| 1. |
- Gyllenberg, A, et al.
(författare)
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Variability in the CIITA gene interacts with HLA in multiple sclerosis.
- 2014
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Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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| 2. |
- Sun, Chengjun, et al.
(författare)
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CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
- 2012
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Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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| 3. |
- Cuzick, Jack, et al.
(författare)
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Prevention and early detection of prostate cancer.
- 2014
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Ingår i: The Lancet Oncology. - 1470-2045 .- 1474-5488. ; 15:11, s. e484-92
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a common malignancy in men and the worldwide burden of this disease is rising. Lifestyle modifications such as smoking cessation, exercise, and weight control offer opportunities to reduce the risk of developing prostate cancer. Early detection of prostate cancer by prostate-specific antigen (PSA) screening is controversial, but changes in the PSA threshold, frequency of screening, and the use of other biomarkers have the potential to minimise the overdiagnosis associated with PSA screening. Several new biomarkers for individuals with raised PSA concentrations or those diagnosed with prostate cancer are likely to identify individuals who can be spared aggressive treatment. Several pharmacological agents such as 5α-reductase inhibitors and aspirin could prevent development of prostate cancer. In this Review, we discuss the present evidence and research questions regarding prevention, early detection of prostate cancer, and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer.
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| 4. |
- Holmberg, L. Joakim, 1971-
(författare)
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Musculoskeletal Biomechanics in Cross-country Skiing
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Why copy the best athletes? When you finally learn their technique, they may have already moved on. Using muscluloskeletal biomechanics you might be able to add the "know-why" so that you can lead, instead of being left in the swells.This dissertation presents the theoretical framework of musculoskeletal modeling using inverse dynamics with static optimization. It explores some of the possibilities and limitations of musculoskeletal biomechanics in cross-country skiing, especially double-poling. The basic path of the implementation is shown and discussed, e.g. the issue of muscle model choice. From that discussion it is concluded that muscle contraction dynamics is needed to estimate individual muscle function in double-poling. Several computer simulation models, using The Anybody Modeling System™, have been created to study different cross-country skiing applications. One of the applied studies showed that the musculoskeletal system is not a collection of discrete uncoupled parts because kinematic differences in the lower leg region caused kinetic differences in the other end of the body. An implication of the results is that the kinematics and kinetics of the whole body probably are important when studying skill and performance in sports. Another one of the applied studies showed how leg utilisation may affect skiing efficiency and performance in double-poling ergometry. Skiing efficiency was defined as skiing work divided by metabolic muscle work, performance was defined as forward impulse. A higher utilization of the lower-body increased the performance, but decreased the skiing efficiency. The results display the potential of musculoskeletal biomechanics for skiing efficiency estimations. The subject of muscle decomposition is also studied. It is shown both analytically and with numerical simulations that muscle force estimates may be affected by muscle decomposition depending on the muscle recruitment criteria. Moreover, it is shown that proper choices of force normalization factors may overcome this issue. Such factors are presented for two types of muscle recruitment criteria.To sum up, there are still much to do regarding both the theoretical aspects as well as the practical implementations before predictions on one individual skier can be made with any certainty. But hopefully, this disseration somewhat furthers the fundamental mechanistic understanding of cross-country skiing, and shows that musculoskeletal biomechanics will be a useful complement to existing experimental methods in sports biomechanics.
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| 5. |
- McClune, Brian L., et al.
(författare)
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Allotransplantation for Patients Age >= 40 Years with Non-Hodgkin Lymphoma : Encouraging Progression-Free Survival
- 2014
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Ingår i: Biology of blood and marrow transplantation. - : Elsevier BV. - 1083-8791 .- 1523-6536. ; 20:7, s. 960-968
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Tidskriftsartikel (refereegranskat)abstract
- Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood and Marrow Transplant Research data on 1248 patients age >= 40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age >= 65; P = .0008). Fewer patients aged >= 65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% [95% confidence interval (CI), 19% to 26%] for age 40 to 54, 27% [95% CI, 23% to 31%] for age 55 to 64, and 34% [95% CI, 24% to 44%] for age >= 65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% [95% CI, 50% to 58%] for age 40 to 54; 40% [95% CI, 36% to 44%] for age 55 to 64, and 39% [95% CI, 28% to 50%] for age >= 65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age >= 55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age >= 55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL.
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| 9. |
- Strömsöe, Anneli, 1969, et al.
(författare)
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Education in cardiopulmonary resuscitation in Sweden and its clinical consequences.
- 2010
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 81:2, s. 211-6
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Tidskriftsartikel (refereegranskat)abstract
- To describe the use of cardiopulmonary resuscitation (CPR) training programmes in Sweden for 25 years and relate those to changes in the percentage of patients with out of hospital cardiac arrest (OHCA) who receive bystander CPR.
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