| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 3. |
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| 4. |
- Sodergren, Erica, et al.
(författare)
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The genome of the sea urchin Strongylocentrotus purpuratus.
- 2006
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 314:5801, s. 941-52
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Tidskriftsartikel (refereegranskat)abstract
- We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus, a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.
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| 5. |
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| 6. |
- Ballantyne, C., et al.
(författare)
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Collaborative meta-analysis of individual participant data from observational studies of Lp-PLA2 and cardiovascular diseases
- 2007
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Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation. - : Oxford University Press (OUP). - 1741-8267 .- 1741-8275 .- 2047-4873. ; 14:1, s. 3-11
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: A large number of observational epidemiological studies have reported generally positive associations between circulating mass and activity levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and the risk of cardiovascular diseases. Few studies have been large enough to provide reliable estimates in different circumstances, such as in different subgroups (e.g., by age group, sex, or smoking status) or at different Lp-PLA2 levels. Moreover, most published studies have related disease risk only to baseline values of Lp-PLA2 markers (which can lead to substantial underestimation of any risk relationships because of within-person variability over time) and have used different approaches to adjustment for possible confounding factors. OBJECTIVES: By combination of data from individual participants from all relevant observational studies in a systematic 'meta-analysis', with correction for regression dilution (using available data on serial measurements of Lp-PLA2), the Lp-PLA2 Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age and sex-specific associations of plasma Lp-PLA2 with coronary heart disease (and, where data are sufficient, with other vascular diseases, such as ischaemic stroke). It will also help to determine to what extent such associations are independent of possible confounding factors and to explore potential sources of heterogeneity among studies, such as those related to assay methods and study design. It is anticipated that the present collaboration will serve as a framework to investigate related questions on Lp-PLA2 and cardiovascular outcomes. METHODS: A central database is being established containing data on circulating Lp-PLA2 values, sex and other potential confounding factors, age at baseline Lp-PLA2 measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of Lp-PLA2 and potential confounding factors has been sought to allow adjustment for possible confounding and correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available observational studies of Lp-PLA2 will yield information on a total of about 15 000 cardiovascular disease endpoints.
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| 8. |
- Carlsson, Jorg, et al.
(författare)
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Outcome of Drug-Eluting Versus Bare-Metal Stenting Used According to On- and Off-Label Criteria
- 2009
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Ingår i: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 53:16, s. 1389-1398
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to investigate the outcome of bare-metal stents (BMS) versus drug-eluting stents (DES) after on-label as well as off-label use. Background DES lower restenosis rates while not influencing the risk for death and myocardial infarction when used in Federal Food and Drug Administration (FDA)-approved indications. It is debated whether the clinical results of this so-called on-label use might be extrapolated to off-label situations. Methods The SCAAR (Swedish Coronary Angiography and Angioplasty Registry) was used to investigate the outcomes in 17,198 patients who underwent stenting with an on-label indication (10,431 BMS and 6,767 DES patients) and 16,355 patients in the context of an off-label indication (9,907 BMS and 6,448 DES patients). The patients were included from 2003 to 2005 with a minimum follow-up of 1 year and a maximum of 4 years. The analysis was adjusted for differences in baseline characteristics. Results There were not significant differences between on-label DES and BMS (adjusted hazard ratio: 1.02; 95% confidence interval: 0.92 to 1.13) or between off-label DES and BMS (adjusted hazard ratio: 0.95; 95% confidence interval: 0.87 to 1.04) use with regard to the incidence of myocardial infarction and death. Off-label use of DES did not lead to significant differences in the combined risk of death and myocardial infarction compared with BMS throughout the whole spectrum of clinical indications. Conclusions In contemporary Swedish practice, neither on-nor off-label use of DES is associated with worse outcome than use of BMS.
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| 9. |
- Frobert, Ole, et al.
(författare)
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Differences in Restenosis Rate With Different Drug-Eluting Stents in Patients With and Without Diabetes Mellitus A Report From the SCAAR (Swedish Angiography and Angioplasty Registry)
- 2009
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Ingår i: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 53:18, s. 1660-1667
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Our aim was to evaluate restenosis rate of drug-eluting stents (DES) in patients with and without diabetes mellitus (DM) in a real-world setting. Background DES seem less effective in patients with DM. Methods The SCAAR (Swedish Coronary Angiography and Angioplasty Registry) includes all patients undergoing percutaneous coronary intervention in Sweden. From April 1, 2004, to April 20, 2008, all restenoses detected at a subsequent angiography and all DES types implanted at more than 500 occasions were assessed using Cox regression. Results Four DES types qualified for inclusion. In total, 35,478 DES were implanted at 22,962 procedures in 19,004 patients and 1,807 restenoses were reported over a mean 29 months follow-up. In the entire population, the restenosis rate per stent was 3.5% after 1 year and 4.9% after 2 years. The adjusted risk of restenosis was higher in patients with DM compared with that in patients without DM (relative risk [RR]: 1.23, 95% confidence interval [CI]: 1.10 to 1.37). In patients with DM, restenosis was twice as frequent with the zotarolimus-eluting Endeavor stent (Medtronic, Minneapolis, Minnesota) compared with that in the other DES types. The Endeavor stent and the sirolimus-eluting Cypher stent (Cordis, Johnson & Johnson, Miami, Florida) had higher restenosis rates in patients with DM compared with those in patients without DM (RR: 1.77, 95% CI: 1.29 to 2.43 and RR: 1.25, 95% CI: 1.04 to 1.51). Restenosis rate with the paclitaxel-eluting Taxus Express and Liberte (Boston Scientific, Natick, Massachusetts) stents was unrelated to DM. Mortality did not differ between different DES. Conclusions Restenosis rate with DES was higher in patients with DM compared with that in patients without DM. There seem to be important differences between different brands of DES.
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| 10. |
- James, Stefan K, et al.
(författare)
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An acute inflammatory reaction induced by myocardial damage is superimposed on a chronic inflammation in unstable coronary artery disease
- 2005
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 149:4, s. 619-626
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Inflammation plays an important role in unstable coronary artery disease (CAD). We assessed the kinetics of inflammatory markers from symptom onset in patients with unstable CAD and their relation to myocardial damage.METHODS:Serial measurements of inflammatory mediators were performed in consecutive patients with unstable CAD enrolled at selected sites in the FRISC II (n = 558) and the GUSTO IV (n = 404) trials. The time from symptom onset was calculated for every serum sample (total 4400 samples).RESULTS:Median levels of interleukin 6 and C-reactive protein reached their peaks at 36 to 42 hours and at 48 to 54 hours, respectively, from symptom onset and returned to early postsymptom levels within 6 weeks. The early increase occurred almost exclusively in patients with baseline troponin T elevation (>0.01 microg/L). In contrast, median levels of fibrinogen increased continuously up to 120 hours after symptom onset, independently of myocardial damage. At 6 months, fibrinogen levels were still higher than in the early phase after symptom onset. The median levels of interleukin 6, C-reactive protein, and fibrinogen were still higher at 6 months than in healthy controls matched for age and sex to a population with unstable CAD.CONCLUSIONS:An early acute inflammatory reaction induced by myocardial damage seems to be superimposed on a chronic inflammatory condition, both of which might influence long-term outcome in unstable CAD.
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