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- Fakhrai-Rad, H, et al.
(författare)
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Insulin-degrading enzyme identified as a candidate diabetes susceptibility gene in GK rats.
- 2000
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 9:14, s. 2149-58
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Tidskriftsartikel (refereegranskat)abstract
- Genetic analysis of the diabetic GK rat has revealed several diabetes susceptibility loci. Congenic strains have been established for the major diabetes locus, Niddm1, by transfer of GK alleles onto the genome of the normoglycemic F344 rat. Niddm1 was dissected into two subloci, physically separated in the congenic strains Niddm1b and Niddm1i, each with at least one disease susceptibility gene. Here we have mapped Niddm1b to 1 cM by genetic and pathophysiological characterization of new congenic substrains for the locus. The gene encoding insulin-degrading enzyme (IDE:) was located to this 1 cM region, and the two amino acid substitutions (H18R and A890V) identified in the GK allele reduced insulin-degrading activity by 31% in transfected cells. However, when the H18R and A890V variants were studied separately, no effects were observed, demonstrating a synergistic effect of the two variants on insulin degradation. No effect on insulin degradation was observed in cell lysates, indicating that the effect is coupled to receptor-mediated internalization of insulin. Congenic rats with the IDE: GK allele displayed post-prandial hyperglycemia, reduced lipogenesis in fat cells, blunted insulin-stimulated glucose transmembrane uptake and reduced insulin degradation in isolated muscle. Analysis of additional rat strains demonstrated that the dysfunctional IDE: allele was unique to GK. These data point to an important role for IDE: in the diabetic phenotype in GK.
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| 5. |
- Fernström, Elisabeth A.C., et al.
(författare)
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Alterations in shoulder muscle activity due to changes in data entry organisation
- 1999
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Ingår i: International Journal of Industrial Ergonomics. - 0169-8141 .- 1872-8219. ; 23:3, s. 231-240
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate how changed work organisation and different work tasks influence shoulder muscular load and to quantify the magnitude, duration and frequency of rest periods from shoulder muscular load during a working day. Shoulder muscular load was measured in 22 females working at their data entry workplaces, during a whole working day. The activity from both trapezius muscles was measured with EMG before (1991) and after (1992) a reorganisation programme intended to redistribute repetitive work and provide new work tasks.The change in work organisation did not change the magnitude of muscular load or the duration and frequency of rest periods, but decreased musculoskeletal problems. The subjects' increased desk work involved greater muscular load than the data entry did, but also allowed more movement. The changes in work tasks seemed to be important, although small. In repetitive work, organisational changes aimed at reducing musculoskeletal disorders should focus on providing employees with tasks that afford variation in muscular load. Relevance to industry. The paper discusses the need of physical work task variation in repetitive work in order to minimise the risk of musculoskeletal disorders. It seems more important to vary the tasks than to minimise the shoulder muscular load. Copyright
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| 6. |
- Fernström, E A, et al.
(författare)
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Upper-arm elevation during office work.
- 1996
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 39:10, s. 1221-30
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Tidskriftsartikel (refereegranskat)abstract
- The present aim was to measure and quantify upper-arm elevation and to find how changed work organization and work tasks influence arm movement during a working day. Sixteen female office workers participated in the study. Their main work was statistical data entry. Upper-arm elevation was measured on two occasions separated by 18 months, i.e., before and after a change of work organization. The measurements were performed during the whole of one ordinary working day. The differences between the two measurements were mostly non-significant. Arm elevation remained essentially below 30 degrees during the main time of the working day, and the subjects worked with limited arm movements. Despite new alternative office tasks, they did not achieve a change in their habitual arm postures, or in their neck-and-shoulder disorders.
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| 7. |
- Fernström, Johan, et al.
(författare)
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Blood-based mitochondrial respiratory chain function in major depression
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Mitochondrial dysfunction has been implicated in major depressive disorder (MDD). A measure of mitochondrial respiratory chain (RC) enzymatic activity—the Mitochondrial Health Index (MHI)—has previously been found to correlate with stress and emotional states in caregivers. We here report mitochondrial RC activities, mitochondrial DNA copy number (mtDNAcn), and the composite MHI in unmedicated and somatically healthy subjects with MDD (n = 47) and healthy controls (HC) (n = 11). We also explore, in a subset of the MDD sample (n = 33), whether these markers are associated with response to 8 weeks of SSRI treatment. Mitochondrial RC complexes I, II, IV, citrate synthase (CS), mtDNAcn, and the MHI were assayed in peripheral blood mononuclear cells. Treatment response was defined as >50% decrease on the 25-item Hamilton Depression Rating Scale (HRDS-25). There were no significant differences in MHI or any of the mitochondrial markers between MDD subjects and HCs. Compared to SSRI nonresponders, SSRI responders had significantly higher baseline mitochondrial content markers CS (p = 0.02) and mtDNAcn (p = 0.02), and higher complex I activity (p = 0.01). Complex II activity increased significantly over treatment, irrespective of clinical response (p = 0.03). Complex I activity decreased in responders (n = 9), but increased in nonresponders (n = 18) (group x time interaction, p = 0.02). Absolute treatment-associated change in HDRS-25 scores correlated significantly with change in complex I activity between baseline and week 8 (r = 0.47, p = 0.01). Although mitochondrial markers did not distinguish MDD from controls, they did distinguish SSRI responders from nonresponders. If larger studies validate these mitochondrial differences, they may become useful biomarkers and identify new drug targets.
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| 8. |
- Hjeltnes, N, et al.
(författare)
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Regulation of UCP2 and UCP3 by muscle disuse and physical activity in tetraplegic subjects.
- 1999
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 42:7, s. 826-30
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: The regulation of uncoupling protein 2 and uncoupling protein 3 gene expression in skeletal muscle has recently been the focus of intense interest. Our aim was to determine expression of uncoupling protein 2 and 3 in skeletal muscle from tetraplegic subjects, a condition representing profound muscle inactivity. Thereafter we determined whether exercise training would modify expression of these genes in skeletal muscle.METHODS: mRNA expression of uncoupling protein 2 and 3 was determined using quantitative reverse transcription-polymerase chain-reaction.RESULTS: Expression of uncoupling protein 2 and 3 mRNA was increased in skeletal muscle from tetraplegic compared with able-bodied subjects (3.7-fold p < 0.01 and 4.1-fold, p < 0.05, respectively). A subgroup of four tetraplegic subjects underwent an 8-week exercise programme consisting of electrically-stimulated leg cycling (ESLC, 7 ESLC sessions/week). This training protocol leads to increases in whole body insulin-stimulated glucose uptake and expression of genes involved in glucose metabolism in skeletal muscle from tetraplegic subjects. After ESLC training, uncoupling protein 2 expression was reduced by 62% and was similar to that in able-bodied people. Similarly, ESLC training was associated with a reduction of uncoupling protein 3 expression in skeletal muscle from three of four tetraplegic subjects, however, post-exercise levels remained increased compared with able-bodied subjects.CONCLUSION/INTERPRETATION: Tetraplegia is associated with increased mRNA expression of uncoupling protein 2 and 3 in skeletal muscle. Exercise training leads to normalisation of uncoupling protein 2 expression in tetraplegic subjects. Muscle disuse and physical activity appear to be powerful regulators of uncoupling protein 2 and 3 expression in human skeletal muscle.
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| 9. |
- Indurain, A, et al.
(författare)
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Uremic klåda
- 2010
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Ingår i: Incitament. - 1103-503X.
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Tidskriftsartikel (populärvet., debatt m.m.)
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| 10. |
- Lindqvist, D., et al.
(författare)
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Increased plasma levels of circulating cell-free mitochondrial DNA in suicide attempters : associations with HPA-axis hyperactivity
- 2016
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Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 6:12
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Tidskriftsartikel (refereegranskat)abstract
- Preclinical data suggest that chronic stress may cause cellular damage and mitochondrial dysfunction, potentially leading to the release of mitochondrial DNA (mtDNA) into the bloodstream. Major depressive disorder has been associated with an increased amount of mtDNA in leukocytes from saliva samples and blood; however, no previous studies have measured plasma levels of free-circulating mtDNA in a clinical psychiatric sample. In this study, free circulating mtDNA was quantified in plasma samples from 37 suicide attempters, who had undergone a dexamethasone suppression test (DST), and 37 healthy controls. We hypothesized that free circulating mtDNA would be elevated in the suicide attempters and would be associated with hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity. Suicide attempters had significantly higher plasma levels of free-circulating mtDNA compared with healthy controls at different time points (pre- and post-DST; all P-values < 2.98E - 12, Cohen's d ranging from 2.55 to 4.01). Pre-DST plasma levels of mtDNA were positively correlated with post-DST cortisol levels (rho = 0.49, P < 0.003). Suicide attempters may have elevated plasma levels of free-circulating mtDNA, which are related to impaired HPA-axis negative feedback. This peripheral index is consistent with an increased cellular or mitochondrial damage. The specific cells and tissues contributing to plasma levels of free-circulating mtDNA are not known, as is the specificity of this finding for suicide attempters. Future studies are needed in order to better understand the relevance of increased free-circulating mtDNA in relation to the pathophysiology underlying suicidal behavior and depression.
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