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| 2. |
- Deloukas, Panos, et al.
(författare)
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Large-scale association analysis identifies new risk loci for coronary artery disease
- 2013
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Ingår i: Nature Genetics. - 1061-4036. ; 45:1, s. 25-33
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Tidskriftsartikel (refereegranskat)abstract
- Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r2 < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
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- Heid, Iris M., et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.
- 2010
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Ingår i: Nature genetics. - 1546-1718. ; 42:11, s. 949
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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- Andersson-Engels, Stefan, et al.
(författare)
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Integrated system for interstitial photodynamic therapy
- 2003
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - The International Society for Optical Engineering. - 0277-786X. ; 5142, s. 42-49
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Konferensbidrag (refereegranskat)abstract
- A novel photodynamic therapy system based on interstitial illumination using multiple fibres is under development. The aim with this system is to enable treatment of large tumour volumes and also to utilise real-time measurements to allow on-line dosimetry. Important dosimetric parameters to measure are light fluence rate, sensitizer fluorescence intensity and local blood oxygenation. A construction which allows all functions to be readily performed with a single system is presented. We believe that interstitial PDT utilising this technique may be attractive in many clinical situations.
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| 7. |
- Appelqvist, Hanna, et al.
(författare)
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Lysosome-Mediated Apoptosis is Associated with Cathepsin D-Specific Processing of Bid at Phe24,Trp48, and Phe183
- 2012
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Ingår i: Annals of Clinical and Laboratory Science. - Institute for Clinical Science. - 0091-7370. ; 42:3, s. 231-242
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Tidskriftsartikel (refereegranskat)abstract
- Bax-mediated permeabilization of the outer mitochondrial membrane and release of apoptogenic factors into the cytosol are key events that occur during apoptosis. Likewise, apoptosis is associated with permeabilization of the lysosomal membrane and release of lysosomal cathepsins into the cytosol. This report identifies proteolytically active cathepsin D as an important component of apoptotic signaling following lysosomal membrane permeabilization in fibroblasts. Lysosome-mediated cell death is associated with degradation of Bax sequestering 14-3-3 proteins, cleavage of the Box activator Bid, and translocation of Box to mitochondria, all of which were cathepsin D-dependent. Processing of Bid could be reproduced by enforced lysosomal membrane permeabilization, using the lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride (MSDH). We identified three cathepsin D-specific cleavage sites in Bid, Phe24, Trp48, and Phe183. Cathepsin D-cleaved Bid induced Bax-mediated release of cytochrome c from purified mitochondria, indicating that the fragments generated are functionally active. Moreover, apoptosis was associated with cytosolic acidification, thereby providing a more favorable environment for the cathepsin D-mediated cleavage of Bid. Our study suggests that cytosolic cathepsin D triggers Bax-mediated cytochrome c release by proteolytic activation of Bid.
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| 9. |
- Austeng, Dordi, et al.
(författare)
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Incidence of and risk factors for neonatal morbidity after active perinatal care: extremely preterm infants study in Sweden (EXPRESS)
- 2010
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Ingår i: Acta Paediatrica. - Wiley InterScience. - 0803-5253. ; 99:7, s. 978-992
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The aim of this study was to determine the incidence of neonatal morbidity in extremely preterm infants and to identify associated risk factors. Methods: Population based study of infants born before 27 gestational weeks and admitted for neonatal intensive care in Sweden during 2004-2007. Results: Of 638 admitted infants, 141 died. Among these, life support was withdrawn in 55 infants because of anticipation of poor long-term outcome. Of 497 surviving infants, 10% developed severe intraventricular haemorrhage (IVH), 5.7% cystic periventricular leucomalacia (cPVL), 41% septicaemia and 5.8% necrotizing enterocolitis (NEC); 61% had patent ductus arteriosus (PDA) and 34% developed retinopathy of prematurity (ROP) stage >= 3. Eighty-five per cent needed mechanical ventilation and 25% developed severe bronchopulmonary dysplasia (BPD). Forty-seven per cent survived to one year of age without any severe IVH, cPVL, severe ROP, severe BPD or NEC. Tocolysis increased and prolonged mechanical ventilation decreased the chances of survival without these morbidities. Maternal smoking and higher gestational duration were associated with lower risk of severe ROP, whereas PDA and poor growth increased this risk. Conclusion: Half of the infants surviving extremely preterm birth suffered from severe neonatal morbidities. Studies on how to reduce these morbidities and on the long-term health of survivors are warranted.
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| 10. |
- Austeng, Dordi, et al.
(författare)
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Screening for retinopathy of prematurity in infants born before 27 weeks' gestation in Sweden.
- 2011
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Ingår i: Archives of ophthalmology. - 1538-3601. ; 129:2, s. 167-72
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To analyze screening for retinopathy of prematurity (ROP) during a 3-year period in a national cohort of infants born before 27 weeks' gestation. Methods: A national prospective study of neonatal morbidity in extremely preterm infants was performed in Sweden between April 1, 2004, and March 31, 2007. Screening for ROP was to start in the fifth postnatal week and to continue weekly until complete vascularization of the retina or until regression of ROP. Results: The first eye examination was performed no later than the sixth postnatal week in 84.8% of 506 infants, and the last examination was performed at postmenstrual age (PMA) of 38 weeks or later in 96.2% of infants. The mean and median numbers of days between examinations in the total cohort were 8.6 and 7.9 days, respectively (range, 1-27.8 days), and the mean and me-dian numbers of examinations were 12 and 10, respectively. Most infants were treated during a limited period (eg, at PMA of 39 weeks, 75.0% of infants had been treated). Conclusions: The objective of screening for ROP is timely detection of ROP before reaching treatment of criteria, ie, type 1 ROP, according to the Early Treatment for ROP recommendations. In our population of infants born before 27 weeks' gestation, the first examination could safely be postponed until PMA of 31 weeks because the onset of ROP stage 3 did not occur before then and criteria for treatment were not reached before PMA of 32 weeks. Gestational age at birth and PMA at the time of examination should be considered when deciding when and where the next examination should be performed.
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