| 1. |
- Eliasson, Jonas, et al.
(författare)
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The Stockholm Congestion-Charging Trial 2006 : Overview of the effects
- 2009
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Ingår i: Transportation Research Part A. - Amsterdam : Elsevier BV. - 0965-8564 .- 1879-2375. ; 43:3, s. 240-250
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Tidskriftsartikel (refereegranskat)abstract
- The Stockholm congestion charging trial in 2006 demonstrated the effects of a full-scale time-differentiated urban road toll scheme. Improvements in travel times were large enough to be perceived by the general public. This was pivotal to the radical change of public attitudes that occurred during the trial and that resulted in a positive outcome of a subsequent referendum on a proposal for making the system permanent. This paper summarises the effects of the trial and analyses to what extent targets were met. Effects on congestion reduction were larger than anticipated, which also resulted in favourable economic and environmental effects. The trial showed that a single-cordon toll could affect traffic within a large area, i.e., not just close to the zone limits.
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| 2. |
- Jones, Helena, et al.
(författare)
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beta-cell PDE3B regulates Ca(2+)-stimulated exocytosis of insulin.
- 2007
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Ingår i: Cellular Signalling. - : Elsevier BV. - 1873-3913 .- 0898-6568. ; 19:Feb 12, s. 1505-1513
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Tidskriftsartikel (refereegranskat)abstract
- cAMP signaling is important for the regulation of insulin secretion in pancreatic beta-cells. The level of intracellular cAMP is controlled through its production by adenylyl cyclases and its breakdown by cyclic nucleotide phosphodiesterases (PDEs). We have previously shown that PDE3B is involved in the regulation of nutrient-stimulated insulin secretion. Here, aiming at getting deeper functional insights, we have examined the role of PDE3B in the two phases of insulin secretion as well as its localization in the beta-cell. Depolarization-induced insulin secretion was assessed and in models where PDE3B was overexpressed [islets from transgenic RIP-PDE3B/7 mice and adenovirally (AdPDE3B) infected INS-I (832/13) cells], the first phase of insulin secretion, occurring in response to stimulation with high K+ for 5 min, was significantly reduced (similar to 25% compared to controls). In contrast, in islets from PDE3B(-/-) mice the response to high K+ was increased. Further, stimulation of isolated beta-cells from RIP-PDE3B/7 islets, using successive trains of voltage-clamped depolarizations, resulted in reduced Ca2+-triggered first phase exocytotic response as well as reduced granule mobilization-dependent second phase, compared to wild-type beta-cells. Using sub-cellular fractionation, confocal microscopy and transmission electron microscopy of isolated mouse islets and INS-1 (832/13) cells, we show that endogenous and overexpressed PDE3B is localized to insulin granules and plasma membrane. We conclude that PDE3B, through hydrolysis of cAMP in pools regulated by Ca2+, plays a regulatory role in depolarization-induced insulin secretion and that the enzyme is associated with the exocytotic machinery in beta-cells. (c) 2007 Elsevier Inc. All rights reserved.
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| 3. |
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| 4. |
- Björkqvist, Maria, et al.
(författare)
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Somatostatin, misoprostol and galanin inhibit gastrin- and PACAP-stimulated secretion of histamine and pancreastatin from ECL cells by blocking specific Ca(2+) channels.
- 2005
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Ingår i: Regulatory Peptides. - : Elsevier BV. - 1873-1686 .- 0167-0115. ; 130:1-2, s. 81-90
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Tidskriftsartikel (refereegranskat)abstract
- The oxyntic mucosa is rich in ECL cells. They secrete histamine and chromogranin A-derived peptides, such as pancreastatin, in response to gastrin and pituitary adenylate cyclase-activating peptide (PACAP). Secretion is initiated by Ca2+ entry. While gastrin stimulates secretion by opening L-type and N-type Ca2+ channels, PACAP stimulates secretion by activating L-type and receptor-operated Ca2+ channels. Somatostatin, galanin and prostaglandin E2 (PGE2) inhibit gastrin- and PACAP-stimulated secretion from the ECL cells. In the present study, somatostatin and the PGE2 congener misoprostol inhibited gastrin- and PACAP-stimulated secretion 100%, while galanin inhibited at most 60–65%. Bay K 8644, a specific activator of L-type Ca2+ channels, stimulated ECL-cell secretion, an effect that was inhibited equally effectively by somatostatin, misoprostol and galanin (75–80% inhibition). Pretreatment with pertussis toxin, that inactivates inhibitory G-proteins, prevented all three agents from inhibiting stimulated secretion (regardless of the stimulus). Pretreatment with nifedipine (10 μM), an L-type Ca2+ channel blocker, reduced PACAP-evoked pancreastatin secretion by 50–60%, gastrin-evoked secretion by not, vert, similar 80% and abolished the response to Bay K 8644. The nifedipine-resistant response to PACAP was abolished by somatostatin and misoprostol but not by galanin. Gastrin and PACAP raised the intracellular Ca2+ concentration in a biphasic manner, believed to reflect mobilization of internal Ca2+ followed by Ca2+ entry. Somatostatin and misoprostol blocked Ca2+ entry (and histamine and pancreastatin secretion) but not mobilization of internal Ca2+. The present observations on isolated ECL cells suggest that Ca2+ entry rather than mobilization of internal Ca2+ triggers exocytosis, that gastrin and PACAP activate different (but over-lapping) Ca2+ channels, that somatostatin, misoprostol and galanin interact with inhibitory G-proteins to block Ca2+ entry via L-type Ca2+ channels, and that somatostatin and misoprostol (but not galanin) in addition block N-type and/or receptor-operated Ca2+ channels.
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| 5. |
- Börstler, Jürgen, 1960-, et al.
(författare)
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Transitioning to OOP/Java : A never ending story
- 2008
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Ingår i: Reflections on the teaching of programming. - Berlin, Heidelberg : Springer. - 9783540779339 ; , s. 80-97
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Bokkapitel (refereegranskat)
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| 6. |
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| 7. |
- Collins, S. C., et al.
(författare)
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Long-term exposure of mouse pancreatic islets to oleate or palmitate results in reduced glucose-induced somatostatin and oversecretion of glucagon
- 2008
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:9, s. 1689-1693
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Long-term exposure to NEFAs leads to inhibition of glucose-induced insulin secretion. We tested whether the release of somatostatin and glucagon, the two other major islet hormones, is also affected. Methods Mouse pancreatic islets were cultured for 72 h at 4.5 or 15 mmol/l glucose with or without 0.5 mmol/l oleate or palmitate. The release of glucagon and somatostatin during subsequent 1 h incubations at 1 or 20 mmol/l glucose as well as the islet content of the two hormones were determined. Lipid-induced changes in islet cell ultrastructure were assessed by electron microscopy. Results Culture at 15 mmol/l glucose increased islet glucagon content by similar to 50% relative to that observed following culture at 4.5 mmol/l glucose. Inclusion of oleate or palmitate reduced islet glucagon content by 25% (at 4.5 mmol/l glucose) to 50% (at 15 mmol/l glucose). Long-term exposure to the NEFA increased glucagon secretion at 1 mmol/l glucose by 50% (when islets had been cultured at 15 mmol/l glucose) to 100% (with 4.5 mmol/l glucose in the culture medium) and abolished the inhibitory effect of 20 mmol/l glucose on glucagon secretion. Somatostatin content was unaffected by glucose and lipids, but glucose-induced somatostatin secretion was reduced by similar to 50% following long-term exposure to either of the NEFA, regardless of whether the culture medium contained 4.5 or 15 mmol/l glucose. Ultrastructural evidence of lipid deposition was seen in < 10% of non-beta cells but in > 80% of the beta cells. Conclusions/interpretation Long-term exposure to high glucose and/or NEFA affects the release of somatostatin and glucagon. The effects on glucagon secretion are very pronounced and in type 2 diabetes in vivo may aggravate the hyperglycaemic effects due to lack of insulin.
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| 9. |
- Dekker Nitert, Marloes, et al.
(författare)
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CaV1.2 rather than CaV1.3 is coupled to glucose-stimulated insulin secretion in INS-1 832/13 cells.
- 2008
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Ingår i: Journal of Molecular Endocrinology. - 1479-6813. ; 41:1, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- In clonal beta-cell lines and islets from different species, a variety of calcium channels are coupled to glucose-stimulated insulin secretion. The aim of this study was to identify the voltage-gated calcium channels that control insulin secretion in insulinoma (INS)-1 832/13 cells. The mRNA level of Ca(V)1.2 exceeded that of Ca(V)1.3 and Ca(V)2.3 two-fold. Insulin secretion, which rose tenfold in response to 16.7 mM glucose, was completely abolished by 5 microM isradipine that blocks Ca(V)1.2 and Ca(V)1.3. Similarly, the increase in intracellular calcium in response to 15 mM glucose was decreased in the presence of 5 microM isradipine, and the frequency of calcium spikes was decreased to the level seen at 2.8 mM glucose. By contrast, inhibition of Ca(V)2.3 with 100 nM SNX-482 did not significantly affect insulin secretion or intracellular calcium. Using RNA interference, Ca(V)1.2 mRNA and protein levels were knocked down by approximately 65% and approximately 34% respectively, which reduced insulin secretion in response to 16.7 mM glucose by 50%. Similar reductions in calcium currents and cell capacitance were seen in standard whole-cell patch-clamp experiments. The remaining secretion of insulin could be reduced to the basal level by 5 microM isradipine. Calcium influx underlying this residual insulin secretion could result from persisting Ca(V)1.2 expression in transfected cells since knock-down of Ca(V)1.3 did not affect glucose-stimulated insulin secretion. In summary, our results suggest that Ca(V)1.2 is critical for insulin secretion in INS-1 832/13 cells.
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| 10. |
- Eliasson, A. C., et al.
(författare)
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The Manual Ability Classification System (MACS) for children with cerebral palsy: scale development and evidence of validity and reliability
- 2006
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Ingår i: Dev Med Child Neurol. - 0012-1622 .- 1469-8749. ; 48:7, s. 549-54
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Tidskriftsartikel (refereegranskat)abstract
- The Manual Ability Classification System (MACS) has been developed to classify how children with cerebral palsy (CP) use their hands when handling objects in daily activities. The classification is designed to reflect the child's typical manual performance, not the child's maximal capacity. It classifies the collaborative use of both hands together. Validation was based on the experience within an expert group, a review of the literature, and thorough analysis of children across a spectrum of function. Discussions continued until consensus was reached, first about the constructs, then about the content of the five levels. Parents and therapists were interviewed about the content and the description of levels. Reliability was tested between pairs of therapists for 168 children (70 females, 98 males; with hemiplegia [n=52], diplegia [n=70], tetraplegia [n=19], ataxia [n=6], dyskinesia [n=19], and unspecified CP [n=2]) between 4 and 18 years and between 25 parents and their children's therapists. The results demonstrated that MACS has good validity and reliability. The intraclass correlation coefficient between therapists was 0.97 (95% confidence interval 0.96-0.98), and between parents and therapist was 0.96 (0.89-0.98), indicating excellent agreement.
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