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Uptake of CCR7 by KIR2DS4+ NK Cells Is Induced upon Recognition of Certain HLA-C Alleles

Pesce, Silvia; Carlomagno, Simona; Moretta, Alessandro; Sivori, Simona; Marcenaro, Emanuela
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN
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The KIR2DS4 receptor is the oldest KIR2DS expressed by human NK lymphocytes. The specificity of recognition of this receptor for various HLA class I alleles has been demonstrated; however it remains poorly understood whether these interactions may result in the activation of some specific functions in NK cells. Here, we examined the functional outcome of the KIR2DS4/HLA class I interaction by the use of an alternative functional system based on the ability of KIR2DS4 to regulate the mechanism of trogocytosis by NK cells. We demonstrate that KIR2DS4 can induce the uptake of CCR7 by KIR2DS4+ NKG2A+ NK cell clones after interacting with CCR7+ target cells expressing HLA-Cw4 and HLA-Cw6 alleles. However this interaction is not always sufficient to override the inhibition generated by NKG2A expressed on the same NK cells. The recognition of HLA-Cw4 was confirmed by experiments of cytotoxicity against HLA-C-transfected cells. We also show that, different from resting NK cells, the acquisition of CCR7 in response to IL-18 cannot occur in IL2-activated NK cells because of a marked downregulation in their IL-18Rα expression. As a consequence trogocytosis represents the major mechanism by which KIR2DS4+ activated NK cells acquire the expression of this chemokine receptor.

Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase

Moccia, Marialuisa; Liu, Qingsong; Guida, Teresa; Federico, Giorgia; Brescia, Annalisa; Zhao, Zheng; Choi, Hwan Geun; Deng, Xianming; Tan, Li; Wang, Jinhua; Billaud, Marc; Gray, Nathanael S.; Carlomagno, Francesca; Santoro, Massimo
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 05/06/2015 EN
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Oncogenic mutation of the RET receptor tyrosine kinase is observed in several human malignancies. Here, we describe three novel type II RET tyrosine kinase inhibitors (TKI), ALW-II-41-27, XMD15-44 and HG-6-63-01, that inhibit the cellular activity of oncogenic RET mutants at two digit nanomolar concentration. These three compounds shared a 3-trifluoromethyl-4-methylpiperazinephenyl pharmacophore that stabilizes the ‘DFG-out’ inactive conformation of RET activation loop. They blocked RET-mediated signaling and proliferation with an IC50 in the nM range in fibroblasts transformed by the RET/C634R and RET/M918T oncogenes. They also inhibited autophosphorylation of several additional oncogenic RET-derived point mutants and chimeric oncogenes. At a concentration of 10 nM, ALW-II-41-27, XMD15-44 and HG-6-63-01 inhibited RET kinase and signaling in human thyroid cancer cell lines carrying oncogenic RET alleles; they also inhibited proliferation of cancer, but not non-tumoral Nthy-ori-3-1, thyroid cells, with an IC50 in the nM range. The three compounds were capable of inhibiting the ‘gatekeeper’ V804M mutant which confers substantial resistance to established RET inhibitors. In conclusion, we have identified a type II TKI scaffold...

Immunosuppression and Multiple Primary Malignancies in Kidney-Transplanted Patients: A Single-Institute Study

Santangelo, Michele L.; Criscitiello, Carmen; Renda, Andrea; Federico, Stefano; Curigliano, Giuseppe; Dodaro, Concetta; Scotti, Alessandro; Tammaro, Vincenzo; Calogero, Armando; Riccio, Eleonora; Pisani, Antonio; Carlomagno, Nicola
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
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Immunodeficiency is associated with higher cancer incidence. However, it is unknown whether there is a link between immunodeficiency and development of multiple primary malignancies. In the present study we analyse this link focusing on kidney-transplanted patients, as they are at higher risk of developing cancer due to the chronic assumption of immunosuppressants. We followed up 1200 patients who underwent kidney transplantation between 1980 and 2012. A total of 77/1200 kidney-transplanted patients developed cancer and 24 of them developed multiple cancers. Most multiple cancers were synchronous with a nonsignificant association between cancer and rejection episodes. In the general cancer population, one-ninth of patients are at higher risk of developing a second tumor over a lifetime; hence it would be reasonable to conclude that, from a merely theoretical and statistical viewpoint, long-term transplanted patients potentially have a higher risk of developing MPMs. However, data did not confirm this assumption, probably because these patients die before a second primary malignancy appears. Despite many observations on the increased incidence of different tumor types in immunodeficient patients and despite immunosuppression certainly being a predisposing factor for the multicancer syndrome...

Multiple splenic hamartomas and familial adenomatous polyposis: a case report and review of the literature

Carlomagno, Nicola; Duraturo, Francesca; Candida, Maria; De Rosa, Marina; Varone, Valeria; Ciancia, Giuseppe; Calogero, Armando; Santangelo, Michele L
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em 04/07/2015 EN
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Mitral peak early diastolic filling velocity to deceleration time ratio as a predictor of prognosis in patients with chronic heart failure and preserved or reduced ejection fraction

Pirozzi, Flora; Paglia, Antonella; Sasso, Laura; Abete, Pasquale; Carlomagno, Angelo; Tocchetti, Carlo G; Bonaduce, Domenico; Petretta, Mario
Fonte: Science Press Publicador: Science Press
Tipo: Artigo de Revista Científica
Publicado em /07/2015 EN
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16.54%

Ipilimumab in the treatment of metastatic melanoma: management of adverse events

Della Vittoria Scarpati, Giuseppina; Fusciello, Celeste; Perri, Francesco; Sabbatino, Francesco; Ferrone, Soldano; Carlomagno, Chiara; Pepe, Stefano
Fonte: Dove Medical Press Publicador: Dove Medical Press
Tipo: Artigo de Revista Científica
EN_US
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Recently, “ipilimumab,” an anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) monoclonal antibody, has been demonstrated to improve overall survival in metastatic melanoma. “CTLA-4” is an immune-checkpoint molecule that downregulates pathways of T-cell activation. Ipilimumab, by targeting CTLA-4, is able to remove the CTLA-4 inhibitory signal, allowing the immune system to react to cancer cells. Due to its immune-based mechanism of action, ipilimumab causes the inhibition of CTLA-4-mediated immunomodulatory effects, the enhancement of antitumor specific immune response mediated by the weakening of self-tolerance mechanisms while exacerbating the development of autoimmune diseases and immune-related adverse events, including dermatitis, hepatitis, enterocolitis, hypophysitis, and uveitis.

Identification of Novel Small Molecule Inhibitors of Oncogenic RET Kinase

Moccia, Marialuisa; Liu, Qingsong; Guida, Teresa; Federico, Giorgia; Brescia, Annalisa; Zhao, Zheng; Choi, Hwan Geun; Deng, Xianming; Tan, Li; Wang, Jinhua; Billaud, Marc; Gray, Nathanael S.; Carlomagno, Francesca; Santoro, Massimo
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
EN_US
Relevância na Pesquisa
16.54%
Oncogenic mutation of the RET receptor tyrosine kinase is observed in several human malignancies. Here, we describe three novel type II RET tyrosine kinase inhibitors (TKI), ALW-II-41-27, XMD15-44 and HG-6-63-01, that inhibit the cellular activity of oncogenic RET mutants at two digit nanomolar concentration. These three compounds shared a 3-trifluoromethyl-4-methylpiperazinephenyl pharmacophore that stabilizes the ‘DFG-out’ inactive conformation of RET activation loop. They blocked RET-mediated signaling and proliferation with an IC50 in the nM range in fibroblasts transformed by the RET/C634R and RET/M918T oncogenes. They also inhibited autophosphorylation of several additional oncogenic RET-derived point mutants and chimeric oncogenes. At a concentration of 10 nM, ALW-II-41-27, XMD15-44 and HG-6-63-01 inhibited RET kinase and signaling in human thyroid cancer cell lines carrying oncogenic RET alleles; they also inhibited proliferation of cancer, but not non-tumoral Nthy-ori-3-1, thyroid cells, with an IC50 in the nM range. The three compounds were capable of inhibiting the ‘gatekeeper’ V804M mutant which confers substantial resistance to established RET inhibitors. In conclusion, we have identified a type II TKI scaffold...

Efeito do ambiente sobre o per?odo cr?tico de plasticidade do c?rtex pr?-frontal de ratos

FOLHA, Otavio Augusto de Araujo Costa
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Dissertação de Mestrado
POR
Relevância na Pesquisa
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O per?odo cr?tico de plasticidade do c?rtex cerebral ? a etapa do desenvolvimento p?s-natal do sistema nervoso onde os circuitos neurais s?o mais suscet?veis ? mudan?as influenciadas por informa??es oriundas do ambiente. No c?rtex pr?-frontal de humanos, respons?vel pelas fun??es executivas, o per?odo cr?tico de plasticidade estende-se desde o nascimento at? o final da adolesc?ncia e in?cio da vida adulta. Isto ? definido, entre outros fatores, pelo amadurecimento das redes perineuronais, uma estrutura especializada da matriz extracelular, localizada em volta do corpo celular e dendritos proximais de interneur?nios inibit?rios. O objetivo desta pesquisa foi verificar o efeito do ambiente em etapas distintas da adolesc?ncia sobre a estrutura e a fun??o do c?rtex pr?-frontal de ratos e a distribui??o da express?o espacial e temporal das redes perineuronais sob estas condi??es. As fun??es executivas foram avaliadas atrav?s de testes comportamentais medindo a capacidade de mem?ria operacional e a inibi??o comportamental. Observamos que est?mulos estressores cr?nicos imprevis?veis provocam altera??es no per?odo cr?tico de plasticidade do c?rtex pr?-frontal e, consequentemente, influenciam o amadurecimento das fun??es executivas. Observamos tamb?m que o estresse cr?nico induz modifica??o no padr?o de amadurecimento das redes perineuronais no c?rtex pr?-frontal. Estes resultados indicam a vulnerabilidade do c?rtex pr?-frontal de ratos adolescentes para os efeitos negativos de est?mulos ambientais estressores sobre o per?odo cr?tico de plasticidade.; ABSTRACT: The critical period of plasticity is a period of postnatal brain development in which neural circuits are most susceptible to environmental influence. The critical period of plasticity of the human prefrontal cortex...

Indu??o de plasticidade cerebral por remo??o da matriz extracelular ap?s les?o isqu?mica no c?rtex sens?rio-motor de ratos

SOARES, Soanne Chyara da Silva
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Dissertação de Mestrado
POR
Relevância na Pesquisa
16.54%
O acidente vascular cerebral (AVC) ? a terceira maior causa de mortalidade e incapacidade no mundo e a principal causa de mortes no Brasil. Ap?s a les?o isqu?mica, pela capacidade limitada do Sistema Nervoso Central (SNC) se regenerar, os d?ficits funcionais geralmente s?o incapacitantes e permanentes. A incapacidade de regenera??o decorre, dentre outros fatores, do ac?mulo de proteoglicanos de sulfato de condroitina (PGSC) no local da les?o, inibindo a plasticidade no microambiente extracelular. A enzima condroitinase ABC (ChABC) tem se mostrado eficiente para degradar os PGSC, proporcionando plasticidade. Esta pesquisa se prop?e a avaliar o efeito da remo??o de PGSC ap?s uma les?o isqu?mica no c?rtex sens?rio-motor prim?rio de ratos. Para tal, utilizou-se 20 ratos Wistar, em 4 grupos experimentais, controle e tratado, com tempo de sobrevida de 7 e 14 dias. Induziu-se uma les?o isqu?mica atrav?s de microinje??es do vasoconstritor ET-1 (Endotelina-1) no c?rtex sens?rio-motor, implantou-se um pol?mero de Etileno vinil acetato saturado com ChABC (tratado) ou BSA (controle). Morfologicamente, avaliamos a ?rea de les?o, que se mostrou sem diferen?a estat?stica entre grupo controle 7 dias (m?dia de 1653,8 ? 162,57mm?), tratado 7 dias (m?dia de 2067...

Efeitos do exerc?cio voluntario na recupera??o de hemissec??o da medula espinhal: mudan?as na rede perineuronal e acetila??o de histonas

SFAIR, M?rcio Jos? Teixeira
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Dissertação de Mestrado
POR
Relevância na Pesquisa
16.54%
A pr?tica regular de exerc?cios f?sicos previne e combate v?rias doen?as ao longo do tempo, destacando-se como excelente ferramenta terap?utica para o tratamento de les?es no sistema nervoso central (SNC). Ap?s uma transec??o (completa ou incompleta/hemissec??o) da medula espinhal, c?lulas gliais reativas secretam subst?ncias inibit?rias ? regenera??o axonal como, por exemplo, as mol?culas de proteoglicanas de sulfato de condroitina (PGSCs) que exercem papel importante na forma??o de uma barreira f?sico-qu?mica, chamada cicatriz glial, que impede o crescimento dos ax?nios danificados pela les?o. Pesquisas que envolvem modelo experimental de les?o da medula espinhal e reabilita??o por exerc?cio f?sico t?m obtido promissores resultados. No entanto, os mecanismos fisiol?gicos e moleculares pelos quais promovem esses resultados positivos ainda s?o pouco conhecidos. O objetivo do presente trabalho foi analisar a recupera??o da fun??o motora da pata posterior ap?s protocolo de exerc?cio f?sico voluntario em modelo experimental de hemissec??o da medula espinhal e investigar dois mecanismos moleculares envolvidos na recupera??o funcional: a degrada??o de PGSCs nas redes perineuronais e acetila??o de histonas. Para isso, vinte e quatro (24) ratos da linhagem Wistar (Rattus novergicus) foram utilizados e separados em 3 grupos (controle...

Efeito combinado do exerc?cio f?sico e da degrada??o da matriz extracelular na plasticidade do c?rtex cerebral ap?s isquemia

CASTRO, Ketlin Jaquelline Santana de
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Dissertação de Mestrado
POR
Relevância na Pesquisa
16.54%
O acidente vascular cerebral (AVC) ? a maior causa de mortes e incapacidades neurol?gicas no Brasil, e mais de 80% deles s?o decorrentes de evento isqu?mico. Os sobreviventes de AVC apresentam uma variedade de d?ficits motores, cognitivos e sensoriais, que prejudicam suas atividades de vida di?ria, limitando assim sua independ?ncia. Portanto, torna-se cada vez mais necess?rio elaborar estrat?gias terap?uticas que promovam a recupera??o funcional de pacientes acometidos por AVC. Ap?s isquemia do tecido nervoso, ocorre no meio extracelular a super express?o de mol?culas inibit?rias a regenera??o neuronal e ? plasticidade sin?ptica, como os proteoglicanos de sulfato de condroitina (PGSCs), o principal componente das redes perineuronais (RPNs). A remo??o destas mol?culas com a a??o da enzima condroitinase ABC (ChABC) tem sido usada como estrat?gia para induzir a plasticidade neuronal. Outro fator que tem sido utilizado para estimular a neuroplasticidade ? o exerc?cio f?sico espec?fico para o membro afetado ap?s AVC. O exerc?cio f?sico est? relacionado ? libera??o de neurotrofinas, importantes para a regenera??o do sistema nervoso. Portanto, a remo??o dos PGSCs junto com o exerc?cio f?sico pode potencializar a indu??o da plasticidade cerebral e recupera??o funcional ap?s les?o isqu?mica experimental na ?rea sens?rio-motora de ratos. Para testar nossa hip?tese...

El Midi de los viñedos. Desde Carlomagno al Mercado Común

Gavignaud, Geneviéve
Fonte: Murcia : Editora Regional de Murcia Publicador: Murcia : Editora Regional de Murcia
Tipo: Artigo de Revista Científica Formato: application/pdf
SPA
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16.54%

Roncesvalles

Rubio García, Luis
Fonte: Murcia: Universidad, Secretariado de Publicaciones Publicador: Murcia: Universidad, Secretariado de Publicaciones
Tipo: Artigo de Revista Científica Formato: application/pdf
SPA
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El "ius commune europaeum" de ayer y de hoy

Tomás y Valiente, Francisco
Fonte: Murcia, Universidad de Murcia, Instituto de Derecho Común Europeo Publicador: Murcia, Universidad de Murcia, Instituto de Derecho Común Europeo
Tipo: Artigo de Revista Científica Formato: application/pdf
SPA
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Europa es un fenómeno cultural que nace con Carlomagno, en la que se configuran y contraponen el "ius commune eurupaeum" y los "iura propria". La unidad jurídica obtenida, en la que tienen un protagonismo especial los juristas formados en las Universidades, se rompe con la iiustración y la Codificación. Pero al mismo tiempo que que se extingue el viejo "ius commune" aparece un nuevo derecho común europeo, un derecho del ciudadano, fuente primera y destinatario último de todo poder. Europe is a cultural phenomenon, bom with Charlemagne, in which the "ius commune europaeum" and the "iura propria" take shape and are set against each other. The juridical unity achieved, in which the special protagonists are the jurists educated in the Universities, is broken down with the Illustration and the Codification. But simultaneously with the extinction of the old "ius cornmune", a new "ius commune europaeum" comes into sight, a law of the citizen, primary source and last addresee of ail power.

La historiografía carolingia de Ermoldo a Notker: estado de la cuestión

Rodríguez, Gerardo
Fonte: Murcia: Universidad de Murcia, Editum Publicador: Murcia: Universidad de Murcia, Editum
Tipo: Artigo de Revista Científica Formato: application/pdf
SPA
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En este artículo propongo realizar un estado de la cuestión referido a las formas en que la historiografía de los siglos XIX a XXI abordó la construcción de la figura ideal del soberano carolingio a partir del análisis de las obras de Ermoldo, Eginardo, Thegan, el Astrónomo, Nitardo y Notker, construcción a que su vez lleva implícita la elaboración de una tradición franco-carolingia, que aúna en las diferentes estrategias discursivas épica, literatura e historia.; In this article I propose to clarify the status of the issue of the ways in which the historiography of the 19th to the 21th centuries dealt with the construction of the ideal figure of the Carolingian sovereign from the analysis of the works of Ermoldo, Eginardo, Thegan, The Astronomer, Nitardo and Notker. This construction in turn implies the development of a Franco-Carolingian tradition, which brings epics, literature and history together in different discursive strategies.; Le propos de cette étude est de présenter un état de la question sur la façon dont l’historiographie du XIXe au XXIe siècle, en s’inspirant des oeuvres d’Ermold, d’Eghinard, de Thegan, de l’Astronome, de Nithard et de Notker, a abordé la construction de l’image idéale du souverain carolingien. Par ailleurs...

Discovering common trends in a large set of disaggregates: statistical procedures and their properties

Carlomagno, Guillermo; Espasa, Antoni
Fonte: Universidade Carlos III de Madrid Publicador: Universidade Carlos III de Madrid
Tipo: info:eu-repo/semantics/draft; info:eu-repo/semantics/workingPaper
Publicado em 01/09/2015 ENG
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The objective of this paper is to model all the N components of a macro or business variable. Our contribution concerns cases with a large number (hundreds) of components, for which multivariate approaches are not feasible. We extend in several directions the pairwise approach originally proposed by Espasa and Mayo-Burgos (2013) and study its statistical properties. The pairwise approach consists on performing common features tests between the N(N-1)/2 pairs of series that exist in the aggregate. Once this is done, groups of series that share common features can be formed. Next, all the components are forecast using single equation models that include the restrictions derived by the common features. In this paper we focus on discovering groups of components that share single common trends. We study analytically the asymptotic properties of the procedure. We also carry out a comparison with a DFM alternative; results indicate that the pairwise approach dominates in many empirically relevant situations. A clear advantage of the pairwise approach is that it does not need common features to be pervasive.; Both authors gratefully acknowledge financial support from the Spanish Government project ECO2012-32401.; This paper is a more elaborated version of a part of a previous paper distributed as "The pairwise approach a large set of disaggregates with common trends".

Forecasting a large set of disaggregates with common trends and outliers

Carlomagno, Guillermo; Espasa, Antoni
Fonte: Universidade Carlos III de Madrid Publicador: Universidade Carlos III de Madrid
Tipo: info:eu-repo/semantics/draft; info:eu-repo/semantics/workingPaper
Publicado em 01/09/2015 ENG
Relevância na Pesquisa
16.54%
This paper deals with macro variables which have a large number of components and our aim is to model and forecasts all of them. We adopt a basic statistical procedure for discovering common trends among a large set of series and propose some extensions to take into account data irregularities and small samples issues. The forecasting strategy consists on estimating single-equation models for all the components, including the restrictions derived from the existence of common trends. An application to the disaggregated US CPI shows the usefulness of the procedure in real data problems.; Both authors gratefully acknowledge financial support from the Spanish Government project ECO2012-32401; This paper is a more elaborated version of a part of a previous paper distributed as "The pairwise approach a large set of disaggregates with common trends"

Prédica con la cruz y la espada: la evangelización de los pueblos sajones en el Siglo VIII

Perl Garrido, Jonathan D.
Fonte: Universidad Andrés Bello (Chile) Publicador: Universidad Andrés Bello (Chile)
Tipo: Artículo de revista
ES
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Indexación: Revista UNAB; El artículo aborda uno de los elementos de la expansión políticocultural de la Cristiandad Occidental en el norte de Europa. Se distinguen dos periodos; el primero, con la acción evangelizadora de los misioneros anglosajones en las fronteras del reino franco, caracterizada por la prédica y la persuasión. El segundo, determinado por la intervención del poderío militar franco para imponer el cristianismo. Abstract: The article approaches one of the elements of the political-cultural expansion of the Westem Christianity in the north of Europe. Two periods are distinguished: first, with the evangelist action of the Anglo-Saxon missionaries in the Frankish kingdom's borders, characterized by preach and persuasion. The second is determined by the intervention of the Frankish military power to impose Christianity upon them.

The pairwise approach to model a large set of disaggregates with common trends

Carlomagno, Guillermo; Espasa, Antoni
Fonte: Universidade Carlos III de Madrid Publicador: Universidade Carlos III de Madrid
Tipo: info:eu-repo/semantics/draft; info:eu-repo/semantics/workingPaper
Publicado em /05/2014 ENG
Relevância na Pesquisa
16.54%
The objective of this paper is to model and forecast all the components of a macro orbusiness variable. Our contribution concerns cases with a large number (hundreds) ofcomponents where multivariate approaches are not feasible. We extend in several directions the pairwise approach originally proposed by Espasa and Mayo-Burgos(2013) and study its statistical properties. The pairwise approach consists on performing common features tests between the N(N-1)/2 pairs of series that exist in a group of N of them. Once this is done, groups of series that share common features can be formed. Next, all the components are forecast using single equation models that include the restrictions derived by the common features. In this paper we focus on discovering groups of components that share single common trends. The asymptotic properties of the procedure are studied analytically. Monte Carlo evidence on the small samples performance is provided and a small samples correction procedure designed. A comparison with a DFM alternative is also carried out, and results indicate that the pairwise approach dominates in many empirically relevant situations. A relevant advantage of the pairwise approach is that it does not need common features to be pervasive. A strategy for dealing with outliers and breaks in the context of the pairwise procedure is designed and its properties studied by Monte Carlo. Results indicate that the treatment of these observations may considerably improve the procedure's performance when series are 'contaminated'.

An?lise citogen?tica como bioindicador para pacientes com diagn?stico sugestivo de Alzheimer

NEGR?O, Igor Patrick Ramos
Fonte: Universidade Federal do Pará Publicador: Universidade Federal do Pará
Tipo: Dissertação de Mestrado
POR
Relevância na Pesquisa
16.54%
A doen?a de Alzheimer (DA) ? uma doen?a neurodegenerativa que provoca morte neuronal e consequente perda progressiva das fun??es cognitivas, reduzindo as capacidades de trabalho, interferindo na rela??o social e no comportamento do paciente. Entre as doen?as causadoras de dem?ncia, a DA ? a mais incidente que as de cunho vascular, numa propor??o de 4:1, respectivamente. Al?m das terapias farmacol?gicas, os m?todos diagn?sticos auxiliam na identifica??o precoce da doen?a auxiliando o tratamento pr?vio, assim diminu?do a progress?o da doen?a. Atualmente estudos citogen?ticos v?m demonstrando altera??es cromoss?micas em portadoras da DA e podem auxiliar no diagn?sticos da doen?a. O objetivo desse trabalho foi verificar o potencial da an?lise cariot?pica de linf?citos do sangue perif?rico como bioindicador diagnostico da doen?a de Alzheimer. Para a realiza??o deste trabalho, utilizamos dois grupos de mulheres com 65 anos ou mais, sendo um grupo com (10) portadoras de DA e outro grupo (10) normais. Cada indiv?duo foi submetida ao question?rio socioecon?mico, teste de rastreio cognitivo (MEEM) e ? coleta de sangue venoso para cultura de linf?citos e an?lise cromoss?mica. Nossos resultados demonstram que o grupo de mulheres portadoras da DA apresentaram elevada taxa de monossomia e trissomia em rela??o ?s mulheres normais. Atrav?s de estudo de anamnese via question?rio...