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21.
Fang Fang Unnur Valdimarsdóttir Lorelei Mucci Pär Sparén Weimin Ye Katja Fall 《Cancer epidemiology》2010,34(5):644-647
Purpose: To examine the potential role of nonsteroidal anti-inflammatory drugs (NSAIDs) use on prostate cancer (PCa) specific mortality. Methods: We studied the association between hospitalization for osteoarthritis prior to PCa diagnosis, as a surrogate for heavy use of NSAIDs, and PCa specific mortality in a large population of PCa patients in Sweden in 1980–2004. Results: Hospitalization for osteoarthritis before PCa diagnosis was associated to a lower PCa specific mortality (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.88–0.96), but not to the risk of death from other causes (HR, 1.03; 95% CI, 0.99–1.08). The association was stronger among younger patients and patients diagnosed in earlier calendar years. Conclusions: Our data demonstrate a modestly decreased PCa specific mortality among PCa patients with hospitalization for osteoarthritis prior to PCa diagnosis, compared to those without such experience. This finding lends support to the hypothesis that NSAIDs use may influence PCa progression. 相似文献
22.
Palsdottir A Helgason A Palsson S Bjornsson HT Bragason BT Gretarsdottir S Thorsteinsdottir U Olafsson E Stefansson K 《PLoS genetics》2008,4(6):e1000099
Hereditary cystatin C amyloid angiopathy (HCCAA) is an autosomal dominant disease with high penetrance, manifest by brain hemorrhages in young normotensive adults. In Iceland, this condition is caused by the L68Q mutation in the cystatin C gene, with contemporary carriers reaching an average age of only 30 years. Here, we report, based both on linkage disequilibrium and genealogical evidence, that all known copies of this mutation derive from a common ancestor born roughly 18 generations ago. Intriguingly, the genealogies reveal that obligate L68Q carriers born 1825 to 1900 experienced a drastic reduction in life span, from 65 years to the present-day average. At the same time, a parent-of-origin effect emerged, whereby maternal inheritance of the mutation was associated with a 9 year reduction in life span relative to paternal inheritance. As these trends can be observed in several different extended families, many generations after the mutational event, it seems likely that some environmental factor is responsible, perhaps linked to radical changes in the life-style of Icelanders during this period. A mutation with such radically different phenotypic effects in reaction to normal variation in human life-style not only opens the possibility of preventive strategies for HCCAA, but it may also provide novel insights into the complex relationship between genotype and environment in human disease. 相似文献
23.
Jianwei Zhu Donghao Lu Olafur Sveinsson Karin Wirdefeldt Katja Fall Fredrik Piehl Unnur Valdimarsdóttir Fang Fang 《PloS one》2015,10(4)
Background
Psychological stress has been associated with transient global amnesia (TGA). Whether a cancer diagnosis, a severely stressful life event, is associated with subsequent risk of TGA has not been studied.Methods
Based on the Swedish Cancer Register and Patient Register, we conducted a prospective cohort study including 5,365,608 Swedes at age 30 and above during 2001–2009 to examine the relative risk of TGA among cancer patients, as compared to cancer-free individuals. Incidence rate ratios (IRRs) and their 95% confidence intervals (CIs) derived from Poisson regression were used as estimates of the association between cancer diagnosis and the risk of TGA.Results
During the study 322,558 individuals (6.01%) received a first diagnosis of cancer. We identified 210 cases of TGA among the cancer patients (incidence rate, 0.22 per 1000 person-years) and 4,887 TGA cases among the cancer-free individuals (incidence rate, 0.12 per 1000 person-years). Overall, after adjustment for age, sex, calendar year, socioeconomic status, education and civil status, cancer patients had no increased risk of TGA than the cancer-free individuals (IRR, 0.99; 95% CI, 0.86–1.13). The IRRs did not differ over time since cancer diagnosis or across individual cancer types. The null association was neither modified by sex, calendar period or age.Conclusion
Our study did not provide support for the hypothesis that patients with a new diagnosis of cancer display a higher risk of TGA than cancer-free individuals. 相似文献24.
25.
TIMP-1 inhibits microvascular endothelial cell migration by MMP-dependent and MMP-independent mechanisms 总被引:10,自引:0,他引:10
Akahane T Akahane M Shah A Connor CM Thorgeirsson UP 《Experimental cell research》2004,301(2):158-167
It was reported over a decade ago that tissue inhibitor of metalloproteinases-1 (TIMP-1) suppresses angiogenesis in experimental models but the mechanism is still incompletely understood. This in vitro study focused on the molecular basis of TIMP-1-mediated inhibition of endothelial cell (EC) migration, a key step in the angiogenic process. Both recombinant human TIMP-1 and the synthetic MMP inhibitors, GM6001 and MMP-2-MMP-9 Inhibitor III, suppressed migration of human dermal microvascular endothelial cells (HDMVEC) in a dose-dependent fashion. The MMP-dependent inhibition of migration was associated with increased expression of the junctional adhesion proteins, VE-cadherin and PECAM-1, and VE-cadherin accumulation at cell-cell junctions. TIMP-1 also caused MMP-independent dephosphorylation of focal adhesion kinase (FAK) (pY397) and paxillin, which was associated with reduced number of F-actin stress fibers and focal adhesions. Moreover, TIMP-1 stimulated expression of PTEN that has been shown to reduce phosphorylation of FAK and inhibit cell migration. Our data suggest that TIMP-1 inhibits HDMVEC migration through MMP-dependent stimulation of VE-cadherin and MMP-independent stimulation of PTEN with subsequent dephosphorylation of FAK and cytoskeletal remodeling. 相似文献
26.
Styrkarsdottir U Halldorsson BV Gudbjartsson DF Tang NL Koh JM Xiao SM Kwok TC Kim GS Chan JC Cherny S Lee SH Kwok A Ho S Gretarsdottir S Kostic JP Palsson ST Sigurdsson G Sham PC Kim BJ Kung AW Kim SY Woo J Leung PC Kong A Thorsteinsdottir U Stefansson K 《PloS one》2010,5(10):e13217
Most genome-wide association (GWA) studies have focused on populations of European ancestry with limited assessment of the influence of the sequence variants on populations of other ethnicities. To determine whether markers that we have recently shown to associate with Bone Mineral Density (BMD) in Europeans also associate with BMD in East-Asians we analysed 50 markers from 23 genomic loci in samples from Korea (n = 1,397) and two Chinese Hong Kong sample sets (n = 3,869 and n = 785). Through this effort we identified fourteen loci that associated with BMD in East-Asian samples using a false discovery rate (FDR) of 0.05; 1p36 (ZBTB40, P = 4.3×10−9), 1p31 (GPR177, P = 0.00012), 3p22 (CTNNB1, P = 0.00013), 4q22 (MEPE, P = 0.0026), 5q14 (MEF2C, P = 1.3×10−5), 6q25 (ESR1, P = 0.0011), 7p14 (STARD3NL, P = 0.00025), 7q21 (FLJ42280, P = 0.00017), 8q24 (TNFRSF11B, P = 3.4×10−5), 11p15 (SOX6, P = 0.00033), 11q13 (LRP5, P = 0.0033), 13q14 (TNFSF11, P = 7.5×10−5), 16q24 (FOXL1, P = 0.0010) and 17q21 (SOST, P = 0.015). Our study marks an early effort towards the challenge of cataloguing bone density variants shared by many ethnicities by testing BMD variants that have been established in Europeans, in East-Asians. 相似文献
27.
Pathways activated during human asthma exacerbation as revealed by gene expression patterns in blood
Bjornsdottir US Holgate ST Reddy PS Hill AA McKee CM Csimma CI Weaver AA Legault HM Small CG Ramsey RC Ellis DK Burke CM Thompson PJ Howarth PH Wardlaw AJ Bardin PG Bernstein DI Irving LB Chupp GL Bensch GW Bensch GW Stahlman JE Karetzky M Baker JW Miller RL Goodman BH Raible DG Goldman SJ Miller DK Ryan JL Dorner AJ Immermann FW O'Toole M 《PloS one》2011,6(7):e21902
Background
Asthma exacerbations remain a major unmet clinical need. The difficulty in obtaining airway tissue and bronchoalveolar lavage samples during exacerbations has greatly hampered study of naturally occurring exacerbations. This study was conducted to determine if mRNA profiling of peripheral blood mononuclear cells (PBMCs) could provide information on the systemic molecular pathways involved during asthma exacerbations.Methodology/Principal Findings
Over the course of one year, gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared using oligonucleotide arrays. For each of 118 subjects who experienced at least one asthma exacerbation, the gene expression patterns in a sample of peripheral blood mononuclear cells collected during an exacerbation episode were compared to patterns observed in multiple samples from the same subject collected during quiescent asthma. Analysis of covariance identified genes whose levels of expression changed during exacerbations and returned to quiescent levels by two weeks. Heterogeneity among visits in expression profiles was examined using K-means clustering. Three distinct exacerbation-associated gene expression signatures were identified. One signature indicated that, even among patients without symptoms of respiratory infection, genes of innate immunity were activated. Antigen-independent T cell activation mediated by IL15 was also indicated by this signature. A second signature revealed strong evidence of lymphocyte activation through antigen receptors and subsequent downstream events of adaptive immunity. The number of genes identified in the third signature was too few to draw conclusions on the mechanisms driving those exacerbations.Conclusions/Significance
This study has shown that analysis of PBMCs reveals systemic changes accompanying asthma exacerbation and has laid the foundation for future comparative studies using PBMCs. 相似文献28.
Johanna E. Torfadottir Unnur A. Valdimarsdottir Lorelei A. Mucci Julie L. Kasperzyk Katja Fall Laufey Tryggvadottir Thor Aspelund Orn Olafsson Tamara B. Harris Eirikur Jonsson Hrafn Tulinius Vilmundur Gudnason Hans-Olov Adami Meir Stampfer Laufey Steingrimsdottir 《PloS one》2013,8(4)
Objective
To examine whether fish and fish oil consumption across the lifespan is associated with a lower risk of prostate cancer.Design
The study was nested among 2268 men aged 67–96 years in the AGES-Reykjavik cohort study. In 2002 to 2006, dietary habits were assessed, for early life, midlife and later life using a validated food frequency questionnaire. Participants were followed for prostate cancer diagnosis and mortality through 2009 via linkage to nationwide cancer- and mortality registers. Adjusting for potential confounders, we used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for prostate cancer according to fish and fish oil consumption.Results
Among the 2268 men, we ascertained 214 prevalent and 133 incident prostate cancer cases, of which 63 had advanced disease. High fish consumption in early- and midlife was not associated with overall or advanced prostate cancer. High intake of salted or smoked fish was associated with a 2-fold increased risk of advanced prostate cancer both in early life (95% CI: 1.08, 3.62) and in later life (95% CI: 1.04, 5.00). Men consuming fish oil in later life had a lower risk of advanced prostate cancer [HR (95%CI): 0.43 (0.19, 0.95)], no association was found for early life or midlife consumption.Conclusions
Salted or smoked fish may increase risk of advanced prostate cancer, whereas fish oil consumption may be protective against progression of prostate cancer in elderly men. In a setting with very high fish consumption, no association was found between overall fish consumption in early or midlife and prostate cancer risk. 相似文献29.
Védís Helga Eiríksdóttir Tinna Laufey ásgeirsdóttir Ragnheieur Ingibj?rg Bjarnadóttir Robert Kaestner Sven Cnattingius Unnur Anna Valdimarsdóttir 《PloS one》2013,8(12)
Objective
Infants born small for gestational age (SGA) or preterm have increased rates of perinatal morbidity and mortality. Stressful events have been suggested as potential contributors to preterm birth (PB) and low birth weight (LBW). We studied the effect of the 2008 economic collapse in Iceland on the risks of adverse birth outcomes.Study design
The study population constituted all Icelandic women giving birth to live-born singletons from January 1st 2006 to December 31st 2009. LBW infants were defined as those weighing <2500 grams at birth, PB infants as those born before 37 weeks of gestation and SGA as those with a birth weight for gestational age more than 2 standard deviations (SD''s) below the mean according to the Swedish fetal growth curve. We used logistic regression analysis to estimate odds ratios [OR] and corresponding 95 percent confidence intervals [95% CI] of adverse birth outcomes by exposure to calendar time of the economic collapse, i.e. after October 6th 2008.Results
Compared to the preceding period, we observed an increased adjusted odds in LBW-deliveries following the collapse (aOR = 1.24, 95% CI [1.02, 1.52]), particularly among infants born to mothers younger than 25 years (aOR = 1.85, 95% CI [1.25, 2.72]) and not working mothers (aOR = 1.61, 95% CI [1.10, 2.35]). Similarly, we found a tendency towards higher incidence of SGA-births (aOR = 1.14, 95% CI [0.86, 1.51]) particularly among children born to mothers younger than 25 years (aOR = 1.87, 95% CI [1.09, 3.23]) and not working mothers (aOR = 1.86, 95% CI [1.09, 3.17]). No change in risk of PB was observed. The increase of LBW was most distinct 6–9 months after the collapse.Conclusion
The results suggest an increase in risk of LBW shortly after the collapse of the Icelandic national economy. The increase in LBW seems to be driven by reduced fetal growth rate rather than shorter gestation. 相似文献30.
Kaye Phillips Jillian Clare Kohler Peter Pennefather Halla Thorsteinsdottir Joseph Wong 《PLoS neglected tropical diseases》2013,7(12)