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2.
  • Engelmark, Malin T., et al. (författare)
  • Identification of susceptibility loci for cervical carcinoma by genome scan of affected sib-pairs
  • 2006
  • Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 15:22, s. 3351-3360
  • Tidskriftsartikel (refereegranskat)abstract
    • Cervical cancer is caused by a combination of environmental and genetic risk factors. Infection by oncogenic types of human papillomavirus is recognized as the major environmental risk factor and epidemiological studies indicate that host genetic factors predispose to disease development. A number of genetic susceptibility factors have been proposed, but with exception of the human leukocyte antigen CHLA, class II, have not shown consistent results among studies. We have performed the first genomewide linkage scan using 278 affected sib-pairs to identify loci involved in susceptibility to cervical cancer. A two-step qualitative non-parametric linkage analysis using 387 microsatellites with an average spacing of 10.5 cM revealed excess allelic sharing at nine regions on eight chromosomes. These regions were further analysed with 125 markers to increase the map density to 1.28 cM. Nominal significant linkage was found for three of the nine loci [9q32 (maximum lod-score, MLS) =1.95, P < 0.002), 12q24 (MLS=1.25, P < 0.015) and 16q24 (MLS=1.35, P < 0.012)]. These three regions have previously been connected to human cancers that share characteristics with cervical carcinoma, such as esophageal cancer and Hodgkin's lymphoma. A number of candidate genes involved in defence against viral infections, immune response and tumour suppression are found in these regions. One such gene is the thymic stromal co-transporter (TSCOT). Analyses of TSCOT single nucleotide polymorphisms further strengthen the linkage to this region (MLS=2.40, P < 0.001). We propose that the 9q32 region contains susceptibility locus for cervical cancer and that TSCOT is a candidate gene potentially involved in the genetic predisposition to this disease.
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  • Magnusson, Lennart, 1959, et al. (författare)
  • A prospective, randomized, clinical and radiographic study after arthroscopic Bankart reconstruction using 2 different types of absorbable tacks
  • 2006
  • Ingår i: Arthroscopy. - 1526-3231. ; 22:2, s. 143-51
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The aim of the study was to compare the clinical and radiographic results after arthroscopic Bankart reconstruction using 2 different types of absorbable implant. TYPE OF STUDY: Randomized controlled trial. METHODS: A randomized series of 40 patients who had recurrent, unidirectional, post-traumatic shoulder instability were included in the study. All patients underwent an arthroscopic Bankart reconstruction involving either polygluconate co-polymer (PGACP group, n = 20) or self-reinforced poly-L-lactic acid polymer (PLLA group, n = 20) tack implants. The patients underwent clinical and radiographic assessments preoperatively and at 2 years. Additional radiographic assessments were performed at 6 months. RESULTS: Preoperatively, the study groups were comparable in terms of demographics as well as clinical parameters. One patient in each group had a redislocation (5%) during the follow-up period of 2 years. No subluxations were registered. No statistically significant differences were found between the study groups in terms of strength in abduction, range of motion, and Rowe or Constant scores. There was a significant increase in degenerative changes during the follow-up period in both study groups (P = .004). However, no significant differences in degenerative changes were registered between the study groups either preoperatively or at the 2-year follow-up. There were no significant differences in the radiographic visibility of the drill holes used for the absorbable implants between the study groups at the 6-month assessment. However, at the 2-year assessment, the radiographic visibility of the drill holes was significantly greater (P = .004) in the patients in the PLLA group than those in the PGACP group. At the 2-year assessment, no correlation was found between the appearance of the drill holes and the degenerative findings (PGACP group, rho = 0.44; PLLA group, rho = 0.42). CONCLUSIONS: Two years after arthroscopic Bankart reconstruction using either PGA polymer or PLA polymer implants, the overall clinical results were comparable. Radiographic assessments revealed that the degenerative changes increased in both study groups during the follow-up period. Furthermore, the visibility of the drill holes on the 2-year radiographs was greater after using PLLA implants than after using PGACP implants. LEVEL OF EVIDENCE: Level I.
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5.
  • Magnusson, Lennart, 1959, et al. (författare)
  • Absorbable implants for open shoulder stabilization. A 7-8-year clinical and radiographic follow-up
  • 2006
  • Ingår i: Knee Surg Sports Traumatol Arthrosc. - 0942-2056. ; 14:2, s. 182-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Eighteen consecutive patients who had recurrent, unidirectional, post-traumatic shoulder instability were included. All these patients underwent surgery using an open Bankart technique involving absorbable suture anchors. The median age at the index operation was 27 (16-50) years. One subluxation and two re-dislocations occurred during the follow-up period of 90 (80-95) months. At the 90-month control, the Rowe and Constant scores were 94 (63-100) points and 88.5 (65-100) points, respectively. The strength measurements on the index side in 90 degrees abduction revealed 8.1 (3.7-17.2) kg compared with 7.6 (2.7-17.6) kg on the contra lateral side (n.s.). The external rotation in abduction was 80 (60-95) degrees compared with 100 (70-120) degrees for the contra lateral side (p = 0.0015). Signs of minor or moderate degeneration were found in five of 18 patients (28%) on the preoperative radiographs. There was a significant continuous increase in degenerative changes during the follow-up period as seen on the seven, 33 and 90-month radiographs (p = 0.01, 0.03 and 0.01, respectively). On the 90-month radiographs, 12 of 18 patients (67%) had minor, moderate or severe degenerative changes (p = 0.0004 preoperative vs. 90 months). On the 7-month radiographs, two of 18 patients (11%) had invisible or hardly visible drill holes in conjunction with the absorbable implants. On the 90-month radiographs, 12 of 18 patients (67%) had invisible or hardly visible drill holes (p = 0.003 7 months vs. 90 months). In the long term, the method resulted in stable, well-functioning shoulders in 15 of 18 patients (83%). The stabilisation was not, however, able to prevent further increases in radiographic degenerative changes during the 7-8-year follow-up. The drill holes used for the absorbable suture anchors appeared to heal in the majority of patients during the follow-up period.
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6.
  • Magnusson, S., et al. (författare)
  • Expression of carbohydrate xenoantigens on porcine peripheral nerve
  • 2005
  • Ingår i: Xenotransplantation. - : Wiley. - 0908-665X .- 1399-3089. ; 12:1, s. 49-58
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The use of thin easily revascularized cutaneous nerve autografts, which has been the gold standard, or the alternative use of nerve allografts or artificial grafts for nerve reconstructing have all their pros and cons. Nerve xenotransplantation may offer a potential alternative. In a potential pig to human nerve xenograft transplantation set-up several porcine antigen barriers have to be considered such as carbohydrate antigens system like the blood group A/O, the Galalpha1-3Gal (alphaGal) and the Hanganutziu-Deicher (HD) antigens. The swine leukocyte protein antigens system may also have to bee considered. The knowledge of the antigen expression on pig peripheral nerves is today limited. The present study describes the distribution of glycolipid based carbohydrate xenoantigens in ischiadicus nerve from blood group A and O pigs. METHODS: Glycolipid fractions were separated on thin layer chromatography plates and immunostained with human AB sera, biotinylated Griffonia simplicifolia isolectin B4, monoclonal antibodies reacting with the HD antigen and with blood group A antigens based on different core saccharide structures. In addition, the subcellular distribution of alphaGal and HD antigens were studied by light- and electron-microscopical immunohistochemistry. The total amount of neutral glycolipids was 15 mg/g tissue for both blood group A and O nerves with mono-glycosylceramides as the dominating component. RESULTS and CONCLUSIONS: The total amount of acidic glycolipids (gangliosides and sulpholipids) was 9 mg/g tissue for both the blood group O and A nerves with sulphatides as the dominating components. Analyses of the glycolipid fractions showed strong expression of both the alphaGal and the HD antigens in nerves from both blood group A and O pigs. In addition, small amounts of blood group A antigens were expressed in nerves from blood group A pigs. Staining of neutral glycolipids from blood group A pigs using monoclonal antibodies reacting with A antigen having different core structures suggested that the A epitope expressed on pig ischiadicus nerves is based on the type 1 core chain structure. Light and electron microscopical studies on the alphaGal and HD-antigen distribution revealed that the neural cells were alphaGal antigen negative. Endothelial cells of blood vessels, and lymphatic and perineural cells expressed alphaGal antigen. Both endothelial cells and myelinized axons revealed positively labelled for the HD antigen.
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  • Walker, M. D., et al. (författare)
  • Plant community responses to experimental warming across the tundra biome
  • 2006
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 103:5, s. 1342-1346
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent observations of changes in some tundra ecosystems appear to be responses to a warming climate. Several experimental studies have shown that tundra plants and ecosystems can respond strongly to environmental change, including warming; however, most studies were limited to a single location and were of short duration and based on a variety of experimental designs. In addition, comparisons among studies are difficult because a variety of techniques have been used to achieve experimental warming and different measurements have been used to assess responses. We used metaanalysis on plant community measurements from standardized warming experiments at 11 locations across the tundra biome involved in the International Tundra Experiment. The passive warming treatment increased plant-level air temperature by 1-3 degrees C, which is in the range of predicted and observed warming for tundra regions. Responses were rapid and detected in whole plant communities after only two growing seasons. Overall, warming increased height and cover of deciduous shrubs and graminoids, decreased cover of mosses and lichens, and decreased species diversity and evenness. These results predict that warming will cause a decline in biodiversity across a wide variety of tundra, at least in the short term. They also provide rigorous experimental evidence that recently observed increases in shrub cover in many tundra regions are in response to climate warming. These changes have important implications for processes and interactions within tundra ecosystems and between tundra and the atmosphere.
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  • Aulchenko, Yurii S, et al. (författare)
  • Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 41:1, s. 47-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
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10.
  • Babakov, V.N., et al. (författare)
  • RelA/NF-?B transcription factor associates with a-actinin-4
  • 2008
  • Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 314:5, s. 1030-1038
  • Tidskriftsartikel (refereegranskat)abstract
    • The NF-?B/RelA family of transcription factors regulates inducible transcription of a large number of genes in response to diverse stimuli. Little is known, however, about the location of NF-?B in the cytoplasm and the transport mechanism to the nucleus. We found that NF-?B is associated with the actin-binding protein a-actinin-4. NF-?B and a-actinin-4 co-localized along actin stress fibers and in membrane lamellae in A431 cells. After a 30-min stimulation with EGF or TNF-a, a-actinin-4 and p65 were found in the nucleus. Disruption of cytoskeleton by cytochalasin D prior to treatment with TNF-a led to increase of p65 nuclear translocation. Antibodies to p65 subunit of NF-?B co-immunoprecipitated a-actinin-4 from A431 cell lysates and nuclear extracts, but a-actinin-1 and ß-actin were not found in the precipitates. Affinity chromatography experiments displayed that p65 and p50 subunits of NF-?B can bind to matrix-bound chicken gizzard a-actinin. We suggest that the a-actinin-4 is important for the NF-?B nuclear translocation and its functions inside the nucleus. © 2007 Elsevier Inc. All rights reserved.
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  • Björkman, Henrik, et al. (författare)
  • Split renal function in patients with suspected renal artery stenosis : a comparison between gamma camera renography and two methods of measurements with computed tomography
  • 2006
  • Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 47:1, s. 107-113
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: To validate a method for calculating split renal function from computed tomography (CT) compared with gamma camera renography, and to test a new method for the measurement based on a volume-rendering technique. MATERIAL AND METHODS: Thirty-eight patients, aged 65.7 +/- 11.6 (range 37.8-82.1) years, who had undergone both CT angiography and gamma camera renography for a suspected renal artery stenosis were included in this study. Split renal function was calculated from the CT examinations by measuring area and mean attenuation in the image slices of the kidneys, and also by measuring volume and mean attenuation from a 3D reconstruction of the kidneys. Gamma camera renography with 99mTc-MAG3 with or without captopril enhancement was used as a reference. RESULTS: The 2D CT method had good correlation with renography (r=0.93). Mean difference was 4.7 +/- 3.6 (0-12) percentage points per kidney. There was also excellent correlation between the two CT methods (r=1.00). CONCLUSION: CT is equivalent to renography in determining split renal function, and the measurement from the CT examination can be made more quickly and equally accurately with a 3D technique.
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12.
  • Björkqvist, Maria, et al. (författare)
  • A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.
  • 2008
  • Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205, s. 1869-1877
  • Tidskriftsartikel (refereegranskat)abstract
    • Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.
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  • Bolshakova, A., et al. (författare)
  • Extra-cellular matrix proteins induce re-distribution of a-actinin-1 and a-actinin-4 in A431 cells
  • 2007
  • Ingår i: Cell Biology International. - : Wiley. - 1065-6995 .- 1095-8355. ; 31:4 SPEC. ISS., s. 360-365
  • Tidskriftsartikel (refereegranskat)abstract
    • Alpha-actinins are actin-binding proteins of non-muscle cells, which can participate in the regulation of transcription factor activity. We describe the distribution of a-actinin-1 and -4 depending on different actin cytoskeleton formed as a result of cell adhesion to extracellular matrix proteins, such as fibronectin and laminin 2/4. Immunofluorescent studies show a difference in the distribution of a-actinin and -4. Both isoforms localise along stress-fibres, but a-actinin-1 localises in the perinuclear region more abundantly than a-actinin-4. Western blot analysis demonstrated existence of truncated forms of both isoforms. Truncated a-actinin-1 appears in cells spread on fibronectin or laminin. Cell spreading also correlated with more tight association of a-actinin-4 with chromatin. Basing on our previous finding of an interaction of a-actinin-4 with p65 subunit of the NF-?B, we checked the possible influence of immobilised ligands on its redistribution in nuclear complexes containing p65. a-Actinin-4 seems to be present in some but not all nuclear complexes containing p65. Immobilised ligands may affect the interaction of a-actinin-4/p65 complexes with chromatin. The data suggest that adhesion to extra-cellular matrix may interfere in cellular reactions mediated by a-actinin-1 and -4. © 2007 International Federation for Cell Biology.
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  • Dahlander, L., et al. (författare)
  • Relationships between Open Source Software Companies and Communities : Observations from Nordic Firms
  • 2005
  • Ingår i: Research Policy. - : Elsevier BV. - 0048-7333 .- 1873-7625. ; 34:4, s. 481-493
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper deals with the relationships between firms and communities in open source software (OSS). A particular feature of OSS is that important resources are not directly controlled by firms, but partly reside within communities that co-exist with the firms. Despite this, firms explicitly try to utilize the resources within these communities in order to create and appropriate value. Consequently, the relationships that firms have to these communities influence their way of doing business. Based on case studies of Nordic OSS firms, a typology consisting of symbiotic, commensalistic, and parasitic approaches to handle the firm-community relationship is developed. Depending on the chosen approach, firms encounter different managerial issues and also use different operational means of subtle control. While firms relying on a symbiotic approach have greater possibility to influence the community through subtle means of control, they are also confronted with more challenging managerial issues.
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  • Dorkhan, M, et al. (författare)
  • Glycemic and non-glycemic effects of pioglitazone in triple oral therapy in patients with type 2 diabetes mellitus
  • 2006
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 260:2, s. 125-133
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To examine pioglitazone as add-on to metformin and insulin secretagogues in patients with type 2 diabetes and inadequate glycaemic control and its effect on glycaemic control, surrogate measures of insulin sensitivity (adiponectin) and beta-cell function (proinsulin/insulin) and fluid retention.DESIGN AND SETTING: Prospective open-label study of 54 patients with type 2 diabetes and HbA1c>or=6.5% admitted to outpatient unit at Malmö University Hospital. The patients received 30-45 mg pioglitazone daily during 26 weeks in addition to their existing antidiabetic medication. After 26 weeks, one-third of patients were followed for 3 months without pioglitazone.RESULTS: HbA1c decreased (7.8+/-0.9-6.3+/-0.9%, P<0.001) with 61% of patients achieving levels<6.5%. However, in the group followed for another 3 months HbA1c increased (6.1+/-0.73-7.1+/-0.9, n=18, P<0.001) after pioglitazone withdrawal. Adiponectin increased (6.1+/-2.8-13.2+/-5.8 microg mL-1, P<0.001) and the proinsulin to insulin ratio decreased (0.89+/-0.66-0.66+/-0.53, P<0.001). Nt-proBNP increased from 487.3+/-252.2 to 657.8+/-392.1 pmol L-1 (P<0.001).CONCLUSIONS: Pioglitazone is effective in achieving glycaemic targets and reducing risk factors involved in atherosclerosis and improving beta-cell function when used as part of triple oral therapy in patients with type 2 diabetes and secondary drug failure. Nt-proBNP increase with concomitant decrease in haemoglobin suggests a subclinical sign of fluid retention.
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  • Ellison, S L R, et al. (författare)
  • Treatment of uncorrected measurement bias in uncertainty estimation for chemical measurements
  • 2008
  • Ingår i: Anal Bioanl Chem.. ; 390, s. 201-213
  • Tidskriftsartikel (refereegranskat)abstract
    • Consistent treatment of measurement bias, including the question of whether or not to correct for bias, is essential for the comparability of measurement results. The case for correcting for bias is discussed, and it is shown that instances in which bias is known or suspected, but a specific correction cannot be justified, are comparatively common. The ISO Guide to the Expression of Uncertainty in Measurement does not provide well for this situation. It is concluded that there is a need for guidance on handling cases of uncorrected bias. Several different published approaches to the treatment of uncorrected bias and its uncertainty are critically reviewed with regard to coverage probability and simplicity of execution. On the basis of current studies, and taking into account testing laboratory needs for a simple and consistent approach with a symmetric uncertainty interval, we conclude that for most cases with large degrees of freedom, linear addition of a bias term adjusted for exact coverage (“Ue”) as descibed by Synek is to be preferred. This approach does, however, become more complex if degrees of freedom are low. For modest bias and low degrees of freedom, summation of bias, bias uncertainty and observed value uncertainty in quadrature (“RSSu”) provides a similar interval and is simpler to adapt to reduced degrees of freedom, at the cost of a more restricted range of application if accurate coverage is desired.
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18.
  • Gomez, S., et al. (författare)
  • Differences between body movement adaptation to calf and neck muscle vibratory proprioceptive stimulation
  • 2009
  • Ingår i: Gait & Posture. - : Elsevier BV. - 1879-2219 .- 0966-6362. ; 30:1, s. 93-99
  • Tidskriftsartikel (refereegranskat)abstract
    • Adaptation is essential in maintaining stability during balance-challenging situations. We studied, ill standing subjects with eyes open and closed, adaptive responses of the anteroposterior head, shoulder, hip and knee movements: gastrocnemius and tibialis anterior EMG activity and anteroposterior body Posture when proprioceptive information from the neck or calf muscles underwent vibratory perturbations. After 30 s of quiet stance, vibratory stimuli were applied repeatedly for 200 s, and adaption to stimulation was analyzed in four successive 50 s periods. Repeated neck and calf vibration significantly increased linear body movement variance at all recorded sites (p < 0.001, except neck stimulation with eyes closed, EC-neck), increased tibialis anterior (p < 0.001, except EC-neck) and gastrocnemious muscle activity (p < 0.001). Most body movement variances and tibialis anterior EMG activity decreased significantly over time (most p-values < 0.01 or lower) and overall, the body leaning forward increased from 5.5 degrees to 6.5 degrees (p < 0.01). The characteristics of the responses were influenced by vision and site of vibration, e.g., neck vibration affected body Posture more rapidly than calf vibration. Our findings support the notion that proprioceptive perturbations have different effects in terms of nature, degree and adaptive response depending on site of vibratory proprioceptive stimulation, a factor that needs consideration in clinical investigations and design of rehabilitation programs. (C) 2009 Elsevier B.V. All rights reserved.
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19.
  • Grdic, D, et al. (författare)
  • Splenic marginal zone dendritic cells mediate the cholera toxin adjuvant effect : Dependence on the ADP-ribosyltransferase activity of the holotoxin
  • 2005
  • Ingår i: Journal of Immunology. - 0022-1767 .- 1550-6606. ; 175:8, s. 5192-5202
  • Tidskriftsartikel (refereegranskat)abstract
    • The in vivo mechanisms of action of most vaccine adjuvants are poorly understood. In this study, we present data in mice that reveal a series of critical interactions between the cholera toxin (CT) adjuvant and the dendritic cells (DC) of the splenic marginal zone (MZ) that lead to effective priming of an immune response. For the first time, we have followed adjuvant targeting of MZ DC in vivo. We used CT-conjugated OVA and found that the Ag selectively accumulated in MZ DC following i.v. injections. The uptake of Ag into DC was GM1 ganglioside receptor dependent and mediated by the B subunit of CT (CTB). The targeted MZ DC were quite unique in their phenotype: CD11c(+), CD8 alpha(-), CD11b(-), B220(-), and expressing intermediate or low levels of MHC class II and DEC205. Whereas CTB only delivered the Ag to MZ DC, the ADP-ribosyltransferase activity of CT was required for the maturation and migration of DC to the T cell zone, where these cells distinctly up-regulated CD86, but not CD80. This interaction appeared to instruct Ag-specific CD4(+) T cells to move into the B cell follicle and strongly support germinal center formations. These events may explain why CT-conjugated Ag is substantially more immunogenic than Ag admixed with soluble CT and why CTB-conjugated Ag can tolerize immune responses when given orally or at other mucosal sites.
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21.
  • Hanson, E, et al. (författare)
  • Working together with persons with early stage dementia and their family members to design a user-friendly technology based support service
  • 2007
  • Ingår i: Dementia. - : Sage Publications Ltd.. - 1471-3012 .- 1741-2684. ; 6:3, s. 411-434
  • Tidskriftsartikel (refereegranskat)abstract
    • This article describes how researchers, practitioners and technicians in West Sweden worked together with older people with early stage dementia and their family members to develop a user-friendly technology-based information, education and support service, based on the generic ACTION participatory design model. Ways of working in partnership with older people with early stage dementia and their family members are explored, and key lessons learned are highlighted. The overriding message is that elders with early stage dementia can be actively involved throughout the entire research and development process. Essential prerequisites are time and ongoing support by skilled practitioners and family members. Preliminary findings reveal that older people with early stage dementia can learn and benefit from user-friendly technology, especially when used together with others in a similar situation.
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22.
  • Hansson, J, et al. (författare)
  • Use of snus and risk for cardiovascular disease : results from the Swedish Twin Registry
  • 2009
  • Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 265:6, s. 717-724
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVETo study the association between snus use and the risk for cardiovascular disease, i.e. ischemic heart disease and stroke. DESIGNCohort study. SETTINGSweden. SUBJECTSSixteen thousand six hundred and forty-two male Swedish twins participating in the Screening Across the Lifespan Twin Study, conducted in 1998- 2002, were followed for incident cardiovascular disease. Participants were without a history of cardiovascular disease at baseline and incident cases were identified via the Swedish Cause of Death Register and Hospital Discharge Register.RESULTSOverall, there was no association between use of snus and risk for cardiovascular disease. Current snus users, without a smoking history, had a relative risk of 1.00 (95% confidence interval 0.69-1.46) for cardiovascular disease as compared to non users. Corresponding relative risks for ischemic heart disease and stroke were 0.85 (95% confidence interval 0.51-1.41) and 1.18 (95% confidence interval 0.67-2.08), respectively. In smoking adjusted models, risk estimates for ischemic heart disease in relation to snus use were all close to unity regardless of timing or intensity of snus use. However, current heavy snus users (consuming more than four cans week(-1)) had a relative risk for stroke of 1.75 (95% confidence interval 0.95-3.21). CONCLUSIONThese data do not support any strong association between snus use and risk for cardiovascular disease.
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23.
  • Helgadottir, Anna, et al. (författare)
  • The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
  • 2008
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
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24.
  • Islam, Quamrul, 1952-, et al. (författare)
  • Functional characterization of cell hybrids generated by induced fusion of primary porcine mesenchymal stem cells with an immortal murine cell line
  • 2006
  • Ingår i: Cell and Tissue Research. - : Springer Science and Business Media LLC. - 0302-766X .- 1432-0878. ; 326:1, s. 123-137
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone marrow mesenchymal stem cells (MSC) integrate into various organs and contribute to the regeneration of diverse tissues. However, the mechanistic basis of the plasticity of MSC is not fully understood. The change of cell fate has been suggested to occur through cell fusion. We have generated hybrid cell lines by polyethylene-glycol-mediated cell fusion of primary porcine MSC with the immortal murine fibroblast cell line F7, a derivative of the GM05267 cell line. The hybrid cell lines display fibroblastic morphology and proliferate like immortal cells. They contain tetraploid to hexaploid porcine chromosomes accompanied by hypo-diploid murine chromosomes. Interestingly, many hybrid cell lines also express high levels of tissue-nonspecific alkaline phosphatase, which is considered to be a marker of undifferentiated embryonic stem cells. All tested hybrid cell lines retain osteogenic differentiation, a few of them also retain adipogenic potential, but none retain chondrogenic differentiation. Conditioned media from hybrid cells enhance the proliferation of both early-passage and late-passage porcine MSC, indicating that the hybrid cells secrete diffusible growth stimulatory factors. Murine F7 cells thus have the unique property of generating immortal cell hybrids containing unusually high numbers of chromosomes derived from normal cells. These hybrid cells can be employed in various studies to improve our understanding of regenerative biology. This is the first report, to our knowledge, describing the generation of experimentally induced cell hybrids by using normal primary MSC. © Springer-Verlag 2006.
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25.
  • Islam, Quamrul, 1952-, et al. (författare)
  • Polyethylene glycol-mediated fusion between primary mouse mesenchymal stem cells and mouse fibroblasts generates hybrid cells with increased proliferation and altered differentiation
  • 2006
  • Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1547-3287 .- 1557-8534. ; 15:6, s. 905-919
  • Tidskriftsartikel (refereegranskat)abstract
    • Bone marrow-derived mesenchymal stem cells (MSCs) can differentiate into different cell lineages with the appropriate stimulation in vitro. Transplantation of MSCs in human and other animal models was found to repair tissues through the fusion of transplanted MSCs with indigenous cells. We have generated mouse-mouse hybrid cell lines in vitro by polyethylene glycol-mediated fusion of primary mouse MSCs with mouse fibroblasts to investigate the characteristics of hybrid cells, including their potentials for proliferation and differentiation. Similar to the parental MSCs, hybrid cells are positive for the cell-surface markers CD29, CD44, CD49e, and Sca-1, aed negative for Gr1, CD11b, CD13, CD18, CD31, CD43, CD45, CD49d, CD90.2, CD445M/B220, and CD117 markers. The hybrid cells also produce a high level of tissue nonspecific alkaline phosphatase compared to the parental cells. Conditioned medium of hybrid cells contain biologically active factors that are capable of stimulating proliferation of other cells. Although the parental MSCs can differentiate into adipogenic and osteogenic lineages, hybrid cells held disparate differentiation capacity. Hybrid cell lines in general have increased proliferative capacity than the primary MSCs. Our study demonstrates that proliferative hybrid cell lines can be generated in vitro by induced fusion of both im-mortal and primary somatic cells with primary MSCs. © Mary Ann Liebert, Inc.
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26.
  • Ivansson, Emma L, et al. (författare)
  • Temporal trends over 3 decades and intrafamilial clustering of HPV types in Swedish patients with cervical cancer in situ
  • 2009
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:12, s. 2930-2935
  • Tidskriftsartikel (refereegranskat)abstract
    • Information on HPV type distribution in cervical cancer in situ in different populations is needed for evaluation of prophylactic vaccination programs targeting HPV 16 and 18. In our study, the HPV type prevalence in 1,079 Swedish women from multicase families diagnosed with cervical cancer in situ 1965-1993 was investigated using real-time PCR and archival tissue material. HPV type information was obtained for 974 samples. Among these, HPV 16 (61%) was the dominant type followed by HPV 33/52/58 (24%), HPV 31 (13%) and HPV 18/45 (12%). The detected prevalence of HPV 16 among cancer in situ decreased by 13% over the study period while the group of low frequency high-risk types increased. Related women were not prone to infection by the same type. These data suggest that the prevalence of individual HPV types has changed over time in Swedish patients with cervical cancer in situ. Large-scale studies of pathology biobank materials will enable further insight into the temporal changes of individual HPV types, as baseline information to properly evaluate the effect of vaccine programs. The findings also indicate that genetic susceptibility to cervical cancer operates through general and not type specific susceptibility to HPV infection.
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27.
  • Johansson, Åsa, et al. (författare)
  • Endothelial cell signalling supports pancreatic beta cellfunction in the rat
  • 2009
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 52:11, s. 2385-2394
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis The proximity of endothelial cells andbeta cells in islets by necessity means that they are exposedto each other’s products. Whereas islet endothelial cellsrequire signals from beta cells to function properly,endothelin-1, thrombospondin-1 and laminins, amongothers, have been identified as endothelial-derived molecules,although their full effects on beta cells have not beenexplored. We tested the hypothesis that islet endothelialderivedproducts affect beta cell function.Methods Endothelial cells from rat islets were proliferatedand purified. Endothelium-conditioned culture medium(ECCM) was obtained by maintaining the endothelial cellsin culture medium. Islet function was evaluated followingexposure of cultured islets to standard culture medium orECCM. Changes in mRNA levels for key beta cellmetabolic enzymes were also measured in islets afterECCM exposure.Results Glucose-stimulated insulin release and islet insulincontent were markedly enhanced by exposure to ECCM.This was at least partly explained by improved mitochondrialfunction, as assessed by glucose oxidation and anupregulation of the mitochondrial gene for glycerol-3-phosphate dehydrogenase (mGpdh [also known as Gpd2]),combined with upregulation of the rate-limiting enzyme inthe glycolysis, glucokinase, in the islets. The intracellulardegradation of insulin was also decreased in the islets. Isletendothelial cells produced laminins, and the positive effectsof islet endothelial cells were prevented by addition of aneutralising antibody to the β1-chain of laminin. Additionof exogenous laminin stimulated islet function.Conclusions/interpretation This study provides proof ofprinciple that endothelial cells can affect the function of betacells in their vicinity and that this is at least partially mediatedby laminins.
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28.
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29.
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30.
  • Khotin, M.G., et al. (författare)
  • Analysis of nuclear protein complexes comprising a-actinin-4 by 2D-electrophoresis and mass-spectrometry
  • 2009
  • Ingår i: Tsitologiya. - : SP MAIK Nauka/Interperiodica. - 0041-3771. ; 51:8, s. 684-690
  • Tidskriftsartikel (refereegranskat)abstract
    • Actin-binding protein a-actinin-4 is a member of spectrin super family. It is located in the cytoplasm and in the nucleus. However, nuclear functions of a-actinin-4 are still not clear. In this study, we analyzed composition of nuclear protein complexes associated with a-actinin-4 in A431 cells. Using 2D electrophoresis, we have determined that about 50 different proteins may be associated with nuclear a-actinin-4. Using mass-spectrometry, we analyzed major proteins of these complexes. ß-Actin, a- and ß-tubulins, ribonucleoprotein A2/B1, which regulates splicing and is associated with ß-actin, peroxiredoxin-1, which is involved in oxidative stress, and glycolytic enzyme D-3-phosphoglycerate dehydrogenase were identified by MALDI-TOF. Detection of these proteins in nuclear complexes with a-actinin-4 may suggest that a-actinin-4 is involved in transcription and splicing. Presence of a-actin in the investigated complexes was confirmed by tandem mass-spectrometry (MALDITOF-TOF). Immunoprecipitation of nuclear proteins with antibodies against a-tubulin confirmed association of a-actinin-4 with a-tubulin in the protein complex. Nuclear a-actinin-4 constitutes of 105 KDa fullsize isoform and two truncated isoforms of 65 and 75 kDa, whereas only the truncated isoform have been found in nuclear complexes with a-tubulin. These data suggest that a-actinin-4 is associated with a number of different nuclear protein complexes which may carry out different functions in the cell nucleus.
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31.
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32.
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33.
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34.
  • Laxdal, Gauti, 1966, et al. (författare)
  • Outcome and risk factors after anterior cruciate ligament reconstruction: a follow-up study of 948 patients
  • 2005
  • Ingår i: Arthroscopy. - : Elsevier BV. - 1526-3231. ; 21:8, s. 958-964
  • Tidskriftsartikel (refereegranskat)abstract
    • PURPOSE: The aim of the study was to assess the outcome and risk factors after anterior cruciate ligament (ACL) reconstruction in a large group of patients. TYPE OF STUDY: Case series. METHODS: Included in this retrospective study were 948 patients (323 female, 625 male) with a symptomatic unilateral ACL rupture, who underwent arthroscopic reconstruction using patellar tendon autograft and interference screw fixation at 3 Swedish hospitals. The median age of the patients at the time of the index operation was 26 years (range, 14 to 53 years). The patients underwent surgery at a median of 12 months (range, 0.5 to 360 months) after their injury. Independent physiotherapists performed the follow-up examinations at a median of 32 months (range, 21 to 117 months) postoperatively. RESULTS: Of the 948 patients, 550 (58%) underwent meniscal surgery before, during, or after the ACL reconstruction. The median Tegner activity level was 8 (range, 2-10) before injury, 3 (range, 0-9) preoperatively, and 6 (range, 1-10) at follow-up (P < .0001 preoperative v follow-up). At follow-up, the median Lysholm score was 90 points (range, 14-100), the median KT-1000 anterior side-to-side laxity difference was 1.5 mm (range, -6 to 13 mm), and the median 1-leg hop test quotient was 95% (0% to 167%) compared with the contralateral normal side. At follow-up, 69.3% of the patients were classified as normal or nearly normal according to the International Knee Documentation Committee evaluation system. However, 36% of the patients were unable to or had severe problems performing the knee-walking test. Inferior results correlated with increased time period between the index injury and reconstruction and concomitant joint damage found at the index operation. CONCLUSIONS: Overall, the results were good after ACL reconstruction using patellar tendon autograft and interference screw fixation. Concomitant joint damage and a long time period between the injury and reconstruction are major risk factors for inferior outcome after ACL reconstruction. LEVEL OF EVIDENCE: Level IV, case series.
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35.
  • Ljungvall, K, et al. (författare)
  • Delayed effects on plasma concentration of testosterone and testicular morphology by intramuscular low-dose di(2-ethylhexyl)phthalate or oestradiol benzoate in the prepubertal boar
  • 2005
  • Ingår i: Theriogenology. - : Elsevier. - 0093-691X .- 1879-3231. ; 64:5, s. 1170-1184
  • Tidskriftsartikel (refereegranskat)abstract
    • The immediate and delayed effects of prepubertal exposure to di(2-ethylhexyl)phthalate (DERP) or oestradiol benzoate on the plasma concentrations of testosterone, oestradiol and LH, as well as testicular morphology were examined in prepubertal boars. In a split litter design experiment, prepubertal boars were intramuscularly exposed to DEHP, oestradiol or vehicle during five weeks, starting at six weeks of age. The dose of DEHP was 50 mg/kg of bodyweight twice weekly, which is in the same range as recently used oral doses in rodents. Oestradiol-benzoate was administered at 0.25 mg/kg of bodyweight twice weekly. One set of animals was examined immediately after the exposure, and the other set was examined at an age of 7.5 months. During the exposure period concentrations of LH in plasma were lower (p = 0.02) in the oestradiol-treated animals than in the control group. In the group exposed to oestradiol, the relative to the body weight of the testicles tended to be lower (p = 0.07) than control immediately after five weeks of exposure, and the relative to the body weight of the seminal vesicles tended to be lower (p = 0.05) than control at 7.5 months of age. In the DEHP-exposed group an elevated (p = 0.005) concentration of testosterone and increased (p = 0.04) area of the Leydig cells in the testicles compared to the control group were seen at 7.5 months of age. These data suggest that DEHP early in life causes delayed effects on the reproductive system in the adult. (c) 2005 Elsevier Inc. All rights reserved.
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36.
  • Ljungvall, K, et al. (författare)
  • Early post-natal exposure to low dose oral di(2ethylhexyl) phthalate affects the peripheral LH-concentration in plasma, but does not affect mating behavior in the post-pubertal boar
  • 2006
  • Ingår i: Reproductive Toxicology. - : Elsevier. - 0890-6238 .- 1873-1708. ; 21:2, s. 160-166
  • Tidskriftsartikel (refereegranskat)abstract
    • In a split-litter design experiment, boars were exposed orally three times weekly to 300 mg/kg of di(2-ethylhexyl) phthalate (DEHP) between 3 and 7 weeks of age. Post-puberty, i.e. at 6 months of age the effects on endocrinology and mating behavior were examined. The response to stimulation with a synthetic GnRH-analogue at 9 months of age resulted initially in lower concentration of LH in the exposed animals, compared to the control animals. We did not find any effects of DEHP on the mating behavior. Also, the effects of DEHP during the treatment period on the plasma concentrations of testosterone, oestradiol and LH were examined. During the exposure period there was a transient decrease in plasma concentrations of LH in the control group, which did not occur in the boars exposed to DEHR The data suggest that DEHP in low repeated oral doses causes lasting effects on the hypothalamus-pituitary-gonadal axis. (c) 2005 Elsevier Inc. All rights reserved.
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37.
  • Lutgendorff, Femke, et al. (författare)
  • Probiotics prevent intestinal barrier dysfunction in acute pancreatitis in rats via induction of ileal mucosal glutathione biosynthesis.
  • 2009
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 4:2, s. e4512-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: During acute pancreatitis (AP), oxidative stress contributes to intestinal barrier failure. We studied actions of multispecies probiotics on barrier dysfunction and oxidative stress in experimental AP. METHODOLOGY/PRINCIPAL FINDINGS: Fifty-three male Spraque-Dawley rats were randomly allocated into five groups: 1) controls, non-operated, 2) sham-operated, 3) AP, 4) AP and probiotics and 5) AP and placebo. AP was induced by intraductal glycodeoxycholate infusion and intravenous cerulein (6 h). Daily probiotics or placebo were administered intragastrically, starting five days prior to AP. After cerulein infusion, ileal mucosa was collected for measurements of E. coli K12 and (51)Cr-EDTA passage in Ussing chambers. Tight junction proteins were investigated by confocal immunofluorescence imaging. Ileal mucosal apoptosis, lipid peroxidation, and glutathione levels were determined and glutamate-cysteine-ligase activity and expression were quantified. AP-induced barrier dysfunction was characterized by epithelial cell apoptosis and alterations of tight junction proteins (i.e. disruption of occludin and claudin-1 and up-regulation of claudin-2) and correlated with lipid peroxidation (r>0.8). Probiotic pre-treatment diminished the AP-induced increase in E. coli passage (probiotics 57.4+/-33.5 vs. placebo 223.7+/-93.7 a.u.; P<0.001), (51)Cr-EDTA flux (16.7+/-10.1 vs. 32.1+/-10.0 cm/s10(-6); P<0.005), apoptosis, lipid peroxidation (0.42+/-0.13 vs. 1.62+/-0.53 pmol MDA/mg protein; P<0.001), and prevented tight junction protein disruption. AP-induced decline in glutathione was not only prevented (14.33+/-1.47 vs. 8.82+/-1.30 nmol/mg protein, P<0.001), but probiotics even increased mucosal glutathione compared with sham rats (14.33+/-1.47 vs. 10.70+/-1.74 nmol/mg protein, P<0.001). Glutamate-cysteine-ligase activity, which is rate-limiting in glutathione biosynthesis, was enhanced in probiotic pre-treated animals (probiotics 2.88+/-1.21 vs. placebo 1.94+/-0.55 nmol/min/mg protein; P<0.05) coinciding with an increase in mRNA expression of glutamate-cysteine-ligase catalytic (GCLc) and modifier (GCLm) subunits. CONCLUSIONS: Probiotic pre-treatment diminished AP-induced intestinal barrier dysfunction and prevented oxidative stress via mechanisms mainly involving mucosal glutathione biosynthesis.
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38.
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39.
  • Magnusson Hanson, Linda L, et al. (författare)
  • Demand, control and social climate as predictors of emotional exhaustion symptoms in working Swedish men and women.
  • 2008
  • Ingår i: Scand J Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 36:7, s. 737-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Demand, control and social climate as predictors of emotional exhaustion symptoms in working Swedish men and women.Magnusson Hanson LL, Theorell T, Oxenstierna G, Hyde M, Westerlund H.Stress Research Institute, Stockholm University, SE-106 91 Stockholm, Sweden. linda.hanson@stressforskning.su.seAIMS: Most studies on burnout have been cross-sectional and focused on specific occupations. In the present study we prospectively investigated the association between demands, control, support and conflicts as well as downsizing and emotional exhaustion in men and women derived from a representative sample of the working population in Sweden. METHODS: The study comprised working men (1,511) and women (1,493), who participated in the Swedish Work Environment Survey (SWES) in 2003 and had no physical exhaustion and prior sick leave at baseline. These participants were followed up in 2006 as part of the Swedish Longitudinal Occupational Survey of Health (SLOSH). Demands, decision authority, support from fellow workers and superiors, conflicts with fellow workers and superiors, and downsizing were utilized as predictors and the Maslach Burnout Inventory subscale of emotional exhaustion as the outcome in multiple logistic regression analyses. RESULTS: High demands were a highly significant predictor of symptoms of emotional exhaustion (>/=75th percentile). Downsizing and lack of support from superiors were also independent predictors for men as well as lack of support from fellow workers and low decision authority for women. CONCLUSIONS: This study indicates that high demands, low decision authority, lack of support at work and downsizing could be important predictors of emotional exhaustion symptoms among working men and women.
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40.
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41.
  • Magnusson, Linda L (författare)
  • Parental exposures and occurence of adverse pregnancy outcomes and childhood atopic diseases
  • 2006
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of this thesis was to investigate whether parental laboratory work is associated with adverse pregnancy outcomes, and if maternal occupation as well as exposure to organic solvents and smoking during pregnancy are associated with atopic diseases in childhood. The studies were based on two different study populations. (1) A Swedish source cohort of female and male biomedical laboratory and non-laboratory university employees, 1970-1989. In order to identify pregnancies, outcomes, and additional data, the males were linked to the multi-generation register and their partners, as well as all female employees, to the Swedish Medical Birth Register. Exposure data was based on employee records and questionnaires, sent to research group leaders, concerning the use of agents and techniques. The final study populations consisted of 3003 female pregnancies and 4190 male pregnancies. (2) A Danish cohort encompassing pregnant mothers from Odense and Aalborg 1984-1987. Information on smoking and occupational job titles was collected during pregnancy, and an assessment of organic solvent exposure was performed by occupational specialists. The children were later followed up by questionnaires to parents, at age 14-18, to retrieve information about health parameters such as atopic diseases during childhood. This resulted in a final study population of 7844 children. Logistic regression analyses did not show any significant associations between female or male laboratory work in general and adverse pregnancy outcomes. However, when analyses were based on specific agents/techniques, maternal organic solvent exposure "periconceptionally" gave an increased odds ratio (OR) of 2.5 and 95% confidence interval (CI) of 1.0-6.0 for major malformations. Maternal work with benzene resulted in increased risk estimates for major malformations, especially neural crest malformations (OR 5.3, Cl 1.4-2 1. 1). An increased OR for neural crest malformations was found for paternal work with carcinogens. Paternal work with radioactive isotopes also showed a slightly increased ratio for high birth weight (OR 1.8, CI 1.0-3.2) and altered male/female sex ratio (relative risk 1.2, CI 1.0-1.4). Maternal smoking in pregnancy was associated with wheezing (OR 1.2, Cl 1.1-1.5), in a dose response pattern. No association was seen with asthma. Shift work was marginally associated with asthma (OR 1.2, CI 1.0-1.5), and there was a tendency towards an increased risk for asthma and hay fever in association with high solvent exposure, with ORs of 2.0 (CI 0.7-6. 1) and 2.6 (CI 1.0-6.9), respectively. Moreover, in an explorative analysis we found elevated risk estimates for a number of occupational groups; e.g. "bakers, pastry cooks, and confectionary makers", dental assistants, "electrical and electronic assemblers", "sewers and embroiders", and "bookbinders and related workers". In conclusion, the results do not suggest an association between parental biomedical laboratory work in general and pregnancy outcomes. However, specific exposures could be of concern for both female and male employees, most notably maternal organic solvent use. The results on maternal smoking in pregnancy supported an association with wheezing. Certain female occupations in pregnancy might also be associated with childhood atopic diseases, and one potential risk factor could be organic solvent exposure.
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42.
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43.
  • Magnusson, Marianne L., et al. (författare)
  • Motor Control Learning in Chronic Low Back Pain
  • 2008
  • Ingår i: Spine. - Hagerstown, Md. : Harper & Row. - 0362-2436 .- 1528-1159. ; 33:16, s. E532-E538
  • Tidskriftsartikel (refereegranskat)abstract
    • Study design: A randomized prospective cohort study of participants with chronic low back pain, seeking physical therapy, with follow-up at weeks 6 and 28. Effects of conventional physiotherapy and physiotherapy with the addition of postural biofeedback were compared.Objective: To evaluate the benefits of postural biofeedback in chronic low back pain participants.Summary of background data: Biofeedback using electromyographic signals has been used in chronic low back pain with mixed results. Postural feedback had not been previously used.Methods: Demographic and psychological baseline data along with range of motion were analyzed from a sample of 47 chronic participants with low back pain randomized into conventional physiotherapy with or without the addition of postural biofeedback.Results: After 6 months, there were 21 dropouts. The participants with biofeedback had markedly improved status in visual analog pain scales, short form FS36, and range of motion.Conclusion: The study strongly suggests that postural feedback is a useful adjunct to conventional physiotherapy of chronic low back pain participants.
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44.
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45.
  • Magnusson, MB, et al. (författare)
  • Misunderstandings in multilingual counselling settings involving school nurses and obese/overweight pupils
  • 2009
  • Ingår i: Communication & Medicine. - 1612-1783 .- 1613-3625. ; 6:2, s. 153-164
  • Tidskriftsartikel (refereegranskat)abstract
    • School nurses' counselling is pivotal in stemming the obesity epidemic. Barriers for good counselling such as nurses' misunderstandings and ambiguities when relating to overweight and obesity need to be addressed. In this study, we explored misunderstandings in school nurses' counselling of overweight pupils in multilingual settings, together with how school nurses talk about the condition. Counselling sessions involving eight nurses and 20 pupils (aged 8-16 years) were audio-recorded and analysed using theme-oriented discourse analysis. Statistical methods were used as a complement. The focal themes were misunderstandings and nurses' talk about overweight and obesity. Analytical themes were framing, footing and facework. Data analyses revealed three main origins of misunderstandings occurring in school nurses' counselling of obese and overweight pupils: (1) nurses' illusion that they know what advice the pupils need; (2) nurses' insensitivity to the pupils' and parents' concerns; and (3) lack of lingual understanding. School nurses' apparent difficulties to talk about overweight and obesity suggest a need to reflect on how to name these issues during counselling. School nurses' dominance and pupils'passivity were obvious. We suggest that counselling should be regarded as learning contexts and be subjected to possible quality assurance in the future.
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46.
  • Magnusson, M O, et al. (författare)
  • Pharmacodynamics of carbamazepine-mediated induction of CYP3A4, CYP1A2, and Pgp as assessed by probe substrates midazolam, caffeine, and digoxin
  • 2008
  • Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 84:1, s. 52-62
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to develop a model describing the carbamazepine autoinduction and the carbamazepine-mediated induction of CYP3A4, CYP1A2, and P-glycoprotein. Seven healthy volunteers were dosed with carbamazepine over 16 consecutive days. The CYP3A4, CYP1A2, and P-glycoprotein activities were assessed, using midazolam, caffeine, and digoxin as probe substrates, on 12 occasions, covering the preinduced state and the onset and termination of the induction process. The data were evaluated using a mechanistic pharmacokinetic approach in NONMEM. The induction processes were described using turnover models, with carbamazepine and carbamazepine-10,11-epoxide as the driving force of the induction. The half-lives of CYP3A4 and CYP1A2 were estimated to be 70 and 105 h, respectively. P-glycoprotein was not affected by the carbamazepine treatment. The possibility of modeling the pharmacodynamics of enzyme induction using a turnover model was illustrated, and the time course of the process was estimated with good precision.
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47.
  • Magnusson-Olsson, AnneLiese, et al. (författare)
  • Effect of maternal triglycerides and free fatty acids on placental LPL in cultured primary trophoblast cells and in a case of maternal LPL deficiency.
  • 2007
  • Ingår i: Am J Physiol Endocrinol Metab. ; 293:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Maternal hypertriglyceridemia is a normal condition in late gestation and is an adaptation to ensure an adequate nutrient supply to the fetus. Placental lipoprotein lipase (LPL) is involved in the initial step in transplacental fatty acid transport as it hydrolyzes maternal triglycerides (TG) to release free fatty acids (FFA). We investigated LPL activity and protein (Western blot) and mRNA expression (real-time RT-PCR) in the placenta of an LPL-deficient mother with marked hypertriglyceridemia. The LPL activity was fourfold lower, LPL protein expression 50% lower, and mRNA expression threefold higher than that of normal, healthy placentas at term (n = 4-7). To further investigate the role of maternal lipids in placental LPL regulation, we isolated placental cytotrophoblasts from term placentas and studied LPL activity and protein and mRNA expression after incubation in Intralipid (as a source of TG) and oleic, linoleic, and a combination of oleic, linoleic, and arachidonic acids as well as insulin. Intralipid (40 and 400 mg/dl) decreased LPL activity by approximately 30% (n = 10-14, P < 0.05) and 400 microM linoleic and linoleic-oleic-arachidonic acid (n = 10) decreased LPL activity by 37 and 34%, respectively. No major changes were observed in LPL protein or mRNA expression. We found no effect of insulin on LPL activity or protein expression in the cultured trophoblasts. To conclude, the activity of placental LPL is reduced by high levels of maternal TG and/or FFA. This regulatory mechanism may serve to counteract an excessive delivery of FFA to the fetus in conditions where maternal TG levels are markedly increased.
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48.
  • Magnusson-Olsson, AnneLiese, et al. (författare)
  • Gestational and hormonal regulation of human placental lipoprotein lipase
  • 2006
  • Ingår i: J Lipid Res. ; 47:11, s. 2551-61
  • Tidskriftsartikel (refereegranskat)abstract
    • The fetal demand for FFA increases as gestation proceeds, and LPL represents one potential mechanism for increasing placental lipid transport. We examined LPL activity and protein expression in first trimester and term human placenta. The LPL activity was 3-fold higher in term (n = 7; P < 0.05) compared with first trimester (n = 6) placentas. The LPL expression appeared lower in microvillous membrane from first trimester (n = 2) compared with term (n = 2) placentas. We incubated isolated placental villous fragments with a variety of effectors [GW 1929, estradiol, insulin, cortisol, epinephrine, insulin-like growth factor-1 (IGF-1), and tumor necrosis factor-alpha] for 1, 3, and 24 h to investigate potential regulatory mechanisms. Decreased LPL activity was observed after 24 h of incubation with estradiol (1 micro g/ml), insulin, cortisol, and IGF-1 (n = 12; P < 0.05). We observed an increase in LPL activity after 3 h of incubation with estradiol (20 ng/ml) or hyperglycemic medium plus insulin (n = 7; P < 0.05). To conclude, we suggest that the gestational increase in placental LPL activity represents an important mechanism to enhance placental FFA transport in late pregnancy. Hormonal regulation of placental LPL activity by insulin, cortisol, IGF-1, and estradiol may be involved in gestational changes and in alterations in LPL activity in pregnancies complicated by altered fetal growth.
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49.
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50.
  • Magnusson, Peetra U., et al. (författare)
  • Platelet-derived growth factor receptor-beta constitutive activity promotes angiogenesis in vivo and in vitro
  • 2007
  • Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 27:10, s. 2142-2149
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE - Knockout studies have demonstrated crucial roles for the platelet-derived growth factor-B and its cognate receptor, platelet-derived growth factor receptor-β (PDGFR-β), in blood vessel maturation, that is, the coverage of newly formed vessels with mural cells/pericytes. This study describes the consequences of a constitutively activating mutation of the PDGFR-β (Pdgfrb) introduced into embryonic stem cells with respect to vasculogenesis/angiogenesis in vitro and in vivo. METHODS AND RESULTS - Embryonic stem cells were induced to either form teratomas in vivo or embryoid bodies, an in vitro model for mouse embryogenesis. Western blotting studies on embryoid bodies showed that expression of a single allele of the mutant Pdgfrb led to increased levels of PDGFR-β tyrosine phosphorylation and augmented downstream signal transduction. This was accompanied by enhanced vascular development, followed by exaggerated angiogenic sprouting with abundant pericyte coating as shown by immunohistochemistry/immunofluorescence. Pdgfrb embryoid bodies were characterized by increased expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor-2; neutralizing antibodies against VEGF-A/VEGF receptor-2 blocked vasculogenesis and angiogenesis in mutant embryoid bodies. Moreover, Pdgfrb embryonic stem cell-derived teratomas in nude mice were more densely vascularized than wild-type teratomas. CONCLUSION - Increased PDGFR-β kinase activity is associated with elevated expression of VEGF-A and VEGF receptor-2, acting directly on endothelial cells and resulting in increased vessel formation.
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