323,158 research outputs found
Activation of Type I and Type III Interferons in Chronic Hepatitis C
No full textInfection with hepatitis C virus (HCV) results in chronic and progressive liver disease. Persistency rates add up to 85%. Despite recognition of the virus by the human host in peripheral blood and in the liver, immune response appears to be ineffective in clearing infection. The ability to spontaneously eradicate the virus as well as the outcome of infection upon therapy with human recombinant interferon-alpha (IFN-alpha) was found to correlate most closely with genetic variations within the region encoding the IFN-lambda genes, as revealed by genome-wide association studies on main ethnic populations in 2009. This review summarizes the induction of type I and type III IFN genes and their effectors, the IFN-stimulated genes. It focusses on the in vivo situation in chronic HCV infection in man both in the peripheral blood compartment and in the liver. It also addresses the impact of genetic polymorphisms in the region of type III IFN genes on their activation. Finally, it discusses how antiviral drugs (i.e. IFN-alpha, ribavirin and the direct-acting antivirals) may complementarily control the activation of endogenous IFNs and succeed in combatting infections. (C) 2015 S. Karger AG, Base
Positiones Theologicae, Quas Auspice Deo, Ad Consequendos Supremos In Theologia Honores : Fuldae In Aula Academica Die XXX Augusti, Anno MDCCLXXXVIII, horis ante & post meridiem consuetis
No full textPublice Propugnabut P. Quinibertus Mihm, O.S.B. In Perillustri Ad S. Salvat. Conventu Fuldae Professus, Theologiae et Philosophiae Moralis Professor P. Et O.Autopsie nach Ex. der ULB DüsseldorfVorlageform der Veröffentlichungsangabe: Typis StahelianisFulda, Dissertation, 30. Aug. 178
Hepatitis C Virus, Diabetes and Steatosis: Clinical Evidence in Favor of a Linkage and Role of Genotypes
No full textInfection with hepatitis C virus (HCV) primarily causes chronic liver disease with characteristic histopathologic features, including hepatic steatosis. Moreover, chronic hepatitis C is also closely related to insulin resistance (IR) and an increased risk of type 2 diabetes mellitus (DM). This review summarizes the available clinical evidence for a linkage of chronic HCV infection and developing IR or DM that comprises (i) retro- and prospective clinical studies, (ii) the excess risk of chronic hepatitis C patients to develop DM compared to hepatitis B patients, (iii) a preferential relationship of IR with HCV type-1, -2 or -4 infections, (iv) a correlation between IR, viral load and responsiveness to antiviral treatment and (v) a decreased incidence of DM in chronic hepatitis C after sustained virological response. This review further refers to the clinical evidence of a preferential relationship between hepatic steatosis and HCV type-3 infection, and that two distinct genotype-specific pathogenic mechanisms underlie steatosis in hepatitis C. In HCV type-3 infections, steatosis is related to viral load but not to metabolic factors, and, thus, is termed 'viral steatosis'. In HCV type-1, -2 or -4 infections, steatosis appears to be secondary to IR and regarded as 'metabolic steatosis'. In conclusion, multiple lines of clinical evidence support a linkage of HCV infection and both hepatic carbohydrate and lipid metabolism. The extent to which targeting the host's metabolism by drugs or by lifestyle change translates into an improvement of health or in a better response to interferon-alpha will provide further valuable insights into virus-host interactions, and is topic which is currently addressed in clinical studies. Copyright (C) 2010 S. Karger AG, Base
Functional relevance of the IRF-1 promoter polymorphism rs2549009 on transcriptional activity in a native genomic environment
No full textInterferon regulatory factor-1 (IRF-1), a transcription regulator involved both in inducing and in mediating the effects of interferon, is encoded by a highly polymorphic gene in different ethnic populations. Some of these genetic variations have been described to be associated to disease traits in hepatitis C virus and in human immunodeficiency virus infection, including one single-nucleotide polymorphism rs2549009 within the promoter region. This study aimed at investigating the functional relevance of rs2549009 on IRF-1 transcriptional activity in peripheral blood mononuclear cells in its natural genomic environment. Haplotype-specific chromatin immunoprecipitation using antibodies directed against both the transcriptionally inactive and active RNA polymerase II (RNAPII) and allele-specific transcript quantification techniques were applied to ex vivo-derived samples from healthy heterozygous donors. Inactive serine 5 phosphorylated RNAPII was found to be preferentially bound to the rs2549009 A allele in all donors investigated. Active serine 2 phosphorylated (ser2-P) RNAPII, in contrast, was found to be precipitable, depending on the donor, preferentially either with the A or the G promoter variants or without any preference. The ratio of rs2549009 A/G promoter variants engaged by ser2-P RNAPII was closely related to the relative frequency of the respective IRF-1 transcripts, and relative allelic expression was found to be associated to total IRF-1 gene expression. These results provide evidence for a bidirectional IRF-1 gene expression imbalance that appears not to be solely controlled by rs2549009 in cis and may rely on a yet unidentified variant or haplotype or on environmental control in trans.Deutsche Forschungsgemeinschaft [MI 474/1-1
Downregulation of T cell growth factor production by ornithine decarboxylase and its product putrescine: D,L-alpha-difluoromethylornithine suppresses general protein synthesis but augments simultaneously the production of interleukin-2
No full textHigh Predictability of a Sustained Virological Response (87%) in Chronic Hepatitis C Virus Genotype 1 Infection Treatment by Combined IL28B Genotype Analysis and gamma-Glutamyltransferase/Alanine Aminotransferase Ratio: A Retrospective Single-Center Study
No full textBackground: Chronic hepatitis C virus genotype 1 (HCV-G1) infection is treated with pegylated interferon-a and ribavirin. Predictive factors for treatment success are even more important now as direct-acting antiviral agents are available. Methods: Clinical and laboratory parameters were analyzed by uni- and multivariate statistical means in 264 patients with HCV-G1 infections with regard to treatment outcome. Results:The overall sustained virological response (SVR) rate was 44%. Univariate analyses revealed SVRs to be associated with age, high alanine aminotransferase (ALT) and low gamma-glutamyltransferase (gamma-GT) serum activities, a low pretreatment gamma-GT/ALT ratio, rapid virological response (RVR), and absence of steatosis. Multivariate analyses unveiled IL28B rs12979860 genotype (CC vs. CT: OR = 2.8, CI: 1.5-4.9, p = 0.001; CC vs. TT: OR = 7.1, CI: 3.1-16.7, p < 0.001), low pretreatment gamma-GT/ALT ratio (OR = 2.5, CI: 1.7-3.3, p <0.001), age (OR = 0.96, CI: 0.94-0.98, p = 0.001) and RVR (OR = 4.18, CI: 2.85-8.65, p <0.001) to be significantly related to treatment outcome. Patients with the IL28B rs12979860 CC genotype and a low pretreatment gamma-GT/ALT ratio achieved the highest rate of a SVR with the highest predictive values (OR = 26.7, 95% CI: 10-71.1, p<0.0001). Conclusion: The pretreatment gamma-GT/ALT ratio significantly enhances the predictability of the IL28B genotype. Employing this combination will help to identify patients who will most likely benefit from an interferon-alpha-based combination therapy in a nontriaged ordinary setting. Copyright (C) 2012 S. Karger AG, Base
Healthcare Utilization and Costs of Human Papillomavirus (HPV) Associated Anogenital Diseases in Young Women: An Analysis of Statutory Health Insurance Claims Data from Germany
No full textReuschenbach M, Mihm S, Woelle R, et al. Healthcare Utilization and Costs of Human Papillomavirus (HPV) Associated Anogenital Diseases in Young Women: An Analysis of Statutory Health Insurance Claims Data from Germany. In: Emerging Frontiers and Opportunities. Value in Health . Vol 25. Elsevier ; 2022: S88
The 5/9 monoclonal antibody defines an activation antigen expressed on human T cells and T cell precursors
No full textRegulation of interleukin-2 production by ornitine decarboxylase and its product putescine
No full textDiffusive author(s), cohesive author: Analysis of S/N (1994)
No full textThis study indicates the ways in which various aspects of the author(s) are brought forth in Dumb type’s performance art, the S/N production. Previous research has suggested a non-hierarchical organization of Dumb type and the absence of a “privileged author” in Dumb type’s collaborative work, S/N. However, the results that I have investigated from member’s interviews on the creative process of S/N along with my analysis of the recorded images of S/N, indicate a different aspect of the author(s). First, S/N was created through, so to speak, the collective ideas of the members of Dumb type. Further, S/N has at least nine quotations from previous performances, installations, and printed writings, besides the work-in-progress technique. Explicating one of the “author functions” as given by Michel Foucault, each text has plural subjects of the author. However, it has been revealed from members’ interviews that Teiji Furuhashi had a decision-making role in selecting the members’ ideas within the performance. Since then, S/N has had plural subjects of creation; however, Furuhashi is one of the subjects of creation along with the “privileged author.” S/N has plural authors (diffusive authors) yet at the same time, it has a “privileged author,” Teiji Furuhashi (cohesive author)
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