| 1. |
- Broberg Palmgren, Karin, et al.
(författare)
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Association between polymorphisms in RMI1, TOP3A, and BLM and risk of cancer, a case-control study.
- 2009
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 9:May 11
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mutations altering BLM function are associated with highly elevated cancer susceptibility (Bloom syndrome). Thus, genetic variants of BLM and proteins that form complexes with BLM, such as TOP3A and RMI1, might affect cancer risk as well. METHODS: In this study we have studied 26 tagged single nucleotide polymorphisms (tagSNPs) in RMI1, TOP3A, and BLM and their associations with cancer risk in acute myeloid leukemia/myelodysplatic syndromes (AML/MDS; N = 152), malignant melanoma (N = 170), and bladder cancer (N = 61). Two population-based control groups were used (N = 119 and N = 156). RESULTS: Based on consistency in effect estimates for the three cancer forms and similar allelic frequencies of the variant alleles in the control groups, two SNPs in TOP3A (rs1563634 and rs12945597) and two SNPs in BLM (rs401549 and rs2532105) were selected for analysis in breast cancer cases (N = 200) and a control group recruited from spouses of cancer patients (N = 131). The rs12945597 in TOP3A and rs2532105 in BLM showed increased risk for breast cancer. We then combined all cases (N = 584) and controls (N = 406) respectively and found significantly increased risk for variant carriers of rs1563634 A/G (AG carriers OR = 1.7 [95%CI 1.1-2.6], AA carriers OR = 1.8 [1.2-2.8]), rs12945597 G/A (GA carriers OR = 1.5 [1.1-1.9], AA carriers OR = 1.6 [1.0-2.5]), and rs2532105 C/T (CT+TT carriers OR = 1.8 [1.4-2.5]). Gene-gene interaction analysis suggested an additive effect of carrying more than one risk allele. For the variants of TOP3A, the risk increment was more pronounced for older carriers. CONCLUSION: These results further support a role of low-penetrance genes involved in BLM-associated homologous recombination for cancer risk.
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| 2. |
- Englund, Anna-Lena, 1949-, et al.
(författare)
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Värdegrunden reducerad till metod
- 2009
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Ingår i: Pedagogiska magasinet. - Stockholm : Lärarförbundet. - 1401-3320. ; 13:4, s. 18-21
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Det behövs en etisk vändning i diskussionen om främjande och förebyggande program. Alltför stort intresse riktas mot frågan om evidens och effektivitet och alltför lite intresse riktas mot värdefrågorna. Vad innebäör det för lärarens professionalism om manualstyrda aktiviteter ersätter samtal och samspel?
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| 3. |
- Engström, Karin, et al.
(författare)
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Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions.
- 2009
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Ingår i: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. - : Elsevier BV. - 1879-2871 .- 0027-5107. ; 667, s. 4-14
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The susceptibility to arsenic (As)-induced diseases differs greatly between individuals, probably to a large extent due to genetic differences in arsenic metabolism. The aim for this study was to identify genetic variants affecting arsenic metabolism. METHODS: We evaluated the association between urinary metabolite pattern and polymorphisms in three gene-groups related to arsenic metabolism: (1) methyltransferases, (2) other genes involved in one-carbon metabolism and (3) genes involved in reduction reactions. Forty-nine polymorphisms were successfully genotyped in indigenous women (N=104) from northern Argentina, exposed to approximately 200mug/L of arsenic in drinking water, with a unique metabolism with low percent monomethylated arsenic (%MMA) and high percent dimethylated As (%DMA). RESULTS: Genetic factors affecting arsenic metabolite pattern included two polymorphisms in arsenic (+III) methyltransferase (AS3MT) (rs3740400, rs7085104), where carriers had lower %MMA and higher %DMA. These single nucleotide polymorphisms (SNPs) were in strong linkage disequilibrium (LD) with three intronic AS3MT SNPs, previously reported to be associated with arsenic metabolism, indicating the existence of a strongly methylating, population-specific haplotype. The CYP17A1 rs743572, 27kilobasepairs (kbs) upstream of AS3MT, was in strong LD with the AS3MT SNPs and thus had similar effects on the metabolite profile. Smaller effects were also seen for one-carbon metabolism genes choline dehydrogenase (CHDH) (rs9001, rs7626693) and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) (rs1801394) and genes involved in reduction reactions, glutaredoxin (GLRX) (rs3822751) and peroxiredoxin 2 (PRDX2) (rs10427027, rs12151144). Genotypes associated with more beneficial arsenic metabolite profile (low %MMA and/or high %DMA in urine) were more common in this population, which has been exposed to arsenic in drinking water for thousands of years. CONCLUSIONS: Polymorphisms in AS3MT and in genes involved in one-carbon metabolism and reduction reactions affects arsenic metabolism.
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| 4. |
- Engström, Karin, et al.
(författare)
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Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina.
- 2007
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Ingår i: Environmental Health Perspectives. - : Environmental Health Perspectives. - 1552-9924 .- 0091-6765. ; 115:4, s. 599-605
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Tidskriftsartikel (refereegranskat)abstract
- The susceptibility to arsenic-induced diseases differs greatly between individuals, possibly due to interindividual variations in As metabolism that affect retention and distribution of toxic metabolites. To elucidate the role of genetic factors in As metabolism, we studied how polymorphisms in six genes affected the urinary metabolite pattern in a group of indigenous women (n = 147) in northern Argentina who were exposed to approximately 200 mu g/L As in drinking water. These women had low urinary percentages of monomethylated As (MMA) and high percentages of dimethylated As (DMA). MMA has been associated with adverse health effects, and DMA has the lowest body retention of the metabolites. The genes studied were arsenic(+ 111) methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferases mu I (GSTM1) and theta I (GSTT1). We found three intronic polymorphisms in AS3MT (G12390C, C14215T, and G35991A) associated with a lower percentage of MMA (%MMA) and a higher percentage of DMA (%DMA) in urine. The variant homozygotes showed approximately half the %MMA compared with wild-type homozygotes. These polymorphisms were in strong linkage, with high allelic frequencies (72-76%) compared with other populations. We also saw minor effects of other polymorphisms in the multivariate regression analysis with effect modification for the deletion genotypes for GSTM1 (affecting %MMA) and GSTT1 (affecting %MMA and %DMA). For pregnant women, effect modification was seen for the folate-metabolizing genes MTR and MTHFA In conclusion, these findings indicate that polymorphisms in AS3MT-and possibly GSTM1, GSTT1, MTR, and MTHFR-are responsible for a large part of the interindividual variation in As metabolism and susceptibility.
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| 5. |
- Engström, Karin, et al.
(författare)
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Genetic variation in glutathione-related genes and body burden of methylmercury
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - Research Triangle Park, N.C. : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:6, s. 734-739
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to toxic methylmercury (MeHg) through fish consumption is a large problem worldwide, and it has led to governmental recommendations of reduced fish consumption and blacklisting of mercury-contaminated fish. The elimination kinetics of MeHg varies greatly among individuals. Knowledge about the reasons for such variation is of importance for improving the risk assessment for MeHg. One possible explanation is hereditary differences in MeHg metabolism. MeHg is eliminated from the body as a glutathione (GSH) conjugate. OBJECTIVES: We conducted this study to assess the influence of polymorphisms in GSH-synthesizing [glutamyl-cysteine ligase modifier subunit (GCLM-588) and glutamyl-cysteine ligase catalytic subunit (GCLC-129)] or GSH-conjugating [glutathione S-transferase pi 1 (GSTP1-105 and GSTP1-114)] genes on MeHg retention. METHODS: Based on information obtained from questionnaires, 292 subjects from northern Sweden had a high consumption of fish (lean/fat fish two to three times per week or more). We measured total Hg in erythrocytes (Ery-Hg) and long-chain n-3 polyunsaturated fatty acids in plasma (P-PUFA; an exposure marker for fish intake). RESULTS: The GSTP1 genotype modified Ery-Hg; effects were seen for GSTP1-105 and -114 separately, and combining them resulted in stronger effects. We found evidence of effect modification: individuals with zero or one variant allele demonstrated a steeper regression slope for Ery-Hg (p = 0.038) compared with individuals with two or more variant alleles. The GCLM-588 genotype also influenced Ery-Hg (p = 0.035): Individuals with the GCLM-588 TT genotype demonstrated the highest Ery-Hg, but we saw no evidence of effect modification with increasing P-PUFA. CONCLUSIONS: These results suggest a role of GSH-related polymorphisms in MeHg metabolism.
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| 6. |
- Engström, Kerstin, 1959-
(författare)
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Genus & genrer : forskningsanknutna genusdiskurser i dagspress
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- At the centre of this study lies the question of how research-related media texts contribute to the social construction of sex and gender conceptions when they use research, either as a main source, or to support or comment on specific issues and statements, from the political arena, for example. The principal aim of the study has been to analyze and problematize the ways in which different types of newspapers, genres and editorial sections reproduce, or contribute to change, in existing gender discourses.The material was collected from two Swedish newspapers during the year 2001: the national morning paper Dagens Nyheter (DN), and the national evening paper Aftonbladet.The theories of discourse, agenda-setting and -framing in this study are related to the questions: what kinds of knowledge on women and men, and biological, physiological, psychological, social and cultural perspectives on sex/gender are represented; how are they described; and how do content and form contribute to the (re)production of, or change in, gender discourses? The main analytical perspectives are those about gender discourse (re)production, genres as ideological forms, and the epistemologies of journalism.A combination of analytical strategies and methods was used: content and thematic analysis, and qualitative analysis of text and language with methodological tools from different traditions of discourse analysis.In my study, I can see an interplay between research traditions and genre conventions in the (re)production of gender discourses. Since the news sections repeatedly choose to publish research as empiric and in the form of results, and then within that, primarily findings from medicine and the social sciences, these areas are reproduced as important and relevant, and as producers of objective, true knowledge that can be presented as simple facts. Research-related texts in culture journalism, on the other hand, follow the tradition of primarily treating research within the humanities, and nowadays also gender and queer theoretical perspectives within different disciplines. Through the genre conventions of culture journalism, this research is reproduced as something that you can reflect upon, problematize, criticize, form an opinion of, and judge.The study also gives reason to argue that media logic and institutionalized genre conventions contribute to the reproduction of science and research as different worlds and cultures, in which the natural sciences and the humanities are found in different media spaces, and different forms of knowledge about sex/gender are given space on different conditions and in different forms.
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| 7. |
- Harari, Raul, et al.
(författare)
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Exposure and Toxic Effects of Elemental Mercury in Gold Mining Activities
- 2009
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Ingår i: Epidemiology. - : Ovid Technologies (Wolters Kluwer Health). - 1044-3983. ; 20:6, s. 264-265
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Tidskriftsartikel (refereegranskat)abstract
- Elemental mercury (Hg0) is widely used in gold-mining activities in South America, Africa and Asia. Miners use Hg0 to extract gold, and are exposed by inhalation when burning the gold amalgam to get rid of the Hg0. Burning is usually performed only once per 1–3 weeks. Gold buyers again burn the gold to be sure that they only buy gold. Hg0 affects the central nervous system (CNS), but the exposure-response relationship for discrete but important effects is not well known. As indicators of exposure, Hg levels in blood, plasma and urine are useful. It is usually assumed that there is a simple relationship between exposure and these biomarkers. However, recent data indicate that genetic traits may modify the retention of Hg. Also, there is a possibility that such factors may influence the exposure-response curves.
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| 8. |
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| 9. |
- Broo, Helén, 1968, et al.
(författare)
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Non-linear finite-element analysis of the shear response in prestressed concrete bridges
- 2009
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Ingår i: Magazine of Concrete Research. - : Thomas Telford Ltd.. - 1751-763X .- 0024-9831. ; 61:8, s. 591 -608
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Tidskriftsartikel (refereegranskat)abstract
- For the structural assessment of concrete bridges, the non-linear finite-element method has become an important and increasingly used tool. The method has shown a great potential to reveal higher load-carrying capacity compared with conventional assessment methods. However, the modelling method used for reinforced and prestressed concrete members subjected to shear and torsion has been questioned. The aim of this study is to present an analysis method for evaluation of the load-carrying capacity of prestressed concrete bridges, when failure resulting from shear and torsion is the main problem. The modelling method used was previously worked out and verified for shear-type cracking and shear failure. Here, shell elements with embedded reinforcement were used together with non-linear material models, taking into account the fracture energy of cracking plain concrete and the reduction of the concrete compression strength owing to lateral tensile strain. Analyses with the method proposed have shown to predict the shear response and the shear capacity on the safe side. In the work presented here, the load-carrying capacity of a box-girder bridge was evaluated as a case study. The whole bridge was modelled, but only the part that was most critical to shear and torsion was modelled according to the method previously worked out and was combined with beam elements for the rest of the bridge. The case study showed a substantially higher load-carrying capacity for the bridge compared with the assessment with conventional methods. In the evaluation, several possible safety formats were used in combination with the non-linear finite-element method. It was shown that the format using partial safety factors gave unrealistic conservative results; it is more correct to use the semi-probabilistic formats for non-linear finite-element analysis. © 2009 Thomas Telford Ltd.
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| 10. |
- Broo, Helén, 1968, et al.
(författare)
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Reinforced and prestressed concrete beams subjected to shear and torsion
- 2007
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Ingår i: Fracture Mechanics of Concrete and Concrete Structures. - 9780415440660 ; 2, s. 881-888
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Konferensbidrag (refereegranskat)abstract
- Today, the nonlinear finite element method is commonly used by practicing engineers, although design and assessment for shear and torsion in reinforced concrete structures are still made using methods based on sectional forces. By modelling the shear behaviour, using 3D nonlinear FEM, higher load carrying capacity and more favourable load distribution was shown, compared to conventional analysis. A modelling method using four-node curved shell elements with embedded reinforcement was evaluated in this study. Tests of reinforced and prestressed beams loaded in bending, shear and torsion were simulated. The increase in shear capacity, in addition to the reinforcement contribution, was modelled with a relationship for concrete in tension according to the modified compression field theory and compared with the use of a relationship related to the fracture energy of plain concrete. The results show that evaluations of the load-carrying capacity or crack width will be on the safe side, if only the fracture energy is used to define the concrete in tension.
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