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Sökning: WFRF:(Ing A)

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11.
  • Zdzalik, M., et al. (författare)
  • Prevalence of genes encoding extracellular proteases in Staphylococcus aureus - important targets triggering immune response in vivo
  • 2012
  • Ingår i: Fems Immunology and Medical Microbiology. - 0928-8244. ; 66:2, s. 220-229
  • Tidskriftsartikel (refereegranskat)abstract
    • Proteases of Staphylococcus aureus have long been considered to function as important virulence factors, although direct evidence of the role of particular enzymes remains incomplete and elusive. Here, we sought to provide a collective view of the prevalence of extracellular protease genes in genomes of commensal and pathogenic strains of S.aureus and their expression in the course of human and mouse infection. Data on V8 protease, staphopains A and B, aureolysin, and the recently described and poorly characterized group of six Spl proteases are provided. A phylogenetically diverse collection of 167 clinical isolates was analyzed, resulting in the comprehensive genetic survey of the prevalence of protease-encoding genes. No correlation between identified gene patterns with specific infections was established. Humoral response against the proteases of interest was examined in the sera derived from human patients and from a model mouse infection. The analysis suggests that at least some, if not all, tested proteases are expressed and secreted during the course of infection. Overall, the results presented in this study support the hypothesis that the secretory proteases as a group may contribute to the virulence of S.aureus.
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15.
  • Bjarnadóttir, Kristín J., et al. (författare)
  • Body mass index is associated with pulmonary gas and blood distribution mismatch in COVID-19 acute respiratory failure : A physiological study
  • 2024
  • Ingår i: Frontiers in Physiology. - : Frontiers Media S.A.. - 1664-042X. ; 15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The effects of obesity on pulmonary gas and blood distribution in patients with acute respiratory failure remain unknown. Dual-energy computed tomography (DECT) is a X-ray-based method used to study regional distribution of gas and blood within the lung. We hypothesized that 1) regional gas/blood mismatch can be quantified by DECT; 2) obesity influences the global and regional distribution of pulmonary gas and blood; 3) regardless of ventilation modality (invasive vs. non-invasive ventilation), patients’ body mass index (BMI) has an impact on pulmonary gas/blood mismatch.Methods: This single-centre prospective observational study enrolled 118 hypoxic COVID-19 patients (92 male) in need of respiratory support and intensive care who underwent DECT. The cohort was divided into three groups according to BMI: 1. BMI<25 kg/m2 (non-obese), 2. BMI = 25–40 kg/m2 (overweight to obese), and 3. BMI>40 kg/m2 (morbidly obese). Gravitational analysis of Hounsfield unit distribution of gas and blood was derived from DECT and used to calculate regional gas/blood mismatch. A sensitivity analysis was performed to investigate the influence of the chosen ventilatory modality and BMI on gas/blood mismatch and adjust for other possible confounders (i.e., age and sex).Results: 1) Regional pulmonary distribution of gas and blood and their mismatch were quantified using DECT imaging. 2) The BMI>40 kg/m2 group had less hyperinflation in the non-dependent regions and more lung collapse in the dependent regions compared to the other BMI groups. In morbidly obese patients, gas and blood were more evenly distributed; therefore, the mismatch was lower than in other patients (30% vs. 36%, p < 0.05). 3) An increase in BMI of 5 kg/m2 was associated with a decrease in mismatch of 3.3% (CI: 3.67% to −2.93%, p < 0.05). Neither the ventilatory modality nor age and sex affected the gas/blood mismatch (p > 0.05).Conclusion: 1) In a hypoxic COVID-19 population needing intensive care, pulmonary gas/blood mismatch can be quantified at a global and regional level using DECT. 2) Obesity influences the global and regional distribution of gas and blood within the lung, and BMI>40 kg/m2 improves pulmonary gas/blood mismatch. 3) This is true regardless of the ventilatory mode and other possible confounders, i.e., age and sex.Trial Registration: Clinicaltrials.gov, identifier NCT04316884, NCT04474249.
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16.
  • Brisslert, Mikael, 1974, et al. (författare)
  • S100A4 regulates the Src-tyrosine kinase dependent differentiation of Th17 cells in rheumatoid arthritis
  • 2014
  • Ingår i: Biochimica Et Biophysica Acta-Molecular Basis of Disease. - : Elsevier BV. - 0925-4439. ; 1842:11, s. 2049-2059
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the role of S100A4, a calcium-binding regulator of nonmuscle myosin assembly, for T-cell responses in rheumatoid arthritis. Methods: Arthritis was induced in the methylated bovine serum albumin (mBSA)-immunized mice lacking the entire S100A4 protein (S100A4KO) and in wild-type counterparts treated with short hairpin ribonucleic acid (shRNA)-lentiviral constructs targeting S100A4 (S100A4-shRNA). The severity of arthritis was evaluated morphologically. T-cell subsets were characterized by the expression of master transcription factors, and functionally by proliferation activity and cytokine production. The activity of the Scr-kinases Fyn and Lck was assessed by the autophosphorylation of C-terminal thyrosine and by the phosphorylation of the CD5 cytodomain. The interaction between S100A4 and the CD5 cytodomain was analysed by nuclear magnetic resonance spectrophotometry. Results: S100A4-deficient mice (S100A4KO and S100A4-shRNA) had significantly alleviated morphological signs of arthritis and joint damage. Leukocyte infiltrates in the arthritic joints of S100A4-deficient mice accumulated Foxp3(+) Treg cells, while the number of ROR gamma t(+) and (pTyr705)STAT3(+) cells was reduced. S100A4-deficient mice had a limited formation of Th17-cells with low retinoic acid orphan receptor gamma t (ROR gamma t) mRNA and IL17 production in T-cell cultures. S100A4-deficient mice had a low expression and activity of T-cell receptor (TCR) inhibitor CD5 and low (pTyr705)STAT3 (signal transducer and activator of transcription 3), which led to increased (pTyr352)ZAP-70 (theta-chain associated protein kinase of 70 kDa), lymphocyte proliferation and production of IL2. In vitro experiments showed that S100A4 directly binds Lck and Fyn and reciprocally regulates their kinase activity towards the CD5 cytodomain. Spectrometry demonstrates an interaction between the CD5 cytodomain and EF2-binding sites of S100A4. Conclusion: The present. study demonstrates that S100A4 plays an important part in the pathogenesis of arthritis. It controls CD5-dependent differentiation of Th17 cells by regulating the activity of the Src-family kinases Lck and Fyn. (C) 2014 Elsevier B.V. All rights reserved.
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17.
  • Calander, Ann-Marie, 1957, et al. (författare)
  • Impact of staphylococcal protease expression on the outcome of infectious arthritis
  • 2004
  • Ingår i: Microbes Infect. - : Elsevier BV. - 1286-4579. ; 6:2, s. 202-6
  • Tidskriftsartikel (refereegranskat)abstract
    • The exoproteases of Staphylococcus aureus have been proposed as virulence factors during S. aureus infections. To investigate this, we used the wild-type S. aureus strain 8325-4 and its mutants devoid of aureolysin, serine protease, and cysteine protease, respectively, in a well-established model of septic arthritis in mice. The inactivation of the exoprotease genes did not affect the frequency or the severity of joint disease. We conclude that in the model of haematogenously spread staphylococcal arthritis, the bacterial proteases studied do not act as virulence factors.
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19.
  • Dohrn, Ing-Mari, et al. (författare)
  • Device-measured sedentary behavior and physical activity in older adults differ by demographic and health-related factors
  • 2020
  • Ingår i: European Review of Aging and Physical Activity. - : Springer Science and Business Media LLC. - 1813-7253 .- 1861-6909. ; 17:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Our aim was to describe and explore older adults' device-measured sedentary behavior and physical activity (PA) pattern by sex, age, education, marital status, body mass index, and physical function; and to assess agreement regarding fulfillment of PA recommendations, i.e. 150 min/week of moderate-to-vigorous intensity PA (MVPA), between device-measured and self-reported PA. Method We included 656 older adults (64% women), aged 66, 81-87 or >= 90 years from a Swedish population-based cohort study. The activPAL3 accelerometer provided information on sedentary behavior (sedentary time, sedentary bouts, sit-to-stand transitions) and PA. Stepping >= 100 steps/min was considered MVPA; standing and stepping < 100 steps/min were considered light-intensity PA (LPA). Self-reported PA was compared with min/week in MVPA and steps/day. Results On average, 60% of wear time was spent sedentary, 36% in LPA, and 4% in MVPA. Relative to men, women, had significantly (p < 0.05) more sit-to-stand transitions, spent 33 min/day less sedentary and 27 min/day more in LPA, and were more likely to report meeting PA recommendations, but showed no difference in steps/day, MVPA, or sedentary bout duration. Older age was associated with more sedentary time, lower MVPA and fewer steps/day. The prevalence of meeting PA recommendations was 59% device-measured and 88% by self-report with limited agreement between methods (Cohen's Kappa = 0.21, Spearman's rho = 0.28). Age differences were much more pronounced with objective measures than by self-report. Conclusions We found significant sex differences in sedentary behavior and time in LPA in older adults, but not in MVPA, in contrast to previous findings. Sedentary time increased with age, with small differences in accumulation pattern. MVPA time was lower with older age, obesity, and poor physical function. A majority of the participants > 80 years did not meet the PA recommendations. Given the strong relationships between sedentary behavior, PA and health in older adults, programs are needed to address these behaviors. Agreement between device-measured and self-reported fulfillment of PA recommendations was limited. Device-based measurement adds value to PA studies, providing richer and different data than self-report.
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20.
  • Ekelund, Ulf, et al. (författare)
  • Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality : systematic review and harmonised meta-analysis
  • 2019
  • Ingår i: The BMJ. - : BMJ. - 1756-1833 .- 0959-8138. ; 366
  • Forskningsöversikt (refereegranskat)abstract
    • OBJECTIVETo examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality.DESIGNSystematic review and harmonised meta-analysis.DATA SOURCESPubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018.ELIGIBILITY CRITERIAProspective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals.DATA EXTRACTION AND ANALYSISGuidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis.MAIN OUTCOME MEASUREAll cause mortality.RESULTS39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56).CONCLUSIONHigher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults.
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