| 11. |
- Kindmark, Andreas, et al.
(författare)
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Genome-wide pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis
- 2008
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Ingår i: The Pharmacogenomics Journal. - : Springer Science and Business Media LLC. - 1470-269X .- 1473-1150. ; 8:3, s. 186-195
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Tidskriftsartikel (refereegranskat)abstract
- One of the major goals of pharmacogenetics is to elucidate mechanisms and identify patients at increased risk of adverse events (AEs). To date, however, there have been only a few successful examples of this type of approach. In this paper, we describe a retrospective case–control pharmacogenetic study of an AE of unknown mechanism, characterized by elevated levels of serum alanine aminotransferase (ALAT) during long-term treatment with the oral direct thrombin inhibitor ximelagatran. The study was based on 74 cases and 130 treated controls and included both a genome-wide tag single nucleotide polymorphism and large-scale candidate gene analysis. A strong genetic association between elevated ALAT and the MHC alleles DRB1*07 and DQA1*02 was discovered and replicated, suggesting a possible immune pathogenesis. Consistent with this hypothesis, immunological studies suggest that ximelagatran may have the ability to act as a contact sensitizer, and hence be able to stimulate an adaptive immune response.
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| 12. |
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| 13. |
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| 14. |
- Bengtsson, Lars, et al.
(författare)
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Strategisk Planering
- 2008
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Ingår i: Controllerhandboken.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Carlsson, B. G., et al.
(författare)
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Triaxial shape with rotation around the longest principal axis in Gd-142
- 2008
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 78:3
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Tidskriftsartikel (refereegranskat)abstract
- The cranking model is used to describe rotational bands. We investigate the approach of using diabatic configurations and minimizing the particle-number projected energy in a mesh of both lambda, Delta and deformation parameters. We use the method to interpret recent experimental data in Gd-142 and conclude that for the highest spin states observed (I approximate to 30), the nucleus is triaxial and builds spin by rotating around the classically unfavored longest axis.
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| 16. |
- Delbro, Dick, et al.
(författare)
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Nuclear expression of mu-opioid receptors in a human mesothelial cell line
- 2009
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Ingår i: Autonomic & Autacoid Pharmacology. - : Wiley. - 1474-8665 .- 1474-8673. ; 29:4, s. 165-170
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Tidskriftsartikel (refereegranskat)abstract
- 1 Possibly acting via mu-opioid receptors (MORs), morphine inhibits the formation ofexperimentally induced postoperative abdominal adhesions in rats. Mesothelial cells mayparticipate in adhesion formation by secreting mediators that interfere negatively withfibrinolysis. Morphine may prevent adhesions by inhibiting the release of pro-adhesionmediators from mesothelial cells. This study aimed to investigate whether human mesothelialcells express MOR-1; if so, such could constitute a site of action for morphine in adhesionprevention.2 Cells from Met-5A, a human mesothelial cell line were seeded and prepared forimmunocytochemistry and Western blotting.3 Immunocytochemistry showed MOR-1 expression in mesothelial cells, predominantly in thenuclei. Western blotting showed two bands (c. 35 and 50 kDa) which correspond to thoseobtained with a control lysate from cells known to express MORs. In addition, we foundMOR-1 expression with nuclear and cytoplasmatic localization in biopsies from humanabdominal adhesions.4 The current findings may suggest that morphine could interact directly with mesothelial cellsvia MOR-1 receptors, and thereby modulate adhesion formation, possibly by interfering withthe release of pro-adhesion factors from these cells
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| 17. |
- Erqou, Sebhat, et al.
(författare)
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Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality.
- 2009
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Ingår i: JAMA : the journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 302:4, s. 412-23
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein-like particle, may be associated with risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. STUDY SELECTION: Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. DATA EXTRACTION: Individual records were provided for each of 126,634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22,076 first-ever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. DATA SYNTHESIS: Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 person-years and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. CONCLUSION: Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.
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| 18. |
- Florez, Jose C., et al.
(författare)
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The Kruppel-like factor 11 (KLF11) Q62R polymorphism is not associated with type 2 diabetes in 8,676 people
- 2006
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 55:12, s. 3620-3624
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Tidskriftsartikel (refereegranskat)abstract
- Kruppel-like factor 11 is a pancreatic transcription factor whose activity induces the insulin gene. A common glutamine-to-arginine change at codon 62 (Q62R) in its gene KLF11 has been recently associated with type 2 diabetes in two independent samples. Q62R and two other rare missense variants (A347S and T220M) were also shown to affect the function of KLF11 in vitro, and insulin levels were lower in carriers of the minor allele at Q62R. We therefore examined their impact on common type 2 diabetes in several family-based and case-control samples of northern-European ancestry, totaling 8,676 individuals. We did not detect the rare A347S and T220M variants in our samples. With respect to Q62R, despite > 99% power to detect an association of the previously published magnitude, Q62R was not associated with type 2 diabetes (pooled odds ratio 0.97 [95% Cl 0.88-1.08], P = 0.63). In a subset of normoglycemic individuals, we did not observe significant differences in various insulin traits according to genotype at KLF11 Q62R. We conclude that the KLF11 A347S and T220M mutations do not contribute to increased risk of diabetes in European-derived populations and that the Q62R polymorphism has, at best, a minor effect on diabetes risk.
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| 19. |
- Gamborg, Michael, et al.
(författare)
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Birth weight and systolic blood pressure in adolescence and adulthood : meta-regression analysis of sex- and age-specific results from 20 Nordic studies
- 2007
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 166:6, s. 634-645
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Tidskriftsartikel (refereegranskat)abstract
- The authors investigated the shape, sex- and age-dependency, and possible confounding of the association between birth weight and systolic blood pressure (SBP) in 197,954 adults from 20 Nordic cohorts (birth years 1910-1987), one of which included 166,249 Swedish male conscripts. Random-effects meta-regression analyses were performed on estimates obtained from age- and sex-stratified analyses within each of the cohorts. There was an inverse association between birth weight and SBP, irrespective of adjustment for concurrent body mass index. The association was linear for males, but for females with a birth weight greater than 4 kg, SBP increased with birth weight (p < 0.01). The association was stronger in the older age groups (p < 0.05), although this could have been a birth cohort effect. The association was stronger among females than among males (p = 0.005) when birth weight was less than or equal to 4 kg. The estimated effect of birth weight on SBP at age 50 years was -1.52 mmHg/kg (95% confidence interval: -2.27, -0.77) in men and -2.80 mmHg/kg (95% confidence interval: -3.85, -1.76) in women. Exclusion of the Swedish conscripts produced nearly identical results. This meta-analysis supports the evidence of an inverse birth weight-SBP association, regardless of adjustment for concurrent body size. It also reveals important heterogeneity in the shape and strength of the association by sex and age.
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| 20. |
- Hedsten, Karin, 1964, et al.
(författare)
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MEMS-based VCSEL beam steering using replicated polymer diffractive lens
- 2008
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Ingår i: Sensors and Actuators, A: Physical. - : Elsevier BV. - 0924-4247 .- 1873-3069. ; 142:1, s. 336-345
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. This paper describes a fully integrated micro-optical system, in which dynamic angular control of the beam from a VCSEL (vertical cavity surface emitting laser) is realized by laterally moving a collimat¬ing diffractive lens in the light path. The lens is mounted on a translatable silicon stage, which consists of a frame with an opening for the light to traverse the lens and electro-statically driven comb actuators, by which the lateral movement is achieved. Devices implementing both 1D and 2D scanning have been fabricated and evaluated. Integration of the lens onto the translatable silicon stage is done using a newly developed fabrication process based on hot embossing of an amorphous fluorocarbon polymer. This fabrication process relies on a reversed-order protocol, where the structuring of the optical element precedes the silicon microstructuring. Assembly and packaging of the VCSEL-MOEMS system, using LTCC (low temperature cofired ceramic) technique, is also demonstrated. Optical evaluation of the system and beam steering function shows significant beam deflection for a relatively low driving voltage (~70 V).
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