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Sökning: (WFRF:(Holm L.)) srt2:(2005-2009) > (2009)

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  • Aaron, F. D., et al. (författare)
  • Multi-leptons with high transverse momentum at HERA
  • 2009
  • Ingår i: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10
  • Tidskriftsartikel (refereegranskat)abstract
    • Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb(-1). The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e(+)p collision data with a scalar sum of the lepton transverse momenta above 100 GeV while 1.94 +/- 0.17 events are expected. Such events are not observed in e(-)p collisions for which 1.19 +/- 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions.
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  • Mackey, A. L., et al. (författare)
  • Assessment of satellite cell number and activity status in human skeletal muscle biopsies
  • 2009
  • Ingår i: Muscle and Nerve. - : John Wiley & Sons. - 0148-639X .- 1097-4598. ; 40:3, s. 455-465
  • Tidskriftsartikel (refereegranskat)abstract
    • The primary aim of our study was to validate the assessment of myonuclear and satellite cell number in biopsies from human skeletal muscle. We found that 25 type I and 25 type II fibers are sufficient to estimate the mean number of myonuclei per fiber. In contrast, the assessment of satellite cells improved when more fibers were included. Second, we report that small differences in counting satellite cells using CD56 and Pax7 antibodies can be attributed to the different staining profiles. Third, we provide support for the use of Ki67 in evaluating the proportion of active satellite cells. We observed very few (up to 1.3%) active satellite cells in healthy adult skeletal muscle at rest, but they increased significantly (up to 7-fold) following muscle activity. This study provides valuable tools to assess the behavior of satellite cells, both in pathological conditions and in response to physiological stimuli.
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  • Fex, Malin, et al. (författare)
  • A beta cell-specific knockout of hormone-sensitive lipase in mice results in hyperglycaemia and disruption of exocytosis.
  • 2009
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52, s. 271-280
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: The enzyme hormone-sensitive lipase (HSL) is produced and is active in pancreatic beta cells. Because lipids are known to play a crucial role in normal control of insulin release and in the deterioration of beta cell function, as observed in type 2 diabetes, actions of HSL in beta cells may be critical. This notion has been addressed in different lines of HSL knockout mice with contradictory results. METHODS: To resolve this, we created a transgenic mouse lacking HSL specifically in beta cells, and characterised this model with regard to glucose metabolism and insulin secretion, using both in vivo and in vitro methods. RESULTS: We found that fasting basal plasma glucose levels were significantly elevated in mice lacking HSL in beta cells. An IVGTT at 12 weeks revealed a blunting of the initial insulin response to glucose with delayed elimination of the sugar. Additionally, arginine-stimulated insulin secretion was markedly diminished in vivo. Investigation of the exocytotic response in single HSL-deficient beta cells showed an impaired response to depolarisation of the plasma membrane. Beta cell mass and islet insulin content were increased, suggesting a compensatory mechanism, by which beta cells lacking HSL strive to maintain normoglycaemia. CONCLUSIONS/INTERPRETATION: Based on these results, we suggest that HSL, which is located in close proximity of the secretory granules, may serve as provider of a lipid-derived signal essential for normal insulin secretion.
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  • Holm, C, et al. (författare)
  • Phosphorylation of the oestrogen receptor alpha at serine 305 and prediction of tamoxifen resistance in breast cancer
  • 2009
  • Ingår i: JOURNAL OF PATHOLOGY. - : Wiley. - 0022-3417 .- 1096-9896. ; 217:3, s. 372-379
  • Tidskriftsartikel (refereegranskat)abstract
    • Phosphorylation of oestrogen receptor a at serine 305 (ER alpha S305-P) induces tamoxifen resistance in experimental studies, but does not influence response to other endocrine agents, such as fulvestrant. We evaluated ER alpha S305-P using immunohistochemistry in 377 breast carcinomas from premenopausal participants of a randomized trial (n = 248) and patients with advanced disease (n = 129). Among the premenopausal patients, adjuvant tamoxifen improved recurrence-free survival (RFS) for ER alpha S305-P-negative tumours (multivariate HR = 0.53, 95% CI 0.32-0.86, p = 0.010), but not for ER alpha S305-P-positive tumours (multivariate HR = 1.01, 95% CI 0.33-3.05, p = 0.99) (interaction p = 0.131). Notably, ER alpha S305-P was not significantly associated with RFS in patients not treated with tamoxifen (multivariate HR = 0.64, 95% CI 0.30-1.37, p = 0.248), indicating that ER alpha S305-P is a marker for treatment outcome rather than tumour progression. Given the direct experimental link between ER alpha S305-P and tamoxifen resistance and these first clinical data suggesting that premenopausal patients with ER alpha S305-P-positive breast cancer are resistant to adjuvant tamoxifen, further research is encouraged to study whether alternative endocrine treatment should be considered for this subgroup.
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