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- Saxena, Richa, et al.
(author)
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Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
- 2007
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In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 316:5829, s. 1331-1336
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Journal article (peer-reviewed)abstract
- New strategies for prevention and treatment of type 2 diabetes (T2D) require improved insight into disease etiology. We analyzed 386,731 common single-nucleotide polymorphisms (SNPs) in 1464 patients with T2D and 1467 matched controls, each characterized for measures of glucose metabolism, lipids, obesity, and blood pressure. With collaborators (FUSION and WTCCC/UKT2D), we identified and confirmed three loci associated with T2D - in a noncoding region near CDKN2A and CDKN2B, in an intron of IGF2BP2, and an intron of CDKAL1 - and replicated associations near HHEX and in SLC30A8 found by a recent whole-genome association study. We identified and confirmed association of a SNP in an intron of glucokinase regulatory protein (GCKR) with serum triglycerides. The discovery of associated variants in unsuspected genes and outside coding regions illustrates the ability of genome-wide association studies to provide potentially important clues to the pathogenesis of common diseases.
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| 2. |
- Hugosson, Anna, et al.
(author)
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A community outbreak of Legionnaires' disease from an industrial cooling tower: assessment of clinical features and diagnostic procedures.
- 2007
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In: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 39:3, s. 217-24
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Journal article (peer-reviewed)abstract
- An outbreak of Legionnaires' disease (LD) occurred in Lidköping, Sweden, in August 2004. A cooling tower was identified as the probable source of infection. During the outbreak period an unexpected 3-6-fold increase in pneumonia patients was noted at the local hospital. During 7 weeks LD was diagnosed in 15 patients by urinary antigen and/or sputum culture. Additionally, 15 LD patients were diagnosed later by serology. Patients with LD were generally younger, more healthy, and more often smokers compared to other pneumonia patients. On admittance they had more severe symptoms with high fever and raised CRP levels, and more often hyponatraemia, gastrointestinal and CNS symptoms. A causative agent besides Legionella was found in 2 patients only. A significant titre rise for Mycoplasma and/or Chlamydophila pneumoniae was found in 13 of 29 tested patients with confirmed LD. We conclude that the clinical diagnosis of LD is difficult and that available diagnostic methods detect only a minority of patients in the acute phase. Therefore in severe pneumonia, empirically targeted therapy should be instituted on clinical grounds irrespective of the results of diagnostic tests. The observation of increased antibody levels for M. and C. pneumoniae suggests an unspecific immune reaction and merits further study.
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| 5. |
- Svensson, Malin, et al.
(author)
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Altered nucleotide sugar metabolism in Streptococcus thermophilus interferes with nitrogen metabolism
- 2007
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In: International Journal of Food Microbiology. - : Elsevier BV. - 0168-1605. ; 113:2, s. 195-200
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Journal article (peer-reviewed)abstract
- Exopolysaccharide (EPS)-producing Streptococcus thermophilus strains have attracted interest recently, since the EPSs act as natural viscosifiers and texture enhancers of fermented foods. We have previously reported that the low level of EPS production by S. thermophilus LY03 could be improved by altering the activities of enzymes in the central carbon metabolism involved in the nucleotide sugar metabolism. In this study, we observed a reduced growth in milk for the strains with increased UDP-glucose pyrophosphorylase (GalU) activity together with either enhanced phosphoglucomutase activity, and/or enhanced activity of the Leloir enzymes. Rapid growth of these mutants in milk could be restored by the addition of four specific amino acids, i.e. Glu, His, Met, and Val. This amino acid requirement was confirmed in a defined medium. Furthermore, the P-31 NMR spectra showed higher levels of the GalU reactants pyrophosphate (PPi) and UDP-glucose in the engineered strain, TMB 6013, compared to the parent strain, LY03. These products plus Glu and the GalU reactant UTP are known to be involved in the nitrogen regulatory system in many bacteria. Thus, these results suggest that the reaction catalyzed by GalU is connected to the nitrogen demand of these engineered strains. (c) 2006 Elsevier B.V. All rights reserved.
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| 7. |
- van Bezooijen, Rutger L., et al.
(author)
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Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation
- 2007
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In: Journal of Bone and Mineral Research. - 0884-0431 .- 1523-4681. ; 22:1, s. 19-28
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Journal article (peer-reviewed)abstract
- Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that is required for BMP-stimulated osteoblastic differentiation. Introduction: Sclerostin is a member of the Dan family of glycoproteins of which many members have been reported to antagonize BMP activity. Sclerostin has been shown to inhibit BMP-stimulated bone formation, but its mechanism of action seems to be different from classical BMP antagonists. In this study, we investigated the mechanism by which sclerostin inhibits BMP-stimulated bone formation. Materials and Methods: DNA electroporation of calf muscle of mice using expression plasmids for BMP and sclerostin was used to study the effect of sclerostin on BMP-induced bone formation in vivo. Transcriptional profiling using microarrays of osteoblastic cells treated with BMP in the absence or presence of sclerostin was used to find specific growth factor signaling pathways affected by sclerostin. The affected pathways were further studied using growth factor-specific reporter constructs. Results: BMP-induced ectopic bone formation in calf muscle of mice was prevented by co-expression of sclerostin in vivo. Transcriptional profiling analysis of osteoblastic cultures indicated that sclerostin specifically affects BMP and Wnt signaling out of many other growth signaling pathways. Sclerostin, however, did not inhibit stimulation of direct BMP target genes. Furthermore, we did not obtain any evidence for sclerostin acting as a direct BMP antagonist using a BMP-specific reporter construct. In contrast, sclerostin shared many characteristics with the Wnt antagonist dickkopf-1 in antagonizing BMP-stimulated bone formation and BMP- and Wnt-induced Wnt reporter construct activation. Conclusions: Sclerostin inhibits BMP-stimulated bone formation but does not affect BMP signaling. Instead, it antagonizes Wnt signaling in osteoblastic cells. High bone mass in sclerosteosis and van Buchem disease may, therefore, result from increased Wnt signaling.
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| 8. |
- Acosta, Stefan, et al.
(author)
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Epidemiology, risk and prognostic factors in mesenteric venous thrombosis.
- 2008
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In: British Journal of Surgery. - : Oxford University Press (OUP). - 1365-2168 .- 0007-1323. ; Aug 21, s. 1245-1251
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Journal article (peer-reviewed)abstract
- BACKGROUND:: Epidemiological reports on risk and prognostic factors in patients with mesenteric venous thrombosis (MVT) are scarce. METHODS:: Patients with MVT were identified through the inpatient and autopsy registry between 2000 and 2006 at Malmö University Hospital. RESULTS:: Fifty-one patients had MVT, diagnosed at autopsy in six. The highest incidence (11.3 per 100 000 person-years) was in the age category 70-79 years. Activated protein C resistance was present in 13 of 29 patients tested. D-dimer at admission was raised in all five patients tested. Multidetector row computed tomography (CT) in the portal venous phase was diagnostic in all 20 patients investigated, of whom 19 were managed conservatively. The median length of resected bowel in 12 patients who had surgery was 0.6 (range 0.1-2.2) m. The overall 30-day mortality rate was 20 per cent; intestinal infarction (P = 0.046), treatment on a non-surgical ward (P = 0.001) and CT not done (P = 0.022) were associated with increased mortality. Cancer was independently associated with long-term mortality: hazard ratio 4.03, 95 per cent confidence interval 1.03 to 15.85; P = 0.046. CONCLUSION:: Portal venous phase CT appeared sensitive in diagnosing MVT. As activated protein C resistance was a strong risk factor, lifelong anticoagulation should be considered. Copyright (c) 2008 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
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