979 resultados para transforming growth factor alpha
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Background Mucocutaneous lesions in paracoccidioidomycosis are granulomatous and result from tissue responses to Paracoccidioides brasiliensis, the aetiological agent.Objectives and methods In this study we investigate the expression of tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and transforming growth factor (TGF)-beta 1 by immunohistochemistry in skin and mucosa lesions from patients with the chronic form of paracoccidioidomycosis, evaluated before and at day 20 of trimethoprim-sulfamethoxazole treatment. Cytokine production by peripheral blood monocytes was also studied by enzyme immunoassay.Results Intense immunostaining for TNF-alpha was detected in mononuclear cells that infiltrated granulomas in all skin and mucosa lesions before treatment simultaneously with low IL-10 granular deposits in these cells. At day 20 of treatment, there was reduced TNF-alpha and IL-10 deposition. Immunoreactive TGF-beta 1 was observed diffusely in the dermis and generally in the cytoplasm of macrophages and giant cells, before treatment, and as increased TGF-beta 1 deposits in the fibrosis area at day 20 of treatment. Peripheral blood monocytes from patients with paracoccidioidomycosis, evaluated before treatment, produced high endogenous levels of TNF-alpha, TGF-beta 1 and IL-10 in relation to healthy controls. Lipopolysaccharide-stimulated monocytes from patients secreted lower levels of TNF-alpha in both periods of evaluation while no impairment in capacity of IL-10 and TGF-beta production was observed.Conclusions Trimethoprim-sulfamethoxazole therapy was effective in decreasing fungal load in the lesions, allowing patient immune response to control the infection leading to the healing of the lesions.
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OBJETIVO: Analisar o padrão de citocinas pró- e antiinflamatórias e da resposta de fase aguda (RFA) como marcadores de resposta ao tratamento da tuberculose pulmonar. MÉTODOS: Determinação dos níveis de interferon-gama (IFN-γ), tumor necrosis factor-alpha (TNF-α, fator de necrose tumoral-alfa), interleucina-10 (IL-10) e transforming growth factor-beta (TGF-β, fator transformador de crescimento-beta), pelo método ELISA, em sobrenadante de cultura de células mononucleares do sangue periférico e monócitos, assim como dos níveis de proteínas totais, albumina, globulinas, alfa-1-glicoproteína ácida (AGA), proteína C reativa (PCR) e velocidade de hemossedimentação (VHS) em 28 doentes com tuberculose pulmonar, em três tempos: antes (T0), aos três meses (T3) e aos seis meses (T6) de tratamento, em relação aos controles saudáveis, em um único tempo. RESULTADOS: Os pacientes apresentaram valores maiores de citocinas e RFA que os controles em T0, com diminuição em T3 e diminuição (TNF-α, IL-10, TGF-β, AGA e VHS) ou normalização (IFN-γ e PCR) em T6. CONCLUSÕES: PCR, AGA e VHS são possíveis marcadores para auxiliar no diagnóstico de tuberculose pulmonar e na indicação de tratamento de indivíduos com baciloscopia negativa; PCR (T0 > T3 > T6 = referência) pode também ser marcador de resposta ao tratamento. Antes do tratamento, o perfil Th0 (IFN-γ, IL-10, TNF-α e TGF-β), indutor de e protetor contra inflamação, prevaleceu nos pacientes; em T6, prevaleceu o perfil Th2 (IL-10, TNF-α e TGF-β), protetor contra efeito nocivo pró-inflamatório do TNF-α ainda presente. O comportamento do IFN-γ (T0 > T3 > T6 = controle) sugere sua utilização como marcador de resposta ao tratamento.
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Genomic imprinting is defined as a gamete of origin-specific epigenetic modification of DNA leading to differential gene expression in the zygote. Several imprinted genes have been identified and some of them are associated with tumor development. We investigated the expression and the imprinting status of IGF2 and H19 genes in 47 uterine leiomyomas. Using allelic transcription assay, we detected the expression of the IGF2 gene in 10 of a total of 15 informative cases. No loss of imprinting, as determined by the finding of biallelic expression, was detected in any case. The expression of H19 gene was detected in 10 of 20 informative cases and the imprinting pattern was also maintained in all of them. Our data suggest that alterations in IGF2 and H19 genes expression by loss of imprinting do not occur in uterine leiomyomas. (C) 1999 Academic Press.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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A variety of chemicals can adversely affect the immune system and influence tumor development. The modifying potential of chemical carcinogens on the lymphoid organs and cytokine production of rats submitted to a medium-term initiation-promotion bioassay for carcinogenesis was investigated. Male Wistar rats were sequentially initiated with N-nitrosodiethylamine (DEN), N-methyl-N-nitrosourea (MNU), N-butyl-N-(4hydroxybutyl)nitrosamine (BBN), dihydroxy-di-n-propylnitrosamine (DHPN), and 1,2-dimethylhydrazine (DMH) during 4 weeks. Two initiated groups received phenobarbital (PB) or 2-acetyl amino fluorene (2-AAF) for 25 weeks and two noninitiated groups received only PB or 2-AAF. A nontreated group was used as control. Lymphohematopoietic organs, liver, kidneys, lung, intestines, and Zymbal's gland were removed for histological analysis. Interleukin (IL)-2, IL-12, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), IL-10, and transforming growth factor betal (TGF-beta1) levels were determined by ELISA in spleen cell culture supernatants. At the fourth week, exposure to the initiating carcinogens resulted in cell depletion of the thymus, spleen and bone marrow, and impairment of IL-2, IL-12, and IFN-gamma production. However, at the 30th week, no important alterations were observed both in lymphoid organs and cytokine production in the different groups. The results indicate that the initiating carcinogens used in the present protocol exert toxic effects on the lymphoid organs and affect the production of cytokines at the initiation step of carcinogenesis. This early and reversible depression of the immune surveillance may contribute to the survival of initiated cells facilitating the development of future neoplasia. (C) 2003 Elsevier B.V. All rights reserved.
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)