Navegando por Palavras-chave "HTLV-1"
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- ItemSomente MetadadadosAntibody response after vaccination with tetanus and diphtheria toxoids in human T-cell lymphotropic virus type 1 asymptomatic carriers(Elsevier B.V., 2008-06-02) Biasutti, Claudia; Moraes-Pinto, Maria Isabel [UNIFESP]; Segurado, Aluisio C.; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
- ItemAcesso aberto (Open Access)C7a, a Biphosphinic Cyclopalladated Compound, Efficiently Controls the Development of a Patient-Derived Xenograft Model of Adult T Cell Leukemia/Lymphoma(Mdpi Ag, 2011-07-01) Guimarães-Corrêa, Ana Beatriz [UNIFESP]; Crawford, Lindsey B.; Figueiredo, Carlos Rogerio [UNIFESP]; Gimenes, Karina P. [UNIFESP]; Pinto, Lorena A.; Rios Grassi, Maria Fernanda; Feuer, Gerold; Travassos, Luiz Rodolpho [UNIFESP]; Caires, Antonio C. F.; Rodrigues, Elaine Guadelupe [UNIFESP]; Marriott, Susan J.; Baylor Coll Med; Universidade Federal de São Paulo (UNIFESP); SUNY Upstate Med Univ; Fundacao Oswaldo Cruz FIOCRUZ; Univ Mogi das Cruzes; Humurine Technol IncAdult T-cell leukemia/lymphoma (ATLL) is a highly aggressive disease that occurs in individuals infected with the human T lymphotropic virus type 1 (HTLV-1). Patients with aggressive ATLL have a poor prognosis because the leukemic cells are resistant to conventional chemotherapy. We have investigated the therapeutic efficacy of a biphosphinic cyclopalladated complex {Pd-2 [S(-)C2, N-dmpa](2) (mu-dppe)Cl-2}, termed C7a, in a patient-derived xenograft model of ATLL, and investigated the mechanism of C7a action in HTLV-1-positive and negative transformed T cell lines in vitro. in vivo survival studies in immunocompromised mice inoculated with human RV-ATL cells and intraperitoneally treated with C7a led to significantly increased survival of the treated mice. We investigated the mechanism of C7a activity in vitro and found that it induced mitochondrial release of cytochrome c, caspase activation, nuclear condensation and DNA degradation. These results suggest that C7a triggers apoptotic cell death in both HTLV-1 infected and uninfected human transformed T-cell lines. Significantly, C7a was not cytotoxic to peripheral blood mononuclear cells (PBMC) from healthy donors and HTLV-1-infected individuals. C7a inhibited more than 60% of the ex vivo spontaneous proliferation of PBMC from HTLV-1-infected individuals. These results support a potential therapeutic role for C7a in both ATLL and HTLV-1-negative T-cell lymphomas.
- ItemAcesso aberto (Open Access)Caracterização abrangente de pequeno RNA em portadores de HTLV-1 assintomáticos e doentes, com ATLL e HAM/TSP(Universidade Federal de São Paulo (UNIFESP), 2017-12-20) Souza, Daniela Raguer Valadão de [UNIFESP]; Sanabani, Sabri Saeed Mohammed Ahmed Al [UNIFESP]; http://lattes.cnpq.br/8965738600138840; http://lattes.cnpq.br/0699158269241318; Universidade Federal de São Paulo (UNIFESP)The Human T-lymphotropic virus type I (HTLV-I) is the causative agent of a spectrum of clinical manifestations, ranging from asymptomatic infection to a number of human disorders, most notably a malignant ATLL and a chronic progressive neuromyelopathy, termed HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Small non-coding RNAs (sRNAs) evolved to play important roles in virus-host interactions. In the present study, we used the massive parallel sequencing (MPS) approach to investigate the characteristic expression of sRNA during the development of ATLL and HAM/TSP in HTLV-1 infected patients and to identify known and new sRNA genes resident in peripheral blood mononuclear cells (PBMCs). In order to perform an unbiased sRNA profile, 44 samples from HTLV-1 infected individuals, previously known in terms of clonality and proviral load (PVL), were subjected for analysis. Participants were categorized into four groups: asymptomatic polyclonal (ACs-P, n = 8), asymptomatic monoclonal (ACs-M, n = 8), HAM / TSP patients (n = 16) and ATLL patients (n = 12). The analysis strategy involved the comparison of the group of ACs-P subjects with the other groups, namely (ACs-P vs ACs-M), (ACs-P vs HAM/TSP), and (ACs-P vs ATLL). In the ACs-P vs ACs-M group, only one miRNA (miRNA 33a-5p) was significantly down regulated (p <0.001). In the ACs-P vs. HAM / TSP group, 15 sRNAs were significantly deregulated (p <0.001) of which 11 were down regulated and 4 up-regulated. The top 5 most abundantly expressed sRNA were miRNAs 651, 151b, 154-3p, 18b-5p and 539-3p. In the ACs-P vs. ATLL group, 27 sRNAs were significantly deregulated (p <0.001). Of these, 16 were down regulated and 11 were up regulated. The top 5 most significantly and differentially expressed sRNAs were: miRNAs 577, 3194-5p, 4772-5p, 296-5p and 3934 -5p. Most of the miRNAs presented here are already described as involved in other oncological processes, however only miR-1 has already been related to HTLV-1 infection. Further analysis of the expression profile of these 4 groups revealed a characteristically unique and very significant expression profile in ATLL patients with acute leukemic form. The following 10 possible biomarkers are believed to play important role in progression of the disease to leukemic form: miRNAs 3200-3p, 4732-5p, 3688-3p, 3200-5p, 183- 5p, 144-5p, 296-5p, 451a, 577 and 193a-5p. Of these miRs, the miR-144/451 cluster is suggested to be closely involved in the pathogenesis of ATLL. Also, their high expression in acute ATLL can be used as a potential biomarker for the diagnosis of the disease. This study characterized the small RNA in the BPMCs from HTLV-1 patients in different clinical settings using MPS technology for the first time, which provides an opportunity for further understanding of sRNA regulation function during the course of HTLV-1 infection. The small RNA described here, might serve as biomarkers or therapeutic targets in the future.
- ItemAcesso aberto (Open Access)Caracterização molecular do vírus linfotrópico humano de células T, genoma completo e parcial através do sequenciamento de última geração pela plataforma Illumina(Universidade Federal de São Paulo (UNIFESP), 2015-01-31) Farias, Rodrigo Pessoa de [UNIFESP]; Al Sanabani, Sabri Saeed Mohammed Ahmed [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introdução: Nesse trabalho relatamos a variabilidade das sequencias do Vírus Linfotrópico de Célula Humana T tipo 1 (HTLV-1) genoma completo e parcial de 90 indivíduos, destes sendo 48 portadores assintomáticos, 35 pacientes com Paraparesia Espástica tropical/Mielopatia associada ao HTLV-1 (HAM/TSP) e 7 pacientes portadores de leucemia/linfoma de células T adulto, utilizando o sequenciamento de nova geração do aparelho da Illumina (MiSeq). Metodologia: Foram coletadas amostras de sangue dos 90 indivíduos. O DNA foi extraído a partir das células mononucleares do sangue periférico PBMC para medir a carga proviral e amplificar o HTLV-1 em dois fragmentos que se sobrepõem. Os produtos de PCR amplificados foram sequenciados no sequenciador de nova geração MiSeq (Illumina). Os dados gerados foram montados, alinhados e mapeados contra um genoma de HTLV-1 já descrito com semelhança genética para posteriores análises filogenéticas. Resultados: O sequenciamento de alto rendimento por síntese foi utilizado para obter uma média de cobertura de 3210-5200 para cada amostra, obtendo-se genomas parciais (n=14) e genomas completos (n=76) do HTLV-1. Os resultados, utilizando-se as sequencias geradas pelo sequenciamento e baseado em árvores filogenéticas, revelaram que 86 (95,5%) indivíduos são infectados com o grupo A transcontinental e subtipo A cosmopolita (aA) e 4 (4,5%) indivíduos com o subtipo B japonês (aB). Uma comparação entre os ácidos nucléicos e aminoácidos dos genomas completos nas três categorias não apresentou nenhuma relação entre o genótipo e as condições clínicas dos indivíduos. As relações evolutivas entre as sequências do HTLV-1 foram descritas a partir de sequências de nucleotídeos, e estes resultados são consistentes suportando a hipótese de que houve várias entradas do subtipo transcontinental no Brasil. Conclusões: Este estudo aumenta o número de sequências de genomas completos do HTLV-1 disponíveis em banco de dados do subtipo aA de 8 para 81 e aB de 2 para 5. Nossos dados confirmam que o subtipo transcontinental cosmopolita é o mais prevalente na população brasileira. Assim espera-se que as sequencias geradas irão acrescentar a nossa compreensão atual da história evolutiva deste vírus.
- ItemAcesso aberto (Open Access)Determinantes metabólicos do linfoma/leucemia associados ao HTLV-1 e sua relação com a resposta a indução do estresse oxidativo como potencial terapêutico em linhagens tumorais(Universidade Federal de São Paulo, 2024-06-01) Ferraz, Jéssica Dias da Silva [UNIFESP]; Shytaj, Iart Luca; Não possui; http://lattes.cnpq.br/2395792828271999Objetivo: Determinar marcadores de susceptibilidade em células de linfoma de células T do adulto e identificar possíveis formas de intervenção nas alterações celulares relacionadas ao HTLV-1. Métodos: Foram utilizadas as linhagens celulares MT-2, MT-4 e Jurkat. Realizaram-se testes in vitro de citotoxicidade com as drogas cisplatina, L-Buthionine-sulfoximina, auranofina, doxorrubicina e vincristina, além da determinação do perfil metabólico. Foi realizada PCR em tempo real para detecção da infecção pelo HTLV-1 nas linhagens MT-2 e MT-4 e da expressão gênica viral, focando nas proteínas Tax-Rex, Gag e Env, com análise de dados de microarranjos disponíveis na literatura. Resultados: Os experimentos de citotoxicidade determinaram a sensibilidade das células relacionadas ao HTLV-1 à combinação das drogas auranofina e L-Buthionine-sulfoximina. Os resultados foram correlacionados com o perfil metabólico das células e com os dados de microarranjo. Na linhagem MT-4, observou-se alta expressão da via da nicotinamida, associada à síntese de NAD/NADH. Na MT-2, verificou-se maior expressão da cadeia de transporte de elétrons na membrana, relacionada à fosforilação oxidativa. Conclusão: Esses resultados sustentam a eficácia da combinação das drogas, especialmente auranofina e L-Buthionine-sulfoximina, para atingir diferentes vias metabólicas, como a via de fosforilação oxidativa e a via da nicotinamida, superando a resistência a diferentes terapias observada em pacientes com linfoma de células T do adulto.
- ItemSomente MetadadadosHuman leucocyte antigen and human T-cell lymphotropic virus type 1 associated diseases in Brazil(Blackwell Publishing Ltd, 2003-12-01) Borducchi, Davimar Miranda Maciel [UNIFESP]; Gerbase-DeLima, Maria [UNIFESP]; Morgun, Andrey [UNIFESP]; Shulzhenko, Natalia [UNIFESP]; Pombo-de-Oliveira, M. S.; Kerbauy, José [UNIFESP]; Oliveira, José Salvador Rodrigues de [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Inst Nacl Canc
- ItemAcesso aberto (Open Access)Sentidos da interrupção da amamentação devido infeção pelo vírus linfotrópico de células T humanas do tipo 1( HTLV-1)(Univ Fed Sao Paulo, Dept Enfermagen, 2017) Zihlmann, Karina Franco [UNIFESP]; Mazzaia, Maria Cristina [UNIFESP]; de Alvarenga, Augusta TherezaObjective: Understand the meanings of breastfeeding inhibition to prevent vertical transmission among women living with HTLV-1 (WLHTLV). Methods: A qualitative research with participant observation and in-depth interviews was undertaken, using a pretested thematic script, analyzed by means of Bardin's thematic content analysis. The participants were 13 people -11 women and two men -over 18 years of age, diagnosed with HTLV-1 and without co-infections. The study was undertaken at a private room in a specialized center in Sao Paulo between June/2006 and April/2008, where the researcher worked, so that she was familiar with and had access to the users. The subjects were selected by convenience, during the participant observation. The subjects' reports were recorded, transcribed and analyzed in search of senses and meanings to elaborate the categories. Excerpts were presented, identified by fictitious names. Results: Breastfeeding inhibition is a complex decision that is even more difficult in a context in which the health team does not know this infection. Conclusion: The lack of knowledge on HTLV-1 in the hospital context is a risk for the vertical transmission of this virus and entails significant emotional consequences. The health team needs information and education for comprehensive care and welcoming of WLHTLV's specific needs.
- ItemSomente MetadadadosSKELETAL-MUSCLE INVOLVEMENT in TROPICAL SPASTIC PARAPARESIS HTLV-1-ASSOCIATED MYELOPATHY(Wiley-Blackwell, 1994-08-01) Gabbai, Alberto Alain [UNIFESP]; Wiley, C. A.; Oliveira, ASB; Smith, R.; Schmidt, B.; Nobrega, JAM; Bordin, J. O.; Roman, G. C.; Universidade Federal de São Paulo (UNIFESP); UNIV CALIF SAN DIEGO; NINCDSThe frequency of muscle involvement in TSP/HAM is not known, nor is the precise role that HTLV-1 and the diverse cytokines play in the genesis of HTLV-1-associated diseases. in order to better define the frequency and characteristics of the skeletal muscle involvement in TSP/ HAM, we studied 11 affected patients. EMG was performed in 9 patients and muscle biopsy was performed in all 11. Muscle tissue was analyzed using: reverse transcriptase PCR for interleukin-1 in 8; PCR for HTLV-1 proviral DNA in 5; and electron microscopy for viral particles in 3. We found pathologic alterations in all 11 patients. Four patients (36%) had a neurogenic process, while a primary muscle involvement was observed in the rest (64%). Four patients (36%) had polymyositis, and 3 (27%) had a noninflammatory myopathy. Muscle weakness in the upper limbs was significantly associated with inflammation in the muscle biopsy. EMG was abnormal in only 2 of 9 patients. Reverse transcriptase PCR did not demonstrate message for interleukin-1 in any sample examined. PCR did identify HTLV-1 proviral DNA in the muscle of 3 patients. Retroviral-like particles were found, by EM, in only one biopsy. HTLV-1 may play an important role in the pathogenesis of the frequent myopathies associated with HAM/TSP. (C) 1994 John Wiley & Sons, Inc.