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| 2. |
- Barman, Malin, 1983, et al.
(författare)
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Single Nucleotide Polymorphisms in the FADS Gene Cluster but not the ELOVL2 Gene are Associated with Serum Polyunsaturated Fatty Acid Composition and Development of Allergy (in a Swedish Birth Cohort).
- 2015
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 7:12, s. 10100-10115
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Tidskriftsartikel (refereegranskat)abstract
- Exposure to polyunsaturated fatty acids (PUFA) influences immune function and may affect the risk of allergy development. Long chain PUFAs are produced from dietary precursors catalyzed by desaturases and elongases encoded by FADS and ELOVL genes. In 211 subjects, we investigated whether polymorphisms in the FADS gene cluster and the ELOVL2 gene were associated with allergy or PUFA composition in serum phospholipids in a Swedish birth-cohort sampled at birth and at 13 years of age; allergy was diagnosed at 13 years of age. Minor allele carriers of rs102275 and rs174448 (FADS gene cluster) had decreased proportions of 20:4 n-6 in cord and adolescent serum and increased proportions of 20:3 n-6 in cord serum as well as a nominally reduced risk of developing atopic eczema, but not respiratory allergy, at 13 years of age. Minor allele carriers of rs17606561 in the ELOVL2 gene had nominally decreased proportions of 20:4 n-6 in cord serum but ELOVL polymorphisms (rs2236212 and rs17606561) were not associated with allergy development. Thus, reduced capacity to desaturase n-6 PUFAs due to FADS polymorphisms was nominally associated with reduced risk for eczema development, which could indicate a pathogenic role for long-chain PUFAs in allergy development.
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| 3. |
- Hojjat-Farsangi, Mohammad, et al.
(författare)
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The tyrosine kinase receptor ROR1 is constitutively phosphorylated in chronic lymphocytic leukemia (CLL) cells
- 2013
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Ingår i: PLOS ONE. - Stockholm : Karolinska Institutet, Dept of Oncology-Pathology. - 1932-6203.
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Tidskriftsartikel (refereegranskat)abstract
- Phosphorylation of receptor tyrosine kinases (RTKs) has a key role in cellular functions contributing to the malignant phenotype of tumor cells. We and others have previously demonstrated that RTK ROR1 is overexpressed in chronic lymphocytic leukemia (CLL). Silencing siRNA downregulated ROR1 and induced apoptosis of CLL cells. In the present study we analysed ROR1 isoforms and the phosphorylation pattern in CLL cells (n=38) applying western blot and flow-cytometry using anti-ROR1 antibodies and an anti-phospho-ROR1 antibody against the TK domain. Two major ROR1 bands with the size of 105 and 130 kDa respectively were identified, presumably representing unglycosylated (immature) and glycosylated (mature) ROR1 respectively as well as a 260 kDa band which may represent dimerized ROR1. A ROR1 band of 64 kDa that may correspond to a C-terminal fragment was also noted, present only in the nucleus. The 105 kDa ROR1 isoform was more frequently expressed in non-progressive as compared to progressive CLL patients (p=0.03). The 64, 105, 130 and 260 kDa bands were constitutively phosphorylated both at tyrosine and serine residues. Phosphorylation intensity of the mature (130 kDa) isoform was significantly higher in progressive than in non-progressive disease (p<0.001). Incubation of CLL cells with a mouse anti-ROR1 KNG or an anti-ROR1 CRD mAb respectively induced dephosphorylation of ROR1 before entering apoptosis. In conclusion CLL cells expressed different isoforms of ROR1 which were constitutively phosphorylated. The mature, phosphorylated ROR1 isoform was associated with a progressive disease stage. Targeting ROR1 by mAbs induced specific dephosphorylation and leukemic cell death. ROR1 might be an interesting therapeutic target.
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| 4. |
- Holmberg, Lars, et al.
(författare)
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National comparisons of lung cancer survival in England, Norway and Sweden 2001-2004 : differences occur early in follow-up
- 2010
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Ingår i: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 65:5, s. 436-441
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Countries with a similar expenditure on healthcare within Europe exhibit differences in lung cancer survival. Survival in lung cancer was studied in 2001-2004 in England, Norway and Sweden. METHODS Nationwide cancer registries in England, Norway and Sweden were used to identify 250 828 patients with lung cancer from England, 18 386 from Norway and 24 886 from Sweden diagnosed between 1996 and 2004, after exclusion of patients registered through death certificate only or with missing, zero or negative survival times. 5-Year relative survival was calculated by application of the period approach. The excess mortality between the countries was compared using a Poisson regression model. RESULTS In all subcategories of age, sex and follow-up period, the 5-year survival was lower in England than in Norway and Sweden. The age-standardised survival estimates were 6.5%, 9.3% and 11.3% for men and 8.4%, 13.5% and 15.9% for women in the respective countries in 2001-2004. The difference in excess risk of dying between the countries was predominantly confined to the first year of follow-up. The relative excess risk ratio during the first 3 months of follow-up comparing England with Norway 2001-2004 varied between 1.23 and 1.46, depending on sex and age, and between 1.56 and 1.91 comparing England with Sweden. CONCLUSION Access to healthcare and population awareness are likely to be major reasons for the differences, but it cannot be excluded that diagnostic and therapeutic activity play a role. Future improvements in lung cancer management may be seen early in follow-up.
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| 5. |
- Kappert, Kai, et al.
(författare)
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Antioxidants relieve phosphatase inhibition and reduce PDGF signaling in cultured VSMCs and in restenosis
- 2006
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 26:12, s. 2644-2651
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Tidskriftsartikel (refereegranskat)abstract
- Objective - Growth factor- and reactive oxygen species (ROS)-induced activation of VSMCs is involved in vascular disease. This study investigates whether inhibitory oxidation of protein tyrosine phosphatases (PTPs) contributes to signaling in VSMCs in vitro and in vivo, and analyzes whether ROS- and growth factor-dependent vascular smooth muscle cell (VSMC) signaling is blunted by antioxidants that are able to activate oxidized PTPs. Methods and Results - Signaling induced by H2O2 and platelet-derived growth factor (PDGF) was analyzed in VSMCs with or without the antioxidants N-acetyl-cysteine (NAC) and tempol. Effects of antioxidants on PDGF-stimulated chemotaxis and proliferation were determined. In vivo effects of antioxidants were analyzed in the rat carotid balloon-injury model, by analyzing neointima formation, cell proliferation, PDGF beta-receptor status, and PTP expression and activity. NAC treatment prevented H2O2-induced PTP inhibition, and reduced H2O2-and ligand-induced PDGF beta-receptor phosphorylation, PDGF-induced proliferation, and chemotaxis of VSMCs. Antioxidants inhibited neointima formation and reduced PDGF receptor phosphorylation in the neointima and also increased PTP activity. Conclusion - PTP-inhibition was identified as an intrinsic component of H2O2-and PDGF-induced signaling in cultured VSMCs. The reduction in PDGF beta-receptor phosphorylation in vivo, and the increase in PTP activity, by antioxidants indicate activation of oxidized PTPs as a previously unrecognized mechanism for the antirestenotic effects of antioxidants. The findings thus suggest, in general terms, reactivation of oxidized PTPs as a novel antirestenotic strategy.
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| 6. |
- Karlsson, Susann, et al.
(författare)
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Loss of T-Cell Protein Tyrosine Phosphatase Induces Recycling of the Platelet-derived Growth Factor (PDGF) beta-Receptor but Not the PDGF {alpha}-Receptor
- 2006
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 17:11, s. 4846-4855
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Tidskriftsartikel (refereegranskat)abstract
- We have previously shown that the T-cell protein tyrosine phosphatase (TC-PTP) dephosphorylates the platelet-derived growth factor (PDGF) beta-receptor. Here, we show that the increased PDGF beta-receptor phosphorylation in TC-PTP knockout (ko) mouse embryonic fibroblasts (MEFs) occurs primarily on the cell surface. The increased phosphorylation is accompanied by a TC-PTP-dependent, monensin-sensitive delay in clearance of cell surface PDGF beta-receptors and delayed receptor degradation, suggesting PDGF beta-receptor recycling. Recycled receptors could also be directly detected on the cell surface of TC-PTP ko MEFs. The effect of TC-PTP depletion was specific for the PDGF beta-receptor, because PDGF alpha-receptor homodimers were cleared from the cell surface at the same rate in TC-PTP ko MEFs as in wild-type MEFs. Interestingly, PDGF alphabeta-receptor heterodimers were recycling. Analysis by confocal microscopy revealed that, in TC-PTP ko MEFs, activated PDGF beta-receptors colocalized with Rab4a, a marker for rapid recycling. In accordance with this, transient expression of a dominant-negative Rab4a construct increased the rate of clearance of cell surface receptors on TC-PTP ko MEFs. Thus, loss of TC-PTP specifically redirects the PDGF beta-receptor toward rapid recycling, which is the first evidence of differential trafficking of PDGF receptor family members.
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| 7. |
- Littmarck, Sofia, 1983-
(författare)
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Barn, föräldrar, välfärdsstat : Den politiska debatten om föräldrautbildning och föräldrastöd 1964-2009
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The political debate concerning parent education and parenting support between 1964 and 2009 has been scrutinized in this study in the light of the development of and changes in the welfare state. The investigation is based upon the analysis of official government inquiries and parliamentary papers dealing with parent education and parenting support. This study analyzes the different choices in the organization of welfare relevant to children and the family for which political actors have argued, and it examines the views on the relations between children, parents, family and the welfare state that were expressed in the argumentation. Parent education and parenting support aim at changing the living conditions of children by means of the parents. The study shows that the interest in this type of investment has been shared by both the political left and center-right, but from different arguments and political visions on how welfare for children and families with children should be organized, as well as from different views of the role of parent education and parenting support in the welfare.
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| 8. |
- Möller, Henrik, et al.
(författare)
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Breast cancer survival in England, Norway and Sweden : a population-based comparison
- 2010
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 127:11, s. 2630-2638
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Tidskriftsartikel (refereegranskat)abstract
- Several international studies have found that survival from breast cancer is lower in the United Kingdom than in some other European countries. We have compared breast cancer survival between the national populations of England, Norway and Sweden, with a view to identifying subsets of patients with particularly good or adverse survival outcomes. We extracted cases of breast cancer in women diagnosed 1996-2004 from the national cancer registries of the 3 countries. The study comprised 303,657 English cases, 24,919 Norwegian cases and 57,512 cases from Sweden. Follow-up was in 2001-2004. The main outcome measures were 5-year cumulative relative survival and excess death rates, stratified by age and period of follow-up. In comparison with Norway and Sweden, the excess mortality in England was particularly pronounced in the first month and in the first year after diagnosis, and generally more marked in the oldest age groups. Compared with Norwegian patients, 81% of the excess deaths in the English patients occurred in the first 2 years after diagnosis. Our findings emphasise the importance of awareness of symptoms and early detection as the main strategy to improve breast cancer survival in the United Kingdom.
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| 9. |
- Pettersson, Åsa
(författare)
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TV FOR CHILDREN : How the Swedish Public Service Television Imagines a Child Audience
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The study explores how the Swedish public service TV institution imagines a child audience in a societal context where the broadcasting landscape hastransformed greatly over the past thirty years and where TV is seen to constitute both risks and benefits for children. The concept of TV for children is established to broaden the scope for studying what has been broadcast for a child audience on public service TV. The empirical material consists of both broadcasting policy documents and an extensive selection of public service TV programmes targeting children, selected from 1980, 1992 and 2007, which marked before, during and after the abolishment of the Swedish public service broadcasting monopoly. The policy texts, as well as TV content, TV talk and TV visuality, have been studied to investigate how the imagined child audience is configured. The study shows that when the category ‘children’ is mentioned in the broadcasting legislation, they are seen foremost as being at risk of being harmed by commercial messages and only gradually as explicitly entitled to TV programme content meant for them. The broadcasting companies, however, have broadcast programming for the child audience during the whole research period. Adult notions form how children are represented. In the TV programmes, these notions have remained largely unchanged over the studied years, even if technology, legislative demands and approaches to narration also provide opportunities for change. The imagined child TV audience configured in TV for children is knowledgeable, but wanting and in need of more knowledge. This audience is also imagined as being close to nature, eager to interact with the programmes and activate on basically all occasions, which opposes the discursive view according to which children are passivized by television. This study of public service TV for children points to and questions discursive ideas about what it means to be a child in a mediated society.
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| 10. |
- Sandin, Åsa
(författare)
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PTPs : redox controlled regulators of cell signaling and transformation
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Protein tyrosine phosphatases (PTPs) are important redox regulated enzymes that control the tyrosine phosphorylation status in the cell. These studies aimed to increase the understanding on how PTPs are controlled by reversible oxidation in different pathological settings such as hypoxia and restenosis and to which extent oxidized PTPs contribute to certain diseases. Low levels of oxygen - hypoxia - can occur in tumors due to poor vascularization as well as in myocardial infarction and is associated with increased levels of reactive oxygen species (ROS). In our study we found that hypoxia followed by reoxygenation caused reversible oxidation of PTPs. This created an increased amount of inactivated PTPs and was followed by prolonged PDGF receptor activation. The hypoxia induced increase in phosphorylation lead to elevated ERK signaling as well as increased formation of cytoskeletal re-arrangements which could be inhibited by addition of the antioxidant N-acetylcysteine. Decreased phosphatase activity was also seen when analyzed in heart tissues from an ex-vivo model of rat heart exposed to ischemia-reperfusion. Atherosclerosis is a disease characterized by artery wall thickening due to a buildup of fatty materials. A common treatment is to open up the vessel with a balloon catheter and thereby increase the blood flow. A problem with this treatment is that restenosis occur after some time. Restenosis is associated with an elevated ROS production and increase in PDGFβ-receptor signaling. Using a rabbit restenosis model we could show that restenosis could be attenuated by administration of antioxidants. Tissue analysis from vessels in combination with cell culture experiments showed that the beneficial effect of antioxidant treatment was prevention of PTP inactivation. Peroxidized lipids have been found in increased amounts in several diseases with inflammatory components, like atherosclerosis and diabetes. The amounts of peroxidized lipids are tightly regulated by the glutathione peroxidase 4 (GPx4). In an inducible knock out model of GPx4 in cells we found that the rapid accumulation of peroxidized lipids caused PTP oxidation and lead to increased cell signaling. This was the first time peroxidized lipids were shown to oxidize and inactivate PTPs. PTPs are often regarded as inhibitors of cell signaling and therefore as potential tumor suppressors. SHP-2 is however, an exception and is a bona fida oncogene in which phosphatase-activating mutations have been associated with different forms of leukemia and to a smaller proportion with solid tumors. We found that PDGF-BB dependent growth of subcutaneous tumors was compromised when SHP-2 levels were repressed by shRNA. Cell culture experiments indicated that compromised Src activity and reduced ERK activation underlie the inability of these cells to form tumors.
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