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2.
  • Shin, J. H., et al. (författare)
  • IA-2 autoantibodies in incident type I diabetes patients are associated with a polyadenylation signal polymorphism in GIMAP5
  • 2007
  • Ingår i: Genes Immun. - 1466-4879 .- 1476-5470. ; 8:6, s. 503-12
  • Tidskriftsartikel (refereegranskat)abstract
    • In a large case-control study of Swedish incident type I diabetes patients and controls, 0-34 years of age, we tested the hypothesis that the GIMAP5 gene, a key genetic factor for lymphopenia in spontaneous BioBreeding rat diabetes, is associated with type I diabetes; with islet autoantibodies in incident type I diabetes patients or with age at clinical onset in incident type I diabetes patients. Initial scans of allelic association were followed by more detailed logistic regression modeling that adjusted for known type I diabetes risk factors and potential confounding variables. The single nucleotide polymorphism (SNP) rs6598, located in a polyadenylation signal of GIMAP5, was associated with the presence of significant levels of IA-2 autoantibodies in the type I diabetes patients. Patients with the minor allele A of rs6598 had an increased prevalence of IA-2 autoantibody levels compared to patients without the minor allele (OR=2.2; Bonferroni-corrected P=0.003), after adjusting for age at clinical onset (P=8.0 x 10(-13)) and the numbers of HLA-DQ A1*0501-B1*0201 haplotypes (P=2.4 x 10(-5)) and DQ A1*0301-B1*0302 haplotypes (P=0.002). GIMAP5 polymorphism was not associated with type I diabetes or with GAD65 or insulin autoantibodies, ICA, or age at clinical onset in patients. These data suggest that the GIMAP5 gene is associated with islet autoimmunity in type I diabetes and add to recent findings implicating the same SNP in another autoimmune disease.
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3.
  • Sedimbi, S. K., et al. (författare)
  • SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients
  • 2007
  • Ingår i: Genes Immun. - : Nature Publishing Group. - 1466-4879 .- 1476-5470. ; 8:6, s. 518-21
  • Tidskriftsartikel (refereegranskat)abstract
    • SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age- and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.
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4.
  • Resic-Lindehammer, Sabina, et al. (författare)
  • Temporal trends of HLA genotype frequencies of type 1 diabetes patients in Sweden from 1986 to 2005 suggest altered risk
  • 2008
  • Ingår i: Acta Diabetologica. - : Springer. - 0940-5429 .- 1432-5233. ; 45:4, s. 231-235
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this study was to compare the frequency of human leukocyte antigen (HLA) genotypes in 1-18-year-old patients with type 1 diabetes newly diagnosed in 1986-1987 (n = 430), 1996-2000 (n = 342) and in 2003-2005 (n = 171). We tested the hypothesis that the HLA DQ genotype distribution changes over time. Swedish type 1 diabetes patients and controls were typed for HLA using polymerase chain reaction amplification and allele specific probes for DQ A1* and B1* alleles. The most common type 1 diabetes HLA DQA1*-B1*genotype 0501-0201/0301-0302 was 36% (153/430) in 1986-1987 and 37% (127/342) in 1996-2000, but decreased to 19% (33/171) in 2003-2005 (P \ 0.0001). The 0501-0201/0501-0201 genotype increased from 1% in 1986-1987 to 7% in 1996-2000 (P = 0.0047) and to 5% in 2003-2005 (P > 0.05). This study in 1-18-year-old Swedish type 1 diabetes patients supports the notion that there is a temporal change in HLA risk.
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5.
  • Hellgren, K., et al. (författare)
  • Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers
  • 2017
  • Ingår i: Annals of the Rheumatic Diseases. - : British Medical Association. - 0003-4967 .- 1468-2060. ; 76:1, s. 105-111
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Safety data on cancer risks following tumour necrosis factor alpha inhibitors (TNFi) in patients with spondyloarthritis (SpA) (here defined as ankylosing spondylitis (AS), undifferentiated spondarthropaties (SpA UNS), psoriatic arthritis (PsA)) are scarce. Our objective was to assess risks for cancer overall and for common subtypes in patients with SpA treated with TNFi compared with TNFi-naive patients with SpA and to the general population. Methods From the Swedish (Anti-Rheumatic Therapy in Sweden (ARTIS)) and Danish (DANBIO) biologics registers, we assembled 8703 (ARTIS=5448, DANBIO=3255) patients with SpA initiating a first TNFi 2001-2011. From the Swedish National Patient and Population Registers we assembled a TNFi-naive SpA cohort (n=28,164) and a Swedish age-matched and sex-matched general population comparator cohort (n=131 687). We identified incident cancers by linkage with the nationwide Swedish and Danish Cancer Registers 2001-2011, and calculated age-standardised and sex-standardised incidence ratios as measures of relative risk (RR). Results Based on 1188 cancers among the TNFi-naive patients with SpA, RR of cancer overall was 1.1 (95% Cl 1.0 to 1.2). Based on 147 cancers among TNFi initiators with SpA, RR versus TNFi-naive was 0.8 (95% CI 0.7 to 1.0) and results were similar for AS and PsA when analysed separately. Site-specific cancer RRs: prostate 0.5 (95% CI 0.3 to 0.8), lung 0.6 (95% CI 0.3 to 1.3), colorectal 1.0 (95% CI 0.5 to 2.0), breast 1.3 (95% Cl 0.9 to 2.0), lymphoma 0.8 (95% CI 0.4 to 1.8) and melanoma 1.4 (95% CI 0.7 to 2.6). Conclusions In patients with SpA, treatment with TNFi was not associated with increased risks of cancer, neither overall nor for the six most common cancer types.
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8.
  • Zhong, W., et al. (författare)
  • Dramatic changes in blood protein levels during the first week of life in extremely preterm infants
  • 2020
  • Ingår i: Pediatric Research. - : Springer Nature. - 0031-3998 .- 1530-0447.
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Preterm birth and its complications are the primary cause of death among children under the age of 5. Among the survivors, morbidity both perinatally and later in life is common. The dawn of novel technical platforms for comprehensive and sensitive analysis of protein profiles in blood has opened up new possibilities to study both health and disease with significant clinical accuracy, here used to study the preterm infant and the physiological changes of the transition from intrauterine to extrauterine life. Methods We have performed in-depth analysis of the protein profiles of 14 extremely preterm infants using longitudinal sampling. Medical variables were integrated with extensive profiling of 448 unique protein targets. Results The preterm infants have a distinct unified protein profile in blood directly at birth regardless of clinical background; however, the pattern changed profoundly postnatally, expressing more diverse profiles only 1 week later and further on up to term-equivalent age. Clusters of proteins depending on temporal trend were identified. Conclusion The protein profiles and the temporal trends here described will contribute to the understanding of the physiological changes in the intrauterine-extrauterine transition, which is essential to adjust early-in-life interventions to prone a normal development in the vulnerable preterm infants. Impact We have performed longitudinal and in-depth analysis of the protein profiles of 14 extremely preterm infants using a novel multiplex protein analysis platform. The preterm infants had a distinct unified protein profile in blood directly at birth regardless of clinical background. The pattern changed dramatically postnatally, expressing more diverse profiles only 1 week later and further on up to term-equivalent age. Certain clusters of proteins were identified depending on their temporal trend, including several liver and immune proteins. The study contributes to the understanding of the physiological changes in the intrauterine-extrauterine transition.
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9.
  • Askling, Helena H, et al. (författare)
  • Serologic Analysis of Returned Travelers with Fever, Sweden
  • 2009
  • Ingår i: Emerging Infectious Diseases. - Atlanta, GA, USA : U.S. Department of Health and Human Services * Centers for Disease Control and Prevention. - 1080-6040 .- 1080-6059. ; 15:11, s. 1805-1808
  • Tidskriftsartikel (refereegranskat)abstract
    • We studied 1,432 febrile travelers from Sweden who had returned from malaria-endemic areas during March 2005-March 2008. In 383 patients, paired serum samples were blindly analyzed for influenza and 7 other agents. For 21% of 115 patients with fever of unknown origin, serologic analysis showed that influenza was the major cause.
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10.
  • Cakir, B., et al. (författare)
  • Thrombocytopenia is associated with severe retinopathy of prematurity
  • 2018
  • Ingår i: Jci Insight. - : American Society for Clinical Investigation (ASCI). - 2379-3708. ; 3:19
  • Tidskriftsartikel (refereegranskat)abstract
    • Retinopathy of prematurity (ROP) is characterized by abnormal retinal neovascularization in response to vessel loss. Platelets regulate angiogenesis and may influence ROP progression. In preterm infants, we assessed ROP and correlated with longitudinal postnatal platelet counts (n = 202). Any episode of thrombocytopenia (< 100 x 10(9)/l) at >= 30 weeks postmenstrual age (at onset of ROP) was independently associated with severe ROP, requiring treatment. Infants with severe ROP also had a lower weekly median platelet count compared with infants with less severe ROP. In a mouse oxygen-induced retinopathy model of ROP, platelet counts were lower at P17 (peak neovascularization) versus controls. Platelet transfusions at P15 and P16 suppressed neovascularization, and platelet depletion increased neovascularization. Platelet transfusion decreased retinal of vascular endothelial growth factor A (VEGFA) mRNA and protein expression; platelet depletion increased retinal VEGFA mRNA and protein expression. Resting platelets with intact granules reduced neovascularization, while thrombin-activated degranulated platelets did not. These data suggest that platelet releasate has a local antiangiogenic effect on endothelial cells to exert a downstream suppression of VEGFA in neural retina. Low platelet counts during the neovascularization phase in ROP is significantly associated with the development of severe ROP in preterm infants. In a murine model of retinopathy, platelet transfusion during the period of neovascularization suppressed retinopathy.
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