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Sökning: WFRF:(Magnusson Patrik K.) > (2005-2009)

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  • 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. - 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.
  • 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. - 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.
  • Silventoinen, Karri, et al. (författare)
  • Does obesity modify the effect of blood pressure on the risk of cardiovascular disease? : A population-based cohort study of more than one million Swedish men
  • 2008
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 118:16, s. 1637-42
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Some studies have suggested that increased blood pressure has a stronger effect on the risk of cardiovascular disease (CVD) in lean persons than in obese persons, although this is not a universal finding. Given the inconsistency of this result, we tested it using a large population-based cohort data set. METHODS AND RESULTS: Systolic and diastolic blood pressures (BPs) and body mass index were measured in 1 145 758 Swedish men born between 1951 and 1976 who were in young adulthood (median age 18.2 years). During the register-based follow-up, which lasted until the end of 2006, 65 611 new CVD events took place, including 6799 myocardial infarctions and 8827 strokes. Hazard ratios (HRs) per 1-SD increase in systolic and diastolic BP were computed within established body mass index categories (underweight, normal, overweight, or obese) with Cox proportional hazards models. The strongest associations of diastolic BP with CVD (HR 1.18), myocardial infarction (HR 1.22), and stroke (HR 1.13) were observed in the obese category. For systolic BP, the strongest associations were observed in the obese category with CVD (HR 1.16) and stroke (HR 1.29) but in the overweight category with myocardial infarction (HR 1.19). We observed statistically significant interactions (P<0.0001) with body mass index for diastolic BP in relation to CVD and for systolic BP in relation to CVD and stroke. CONCLUSIONS: In contrast to the findings of previous studies, we observed a general increase in the magnitude of the association between blood pressure and subsequent CVD with increasing body mass index. Hypertension should not be regarded as a less serious risk factor in obese than in lean or normal-weight persons.
  • Wetterö, Jonas, et al. (författare)
  • Immobilized chemoattractant peptides mediate adhesion and distinct calcium-dependent cell signaling in human neutrophils
  • 2008
  • Ingår i: Langmuir. - 0743-7463. ; 24:13, s. 6803-6811
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemotaxis is the stimulated directional migration of cells in response to chemotactic factors, manifested for instance during leukocyte interaction with chemoattractants in inflammation. The N-formyl-Met-Leu-Phe (fMLF) bacterial peptide family is particularly potent in attracting and activating neutrophilic granulocytes. To accomplish defined circumstances for recruitment and activation of cells, we fabricated semitransparent gold-coated glass coverslips functionalized with chemoattractant fMLF receptor peptide agonist analogues. Peptides based on a common leading four-amino-acid sequence Gly-Gly-Gly-Cys were thus coupled to two potent fMLF receptor agonists, N-formyl-Tyr-Nle-Phe-Leu- Nle-Gly-Gly-Gly-Cys and N-formyl-Met-Leu-Phe-Gly-Gly-Gly-Cys, and a formylated control peptide, N-formyl-Gly-Gly-Gly-Cys. They were anchored via the SH group of Cys either directly to the gold surface or a mixed self-assembled monolayer composed of maleimide- and hydroxyl-terminated oligo(ethylene glycol) alkyldisulfides. The overall peptide immobilization procedure was characterized with ellipsometry, contact angle measurement, and infrared spectroscopy. When exposed to granulocytes, the agonist surface rapidly recruited neutrophils and the cells responded with extensive spreading and intracellular calcium transients within minutes. The reference peptide generated no such activation, and the cells maintained a more spherical morphology, suggesting that we have been able to immobilize chemoattractant receptor agonist peptides with retained bioactivity. This is a crucial step in designing surfaces with specific effects on cellular behavior. © 2008 American Chemical Society.
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