| 1. |
- Bourdieu, Pierre, et al.
(författare)
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Leve idrottspedagogiken : En vänbok tillägnad Lars-Magnus Engström
- 2005
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Bok (övrigt vetenskapligt/konstnärligt)abstract
- Vem ägnar sig åt idrott? Vilken betydelse har fritiden i barns och ungdomars liv? Vad innebär hälsa i skolämnet idrott och hälsa?Leve idrottspedagogiken! tillägnas Lars-Magnus Engström. Texterna i boken speglar delar av det idrottspedagogiska forskningsområdet i Sverige, vars framväxt Lars-Magnus Engström varit den främste företrädaren för. Läsaren får här ta del av exempelvis idrottskulturen, fritidskulturen och skolans ämne idrott och hälsa. Genomgående handlar texterna om villkoren för barns och ungdomars deltagane och om de olika lärprocesser som sker i anslutning till idrottsutövning.Lars-Magnus Engström har gjort betydande insatser som forskare och lärare samt som professor vid Lärarhögskolan i Stockholm och vid Gymnastik- och idrottshögskolan. I snart fyrtion år har han arbetat med studier kring påverkans- och lärprocesser i idrott. Hans forskning har främst kretsat kring människors idrottsvanor och vilka som utvecklar en fysiskt aktiv livsstil. Idrotts- och motionsutövningar ger både ett så kallat egenvärde och investeringsvärde. Med dessa begrepp bland många andra har Lars-Magnus Engström bidragit till en fördjupad vetenskaplig förståelse av idrottskulturen.De flesta författarna har eller har haft Lars-Magnus Engström som handledare och tillhör forskningsgruppen för pedagogik, idrott och fritidskultur. Redaktörer för boken är Karin Redelius och Håkan Larsson.
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| 2. |
- Eriksson, Anna-Lena, 1971, et al.
(författare)
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SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:12, s. 5029-37
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. OBJECTIVE: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent with 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). MAIN OUTCOME MEASURES: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. RESULTS: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. CONCLUSIONS: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.
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| 3. |
- Jakobsson, Jenny, et al.
(författare)
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Large differences in testosterone excretion in Korean and Swedish men are strongly associated with a UDP-glucuronosyl transferase 2B17 polymorphism.
- 2006
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:2, s. 687-93
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: The reproductive endocrinology in Asians and Caucasians is of great interest in view of large differences in prostate cancer rate and sensitivity to pharmacological male contraception. In addition, interpretation of certain antidoping tests is confounded by interethnic variation in androgen disposition. Uridine diphosphoglucuronosyl transferases have a key role in the homeostasis and metabolism of androgens. Recently a deletion polymorphism was detected in the UGT2B17 gene. OBJECTIVE: The objective of the study was to evaluate the contribution of the UGT2B17 deletion polymorphism to the interindividual and interethnic variation of androgen metabolism and excretion. METHODS AND RESULTS: Urine from 122 Swedish and 74 Korean healthy men was analyzed for several androgen glucuronides including testosterone. The distribution of the natural logarithms of urinary testosterone concentrations showed a distinct bimodal pattern in both groups, suggesting a monogenic inheritance. When the UGT2B17 genotypes were compared with urinary testosterone levels, all of the individuals of the UGT2B17 homozygous deletion/deletion genotype had no or negligible amounts of urinary testosterone. The deletion/deletion genotype was seven times more common in the Korean (66.7%) than the Swedish population (9.3%). In addition, the Swedes had significantly higher levels of serum testosterone, compared with the Koreans. CONCLUSIONS: Our results show that the UGT2B17 polymorphism is strongly associated with the bimodal distribution of the testosterone excretion and also with the large differences in testosterone excretion between Koreans and Swedes.
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| 4. |
- Jakobsson, Mattias, et al.
(författare)
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A unique recent origin of the allotetraploid species Arabidopsis suecica: Evidence from nuclear DNA markers
- 2006
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 23:6, s. 1217-1231
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Tidskriftsartikel (refereegranskat)abstract
- A coalescent-based method was used to investigate the origins of the allotetraploid Arabidopsis suecica, using 52 nuclear microsatellite loci typed in eight individuals of A. suecica and 14 individuals of its maternal parent Arabidopsis thaliana, and four short fragments of genomic DNA sequenced in a sample of four individuals of A. suecica and in both its parental species A. thaliana and Arabidopsis arenosa. All loci were variable in A. thaliana but only 24 of the 52 microsatellite loci and none of the four sequence fragments were variable in A. suecica. We explore a number of possible evolutionary scenarios for A. suecica and conclude that it is likely that A. suecica has a recent, unique origin between 12,000 and 300,000 years ago. The time estimates depend strongly on what is assumed about population growth and rates of mutation. When combined with what is known about the history of glaciations, our results suggest that A. suecica originated south of its present distribution in Sweden and Finland and then migrated north, perhaps in the wake of the retreating ice.
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| 5. |
- Jakobsson Schulze, Jenny
(författare)
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Genetics of androgen disposition : implications for doping tests
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Anabolic androgenic steroids (AAS) are derivatives of testosterone. Doping with AAS is a severe challenge to the vision, moral and ethics in sports and has also become an increasing problem in society. Testosterone abuse is conventionally assessed by the urinary testosterone glucuronide/ epitestosterone glucuronide (T/E) ratio, levels above 4.0 being considered suspicious. However, there is a large inter-individual variation in testosterone glucuronide and epitestosterone glucuronide excretion, which challenges the accuracy of the test. There are reasons to believe that genetic variation is the single most important cause of variation in disposition of many androgenic compounds. Twin studies in men have demonstrated heritability estimates of 85% and 96% for production rates of testosterone and dihydrotestosterone, respectively. The primary aim of this thesis was to investigate the contribution of genetic components to inter-individual variation in androgen disposition. We found that a deletion polymorphism in the UGT2B17 gene was strongly associated with the urinary testosterone glucuronide levels. All individuals homozygous for the deletion had negligible amounts of urinary testosterone glucuronide. It is a common polymorphism with an allele frequency of 29 % in Swedes and 78 % in Koreans. After a single dose of 360 mg testosterone, 40 % of the subjects homozygous for the UGT2B17 deletion never reached the T/E cut off ratio of 4.0. We showed that the sensitivity and specificity of the T/E test could be markedly improved by using genotype-based cut off ratios. A CYP17 T>C promoter polymorphism was associated with urinary epitestosterone glucuronide levels and consequently the T/E ratio. High natural T/E ratios due to low urinary levels of epitestosterone glucuronide may be partly explained by this polymorphism. Considering only individuals with a functional UGT2B17 enzyme, carriers of the CYP17 TT genotype exhibited 64 % higher T/E ratios than men with one or two C-alleles. The frequency of the TT genotype was 35 % in Caucasians. Another polymorphism (E77G) in 17b-hydroxysteroid dehydrogenase type 5 (HSD17B5), an enzyme that catalyses the step between androstenedione and testosterone, was associated with serum testosterone levels in Caucasian men. Considering only individuals with a functional UGT2B17 enzyme, this polymorphism was also associated with urinary testosterone glucuronide levels. The polymorphism had an allele frequency of 4.8 % in Swedes but was completely absent in Koreans. We also found a novel functional promoter polymorphism in the CYP7B1 gene, which was associated with significantly higher promoter activity and had an allele frequency of 4 % in Swedes and 0.65 % in Koreans. In summary, genetic variation has a large impact on androgen disposition. This variation is of the utmost importance for the interpretation of doping test results. The role of this variation for diseases in steroid target organs or for endocrine adverse reactions to drugs remains to be elucidated.
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| 6. |
- Kärrholm, Johan, 1951, et al.
(författare)
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Effects on work resumption of a co-operation project in vocational rehabilitation. Systematic, multi-professional, client-centred and solution-oriented co-operation
- 2006
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Ingår i: Disabil Rehabil. - : Informa UK Limited. - 0963-8288 .- 1464-5165. ; 28:7, s. 457-67
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The present aim was to evaluate the effect of systematic multi-professional co-ordinated rehabilitation (the Stockholm Co-operation Project) on the number of days' sick leave during the first and second half-years after the rehabilitation co-ordination period, compared to the year before. Another aim was to evaluate the economic effects at national level. METHOD: A matched-pairs design was used. The study group was based on 64 rehabilitees employed by a public employer in Stockholm, who took part in a systematic multi-professional co-operation project. To obtain pairs, the 64 individuals were individually matched with 64 people who received conventionally organised rehabilitation. Thus, there were 128 subjects altogether. RESULTS: The study group had substantially less sick leave days per month than the comparison group during the second half-year after the rehabilitation co-ordination period. The effect was even greater in a subgroup with more previous sick leave. During the first half-year after the intervention the comparison group had relatively more sick leave. No effect was found for a subgroup with less previous sick leave. The economic benefit of the intervention was estimated to 1,278 euros per month and person based on the whole group, and to 2,405 euros per month and person based on those with more sick leave. CONCLUSIONS: People who undergo co-ordinated rehabilitation have more working days after the intervention period than those with conventional rehabilitation. This way for rehabilitation actors to co-operate gives better outcomes for rehabilitation cases with long previous sick leave, but not for cases with less previous sick leave. It also generates economic gains at several levels.
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| 7. |
- Kärrholm, Jenny, et al.
(författare)
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Systematic co-operation between employer, occupational health service and social insurance office : A 6-year follow-up of vocational rehabilitation for people on sick-leave, including economic benefits
- 2008
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 40:8, s. 628-636
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate the effects of systematic co-operation among municipal employees on the number of sick-leave days per month and the type of benefit granted by the Social Insurance Office. A further aim was to evaluate the economic consequences for society.Design: A 6-year follow-up study with a matched-pairs design.Methods: Days on sick-leave were calculated for each subject one year before the intervention started and yearly for the following 6-year period. Statistical mixed-model analysis was used. The economic benefit of the intervention was estimated as the increased production stemming from fewer days on sick-leave.Subjects: Sixty-four employees on long-term sick-leave were individually matched with controls from another Social Insurance Office in a county with a socioeconomic structure similar to that of the study group.Results: The study group had 5.7 fewer days on sick-leave per month and person over the 6-year period (p=0.003). The estimated average economic benefit of the intervention was (sic)36,600 per person over the 6-year period. In conclusion, those who received systematic co-operation in vocational rehabilitation had fewer days on sick-leave than their ""treatment-as-usual"" peers. This effect persisted over 6 years, generating substantial net economic gains for society.
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| 8. |
- Kärrholm, Jenny, et al.
(författare)
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The views of sick-listed employees' immediate superiors on co-operation in vocational rehabilitation.
- 2007
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Ingår i: Work. - 1051-9815 .- 1875-9270. ; 29:2, s. 101-111
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of this research was to investigate the views of sick-listed employees' immediate superiors on co-operation in vocational rehabilitation before and during a systematic, multi-professional, client-centred, solution-oriented co-operation project in vocational rehabilitation (SMVR intervention). METHOD: A same-subject study with a questionnaire was used, with 95 immediate superiors giving their views on co-operation both before and during the SMVR intervention. RESULTS AND CONCLUSIONS: The immediate superiors felt that the SMVR intervention was successful in promoting co-operation, and reported a significant decrease in referrals of employees from one organisation to another without the problem being resolved. Hence SMVR co-operation was experienced positively by the immediate superiors and in fact led to a joint responsibility in finding solutions. The immediate superiors saw greater possibilities than before for employees to resume regular or other jobs during the SMVR intervention. A more elaborate co-operation model such as the SMVR intervention increased the immediate superiors' experience of successful vocational rehabilitation. Organizations seeking to increase efficiency in vocational rehabilitation might well analyse their work methods and improve their forms of co-operation.
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| 9. |
- Rolny, Charlotte, et al.
(författare)
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Platelet-derived growth factor receptor-beta promotes early endothelial cell differentiation
- 2006
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 108:6, s. 1877-1886
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Tidskriftsartikel (refereegranskat)abstract
- Platelet-derived growth factor BB (PDGF-BB) has been assigned a critical role in vascular stability by promoting the recruitment of PDGF receptor-beta-expressing perivascular cells. Here we present data indicating that early hematopoietic/endothelial (hemangio) precursors express PDGFR-beta based on coexpression with CD31, vascular endothelial growth factor receptor-2, and CD41 in 2 models: mouse yolk sac (embryonic day 8 [E8]) and differentiating mouse embryonic stem cells (embryoid bodies). Expression of PDGFR-beta on hemangioprecursor cells in the embryoid bodies gradually disappeared, and, at E14, expression appeared on perivascular cells. Activation of the PDGFR-beta on the hemangioprecursors accelerated the differentiation of endothelial cells, whereas differentiation of the hematopoietic lineage was suppressed. In E9.5 yolk sacs derived from recombinant mice expressing kinase-active PDGFR-beta with an aspartic acid to asparagine (D894N) replacement in the kinase activating loop and from mice with ubiquitous expression of PDGF-BB driven by the Rosa26 locus, the number of CD41-expressing early hematopoietic cells decreased by 36% and 34%, respectively, compared with staged wild-type littermates. Moreover, enhanced vascular remodeling was evident in the Rosa26-PDGF-BB yolk sacs. We conclude that PDGFR-beta is expressed on early hemangioprecursor cells, regulating vascular/hematopoietic development.
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| 10. |
- Schulze, Jenny Jakobsson, et al.
(författare)
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Genetic aspects of epitestosterone formation and androgen disposition: influence of polymorphisms in CYP17 and UGT2B enzymes.
- 2008
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Ingår i: Pharmacogenetics and genomics. - 1744-6872. ; 18:6, s. 477-85
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Testosterone is a commonly abused androgen in sports and in the gym culture of the society. Its abuse is conventionally disclosed by urinary assay of the testosterone/epitestosterone (T/E) glucuronide ratio, which should not exceed 4. A noteworthy number of athletes, however, have higher natural ratios than 4, most likely because of decreased excretion of epitestosterone glucuronide. Falsely positive doping test results are of great concern for the legal rights of the sportsman. Our objective was to study the genetic aspects of epitestosterone formation, and to elucidate the impact of genetic variation in androgen-metabolizing enzymes. METHODS: Urine from different study populations was analysed for androgen glucuronides by gas chromatography-mass spectrometry. All men were genotyped for the uridine diphospho-glucuronosyltransferase (UGT) 2B17 deletion polymorphism and single nucleotide polymorphisms in the cytochrome P-450c17alpha (CYP17), UGT2B15 and UGT2B7 genes. Expression of UGT2B15 mRNA in human liver samples was analysed using real-time PCR. RESULTS: A T>C (A1>A2) promoter polymorphism in the CYP17 gene was associated with the urinary glucuronide levels of epitestosterone and its putative precursor androstene-3beta, 17alpha-diol, resulting in 64% higher T/E ratios in A1/A1 homozygotes. Individuals devoid of UGT2B17 had significantly higher UGT2B15 mRNA levels in liver than individuals carrying two functional UGT2B17 alleles. CONCLUSION: The CYP17 promoter polymorphism may partly explain high natural (>4) T/E ratios. Our data indicate that 5-androstene-3beta, 17alpha-diol is an important precursor of epitestosterone and that CYP17 is involved in its production. In addition, we found that lack of the UGT2B17 enzyme may be compensated for by increase in UGT2B15 transcription.
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| 11. |
- Swanson, Charlotte, 1975, et al.
(författare)
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Sex steroid levels and cortical bone size in young men are associated with a uridine diphosphate glucuronosyltransferase 2B7 polymorphism (H268Y).
- 2007
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:9, s. 3697-704
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Sex steroids are involved in the regulation of pubertal cortical bone expansion in males. In vitro studies have indicated that the enzyme uridine diphosphate glucuronosyltransferase (UGT) 2B7 has the capacity to glucuronidate sex steroids and their metabolites. OBJECTIVE: Our objective was to determine the impact of the H(268)Y polymorphism in the UGT2B7 gene on interindividual variation of serum levels of sex steroids and cortical bone dimensions. PARTICIPANTS: The population-based cohort Gothenburg Osteoporosis and Obesity Determinants study consists of 1068 young adult Swedish men (age 18.9 yr). MAIN OUTCOME MEASURES: Serum levels of sex steroids and the three major glucuronidated androgen metabolites, androstane-3alpha,17beta-diol-17glucuronide, androstane-3alpha,17beta-diol-3glucuronide, and androsterone-glucuronide, were analyzed. Cortical and trabecular volumetric bone mineral density and cortical bone size were measured by peripheral quantitative computer tomography. RESULTS: Serum levels of testosterone (YY 9% over HH; P < 0.01), dihydrotestosterone (YY 10% over HH; P < 0.01), and estradiol (YY 8% over HH; P < 0.01) were associated with the UGT2B7 H(268)Y polymorphism. The polymorphism was associated with androstane-3alpha,17beta-diol-17glucuronide and androstane-3alpha,17beta-diol-3glucuronide (P < 0.01), but not with androsterone-glucuronide serum levels. In addition, the UGT2B7 H(268)Y polymorphism was an independent predictor of cortical bone size, reflected by periosteal circumference and cortical moment of inertia (P < 0.01), in both the weight-bearing tibia and nonweight-bearing radius. CONCLUSIONS: The UGT2B7 H(268)Y polymorphism is independently associated with cortical bone size and serum sex steroid levels in young adult men. Subjects homozygous for the Y allele had higher serum testosterone and larger cortical bone size than subjects homozygous for the H allele. However, the underlying mechanism behind these associations is unknown and has to be studied further.
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| 12. |
- Swanson, Charlotte, 1975, et al.
(författare)
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The UDP Glucuronosyltransferase 2B15 D85Y and 2B17 Deletion Polymorphisms Predict the Glucuronidation Pattern of Androgens and Fat Mass in Men.
- 2007
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Ingår i: Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4878-82
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Tidskriftsartikel (refereegranskat)abstract
- Context: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT) 2B15 and UGT2B17 glucuronidate androgens and their metabolites. Objective: To determine in vivo if the UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition. Participants: Two population-based cohorts including young adult (n=1068, age=18.9 years) and elderly (n=1001, age=75.3 years) men. Main Outcome Measures: Serum and urine levels of testosterone (T) and dihydrotestosterone (DHT) measured by GC-MS and serum levels of the major glucuronidated androgen metabolites androstane-3alpha,17beta-diol(androstanediol)-3glucuronide, androstanediol-17glucuronide and androsterone-glucuronide measured by LC-MS/MS. Body composition measured by DXA. Results: Both the UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-17glucuronide (p<0.001) but not with levels of androstanediol-3glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 D(85)Y polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass (p<0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity (p<0.05) as indicated by the HOMA index. Conclusions: The UGT2B15 D(85)Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17 glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17 glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.
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