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Sökning: WFRF:(Wirestam L)

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1.
  • Enocsson, Helena, et al. (författare)
  • Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus
  • 2020
  • Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 106
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE. Methods: Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI). Results: The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03–1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007). Conclusion: Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.
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2.
  • Wirestam, Lina, et al. (författare)
  • Osteopontin and disease activity in patients with recent-onset systemic Lupus Erythematosus : Results from the SLICC Inception Cohort
  • 2019
  • Ingår i: Journal of Rheumatology. - : J Rheumatol Publ Co. - 0315-162X .- 1499-2752. ; 46:5, s. 492-500
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. In cross-sectional studies, elevated osteopontin (OPN) levels have been proposed to reflect, and/or precede, progressive organ damage and disease severity in systemic lupus erythematosus (SLE). We aimed, in a cohort of patients with recent-onset SLE, to determine whether raised serum OPN levels precede damage and/or are associated with disease activity or certain disease phenotypes. Methods. We included 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who had 5 years of followup data available. All patients fulfilled the 1997 American College of Rheumatology (ACR) criteria. Baseline sera from patients and from age- and sex-matched population-based controls were analyzed for OPN using ELISA. Disease activity and damage were assessed at each annual followup visit using the SLE Disease Activity Index 2000 (SLEDAI-2K) and the SLICC/ACR damage index (SDI), respectively. Results. Compared to controls, baseline OPN was raised 4-fold in SLE cases (p < 0.0001). After relevant adjustments in a binary logistic regression model, OPN levels failed to significantly predict global damage accrual defined as SDI ≥ 1 at 5 years. However, baseline OPN correlated with SLEDAI-2K at enrollment into the cohort (r = 0.27, p < 0.0001), and patients with high disease activity (SLEDAI-2K ≥ 5) had raised serum OPN (p < 0.0001). In addition, higher OPN levels were found in patients with persistent disease activity (p = 0.0006), in cases with renal involvement (p < 0.0001) and impaired estimated glomerular filtration rate (p = 0.01). Conclusion. The performance of OPN to predict development of organ damage was not impressive. However, OPN associated significantly with lupus nephritis and with raised disease activity at enrollment, as well as over time.
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3.
  • Wirestam, Lina, et al. (författare)
  • Antibodies against High Mobility Group Box protein-1 (HMGB1) versus other anti-nuclear antibody fine-specificities and disease activity in systemic lupus erythematosus
  • 2015
  • Ingår i: Arthritis Research & Therapy. - : BIOMED CENTRAL LTD. - 1478-6354 .- 1478-6362. ; 17:338
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The non-histone nuclear protein high mobility group box protein-1 (HMGB1) is typically associated with nucleosomes, but may shuttle between the nucleus and the cytoplasm, and under some conditions also be released extracellularly and participate in systemic inflammation. Monoclonal HMGB1-targeting antibodies can ameliorate murine polyarthritis and lupus-like disease. Interestingly, autoantibodies against HMGB1 have also been described in patients with systemic lupus erythematosus (SLE), but their clinical implications remain elusive. The main aims of this study were to detect serum anti-HMGB1 antibodies in patients with SLE and relate them to other types of antinuclear antibodies (ANA), and to disease activity. Methods: 188 Swedish SLE patients meeting the 1982 American College of Rheumatology classification criteria and/or the 2012 Systemic Lupus International Collaborating Clinics classification criteria participated in the study. Anti-HMGB1 antibody levels were analysed in patient and control (n = 112) sera by an in-house ELISA using recombinant histidine-tagged HMGB1. SLE sera were also analysed for ANA by immunofluorescence (IF) microscopy (IF-ANA) using fixed HEp-2 cells, and by a line-blot assay for antigen fine-specificities. To quantify antibodies to double-stranded DNA, a fluoroenzyme-immunoassay was employed. Results: At inclusion, 23 % of the SLE patients were anti-HMGB1 antibody positive compared to 5 % of the controls. Anti-HMGB1 antibodies occurred in 49 % of the IF-ANA positive SLE patients, and in 34 % of IF-ANA negative cases (p = 0.004). Levels of anti-HMGB1 antibodies correlated with anti-dsDNA antibody levels (r = 0.49; p less than 0.001). Significant, but less pronounced correlations were found regarding anti-HMGB1 and SLE disease activity index (SLEDAI-2K: r = 0.15; p = 0.04), classical complement function (r = -0.24; p = 0.002) and complement protein C4 (r = -0.23; p = 0.002). Average anti-HMGB1 antibody levels were significantly higher among patients with homogenous +/- other IF-ANA staining patterns (median 180 AU) compared to IF-ANA negative cases (median 83 AU) (p = 0.004). Rabbit anti-HMGB1 antibodies gave rise to cytoplasmic, but not nuclear, staining of HEp-2 cells. Conclusions: We confirm that anti-HMGB1 antibodies are common in SLE and correlate with disease activity variables. Although anti-HMGB1 antibodies measured by ELISA often coincide with nuclear IF-ANA staining, our results indicate that anti-HMGB1 antibodies do not give rise to nuclear staining of the predominantly used commercial HEp-2 cell slides.
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5.
  • Johansson, Edvin, et al. (författare)
  • Perfusion assessment with bolus differentiation : a technique applicable to hyperpolarized tracers
  • 2004
  • Ingår i: Magnetic Resonance in Medicine. - : John Wiley and Sons. - 0740-3194 .- 1522-2594. ; 52:5, s. 51-1043
  • Tidskriftsartikel (refereegranskat)abstract
    • A new technique for assessing tissue blood flow using hyperpolarized tracers, based on the fact that the magnetization of a hyperpolarized substance can be destroyed permanently, is described. Assessments of blood flow with this technique are inherently insensitive to arterial delay and dispersion, and allow for quantification of the transit time and dispersion in the arteries that supply the investigated tissue. Renal cortical blood flow was studied in six rabbits using a 13C-labeled compound (2-hydroxyethylacrylate) that was polarized by the parahydrogen-induced polarization (PHIP) technique. The renal cortical blood flow was estimated to be 5.7/5.4 +/- 1.6/1.3 ml/min per milliliter of tissue (mean +/- SD, right/left kidney), and the mean transit time and dispersion in the renal arteries were determined to be 1.47/1.42 +/- 0.07/0.07 s and 1.78/1.93 +/- 0.40/0.42 s2, respectively.
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8.
  • Wirestam, Lina, et al. (författare)
  • Interferon-α coincides with suppressed levels of pentraxin-3 (PTX3) in systemic lupus erythematosus and regulates leucocyte PTX3 in vitro
  • 2017
  • Ingår i: Clinical and Experimental Immunology. - : WILEY. - 0009-9104 .- 1365-2249. ; 189:1, s. 83-91
  • Tidskriftsartikel (refereegranskat)abstract
    • Dysfunctional elimination of cell debris, and the role of opsonins such as pentraxins, is of interest regarding systemic lupus erythematosus (SLE) pathogenesis. Interferon (IFN)- is typically elevated during SLE flares, and inhibits hepatocyte production of the pentraxin C-reactive protein' (CRP), partly explaining the poor correlation between CRP levels and SLE disease activity. The extrahepatically produced pentraxin 3' (PTX3) shares waste disposal functions with CRP, but has not been studied extensively in SLE. We analysed serum PTX3 in SLE, and assessed its interference with IFN- in vitro. Serum samples from 243 patients with SLE and 100 blood donors were analysed regarding PTX3. Patient sera were analysed for IFN-, and genotyped for three PTX3 single nucleotide polymorphisms reported previously to associate with PTX3 levels. Stimulated PTX3 release was assessed in the presence or absence of IFN- in blood donor neutrophils and peripheral blood mononuclear cells (PBMC). Serum PTX3 was 44% lower in patients with SLE compared to blood donors (P<00001) and correlated with leucocyte variables. Patients with undetectable IFN- had 29% higher median PTX3 level than patients with detectable IFN- (P=001). PTX3 production by PBMC was inhibited by IFN-, whereas neutrophil degranulation of PTX3 was increased. No differences in PTX3 levels were observed between the SNPs. In conclusion, median serum PTX3 is lower in SLE (especially when IFN- is detectable) compared to blood donors. In addition to its potential consumption during waste disposal, it is plausible that IFN- also attenuates PTX3 by inhibiting synthesis by PBMC and/or exhausting PTX3 storage in neutrophil granules.
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9.
  • Jönsson, Bo-Anders, et al. (författare)
  • EMERALD & EMIT – worldwide computer aided education and training packages in medical physics
  • 2005
  • Ingår i: CAL-laborate. - : UniServe Science. - 1443-4482. ; 13:June, s. 10-15
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper describes the development of two web based education and training packages EMERALD and EMIT designed to meet the training needs of professional medical physicists. The programme has been developed over a number of years by collaboration between hospitals and universities across Europe. The programme concentrates on assisting competence development in five initial areas; diagnostic radiology, nuclear medicine, magnetic resonance tomography, ultrasound and radiotherapy. Each of the topic areas includes around 50 training tasks in 5 hypertext workbooks, which are supplemented by an image database relevant to each topic. The training materials have been extensively refereed during their development and are now in use in 65 countries across the globe. Initial evaluation has shown that the material enhances the training experience and produces a more consistent output.
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