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| 2. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 4. |
- Andersson-Engels, Stefan, et al.
(författare)
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Integrated system for interstitial photodynamic therapy
- 2003
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Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - : SPIE. - 0277-786X .- 1996-756X. ; 5142, s. 42-49
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Konferensbidrag (refereegranskat)abstract
- A novel photodynamic therapy system based on interstitial illumination using multiple fibres is under development. The aim with this system is to enable treatment of large tumour volumes and also to utilise real-time measurements to allow on-line dosimetry. Important dosimetric parameters to measure are light fluence rate, sensitizer fluorescence intensity and local blood oxygenation. A construction which allows all functions to be readily performed with a single system is presented. We believe that interstitial PDT utilising this technique may be attractive in many clinical situations.
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| 6. |
- Appelqvist, Hanna, et al.
(författare)
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Lysosome-Mediated Apoptosis is Associated with Cathepsin D-Specific Processing of Bid at Phe24,Trp48, and Phe183
- 2012
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Ingår i: Annals of Clinical and Laboratory Science. - : Institute for Clinical Science. - 0091-7370 .- 1550-8080. ; 42:3, s. 231-242
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Tidskriftsartikel (refereegranskat)abstract
- Bax-mediated permeabilization of the outer mitochondrial membrane and release of apoptogenic factors into the cytosol are key events that occur during apoptosis. Likewise, apoptosis is associated with permeabilization of the lysosomal membrane and release of lysosomal cathepsins into the cytosol. This report identifies proteolytically active cathepsin D as an important component of apoptotic signaling following lysosomal membrane permeabilization in fibroblasts. Lysosome-mediated cell death is associated with degradation of Bax sequestering 14-3-3 proteins, cleavage of the Box activator Bid, and translocation of Box to mitochondria, all of which were cathepsin D-dependent. Processing of Bid could be reproduced by enforced lysosomal membrane permeabilization, using the lysosomotropic detergent O-methyl-serine dodecylamine hydrochloride (MSDH). We identified three cathepsin D-specific cleavage sites in Bid, Phe24, Trp48, and Phe183. Cathepsin D-cleaved Bid induced Bax-mediated release of cytochrome c from purified mitochondria, indicating that the fragments generated are functionally active. Moreover, apoptosis was associated with cytosolic acidification, thereby providing a more favorable environment for the cathepsin D-mediated cleavage of Bid. Our study suggests that cytosolic cathepsin D triggers Bax-mediated cytochrome c release by proteolytic activation of Bid.
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| 7. |
- Arkkukangas, Marina, et al.
(författare)
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Older persons' experiences of a home-based exercise program with behavioral change support
- 2017
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Ingår i: Physiotherapy Theory and Practice. - : Taylor & Francis. - 0959-3985 .- 1532-5040. ; 33:12, s. 905-913
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is a challenge to promote exercise among older persons. Knowledge is needed regarding the maintenance of exercise aiming at preventing falls and promoting health and well-being in older persons.Purpose: This descriptive study used a qualitative inductive approach to describe older persons' experiences of a fall-preventive, home-based exercise program with support for behavioral change.Methods: Semi-structured interviews were conducted with 12 elderly persons aged 75years or older, and a qualitative content analysis was performed.Results: Four categories emerged: facilitators of performing exercise in everyday life, the importance of support, perceived gains from exercise, and the existential aspects of exercise.Conclusion: With support from physiotherapists (PTs), home-based exercise can be adapted to individual circumstances in a meaningful way. Including exercises in everyday life and daily routines could support the experience of being stronger, result in better physical functioning, and give hope for an extended active life in old age.
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| 9. |
- Bucin, Dragan, et al.
(författare)
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Heart transplantation across the antibodies against HLA and ABO
- 2006
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Ingår i: Transplant International. - : Frontiers Media SA. - 1432-2277 .- 0934-0874. ; 19:3, s. 239-244
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Tidskriftsartikel (refereegranskat)abstract
- We have intentionally performed heart transplantation in a 5-year-old child, despite the most unfavourable risk factors for patient survival; the presence of high level of antibodies against donor's human leucocyte antigen (HLA) class I/II and blood group antigens. Pretransplant treatment by mycophenolate mofetil, prednisolone, tacrolimus, intravenous immunoglobulin, rituximab, protein-A immunoadsorption (IA) and plasma exchange reduced antibody titres against the donor's lymphocytes from 128 to 16 and against the donor's blood group antigen from 256 to 0. The patient was urgently transplanted with a heart from an ABO incompatible donor (A(1) to O). A standard triple-drug immunosuppressive protocol was used. No hyperacute rejection was seen. Antibodies against the donor's HLA antigens remained at a low level despite three acute rejections. Rising anti-A(1) blood group antibodies preceded the second rejection and were reduced by two blood group-specific IAs and remained at a low level. The patient is doing well despite the persistence of donor-reactive antibodies.
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| 10. |
- Byun, Jinyoung, et al.
(författare)
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Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer
- 2022
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Ingår i: Nature Genetics. - : Nature Research. - 1061-4036 .- 1546-1718. ; 54:8, s. 1167-1177
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Tidskriftsartikel (refereegranskat)abstract
- To identify new susceptibility loci to lung cancer among diverse populations, we performed cross-ancestry genome-wide association studies in European, East Asian and African populations and discovered five loci that have not been previously reported. We replicated 26 signals and identified 10 new lead associations from previously reported loci. Rare-variant associations tended to be specific to populations, but even common-variant associations influencing smoking behavior, such as those with CHRNA5 and CYP2A6, showed population specificity. Fine-mapping and expression quantitative trait locus colocalization nominated several candidate variants and susceptibility genes such as IRF4 and FUBP1. DNA damage assays of prioritized genes in lung fibroblasts indicated that a subset of these genes, including the pleiotropic gene IRF4, potentially exert effects by promoting endogenous DNA damage.
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