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Sökning: WFRF:(Haraldsen G)

  • Resultat 1-9 av 9
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  • Pihlstrøm, H. K., et al. (författare)
  • Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients : A Validation Study
  • 2017
  • Ingår i: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 17:2, s. 528-533
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) are designed to investigate single nucleotide polymor-phisms (SNPs) and the association with a clinical phenotype. A previous GWAS performed in 300 renal transplant recipients identified two SNPs (rs3811321 and rs6565887) associated with serum creatinine and clinical outcome. We sought to validate these findings. Genotyping of the two SNPs was performed using Taqman assays in 1638 Caucasians participating in the Assessment of LEscol in Renal Transplant (ALERT) study. Primary endpoint was death-censored graft loss, and secondary endpoint was all-cause mortality. Applying Cox regression, no crude association to graft loss was found for rs3811321 on chromosome 14 (hazard ratio [HR] 0.87, 95% CI 0.59-1.29, p = 0.50) or rs6565887 on chromosome 18 (HR 0.88, CI 0.62-1.25, p = 0.48). Multivariable adjustments did not change results, nor did evaluation of the number of risk alleles formed by the two SNPs. No association with mortality was detected. In conclusion, an impact of two SNPs on chromosomes 14 and 18 on death-censored graft survival or all-cause mortality was not confirmed. Our results emphasize the importance of validating findings from high-throughput genetics studies and call for large collaborative research initiatives in the field of transplantation outcomes.
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  • Gao, S., et al. (författare)
  • Manifolds of magnetic ordered states and excitations in the almost Heisenberg pyrochlore antiferromagnet MgCr2 O4
  • 2018
  • Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 97:13
  • Tidskriftsartikel (refereegranskat)abstract
    • In spinels ACr2O4(A=Mg, Zn), realization of the classical pyrochlore Heisenberg antiferromagnet model is complicated by a strong spin-lattice coupling: the extensive degeneracy of the ground state is lifted by a magneto-structural transition at TN=12.5 K. We study the resulting low-temperature low-symmetry crystal structure by synchrotron x-ray diffraction. The consistent features of x-ray low-temperature patterns are explained by the tetragonal model of Ehrenberg et al. [Pow. Diff. 17, 230 (2002)PODIE20885-715610.1154/1.1479738], while other features depend on sample or cooling protocol. A complex, partially ordered magnetic state is studied by neutron diffraction and spherical neutron polarimetry. Multiple magnetic domains of configuration arms of the propagation vectors k1=(12120),k2=(1012) appear. The ordered moment reaches 1.94(3) μB/Cr3+ for k1 and 2.08(3) μB/Cr3+ for k2, if equal amount of the k1 and k2 phases is assumed. The magnetic arrangements have the dominant components along the [110] and [1-10] diagonals and a smaller c component. We use inelastic neutron scattering to investigate the spin excitations, which comprise a mixture of dispersive spin waves propagating from the magnetic Bragg peaks and resonance modes centered at equal energy steps of 4.5 meV. We interpret these as acoustic and optical spin wave branches, but show that the neutron scattering cross sections of transitions within a unit of two corner-sharing tetrahedra match the observed intensity distribution of the resonances. The distinctive fingerprint of clusterlike excitations in the optical spin wave branches suggests that propagating excitations are localized by the complex crystal structure and magnetic orders.
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  • Kunkel, E J, et al. (författare)
  • Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity
  • 2000
  • Ingår i: Journal of Experimental Medicine. - 1540-9538. ; 192:5, s. 761-768
  • Tidskriftsartikel (refereegranskat)abstract
    • The immune system has evolved specialized cellular and molecular mechanisms for targeting and regulating immune responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes and lamina propria lymphocytes migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC chemokine receptor (CCR)9, a chemoattractant receptor expressed at high levels by essentially all CD4(+) and CD8(+) T lymphocytes in the small intestine. Only a small subset of lymphocytes in the colon are CCR9(+), and lymphocytes from other tissues including tonsils, lung, inflamed liver, normal or inflamed skin, inflamed synovium and synovial fluid, breast milk, and seminal fluid are universally CCR9(-). TECK expression is also restricted to the small intestine: immunohistochemistry reveals that intense anti-TECK reactivity characterizes crypt epithelium in the jejunum and ileum, but not in other epithelia of the digestive tract (including stomach and colon), skin, lung, or salivary gland. These results imply a restricted role for lymphocyte CCR9 and its ligand TECK in the small intestine, and provide the first evidence for distinctive mechanisms of lymphocyte recruitment that may permit functional specialization of immune responses in different segments of the gastrointestinal tract. Selective expression of chemokines by differentiated epithelium may represent an important mechanism for targeting and specialization of immune responses.
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  • Lossius, AH, et al. (författare)
  • Shifts in the Skin Microbiota after UVB Treatment in Adult Atopic Dermatitis
  • 2022
  • Ingår i: Dermatology (Basel, Switzerland). - : S. Karger AG. - 1421-9832 .- 1018-8665. ; 238:1, s. 109-120
  • Tidskriftsartikel (refereegranskat)abstract
    • <b><i>Background:</i></b> The pathophysiology in atopic dermatitis (AD) is not fully understood, but immune dysfunction, skin barrier defects, and alterations of the skin microbiota are thought to play important roles. AD skin is frequently colonized with <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and microbial diversity on lesional skin (LS) is reduced compared to on healthy skin. Treatment with narrow-band ultraviolet B (nb-UVB) leads to clinical improvement of the eczema and reduced abundance of <i>S. aureus</i>. However, in-depth knowledge of the temporal dynamics of the skin microbiota in AD in response to nb-UVB treatment is lacking and could provide important clues to decipher whether the microbial changes are primary drivers of the disease, or secondary to the inflammatory process. <b><i>Objectives:</i></b> To map the temporal shifts in the microbiota of the skin, nose, and throat in adult AD patients after nb-UVB treatment. <b><i>Methods:</i></b> Skin swabs were taken from lesional AD skin (<i>n</i> = 16) before and after 3 treatments of nb-UVB, and after 6–8 weeks of full-body treatment. We also obtained samples from non-lesional skin (NLS) and from the nose and throat. All samples were characterized by 16S rRNA gene sequencing. <b><i>Results:</i></b> We observed shifts towards higher diversity in the microbiota of lesional AD skin after 6–8 weeks of treatment, while the microbiota of NLS and of the nose/throat remained unchanged. After only 3 treatments with nb-UVB, there were no significant changes in the microbiota. <b><i>Conclusion:</i></b> Nb-UVB induces changes in the skin microbiota towards higher diversity, but the microbiota of the nose and throat are not altered.
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  • Nuruddin, Syed, et al. (författare)
  • Elevated mRNA-Levels of Gonadotropin-Releasing Hormone and Its Receptor in Plaque-Bearing Alzheimer's Disease Transgenic Mice
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e103607-
  • Tidskriftsartikel (refereegranskat)abstract
    • Research on Alzheimer's disease (AD) has indicated an association between hormones of the hypothalamic-pituitary-gonadal (HPG) axis and cognitive senescence, indicating that post meno-/andropausal changes in HPG axis hormones are implicated in the neuropathology of AD. Studies of transgenic mice with AD pathologies have led to improved understanding of the pathophysiological processes underlying AD. The aims of this study were to explore whether mRNA-levels of gonadotropin-releasing hormone (Gnrh) and its receptor (Gnrhr) were changed in plaque-bearing Alzheimer's disease transgenic mice and to investigate whether these levels and amyloid plaque deposition were downregulated by treatment with a gonadotropin-releasing hormone analog (Gnrh-a; Leuprorelin acetate). The study was performed on mice carrying the Arctic and Swedish amyloid-b precursor protein (AbPP) mutations (tgArcSwe). At 12 months of age, female tgArcSwe mice showed a twofold higher level of Gnrh mRNA and more than 1.5 higher level of Gnrhr mRNA than age matched controls. Male tgArcSwe mice showed the same pattern of changes, albeit more pronounced. In both sexes, Gnrha treatment caused significant down-regulation of Gnrh and Gnrhr mRNA expression. Immunohistochemistry combined with quantitative image analysis revealed no significant changes in the plaque load after Gnrh-a treatment in hippocampus and thalamus. However, plaque load in the cerebral cortex of treated females tended to be lower than in female vehicle-treated mice. The present study points to the involvement of hormonal changes in AD mice models and demonstrates that these changes can be effectively counteracted by pharmacological treatment. Although known to increase in normal aging, our study shows that Gnrh/Gnrhr mRNA expression increases much more dramatically in tgArcSwe mice. Treatment with Leuprorelin acetate successfully abolished the transgene specific effects on Gnrh/Gnrhr mRNA expression. The present experimental approach should serve as a platform for further studies on the usefulness of Gnrh-a treatment in suppressing plaque development in AD.
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