| 1. |
- Karppinen, S. -M., et al.
(författare)
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Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies
- 2006
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 43:11, s. 856-862
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Tidskriftsartikel (refereegranskat)abstract
- Background: BARD1 was originally identified as a BRCA1- interacting protein but has also been described in tumour-suppressive functions independent of BRCA1. Several studies have indicated that the BARD1 gene is a potential target for germline changes predisposing to breast and ovarian cancer. The C- terminal Cys557Ser change has previously been uncovered to associate with an increased risk of breast cancer and was recently shown to result in defective apoptotic activities. Aim and methods: Conformation- sensitive gel electrophoresis, minisequencing, TaqMan assays, denaturing high- performance liquid chromatography analysis and DNA sequencing were used to investigate the prevalence of the Cys557Ser allele in a large Nordic case - control study cohort consisting of 2906 patients with breast or ovarian cancer, 734 with prostate cancer, 188 with colorectal cancer, 128 men with breast cancer, and 3591 controls from Finland, Iceland, Denmark, Sweden and Norway. Results: The frequency of the BARD1 Cys557Ser variant seemed to increase among patients from families with breast or ovarian cancer lacking BRCA1 or BRCA2 mutations: a significant difference was obtained compared with controls ( 6.8% v 2.7%; p < 0.001; odds ratio ( OR) 2.6; 95% confidence interval (CI) 1.7 to 4.0) and with patients from BRCA1/ BRCA2 mutation- positive families ( 6.8% v 2.2%; p = 0.01; OR 3.2; 95% CI 1.2 to 8.3). In contrast, no major association with male breast, ovarian, colorectal or prostate cancer was observed. Additionally, a novel BARD1 allele resulting in Ser558Pro was identified in familial breast cancer cases. Conclusion: These results provide further evidence that BARD1 Cys557Ser confers a slightly increased risk of breast cancer in women.
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| 2. |
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| 3. |
- Aasa, M., et al.
(författare)
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Temporal changes in TIMI myocardial perfusion grade in relation to epicardial flow, ST-resolution and left ventricular function after primary percutaneous coronary intervention
- 2007
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Ingår i: Coron Artery Dis. - 0954-6928. ; 18:7, s. 513-518
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Myocardial perfusion at the end of reperfusion therapy assessed angiographically with thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade (TMPG) has been associated with recovery of left ventricular (LV) function and survival. The aim of this analysis was to study the evolution of TMPG within the first week following primary percutaneous coronary intervention (PCI) and its association with ECG-derived ST-segment resolution (STRES) and recovery of LV function. METHODS: A total of 76 patients with acute myocardial infarction were pretreated with enoxaparine and abciximab and subjected to primary PCI within a prospective study and evaluated with TMPG assessed on coronary angiography at the end of the procedure and after 5-7 days. STRES was evaluated at 120 min post inclusion and global LV function was assessed by echocardiography after 30 days. RESULTS: Reperfusion (TIMI flow 2-3) was reached in all patients. Forty one percent had 'open myocardium' (i.e. TMPG 2 or 3) after PCI, a number that increased to 61% after 5-7 days (P=0.003). STRES >50% was reached in 73% of the patients and there was a good correlation between TMPG and STRES. Furthermore, those who improved from 'closed' to 'open myocardium' had higher STRES (and similar to those with 'open myocardium' already post-PCI) than those who had 'closed myocardium' at both occasions (80 vs. 52%, P=0.012). CONCLUSION: A significant increase was found in the number of patients with 'open myocardium' within the first week post-primary PCI and STRES seems to predict this improvement.
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| 4. |
- Atar, D., et al.
(författare)
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Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) trial
- 2009
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Ingår i: Journal of the American College of Cardiology. - 1558-3597. ; 53:8, s. 720-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The purpose of this study was to investigate whether FX06 would limit infarct size when given as an adjunct to percutaneous coronary intervention. BACKGROUND: FX06, a naturally occurring peptide derived from human fibrin, has been shown to reduce myocardial infarct size in animal models by mitigating reperfusion injury. METHODS: In all, 234 patients presenting with acute ST-segment elevation myocardial infarction were randomized in 26 centers. FX06 or matching placebo was given as intravenous bolus at reperfusion. Infarct size was assessed 5 days after myocardial infarction by late gadolinium enhanced cardiac magnetic resonance imaging. Secondary outcomes included size of necrotic core zone and microvascular obstruction at 5 days, infarct size at 4 months, left ventricular function, troponin I levels, and safety. RESULTS: There were no baseline differences between groups. On day 5, there was no significant difference in total late gadolinium enhanced zone in the FX06 group compared with placebo (reduction by 21%; p = 0.207). The necrotic core zone, however, was significantly reduced by 58% (median 1.77 g [interquartile range 0.0, 9.09 g] vs. 4.20 g [interquartile range 0.3, 9.93 g]; p < 0.025). There were no significant differences in troponin I levels (at 48 h, -17% in the FX06 group). After 4 months, there were no longer significant differences in scar size. There were numerically fewer serious cardiac events in the FX06-treated group, and no differences in adverse events. CONCLUSIONS: In this proof-of-concept trial, FX06 reduced the necrotic core zone as one measure of infarct size on magnetic resonance imaging, while total late enhancement was not significantly different between groups. The drug appears safe and well tolerated. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury [F.I.R.E.]; NCT00326976).
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| 6. |
- Svensson, L., et al.
(författare)
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Comparison of very early treatment with either fibrinolysis or percutaneous coronary intervention facilitated with abciximab with respect to ST recovery and infarct-related artery epicardial flow in patients with acute ST-segment elevation myocardial infarction: the Swedish Early Decision (SWEDES) reperfusion trial
- 2006
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Ingår i: Am Heart J. - : Mosby, Inc.. - 1097-6744 .- 0002-8703. ; 151:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Results from a number of studies indicate that primary percutaneous coronary intervention (PCI) is superior to fibrinolysis for treatment of acute ST-elevation myocardial infarction. Modern adjunctive antithrombotic treatment with systematic use of low-molecular-weight heparins, fibrin-specific thrombolysis, and glycoprotein IIb/IIIa receptor inhibitors may improve the outcome compared with what was achieved in previous studies. METHODS: Patients with ST-elevation myocardial infarction were randomized to receive enoxaparin followed by reteplase (group A; n = 104) or enoxaparin followed by abciximab and transfer to invasive center for optional PCI (group B; n = 101). Primary end points were ST-segment resolution 120 minutes and TIMI flow at coronary angiography 5 to 7 days after randomization. RESULTS: Forty-two percent of the patients started therapy in the prehospital phase. Time from symptom to treatment was 114 minutes in group A and 202 minutes in group B. Baseline characteristics were similar in the 2 groups. Sixty-four percent in group A and 68% in group B had ST resolution of > 50% at 120 minutes (not significant). At control angiography, 54% in the fibrinolytic group and 71% in the invasive group had TIMI 3 flow (P = .04). At 30 days, the composite of death, stroke, or reinfarction occurred in 8% in the fibrinolytic group compared with 3% in the invasive group (not significant). CONCLUSIONS: Despite much shorter time delay to start of fibrinolysis than PCI, this did not result in signs of superior myocardial reperfusion. Epicardial flow in the infarct-related artery was better after invasive therapy, and there was a trend toward better clinical outcome after this treatment compared with after fibrinolysis.
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| 7. |
- Tjonneland, A., et al.
(författare)
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Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study
- 2009
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 58:12, s. 1606-1611
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dietary linoleic acid, an n-6 polyunsaturated fatty acid, is metabolised to arachidonic acid, a component of colonocyte membranes. Metabolites of arachidonic acid have pro-inflammatory properties and are increased in the mucosa of patients with ulcerative colitis. The aim of this investigation was to conduct the first prospective cohort study investigating if a high dietary intake of linoleic acid increases the risk of developing incident ulcerative colitis. Design and setting: Dietary data from food frequency questionnaires were available for 203 193 men and women aged 30-74 years, resident in the UK, Sweden, Denmark, Germany or Italy and participating in a prospective cohort study, the European Prospective Investigation into Cancer and Nutrition (EPIC). These participants were followed up for the diagnosis of ulcerative colitis. Each case was matched with four controls and the risk of disease calculated by quartile of intake of linoleic acid adjusted for gender, age, smoking, total energy intake and centre. Results: A total of 126 participants developed ulcerative colitis (47% women) after a median follow-up of 4.0 years (range, 1.7-11.3 years). The highest quartile of intake of linoleic acid was associated with an increased risk of ulcerative colitis (odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.23 to 5.07, p = 0.01) with a significant trend across quartiles (OR = 1.32 per quartile increase, 95% CI = 1.04 to 1.66, p = 0.02 for trend). Conclusions: The data support a role for dietary linoleic acid in the aetiology of ulcerative colitis. An estimated 30% of cases could be attributed to having dietary intakes higher than the lowest quartile of linoleic acid intake.
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| 8. |
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| 9. |
- Hart, Andrew R, et al.
(författare)
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Diet in the aetiology of ulcerative colitis: A European prospective cohort study
- 2008
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Ingår i: Digestion. - : S. Karger AG. - 1421-9867 .- 0012-2823. ; 77:1, s. 57-64
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: The causes of ulcerative colitis are unknown, although it is plausible that dietary factors are involved. Case-control studies of diet and ulcerative colitis are subject to recall biases. The aim of this study was to examine the prospective relationship between the intake of nutrients and the development of ulcerative colitis in a cohort study. Methods: The study population was 260,686 men and women aged 20-80 years, participating in a large European prospective cohort study (EPIC). Participants were residents in the UK, Sweden, Denmark, Germany or Italy. Information on diet was supplied and the subjects were followed up for the development of ulcerative colitis. Each incident case was matched with four controls and dietary variables were divided into quartiles. Results: A total of 139 subjects with incident ulcerative colitis were identified. No dietary associations were detected, apart from a marginally significant positive association with an increasing percentage intake of energy from total polyunsaturated fatty acids (trend across quartiles OR = 1.19 (95% CI = 0.99-1.43) p = 0.07). Conclusions: No associations between ulcerative colitis and diet were detected, apart from a possible increased risk with a higher total polyunsaturated fatty acid intake. A biological mechanism exists in that polyunsaturated fatty acids are metabolised to pro-inflammatory mediators.
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| 10. |
- Hedhammar, My, Professor, 1975-, et al.
(författare)
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Structural properties of recombinant nonrepetitive and repetitive parts of major ampullate spidroin 1 from Euprosthenops australis : implications for fiber formation
- 2008
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Ingår i: Journal of Biotechnology. - : American Chemical Society (ACS). - 0168-1656 .- 1873-4863. ; 47:11, s. 3407-17
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Tidskriftsartikel (refereegranskat)abstract
- Spider dragline silk proteins, spidroins, have a tripartite composition; a nonrepetitive N-terminal domain, a central repetitive region built up from many iterated poly-Ala and Gly rich blocks, and a C-terminal nonrepetitive domain. It is generally believed that the repetitive region forms intermolecular contacts in the silk fibers, while precise functions of the terminal domains have not been established. Herein, thermal, pH, and salt effects on the structure and aggregation and/or polymerization of recombinant N- and C-terminal domains, a repetitive segment containing four poly-Ala and Gly rich coblocks, and combinations thereof were studied. The N- and C-terminal domains have mainly alpha-helical structure, and interestingly, both form homodimers. Dimerization of the end domains allows spidroin multimerization independent of the repetitive part. Reduction of an intersubunit disulfide in the C-terminal domain lowers the thermal stability but does not affect dimerization. The repetitive region shows helical secondary structure but appears to lack stable folded structure. A protein composed of this repetitive region linked to the C-terminal domain has a mainly alpha-helical folded structure but shows an abrupt transition to beta-sheet structures upon heating. At room temperature, this protein self-assembles into macroscopic fibers within minutes. The secondary structures of none of the domains are altered by pH or salt. However, high concentrations of phosphate affect the tertiary structure and accelerate the aggregation propensity of the repetitive region. Implications of these results for dragline spidroin behavior in solution and silk fiber formation are discussed.
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