Browsing by Subject "INTERFERON"

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  • Savolainen, Laura E.; Kantele, Anu; Knuuttila, Aija; Pusa, Liana; Karttunen, Riitta; Valleala, Heikki; Tuuminen, Tamara (2016)
    New biomarkers are needed for discriminating active tuberculosis (TB) from latent TB infection (LTBI), especially in vulnerable groups representing the major diagnostic challenge. This pilot study was carried out to explore the diagnostic potential of selected genes, IFN-gamma, IL-17, IL-4, and FoxP3, associated with TB immunity and immunopathology. IFN-gamma, IL-17, IL-4, and FoxP3 mRNA expression levels were measured by quantitative reverse transcription PCR (RT-qPCR) from antigen-stimulated peripheral blood mononuclear cells of patients with active TB (n = 25); patients with miscellaneous inflammatory disorders and concomitant LTBI (n = 20), rheumatoid arthritis (RA) being the most predominant in the group (n = 11); and in healthy Bacillus Calmette Guerin (BCG) vaccinees (n = 8). While the levels of FoxP3 mRNA did not differ between the tested groups, the cumulative expression levels of purified protein derivative -stimulated IFN-gamma, IL-17, and IL-4 mRNAs were found to distinguish active TB from the whole group of LTBI with 48% sensitivity and 85% specificity. When restricting the LTBI group to RA cases only, the sensitivity was 56% and specificity 100%. When interpreting the result as positive in at least one of the mRNAs IFN-gamma, IL-17, or IL-4, sensitivity of 64% and specificities of 75% (heterogeneous group of LTBI) or 100% (LTBI with RA) were achieved. Moderate discrimination of active TB from LTBI with miscellaneous inflammatory underlying conditions by using combined quantitative expression of IFN-gamma, IL-17, and IL-4 mRNA seems not to be of high diagnostic potential.
  • Hjorth-Hansen, Henrik; Stenke, Leif; Soderlund, Stina; Dreimane, Arta; Ehrencrona, Hans; Gedde-Dahl, Tobias; Gjertsen, Bjorn Tore; Hoglund, Martin; Koskenvesa, Perttu; Lotfi, Kourosh; Majeed, Waleed; Markevarn, Berit; Ohm, Lotta; Olsson-Stromberg, Ulla; Remes, Kari; Suominen, Merja; Simonsson, Bengt; Porkka, Kimmo; Mustjoki, Satu; Richter, Johan; NCMLSG (2015)
  • EuroSIDA Study Grp; Amele, S.; Ristola, M.; Mocroft, A.; Aho, I. (2019)
    Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P <0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.
  • Anastasina, Maria; Le May, Nicolas; Bugai, Andrii; Fu, Yu; Soderholm, Sandra; Gaelings, Lana; Ohman, Tiina; Tynell, Janne; Kyttanen, Suvi; Barboric, Matjaz; Nyman, Tuula A.; Matikainen, Sampsa; Julkunen, Ilkka; Butcher, Sarah J.; Egly, Jean-Marc; Kainov, Denis E. (2016)
    Influenza NS1 protein is an important virulence factor that is capable of binding double-stranded (ds) RNA and inhibiting dsRNA-mediated host innate immune responses. Here we show that NS1 can also bind cellular dsDNA. This interaction prevents loading of transcriptional machinery to the DNA, thereby attenuating IAV-mediated expression of antiviral genes. Thus, we identified a previously undescribed strategy, by which RNA virus inhibits cellular transcription to escape antiviral response and secure its replication. (C) 2016 Elsevier B.V. All rights reserved.
  • Hertel, Christina; Fishman, Dmytro; Lorenc, Anna; Ranki, Annamari; Krohn, Kai; Peterson, Pärt; Kisand, Kai; Hayday, Adrian (2019)
    In 2016, we reported four substantial observations of APECED/APS1 patients, who are deficient in AIRE, a major regulator of central T cell tolerance (Meyer et al., 2016). Two of those observations have been challenged. Specifically, 'private' autoantibody reactivities shared by only a few patients but collectively targeting >1000 autoantigens have been attributed to false positives (Landegren, 2019). While acknowledging this risk, our study-design included follow-up validation, permitting us to adopt statistical approaches to also limit false negatives. Importantly, many such private specificities have now been validated by multiple, independent means including the autoantibodies ' molecular cloning and expression. Second, a significant correlation of antibody-mediated IFN a neutralization with an absence of disease in patients highly disposed to Type I diabetes has been challenged because of a claimed failure to replicate our findings (Landegren, 2019). However, flaws in design and implementation invalidate this challenge. Thus, our results present robust, insightful, independently validated depictions of APECED/APS1, that have spawned productive follow-up studies.
  • Hemilä, Harri; Herman, Zelek S (American College of Nutrition, 1995)
    In 1975 Thomas Chalmers analyzed the possible effect of vitamin C on the common cold by calculating the average difference in the duration of cold episodes in vitamin C and control groups in seven placebo-controlled studies. He found that episodes were 0.11 +/- 0.24 (SE) days shorter in the vitamin C groups and concluded that there was no valid evidence to indicate that vitamin C is beneficial in the treatment of the common cold. Chalmers' review has been extensively cited in scientific articles and monographs. However, other reviewers have concluded that vitamin C significantly alleviates the symptoms of the common cold. A careful analysis of Chalmers' review reveals serious shortcomings. For example, Chalmers did not consider the amount of vitamin C used in the studies and included in his meta-analysis was a study in which only 0.025-0.05 g/day of vitamin C was administered to the test subjects. For some studies Chalmers used values that are inconsistent with the original published results. Using data from the same studies, we calculated that vitamin C (1-6 g/day) decreased the duration of the cold episodes by 0.93 +/- 0.22 (SE) days; the relative decrease in the episode duration was 21%. The current notion that vitamin C has no effect on the common cold seems to be based in large part on a faulty review written two decades ago.
  • Hemilä, Harri (1997)
    Although the role of vitamin C in common cold incidence had been studied extensively, the level of vitamin C intake has not been unequivocally shown to affect the incidence of colds. In the present study the six largest vitamin C supplementation (> or = 1 g/d) studies, including over 5000 episodes in all, have been analysed, and it is shown that common cold incidence is not reduced in the vitamin C-supplemented groups compared with the placebo groups (pooled rate ratio (RR) 0.99; 95% CI 0.93, 1.04). Consequently these six major studies give no evidence that high-dose vitamin C supplementation decreases common cold incidence in ordinary people. Nevertheless, the analysis was continued with the hypothesis that vitamin C intake may affect common cold susceptibility in specific groups of people. It was assumed that the potential effect of supplementation might be most conspicuous in subjects with low dietary vitamin C intake. The average vitamin C intake has been rather low in the UK and plasma vitamin C concentrations are in general lower in males than in females. In four studies with British females vitamin C supplementation had no marked effect on common cold incidence (pooled RR 0.95; 95% CI 0.86, 1.04). However, in four studies with British male schoolchildren and students a statistically highly significant reduction in common cold incidence was found in groups supplemented with vitamin C (pooled RR 0.70; 95% CI 0.60, 0.81). Thus, these studies with British males indicate that vitamin C intake has physiological effects on susceptibility to common cold infections, although the effect seems quantitatively meaningful only in limited groups of people and is not very large.