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- Andreassen, A., et al.
(författare)
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2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces genetic changes in murine intestinal tumours and cells with ApcMin mutation
- 2006
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Ingår i: Mutat Res. ; 604:1-2, s. 60-70
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Tidskriftsartikel (refereegranskat)abstract
- 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the mutagenic heterocyclic amines derived from cooked meat. In previous animal studies, spontaneous tumour formation in B6(Min/+) mice was associated with somatic loss of the wild-type Apc+ allele by loss of the entire chromosome 18 or by recombination. The objective of this study was to examine genetic changes caused by PhIP-exposure in a mouse intestinal cell line and in tumours from hybrid mice by keeping track of the chromosomes carrying the two Apc alleles. We transformed the SV40 T-immortalised intestinal epithelial cell line IMCE, derived from the B6(Min/+) mice by exposure to N-OH-PhIP, and studied the effect on Apc status and chromosome 18. Eighteen transformed cultures were obtained and all of them had retained the Apc+ allele. Five of seven transformed cultures were tumorigenic after implantation in nude mice. Chromosomal analysis of these five cultures and the parent IMCE cell line showed that the IMCE cells were near-tetraploid with an average of 77 chromosomes/cell, while the tumorigenic cell cultures were all triploid to hyper-triploid with a range of 61-69 chromosomes/cell. The number of copies of chromosome 18 was about four in the IMCE line and this copy number was retained in the transformed lines derived from IMCE. Changes in chromosome 18 and Apc during tumour development in vivo were examined in spontaneously formed and PhIP-induced intestinal tumours from two hybrid mice strains, i.e. B6(Min/+) - a murine FAP model - crossed with either AKR/J or A/J. We evaluated the allelic status of Apc, and the heterogenic microsatellite markers D18Mit19 and D18Mit4, located at the upper and lower ends of chromosome 18, respectively. In tumours from untreated animals, instability in the D18Mit19 and Apc was observed. Upon PhIP exposure, the B6(Min/A+) hybrid mouse tumours differed distinctly in genetic profile from those obtained from untreated animals and we detected three genetically different tumour groups, all of which had apparently retained Apc+. One group had allelic balance between the Apc(Min) and Apc+, the second had allelic imbalance between the Apc and D18Mit4 alleles, indicative of chromosomal stability in the first group and instability in the lower end of chromosome 18 in the second group, respectively. The third group showed variable allelic status of the three markers. A similar change in genetic profile was also seen in intestinal tumours of PhIP-exposed B6(Min/AKR+) hybrid mice, but it was less pronounced. Chromosomal breaks and/or recombinational events could be alternative explanations for the observed allelic imbalances in chromosome 18 markers in intestinal tumours from PhIP-exposed mice.
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- Jacobsen, M.D., et al.
(författare)
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Quantitative T-wave analysis predicts 1 year prognosis and benefit from early invasive treatment in the FRISC II study population
- 2005
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 26:2, s. 112-118
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To investigate the prognostic value of T-wave abnormalities in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), and whether such ECG changes may predict benefit from an early coronary angiography. Although ST-segment changes are considered the most important ECG feature in NSTE-ACS, T-wave abnormalities are the most common ECG finding. We hypothesize that a new quantitative approach to T-wave analysis could improve the prognostic value of this ECG abnormality. Methods and results: Quantitative T-wave analysis was performed on the admission ECG in 1609 patients with NSTE-ACS. Nine different categories of T-wave abnormality were analysed for their prognostic value concerning clinical outcome in patients not randomized to early coronary angiography. Also, the presence of one category (i.e. T-wave abnormality in >6 leads) was analysed for its predictive value concerning benefit from early coronary angiography. The combined study endpoint was death or myocardial infarction at 1 year follow-up. Patients with >6 leads with abnormal T-waves and concomitant ST-segment depression had a higher risk when not receiving early coronary angiography (24 vs. 12%, respectively, P = 0.003), but could be brought to the same level of risk as the remaining patients with this treatment. For non-invasively treated patients five different categories of T-wave abnormality were significantly associated with an adverse outcome. Conclusion: New quantitative T-wave analysis of the admission ECG gives additional predictive information concerning clinical outcome and identifies patients who benefit from early coronary angiography.
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- Nielsen, TR, et al.
(författare)
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Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis
- 2009
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 15:4, s. 431-436
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Tidskriftsartikel (refereegranskat)abstract
- Background Both human leukocyte antigen (HLA)-DRB1*15 and Epstein-Barr virus infection presenting as infectious mononucleosis (IM) are recognized as risk factors for multiple sclerosis (MS). However, their combined effect and possible interaction on MS risk is not known. Objective To assess the association between HLA-DRB1*15 and risk of MS in persons with and without IM. Methods We compared the prevalence of DRB1*15 in MS patients with ( n = 76) and without ( n = 1,836) IM with the corresponding distributions in blood donors with ( n = 62) and without ( n = 484) IM histories. This allowed us to estimate the relative risk of MS associated with DRB1*15 in the presence and absence, respectively, of previous IM. We then estimated the interaction between DRB1*15 and IM as the ratio of the two individual odds ratios. Results In IM-naïve individuals, DRB1*15 carried a 2.4-fold (95% confidence interval [CI], 2.0–3.0) increased MS risk. In contrast, among persons with IM history, DRB1*15 was associated with a 7.0-fold (95% CI, 3.3–15.4) increased MS risk. Thus, the MS risk conferred by HLA-DRB1*15 was 2.9 (95% CI, 1.3–6.5)-fold stronger in the presence than in the absence of IM. Combined with previous results, this result indicates that DRB1*15-positive persons with a history of IM may be at a 10.0-fold (95% CI, 6.0–17.9) increased risk of MS compared with persons who are DRB1*15 and IM-naïve. Conclusion DRB1*15 and IM may act in synergy causing MS.
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- Svensson, A., et al.
(författare)
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A 60 000 year Greenland stratigraphic ice core chronology
- 2008
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9332. ; 4:1, s. 47-57
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Tidskriftsartikel (refereegranskat)abstract
- The Greenland Ice Core Chronology 2005 (GICC05) is a time scale based on annual layer counting of high-resolution records from Greenland ice cores. Whereas the Holocene part of the time scale is based on various records from the DYE-3, the GRIP, and the NorthGRIP ice cores, the glacial part is solely based on NorthGRIP records. Here we present an 18 ka extension of the time scale such that GICC05 continuously covers the past 60 ka. The new section of the time scale places the onset of Greenland Interstadial 12 (GI-12) at 46.9 +/- 1.0 ka b2k (before year AD 2000), the North Atlantic Ash Zone II layer in GI-15 at 55.4 +/- 1.2 ka b2k, and the onset of GI-17 at 59.4 +/- 1.3 ka b2k. The error estimates are derived from the accumulated number of uncertain annual layers. In the 40-60 ka interval, the new time scale has a discrepancy with the Meese-Sowers GISP2 time scale of up to 2.4 ka. Assuming that the Greenland climatic events are synchronous with those seen in the Chinese Hulu Cave speleothem record, GICC05 compares well to the time scale of that record with absolute age differences of less than 800 years throughout the 60 ka period. The new time scale is generally in close agreement with other independently dated records and reference horizons, such as the Laschamp geomagnetic excursion, the French Villars Cave and the Austrian Kleegruben Cave speleothem records, suggesting high accuracy of both event durations and absolute age estimates.
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