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| 2. |
- Antoniou, A, et al.
(författare)
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Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: A combined analysis of 22 studies
- 2003
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 72:5, s. 1117-1130
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Tidskriftsartikel (refereegranskat)abstract
- Germline mutations in BRCA1 and BRCA2 confer high risks of breast and ovarian cancer, but the average magnitude of these risks is uncertain and may depend on the context. Estimates based on multiple-case families may be enriched for mutations of higher risk and/or other familial risk factors, whereas risk estimates from studies based on cases unselected for family history have been imprecise. We pooled pedigree data from 22 studies involving 8,139 index case patients unselected for family history with female (86%) or male (2%) breast cancer or epithelial ovarian cancer (12%), 500 of whom had been found to carry a germline mutation in BRCA1 or BRCA2. Breast and ovarian cancer incidence rates for mutation carriers were estimated using a modified segregation analysis, based on the occurrence of these cancers in the relatives of mutation-carrying index case patients. The average cumulative risks in BRCA1-mutation carriers by age 70 years were 65% (95% confidence interval 44%-78%) for breast cancer and 39% (18%-54%) for ovarian cancer. The corresponding estimates for BRCA2 were 45% (31%-56%) and 11% (2.4%-19%). Relative risks of breast cancer declined significantly with age for BRCA1-mutation carriers ( P trend .0012) but not for BRCA2-mutation carriers. Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age. We found some evidence for a reduction in risk in women from earlier birth cohorts and for variation in risk by mutation position for both genes. The pattern of cancer risks was similar to those found in multiple-case families, but their absolute magnitudes were lower, particularly for BRCA2. The variation in risk by age at diagnosis of index case is consistent with the effects of other genes modifying cancer risk in carriers.
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| 3. |
- Antoniou, A C, et al.
(författare)
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Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies
- 2005
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 42:7, s. 602-603
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Tidskriftsartikel (refereegranskat)abstract
- A recent report estimated the breast cancer risks in carriers of the three Ashkenazi founder mutations to be higher than previously published estimates derived from population based studies. In an attempt to confirm this, the breast and ovarian cancer risks associated with the three Ashkenazi founder mutations were estimated using families included in a previous meta-analysis of populatrion based studies. The estimated breast cancer risks for each of the founder BRCA1 and BRCA2 mutations were similar to the corresponding estimates based on all BRCA1 or BRCA2 mutations in the meta-analysis. These estimates appear to be consistent with the observed prevalence of the mutations in the Ashkenazi Jewish population.
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| 6. |
- van Duijnhoven, Fraenzel J. B., et al.
(författare)
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Fruit, vegetables, and colorectal cancer risk: the European Prospective Investigation into Cancer and Nutrition
- 2009
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 1938-3207 .- 0002-9165. ; 89:5, s. 1441-1452
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high consumption of fruit and vegetables is possibly associated with a decreased risk of colorectal cancer (CRC). However, the findings to date are inconsistent. Objective: We examined the relation between self-reported usual consumption of fruit and vegetables and the incidence of CRC. Design: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 452,755 subjects (131,985 men and 320,770 women) completed a dietary questionnaire in 1992-2000 and were followed up for cancer incidence and mortality until 2006. A multivariate Cox proportional hazard model was used to estimate adjusted hazard ratios (HRs) and 95% CIs. Results: After an average follow-up of 8.8 y, 2,819 incident CRC cases were reported. Consumption of fruit and vegetables was inversely associated with CRC in a comparison of the highest with the lowest EPIC-wide quintile of consumption (HR: 0.86; 95% CI: 0.75, 1.00; P for trend 0.04), particularly with colon cancer risk (HR: 0.76; 95% CI: 0.63, 0.91; P for trend < 0.01). Only after exclusion of the first 2 y of follow-up were these findings corroborated by calibrated continuous analyses for a 100-g increase in consumption: HRs of 0.95 (95% CI: 0.91, 1.00; P 0.04) and 0.94 (95% CI: 0.89, 0.99; P = 0.02), respectively. The association between fruit and vegetable consumption and CRC risk was inverse in never and former smokers, but positive in current smokers. This modifying effect was found for fruit and vegetables combined and for vegetables alone (P for interaction, 0.01 for both). Conclusions: These findings suggest that a high consumption of fruit and vegetables is associated with a reduced risk of CRC, especially of colon cancer. This effect may depend on smoking status. Am J Clin Nutr 2009;89:1441-52.
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| 9. |
- Wu, Xifeng, et al.
(författare)
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Genetic variation in the prostate stem cell antigen gene PSCA confers susceptibility to urinary bladder cancer.
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:9, s. 991-5
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study on 969 bladder cancer cases and 957 controls from Texas. For fast-track validation, we evaluated 60 SNPs in three additional US populations and validated the top SNP in nine European populations. A missense variant (rs2294008) in the PSCA gene showed consistent association with bladder cancer in US and European populations. Combining all subjects (6,667 cases, 39,590 controls), the overall P-value was 2.14 x 10(-10) and the allelic odds ratio was 1.15 (95% confidence interval 1.10-1.20). rs2294008 alters the start codon and is predicted to cause truncation of nine amino acids from the N-terminal signal sequence of the primary PSCA translation product. In vitro reporter gene assay showed that the variant allele significantly reduced promoter activity. Resequencing of the PSCA genomic region showed that rs2294008 is the only common missense SNP in PSCA. Our data identify rs2294008 as a new bladder cancer susceptibility locus.
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| 12. |
- Axmarker, T., et al.
(författare)
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Long-term survival after self-expanding metallic stent or stoma decompression as bridge to surgery in acute malignant large bowel obstruction
- 2021
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Ingår i: BJS Open. - : Oxford University Press (OUP). - 2474-9842. ; 5:2
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Self-expanding metallic stents (SEMS) as bridge to surgery have been questioned due to the fear of perforation and tumour spread. This study aimed to compare SEMS and stoma as bridge to surgery in acute malignant large bowel obstruction in the Swedish population. METHOD: Medical records of patients identified via the Swedish Colorectal Cancer Register 2007-2009 were collected and scrutinized. The inclusion criterion was decompression intended as bridge to surgery due to acute malignant large bowel obstruction. Patients who underwent decompression for other causes or had bowel perforation were excluded. Primary endpoints were 5-year overall survival and 3-year disease-free survival. Secondary endpoints were 30-day morbidity and mortality rates. RESULTS: A total of 196 patients fulfilled the inclusion criterion (SEMS, 71, and stoma, 125 patients). There was no significant difference in sex, age, ASA score, TNM stage and adjuvant chemotherapy between the SEMS and stoma groups. No patient was treated with biological agents. Five-year overall survival was comparable in SEMS, 56 per cent (40 patients), and stoma groups, 48 per cent (60 patients), P = 0.260. Likewise, 3-year disease-free survival did not differ statistically significant, SEMS 73 per cent (43 of 59 patients), stoma 65 per cent (62 of 95 patients), P = 0.32. In the SEMS group, 1.4 per cent (one patient) did not fulfil resection surgery compared to 8.8 per cent (11 patients) in the stoma group (P = 0.040). Postoperative complication and 30-day postoperative mortality rates did not differ, whereas the duration of hospital stay and proportion of permanent stoma were lower in the SEMS group. CONCLUSION: This nationwide registry-based study showed that long-term survival in patients with either SEMS or stoma as bridge to surgery in acute malignant large bowel obstruction were comparable. SEMS were associated with a lower rate of permanent stoma, higher rate of resection surgery and shorter duration of hospital stay.
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| 13. |
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| 14. |
- Brynjolfsson, E. J., et al.
(författare)
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Black hole thermodynamics and heavy fermion metals
- 2010
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Ingår i: Journal of High Energy Physics (JHEP). - 1126-6708 .- 1029-8479. ; :8, s. 027-
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Tidskriftsartikel (refereegranskat)abstract
- Heavy fermion alloys at critical doping typically exhibit non-Fermi-liquid behavior at low temperatures, including a logarithmic or power law rise in the ratio of specific heat to temperature as the temperature is lowered. Anomalous specific heat of this type is also observed in a simple class of gravitational dual models that exhibit anisotropic scaling with dynamical critical exponent z > 1.
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| 15. |
- Brynjolfsson, E. J., et al.
(författare)
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Holographic models with anisotropic scaling
- 2010
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- We consider gravity duals to d+1 dimensional quantum critical points with anisotropic scaling. The primary motivation comes from strongly correlated electron systems in condensed matter theory but the main focus of the present paper is on the gravity models in their own right. Physics at finite temperature and fixed charge density is described in terms of charged black branes. Some exact solutions are known and can be used to obtain a maximally extended spacetime geometry, which has a null curvature singularity inside a single non-degenerate horizon, but generic black brane solutions in the model can only be obtained numerically. Charged matter gives rise to black branes with hair that are dual to the superconducting phase of a holographic superconductor. Our numerical results indicate that holographic superconductors with anisotropic scaling have vanishing zero temperature entropy when the back reaction of the hair on the brane geometry is taken into account.
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| 16. |
- Brynjolfsson, E. J., et al.
(författare)
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Holographic superconductors with Lifshitz scaling
- 2010
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Ingår i: Journal of physics. A, Mathematical and theoretical. - : IOP Publishing. - 1751-8113 .- 1751-8121. ; 43:6, s. 065401-
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Tidskriftsartikel (refereegranskat)abstract
- Black holes in asymptotically Lifshitz spacetime provide a window onto finite temperature effects in strongly coupled Lifshitz models. We add a Maxwell gauge field and charged matter to a recently proposed gravity dual of (2+ 1)-dimensional Lifshitz theory. This gives rise to charged black holes with scalar hair, which correspond to the superconducting phase of holographic superconductors with z > 1 Lifshitz scaling. Along the way we analyze the global geometry of static, asymptotically Lifshitz black holes at the arbitrary critical exponent z > 1. In all known exact solutions there is a null curvature singularity in the black hole region, and, by a general argument, the same applies to generic Lifshitz black holes.
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| 17. |
- Danielsson, Ulf H, et al.
(författare)
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Black holes in asymptotically Lifshitz spacetime
- 2009
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Ingår i: Journal of High Energy Physics (JHEP). - : Springer Science and Business Media LLC. - 1126-6708 .- 1029-8479. ; :3, s. 070-
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Tidskriftsartikel (refereegranskat)abstract
- A model of 3 + 1 dimensional gravity with negative cosmological constant coupled to abelian gauge fields has been proposed as a gravity dual for Lifshitz like critical phenomena in 2 + 1 dimensions. The finite temperature behavior is described by black holes that are asymptotic to the Lifshitz fixed point geometry. There is a one-parameter family of charged black holes, where the magnitude of the charge is uniquely determined by the black hole area. These black holes are thermodynamically stable and become extremal in the limit of vanishing size. The theory also has a discrete spectrum of localized objects described by non-singular spacetime geometries. The finite temperature behavior of Wilson loops is reminiscent of strongly coupled gauge theories in 3 + 1 dimensions, including screening at large distances.
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| 19. |
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| 20. |
- Gottsäter, Anders, et al.
(författare)
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Aterosklerotisk kärlsjukdom
- 2021. - 5
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Ingår i: Kirurgi. - 9789144134239 ; , s. 504-510
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Bokkapitel (refereegranskat)
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| 21. |
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| 25. |
- Modin, H, et al.
(författare)
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Genome-wide linkage screen of a consanguineous multiple sclerosis kinship
- 2003
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 9:2, s. 128-134
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS), like A lzheimer’s disease (A D) and Parkinson’s disease (PD), is a common neurological disorder thought to be caused by the interaction of several genes with unknown environmental factors. In both A D and PD the identification of disease forms inherited in a classic Mendelian fashion has helped investigators elucidate pathogenetic mechanisms. In this study a whole-genome screen, with an average of 608 successful genotypes per person, was performed on nine members of a consanguineous family: the index case, three of her siblings and her daughter, all of whom have been diagnosed with definite MS; as well as the parents of the index case (first cousins), one of her five healthy siblings and her husband (who is also her first cousin). Nonparametric linkage analysis was performed on genotyping data. Based on the presence of consanguinity, the a priori hypothesis was that the disease is transmitted in an autosomal recessive fashion in the pedigree. Linkage analysis revealed a suggestive logarithm of odds (LO D) score of 2.29 on the long arm of chromosome 9. Four of five affected family members were identically homozygous for a haplotype under this peak, spanning approximately 43 cM, while the fifth affected subject and all unaffected family members were hetero zygous for the haplotype.
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| 26. |
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| 27. |
- Schramm, R, et al.
(författare)
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Leukocyte adhesion in aorta and femoral artery in vivo is mediated by LFA-1
- 2004
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Ingår i: Inflammation Research. - : Springer Science and Business Media LLC. - 1420-908X .- 1023-3830. ; 53:10, s. 523-527
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Cytokine-induced recruitment of leukocytes is an early feature during arterial injury and atherosclerotic plaque formation. The aim of this study was to analyze the role of the beta(2)-integrin lymphocyte function-associated antigen-1 (LFA- 1; CD11a/CD18) in cytokine-triggered firm leukocyte adhesion to arterial endothelium in vivo. Material and Methods: Intravital fluorescence microscopy was used to study leukocyte firm adhesion in the mouse aorta and femoral artery in response to combined local challenge with TNF-alpha and IL-1beta. Results: In wild-type (WT) mice, cytokine stimulation resulted in firm adhesion of 14.6 +/- 2.8 and 11.3 +/- 1.3 leukocytes/mm along the endothelium in the aorta and femoral artery (P < 0.05 vs. PBS-treated controls, n = 5-6). Notably, the number of firmly adherent leukocytes in aorta and femoral artery of cytokine-stimulated LFA-1-deficient animals was reduced by 54% and 92% indicating an important role of LFA-1 in leukocyte adhesion to arterial endothelium (P < 0.05 vs. controls, n = 5-6). In addition, pretreatment of WT mice with a monoclonal antibody (mAb) directed against murine LFA-1 attenuated the leukocyte adhesive response by 60% and 86% in aorta and femoral artery, respectively (P < 0.05 vs. control mAb-treated WT, n = 5-12). Conclusion: These novel data demonstrate that cytokine-induced firm leukocyte adhesion in the mouse aorta and femoral artery is LFA-1-dependent in vivo, which may implicate an important role for this β(2)-integrin leukocyte extravasation. in arterial injury and atherogenesis.
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| 31. |
- Thorgeirsson, Thorgeir E, et al.
(författare)
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A variant associated with nicotine dependence, lung cancer and peripheral arterial disease
- 2008
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 452:7187, s. 9-638
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Tidskriftsartikel (refereegranskat)abstract
- Smoking is a leading cause of preventable death, causing about 5 million premature deaths worldwide each year(1,2). Evidence for genetic influence on smoking behaviour and nicotine dependence (ND)(3-8) has prompted a search for susceptibility genes. Furthermore, assessing the impact of sequence variants on smoking-related diseases is important to public health(9,10). Smoking is the major risk factor for lung cancer (LC)(11-14) and is one of the main risk factors for peripheral arterial disease (PAD)(15-17). Here we identify a common variant in the nicotinic acetylcholine receptor gene cluster on chromosome 15q24 with an effect on smoking quantity, ND and the risk of two smoking- related diseases in populations of European descent. The variant has an effect on the number of cigarettes smoked per day in our sample of smokers. The same variant was associated with ND in a previous genomewide association study that used low- quantity smokers as controls(18,19), and with a similar approach we observe a highly significant association with ND. A comparison of cases of LC and PAD with population controls each showed that the variant confers risk of LC and PAD. The findings provide a case study of a gene - environment interaction(20), highlighting the role of nicotine addiction in the pathology of other serious diseases.
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| 49. |
- Torkvist, L, et al.
(författare)
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Role of CD18-dependent neutrophil recruitment in skin and intestinal wound healing
- 2001
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Ingår i: European surgical research. Europaische chirurgische Forschung. Recherches chirurgicales europeennes. - : S. Karger AG. - 0014-312X. ; 33:4, s. 249-254
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Tidskriftsartikel (refereegranskat)abstract
- CD11/CD18 is an important adhesion molecule mediating recruitment of leukocytes, which, in turn, may cause postoperative injury in the skin and gastrointestinal tract. The objective of the present study was to investigate the effects of inhibiting the function of CD18 on surgery-induced dermal and intestinal infiltration of neutrophils and on the healing of surgical skin flaps and colonic anastomosis. A flap in the dorsal skin or an end-to-end colonic anastomosis were created in Sprague-Dawley rats. Skin necrosis and anastomotic breaking strength were analyzed 6 and 3 days after surgery, respectively. Tissue myeloperoxidase (MPO) was used as a marker of neutrophil recruitment. Administration of a monoclonal antibody directed against rat CD18 (WT.3, 2 mg/kg) significantly decreased dermal and anastomotic MPO activity by more than 80%. Passive immunization against CD18 significantly improved flap survival, i.e. the survival was 80% in the anti-CD18 antibody group as compared to 38% in the control group. In contrast, this passive immunization against CD18 had no effect on the reconstitution of the integrity of the colonic anastomosis, i.e. the anastomotic breaking strength was 1.3 ± 0.1 and 1.3 ± 0.3 N in the control and anti-CD18 antibody group, respectively. These findings suggest that specific inhibition of CD18 function and reduced neutrophil recruitment may improve the survival of experimental skin flaps and, thus, may represent a potential target for therapeutic intervention. In contrast, we also found that blocking CD18-dependent neutrophil infiltration in the intestine had no effect on breaking strength of colonic anastomosis. Thus, neutrophils may influence the wound-healing process differently in specific organs and this needs to be considered when applying an anti-inflammatory treatment regime in order to improve tissue healing.
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