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Sökning: WFRF:(Nielsen Jörn)

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  • Abelein, Axel, et al. (författare)
  • Formation of dynamic soluble surfactant-induced amyloid β peptide aggregation intermediates
  • 2013
  • Ingår i: Journal of Biological Chemistry. - 0021-9258. ; 288:32, s. 23518-23528
  • Tidskriftsartikel (refereegranskat)abstract
    • Intermediate amyloidogenic states along the amyloid β peptide (Aβ) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during Aβ aggregation, we here investigate surfactant-induced Aβ aggregation. This process leads to co-aggregates featuring a β-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in Aβ in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via β-structure to the fully formed α-helical state at high surfactant concentration. The β-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-Aβ co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (k(ex) ∼1100 s(-1)) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with β-structure promoting substances, such as surfactants, Aβ is kinetically driven toward an aggregation-prone state.
  • Albin, Maria, et al. (författare)
  • Astma och eksem hos frisörer.
  • 1998
  • Ingår i: Hygiea. - Svenska Läkaresällskapets Riksstämma. - 0346-6264. ; 1:Band 107:144, s. 137-137
  • Konferensbidrag (refereegranskat)
  • Bergholdt, R, et al. (författare)
  • Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets
  • 2007
  • Ingår i: Genes and Immunity. - Nature Publishing Group. - 1476-5470. ; 8:3, s. 232-238
  • Tidskriftsartikel (refereegranskat)abstract
    • We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1 alpha beta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1 beta (IL-1 beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression in the two approaches were highly similar, supporting the role of these specific gene products in cytokine-induced beta-cell damage. These were genes involved in cytokine signaling, oxidative phosphorylation, defense responses and apoptosis. The analyses, furthermore, revealed several transcription factor binding sites shared by the differentially expressed genes and by genes demonstrating highly similar expression profiles with these genes. Comparable findings in the rat beta-cell line and human islets support the validity of the methods used and support this as a valuable approach for gene mapping and identification of genes with potential functional significance in T1D, within a region of linkage.
  • Blomqvist, A, et al. (författare)
  • Airways symptoms, immunological response and exposure in powder painting
  • 2005
  • Ingår i: International Archives of Occupational and Environmental Health. - Springer. - 1432-1246. ; 78:2, s. 123-131
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Powder painting is an alternative to solvent-based spray painting. Powder paints may contain organic acid anhydrides (OAAs), which are irritants to the airways and may cause sensitisation. The aim of this study was to determine the prevalence of respiratory symptoms and immunological response among powder painters and to describe the exposure to OAAs. Methods: In all, 205 subjects in 32 enterprises participated: 93 exposed and 26 formerly exposed workers in 25 powder paint shops and 86 unexposed workers. They completed a questionnaire about working conditions and symptoms and took part in a medical examination, which included a lung function test. Urine samples, for determination of two OAAs, and blood samples, for analysis of specific antibodies against the OAAs, were taken. In addition, 33 paint samples were analysed for nine OAAs. Results: The powder painters reported more work-related respiratory symptoms than unexposed subjects did. The prevalence of three or more symptoms was 24% in subjects with low exposure, 44% in highly exposed individuals, 46% in formerly exposed subjects and 19% in unexposed workers. Asthma symptoms were frequent, 7%, 40%, 15% and 2%, respectively. Regression analyses of the lung volumes did not show any influence of exposure. IgG, but not IgE, against the OAAs and metabolites of OAAs was found in some subjects, but no associations with the exposure could be observed. OAAs were found in only small amounts in the paint samples. Conclusions: The exposure to organic acid anhydrides was estimated to be low, and yet, IgG antibodies to OAA were observed in some subjects. The prevalence of work-related symptoms from the eyes and the airways was relatively high among the powder painters, and these symptoms, but not the lung volumes, were clearly related to exposure. The symptoms were probably caused by irritative properties of the powder paint dust.
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