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| 2. |
- Nilsson, Sven E, et al.
(författare)
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Långtidsöverlevnaden vid diabetes har successivt förbättrats. Lång sjukdomsduration kan ge information om protektiva möjligheter
- 2005
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Ingår i: Läkartidningen. - 0023-7205. ; 102:28, s. 2066-2070
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Tidskriftsartikel (refereegranskat)abstract
- Studies on patients with long-term diabetes survival without severe complications can give information about protective factors. Therefore, the present study aims to describe the long-term survival of patients with diabetes during successive periods following the introduction of insulin therapy in 1923. After registration in 1973 of the first local diabetic patient in Jonkoping with a fifty-year survival, this group has successively increased. Of those who were diagnosed during the period 1940 through 1949 there was a fifty-year survival in about one third. The successively better survival emphasises the importance of therapeutic progress. The study found no difference in diabetes control between those surviving 50 years and those with an age-matched group with a survival of 15 years. The insulin dose tended to decrease after 30 years duration. Peripheral vibration sensibility as well as renal function deteriorated by longer duration. The serum ratio of HDL-cholesterol to triglycerides increased. The frequency of glaucoma, cataract, and a history of myocardial infarction increased. In spite of long duration, one third of the sample had escaped serious retinopathy.
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| 3. |
- Ling, Charlotte, et al.
(författare)
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Genetic and epigenetic factors are associated with expression of respiratory chain component NDUFB6 in human skeletal muscle.
- 2007
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Ingår i: The Journal of clinical investigation. - 0021-9738. ; 117:11, s. 3427-35
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Tidskriftsartikel (refereegranskat)abstract
- Insulin resistance and type 2 diabetes are associated with decreased expression of genes that regulate oxidative phosphorylation in skeletal muscle. To determine whether this defect might be inherited or acquired, we investigated the association of genetic, epigenetic, and nongenetic factors with expression of NDUFB6, a component of the respiratory chain that is decreased in muscle from diabetic patients. Expression of NDUFB6 was influenced by age, with lower gene expression in muscle of elderly subjects. Heritability of NDUFB6 expression in muscle was estimated to be approximately 60% in twins. A polymorphism in the NDUFB6 promoter region that creates a possible DNA methylation site (rs629566, A/G) was associated with a decline in muscle NDUFB6 expression with age. Although young subjects with the rs629566 G/G genotype exhibited higher muscle NDUFB6 expression, this genotype was associated with reduced expression in elderly subjects. This was subsequently explained by the finding of increased DNA methylation in the promoter of elderly, but not young, subjects carrying the rs629566 G/G genotype. Furthermore, the degree of DNA methylation correlated negatively with muscle NDUFB6 expression, which in turn was associated with insulin sensitivity. Our results demonstrate that genetic, epigenetic, and nongenetic factors associate with NDUFB6 expression in human muscle and suggest that genetic and epigenetic factors may interact to increase age-dependent susceptibility to insulin resistance.
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| 4. |
- Nilsson, Christian, et al.
(författare)
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Nanoparticle-based continuous full filling capillary electrochromatography/electrospray ionization-mass spectrometry for separation of neutral compounds
- 2006
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 1520-6882 .- 0003-2700. ; 78:17, s. 6088-6095
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Tidskriftsartikel (refereegranskat)abstract
- Highly efficient reversed-phase capillary electrochromatography (CEC) separations (plate numbers up to 700 000/m), with electrospray ionization mass spectrometry detection were achieved utilizing novel dextran-coated polymer nanoparticles as a pseudostationary phase. A continuous full filling (CFF) technique in which nanoparticles are continuously introduced into the capillary was employed for separation of neutral analytes (dialkyl phthalates), utilizing an orthogonal electrospray interface to prevent nanoparticles from entering the mass spectrometer. CFF-CEC benefits from that an entirely fresh column is employed for every analysis, avoiding carryover effects associated with stationary-phase contamination. The highly efficient separations obtained were accomplished by optimizing the organic modifier concentration in the electrolyte and by using a high nanoparticle concentration (5 mg/mL), to improve interparticle mass transfer and gain sufficient retention. Nanoparticles, with an average diameter of 600 nm, were prepared by polymerization of methacrylic acid and trimethylolpropane trimethacrylate, which in turn were coated with dextran. These nanoparticles formed stable suspensions in electrolytes having broad ranges of polarities, enabling straightforward optimization of the reversed-phase conditions.
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| 5. |
- Nilsson, K. Peter R., et al.
(författare)
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Imaging distinct conformational states of amyloid-beta fibrils in Alzheimer's disease using novel luminescent probes
- 2007
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560
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Tidskriftsartikel (refereegranskat)abstract
- Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1–42 peptide (Aβ1–42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1–42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APP swe) of Alzheimer’s disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
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| 6. |
- Nilsson, Peter, et al.
(författare)
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Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes
- 2007
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Ingår i: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560
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Tidskriftsartikel (refereegranskat)abstract
- Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
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| 8. |
- Viberg, Peter, et al.
(författare)
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Reversed phase continuous full filling CEC-ESI-MS
- 2007
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Ingår i: Chromatographia. - : Springer Science and Business Media LLC. - 0009-5893 .- 1612-1112. ; 65:5-6, s. 291-297
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Tidskriftsartikel (refereegranskat)abstract
- Nanoparticles were used as a pseudostationary phase in capillary electrochromatography (CEC) electrospray ionisation-mass spectrometry (ESI-MS) for separation of both neutral analytes by a reversed phase mechanism, as well as for cationic analytes by a cation exchange mechanism. Nanoparticles suspended in electrolyte, were injected as a plug prior to the sample using a partial filling technique (PF), or used as electrolyte in a continuous full filling (CFF) technique. An orthogonal ESI probe was used to hinder the nanoparticles from entering the mass spectrometer and to allow detection of analytes co-eluting with concentrated nanoparticle slurries. Two types of nanoparticles were synthesised and used, both of them having a hydrophobic core and a hydrophilic surface. The hydrophobic core gave the nanoparticles reversed phase properties and the hydrophilic surface promoted the formation of stable slurries of nanoparticles in electrolytes with a low concentration of organic modifier. The surface of one of the nanoparticle types was covered with sulphate groups that, besides from enhancing slurry stability and thus enabling reversed phase CEC, also enabled ion exchange CEC. Both nanoparticle types showed reproducible and interpretable retention properties.
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| 9. |
- Zeggini, Eleftheria, et al.
(författare)
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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:5, s. 638-645
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and similar to 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P=5.0 x 10(-14)), CDC123-CAMK1D (P=1.2 x 10(-10)), TSPAN8-LGR5 (P=1.1 x 10(-9)), THADA (P=1.1 x 10(-9)), ADAMTS9 (P=1.2 x 10(-8)) and NOTCH2 (P=4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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| 10. |
- af Sillén, Ulrika, et al.
(författare)
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Self-rated health in relation to age and gender: influence on mortality risk in the Malmö Preventive Project.
- 2005
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 33:3, s. 9-183
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Tidskriftsartikel (refereegranskat)abstract
- Aims: A study was undertaken to examine whether poor self-rated health (SRH) can independently predict all-cause mortality during 22-year follow-up in middle-aged men and women. Subjects and methods: Data are derived from a population-based study in Malmo¨ , Sweden. This included baseline laboratory testing and a self-administered questionnaire. The question on global SRH was answered by 15,590 men (mean age 46.4 years) and 10,089 women (49.4 years). Social background characteristics (occupation, marital status) were based on data from national censuses. Mortality was retrieved from national registers. Results: At screening 4,261 (27.3%) men and 3,085 (30.6%) women reported poor SRH. Among subjects rating their SRH as low, 1,022 (24.0%) men and 228 (7.4%) women died during follow-up. Corresponding figures for subjects rating their SRH as high were 1801 (15.9%) men and 376 (5.4%) women. An analysis of survival in subjects reporting poor SRH revealed an age-adjusted hazard risk ratio (HR, 95%CI) for men HR 1.5 (1.4–1.7), and for women HR 1.4 (1.2–1.6). The corresponding HR after adjusting for possible social confounders was for men HR 1.3 (1.1–1.4), and women HR 1.1 (0.9–1.4). When additional adjustment was made for biological risk factors the association for men was still significant, HR 1.2 (1.1–1.3). Conclusion: Poor SRH predicts increased long-term mortality in healthy, middle-aged subjects. For men the association is independent of both social background and selected biological variables. The adjustment for biological variables can be questioned as they might represent mediating mechanisms in a possible causal chain of events.
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