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- Arkhammar, P., et al.
(författare)
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Protein kinase C modulates the insulin secretory process by maintaining a proper function of the beta-cell voltage-activated Ca2+ channels
- 1994
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Ingår i: Journal of Biological Chemistry. - : Baishideng Publishers. - 0021-9258 .- 1083-351X. ; 269:4, s. 2743-2749
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Tidskriftsartikel (refereegranskat)abstract
- In the present study an attempt was made to further elucidate the molecular mechanisms whereby protein kinase C (PKC) modulates the beta-cell stimulus-secretion coupling. Regulation of Ca2+ channel activity, [Ca2+]i, and insulin release were investigated in both normal pancreatic mouse beta-cells and in similar beta-cells deprived of PKC activity. [Ca2+]i was measured with the intracellular fluorescent Ca2+ indicator fura-2 and the Ca2+ channel activity was estimated by the whole cell configuration of the patch-clamp technique. To reveal the various isoenzymes of PKC present in the mouse beta-cell, proteins were separated by one-dimensional gel electrophoresis and Western blotting was performed. The production of inositol phosphates was measured by ion-exchange chromatography and insulin release was measured radioimmunologically. Acute stimulation with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate resulted in suppression of both the carbamylcholine-induced increase in [Ca2+]i and production of inositol 1,4,5-trisphosphate. Under these conditions the increase in [Ca2+]i in response to glucose was similar to that found in control cells. When beta-cells were deprived of PKC, by exposure to 200 nM 12-O-tetradecanoylphorbol-13-acetate for 24-48 h, there was an enhanced response to carbamylcholine. This response constituted increases in both the [Ca2+]i signal and production of inositol 1,4,5-trisphosphate. Interestingly, cells with down-regulated PKC activity responded more slowly to glucose stimulation, when comparing the initial increase in [Ca2+]i, than control cells. On the other hand, the maximal increase in [Ca2+]i was similar whether or not PKC was present. Moreover, PKC down-regulated cells exhibited a significant reduction of maximal whole cell Ca2+ currents, a finding that may explain the altered kinetics with regard to the [Ca2+]i increase in response to the sugar. Both the alpha and beta 1 forms of the PKC isoenzymes were present in the mouse beta-cell and were also subjected to PKC down-regulation. Hence, either of these isoenzymes or both may be involved in the modulation of phospholipase C and Ca2+ channel activity. Since insulin release under physiological conditions is critically dependent on Ca(2+)-influx through the voltage-gated L-type Ca2+ channels, the kinetics of hormone release was expected to demonstrate a similar delay as that of the [Ca2+]i increase. Although not as pronounced, such a delay was indeed also observed in the onset of insulin release. There was, however, no effect on the total amounts of hormone released. There was,h owever, no effect on thet otal amounts of hormone released. The present study con- firms that PKC has multiple roles and thereby interacta at different sites in the complex series of events consti- tuting the #?-cell signal-transduction pathway. It is sug- gested that PKC may be tonically active and effective in the maintenance of the phosphorylation state of the voltage-gated L-type Ca2+ channel, enabling an appro- priate function of this channel in the insulin secretory process.
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| 4. |
- Starrin, B., et al.
(författare)
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Structural Changes, Ill Health, and Mortality in Sweden, 1963-1983 : A Macroaggregated Study
- 1990
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Ingår i: International Journal of Health Services. - 0020-7314 .- 1541-4469. ; 20:1, s. 27-42
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Tidskriftsartikel (refereegranskat)abstract
- An exploratory time series analysis was performed on selected indicators of structural change, health behavior, and ill health in Sweden in the years 1963-1983. Both synchronic (nonlagged) and asynchronic (lagged) analyses were made. The synchronic analysis of variations in the suicide rate reveals two main contributory factors: level of employment and overtime work. For cardiovascular mortality in men, the synchronic and the two-year time lagged analyses reveal that the sale of alcohol and, to a certain extent, the length of the period of unemployment play a major role. In an analysis with a three-year time lag, only one significant factor for both men and women is revealed, namely the level of employment. In the synchronic analysis of cirrhosis mortality in men, the sale of alcohol plays a dominant role. The results of the synchronic analysis of the variations in sick leave show a similar pattern for both men and women. In both cases, the sale of alcohol is positively associated and the proportion of unemployed industrial workers negatively associated with sick leave. The results give rise to a number of questions. For example, how should these findings be interpreted and how should they be related to existing knowledge about the links between business cycles and changes in the health of the population? The answers to such questions are of importance both from a scientific viewpoint and with regard to health policy. We argue that the answers require further studies of the characteristics of the periods in the business cycle and of how these periods affect people's lives, living conditions, and behavioral patterns in general.
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| 6. |
- J. Tranvik, Lars, et al.
(författare)
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In situ mineralization of chlorinated phenols by pelagic bacteria in lakes of differing humic content
- 1991
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Ingår i: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 10:2, s. 195-200
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Tidskriftsartikel (refereegranskat)abstract
- The microbial mineralization of phenol and three chlorinated phenols (3,4-dichlorophenol, 2,4,5-trichlorophenol and pentachlorophenol) in the water column of 23 pristine, oligotrophic lakes of different humic content was investigated. During short-term (∼2 d) in situ incubations of water samples amended with 14C-labeled phenolic compounds, the fraction of the added pollutant mineralized to 14CO2 was positively correlated with water color (an estimate of humic content) and the total organic carbon concentration of the water. The rate of mineralization per bacterial cell was not correlated with humic content, due to increased bacterial abundance with increasing humic content. Hence, the higher mineralization rate in humic lakes than in clear-water lakes was probably a result of higher bacterial abundance rather than being an effect of bacterial cells having a higher potential for the degradation of such compounds.
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| 7. |
- Larsson, Christer, et al.
(författare)
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Mechanisms of muscarinic receptor-stimulated expression of c-fos in SH-SY5Y cells
- 1994
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Ingår i: European Journal of Pharmacology. - 1879-0712. ; 268:1, s. 19-28
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Tidskriftsartikel (refereegranskat)abstract
- In this study, the signal cascade transducing carbachol stimulation into c-fos expression in SH-SY5Y neuroblastoma cells was investigated. 1,2-Diacylglycerol formation and c-fos expression were mediated via stimulation of muscarinic M1 receptors and the first 5 min of receptor stimulation were critical for these events. Application of 1,2-dioctanoylglycerol induced c-fos expression and this, as well as carbachol-stimulated c-fos expression, was inhibited by protein kinase C inhibitors. Increasing the intracellular Ca2+ concentration had only small effects on c-fos expression. There was a dependency on extracellular Ca2+ for maximal c-fos expression and 1,2-diacylglycerol formation. The carbachol-stimulated c-fos expression was potentiated by application of the protein phosphatase inhibitor okadaic acid. These results demonstrate the importance of 1,2-diacylglycerol formation for muscarinic receptor-stimulated, protein kinase C-mediated c-fos expression in the SH-SY5Y cells and that this cascade is counteracted by an okadaic acid-sensitive protein phosphatase.
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| 8. |
- Lindgren, Arne, et al.
(författare)
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Cerebral lesions on magnetic resonance imaging, heart disease, and vascular risk factors in subjects without stroke. A population-based study
- 1994
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Ingår i: Stroke: a journal of cerebral circulation. - 1524-4628. ; 25:5, s. 929-934
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: To assess the prevalence of asymptomatic abnormalities on magnetic resonance imaging of the brain and their possible relation to hypertension, heart disease, and carotid artery disease, we studied 77 randomly selected subjects (mean age, 65.1 years; range, 36 to 95 years) with no history of focal brain lesions. METHODS: The study protocol included magnetic resonance imaging of the brain, transthoracic and transesophageal echocardiography, ultrasonography of the carotid arteries, and electrocardiographic recording. Deep and periventricular white matter hyperintensities on magnetic resonance imaging were assessed both separately and together. RESULTS: On magnetic resonance imaging of the brain 62.3% (95% confidence interval [CI], 51.5% to 73.2%) of the subjects had white matter hyperintensities. These abnormalities increased significantly with age (chi 2 test; P = .0001), from 13.6% (95% CI, 0% to 28.0%) of subjects aged younger than 55 years to 85.2% (95% CI, 71.8% to 98.6%) of subjects aged 75 years or older. Six subjects had deep gray matter hyperintensities localized in the basal ganglia, and one had a cerebellar infarction. Stepwise logistic regression analysis identified age and a history of heart disease (but not echocardiographic findings) to be independently associated with deep and periventricular white matter hyperintensities. Hypertension was only independently associated with periventricular white matter hyperintensities. Of the 68 subjects examined with both transthoracic and transesophageal echocardiography, potential cardioembolic sources were detected in 38.2% (95% CI, 26.7% to 49.8%) of the subjects with transthoracic echocardiography and in 47.1% (95% CI, 35.2% to 58.9%) of those with transthoracic and transesophageal echocardiography combined. In subjects aged 75 years or older, a possible cardiac embolic source was detected in 64.0% on transthoracic echocardiography and in 72.0% on transthoracic and transesophageal echocardiography combined, compared with 5.3% and 15.8%, respectively, in subjects aged younger than 55 years. CONCLUSIONS: White matter hyperintensities and potential cardioembolic sources are frequently present in asymptomatic individuals, stressing the need for age-matched control subjects in studies of patients with stroke or dementia.
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