Diss. (sammanfattning) Örebro : Örebro universitet, 2009. / Härtill 4 uppsatser.

Thesis (M.Sc. (Hons.)) -- University of Western Sydney, 2007. / A thesis submitted towards the degree of Master of Nursing (Honours) in the University of Western Sydney, College of Health and Science, School of Nursing. Includes bibliographical references.

Thesis (Ph.D.)--University of Alberta, 2009. / A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor in Philosophy in Experimental Surgery, Department of Surgery. Title from pdf file main screen (viewed on October 13, 2009). Includes bibliographical references.

As taxas de resposta viral ao tratamento com Interferon- associado com Ribavirina ainda não estão bem definidas. Muitos estudos associam vários fatores virais e do hospedeiro, tais como a idade, sexo, peso, etnia, nível de enzimas hepáticas, estágio de fibrose, genótipo do HCV com os níveis de RNA viral. Outros estudos associam as células CD8+ específicas para epítopos do HCV com o controle da viremia. O objetivo desse trabalho foi verificar se há aumento na pressão seletiva contra o vírus nos pacientes em tratamento com Interferon- associado à Ribavirina respondedores em comparação com os pacientes não respondedores e associar esse aumento com a ação antiviral do tratamento e/ou com o aumento da resposta imune devido à ação imunomoduladora do Interferon-, utilizando-se modelos de máxima verossimilhança, de cálculo da razão dN/dS e realizando o mapeamento dos epítopos das proteínas NS5A. Nossos resultados demonstram que usando modelos par a par não foi detectado evidência de seleção positiva, entretanto utilizando modelos de máxima verossimilhança nós observamos evidência no grupo que não responde a terapia. O mapeamento dos epítopos revelou que o epítopo VLSDFKTWL estava associado com a resposta efetiva do tratamento com suporte estatístico. Estes resultados indicam que a resposta imunológica aumenta durante o período de tratamento, auxiliando na eliminação do vírus. Além das análises, foi desenvolvida uma ferramenta de mapeamento automático dos epítopos do HCV e análise de seleção natural aplicando modelos de máxima verossimilhança / The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Several studies suggest that viral load is closely associated to viral and host factors, such age, sex, body weight, transaminase levels and HCV genotype. Moreover, an strong CD8+ T-cell immunity in acute resolving hepatitis C is matched by strong and sustained CD4+ T-cell proliferation to multiple recombinant structural and non-structural viral proteins is responsible for the control of viraemia in HCV infection. Here, we investigate the differences in CD8 epitopes frequencies from Los Alamos database between groups of patients that showed distinct response to pegylated alpha interpheron with ribavirin therapy, and test for evidence of natural selection on virus in treatment failure group, using five maximum likelihood evolutionary models. Our results indicated no evidence of positive selection by using pairwise models, however we identify evidence of positive selection in non responder group by applying maximum likelihood models. The epitope mapping showed that the epitope VLSDFKTWL was associated with efective therapy outcome, with statistical support. Those results suggest that the immune response increase during the treatment period, allowing the virus clearance. We also developed a tool for automatic mapping of epitopes of HCV that tests for evidence of natural selection by applying maximum likelihood models

Hepatitis C virus (HCV) is a small single stranded RNA virus, that belongs to the Flaviviridae family. HCV can be classified into six major genotypes and more than 50 subtypes.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Source: Masters Abstracts International, Volume: 46-04, page: 2101. Adviser: Lu-Yu Hwang. Includes bibliographical references.

This thesis is focused on occurrence of viral hepatitises by clients in Psychiatric Hospital Červený Dvůr between 2000 and 2009. In my beachelor thesis was covered years from 2000 to 2004. Now I continue with this diploma thesis where I want the 10 year results join together to show how the situation is developing. The intravenous drug users are the aimed group. These drug users belong to a high-risk group in which hepatitises types A, B or C are spread the most thanks to their high-risk behaviour. These days researches and epidemiologic researches show that the intravenous drug users belong among the main high-risk groups endangered by infectious disease. Viral hepatitises represent a serious problem, mainly hepatitis type C, because there is no way of protection. This hepatitis is occuring without any symptoms of this disease by 50 ? 70 % people. By 70 ? 80 % it passes into a chronic stadium. It is possible to protect yourself by hepatitis type A vaccination. This hepatitis doesn´t change into a chronic stadium. It is easily spread by infected water or food. In our republic there occured several epidemics. Hepatitises started to spread among drug users and then they spread also among the rest of population. The last epidemic occured in 2008. Hepatitis type B represents high risks for the perceptive population. There is a vaccine and population have a chance to protect against it. In the Czech Republic there is vaccination carried out within special vaccination of people who have high-risk job, for example in health service. Children of HBsAg positive mothers are vaccinated after they are born. From 2001 hepatitis vaccination was put into regular vaccination of children aged under 1 year in our republic. Also 12 year old children are vaccinated from 2001. Hepatitis type B often becomes chronic and the mortality is 1 ? 2 %. Intravenous using of drug is important high-risk factor. It is one of the ways of transfering hepatitises type B and C. Next monitored indicators are the age of the clients, achieved level of education, basic drug, the age of the first usage of any drug, the age of intravenous application of drug and occurrence of hepatitises type A, B, C by clients. According to my research I used quantitative research which allows me to analyse problem of viral hepatitises by clients from Psychiatric Hospital in Červený Dvůr. The gained information was worked out by secondary analysis of medical data. The monitored group has 2499 clients in years 2000 ? 2009. The aim of this thesis is to get general knowledge about prevalence of viral hepatitises by clients of Psychiatric Hospital in Červený Dvůr from 2000 to 2009 and to consider their progress. The methodical procedure: there will be used a content analysis of medical data given by Psychiatric Hospital in Červený Dvůr. The result of this thesis is that it indicates and covered the develop of drug scene. Concerning the age the main group consists of 20 ? 24 year old men and women, next large group consists of clients aged 25 ? 29. The monitored group is also changing according to achieved level of education. In the first five years of research there dominated vocational school, but in the last five years there it changed into basic school. Among women there happened no change. There basic school still dominates. Concerning the drugs there also changed something. At the beginning there dominated clients using heroin, in the middle there meth dominated. Hepatitis type A in acute stadium was revealed by only two clients. Hepatitis type B noticed a slight increase. Hepatitis type C also noticed a sligh increase, but it is probably a sign of increase of clients with chronic form of this hepatitis.

As taxas de resposta viral ao tratamento com Interferon- associado com Ribavirina ainda não estão bem definidas. Muitos estudos associam vários fatores virais e do hospedeiro, tais como a idade, sexo, peso, etnia, nível de enzimas hepáticas, estágio de fibrose, genótipo do HCV com os níveis de RNA viral. Outros estudos associam as células CD8+ específicas para epítopos do HCV com o controle da viremia. O objetivo desse trabalho foi verificar se há aumento na pressão seletiva contra o vírus nos pacientes em tratamento com Interferon- associado à Ribavirina respondedores em comparação com os pacientes não respondedores e associar esse aumento com a ação antiviral do tratamento e/ou com o aumento da resposta imune devido à ação imunomoduladora do Interferon-, utilizando-se modelos de máxima verossimilhança, de cálculo da razão dN/dS e realizando o mapeamento dos epítopos das proteínas NS5A. Nossos resultados demonstram que usando modelos par a par não foi detectado evidência de seleção positiva, entretanto utilizando modelos de máxima verossimilhança nós observamos evidência no grupo que não responde a terapia. O mapeamento dos epítopos revelou que o epítopo VLSDFKTWL estava associado com a resposta efetiva do tratamento com suporte estatístico. Estes resultados indicam que a resposta imunológica aumenta durante o período de tratamento, auxiliando na eliminação do vírus. Além das análises, foi desenvolvida uma ferramenta de mapeamento automático dos epítopos do HCV e análise de seleção natural aplicando modelos de máxima verossimilhança / The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Several studies suggest that viral load is closely associated to viral and host factors, such age, sex, body weight, transaminase levels and HCV genotype. Moreover, an strong CD8+ T-cell immunity in acute resolving hepatitis C is matched by strong and sustained CD4+ T-cell proliferation to multiple recombinant structural and non-structural viral proteins is responsible for the control of viraemia in HCV infection. Here, we investigate the differences in CD8 epitopes frequencies from Los Alamos database between groups of patients that showed distinct response to pegylated alpha interpheron with ribavirin therapy, and test for evidence of natural selection on virus in treatment failure group, using five maximum likelihood evolutionary models. Our results indicated no evidence of positive selection by using pairwise models, however we identify evidence of positive selection in non responder group by applying maximum likelihood models. The epitope mapping showed that the epitope VLSDFKTWL was associated with efective therapy outcome, with statistical support. Those results suggest that the immune response increase during the treatment period, allowing the virus clearance. We also developed a tool for automatic mapping of epitopes of HCV that tests for evidence of natural selection by applying maximum likelihood models

Tc17 cells and the semi-invariant human mucosal associated invariant T (MAIT) cells are important CD8+ tissue-homing cell populations. Both are characterized by high expression of CD161 (++) and type-17 differentiation, yet their origins and relationships remain poorly defined. By transcriptional and functional analyses it is demonstrated that a pool of polyclonal, pre-committed type-17 CD161++CD8αβ+ T cells exists in cord blood, from which a prominent MAIT cell (TCR Vα7.2+/Vβ2 or 13.2) population emerges post-natally. During this expansion, CD8αα T-cells appear exclusively within CD161++CD8+/MAIT subset, sharing cytokine production (IL17, IL-22 and IFN-γ), chemokine-receptor expression (CCR2, CCR6 and CXCR6), TCR-usage and transcriptional profiles with their CD161++CD8αβ+ counterparts. These data demonstrate the origin and differentiation pathway of MAIT cells from a naïve type-17 pre-committed CD161++CD8+ T cell pool and the distinct phenotype and function of CD8αα cells in man. The CD161++CD8αβ and CD8αα T cell subsets are reduced in the peripheral circulation in chronic hepatitis B and C and are enriched in the liver in chronic hepatitis C. Their potential role in immunity to chronic viral hepatitis B and C is demonstrated by their expression of activation/exhaustion markers CD69, CD25, HLA-DR and PD-1. In addition a substantial distinct CD161-CD8β^low population is demonstrated in chronic hepatitis B, co-characterised by a CD28^low, HLA-DR^high phenotype and high expression of IFN-γ, with important implications for the development of immunotherapy and vaccination.