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Sökning: WFRF:(Strawbridge Rona J.)

  • Resultat 51-54 av 54
  • Föregående 12345[6]
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  • Paramel Varghese, Geena, 1985-, et al. (författare)
  • NLRP3 Inflammasome Expression and Activation in Human Atherosclerosis
  • 2016
  • Ingår i: ; 5:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The NLR family, pyrin domain containing 3 (NLRP3) inflammasome is an interleukin (IL)-1β and IL-18 cytokine processing complex that is activated in inflammatory conditions. The role of the NLRP3 inflammasome in the pathogenesis of atherosclerosis and myocardial infarction is not fully understood.Methods and Results: Atherosclerotic plaques were analyzed for transcripts of the NLRP3 inflammasome, and for IL-1β release. The Swedish First-ever myocardial Infarction study in Ac-county (FIA) cohort consisting of DNA from 555 myocardial infarction patients and 1016 healthy individuals was used to determine the frequency of 4 single nucleotide polymorphisms (SNPs) from the downstream regulatory region of NLRP3. Expression of NLRP3, Apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 (CASP1), IL1B, and IL18 mRNA was significantly increased in atherosclerotic plaques compared to normal arteries. The expression of NLRP3 mRNA was significantly higher in plaques of symptomatic patients when compared to asymptomatic ones. CD68-positive macrophages were observed in the same areas of atherosclerotic lesions as NLRP3 and ASC expression. Occasionally, expression of NLRP3 and ASC was also present in smooth muscle cells. Cholesterol crystals and ATP induced IL-1β release from lipopolysaccharide-primed human atherosclerotic lesion plaques. The minor alleles of the variants rs4266924, rs6672995, and rs10733113 were associated with NLRP3 mRNA levels in peripheral blood mononuclear cells but not with the risk of myocardial infarction.Conclusions: Our results indicate a possible role of the NLRP3 inflammasome and its genetic variants in the pathogenesis of atherosclerosis.
  • Strawbridge, Rona J (författare)
  • Analysis of functional genetic polymorphisms in prostate cancer and type 2 diabetes : Mucin 1 and growth hormone receptor
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Prostate cancer and type 2 diabetes are complex diseases, the genetic and environmental basis of which are not well established. Epidimiology suggests a link between the two diseases, with type 2 diabetes redusing the risk of prostate cancer, and faily history of prostate cancer reducing the risk of type 2 diabetes. Common genetic variations are believed to influence risk of both diseases, with very little overlap between the genes implicated. Metabolism may be a link between the two diseases: diabetes is characterised by abberant utilization and storage of dietary energy, where as prostate cancer has a high demand for energy input. It is plausible that genes and thier variants which alter metabolic homeostasis influence risk of both diseases in the opposite directions. In order to investigate whether this hypothesis is correct, we investigated common genetic variation of two genes, GHR and MUC1, in prostate cancer and type 2 diabetes. Bothe genes have previously been implicated in prostate cancer, with some evidence suggesting a role for MUC1 as a biomarker for prostate cancer. The GH-IGF-I-Insulin axis is key to metabolism, thus is likely ot be important in diabetes. The suggestion of a role for MUC1 in type 2 diabetes is a novel. A number of MUC1 isoforms, some of which have been implicated in various cancers, are determined by a SNP in exon 2. Functional differences between the variants are as yet unknown. A polymorphism in the GHR where by exon 3 is excluded is believed to have increased bioactivity compared to the full length form, although this is much debated. In this thesis we demonstrated that the GHR exon 3 polyorphism reduces risk of type 2 diabetes, and is associated with increased BMI, CRP and IGF-I levels in diabetic subjects. The variant allele of MUC1 was associated with an increased risk of type 2 diabetes and lower IGF-I levels. Subjects homozygous for the variant allele had increased LDL and CRP levels In conclusion, these genetic variations of GHR and MUC1 have potential as biomarkers for type 2 diabetes, and its complications. Genetic variation of MUC1 in blood DNA samples does not influence prostate cancer risk or survival, however tumour-specific genetic alterations may be important. Sequence analysis indicates that MUC1 isoforms may have distinct differences.
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  • Resultat 51-54 av 54
  • Föregående 12345[6]
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