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Sökning: WFRF:(Olsson Marita)

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  • Alamidi, Daniel F, et al. (författare)
  • T1 Relaxation Time in Lungs of Asymptomatic Smokers.
  • 2016
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Interest in using T1 as a potential MRI biomarker of chronic obstructive pulmonary disease (COPD) has recently increased. Since tobacco smoking is the major risk factor for development of COPD, the aim for this study was to examine whether tobacco smoking, pack-years (PY), influenced T1 of the lung parenchyma in asymptomatic current smokers.
  • Alamidi, Daniel F, et al. (författare)
  • Variable Flip Angle 3D Ultrashort Echo Time (UTE) T-1 Mapping of Mouse Lung: A Repeatability Assessment
  • 2018
  • Ingår i: Journal of Magnetic Resonance Imaging. - 1053-1807. ; 48:3, s. 846-852
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lung T1 is a potential translational biomarker of lung disease. The precision and repeatability of variable flip angle (VFA) T1 mapping using modern 3D ultrashort echo time (UTE) imaging of the whole lung needs to be established before it can be used to assess response to disease and therapy. Purpose: To evaluate the feasibility of regional lung T1 quantification with VFA 3D-UTE and to investigate long- and short-term T1 repeatability in the lungs of naive mice. Study type: Prospective preclinical animal study. Population: Eight naive mice and phantoms. Field strength/Sequence: 3D free-breathing radial UTE (8 μs) at 4.7T. Assessment: VFA 3D-UTE T1 calculations were validated against T1 values measured with inversion recovery (IR) in phantoms. Lung T1 and proton density (S0) measurements of whole lung and muscle were repeated five times over 1 month in free-breathing naive mice. Two consecutive T1 measurements were performed during one of the imaging sessions. Statistical Tests: Agreement in T1 between VFA 3D-UTE and IR in phantoms was assessed using Bland-Altman and Pearson 's correlation analysis. The T1 repeatability in mice was evaluated using coefficient of variation (CV), repeated-measures analysis of variance (ANOVA), and paired t-test. Results: Good T1 agreement between the VFA 3D-UTE and IR methods was found in phantoms. T1 in lung and muscle showed a 5% and 3% CV (1255±63 msec and 1432±42 msec, respectively, mean±SD) with no changes in T1 or S0 over a month. Consecutive measurements resulted in an increase of 2% in both lung T1 and S0. Data Conclusion: VFA 3D-UTE shows promise as a reliable T1 mapping method that enables full lung coverage, high signal-to-noise ratio (∼25), and spatial resolution (300 μm) in freely breathing animals. The precision of the VFA 3D-UTE method will enable better design and powering of studies.
  • Berg, Tove, et al. (författare)
  • Gene expression analysis of membrane transporters and drug-metabolizing enzymes in the lung of healthy and COPD subjects.
  • 2014
  • Ingår i: Pharmacology research & perspectives. - John Wiley and Sons Inc.. - 2052-1707. ; 2:4, s. 00054-00054
  • Tidskriftsartikel (refereegranskat)abstract
    • This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD subjects. The majority of the differentially expressed genes were higher expressed in the central airways such as the transporters SLC2A1 (GLUT1), SLC28A3 (CNT3), and SLC22A4 (OCTN1) and the drug-metabolizing enzymes GSTZ1, GSTO2, and CYP2F1. Together, this increased knowledge of local pharmacokinetics in diseased and normal lung may improve modeling of clinical outcomes of new chemical entities intended for inhalation therapy delivered to COPD patients. In addition, based on the similarities between COPD and healthy subjects regarding gene expression of membrane transporters and drug-metabolizing enzymes, our results suggest that clinical pharmacological studies in healthy volunteers could be a valid model of COPD patients regarding drug disposition of inhaled drugs in terms of drug metabolism and drug transporters.
  • Hedelin, M., et al. (författare)
  • Dietary intake of fish, omega-3, omega-6 polyunsaturated fatty acids and vitamin D and the prevalence of psychotic-like symptoms in a cohort of 33 000 women from the general population
  • 2010
  • Ingår i: BMC Psychiatry. - 1471-244X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Low intake of fish, polyunsaturated fatty acids (PUFA) and vitamin D deficiency has been suggested to play a role in the development of schizophrenia. Our aim was to evaluate the association between the intake of different fish species, PUFA and vitamin D and the prevalence of psychotic-like symptoms in a population-based study among Swedish women. Methods: Dietary intake was estimated using a food frequency questionnaire among 33 623 women aged 30-49 years at enrolment (1991/92). Information on psychotic- like symptoms was derived from a follow-up questionnaire in the years 2002/03. Participants were classified into three predefined levels: low, middle and high frequency of symptoms. The association between diet and psychotic- like symptoms was summarized in terms of relative risks (RR) and corresponding 95% confidence intervals and was evaluated by energy-adjusted multinomial logistic regression. Results: 18 411 women were classified as having a low level of psychotic- like symptoms, 14 395 as middle and 817 as having a high level. The risk of high level symptoms was 53% (95% CI, 30-69%) lower among women who ate fish 3-4 times per week compared to women who never ate fish. The risk was also lower for women with a high intake of omega-3 and omega-6 PUFA compared to women with a lower intake of these fatty acids. The effect was most pronounced for omega-6 PUFAs. The RR comparing the highest to the lowest quartile of omega-6 PUFAs intake was 0.78 (95% CI, 0.64-0.97). The associations were J-shaped with the strongest reduced risk for an intermediate intake of fish or PUFA. For fatty fish (herring/mackerel, salmon-type fish), the strongest inverse association was found for an intermediate intake (RR: 0.81, 95% CI, 0.66-0.98), whereas a high intake of fatty fish was associated with an increased risk of psychotic- like symptoms (RR: 1.90, 95% CI, 1.34-2.70). Women in the highest compared with the lowest quartile of vitamin D consumption experienced a 37% (95% CI, 22-50%) lower risk of psychotic- like symptoms. Conclusion: Our findings raise a possibility that adult women with a high intake of fish, omega-3 or omega-6 PUFA and vitamin D have a lower rate of psychotic- like symptoms.
  • Hov, J. R., et al. (författare)
  • Electrostatic Modifications of the Human Leukocyte Antigen-DR P9 Peptide-Binding Pocket and Susceptibility to Primary Sclerosing Cholangitis
  • 2011
  • Ingår i: Hepatology. - 1527-3350 .- 0270-9139. ; 53:6, s. 1967-1976
  • Tidskriftsartikel (refereegranskat)abstract
    • The strongest genetic risk factors for primary sclerosing cholangitis (PSC) are found in the human leukocyte antigen (HLA) complex at chromosome 6p21. Genes in the HLA class II region encode molecules that present antigen to T lymphocytes. Polymorphisms in these genes are associated with most autoimmune diseases, most likely because they contribute to the specificity of immune responses. The aim of this study was to analyze the structure and electrostatic properties of the peptide-binding groove of HLA-DR in relation to PSC. Thus, four-digit resolution HLA-DRB1 genotyping was performed in 356 PSC patients and 366 healthy controls. Sequence information was used to assign which amino acids were encoded at all polymorphic positions. In stepwise logistic regressions, variations at residues 37 and 86 were independently associated with PSC (P = 1.2 x 10(-32) and P = 1.8 x 10(-22) in single-residue models, respectively). Three-dimensional modeling was performed to explore the effect of these key residues on the HLA-DR molecule. This analysis indicated that residue 37 was a major determinant of the electrostatic properties of pocket P9 of the peptide-binding groove. Asparagine at residue 37, which was associated with PSC, induced a positive charge in pocket P9. Tyrosine, which protected against PSC, induced a negative charge in this pocket. Consistent with the statistical observations, variation at residue 86 also indirectly influenced the electrostatic properties of this pocket. DRB1*13:01, which was PSC-associated, had a positive P9 pocket and DRB1*13:02, protective against PSC, had a negative P9 pocket. Conclusion: The results suggest that in patients with PSC, residues 37 and 86 of the HLA-DR beta chain critically influence the electrostatic properties of pocket P9 and thereby the range of peptides presented. (HEPATOLOGY 2011;53:1967-1976)
  • Næss, Sigrid, et al. (författare)
  • Refinement of the MHC risk map in a scandinavian primary sclerosing cholangitis population
  • 2014
  • Ingår i: PLoS ONE. - 1932-6203. ; 9:12, s. e114486
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within the major histocompatibility complex (MHC) represent the strongest genetic susceptibility factors for primary sclerosing cholangitis (PSC). Identifying the causal variants within this genetic complex represents a major challenge due to strong linkage disequilibrium and an overall high physical density of candidate variants. We aimed to refine the MHC association in a geographically restricted PSC patient panel.
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