that individual characteristics, including genetic factors, play an important role in tendinopathy. The matrix metalloproteinases (MMP) are enzymes responsible for degrading and remodeling the collagen, the main compomente tendons The objective of the present study is to investigate the association of -77 (rs2252070) matrix metalloproteinase-13 (MMP-13) polymorphism and its haplotypes with -1607 (rs1799750), -519 (rs1144393) MMP-1 and -799 (rs11225395) MMP-8 and risk of PTT dysfunction. The sample of 200 selected patients was divided into test group: 100 patients undergoing surgical procedures and pathological diagnosis of degenerative lesions of the posterior tibial tendon, and control group: 100 patients with posterior tibial tendon intact and no signs of degeneration. The DNA of the volunteers was obtained from oral mucosa epithelial cells, by extraction with ammonium acetate. PCR and RFLP were used for analysis of genotypes. Statistical analysis of results was performed by Man Whitney U test (age), Fisher's Exact (IMC), multiple logistic regression, analysis by combining and Chi-squared (allelic and genotype frequency) and SNPstats (haplotype), test with significance level of 5%. There was a significant difference in the presence of the different alleles and genotypes between the control group and test group for the -77 MMP-13,-519 and -1607 MMP-1, -799 MMP-8, polymorphism. Global haplotype analysis indicated a significant difference between both groups. According to our results, -77 MMP-13polymorphism isolated and its haplotypes with -519, -1607 MMP-1 and -799 MMP-8 are associated to tendinopathy in posterior tibial tendon. Keywords: MMPs, MMP-1, MMP-8, MMP-13, metalloproteinases, Polymorphisms in MMPs, Posterior Tibial Tendinopathy.
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Sánchez, Crespo Guadalupe, Gómez Fernando Jiménez, and Rueda Amada Ampudia. "Detecting the simulation profile in MMPI-2: A proposal based on research." Pontificia Universidad Católica del Perú, 2012. http://repositorio.pucp.edu.pe/index/handle/123456789/101113.
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The aim of this study is to offer a profile detector of the falsifications that could be done to the MMPI-2. We propose minimal changes in the reversed order of the direct punctuations of L y K and the addition of four new specific scales: Odecp, Ds-r, S, F-K. Two groups were used: a control group, composed by normal and clinical subgroups who answered to the MMPI-2 according to standard procedure, and an experimental group, composed by three subgroups with different answer instructions: to give a good image, a bad image or an inconsistent answer. The result is a profile with the proposed scales of validity that initially allow the detection of different falsifications by the subjects when answering the MMPI-2 test.Se propone un perfil detector de las falsificaciones que se dan con el MMPI-2, proponiendo la inversión de las puntuaciones directas de L y K y añadiendo cuatro nuevas escalas específicas: Odecp, Ds-r, S, F-K. Para esto se formaron dos grupos: control, compuesto por los subgrupos normal y clínico que contestan de forma estándar al MMPI-2, y experimental, formado por tres subgrupos instruidos para contestar al MMPI-2 de una manera determinada: mostrando buena imagen, mala imagen y de forma inconsistente. El resultado de este estudio es un perfil con las escalas de validez propuestas para la detección de las distintas falsificaciones que pueden realizar los sujetos que han contestado al cuestionario del MMPI-2.
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Westin, Maria Cristina do Amaral 1949. "Expressão das proteínas MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 e VEGF-A na NIC 3 e no carcinoma invasor do colo do útero = Expression of the proteins MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 and VEGF-A in the CIN 3 and cervical cancer." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/313599.
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Orientadores: Luiz Carlos Zeferino, Silvia Helena Rabelo dos SantosTexto em português e inglês
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: O carcinoma escamoso do colo uterino é precedido pela neoplasia intraepitelial cervical grau 3 (NIC 3). A invasão tumoral envolve a degradação da matriz extracelular e membrana basal do epitélio por enzimas proteolíticas denominadas metaloproteinases (MMPs). Os inibidores teciduais das metaloproteinases (TIMPs) também interferem no processo de invasão. Angiogênese é condição indispensável para a progressão tumoral. Objetivo: Analisar a expressão de MMP-2, MMP-9, MMP-14, TIMP-1, TIMP-2 e VEGF-A na NIC 3 e carcinoma do colo uterino. Sujeito e Métodos: Estudo do tipo comparativo observacional constituído de três grupos:- Grupo 1: 55 casos com diagnóstico de NIC 3, Grupo 2: 30 casos com NIC 3 e carcinoma associados e Grupo 3: 46 casos com carcinoma. A expressão protéica foi pesquisada separadamente nas células tumorais e estromais por reação imunoistoquímica. Para estabelecer a porcentagem de células imunopositivas utilizou-se software morfométrico. Análise Estatística: Aplicou-se o Teste T-pareado ou de Mann-Whitney ou Wilcoxon Signed Rank. Resultados: Em todos os grupos, a expressão tumoral de MMP-14 foi maior que a estromal. Inversamente, a expressão de TIMP-2 foi maior nas células estromais que nas tumorais, em cada grupo diagnóstico. A expressão de MMP-9 foi maior nas células estromais que nas tumorais, com exceção do componente invasor do Grupo 2. A expressão estromal de TIMP-1 foi maior que a tumoral no carcinoma e, ao contrário, sua expressão foi maior nas células tumorais da NIC 3. A expressão de VEGF-A foi maior apenas nas células tumorais da NIC 3. Comparando a expressão dos marcadores entre os grupos, foram encontradas as maiores diferenças entre grupos extremos, ou seja, entre NIC 3 e carcinoma. A expressão de MMP-2 nas células estromais foi maior no componente NIC 3 do Grupo 2 que no NIC 3 do Grupo 1. A expressão de VEGF-A nas células estromais do carcinoma foi maior que nas células estromais da NIC 3. Conclusões: Os resultados deste estudo sugerem que a expressão de TIMP-1 aumenta nas células do estroma e diminui nas células tumorais quando a NIC 3 progride para carcinoma invasor. MMP-9 e TIMP-2 tiveram expressão similar na NIC 3 e no carcinoma, o que limita inferências sobre seu papel na progressão neoplásica. O padrão imunoistoquímico da expressão das MMPs, TIMPs e VEGF-A na NIC 3 e no carcinoma invasivo, quando estas lesões estavam associadas, foi semelhante. A expressão do VEGF-A foi maior nas células tumorais do que nas estromais da NIC 3, porém quando esta lesão progride para carcinoma invasivo sua expressão aumenta nas células do estroma e não se altera nas tumorais. A expressão de MMP-14, MMP-2, TIMP-1 e VEGF-A aumentou com a gravidade da neoplasia
Abstract: Introduction: Squamous cell carcinoma of the cervix is preceded by cervical intraepithelial neoplasia grade 3 (CIN 3). Tumor invasion involves degradation of extracellular matrix and epithelium basement membrane by proteolytic enzymes called metalloproteinases (MMPs). Tissue inhibitors of metalloproteinases (TIMPs) are also involved in the invasion process. Angiogenesis is a prerequisite for tumor progression. Objective: To analyze the expression of MMP-2, MMP-9 and MMP-14, TIMP-1, TIMP-2 and VEGF-A in CIN 3 and invasive carcinoma. Subject and Methods: This comparative observational study was consists of three groups: Group 1: 55 cases diagnosed with CIN 3, Group 2: 30 cases with CIN 3 associated with invasive carcinoma and Group 3: 46 cases with invasive carcinoma. Protein expression was investigated separately in tumor and stromal cells by immunohistochemistry and evaluated by the percentage of cells positive for immunostaining using morphometric software. Statistical Analysis: Was performed applying paired t-test or Mann-Whitney or Wilcoxon Signed Rank. Results: In each diagnostic group, expression markers were significantly higher: MMP-14 in tumor cells, and TIMP-2 in stromal cells; also MMP-9 expression was significantly higher in stromal cells, except in invasive component of group 2, and TIMP-1 had significantly higher expression in stromal cells of invasive carcinoma and in tumor cells of CIN 3. VEGF-A expression was significantly higher only in tumor cells CIN 3. Comparing the expression of markers between groups, two by two, we find the greatest differences between the extreme groups, i.e. between invasive carcinoma and CIN 3. The expression of MMP-2 was significantly greater in the stromal component CIN 3 in group 2 than in CIN 3 only. The expression of VEGF-A was significantly higher in the group stromal cell carcinoma when compared to stromal cells CIN 3. Conclusions: The results of this study suggest that the expression of TIMP-1 increases in the stromal cells and decreases in tumor cells when CIN 3 progresses to invasive carcinoma. MMP-9 and TIMP-2 had similar expression in CIN 3 and invasive carcinoma, which limits inferences about its role in neoplastic progression. The immunohistochemical pattern of expression of MMPs, TIMPs and VEGF-A in CIN 3 and invasive carcinoma, as these lesions were associated, was similar. The expression of VEGF-A was higher in tumor cells than in stromal cells in CIN 3, but when the lesion progresses to invasive carcinoma its expression increases in the stromal cells and the tumor cells does not change. The expression of MMP-14, MMP-2, TIMP-1 and VEGF-A was increased with the severity of the neoplasia
Doutorado
Oncologia Ginecológica e Mamária
Doutora em Ciências da Saúde
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Ayoub, Albert E. "On the contribution of MMP-2 and MMP-9 to the postnatal cerebellar corticogenesis." Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=3137.
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Thesis (Ph. D.)--West Virginia University, 2003.Title from document title page. Document formatted into pages; contains viii, 153 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 107-135).
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Crowther, Mathew. "The MMP-2/MT1-MMP/TIMP-2 enzyme system in abdominal aortic aneurysm disease." Thesis, University of Leicester, 1999. http://hdl.handle.net/2381/29593.
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Abdominal aortic aneurysm (AAA) represents a complex biochemical pathology, characterised by marked tissue remodelling and severe inflammation. The weakening of the arterial wall is assessed with elevated production of matrix metalloproteinases (MMPs), enzymes that degrade extracellular matrix components causing a reduction in tensile strength and mechanical integrity. However, the cause of this overproduction of MMPs remains poorly understood. Analysis of small AAAs has demonstrated that MMP-2 is the most prominent MMP, an enzyme known to be produced by most mesenchymal cells. The present thesis investigated the hypothesis that aortic smooth muscle cells (SMCs) are the source of excess MMP-2, which may degrade elastin fibres and initiate the degenerative and inflammatory process characteristic of aneurysmal disease. Histological analysis of control and aneurysm tissue was followed by focused testing of the hypothesis, by isolating and comparing SMCs from control and aneurysmal aortas. Aneurysmal SMCs expressed significantly more MMP-2 than control cells, but levels of MT1-MMP and TIMP-2 were not significantly different. MMP-2 was shown to be capable of inducing elastolytic changes characterise of aneurysm disease in a porcine in vitro model of AAA. Similar methods suggested that this was not the case in dermal fibroblasts, providing evidence that the elevated level of MMP-2 in SMCs was not reflected in all mesenchyme-derived tissues. Published evidence suggested that AAA may be a local manifestation of a generalised dilating process, and this hypothesis was addressed by examining the MMP expression of vascular tissue remote from the aneurysm site. Inferior mesenteric vein from AAA patients produced elevated levels of MMP-2 compared to control vein, suggesting that this phenomenon may be systemic but vascular tissue-specific in nature. These data suggest that AAA patients may be predisposed to vascular elastolysis, manifesting itself in later life as aneurysmal dilatation of the aorta. In conclusion, a novel model of AAA aetiology is proposed.
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Dourado, Ana Lúcia de Oliveira. "Investigação da integridade das barreiras oculares, da presença de Pro-MMP-2, MMP-2, Pro-MMP-9, MMP-9, e Dosagem de Proteínas no humor aquoso de cães naturalmente infectados por Leishmania infantum /." Araçatuba, 2019. http://hdl.handle.net/11449/191061.
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Orientador: Gisele Fabrino MachadoResumo: A leishmaniose visceral (LV) é uma antropozoonose sistêmica de evolução crônica, causada pela Leishmania infantum, de distribuição mundial, acometendo cães e humanos no ambiente urbano. Nos cães, são observados sinais clínicos frequentes tais como emagrecimento e linfoadenomegalia; e existem sinais clínicos menos estudados como as alterações inflamatórias no globo ocular. A hipótese deste estudo é que a ativação de MMPs pode estar envolvida na alteração da permeabilidade das barreiras oculares. Para verificar isto a presença e/ou ativação das metaloproteinases (MMP) 2 e 9, foram quantificadas por meio de zimografia do humor aquoso de 28 cães com LVC e 4 cães do grupo controle. A presença de Pro-MMP-2 foi detectada no humor aquoso de 27 animais do grupo infectado (27/28 cães) e também no grupo controle, sem diferir estatisticamente. A MMP-2 foi detectada no humor aquoso de um animal infectado. Já Pro-MMP-9 (10/28) e/ou sua forma ativa, (11/28) foram observadas em animais infectados e não no grupo controle. Para verificar se a presença das MMPs ativas poderia interferir com a integridade das barreiras oculares em cães com LVC, foi quantificada a presença de proteínas totais no soro e no humor aquoso destes cães. A quantificação de proteínas totais, albumina e globulinas no soro foram semelhantes aos valores citados na literatura no soro de animais com LV. No humor aquoso os valores individuais de proteína total, determinados pelo método Microprot apresentaram variação individua... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Visceral leishmaniasis (VL) is a systemic anthropozoonosis of chronic evolution, caused by Leishmania infantum, worldwide, affecting dogs and humans in the urban environment. In dogs, frequent clinical signs such as weight loss and lymphadenomegaly are observed; and there are less studied clinical signs such as inflammatory changes in the eyeball. The hypothesis of this study is that the activation of MMPs may be involved in altering the permeability of eye barriers. To verify this the presence and / or activation of metalloproteinases (MMP) 2 and 9 were quantified by aqueous humor zymography of 28 dogs with CVL and 4 dogs of the control group. The presence of Pro-MMP-2 was detected in the aqueous humor of 27 animals of the infected group (27/28 dogs) and also in the control group, without statistically differing. MMP-2 was detected in the aqueous humor of an infected animal. Pro-MMP-9 (10/28) and / or its active form (11/28) were observed in infected animals and not in the control group. To verify whether the presence of active MMPs could interfere with the integrity of eye barriers in dogs with CVL, the presence of total proteins in serum and aqueous humor of these dogs was quantified. The quantification of serum total proteins, albumin and globulins were similar to those reported in the literature of serum from animals with VL. In aqueous humor the individual values of total protein determined by the Microprot method showed very large individual variation in both groups, a... (Complete abstract click electronic access below)
Mestre
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Johnson, Raiman K. "MMPI, prediction of success in National Guard enlistees." Virtual Press, 1986. http://liblink.bsu.edu/uhtbin/catkey/469338.
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The purpose of this study was to determine if certain mean T scores on the MMPI would vary significantly for careerists in National Guard Units when compared to typical non-clinical scores. It was also an attempt to observe differences between certain MMPI scales to determine whether further study of these scales as gross predictors of candidates more likely to succeed in a military environment appears appropriate.Eleven scales of the MMPI were selected for this purpose and this study attempted to evaluate the scales which might be used. Among the scales studied were: L (Lie); 3 (Conversion Hysteria); 4 (Psychopathic Deviate); 5 (Masculinity-Femininity); Es (Ego Strength); Re (Social Responsibility); A (Conscious Anxiety); and Dy (Dependency). Three directional hypotheses were developed: (1) careerists, in general, will score lower on the 3, 4, 5 (males only), 8, A and Dy scales while they will score higher on the L, 5 (females only) 9, Es Re and Cn than will a typical non-clinical population. (2) Certain personality characteristics, measured by the MMPI, have a significant correlation to the proclivity of an individual to enter and continue in part- or full-time military service. (3) The identified scales can then be considered for further study to determine the feasibility of their use in a screening program to predict success or failure of enlistees as reported by their intention to remain in service upon completion of their initial enlistment obligation.Participants were volunteers from Indiana National Guard Units in both rural and urban areas. Each participant was provided a copy of the self-administered MMPI and requested to complete it in accordance with the written instructions. In addition, they were provided an informed consent form containing a written explanation of the purpose for their participation and delineating the scope of the study.To analyze the data an analysis of variance was used which demonstrated significant differences between male and female careerists and their "civilian" counterparts on seven of the 11 scales, supporting the first hypothesis. After completing correlation matrices for the eleven scales and an analysis of variance, using age as the covariate for the respondents, the data were reviewed. This revealed that, for the limited female population seven of the 11 scales supported the third hypothesis but only three scales were found significant for males suggesting the need for further study to clarify this disparity.
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Prouty, Kathleen Veronica. "MMPI patterns in codependency: Before and after treatment." Diss., The University of Arizona, 1992. http://hdl.handle.net/10150/185762.
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The term "codependency" is emerging in the mental health field on a daily basis. However, along with this term comes confusion regarding what "codependency" is and how to effectively treat it. Since the term originated within the addiction studies arena, Twelve-Step programs have taken on the challenge of treating the fast-growing population of "codependents". The purpose of the present study was twofold. First, it investigated personality characteristics and traits shared by individuals having been treated for codependency issues. And second, it investigated the effects of a Twelve-Step, intensive, residential treatment program on these individuals. The subjects used in this study were identified as "codependents" due to significant, dysfunctional relationships within their lives. The research questions investigated by this study included the following: (1) What are the common demographic, personality or behavioral characteristics seen in individuals with codependency issues? And are there other identifiable factors considered contributory to treatment outcome? (2) Is intensive, short-term, residential treatment based on the Twelve-Step model, an effective approach with individuals dealing with codependency issues? (3) Do changes made during the course of treatment remain stable over time? The instruments utilized in this study to answer the above research questions included the MMPI and a Self-Evaluation Questionnaire developed by the investigator. Individuals who had been out of treatment for at least three months were solicited for their participation. Fifty subjects were used. Results showed that individuals treated for codependency tend to have low self-esteem, self-deprecation, stress, rebellion and anger, physical complaints, depression, high dependency needs, mistrust in others, and limited ego strength. They shared many diagnostic characteristics with the Self-defeating, Borderline and Dependent Personality Disorders. Treatment intervention proved to be effective in diminishing elevated levels of psychopathology. The results obtained at the time of discharge from treatment remained stable over an extended period of time.
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Candiani, Gabriele. "TNF-a et MMPs dans le remodelage cardiaque." Paris 11, 2006. http://www.theses.fr/2006PA11T016.
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Funk, Russell. "MMPI and the juvenile sex offender Russell Funk." PDXScholar, 1988. https://pdxscholar.library.pdx.edu/open_access_etds/3810.
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This study examined the effectiveness of the MMPI in identifying juvenile sex offenders. This study examined the hypothesis that previously identified subscales of the MMPI (i.e., Toobert et al. (1959) Pe scale and Dolan (1986) Ic scale) could be used in discriminating juvenile sex offenders (n=l 02) (and subgroups of juvenile sex offenders i.e., pedophiles n=79, and incest perpetrators n=41) from a control group of 40 juvenile offenders who had been adjudicated for non-sex related crimes. The study yielded results which indicate that the Pe subscale was not effective in discriminating pedophiles from non-pedophile sex offenders or from the control group. The results also indicated that the Ic subscale was not effective in discriminating incest perpetrators from non-incest sex offenders or the control group. The results from the data also indicate that the control group appeared more pathological than the sex offender group, based on their respective MMPI profiles. In addition, in comparison with previous research on adult sex offenders, there appears to be differences between adult sex offenders and juvenile sex offenders when comparing mean two point code scores. Problems in defining subgroups were discussed. A lack of research in the area of juvenile sex offenders was identified and a strong recommendation for further research in this area was made.
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Smith, Ashley M. "Assessing Personality Disorders Using the MMPI-2-RF." Kent State University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=kent1279132568.
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Lander, Bradley Norman. "The identification of cocaine addiction with the MMPI /." The Ohio State University, 1989. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487672245899867.
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Scheemann, Katja. "Bedeutung von MMP-2 und MMP-9 bei der Lungenschädigung nach extrakorporaler Zirkulation im Tiermodell." [S.l.] : [s.n.], 2001. http://www.diss.fu-berlin.de/2002/128/index.html.
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Salmon, Cristiane Ribeiro. "Expressão de colageno tipo I, MMP-2, MMP-8, MMP-14 eTIMPS no ligamento periodontal de incisivos de ratos em condições funcionais normal e alteradas." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288487.
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Orientador: Pedro Duarte NovaesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O ligamento periodontal de incisivos de ratos é um tecido conjuntivo com a função de ancoragem, suporte do dente e provável papel na erupção dental. Esse tecido possui um alto grau de remodelação, cujo colágeno tipo I (Col-1) é um dos seus componentes principais. As metaloproteinases (MMPs) são enzimas que estão presentes no ligamento periodontal e degradam quase todos os constituintes da matriz extracelular. Alterações nas condições funcionais do dente podem provocar mudanças no metabolismo das células do ligamento, modificando o balanço entre a síntese das proteínas da matriz extracelular e a degradação pelas MMPs. O objetivo desse estudo é quantificar a expressão de mRNA de Col-1, MMP-2, MMP- 8, MMP-14, TIMP-1 e TIMP-2, identificar as células que expressam esses mRNAs e a localizar as proteínas no ligamento periodontal de incisivos de ratos submetidos a condições funcionais alteradas experimentalmente. Ratos Lewis machos foram utilizados, subdivididos em 4 grupos de acordo com as seguintes condições funcionais a que os incisivos inferiores foram submetidos por um período de 7 e 14 dias: normofuncional, hiperfuncional, hipofuncional e erupção contida. Os incisivos foram extraídos e o ligamento periodontal coletado por meio de leve raspagem de suas superfícies distal, lingual e mesial. Após a extração do RNA total e a síntese de cDNA, foi feita a quantifição relativa por PCR em Tempo Real. Para a localização do mRNA e das proteínas de interesse no ligamento periodontal foram utilizadas as técnicas de hibridização in situ e imunohistoquímica, utilizando-se 5 ratos para cada condição funcional e por período. Decorridos os tempos os animais foram sacrificados, tiveram as hemimandíbulas removidas, fixadas e processadas para a obtenção de cortes histológicos transversais. A análise da expressão gênica mostrou uma redução nos níveis de mRNA para o Col-1, MMPs e TIMPs em todos os grupos experimentais quando comparados ao normofuncional. Redução significativa foi encontrada nos grupos tratados por 7 dias, e houve aumento dos níveis de mRNA aos 14 dias para os genes estudados. Aumento significante nos níveis de mRNA (p<0,05) foi encontrado somente para MMP-2 no grupo hipofuncional por 7 dias. A redução (p<0,05) dos níveis de MMP- 8 no grupo contido por 7 e 14 dias parece estar relacionada ao aumento do inibidor TIMP-1. As MMPs e TIMPs citadas foram localizadas no ligamento periodontal e os resultados sugerem que esses genes são expressos por fibroblastos, cementoblastos, osteoblastos e osteoclastos. O Col-1 foi imunolocalizado no ligamento periodontal na região junto ao osso alveolar, enquanto a TIMP-2 estava mais concentrada na região adjacente ao dente. Os resultados sugerem que as alterações nas condições funcionais dos incisivos de rato provocam uma modificações no metabolismo do ligamento periodontal pelas mudanças nos níveis de expressão de Col-1, MMPs e TIMPs, ocorrendo picos de aumento ou redução da expressão com tendência de retorno à normalidade. O balanço entre a produção de Col-1, MMPs e TIMPS parece ter um importante papel no controle da taxa de erupção dos incisivos de ratos
Abstract: Periodontal ligament is a connective tissue that provides anchorage and support to the tooth, and it has a probable role in the tooth eruption. The extracelular matrix consists predominantly of collagen type I (Col-1) and the turnouver of collagen fibers is intense. Matrix metalloproteinases (MMPs) are members of a family of enzymes capable to degrade almost all components of the extracellular matrix. They are present in the periodontal ligament. It is supposed that tooth functional conditions alterations may promote changes in the metabolism of periodontal ligament cells, modifying the balance between the synthesis of extracellular matrix proteins and their degradation by MMPs. The aim of the present study is to quantify the levels of mRNA of Col-1, MMP-2, MMP-8, MMP-14, TIMP-1 and TIMP-2, identify the cells expressing these mRNA and locate these proteins in the periodontal ligament of rat incisors submitted to altered functional conditions. Lewis male rats were randomly assigned to 4 groups and their lower incisors were submitted to different functional conditions: normofunctional, hipofunctional, hiperfunctional and restraint, during 7 or 14 days. The teeth were extracted and the periodontal ligament was collected by gently scaling of the distal, lingual and mesial tooth surface. Total RNA was extracted and the synthesis of the cDNA was performed for Relative PCR Quantification. In situ hybridization and immunohistochemistry were performed to detect the cell expression and the proteins localization in the periodontal ligament. Five rats for each functional condition were sacrified after 7 and 14 experimental days.The rat hemimandubles were removed for histological processing to obtain 3µm transversal sections. Analysis of the expression of Col-1, MMPs and TIMPs showed a down-regulation for all genes in the groups studied in relation to the normofuctional group. Significant down-regulation (p<0,05) was found in the groups treated during 7 days, and increased levels of mRNA was related to 14 days of treatment. Significant increased levels of mRNA (p<0,05) were found only for MMP-2 to the hipofunctional group at 7 days. Reduction (p<0,05) of the levels of mRNA for MMP-8 in the restraint group at 7 and 14 days seems to be related to the increased levels of its inhibitor, TIMP-1. MMPs and TIMPs were found been expressed in the periodontal ligament by fibroblasts, cementoblasts, osteoblasts and osteoclasts. Col-1 was localized at the region adjacent to the alveolar bone, whereas TIMP-2 was concentrated adjacent to the tooth region of the periodontal ligament. The results obtained suggest that the alterations on the functional conditions of the rat incisors produce changes in the metabolism of the periodontal ligament tissue by changing the levels of COL-1, MMPs and TIMPs. Up-regulation peaks or downregulation peaks seem to be conduced to the normal levels of expression along the experimental time. The balance between production of Col-1, MMPs and TIMPs may have an important role in the control of the eruption rate of rat incisors
Doutorado
Histologia e Embriologia
Doutor em Biologia Buco-Dental
50
Bonnet, Amandine. "Etudes de trois métalloprotéases matricielles, MT1-MMP, MT5-MMP et MMP-12 dans l'amyloïdogenèse et les atteintes inflammatoires et vasculaires associées à la maladie d'Alzheimer." Thesis, Aix-Marseille, 2017. http://www.theses.fr/2017AIXM0036.
Full textAbstract:
La maladie d’Alzheimer (MA) est la maladie neurodégénérative la plus commune et reste à ce jour incurable. Elle se caractérise par l’accumulation dans le cerveau du peptide neurotoxique bêta-amyloïde (Aβ), par une neuroinflammation et des atteintes neurovasculaires, qui ensemble induisent la mort des neurones et des déficits cognitifs. En raison de leurs activités multiples, les métalloprotéases matricielles (MMPs) émergent comme des acteurs importants dans la MA. Mes travaux ont permis de mieux comprendre l’implication de 3 de ces MMPs dans la MA et soulignent le caractère spécifique et complémentaire de MT1- et MT5-MMP, directement impliquées dans la production d’Aβ, et le rôle de MMP-12 dans la neuroinflammation et dans la perte d’intégrité de la barrière hémato-encéphalique, un système vasculaire particulier qui protège efficacement le cerveau. Mes travaux ouvrent des perspectives dans le développement de nouvelles stratégies thérapeutiques basées sur la modulation de ces MMPsAlzheimer's disease (AD) is the most common neurodegenerative disease and remains to this day incurable. It is characterized by the accumulation in the brain of the beta-amyloid (Aß) neurotoxic peptide, by neuroinflammation and neurovascular damage, which together induce neuronal death and cognitive deficits. Because of their multiple activities, matrix metalloproteinases (MMPs) are emerging as important players in AD. My work has provided insight into the involvement of 3 of these MMPs in AD and highlight the specific and complementary nature of MT1- and MT5-MMP, directly involved in the production of Aß, and the role of MMP-12 in neuroinflammation and in the loss of integrity of the blood-brain barrier, a particular vascular system, which effectively protects the brain. My work opens perspectives in the development of new therapeutic strategies based on the modulation of these MMPs