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Sökning: WFRF:(Thulin P)

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  • Aminoff, A, et al. (författare)
  • Allele-specific regulation of MTTP expression influences the risk of ischemic heart disease.
  • 2010
  • Ingår i: Journal of lipid research. - 0022-2275. ; 51:1, s. 103-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Promoter polymorphisms in microsomal triglyceride transfer protein (MTTP) have been associated with decreased plasma lipids but an increased risk for ischemic heart disease (IHD), indicating that MTTP influences the susceptibility for IHD independent of plasma lipids. The objective of this study was to characterize the functional promoter polymorphism in MTTP predisposing to IHD and its underlying mechanism. Use of pyrosequencing technology revealed that presence of the minor alleles of the promoter polymorphisms -493G>T and -164T>C result in lower transcription of MTTP in vivo in the heart, liver, and macrophages. In vitro experiments indicated that the minor -164C allele mediates the lower gene expression and that C/EBP binds to the polymorphic region in an allele-specific manner. Furthermore, homozygous carriers of the -164C were found to have increased risk for IHD as shown in a case-control study including a total of 544 IHD patients and 544 healthy control subjects. We concluded that carriers of the minor -164C allele have lower expression of MTTP in the heart, mediated at least partly by the transcription factor CCAAT/enhancer binding protein, and that reduced concentration of MTTP in the myocardium may contribute to IHD upon ischemic damage.
  • Braunerhjelm, P, et al. (författare)
  • The relationship between domestic and outward foreign direct investment: The role of industry-specific effects
  • 2005
  • Ingår i: International Business Review. - Elsevier. - 0969-5931 .- 1873-6149. ; 14:6, s. 677-694
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous research has been inconclusive as regards the effect of outward foreign direct investment (FDI) on domestic investments. In this article, we show that this inconclusiveness can be explained at a disaggregated level as a function of the way industries are organized. Based on a simple theoretical framework including monitoring and trade costs, we argue that a complementary relationship can be expected to prevail in vertically integrated industries, whereas a substitutionary relationship can be expected in horizontally organized production. The empirical analysis confirms a significant difference between the two categories of industry as regards the impact of outward FDI on domestic investment. The results may thus have profound policy implications. JEL no. F12, F21, F23, G34.
  • Boyce, SW, et al. (författare)
  • Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: Results of the CABG surgery cohort of the GUARDIAN study
  • 2003
  • Ingår i: Journal of Thoracic and Cardiovascular Surgery. - American Association for Thoracic Surgery. - 0022-5223. ; 126:2, s. 420-427
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk,of myocardial necrosis after coronary artery bypass graft surgery. Methods: In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients greater than or equal to 18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and 2 :2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint. Results: Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P = .027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P = .005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P = .033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population. Conclusions: Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.
  • Elmberg, Johan, et al. (författare)
  • Farmed European mallards are genetically different and cause introgression in the wild population following releases
  • 2016
  • Konferensbidrag (refereegranskat)abstract
    • The practice of restocking already viable populations to increase harvest potential has since long been common in forestry, fisheries and wildlife management. The potential risks of restocking native species have long been overshadowed by the related issue of invasive alien species. However, during the last decade releases of native species with potentially non-native genome have received more attention. A suitable model to study genetic effects of large-scale releases of native species is the Mallard Anas platyrhynchos, being the most widespread duck in the world, largely migratory, and an important quarry species. More than 3 million unfledged hatchlings are released each year around Europe to increase local harvest. The aims of this study were to determine if wild and released farmed Mallards differ genetically, if there are signs of previous or ongoing introgression between wild and farmed birds, and if the genetic structure of the wild Mallard population has changed since large-scale releases started in Europe in the 1970s. Using 360 Single Nucleotide Polymorphisms (SNPs) we found that the genetic structure differed among historical wild, present-day wild, and farmed Mallards in Europe. We also found signs of introgression in the wild Mallard population, that is, individuals with a genetic background of farmed stock are part of the present free-living population. Although only a small proportion of the released Mallards appears to survive to merge with the free-living breeding population, their numbers are still so large that the genetic impact may have significance for the wild population in terms of individual survival and longterm fitness.
  • Johansson, Linda, et al. (författare)
  • Cathelicidin LL-37 in Severe Streptococcus pyogenes Soft Tissue Infections in Humans
  • 2008
  • Ingår i: Infection and Immunity. - American Society for Microbiology. - 0019-9567 .- 1098-5522. ; 76:8, s. 3399-3404
  • Tidskriftsartikel (refereegranskat)abstract
    • Severe soft tissue infections, such as necrotizing fasciitis and severe cellulitis, caused by group A streptococcus (GAS) are rapidly progressing life-threatening infections characterized by massive bacterial load in the tissue even late after onset of infection. Antimicrobial peptides are important components of the innate host defence and cathelicidins have been shown to protect against murine necrotic skin infection caused by GAS. However, the streptococcal cysteine protease SpeB has been demonstrated to proteolytically inactivate the human cathelicidin LL-37 in vitro. Here we have investigated the expression of LL-37 and its interaction with GAS and SpeB during acute severe soft tissue infections by analyses of patient tissue biopsies. The results showed high amounts of LL-37, both the proform (hCAP18) and the mature peptide, present in the tissue. Confocal microscopy identified neutrophils as the main source of the peptide. A distinct co-localization between the bacteria and LL-37 could be noted, and bacterial load showed a positive correlation to the LL-37 levels. Areas with high LL-37 levels coincided with areas with high amounts of SpeB. Confocal microscopy confirmed a strong co-localization of GAS, SpeB and LL-37 at the bacterial surface. Taken together the findings of this study provides in vivo support that SpeB-mediated inactivation of LL-37 at the streptococcal surface represent a bacterial resistance mechanism at the infected tissue site in patients with severe GAS tissue infections.
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