987 resultados para Interferon Teses
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A REEUSP uma revista trimestral desde 1998, que publica de 11 a 13 artigos por nmero nas diferentes subreas da Enfermagem, na sua maioria sobre ensino, tecnologia em sade, sade do adulto (nas suas diferentes especialidades), sade mental e psiquitrica. O enfoque dos artigos e pesquisas continua a ser hospitalar. Por estar ligada a uma unidade de ensino, apresenta qualidade nas suas publicaes, muitas vezes geradas de teses e dissertaes. Enfrenta o desafio de estimular a publicao de autores de outras instituies, para no se tornar endgena. Nos ltimos 10 anos recebeu e publicou artigos de 18 estados brasileiros e de vrias cidades do interior de So Paulo. Seu projeto grfico tambm foi remodelado para 2003, permitindo maior legibilidade e facilidade na leitura. Aceita permuta com outros peridicos e indexada em vrias Bases de Dados. Recebeu a classificao C internacional pela CAPES.
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Summary1 SummaryCancer patients have a better clinical outcome when their tumours display marked infiltration by memory Τ cells. Moreover, the overrepresentation of Th1 gene signatures in primary tumours correlates with favourable prognosis. Thus, vaccination to induce Τ cells capable of infiltrating and eradicating the tumour seems a promising strategy for the treatment of cancer. Here, I monitored CD4 Τ cell responses in melanoma patients vaccinated with the long synthetic peptides Melan- A16-35(A27L) and NY-ESO-179.108. Most of the patients developed strong and diverse peptide antigen specific CD4 Τ cell responses. Analysis of the fine specificity of CD4 Τ cell antigen recognition led to the identification of two new epitopes. The peptide Melan-A16_35(A27L) was delivered by virus-like particles (VLPs) derived from bacteriophage Οβ, which themselves displayed strong immunogenicity. I show evidence for induction of Οβ- and Melan-A specific CD4 Τ cell responses that developed a Th1 functional profile after repeated vaccination cycles. They also specifically released the chemokines CCL-3 and CCL-4, which play important roles in attracting CD8 Τ cells to the APC surface for priming and formation of Τ cell memory. We further found induction of robust humoral IgG responses upon VLP vaccination, and the lgG1-lgG4 isotype composition depended on the adjuvant used. Since heavy chain class switching largely dpends on the presence of CD4 Τ cell help, this result suggests that the adjuvant can influence the differentiation of elicited CD4 Τ cells, thereby contributing to the quality and function of both Β cells and CD8 Τ cells. The nature of the inflammatory processes in the tumour microenvironment can modulate CD8 Τ cell function. A collaboration was established for the investigation regulation of inflammasome activation in human primary monocytes. We identified IL- 4 and TGF-β as strong inhibitors of IL-1 β secretion, Indicating some level of regulation from effector Th2 and Treg responses. We further found a potent inhibition of inflammasome activation by type I interferon, and demonstrated in vivo inhibition of IL-1 β responses in monocytes from active multiple sclerosis patients under IFN-β therapy. This finding further offers a possible explanation for its success, which mechanism of action is still largely unclear. Interestingly, type I interferon is also being used as adjuvant treatment for tumour free metastatic cutaneous melanoma patients. While its clinical benefit has remained controversial, recent data suggest that the subset of patients with ulcerated primary melanoma lesions can benefit from this therapy. Future investigations will shed light on the implication of the inflammasome in this context, and may offer new strategies for improved adjuvant treatments of melanoma.2 RsumLes patients atteints de cancer ont une meilleure chance de survie si leurs tumeurs s'avrent tre largement infiltres par des cellules Τ mmoires. De plus, la surreprsentation d'une signature gnique Th1 est en corrlation avec un pronostic favorable. Ainsi, la vaccination visant induire des cellules Τ capables d'infiltrer et de dtruire la tumeur parait tre une stratgie prometteuse pour le traitement du cancer. Dans ce travail, j'ai procd au monitoring de la rponse des cellules Τ CD4 dans des patients atteints de mlanome vaccins avec les longs peptides synthtiques Melan-A16_35(A27L) et NY-ESO-179_108. Ces peptides reprsentent des antignes tumoraux reconnus par des lymphocytes T. La majorit des patients a dvelopp une rponse forte et diversifie des cellules Τ CD4 spcifiques contre les peptides. L'analyse de la spcificit fine de la reconnaissance antignique des cellules Τ CD4 nous a conduits l'identification de deux nouveaux pitopes. Le peptide Melan-Aie. 35(A27L) a t dlivr par des particules de type viral (VLPs) drivs de bactriophages Qβ, qui ont eux-mmes dmontr une forte immunognicit. Mon travail montre les preuves d'une induction de rponses spcifiques des cellules Τ CD4 contre les Qβ et Melan-A dveloppant un profil fonctionnel Th1 aprs plusieurs cycles de vaccination. Elles secrtent aussi spcifiquement les chimiokines CCL-3 et CCL-4, qui jouent un rle important dans l'attraction des cellules Τ CD8 la surface des cellules prsentatrices d'antignes et contribuent ainsi induire et former la mmoire cellulaire Τ CD8. Nous avons galement remarqu une induction de fortes rponses humorales IgG aprs vaccination avec les VLPs, et que la composition des isotypes lgG1-lgG4 dpendait de l'adjuvant utilis. Etant donn qu'une commutation de classe de la chane lourde dpend largement ie l'aide des cellules Τ CD4, ce rsultat suggre que l'adjuvant puisse influencer la diffreritiation de cellules Τ CD4 en diffrent types, contribuant ainsi la qualit et la fonction des cellules Β et des cellules Τ CD8.La nature des processus d'inflammation dans le microenvironnement tumoral peut moduler la fonction des cellules Τ CD8. Une collaboration a t tablie pour investiguer la rgulation de l'activation de l'inflammasome dans des monocytes primaires humains. Nous avons identifi l'IL-4 et le TGF-β comme tant de puissants inhibiteurs de la scrtion de IL-Ιβ, indiquant une certaine rgulation de la rponse inflammatoire induite par les cellules Th2 et Τ rgulatrices. Nous avons galement trouv une forte inhibition de l'activation de l'inflammasome par l'interfron type I, et nous avons dmontr une inhibition in vivo de la rponse IL-1 β dans des monocytes de patients atteints d'une sclrose en plaque active sous traitement IFN-β. Ce rsultat nous offre une possible explication du succs de cette thrapie, dont le mcanisme reste ce jour encore largement obscur. Il est intressant de noter que l'interfron de type I est galement utilis pour le traitement de patients atteints de mlanome cutan mtastasique sans tumeurs. Bien que le bnfice clinique de ce traitement reste controvers, des tudes rcentes montrent qu'une partie des patients atteints de mlanome primaire ulcr peut tirer bnfice de cette thrapie. De futures investigations pourront mieux nous renseigner sur l'implication de l'inflammasome dans ce contexte et offrir de nouvelles stratgies pour amliorer les traitements adjuvants du mlanome.
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Murine macrophages activated by interferon-gamma and lipopolysaccharide become leishmanicidal through a process involving L-arginine-derived nitrogen oxidation products. Both nitrite secretion and parasite killing by activated macrophages were inhibited by 3-amino-1,2,4-triazole as well as the related compound, 3-amino-1,2,4-triazine. Moreover, NO synthase activity in cytosolic extracts of activated cells was inhibited by both compounds. 4-amino-1,2,4-triazole, an isomer of 3-amino-1,2,4-triazole, was without effect. Our results suggest that besides its known inhibitory effect on catalases and peroxidases, 3-amino-1,2,4-triazole is an inhibitor of NO synthase. The resemblance between the tautomeric form of 3-amino-1,2,4-triazole and the guanidino group of L-arginine, the natural substrate for NO synthase, might be responsible for the observed inhibition.
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O Programa Interunidades de Doutoramento em Enfermagem foi o primeiro a ser criado na Amrica Latina e titulou 290 enfermeiros, at o primeiro semestre de 2004. Este estudo apresenta algumas caractersticas das teses defendidas no programa, focalizando as reas temticas e mtodos de pesquisa utilizados. Foram analisados os resumos de 287 teses, defendidas at o primeiro semestre de 2004. As reas mais investigadas, at o momento foram: Sade da Criana, da Mulher, do Adulto/Idoso e Educao. O mtodo de pesquisa quantitativo predominou at final da dcada de 1980, havendo uma intensa produo de pesquisas no mtodo qualitativo a partir desse perodo. Ainda na primeira dcada do programa, os temas passaram a versar sobre os aspectos que relacionam a prtica da enfermagem aos contextos polticos e sociais, convergindo para o atual eixo paradigmtico do programa: "Bases tericas, filosficas, histricas do saber e da prtica de enfermagem".
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O presente estudo teve como objetivo identificar e analisar a produo do conhecimento na rea de concentrao Administrao de Servios de Enfermagem, no Curso de Mestrado e Doutorado da EEUSP. Trata-se de um estudo exploratrio, descritivo, retrospectivo, pautado na anlise documental. A populao foi constituda por 128 produes cientficas, sendo 102 (79,7%) dissertaes de mestrado e 26 (20,3%) teses de doutorado produzidas no perodo de 1977 a maro de 2004. Esses estudos foram analisados de acordo com o agrupamento dos temas, nas categorias propostas por Castro e Ciampone (2002). Os resultados permitiram visualizar a distribuio da produo por temtica, dcada, mtodo e correntes de pensamento adotadas nesses estudos. Permitiram, tambm, traar consideraes a respeito da trajetria, necessidades e perspectivas das pesquisas em Gerenciamento em Enfermagem no mbito do Programa.
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Aps quase 30 anos de criao da rea de Concentrao Enfermagem Psiquitrica, no Programa de Ps-Graduao da Escola de Enfermagem da USP, importante olhar a produo cientfica gerada para que fundamentem reflexes sobre este ensino. Este estudo descritivo-exploratrio, usou como fonte os registros do Servio de Ps-Graduao, resumos de dissertaes e teses; memorandos e ofcios; os dados coletados foram analisados luz das transformaes ocorridas na estrutura que titulou 60 alunos, dos quais 50 cursaram mestrado e 10 doutorado e que vem reestruturando suas disciplinas, linhas de pesquisa e projetos com o objetivo de atender as avaliaes internas e externas e s diretrizes das agncias de fomento do Pas. A produo cientfica, atualmente, evidncia alinhamento com as diretrizes da Reforma Psiquitrica e tendncia de produzir conhecimentos a partir das prticas concretas dos trabalhadores nos campos da assistncia, a gesto e ensino de Sade Mental.
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A preocupao com programas para capacitar o enfermeiro, para atuar em enfermagem psiquitrica, levou-nos a este estudo, o primeiro da linha de pesquisa "Desenvolvimento do pessoal de enfermagem na rea da psiquiatria e sade mental". O objetivo deste foi fazer uma reflexo sobre os conceitos de educao continuada, em servio e permanente existentes na literatura mais recente sobre o assunto. Para o levantamento bibliogrfico dos conceitos em pauta, utilizamos as bases de dados MEDLINE e LILACS, dissertaes e teses da rea da enfermagem e alguns ttulos clssicos sobre o assunto. Aps anlise dos conceitos e discusso com peritos, conclumos que a denominao educao contnua em servio a que guarda mais consonncia com os autores e peritos consultados e a que mais atende s demandas de conhecimento existentes na rea de assistncia de enfermagem psiquitrica rumo qualidade da assistncia.
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A liderana uma das ferramentas imprescindvel no processo de trabalho do enfermeiro. Este estudo teve como objetivos fazer um levantamento bibliogrfico sobre liderana no contexto da enfermagem e caracterizar tal produo cientfica encontrada, com base nas variveis: ano, local de publicao e categorizao dos temas. Tratou-se de uma reviso de literatura realizada on-line na base de dados LILACS, considerando peridicos, dissertaes e teses disponveis em lngua portuguesa e espanhola, nos ltimos vinte anos. Dos 31 trabalhos selecionados, 17 (54,8%) em revista de enfermagem internacional, 10 artigos (32,2%) foram publicados em peridicos de enfermagem nacional, 3 dissertaes de mestrado (9,8%) e 1 tese de livre-docncia (3,2%), com maior predomnio de divulgao entre 1997 e 1998 (22,6%). Ao categorizar as referncias teve-se: 14 trabalhos (45,2%) sobre estilo de liderana exercido pelos enfermeiros, 15 (48,4%) reflexes sobre liderana e 2 publicaes (6,4%) discorrendo a respeito de liderana e comunicao.
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Objetivando estudar a compreenso sobre doena mental de pacientes e familiares, realizamos um estudo bibliogrfico de publicaes em peridicos nacionais, dissertaes e teses, no perodo de 1993 a 2003. A identificao das fontes foi realizada por meio dos sistemas informatizados de busca Literatura Latino Americano de Cincias da Sade (LILACS) e o Banco de Dados Bibliogrficos da USP Catlogo on-line Global (DEDALUS). Foram selecionados 19 trabalhos e identificados quatro categorias: dificuldade de relacionamento familiar com o doente; preconceito e estigma; explicao orgnica/biolgica para a doena; o medo e a dor da loucura. A maioria dos trabalhos nos mostra que, em relao assistncia, h necessidade de apoio e expanso da rede de sade para atender essa demanda. Acredita-se que o nmero de publicaes seja pequeno diante da importncia do problema, mostrando a necessidade de novas pesquisas.
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Peripheral blood mononuclear cells from subjects never exposed to Leishmania were stimulated with Leishmania guyanensis. We demonstrated that L. guyanensis-stimulated CD8(+) T cells produced interferon (IFN)- gamma and preferentially expressed the V beta 14 T cell receptor (TCR) gene family. In addition, these cells expressed cutaneous lymphocyte antigen and CCR4 surface molecules, suggesting that they could migrate to the skin. Results obtained from the lesions of patients with localized cutaneous leishmaniaisis (LCL) showed that V beta 14 TCR expression was increased in most lesions (63.5%) and that expression of only a small number of V beta gene families (V beta 1, V beta 6, V beta 9, V beta 14, and V beta 24) was increased. The presence of V beta 14 T cells in tissue confirmed the migration of these cells to the lesion site. Thus, we propose the following sequence of events during infection with L. guyanensis. After initial exposure to L. guyanensis, CD8(+) T cells preferentially expressing the V beta 14 TCR and secreting IFN- gamma develop and circulate in the periphery. During the infection, these cells migrate to the skin at the site of the parasitic infection. The role of these V beta 14 CD8(+) T cells in resistance to infection remains to be determined conclusively.
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Este trabalho objetivou identificar a produo cientfica sobre orientao ao ostomizado, publicada entre 1970 e 2004 e classific-la segundo quantidade, cronologia de publicao, funo exercida pelos autores, procedncia, tipo, assunto, origem e palavras-chave; utilizando a metodologia bibliomtrica. As 27 publicaes foram coletadas no banco de dados DEDALUS, nas bases de dados LILACS, MEDLINE e de uma docente da EEUSP (referncia nacional em ostomia). No total, 19 so nacionais, oito internacionais e escritas principalmente por enfermeiros e estomaterapeutas. Os tipos so: dissertaes, teses, folhetos, livros e artigos. A procedncia dos materiais da academia, laboratorial e hospitalar. A dcada de noventa a que concentra o maior nmero de trabalhos nesta rea temtica. Todos tm como finalidade elevar a auto-estima dos pacientes para faz-los sentir que, mesmo com uma ostomia, eles podem levar uma vida normal. Assim, o estudo mostrou que a enfermeira como educadora de um ostomizado deve conhecer tais publicaes para melhorar a assistncia.
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Objetivou-se verificar a clareza na organizao dos sistemas sociais da Teoria de Alcance de Metas. Estudo terico-reflexivo, tendo como referencial para anlise um Modelo de Anlise de Teorias. Desenvolvido nos meses de abril, maio e junho de 2005, sendo analisadas uma Dissertao e duas Teses. Quanto definio operacional dos conceitos, as trs pesquisas definiram adequadamente os conceitos que o Modelo Conceitual aponta. Em relao validade de contedo e construto, foram identificadas lacunas. Em um estudo, por exemplo, os grupos de trabalho nos quais os indivduos estavam inseridos no foram condizentes com o conceito de sistema social apresentado pela Teoria. Dessa forma, os estudos necessitam ainda de ateno quanto utilizao de conceitos apresentados em teorias ou em modelos tericos.
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S100B is a prognostic factor for melanoma as elevated levels correlate with disease progression and poor outcome. We determined its prognostic value based on updated information using serial determinations in stage IIb/III melanoma patients. 211 Patients who participated in the EORTC 18952 trial, evaluating efficacy of adjuvant intermediate doses of interferon α2b (IFN) versus observation, entered a corollary study. Over a period of 36 months, 918 serum samples were collected. The Cox time-dependent model was used to assess prognostic value of the latest (most recent) S100B determination. At first measurement, 178 patients had S100B values <0.2 μg/l and 33 ≥ 0.2 μg/l. Within the first group, 61 patients had, later on, an increased value of S100B (≥ 0.2 μg/l). An initial increased value of S100B, or during follow-up, was associated with worse distant metastasis-free survival (DMFS); hazard ratio (HR) of S100B ≥ 0.2 versus S100B < 0.2 was 5.57 (95% confidence interval (CI) 3.81-8.16), P < 0.0001, after adjustment for stage, number of lymph nodes and sex. In stage IIb patients, the HR adjusted for sex was 2.14 (95% CI 0.71, 6.42), whereas in stage III, the HR adjusted for stage, number of lymph nodes and sex was 6.76 (95% CI 4.50-10.16). Similar results were observed regarding overall survival (OS). Serial determination of S100B in stage IIb-III melanoma is a strong independent prognostic marker, even stronger compared to stage and number of positive lymph nodes. The prognostic impact of S100B ≥ 0.2 μg/l is more pronounced in stage III disease compared with stage IIb.
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Aims: The adaptive immune response against hepatitis C virus (HCV) is significantly shaped by the host's composition of HLA alleles. Thus, the HLA phenotype is a critical determinant of viral evolution during adaptive immune pressure. Potential associations of HLA class I alleles with polymorphisms of HCV immune escape variants are largely unknown. Methods: Direct sequence analysis of the genes encoding the HCV proteins E2, NS3 and NS5B in a cohort of 159 patients with chronic HCV genotype 1 infection who were treated with pegylated interferon-alfa 2b and ribavirin in a prospective controlled trial for 48 weeks was exhibited. HLA class I genotyping was performed by strand-specific reverse hybridization with the INNO-LiPA line probe assays for HLA-A and HLA-B and by strand-specific PCR-SSP. We analyzed each amino acid position of HCV proteins using an extension of Fisher's exact test for associations with HLA alleles. In addition, associations of specific HLA alleles with inflammatory activity, liver fibrosis, HCV RNA viral load and virologic treatment outcome were investigated. Results: Separate analyses of HCV subtype 1a and 1b isolates revealed substantially different patterns of HLA-restricted polymorphisms between subtypes. Only one polymorphism within NS5B (V2758x) was significantly associated with HLA B*15 in HCV genotype 1b infected patients (adjusted p=0,048). However, a number of HLA class I-restricted polymorphisms within novel putative HCV CD8+ T cell epitopes (genotype 1a: HLA-A*11 GTRTIASPK1086-1094 [NS3], HLA-B*07 WPAPQGARSL1111-1120 [NS3]; genotype 1b: HLA-A*24 HYAPRPCGI488-496 [E2], HLA-B*44 GENETDVLL530-538 [E2], HLA-B*15 RVFTEAMTRY2757-2766 [NS5B]) were observed with high predicted epitope binding scores assessed by the web-based software SYFPEITHI (>21). Most of the identified putative epitopes were overlapping with already otherwise published epitopes, indicating a high immunogenicity of the accordant HCV protein region. In addition, certain HLA class I alleles were associated with inflammatory activity, stage of liver fibrosis, and sustained virologic response to antiviral therapy. Conclusions: HLA class I restricted HCV sequence polymorphisms are rare. HCV polymorphisms identified within putative HCV CD8+ T cell epitopes in the present study differ in their genomic distribution between genotype 1a and 1b isolates, implying divergent adaptation to the host's immune pressure on the HCV subtype level.
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Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. CONCLUSION: In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.
