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Träfflista för sökning "WFRF:(Widegren B.) "

Search: WFRF:(Widegren B.)

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  • Benziane, B, et al. (author)
  • Effect of exercise and training on phospholemman phosphorylation in human skeletal muscle
  • 2011
  • In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 301:3, s. E456-E466
  • Journal article (peer-reviewed)abstract
    • Phospholemman (PLM, FXYD1) is a partner protein and regulator of the Na+-K+-ATPase (Na+-K+pump). We explored the impact of acute and short-term training exercise on PLM physiology in human skeletal muscle. A group of moderately trained males ( n = 8) performed a 1-h acute bout of exercise by utilizing a one-legged cycling protocol. Muscle biopsies were taken from vastus lateralis at 0 and 63 min (non-exercised leg) and 30 and 60 min (exercised leg). In a group of sedentary males ( n = 9), we determined the effect of a 10-day intense aerobic cycle training on Na+-K+-ATPase subunit expression, PLM phosphorylation, and total PLM expression as well as PLM phosphorylation in response to acute exercise (1 h at ∼72% V̇o2peak). Biopsies were taken at rest, immediately following, and 3 h after an acute exercise bout before and at the conclusion of the 10-day training study. PLM phosphorylation was increased both at Ser63and Ser68immediately after acute exercise (75%, P < 0.05, and 30%, P < 0.05, respectively). Short-term training had no adaptive effect on PLM phosphorylation at Ser63and Ser68, nor was the total amount of PLM altered posttraining. The protein expressions of α1-, α2-,and β1-subunits of Na+-K+-ATPase were increased after training (113%, P < 0.05, 49%, P < 0.05, and 27%, P < 0.05, respectively). Whereas an acute bout of exercise increased the phosphorylation of PKCα/βII on Thr638/641pre- and posttraining, phosphorylation of PKCζ/λ on Thr403/410was increased in response to acute exercise only after the 10-day training. In conclusion, we show that only acute exercise, and not short-term training, increases phosphorylation of PLM on Ser63and Ser68, and data from one-legged cycling indicate that this effect of exercise on PLM phosphorylation is not due to systemic factors. Our results provide evidence that phosphorylation of PLM may play a role in the acute regulation of the Na+-K+-ATPase response to exercise.
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  • C Johansson, Anna, et al. (author)
  • Computerized image analysis as a tool to quantify infiltrating leukocytes : a comparison between high- and low-magnification images
  • 2001
  • In: Journal of Histochemistry and Cytochemistry. - 0022-1554. ; 49:9, s. 79-1073
  • Journal article (peer-reviewed)abstract
    • The purpose of the present study was to establish a rapid and reproducible method for quantification of tissue-infiltrating leukocytes using computerized image analysis. To achieve this, the staining procedure, the image acquisition, and the image analysis method were optimized. Because of the adaptive features of the human eye, computerized image analysis is more sensitive to variations in staining compared with manual image analysis. To minimize variations in staining, an automated immunostainer was used. With a digital scanner camera, low-magnification images could be sampled at high resolution, thus making it possible to analyze larger tissue sections. Image analysis was performed by color thresholding of the digital images based on values of hue, saturation, and intensity color mode, which we consider superior to the red, green, and blue color mode for analysis of most histological stains. To evaluate the method, we compared computerized analysis of images with a x100 or a x12.5 magnification to assess leukocytes infiltrating rat brain tumors after peripheral immunizations with tumor cells genetically modified to express rat interferon-gamma (IFN-gamma) or medium controls. The results generated by both methods correlated well and did not show any significant differences. The method allows efficient and reproducible processing of large tissue sections that is less time-consuming than conventional methods and can be performed with standard equipment and software.(J Histochem Cytochem 49:1073-1079, 2001)
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  • Langefors, Åsa, et al. (author)
  • Allelic variation of Mhc class II in Atlantic salmon; a population genetic analysis
  • 1998
  • In: Heredity. - : Springer Science and Business Media LLC. - 1365-2540 .- 0018-067X. ; 80:5, s. 568-575
  • Journal article (peer-reviewed)abstract
    • We have studied the degree of genetic variation at a variable Mhc class II beta gene in four populations of Atlantic salmon Salmo salar by using RFLPs. The class II beta gene encodes the part of the Mhc class II molecule that contains the antigen binding region and is therefore essential for disease resistance. There was extensive genetic variation in all four populations; the expected heterozygosity (H-si) varied between 0.50 and 0.81. Heterozygosity tended to be higher in broods surviving a syndrome causing high mortalities (60-95%) in Swedish salmon hatcheries. Populations that had experienced more incidences of genetic bottlenecks (years when fewer than 60 adults had been used for breeding) and had a lower average effective population size (N-e), had a lower degree of heterozygosity. The four populations differed significantly in allele frequencies as measured by F-ST = 0.13 and Nei's genetic distance (D = 0.09 - infinity). Pairwise F-ST values varied between 0.01 and 0.23, all but one being highly significant, indicating a differentiation between the populations in Mhc class II beta. This study shows that the four populations of Atlantic salmon have a high degree of polymorphism in the Mhc class II beta gene. However, there was great variation between different hatcheries, both in heterozygosity levels and allele frequencies.
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  • Schiött, A, et al. (author)
  • Effects of transforming growth factor beta1 expression in a rat colon carcinoma : growth inhibition, leukocyte infiltration and production of interleukin-10 and tumor necrosis factor alpha
  • 2000
  • In: Cancer Immunology and Immunotherapy. - 1432-0851. ; 48:10, s. 579-587
  • Journal article (peer-reviewed)abstract
    • The cytokine transforming growth factor beta-1 (TGFbeta1), was transfected into a TGFbeta1-negative rat colon carcinoma. The growth of isografts of TGFbeta1-expressing tumors was compared to that of vector control transfectants. The TGFbeta1 transfectant grew significantly more slowly after intrahepatic isografting than did vector control and wild-type tumors. The TGFbeta1-transfected tumor tissue had significantly greater infiltration of both CD4+ and CD8+ T lymphocytes than did the vector control tumor. The tumor-infiltrating leukocytes (TIL) from TGFbeta1-transfected tumor secreted significantly more of the cytokines interleukin-10 (IL-10) and tumor necrosis factor alpha (TNFalpha) than did TIL from the vector control tumor. The TGFbeta1 transfectant also demonstrated a significantly slower outgrowth in immunodeficient SCID mice, supporting a non-T-lymphocyte-dependent mechanism for the tumor retardation. In SCID mice, the TGFbeta1-transfected tumor demonstrated significantly greater infiltration of both granulocytes and macrophages than did the vector control transfectant. We also demonstrated a direct inhibitory effect of rat TNFalpha on tumor proliferation in vitro. These results suggest that TGFbeta1 induces a local secretion of immunomodulating cytokines and that this may influence monocytes, lymphocytes and granulocytes to retard tumor outgrowth.
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  • Visse, E, et al. (author)
  • Immunohistochemical analysis of glioma-infiltrating leucocytes after peripheral therapeutic immunization with interferon-gamma-transfected glioma cells
  • 2000
  • In: Cancer Immunology and Immunotherapy. - : Springer Science and Business Media LLC. - 1432-0851 .- 0340-7004. ; 49:3, s. 142-151
  • Journal article (peer-reviewed)abstract
    • We have shown previously that rejection of preinduced rat brain tumours is possible following therapeutic immunizations with interferon-gamma (IFN gamma)-transfected glioma cells (N32-IFN gamma). In the present study we have used the same model to evaluate whether quantitative differences in tumour-infiltrating lymphocytes can be detected between animals receiving therapeutic immunizations with either IFN gamma-transfected glioma cells, wild-type glioma cells or no treatment. Since leucocyte transpedesis into the tumour can be anticipated to depend on the state of vascularization, we have mapped the development of microvessels in the tumour in parallel with the leucocyte infiltration. Our results show that microvessels start to form at day 7 and then gradually increase in number and size, indicating the establishment of an extensive vascularization by day 24. Leucocyte infiltration displays a biphasic pattern after tumour grafting. We have therefore studied the infiltration kinetics after an early immunization (1 day after intracerebral isografting) and compared the effects with those of a late immunization (10 days after intracerebral isografting) with N32-IFN gamma or wild-type N32. Our results show (1) an early infiltration of granulocytes 3 days after isografting; (2) a T-cell-receptor-positive (TCR+) T-cell infiltration starting on day 10; (3) a macrophage infiltration starting on day 13; (4) a CD8+ cell infiltration starting on day 13. The proportions of TCR+ T cells, CD8+ cells and natural killer cells differs significantly between animals immunized with N32-IFN gamma and those receiving wild-type N32, when analysed 14 days after immunization at day 10. This difference can only be detected when animals are immunized at later stages of tumour growth. We propose that this could depend on an early-immunization-independent leucocyte infiltration during tumour establishment. This has to be considered when evaluating studies of leucocyte infiltration in experimental tumours.
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  • Visse, E, et al. (author)
  • Regression of intracerebral rat glioma isografts by therapeutic subcutaneous immunization with interferon-gamma, interleukin-7, or B7-1-transfected tumor cells
  • 1999
  • In: Cancer Gene Therapy. - : Springer Science and Business Media LLC. - 0929-1903 .- 1476-5500. ; 6:1, s. 37-44
  • Journal article (peer-reviewed)abstract
    • Progress in the definition of the roles of various costimulators and cytokines in determining the type and height of immune responses has made it important to explore genetically altered tumor cells expressing such molecules for therapeutic immunizations. We have studied the effect of therapeutic subcutaneous (s.c.) immunizations on the growth of preexisting intracerebral brain tumor isografts in the rat. Transfectant glioma cell clones expressing either rat interferon-gamma (IFN-gamma), rat interleukin-7 (IL-7), or rat B7-1 were selected. After irradiation (80 Gy) the clones were used for immunization (administered in up to four s.c. doses in a hind leg over 14-day intervals starting 1 day after the intracranial isografting of the parental tumor). Significant growth inhibition of the intracerebral parental tumors was induced by transfectants expressing IFN-gamma and IL-7, respectively. The strongest effect was observed with IFN-gamma-expressing cells, resulting in cures in 37% of the males and in 100% of the females. Immunization with IL-7 had a similar, strong initial effect, with significantly prolonged survival in the majority of the rats but a lower final cure rate (survival for >150 days). The B7-1-expressing tumor clones induced cures in seven of eight female rats; however, no cures were seen in the male rats. It was also shown that the B7-1-expressing cells were themselves strongly immunogenic in female rats, requiring high cell numbers to result in a progressively growing tumor upon s.c. isografting; this was not the case in male rats. As a whole, the results imply that despite the unfavorable location of intracerebral tumors, therapeutic s.c. immunizations with certain types of genetically altered tumor cells can induce complete regressions with permanent survival and without gross neurological or other apparent signs of brain damage. The present results demonstrate complete regressions when immunizations are initiated shortly after intracranial isografting, when the intracerebral tumor is small.
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