| 1. |
- Hagberg, Niklas, 1977-, et al.
(author)
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The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE
- 2018
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In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 77:7, s. 1070-1077
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Journal article (peer-reviewed)abstract
- Objectives Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE.Methods Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs.Results In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8+ T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8+ and CD4+ T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively.Conclusions T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment.
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| 2. |
- Joelsson, Lars Magnus T., et al.
(author)
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Tailored chemical mechanisms for simulation of urban air pollution
- 2018
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In: WIT Transactions on Ecology and the Environment. - 1746-448X. ; 230, s. 165-176
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Journal article (peer-reviewed)abstract
- A semi-stochastic, statistical reduction method for chemical kinetic schemes based on the ant colony optimization method, is developed for atmospheric chemistry simulations. The prime application is coupled dynamic and chemistry models for simulation of the dispersion and reactivity of chemical species on street scale, i.e. the modelling of urban air pollution in street canyons. The method is designed so that it will optimize the reduction process for any simulation case, as given by user-specific inputs, such as initial concentrations of reactive species, temperature, humidity, residence time, and solar radiation. These inputs will correspond to, or be deduced from, actual variables such as season, time-of-day, geographic location, proximity to volatile organic carbon or nitrogen oxides sources (e.g. forests, roads, industry, harbours etc.) and their source strengths, weather, composition of vehicle fleet, and traffic load inside the street canyon. The method is evaluated against three box model case studies (laboratory and atmospheric simulations) previously described in the literature. The method reduces the mechanism sizes with 62.5%, 84.7%, and 97.7% respectively, retaining the average accuracy for the prediction of the target compound (O3, NO2, and NO) concentrations by 94.1%, 90.3%, and 91.2% respectively. These preliminary results illustrate the potential for the method. Further developments, such as inclusion of lumping or short-cutting of reaction paths, can be considered.
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| 3. |
- Joelsson, Magnus, et al.
(author)
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Does smoking influence the risk of pouchitis following ileal pouch anal anastomosis for ulcerative colitis?
- 2006
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In: Scandinavian journal of gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 41:8, s. 929-33
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Journal article (peer-reviewed)abstract
- OBJECTIVE: According to epidemiological studies, smoking habit is strongly associated with inflammatory bowel disease. Non-smokers, and especially recent ex-smokers, have an increased risk of ulcerative colitis (UC). Conversely, concerning Crohn's disease, the risk is increased among smokers. Pouchitis is the major long-term complication of restorative proctocolectomy for UC, and seems to be pathogenetically related to this condition. The aims of this study were to test the hypothesis that smoking reduces the risk of pouchitis, and to investigate whether cessation of smoking precedes the onset of the inflammation. MATERIAL AND METHODS: All living patients operated on for UC with proctocolectomy and ileal pouch anal anastomosis (IPAA) between November 1982 and November 1996 at Sahlgren's University Hospital were included in the study (n=410). Data concerning smoking habits and pouchitis were obtained from questionnaires and from medical records. The correlation between smoking habits and incidence of pouchitis was statistically evaluated by means of a survival test and a multivariate analysis, i.e. a Poisson model. RESULTS: In all, 327 patients (80%) completed the questionnaires. Ninety-six (29%) of these patients had had at least one episode of pouchitis. Smoking habits during follow-up did not significantly influence the risk of pouchitis (p=0.29). Nor did smoking habits before and at the time of IPAA correlate with the incidence of pouchitis. Women had a decreased risk of pouchitis, compared to men (p=0.014). There was a non-significant tendency for smoking to increase the risk, which was more pronounced in women. CONCLUSIONS: Smoking does not decrease the risk of pouchitis following IPAA for UC, and in this respect the pathogenetic model of pouchitis, suggested to be a manifestation of UC, is not supported.
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| 4. |
- Molina-Aldareguia, J.M., et al.
(author)
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Deformation structures under indentations in TiN/NbN single-crystal multilayers deposited by magnetron sputtering at different bombarding ion energies
- 2002
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In: Philosophical magazine. A. Physics of condensed matter. Defects and mechanical properties. - 0141-8610. ; 82:10 SPEC., s. 1983-1992
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Journal article (peer-reviewed)abstract
- Work elsewhere has suggested that multilayer films with layer thicknesses of a few nanometres can be much harder than monolithic films, although there is considerable variation in the observed magnitude of this effect. To investigate this, multilayer TiN/NbN films have been deposited by reactive magnetron sputtering on to MgO single crystals. The hardnesses measured were similar to those of the TiN and NbN alone, which is consistent with the observation by transmission electron microscopy (TEM) that deformation across the interfaces was not prevented. Varying the electrical potential at which the film was grown from -10 to -200 V and the corresponding ion energy from 10 to 200 eV increased the hardness from 19 to 25 GPa, further decreases in the potential caused the hardness to decrease. Using TEM, deformation was observed to occur along the apparent columnar boundaries within the films, suggesting that the effect of the electrical potential on the measured hardness was caused by changes in the apparent strength of the columnar boundaries, possibly associated with the variations in the volume fraction of voids that were observed on these boundaries.
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| 5. |
- Rondahl, E., et al.
(author)
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The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer
- 2014
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In: Journal of Clinical Virology. - : Elsevier BV. - 1386-6532 .- 1873-5967. ; 60:2, s. 172-173
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Journal article (peer-reviewed)abstract
- Background: Hepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination. Objectives: The aim of this study was to evaluate the risk of such contamination in a proposed clinical setting. Study design: In the present study, known HCV RNA positive (n= 149) and negative (n= 149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination. Results: In subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33. IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low. Conclusions: We conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000. IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity. © 2014 The Authors.
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