• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 36
  • 33
  • 11
  • 5
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 1
  • 1
  • 1
  • 1
  • Tagged with
  • 99
  • 23
  • 22
  • 20
  • 20
  • 19
  • 18
  • 16
  • 15
  • 12
  • 12
  • 12
  • 11
  • 11
  • 11
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Regulation of the human interferon-b promoter

Xanthoudakis, Steven January 1990 (has links)
No description available.
2

Regulation of the human interferon-b promoter

Xanthoudakis, Steven January 1990 (has links)
Human type I interferons offer a relevant system to examine cell-specific inducible gene expression. Interferon genes are transcriptionally activated in a variety of cell types following induction by synthetic double-stranded RNA (poly I:C) and viruses. A transient expression system was developed which permits regulated expression of different IFN-CAT (chloramphenicol acetyltransferase) hybrid genes in human cells. Using this system in vivo competition assays identified positive and negative cellular factors interacting with the IFN-$ beta$ promoter. A factor that recognizes negative upstream regulatory sequences was also identified in uninduced myeloid cell extracts. Complementary studies demonstrated that transcription of the IFN-$ beta$ gene in vitro could be inhibited by a 44 bp synthetic oligonucleotide corresponding to the interferon regulatory element (IRE). This element is comprised of two genetically distinct positive regulatory domains, PRDI and PRDII, that are essential for maximal induction by virus or poly I:C. Binding and competition analysis showed that the PRDI element interacts with a factor(s) present in uninduced and virus-induced Hela extracts. The DNA-binding specificity of the PRDI factor(s) is characteristic of proteins recently shown to be involved in IFN-stimulated gene transcription. The PRDII domain is unrelated to PRDI, but shares 80% nucleotide homology with the NF-$ kappa$B binding site in the immunoglobulin kappa enhancer. PRDII was found to interact with an NF-$ kappa$B-like activity in both lymphoid and non-lymphoid cell extracts. An HIV-1 enhancer oligonucleotide containing two repeated $ kappa$B elements was interchangeable with PRDII in the gel retardation assay. UV-crosslinking analysis further revealed that several distinct inducible and constitutive proteins bind specifically to PRDII in different cell types, and suggests that multiple factors may interact with this element to regulate IFN-$ beta$ transcription. Taken togeth
3

Interferon gamma production in HIV-1 exposed uninfected infants

Anthony, Fiona Sharon 25 November 2008 (has links)
Abstract The immaturity of the neonatal immune system places infants at an increased risk of infections and also affects the effective induction of protective immune responses by vaccines. In utero sensitisation to infectious pathogens results in immune activation and can establish immunological memory and may influence the immune response to unrelated antigens. In this study, we investigated in early life (birth to 6-10 weeks) the development of interferon-gamma (IFN-g) responses in uninfected infants born to HIV-1 infected mothers (exposed uninfected (EU) infants). Whole blood cell cultures stimulated with phytohaemagglutinin (PHA) or Mycobacterium bovis bacillus Calmette-Guérin (BCG) showed that EU infants have a greater ability to produce IFN-g in response to PHA and BCG at birth compared to control infants (born to HIV-1 uninfected mothers). However, by six weeks of age control infants produced significantly more IFN-g in response to PHA only. These results suggest that responses amongst EU infants establish and mature earlier than in control infants. In fact, over time a greater number of EU infants have a reduced ability or an inability to respond to stimuli such as PHA or BCG compared to control infants (when comparing responses at six weeks of age to responses of the matched birth samples). Full blood counts (FBC) counts were carried out using an automated AcT 5 diff haematology analyser which measures proportions and absolute counts of the five groups of white blood cells, namely, lymphocytes, monocytes, neutrophils, eosinophils and basophils. Importantly, there were no significant differences in the absolute lymphocyte counts of control infants and EU infants either at birth or at six weeks which could account for the IFN-g production differences noted between these infant groups, although the EU infants did exhibit a trend of higher absolute lymphocyte counts at six weeks than control infants. Age-dependent maturational changes in cell counts were observed in both control and EU infant groups, with neutrophils predominating at birth and lymphocytes predominating by six weeks, indicative of immune development with age in both infant groups. Short-course antiretroviral exposure increased basophil counts of infants at birth but did not affect counts by six weeks. Flow Cytometry studies using an Intracellular Cytokine (ICC) assay were conducted to establish which mononuclear cell types are predominantly responsible for producing IFN-g in infants. ICC assays done on whole blood revealed that natural killer cells (NK) were predominantly responsible for the IFN-g produced by 10 week old EU infants, and also at birth (control and EU infants). At birth whole blood cultures of 48% of EU infants already showed BCG-induced IFN-g responses (prior to BCG vaccination); this could be explained by a non-specific response (NK cells) to the antigen but could also involve T cell responses (CD4+ and/or CD8+ T cells) as supported by ICC data obtained from control and EU newborn infants. The infant immune system was clearly unique from that of their mothers. In particular, mothers’ demonstrated significant changes in blood counts from labour to six weeks postpartum indicative that immuno-modulation plays an essential role in a successful pregnancy. The single dose of nevirapine (sdNVP) taken by the mother at the onset of labour did not influence maternal blood counts significantly and maternal CD4+ and CD8+ T cells, and NK cells produced significantly more IFN-g than the CD14+ monocytes and CD19+ B cells, with CD8+ T cells producing the most. Our results have shown that EU infants are distinct from control infants with respect to immunological responses as measured by IFN-g production, and that maturational differences do exist between control and HIV-1 exposed infants. While the clinical importance of these results remains undetermined it is important to establish whether such immunological changes may result in altered susceptibility to infectious diseases in this already vulnerable population, and how this may impact on the induction of protective immune responses by vaccines. It remains important to identify neonatal immune system deficiencies and understand the consequences of exposure to maternal HIV-1 (in the absence of acquiring HIV-1 infection), the understanding of which could contribute to the development of more effective vaccines to HIV-1 and other infectious diseases.
4

Busca de fatores genéticos associados à resposta ao tratamento do HCV genótipo 3. / Search for genetic factors associated with treatment response in HCV genotype 3.

Luna, Alexandre La 30 July 2012 (has links)
Recentemente estudos demonstraram que os SNPs (polimorfismos de base única) rs8099917 e rs12979860 localizados próximos ao gene da IL28B explicam a variação de resposta à infecção e tratamento do paciente contra o genótipo 1 do HCV, porém não para o genótipo 3 deste vírus. Este trabalho encontrou associação significativa entre resposta à infecção devida ao genótipo 3 pelo tratamento (PEG-INF e RBV) e o polimorfismo rs8099917 em uma amostra da população de Santos - SP. Para o polimorfismo rs12979860, esta associação somente foi encontrada ao se parear indivíduos para sexo, idade e grau de fibrose hepática, demonstrando a importância da retirada de efeitos de estratificação neste tipo de análise. Estes resultados se confirmam ao se agregar dados de uma população proveniente da Bahia em uma meta-análise. Além disso, fez-se um estudo GWAS a fim de se conhecer outras variações genéticas envolvidas nessa resposta. Esta análise indicou a existência de alguns SNPs candidatos com sugestão de associação, dentre eles a tiroglobulina, relacionada aos hormônios da tireóide. / Recently, studies have shown that SNPs (single nucleotide polymorphisms) rs8099917 and rs12979860, located near the gene IL28B explain the changes in the response to infection and treatment of a patient against the HCV genotype 1, but not for the genotype 3 of the virus. This study found a significant association between response to infection due to treatment by genotype 3 (PEG-INF and RBV) and the rs8099917 polymorphism in a population sample from Santos - SP. To the rs12979860 polymorphism, this association was only found when individuals are paired for sex, age and degree of hepatic fibrosis, demonstrating the importance of the withdrawal effects of stratification in this type of analysis. These results confirm the aggregate data from a population of Bahia in a meta-analysis. In addition, a GWAS was made in order to search other genetic variations involved in this response. This analysis indicated the existence of some candidate SNPs with suggestion of association, including thyroglobulin, thyroid hormones related to.
5

Busca de fatores genéticos associados à resposta ao tratamento do HCV genótipo 3. / Search for genetic factors associated with treatment response in HCV genotype 3.

Alexandre La Luna 30 July 2012 (has links)
Recentemente estudos demonstraram que os SNPs (polimorfismos de base única) rs8099917 e rs12979860 localizados próximos ao gene da IL28B explicam a variação de resposta à infecção e tratamento do paciente contra o genótipo 1 do HCV, porém não para o genótipo 3 deste vírus. Este trabalho encontrou associação significativa entre resposta à infecção devida ao genótipo 3 pelo tratamento (PEG-INF e RBV) e o polimorfismo rs8099917 em uma amostra da população de Santos - SP. Para o polimorfismo rs12979860, esta associação somente foi encontrada ao se parear indivíduos para sexo, idade e grau de fibrose hepática, demonstrando a importância da retirada de efeitos de estratificação neste tipo de análise. Estes resultados se confirmam ao se agregar dados de uma população proveniente da Bahia em uma meta-análise. Além disso, fez-se um estudo GWAS a fim de se conhecer outras variações genéticas envolvidas nessa resposta. Esta análise indicou a existência de alguns SNPs candidatos com sugestão de associação, dentre eles a tiroglobulina, relacionada aos hormônios da tireóide. / Recently, studies have shown that SNPs (single nucleotide polymorphisms) rs8099917 and rs12979860, located near the gene IL28B explain the changes in the response to infection and treatment of a patient against the HCV genotype 1, but not for the genotype 3 of the virus. This study found a significant association between response to infection due to treatment by genotype 3 (PEG-INF and RBV) and the rs8099917 polymorphism in a population sample from Santos - SP. To the rs12979860 polymorphism, this association was only found when individuals are paired for sex, age and degree of hepatic fibrosis, demonstrating the importance of the withdrawal effects of stratification in this type of analysis. These results confirm the aggregate data from a population of Bahia in a meta-analysis. In addition, a GWAS was made in order to search other genetic variations involved in this response. This analysis indicated the existence of some candidate SNPs with suggestion of association, including thyroglobulin, thyroid hormones related to.
6

Cellular recognition of RNA virus infection leading to activation of interferon regulatory factors three and seven and establishment of the antiviral state

TenOever, Benjamin R. January 2004 (has links)
No description available.
7

Cellular recognition of RNA virus infection leading to activation of interferon regulatory factors three and seven and establishment of the antiviral state

TenOever, Benjamin R. January 2004 (has links)
Virus infection represents an intracellular invasion of host cells for the sole purpose of multiplication. Successful virus replication requires entry into tropic cells, usurping of the cellular machinery, and the production of progeny virions to initiate further rounds of infection. Establishment of the antiviral state in response to virus begins at the site of infection and requires the initiation of a preexisting signaling network designed to inhibit virus replication and aid in the establishment of this coordinated immune response. Integral components of this network include the IRF-3 and IRF-7 transcription factors that play essential roles in the cellular response to infection through virus induced phosphorylation by an unknown virus activated kinase. The objective of this research was to elucidate the viral antigen(s) required to induce the phosphorylation and subsequent activation of IRF-3 and IRF-7, to identify the molecular component(s) required in this activation process, and to decipher the mechanism(s) by which cellular recognition of virus infection initiates this antiviral response. We demonstrate that activation of this signaling network, following RNA virus infection, is dependent on viral entry, viral transcription, and viral translation and propose that the molecular requirements governing activation of IRF-3 and IRF-7 are the result of viral byproducts formed during the process of cytoplasmic RNA self replication; including both the formation of double stranded RNA and ribonucleoprotein complexes. Following cellular recognition of these motifs, signal transduction networks converge onto an IKK-related kinase structure composed of adaptor proteins bound to two kinase subunits, TBK-1 and IKKepsilon, which we propose to be essential components of the virus activated kinase. We demonstrate that TBK-1 or IKKepsilon activation results in the establishment of an antiviral state that renders cells non permissive to viral replic
8

Interferons in multiple sclerosis and optic neuritis

Salonen, Reijo. January 1983 (has links)
Thesis (doctoral)--University of Turku. / Includes reprints of 5 articles on which thesis is based.
9

Comparação das reações adversas do tratamento da hepatite crônica pelo vírus C com alfainterferona ou alfapeginterferona associados à ribavirina

Gonçalves, Candice Beatriz Treter January 2009 (has links)
Introdução: A hepatite C crônica representa um dos maiores problemas de saúde pública no mundo com estimativa de prevalência global média próxima de 3%. Seu tratamento é realizado com os medicamentos antivirais alfainterferona (IFN) e alfapeginterferona (PEGIFN), ambos associados à ribavirina, tendo como objetivo primário a supressão sustentada da replicação viral. Em virtude do perfil de reações adversas associadas ao tratamento medicamentoso, o acompanhamento farmacoterapêutico dos pacientes bem como uma farmacovigilância ativa pós comercialização se faz necessária. No Brasil, o tratamento da Hepatite C crônica é totalmente financiado pelo Sistema Único de Saúde, que também preconiza um acompanhamento destes pacientes através da criação de centros de referência. Objetivos: Este estudo teve como objetivo primário comparar a freqüência das reações adversas associadas ao IFN ou PEGIFN combinados com a ribavirina, bem como realizar uma farmacovigilância ativa destas RAM. Métodos: Realizou-se busca ativa, em entrevistas mensais com pacientes portadores de hepatite crônica pelo vírus C, atendidos em um serviço especializado da Secretaria Estadual de Saúde do Rio Grande do Sul (SES/RS). Trata-se de um estudo de coorte prospectivo que acompanhou pacientes tratados com IFN e ribavirina e PEGIFN e ribavirina. Através de entrevistas mensais semi-estruturadas as RAMs foram coletadas por um período de 24 semanas e classificadas de acordo com a severidade, a gravidade e a causalidade. Interrupções de tratamento e reduções de dose dos medicamentos por RAM também foram aferidas. Resultados: Foram acompanhados 283 pacientes destes 136 receberam IFN e 147 receberam PEGIFN ambos associados à ribavirina. Os tratamentos com IFN e PEGIFN foram no geral bem tolerados com perfil de RAMs semelhantes. As seis RAMs mais freqüentes no grupo IFN e PEGIFN, respectivamente, foram: fadiga (76,5% e 72,8%), cefaléia (72,1% e 75,5%), irritabilidade (66,2% e 63,9%), mialgia (61,8% e 61,2%), perda de apetite (57,4% e 66%) e febre (53,7% e 66,7%). A febre foi significativamente mais freqüente no grupo PEGIFN, comparado com o grupo IFN (p= 0,035). A anemia, neutropenia e plaquetopenia foram as RAMs hematológicas mais freqüentes com incidência maior no grupo PEGIFN (p<0,001, p<0,001 e p=0,031, respectivamente). A gravidade das RAM não foi diferente entre os grupos, demonstrando número semelhante de pacientes que apresentaram alguma RAM grave. Interrupções de tratamento e reduções de dose do IFN/PEGIFN por RAM foram mais frequentes no grupo PEGIFN (p<0,001 e p=0,008, respectivamente). Reduções de dose da ribavirina foram semelhantes nos dois grupos. Conclusão: O perfil de RAMs relatados, embora semelhante aos observados em estudos clínicos e esperados de acordo com o efeito biológico do medicamento, teve maior freqüência nesta coorte. Comparado ao IFN, o PEGIFN demonstrou maior freqüência de RAMs hematológicas e não-hematológicas, maior taxa de interrupções de tratamento e de redução de dose devidas as RAMs.
10

Comparação das reações adversas do tratamento da hepatite crônica pelo vírus C com alfainterferona ou alfapeginterferona associados à ribavirina

Gonçalves, Candice Beatriz Treter January 2009 (has links)
Introdução: A hepatite C crônica representa um dos maiores problemas de saúde pública no mundo com estimativa de prevalência global média próxima de 3%. Seu tratamento é realizado com os medicamentos antivirais alfainterferona (IFN) e alfapeginterferona (PEGIFN), ambos associados à ribavirina, tendo como objetivo primário a supressão sustentada da replicação viral. Em virtude do perfil de reações adversas associadas ao tratamento medicamentoso, o acompanhamento farmacoterapêutico dos pacientes bem como uma farmacovigilância ativa pós comercialização se faz necessária. No Brasil, o tratamento da Hepatite C crônica é totalmente financiado pelo Sistema Único de Saúde, que também preconiza um acompanhamento destes pacientes através da criação de centros de referência. Objetivos: Este estudo teve como objetivo primário comparar a freqüência das reações adversas associadas ao IFN ou PEGIFN combinados com a ribavirina, bem como realizar uma farmacovigilância ativa destas RAM. Métodos: Realizou-se busca ativa, em entrevistas mensais com pacientes portadores de hepatite crônica pelo vírus C, atendidos em um serviço especializado da Secretaria Estadual de Saúde do Rio Grande do Sul (SES/RS). Trata-se de um estudo de coorte prospectivo que acompanhou pacientes tratados com IFN e ribavirina e PEGIFN e ribavirina. Através de entrevistas mensais semi-estruturadas as RAMs foram coletadas por um período de 24 semanas e classificadas de acordo com a severidade, a gravidade e a causalidade. Interrupções de tratamento e reduções de dose dos medicamentos por RAM também foram aferidas. Resultados: Foram acompanhados 283 pacientes destes 136 receberam IFN e 147 receberam PEGIFN ambos associados à ribavirina. Os tratamentos com IFN e PEGIFN foram no geral bem tolerados com perfil de RAMs semelhantes. As seis RAMs mais freqüentes no grupo IFN e PEGIFN, respectivamente, foram: fadiga (76,5% e 72,8%), cefaléia (72,1% e 75,5%), irritabilidade (66,2% e 63,9%), mialgia (61,8% e 61,2%), perda de apetite (57,4% e 66%) e febre (53,7% e 66,7%). A febre foi significativamente mais freqüente no grupo PEGIFN, comparado com o grupo IFN (p= 0,035). A anemia, neutropenia e plaquetopenia foram as RAMs hematológicas mais freqüentes com incidência maior no grupo PEGIFN (p<0,001, p<0,001 e p=0,031, respectivamente). A gravidade das RAM não foi diferente entre os grupos, demonstrando número semelhante de pacientes que apresentaram alguma RAM grave. Interrupções de tratamento e reduções de dose do IFN/PEGIFN por RAM foram mais frequentes no grupo PEGIFN (p<0,001 e p=0,008, respectivamente). Reduções de dose da ribavirina foram semelhantes nos dois grupos. Conclusão: O perfil de RAMs relatados, embora semelhante aos observados em estudos clínicos e esperados de acordo com o efeito biológico do medicamento, teve maior freqüência nesta coorte. Comparado ao IFN, o PEGIFN demonstrou maior freqüência de RAMs hematológicas e não-hematológicas, maior taxa de interrupções de tratamento e de redução de dose devidas as RAMs.

Page generated in 0.4257 seconds