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1.
  • Benrick, Anna, 1979, et al. (författare)
  • A non-conservative polymorphism in the IL-6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population.
  • 2008
  • Ingår i: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 146:1-3, s. 189-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Inflammation is a key component in the development of atherosclerosis, and myocardial infarction (MI); therefore we investigated the association between an interleukin-6 signal transducer (IL6ST)/gp130 polymorphism, gp130 function and risk of MI. Structural modeling suggested that a non-conservative single nucleotide polymorphism in the gp130, Gly148Arg, can change the stability and functional properties of the molecule. In vitro studies were done with BAF/3 cells lacking endogenous gp130. Cells stably transfected with the gp130 148Arg variant proliferated less and showed slightly lower STAT-3 phosphorylation in response to gp130 stimulation as compared to cells transfected with gp130 148Gly. In a prospectively followed hypertensive cohort we identified 167 patients who suffered a MI during the study and compared them to matched controls (mean age 57 years, 73% males, n=482). Carriers of the 148Arg variant (f(Arg)=0.12) of the gp130 receptor had decreased odds ratio for MI in univariate analysis (0.56, 95% CI 0.34-0.91, p=0.02). In conclusion, a genetically determined structural variant of the IL-6 receptor subunit gp130 is, independently of other known risk factors, associated with decreased risk of MI. The variant is also associated with decreased IL-6 responsiveness and could lead to a configuration change in the gp130 receptor.
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2.
  • Eriksson, Anna-Lena, 1971, et al. (författare)
  • The COMT val158met polymorphism is associated with prevalent fractures in Swedish men.
  • 2008
  • Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 42:1, s. 107-12
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Sex steroids are important for growth and maintenance of the skeleton. Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT val158met polymorphism results in a 60-75% difference in enzyme activity between the val (high activity=H) and met (low activity=L) variants. We have previously reported that this polymorphism is associated with bone mineral density (BMD) in young men. The aim of this study was to investigate associations between COMT val158met, BMD and fractures in elderly men. METHODS: Population-based study of Swedish men 75.4, SD 3.2, years of age. Fractures were reported using standardized questionnaires. Fracture and genotype data were available from 2,822 individuals. RESULTS: Total number of individuals with self-reported fracture was 989 (35.0%). Prevalence of >or=1 fracture was 37.2% in COMT(LL), 35.7% in COMT(HL) and 30.4% in COMT(HH) (p<0.05). Early fractures (50 years of age). The OR for fracture of the non-weight bearing skeleton in COMT(HH) compared with COMT(LL+HL) was 0.74 (95% CI 0.59-0.92). No associations between COMT val158met and BMD were found in this cohort of elderly men. CONCLUSIONS: The COMT val158met polymorphism is associated with life time fracture prevalence in elderly Swedish men. This association is mainly driven by early fractures (
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3.
  • Mellström, Dan, et al. (författare)
  • Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men : MrOS Sweden
  • 2006
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 21:4, s. 529-535
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.
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4.
  • Mellström, Dan, 1945, et al. (författare)
  • Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden.
  • 2006
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 21:4, s. 529-35
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of androgens for bone health in elderly men is unclear. We show that free testosterone within the normal range is a predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly Swedish men. INTRODUCTION: Osteoporosis-related fractures constitute a major health concern not only in women but also in men. Previous studies have clearly shown that serum levels of estradiol are associated with BMD, whereas more conflicting data have been presented regarding the predictive value of testosterone (T) for bone health in elderly men. The aim of this study was to investigate if serum levels of T are associated with BMD and/or prevalent fractures in a large cohort of elderly men. MATERIALS AND METHODS: In the Swedish part of the MrOS study (n = 2908; average age, 75.4 years), bone parameters were measured using DXA, and prevalent fractures were recorded using standardized questionnaires and by vertebral X-ray analyses. Serum levels of total T, total estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by radioimmunoassay, and free T (FT) and free E2 (FE2) were derived from the mass action equations. Height, weight, age, physical activity, smoking habits, and calcium intake were included together with FT and FE2 in regression models for BMD. RESULTS: FT was an independent positive predictor of BMD in total body, total hip, femur trochanter, and arm but not in the lumbar spine. The highest independent predictive value of FT was found in the arm and the hip (with a relatively high content of cortical bone). FE2 was an independent predictor of BMD at all bone sites studied, and the highest predictive value was seen for lumbar spine (with relatively high content of trabecular bone) BMD. FT but not FE2 was a positive predictor of total body bone area and BMC. FT levels below the median were independent predictors of prevalent osteoporosis-related fractures (OR, 1.56; 95% CI, 1.14-2.14; p < 0.01) and X-ray-verified vertebral fractures (OR, 2.00; 95% CI, 1.34-2.86; p < 0.001). The predictive value of FT for prevalent fractures was not affected by adjustment for BMD. CONCLUSIONS: These findings show that variation of FT within the normal range is an independent but modest predictor of BMD at predominantly cortical bone sites and of previous osteoporosis-related fractures in elderly men. Our data indicate that not only estrogens but also androgens are of importance for bone health in elderly men. Longitudinal studies investigating the predictive value of T for fracture risk in elderly men are required.
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5.
  • Monstein, Hans-Jurg, 1946-, et al. (författare)
  • Vasopressin receptor mRNA expression in the human gastrointestinal tract
  • 2008
  • Ingår i: European Surgical Research. - : S. Karger AG. - 0014-312X .- 1421-9921. ; 40:1, s. 34-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Background/Aim: Vasopressin and oxytocin are closely related peptides, and both exert effects on the gastrointestinal function. In the present study, we wanted to map the expression of vasopressin receptor mRNAs (V1a, V1b/V3, and V2) in nontumorous tissue biopsy specimens of human gastrointestinal tract and surrounding tissues. Methods: Total and polyA+ RNAs were isolated from human tissue biopsy specimens using an automated nucleic acid extractor and, subsequently, converted into single-stranded cDNA. Seminested PCR amplifications were carried out, using gene-specific V1a, V1b/V3, and V2 receptor primers. The PCR amplicons were partially sequenced to confirm their identity. Results: The present study demonstrated the expression of vasopressin receptor mRNAs in human gastrointestinal tract, pancreas, kidney, lung, brain, and ovary. The expression pattern varied between different parts of the gastrointestinal tract. In the colon ascendens, V1a receptor mRNA expression could not be detected in 3 out of 4 analyzed tissue biopsy specimens. On the other hand, all the vasopressin receptor mRNAs were expressed in all colon transversum biopsy samples. Conclusions: V1a, V1b/V3, and V2 receptor mRNAs are widely expressed throughout human gastrointestinal tract and surrounding tissues. The data obtained provide information for further mapping and determination of the physiological role of the vasopressin receptor mRNA expression in normal and tumorous tissues.
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6.
  • Strandberg, Louise, 1981, et al. (författare)
  • IL6 and IL1B polymorphisms are associated with fat mass in older men: the MrOS Study Sweden.
  • 2008
  • Ingår i: Obesity (Silver Spring, Md.). - : Wiley. - 1930-7381 .- 1930-739X. ; 16:3, s. 710-3
  • Tidskriftsartikel (refereegranskat)abstract
    • There is growing evidence that immune functions are linked to the regulation of body fat. Our studies of knockout mice indicate that both endogenous interleukin (IL)-6 and IL-1 can suppress mature-onset obesity. We now investigated whether four common polymorphisms of the IL6 and IL1 systems are associated with the fat mass measured with dual-energy X-ray absorptiometry (DXA) in elderly men (n = 3,014). The study subjects were from the Swedish part of the MrOS multicenter population study and 69-81 years of age. The IL6 -174 G>C (Minor allele frequency (MAF) = 48%) gene promoter polymorphism was associated with the primary outcome total fat mass (P = 0.006) and regional fat masses, but not with lean body mass. The IL1B -31T>C (MAF = 34%) polymorphism was also associated with total fat (P = 0.007) and regional fat masses, but not lean body mass. The IL-1 receptor antagonist (IL-1ra) gene (IL1RN) +2018 T>C (MAF = 27%) polymorphism (in linkage disequilibrium (LD) with a well-studied variable number tandem repeat of 86 base pair (bp)) and IL1B +3953 C>T (MAF = 26%) polymorphism were not associated with total fat mass. In conclusion, the IL-1 and IL-6 systems, shown to suppress mature-onset obesity in experimental animals, contain gene polymorphisms that are associated with fat, but not lean, mass in elderly men.
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7.
  • Blomqvist, Evalena, et al. (författare)
  • Optimerad rening av HCI och SO2 med minskade kalktillsatser vid torr rökgasrening
  • 2007
  • Rapport (populärvet., debatt m.m.)abstract
    • Fokus för detta projekt är att optimera rening av saltsyra (HCl) och svaveldioxid (SO2) i ett torrt reningssystem kopplat till en avfallsförbränningsprocess. För att uppnå effektiv rening av HCl och SO2 från rökgasen tillsätts ofta stora mängder absorbent. En minskad absorbentförbrukning ger dubbel ekonomisk vinning för anläggningsägaren då både förbruknings- och deponeringskostnader kan reduceras. Syftet med projektet är att studera effekten av temperatur och vattenhalt i rökgasen, dvs relativ fukthalt (RH) för absorption av HCl och SO2 med normal släckt kalk. Effektiviteten hos en absorbenter med högre porvolym och specifik yta (sprängd släckt kalk) undersöktes också. Resultat från 26 mätdygn, utförda på Borås Energi och Miljö (BEMABs) 20 MW avfallsförbränningsanläggning, visar en positiv korrelation mellan effektiviteten hos normal släckt kalk och RH. Variation i RH uppnåddes genom att sänka rökgastemperaturen i filtret och/eller genom att befukta det inkommande bränslet. Genom att enbart befukta bränslet, motsvarande en 20 % vattenhalt i rökgasen, ökade endast RH marginellt till 3,62 % jämfört med normalnivå på 3,28 %. Mängden tillsatt kalk reducerades under dessa förhållanden endast med 5 %. En 10 ºC temperatursänkning av rökgasen till 143 ºC vid filtret resulterade i en ökning av RH till 4,06%, vilket medförde en 13 % reduktion av kalkförbrukningen. En kombinationen av både lägre rökgas och befuktat bränsle genererade den kraftigaste ökning av RH, 4,84%, och således också den kraftigaste reduktion (26 %) av mängden tillsatt normal släckt kalk. Effektiviteten hos sprängd släckt kalk testades också vid normala driftsförhållanden under sju mätdygn. Dessa experiment visade på en halverad förbrukning jämfört med motsvarande förbrukning av normal släckt kalk. Vidare indikerade testen att den sprängda kalken besitter samma känslighet för variation i RH som normal släckt kalk inom det naturligt uppkomna temperaturvariationerna i processen (145-165 oC). Detta antyder att det finns utrymme för ytterligare effektiviseringspotentialer och därmed minskade tillsattsmängder även för den sprängda kalken. Det finns stora kostnadsreduktioner att vinna med minskad absorbentförbrukning. Genom att optimera BEMABs anläggning med avseende på RH kan en 20% reduktion av normal släckt kalk erhållas. En optimering som motsvara en minskning av kostnaderna med dryga 700 000 SEK. Om sprängd släckt kalk skulle användas i stället skulle kostnaderna reduceras med ytterligare ca 700 000 SEK. Ett FTIR-system för on-line mätning av HCl och SO2 i partikelhaltiga rökgaser utvärderades inom projektet. Mätmetoden anger relativa förändringar i halter med tiden och mäter inte absolut. Validering av systemet visade att 80% av HCl och 20% av SO2 återfinns i gasfasen. Det bör dock noteras att SO2 halterna var mycket låga. Nyckelord: Kalkeffektivitet, relativ fukthalt, HCl, SO2, absorption, avfallsförbränning, Rökgasrening
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8.
  • Christiernin, Maria, et al. (författare)
  • Analysis of lignin isolated from poplar cell suspension cultures
  • 2005
  • Ingår i: 59th Appita Annual Conference and Exhibition, incorporating the 13th ISWFPC. ; , s. 81-86
  • Konferensbidrag (refereegranskat)abstract
    • We have investigated lignin structures in pure primary cell walls. Poplar cell suspension cultures, Populus tremula x tremuloides, were harvested after 7, 14 and 21 days of growth. Carbohydrate monomer analysis also points at the presence of primary wall exclusively. Confocal microscopy of the cells dyed with acriflavin demonstrates that lignin is present. Klason content increases during growth from 0.7 to 3.9 percent. GC analysis of samples subjected to thioacidolysis shows that the lignin constitutes of guaiacyl units as compared to poplar wood which have syringyl as the main monomer. The amount of monomers per unit Klason lignin is lower than in wood and it decreases during cultivation possibly indicating a larger relative content of carbon-carbon bonds in the polymeric lignin in the cell cultures as compared to wood. Five lignin structures were identified with massspectrometry.
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9.
  • Christiernin, Maria, et al. (författare)
  • Lignin isolated from primary walls of hybrid aspen cell cultures indicates significant differences in lignin structure between primary and secondary cell wall
  • 2005
  • Ingår i: Plant physiology and biochemistry (Paris). - : Elsevier BV. - 0981-9428 .- 1873-2690. ; 43:8, s. 777-785
  • Tidskriftsartikel (refereegranskat)abstract
    • Hybrid aspen (Populus tremula x tremuloides) cell cultures were grown for 7, 14 and 21 days. The cell cultures formed primary cell walls but no secondary cell wall according to carbohydrate analysis and microscopic characterization. The primary walls were lignified, increasingly with age, according to Klason lignin analysis. Presence of lignin in the primary walls, with a higher content in 21-day old cells than in 7-day old cells, was further Supported by phloroglucinol/HCI reagent test and confocal microscopy after both immunolocalization and staining with acriflavin. Both laccase and peroxidase activity were found in the cultures and the activity increased during lignin formation. The lignin from the cell culture material was compared to lignin from mature aspen wood, where most of the lignin originates in the secondary cell wall, and which served as our secondary cell wall control. Lignin from the cell walls was isolated and characterized by thioacidolysis followed by gas chromatography and mass spectrometry. The lignin in the cell cultures differed from lignin of mature aspen wood in that it consisted exclusively of guaiacyl units, and had a more condensed structure. Five lignin structures were identified by mass spectrometry in the cell suspension cultures. The results indicate that the hybrid aspen cell culture used in this investigation may be a convenient experimental system for studies of primary cell wall lignin.
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10.
  • Eriksson, Anna-Lena, 1971, et al. (författare)
  • Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men.
  • 2009
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94:3, s. 1033-41
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: The risk of many conditions, including prostate cancer, breast cancer, and osteoporosis, is associated with serum levels of sex steroids. OBJECTIVE: The aim of the study was to identify genetic variations in sex steroid-related genes that are associated with serum levels of estradiol (E2) and/or testosterone in men. DESIGN: Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid-related candidate genes was performed in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n = 1041 men; age, 18.9 +/- 0.6 yr). Replications of significant associations were performed in the Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2568 men; age, 75.5 +/- 3.2 yr) and in the MrOS US study (n = 1922 men; age, 73.5 +/- 5.8 yr). Serum E2, testosterone, and estrone (E1) levels were analyzed using gas chromatography/mass spectrometry. RESULTS: The screening in the GOOD cohort identified the single nucleotide polymorphism rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible for the final step of the biosynthesis of E2 and E1, to be most significantly associated with serum E2 levels (P = 2 x 10(-6)). This association was confirmed both in the MrOS Sweden study (P = 9 x 10(-7)) and in the MrOS US study (P = 1 x 10(-4)). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2 (P = 2 x 10(-14)) and E1 (P = 8 x 10(-19)) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P < 0.01) and prevalent self-reported fractures (P < 0.05). CONCLUSIONS: rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men.
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11.
  • Eriksson, Anna-Lena, 1971, et al. (författare)
  • 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
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:12, s. 5029-37
  • 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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12.
  • Eriksson, Anna-Lena, 1971, et al. (författare)
  • The COMT val158met polymorphism is associated with early pubertal development, height and cortical bone mass in girls.
  • 2005
  • Ingår i: Pediatric research. - 0031-3998. ; 58:1, s. 71-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogens are involved in accretion of bone mass during puberty. Catechol-O-Methyltransferase (COMT) is involved in the degradation of estrogens. In this cross-sectional study we investigated associations between the COMT val158met polymorphism, which results in a 60-75% difference in enzyme activity between the val (high activity = H) and the met (low activity = L) variant, and skeletal phenotypes in 246 healthy pre/early pubertal girls. Girls with COMT(LL) were 5.4 cm taller than COMT(HH) girls. Dual x-ray absorptiometry showed higher values of bone mineral content (BMC), and larger areas of total body, femur and spine in COMT(LL). Cortical BMC, measured by peripheral quantitative computerized tomography in the tibia, was 9.8% higher in COMT(LL) compared with COMT(HH). This was due to a larger cortical cross sectional area while the cortical volumetric bone mineral density was not associated with COMT genotype. COMT(LL) girls had higher serum levels of free estradiol and insulin like growth factor. Regression models indicated that COMT genotype exerted effects on skeletal growth mainly via a regulation of free estradiol, resulting in an affected pubertal development (Tanner staging). We propose that the COMT(LL) genotype results in higher free estradiol levels and earlier pubertal development, leading to an increased skeletal growth in pre/early pubertal girls. Possible consequences for the adult skeleton however can be determined only after cessation of growth.
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13.
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14.
  • García, Maria C, et al. (författare)
  • Mature-onset obesity in interleukin-1 receptor I knockout mice.
  • 2006
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 55:5, s. 1205-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Interleukin-1 (IL-1) is a major mediator of inflammation that exerts its biological activities through the IL-1 type I receptor (IL-1RI). The body weights of IL-1RI(-/-) mice of both sexes started to deviate from those of wild-type mice at 5-6 months of age and were 20% higher at 9 months of age. Visceral and subcutaneous fat mass, measured by dual-energy X-ray absorptiometry and magnetic resonance imaging, was markedly (1.5- to 2.5-fold) increased. Lean body mass and crown-rump length were also slightly (11 and 5%, respectively) increased, as was serum IGF-I. Obese IL-1RI(-/-) mice were insulin resistant, as evidenced by hyperinsulinemia, decreased glucose tolerance, and insulin sensitivity. To elucidate the mechanisms for the development of obesity, young pre-obese IL-1RI(-/-) mice were investigated. They showed decreased suppression of body weight and food intake in response to systemic leptin treatment. The decreased leptin responsiveness was even more pronounced in older obese animals. Moreover, spontaneous locomotor activity and fat utilization, as measured by respiratory quotient, were decreased in pre-obese IL-1RI(-/-) mice. In conclusion, lack of IL-1RI-mediated biological activity causes mature-onset obesity. This obese phenotype is preceded by decreased leptin sensitivity, fat utilization, and locomotor activity.
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15.
  • Gréen, Anna, 1973- (författare)
  • Histone H1 : Subtypes and phosphorylation in cell life and death
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The genetic information of a human diploid cell is contained within approximately 2 metres of linear DNA. The DNA molecules are compacted and organized in various ways to fit inside the cell nucleus. Various kinds of histones are involved in this compaction. One of these histones, histone H1 is the topic of the present thesis. In addition to its structural role, H1 histones have been implicated in various processes, for example gene regulation and inhibition of chromatin replication.H1 histones, also termed linker histones, are relatively conserved proteins, and the various subtypes seem to have different and important functions even though redundancy between the subtypes has been demonstrated. Despite the sequence conservation of H1 subtypes, two sequence variations were detected within the H1.2 and H1.4 subtypes using hydrophilic interaction liquid chromatographic separation of H1 proteins from K562 and Raji cell lines in Paper I in the present thesis. The variations were confirmed by genetic analysis, and the H1.2 sequence variation was also found in genomic DNA of normal blood donors, in an allele frequency of 6.8%. The H1.4 sequence variation was concluded to be Raji specific. The significance of H1 microsequence variants is unclear, since the physiological function of H1 histones remains to be established.H1 histones can be phosphorylated at multiple sites. Changes in H1 phosphorylation has been detected in apoptosis, the cell cycle, gene regulation, mitotic chromatin condensation and malignant transformation. Contradictory data have been obtained on H1 phosphorylation in apoptosis, and many results indicate that H1 dephosphorylation occurs during apoptosis. We and others hypothesized that cell cycle effects by the apoptosis inducers may have affected previous studies. In Paper II, the H1 phosphorylation pattern was investigated in early apoptosis in Jurkat cells, taking cell cycle effects into account. In receptor-mediated apoptosis, apoptosis occurs with a mainly preserved phosphorylation pattern, while Camptothecin induced apoptosis results in rapid dephosphorylation of H1 subtypes, demonstrating that H1 dephosphorylation is not a general event in apoptosis, but may occur upon apoptosis induction via the mitochondrial pathway. The dephosphorylation may also be a result of early cell cycle effects or signalling.Therefore, the H1 phosphorylation pattern in the cell cycle of normal activated T cells was investigated in Paper IV in this thesis. Some studies, which have been made using cancer cell lines from various species and cell synchronization, have indicated a sequential addition of phosphate groupsacross the cell cycle. Normal T cells and cell sorting by flow cytometry were used to circumvent side-effects from cell synchronization. The data demonstrate that a pattern with phosphorylated serines is established in late G1/early S phase, with some additional phosphorylation occurring during S, and further up-phosphorylation seems to occur during mitosis. Malignant transformation may lead to an altered G1 H1 phosphorylation pattern, as was demonstrated using sorted Jurkat T lymphoblastoid cells.During mitosis, certain H1 subtypes may be relocated to the cytoplasm. In Paper III, the location of histones H1.2, H1.3 and H1.5 during mitosis was investigated. Histone H1.3 was detected in cell nuclei in all mitotic stages, while H1.2 was detected in the nucleus during prophase and telophase, and primarily in the cytoplasm during metaphase and early anaphase. H1.5 was located mostly to chromatin during prophase and telophase, and to both chromatin and cytoplasm during metaphase and anaphase. Phosphorylated H1 was located in chromatin in prophase, and in both chromatin and cytoplasm during metaphase, anaphase and telophase, indicating that the mechanism for a possible H1 subtype relocation to the cytoplasm is phosphorylation.In conclusion, data obtained during this thesis work suggest that H1 histones and their phosphorylation may participate in the regulation of events in the cell cycle, such as S-phase progression and mitosis, possibly through altered interactions with chromatin, and/or by partial or complete removal of subtypes or phosphorylated variants from chromatin.
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16.
  • Grundberg, E, et al. (författare)
  • Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
  • 2007
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:6, s. 829-837
  • Tidskriftsartikel (refereegranskat)abstract
    • Summary  Herein we investigated the association between polymorphisms in the LRP5 gene and bone phenotypes and fractures in three large male cohorts based on the rationale that mutations in LRP5 cause severe bone phenotypes. Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men. Introduction  The low-density lipoprotein receptor-related protein 5 (LRP5)-Wnt signalling system is of importance for regulating osteoblastic activity, which became clear after findings that inactivating mutations in LRP5 cause osteoporosis. The overall aim of this study was to investigate the association between polymorphisms in the LRP5 gene and bone mineral density (BMD) in three large cohorts of young and elderly men. Methods  The cohorts used were MrOS Sweden (n = 3014, aged 69–81 years) and MrOs Hong Kong (n = 2000, aged  > 65 years) and the Swedish GOOD study (n = 1068, aged 18–20 years). The polymorphisms Val667Met and Ala1330Val were genotyped using a TaqMan assay. Results  When combining the data from the Swedish cohorts in a meta-analysis (n = 3,800), men carrying the 667Met-allele had 3% lower BMD at lumbar spine compared with non-carriers (p < 0.05). The Val667Met SNP was not polymorphic in the Hong Kong population and thus were not included. There were no associations between the Ala1330Val SNP and bone phenotypes in the study populations. No associations between the LRP5 polymorphisms and self-reported fractures were seen in MrOs Sweden. Conclusions  Results from these three large cohorts indicate that the Val667Met polymorphism but not the Ala1330Val contributes to the observed variability in BMD in the Swedish populations.
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17.
  • Grundberg, Elin, et al. (författare)
  • The impact of estradiol on bone mineral density is modulated by the specific estrogen receptor-alpha cofactor retinoblastoma-interacting zinc finger protein-1 insertion/deletion polymorphism.
  • 2007
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:6, s. 2300-6
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ERalpha cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ERalpha function in the presence of estrogen. OBJECTIVE: The objective of the study was to determine whether a RIZ P704 insertion (+)/deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. DESIGN: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmö OPRA Study, respectively. SETTING: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmö University Hospital, and Uppsala University Hospital. PARTICIPANTS: In total, 4058 men and women, aged 69-81 yr, were randomly selected from population registries. MAIN OUTCOME MEASURES: BMD (grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. RESULTS: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(-/-) group (r = 0.19 vs. r = 0.08, P < 0.05). CONCLUSIONS: These large-scale studies of elderly men and women indicate that the ERalpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.
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18.
  • Grundberg, Elin, et al. (författare)
  • The Impact of Estradiol on Bone Mineral Density is modulated by The Specific Estrogen Receptor-{alpha} Cofactor RIZ1 Insertion/Deletion Polymorphism.
  • 2007
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 92:Mar 13, s. 2300-2306
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Estrogens regulate bone mass by binding to the estrogen receptor (ER)-alpha as well as ER-beta. The specific ER -cofactor retinoblastoma-interacting zinc finger protein (RIZ)-1 enhances ER alpha function in the presence of estrogen. Objective: The objective of the study was to determine whether a RIZ P704 insertion (+)/ deletion (-) (indel) polymorphism modulates the impact of estradiol on bone mineral density (BMD) and study the association between the polymorphism and BMD in elderly subjects. Design: This was a population-based, prospective, and cross-sectional study, the Swedish MrOS Study, and the Malmo OPRA Study, respectively. Setting: The study was conducted at three academic medical centers: Sahlgrenska Academy in Gothenburg, Malmo University Hospital, and Uppsala University Hospital. Participants: In total, 4058 men and women, aged 69 -81 yr, were randomly selected from population registries. Main Outcome Measures: BMD(grams per square centimeter) was measured at femoral neck, trochanter, lumbar spine, and total body. Results: The RIZ P704(+/+) genotype was associated with low BMD in both women (femoral neck, P < 0.001; trochanter, P < 0.01; lumbar spine, P < 0.05; total body, P < 0.01) and men (lumbar spine, P < 0.05). However, the association between the polymorphism and BMD was dependent on estradiol status. The positive correlation between serum estradiol and BMD was significantly modulated by the genotype with a stronger correlation in the P704(+/+) group than the P704(+/+) group (r = 0.19 vs. r = 0.08, P < 0.05). Conclusions: These large-scale studies of elderly men and women indicate that the ER alpha cofactor RIZ gene has a prominent effect on BMD, and the P704 genotype modulates the impact of estradiol on BMD. Further studies are required to determine whether this polymorphism modulates the estrogenic response to estradiol treatment.
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19.
  • Grundberg, Elin, et al. (författare)
  • Vitamin D receptor 3' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: the MrOS Study in Sweden and Hong Kong.
  • 2007
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - : Wiley. - 0884-0431. ; 22:6, s. 832-40
  • Tidskriftsartikel (refereegranskat)abstract
    • The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. INTRODUCTION: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. MATERIALS AND METHODS: Here, we reconstructed common haplotypes in the VDR 3' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. RESULTS: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% CI, 1.146-2.391; p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (p < 0.05). The VDR gene was also shown to exhibit a 3' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. CONCLUSIONS: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.
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20.
  • Grundberg, Elin, et al. (författare)
  • Vitamin D receptor 3 ' haplotypes are unequally expressed in primary human bone cells and associated with increased fracture risk: The MrOS study in Sweden and Hong kong
  • 2007
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 22:6, s. 832-840
  • Tidskriftsartikel (refereegranskat)abstract
    • The VDR is a prime candidate gene for osteoporosis. Here, we studied three common VDR haplotypes in relation to bone phenotypes in 5014 participants of the global MrOS Study. We also studied the relative expression of the haplotypes in human bone cells. One haplotype was associated with increased fracture risk and differently expressed in primary human bone cells. Introduction: Vitamin D plays an essential role in skeletal metabolism by binding to its nuclear steroid receptor, the vitamin D receptor (VDR). The heritability of BMD is well established, and the VDR gene is considered a prime candidate suggested to partially account for genetically controlled BMD variance in the population. Materials and Methods: Here, we reconstructed common haplotypes in the VDR 3 ' untranslated region (UTR) and studied the association to BMD and risk of vertebral fractures in elderly men from Sweden (n = 3014) and Hong Kong (n = 2000), all participants of the global MrOS Study. To assess any functional implications of the VDR polymorphisms, we studied allele-specific expressions of the different VDR 3 ' UTR haplotypes in the normal chromosomal context of 70 unrelated human trabecular bone samples. This was performed by quantitative genotyping of coding polymorphisms in RNA samples and in corresponding DNA samples isolated from the bone samples. Results: Three major haplotypes were reconstructed and in agreement with the previously well-defined baT, BAt, and bAT haplotypes, herein denoted Hap1, Hap2, and Hap3. The Hap1 haplotype was independently associated with increased risk of vertebral fractures in Swedish men (OR, 1.655; 95% Cl, 1.146-2.391;p < 0.01) and with lower lumbar spine BMD in elderly men from Sweden (p < 0.01) and Hong Kong (P < 0.05). The VDR gene was also shown to exhibit a 3 ' UTR haplotype dependent allelic imbalance, indicating that the VDR Hap1 allele was overexpressed in human trabecular bone samples. Conclusions: The results indicate that the relatively overexpressed VDR Hap1 haplotype could be considered a risk allele for osteoporosis regardless of ethnicity.
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21.
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22.
  • Jansson, John-Olov, 1954, et al. (författare)
  • Leukemia inhibitory factor reduces body fat mass in ovariectomized mice
  • 2006
  • Ingår i: Eur J Endocrinol. - : Oxford University Press (OUP). - 0804-4643. ; 154:2, s. 349-54
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Ovariectomized (OVX) mice are known to gain body fat while exposure to estrogens decreases fat mass. We have previously shown that estrogen replacement therapy enhances the expression of receptors for the cytokine, leukemia inhibitory factor (LIF). LIF and other cytokines acting via the gp130 signal transducing receptor have been reported to decrease obesity. In the present study, we investigated whether LIF treatment can reduce obesity in OVX mice. DESIGN: Eight-week-old female C57Bl/6 mice were OVX or sham-operated. The mice were treated with LIF, 30 microg/kg or PBS via daily i.p. injections for 15 days (n = 9-10). METHODS: Dual X-ray absorptiometry and computerized tomography. RESULTS: We found that LIF treatment of OVX mice caused a significant reduction in the weight of white fat depots (P = 0.017) and serum leptin levels (P = 0.011). LIF also caused a significant decrease in brown fat mass (P = 0.036). Treatment with LIF decreased thymus weight but did not affect crown-rump length, femur length, trabecular bone mineral density or the weight of several non-fat organs including the uterus. CONCLUSION: The cytokine, LIF, decreases body fat mass in OVX mice, suggesting that estrogen signaling is not required for this effect.
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23.
  • Jochems, Caroline, 1973, et al. (författare)
  • Role of raloxifene as a potent inhibitor of experimental postmenopausal polyarthritis and osteoporosis
  • 2007
  • Ingår i: Arthritis Rheum. - : Wiley. - 0004-3591. ; 56:10, s. 3261-3270
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: In postmenopausal rheumatoid arthritis (RA), both estrogen deficiency and the inflammatory disease contribute to the development of generalized osteoporosis. Hormone replacement therapy (HRT) with estradiol preserves bone mineral density (BMD) and ameliorates arthritis, but long-term therapy is no longer an option due to significant side effects. We therefore used a mouse model of human RA to test the hypothesis that a selective estrogen receptor modulator (SERM), the raloxifene analog LY117018, could be beneficial in the treatment of both arthritis and osteoporosis. METHODS: Female DBA/1 mice were ovariectomized and arthritis was induced with collagen immunization. Mice received an injection of raloxifene, estradiol, or vehicle control, administered prophylactically or therapeutically, and thereafter the clinical arthritis score was evaluated continuously. At termination, BMD was analyzed with peripheral quantitative computed tomography. Paws were collected for histology, and sera were analyzed for cytokines and markers of bone and cartilage turnover. Levels of cytokine messenger RNA (mRNA) were investigated with real-time polymerase chain reaction. RESULTS: Treatment with raloxifene dramatically decreased the frequency and severity of arthritis. Effective preservation of bone and cartilage was seen in raloxifene-exposed mice, as demonstrated by increased BMD and decreased serum levels of cartilage oligomeric matrix protein in the raloxifene-treated mice compared with controls. Decreased levels of mRNA for both tumor necrosis factor alpha and RANKL in spleen cells from raloxifene-treated arthritic mice indicated an immunosuppressive action of this SERM. CONCLUSION: In a well-established model of postmenopausal RA, the raloxifene analog LY117018 potently inhibits the progression of arthritis and the associated development of osteoporosis, both in a prophylactic and in a therapeutic regimen. Since long-term HRT has been associated with significant side effects, raloxifene may be a useful adjuvant treatment for postmenopausal RA.
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24.
  • Lindahl, Katarina, et al. (författare)
  • Heterozygosity for a coding SNP in COL1A2 confers a lower BMD and an increased stroke risk.
  • 2009
  • Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 384:4, s. 501-5
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variation plays an important role in osteoporosis and a prime candidate gene is Collagen alpha2(I) (COL1A2). A coding polymorphism (rs42524) in COL1A2 has previously been associated with intracranial aneurysms. Here the effects of this polymorphism have been studied in relation to bone mineral density (BMD) and prevalences of stroke and myocardial infarction (MI). rs42524 was genotyped in elderly men (n = 2004) from the Swedish MrOS cohort. Genotypes were analysed for association to BMD and certain health parameters. Significant associations (overall P < 0.05), were observed between rs42524 genotype and BMD at several skeletal sites. Surprisingly, the heterozygote genotype class exhibited lower BMD than either homozygote group. When subjects were classified as heterozygotes or homozygotes, the heterozygous genotype was found to confer a lower BMD at total hip, femoral neck and trochanter Furthermore, the heterozygote genotype had an increased risk of stroke and MI, with population Attributable Risks being 0.12 and 0.08, respectively.
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25.
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26.
  • Lindhé, Cecilia, 1973- (författare)
  • Visuella vändningar : Bild och estetik i Kerstin Ekmans romankonst
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • This is a dissertation on how an aesthetics of fiction is formulated at the intersection of, and oscillation between, image-construction and image-criticism in three novels by Kerstin Ekman: En stad av ljus (1983), Händelser vid vatten (1993), and Gör mig levande igen (1996). The purpose of the dissertation is to analyze the movement of this oscillation and demonstrate how it is intertwined, not only with the aesthetic practice characterizing these novels, but also with their interpretation of the past and the contemporary. Kerstin Ekman’s oeuvre formulates a criticism of images and their various representational forms (for example paintings, photographs, the images of virtual reality), while integrating different media’s aesthetic expressions by theme and narrative technique. Occasionally, images are represented as deserving credence, as possible to describe in words, but also with a faith in their power to animate or recreate the past, capture the moment and freeze time. But as often as being utilized as tools for creation, images are employed for careful aim of the critique of civilization that characterizes Ekman’s entire body of work. The tension between image-construction and image-criticism is intimately connected to the issues that at their core are bound up with the relation between verbal art and visual art which constitutes a fundamental trait of Ekman’s aesthetic practice. In addition to novels in various genres, Ekman has also worked with film, computer programming and hypertext. The interplay with other media is an important building block of Ekman’s fiction, and the classical opposition between verbal and visual arts is figured foremost through the camera, the film camera, and the computer. The dissertation also examines Ekman’s early fiction, from her debut novel, the detective story 30 meter mord (1959), to Mörker och blåbärsris (1972), and introduces the hypertext Hotagens minne (2006) and the computer game Rymdresa (1991).
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27.
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28.
  • Lorentzon, Mattias, 1970, et al. (författare)
  • Association between physical activity and BMD in young men is modulated by catechol-O-methyltransferase (COMT) genotype: the GOOD study
  • 2007
  • Ingår i: J Bone Miner Res. - : Wiley. - 0884-0431 .- 0884-0431. ; 22:8, s. 1165-72
  • Tidskriftsartikel (refereegranskat)abstract
    • In this large population-based study in young men, we show that the COMT val158met polymorphism modulates the association between physical activity, aBMD (DXA), and trabecular vBMD (pQCT). INTRODUCTION: Peak BMD is an important predictor of future risk of osteoporosis and is largely determined by genetic factors but also by environmental factors, among which physical activity (PA) is a strong contributor. Estrogens are believed to influence the mechanical strain signal generated by bones subjected to mechanical loading. Catechol-O-methyltransferase (COMT) is involved in the degradation of estrogens. A functional polymorphism in the COMT gene (val158met), results in a 60-75% difference in enzyme activity between the val (high activity = H) and met (low activity = L) variants. The aim of this study was to determine if the COMT val158met polymorphism modulates the association between PA and BMD in young men. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (age, 18.9 +/- 0.6 yr). Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular volumetric BMD (vBMD) were measured by pQCT. Study subjects were genotyped and classified as COMT(LL), COMT(HL), or COMT(HH). The amount (h/wk) of PA was determined through questionnaires. RESULTS: Using a linear regression model (including age, height, weight, smoking, and calcium intake as covariates), significant interactions between the COMT genotype and PA were seen for aBMD at all sites and for trabecular vBMD in both the radius and the tibia. The difference in adjusted aBMD and trabecular vBMD between high (>or=4 h/wk) and low PA (<4 h/wk) was greater in COMT(LL) subjects than in subjects homozygous for the COMT(HH) (total body aBMD: COMT(LL) 4.2% versus COMT(HH) 1.5%, p = 0.02; lumbar spine aBMD: COMT(LL) 7.8% versus COMT(HH) 3.9%, p = 0.04; tibia trabecular vBMD: COMT(LL) 7.1% versus COMT(HH) 1.0%, p < 0.01). The COMT polymorphism was associated with aBMD, at all sites and with trabecular vBMD in the low-PA subjects, but not in their high-PA counterparts. CONCLUSIONS: We show that the COMT val158met polymorphism modulates the association between PA, aBMD, and trabecular vBMD, suggesting that this polymorphism is of importance for BMD in subjects with a low level of PA.
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29.
  • Lorentzon, Mattias, 1970, et al. (författare)
  • Polymorphisms in the aromatase gene predict areal BMD as a result of affected cortical bone size: the GOOD study.
  • 2006
  • Ingår i: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. - 0884-0431. ; 21:2, s. 332-9
  • Tidskriftsartikel (refereegranskat)abstract
    • The association between aromatase gene polymorphisms, bone parameters, and sex steroid levels was studied in 1068 men (18.9 +/- 0.6 years of age). Several aromatase gene polymorphisms were found to be associated with serum testosterone levels and cortical bone size but not with trabecular volumetric BMD. INTRODUCTION: Both testosterone and estrogens are important for the male skeleton. Aromatase, the product of the CYP19 gene, is the key enzyme in the conversion of testosterone to estradiol. A functional aromatase enzyme has been shown to be crucial for the normal development of the male skeleton. The role of genetic polymorphisms in the aromatase gene for trabecular volumetric BMD (vBMD) and cortical bone size has not previously been studied in men. MATERIALS AND METHODS: The Gothenburg Osteoporosis and Obesity Determinants (GOOD) study consists of 1068 men (18.9 +/- 0.6 years of age). The TTTA repeat polymorphism (TTTAn) and three single nucleotide polymorphisms (SNPs), including the Val80 SNP, in the CYP19 gene, were analyzed. Serum levels of testosterone and estradiol were measured. Areal BMD (aBMD) was measured by DXA, whereas cortical and trabecular vBMD and cortical bone size were measured by pQCT. RESULTS: The TTTAn and the Val80 genotypes were independent predictors of aBMD of the radius, lumbar spine, total body, and cortical bone size (cortical cross-sectional area and thickness) of both the radius and tibia. In contrast, trabecular vBMD was not associated with CYP19 polymorphisms. Homozygosity for the long allele (>9 repeats) of the TTTAn and for the G allele of the Val80 SNP was associated with the highest aBMD and testosterone levels as well as with the greatest cortical bone size. Regression analyses indicated that the association with aBMD was mediated through affected cortical bone size. CONCLUSIONS: We showed, in a large well-characterized cohort of men at the age of peak bone mass, that several common aromatase polymorphisms are associated with cortical bone size but not with trabecular vBMD. One may speculate that affected CYP19 activity, resulting in altered testosterone levels during pubertal development, might contribute to the association between CYP19 polymorphisms and cortical bone size.
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30.
  • Mellström, Dan, 1945, et al. (författare)
  • Older men with low serum estradiol and high serum SHBG have an increased risk of fractures.
  • 2008
  • Ingår i: Journal of bone and mineral research. - 1523-4681. ; 23:10, s. 1552-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Osteoporosis-related fractures constitute a major health concern not only in women but also in men. To study the predictive role of serum sex steroids for fracture risk in men, serum sex steroids were analyzed by the specific gas chromatography-mass spectrometry technique at baseline in older men (n = 2639; mean, 75 yr of age) of the prospective population-based MrOS Sweden cohort. Fractures occurring after baseline were validated (average follow-up of 3.3 yr). The incidence for having at least one validated fracture after baseline was 20.9/1000 person-years. Estradiol (E2; hazard ratio [HR] per SD decrease, 1.34; 95% CI, 1.22-1.49), free estradiol (fE2; HR per SD decrease, 1.41; 95% CI, 1.28-1.55), testosterone (T; HR per SD decrease, 1.27; 95% CI, 1.16-1.39), and free testosterone (fT; HR per SD decrease, 1.32; 95% CI, 1.21-1.44) were all inversely, whereas sex hormone-binding globulin (SHBG; HR per SD increase, 1.41; 95% CI, 1.22-1.63) was directly related to fracture risk. Multivariable proportional hazards regression models, adjusted for age, suggested that fE2 and SHBG (p < 0.001), but not fT, were independently associated with fracture risk. Further subanalyses of fracture type showed that fE2 was inversely associated with clinical vertebral fractures (HR per SD decrease, 1.57; 95% CI, 1.36-1.80), nonvertebral osteoporosis fractures (HR per SD decrease, 1.42; 95% CI, 1.23-1.65), and hip fractures (HR per SD decrease, 1.44; 95% CI, 1.18-1.76). The inverse relation between serum E2 and fracture risk was nonlinear with a strong relation <16 pg/ml for E2 and 0.3 pg/ml for fE2. In conclusion, older Swedish men with low serum E2 and high SHBG levels have an increased risk of fractures.
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31.
  • Mårtensson, Ulrika, et al. (författare)
  • Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.
  • 2009
  • Ingår i: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:2, s. 687-98
  • Tidskriftsartikel (refereegranskat)abstract
    • In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.
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32.
  • Nilsson, Martin, 1966, et al. (författare)
  • Competitive physical activity early in life is associated with bone mineral density in elderly Swedish men
  • 2008
  • Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 0937-941X .- 1433-2965. ; 19:11, s. 1557-1566
  • Tidskriftsartikel (refereegranskat)abstract
    • In this population-based study of 75-year-old men (n = 498), we investigated the association between physical activity (PA) early in life and present bone mineral density (BMD). We demonstrate that a high frequency of competitive sports early in life is associated with BMD at several bone sites, indicating that increases in BMD following PA are preserved longer than previously believed. Introduction Physical activity (PA) increases bone mineral density (BMD) during growth. It is unclear if the positive effects remain at old age. In this study, we aimed to determine if PA early in life was associated with BMD in elderly men. Methods In this population-based study, 498 men, 75.2 +/- .3 (mean +/- SD) years old, were included. BMD was assessed using DXA. Data concerning lifetime PA, including both competitive (CS) and recreational sports (RS), and occupational physical load (OPL), were collected at interview. Results Subjects in the highest frequency group of CS in the early period (10-35 years), had higher BMD at the total body (4.2%, p < 0.01), total hip (7.0%, p < 0.01), trochanter (8.7%, p < 0.01), and lumbar spine (7.9%, p < 0.01), than subjects not involved in CS. A stepwise linear regression model showed that frequency of CS in the early period independently positively predicted present BMD at the total body (beta=0.12, p < 0.01), total hip (beta=0.11, p < 0.01), trochanter (beta=0.12, p < 0.01), and lumbar spine (beta=0.11, p=0.01). Conclusions We demonstrate that PA in CS early in life is associated with BMD in 75-year-old Swedish men, indicating that increases in BMD following PA are preserved longer than previously believed.
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33.
  • Nordander, Catarina, et al. (författare)
  • Gender differences in workers with identical repetitive industrial tasks: exposure and musculoskeletal disorders.
  • 2008
  • Ingår i: International Archives of Occupational and Environmental Health. - : Springer Science and Business Media LLC. - 1432-1246 .- 0340-0131. ; 81:8, s. 939-947
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: For unknown reasons, females run a higher risk than males of work-related musculoskeletal disorders. The aim of this study was to evaluate whether male and female workers, with identical repetitive work tasks, differ concerning risk of disorders, physical or psychosocial exposures. METHODS: Employees in two industries were studied; one rubber manufacturing and one mechanical assembly plant. These industries were selected since in both, large groups of males and females worked side by side performing identical repetitive work tasks. Physical exposure was measured by technical equipment. Postures and movements were registered by inclinometry for the head and upper arms, and by electrogoniometry for the wrists. Muscular activity (muscular rest and %max) was registered by surface electromyography for m. trapezius and the forearm extensors (18 males and 19 females). Psychosocial work environment was evaluated by the demand-control-support model (85 males and 138 females). Musculoskeletal disorders were assessed (105 males and 172 females), by interview (last 7-days complaints), and by physical examination (diagnoses). RESULTS: Concerning physical exposure, females showed higher muscular activity related to maximal voluntary contractions [(%MVE); m. trapezius: females 18 (SD 9.2), males 12 (SD 4.3); forearm extensors: females 39 (SD 11), males 27 (SD 10), right side, 90th percentile]. Working postures and movements were similar between genders. Also, concerning psychosocial work environment, no significant gender differences were found. Females had higher prevalences of disorders [complaints: age-adjusted prevalence odds ratio (POR) 2.3 (95% CI 1.3-3.8) for neck/shoulders, 2.4 (1.4-4.0) for elbows/hands; diagnoses: neck/shoulder 1.9 (1.1-3.6), elbows/hands 4.1 (1.2-9.3)]. In 225 workers, PORs were adjusted for household work, personal recovery and exercise, which only slightly affected the risk estimates. CONCLUSION: In identical work tasks, females showed substantially higher muscular activity in relation to capacity, and higher prevalence of musculoskeletal disorders of the neck and upper extremity, than did males.
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34.
  • Ohlsson, Anna B., et al. (författare)
  • Cell suspension cultures of Populus tremula x P. tremuloides exhibit a high level of cellulose synthase gene expression that coincides with increased in vitro cellulose synthase activity.
  • 2006
  • Ingår i: Protoplasma. - : Springer Science and Business Media LLC. - 0033-183X .- 1615-6102. ; 228:4, s. 221-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Compared to wood, cell suspension cultures provide convenient model systems to study many different cellular processes in plants. Here we have established cell suspension cultures of Populus tremula L. x P. tremuloides Michx. and characterized them by determining the enzymatic activities and/or mRNA expression levels of selected cell wall-specific proteins at the different stages of growth. While enzymes and proteins typically associated with primary cell wall synthesis and expansion were detected in the exponential growth phase of the cultures, the late stationary phase showed high expression of the secondary-cell-wall-associated cellulose synthase genes. Interestingly, detergent extracts of membranes from aging cell suspension cultures exhibited high levels of in vitro cellulose synthesis. The estimated ratio of cellulose to callose was as high as 50 : 50, as opposed to the ratio of 30 : 70 so far achieved with membrane preparations extracted from other systems. The increased cellulose synthase activity was also evidenced by higher levels of Calcofluor white binding in the cell material from the stationary-phase cultures. The ease of handling cell suspension cultures and the improved capacity for in vitro cellulose synthesis suggest that these cultures offer a new basis for studying the mechanism of cellulose biosynthesis.
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35.
  • Ohlsson, Anna B., et al. (författare)
  • Increased metal tolerance in Salix by nicotinamide and nicotinic acid
  • 2008
  • Ingår i: Plant physiology and biochemistry (Paris). - : Elsevier BV. - 0981-9428 .- 1873-2690. ; 46:7, s. 655-664
  • Tidskriftsartikel (refereegranskat)abstract
    • We have earlier shown that nicotinamide (NIC) and nicotinic acid (NiA) can induce defence-related metabolism in plant cells; e.g. increase the level of glutathione. Here we investigated if NIC and NiA could increase the metal tolerance in metal sensitive clones of Salix viminalis and whether this would be mediated via increased glutathione level. Salix clones, sensitive or tolerant to zinc (Zn), copper (Cu) and cadmium (Cd) were grown in the presence of heavy metals (Cd, Cu or Zn) or NIC and NiA as well as in combination. In addition, the influence of N-acetyl-cystein (NAC) and L-2-oxothiazolidine 4-carboxylate (OTC), stimulators of reduced glutathione (GSH) biosynthesis, and the glutathione biosynthesis inhibitor buthionine sulfoximine (BSO) was analysed. Tolerance was measured as effects on root and shoot dry weight, and the glutathione and metal concentrations in the tissues were analysed. Results showed that NIC and NiA decreased the toxic effects of Cd, Cu and Zn on growth significantly in sensitive clones, but also to some extent in tolerant clones. However, the glutathione level and metal concentration did not change by NIC or NiA addition. Treatment with NAC, OTC or BSO did not per se influence the sensitivity to Cd, although the glutathione level increased in the presence of NAC and OTC and decreased in response to BSO. The results suggest that NIC and NiA increased the defence against heavy metals but not via glutathione formation per se.
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36.
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37.
  • Ohlsson, Anna, 1974- (författare)
  • Myt och manipulation : Radikal psykiatrikritik i svensk offentlig idédebatt 1968-1973
  • 2008
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The aim of the present thesis is to study radical criticism of psychiatry in public discussion in Sweden between 1968 and 1973. Although it was not the first time psychiatry had been challenged, the debate during these years displayed an unprecedented intensity. What is mental illness – a myth, an etiquette, an illusion? Is psychiatry a means of social control? Such were the questions raised at the time. In my thesis, I study the contexts as well as the arguments of these discussions. To this end, a great variety of sources have been consulted: books, newspapers, magazines, films etc.In part, the Swedish debate on psychiatry ran parallel to international discussions on the topic, which have been regarded as a manifestation of anti-psychiatry. This standpoint is often associated with psychiatrists such as R. D. Laing, David Cooper and Thomas Szasz. In my thesis, I challenge the concept of anti-psychiatry, arguing that other concepts are better suited to capture the diversity of the debate in all its nuances. Thus, I make use of radical and reformatory criticism – concepts which have been suggested by the sociologist Tommy Svensson – while also seeking to develop them further.In addition to the international perspective, the psychiatry debate must also be interpreted in its specifically Swedish context. One aspect of this is the Swedish tradition of Government Official Reports: psychiatry had been subject to many investigations prior to the debate in the 1960s and 1970s, and others would follow in its wake. Another characteristic feature of the Swedish debate is two events that formed very suitable targets for critique: Sociopatutredningen and Mentalhälsokampanjen. These events seemed to confirm the most farreaching concerns of the radical critics, namely that psychiatry is a means of social control.
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38.
  • Ohlsson, Anna, et al. (författare)
  • Optimering av kalktillsatser i Borås Energis rökgasreningssystem
  • 2006
  • Rapport (refereegranskat)abstract
    • Today, waste incineration is a hot topic. Since 2002 there are regulations against land filling combustible materials. From 2005 the same applies for organic waste. Due to the new regulations, icineration with energy recovery has increased and will continue to grow. Waste incineration gerenates a lot of residues. The foucs of this report is the common pollutants Sulphur dioxide and Hydrochloric acid. To separate these from the Flue gas an adsorbent, often hydrated lime, is used. Huge amount of the adsorbent has to be added to the process to gain sufficient cleaning. A previous study has showed that the adsorbent conversion efficiency is very low, only around 25%. The objective of this project is to optimize the adsorption process of HCl and SO2 to gain a reduction of lime consumption and to make the process more efficient. This will be achieved by changing selected parameters of the process at Borås Flue gas cleaning plant. Reduced limestone consumption has double benefits; decreased purchase cost and decreased cost due to the land filling fee for filter ash is reduced. The project included the following assignments; a literature study, an interview to gather experience from plant operators, collection and evaluation of plant data. Plant data indicates that the plant operation has changed due to the modification of the process parameters. Theory has shown that humidity plays a key role in the process. High humidity makes the lime more active and reduces the consumption. High humidity can be achieved by lowering the flue gas temperature or adding water to the fuel. These two cases and a combination of them have been tested at the plant. The result has showed a reduction in consumption of lime. There are a lot of cost reductions to gain. A plant with the same size as Borås will with a 10% decrease in lime consumption reduce the cost with appr. 300.000 SEK. Plant data has indicated that a 25% decrease in lime consumption is achievable. This will reduce Borås Energys' cost with appr. 720.000 SEK. Sorbacal is a new product developed for flue gas cleaning. It is estimated to be 2 or 2 times more efficient than regular lime. There are siginificant economical benefits to gain if the product can withstand the expectations. Estimatons shows that a cost reduction as high as 1.2 MSEK is achievable. The products efficiency is shortly going to be tested at Borås Energy flue gas cleaning plant.
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39.
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40.
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41.
  • Ribom, Eva L, et al. (författare)
  • Estimation of physical performance and measurements of habitual physical activity may capture men with high risk to fall--data from the Mr Os Sweden cohort.
  • 2009
  • Ingår i: Archives of gerontology and geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; 49:1
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate if clinically usable estimates of physical performance and level of habitual physical activity are associated with fall risk in elderly men. A population-based sample of 3014 randomly selected men aged 69-80 years was recruited to medical centers in Gothenburg, Malmoe, or Uppsala. The level of physical activity and self-reported falls during the preceding 12 months was evaluated using a questionnaire. The physical performance ability was estimated by measurements of handgrip strength, a timed stands test, a 6-m walking test and a 20-cm narrow walk test. Falls were reported in 16.5% of the men. Fallers performed 6.2+/-19.0% (mean+/-standard deviations; S.D.) less in right handgrip measures, 8.8+/-40.6% slower in the timed stands test, 6.8+/-30.8% slower in the 6-m walking test, and 5.3+/-28.8% slower in the 20-cm narrow walk test (all p<0.001, respectively). The odds ratio for falls among men who performed <-3 S.D. or failed compared to the mean (+1 S.D. to -1 S.D.) in the timed stands test was 3.41 (95% CI 2.31-5.02; p<0.001) and 2.46 (95% CI 1.80-3.34; p<0.001) in 20-cm narrow walk test. There were more fallers that never were physical active (73.0% vs. 65.4%, p<0.001) and who were sitting more (6.4+/-2.5 h/day vs. 6.0+/-2.3 h/day, p<0.05) than among the non-fallers. Fallers scored less than non-fallers in all the estimates of physical performance and they were more sedentary in their life style. The report suggests that clinical usable tests of physical performance and evaluation of habitual physical activity in the clinical situation possibly can be used to predict risk of falls in elderly men.
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42.
  • Shao, Linus Ruijin, 1964, et al. (författare)
  • Down-Regulation of Cilia-Localized IL-6R{alpha} by 17{beta}-Estradiol in Mouse and Human Fallopian Tubes.
  • 2009
  • Ingår i: American journal of physiology. Cell physiology. - : American Physiological Society. - 0363-6143 .- 1522-1563. ; 297:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The action of Interleukin-6 (IL-6) impacts female reproduction. Although IL-6 was recently shown to inhibit cilia activity in human fallopian tubes in vitro, the molecular mechanisms underlying IL-6 signaling to tubal function remain elusive. Here, we investigate the cellular localization, regulation, and possible function of two IL-6 receptors (IL-6Ralpha and gp130) in mouse and human fallopian tubes in vivo. We show that IL-6Ralpha is restricted to the cilia of epithelial cells in both mouse and human fallopian tubes. Exogenous 17beta-estradiol (E2), but not progesterone (P4), causes a time-dependent decrease in IL-6Ralpha expression which is blocked by the estrogen receptor (ER) antagonist ICI 182,780. Exposure of different ER-selective agonists, PTT or DPN, demonstrated an ER subtype-specific regulation of IL-6Ralphaalpha in mouse fallopian tubes. In contrast to IL-6Ralpha, gp130 was detected in tubal epithelial cells in mice but not in humans. In humans, gp130 was found in the muscle cells and was decreased in the periovulatory and luteal phases during the reproductive cycles, indicating a species-specific expression and regulation of gp130 in the fallopian tube. Expression of tubal IL-6Ralpha and gp130 in IL-6 knockout mice was found to be normal; however, E2 treatment increased IL-6Ralpha, but not gp130, in IL-6 knockout mice compared to wild-type mice. Furthermore, expression levels of IL-6Ralpha, but not gp130, decreased in parallel with estrogenic accelerated oocyte-cumulus complex (OCC) transport in mouse fallopian tubes. Our findings unveil a potential role for cilia-specific IL-6Ralpha in the regulation of OCC transport and suggest an estrogen-regulatory pathway of IL-6Ralpha in the fallopian tube. Key words: estrogen, IL-6R, cilia, fallopian tube.
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43.
  • Stålnacke, Britt-Marie, et al. (författare)
  • Serum concentrations of two biochemical markers of brain tissue damage S-100B and neurone specific enolase are increased in elite female soccer players after a competitive game
  • 2006
  • Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 40:4, s. 313-6
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: It is a matter of debate whether or not ordinary heading of the ball in soccer causes injury to brain tissue.OBJECTIVE: To analyse concentrations of the biochemical markers of brain tissue damage S-100B and neurone specific enolase (NSE) in serum of female elite soccer players in association with a competitive game.METHODS: Venous blood samples were obtained from 44 female soccer players before and after a competitive game for analysis. The number of headers and trauma events (falls, collisions, etc) was assessed from videotape recordings for each player.RESULTS: Concentrations of both brain damage markers were increased after the game (S-100B, 0.18 (0.11) v 0.11 (0.05) microg/l (p = 0.000); NSE, 10.14 (1.74) v 9.05 (1.59) microg/l (p = 0.001)). There was a significant correlation between changes in S-100B concentrations and both the number of headers (r = 0.430, p = 0.004) and the number of other trauma events (r = 0.517, p < 0.001).CONCLUSION: The concentrations of both S-100B and NSE were increased by game associated activities and events. The increases in S-100B concentration were significantly related to the number of headers and other trauma events, which indicates that both these factors may have contributed to these increases.
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44.
  • Swanson, Charlotte, 1975, et al. (författare)
  • The UDP Glucuronosyltransferase 2B15 D85Y and 2B17 Deletion Polymorphisms Predict the Glucuronidation Pattern of Androgens and Fat Mass in Men.
  • 2007
  • Ingår i: Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:12, s. 4878-82
  • 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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45.
  • Törneman, Niklas, et al. (författare)
  • Litteraturstudie om kemiska ämnen och nanopartiklar i produkter inför screening 2007
  • 2006
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • SWECO VIAK har på uppdrag av Naturvårdsverket genomfört en litteraturstudie av ett 80 tal ämnen som kan bli aktuella för screening inom den nationella miljöövervakningen. Dessutom har en litteraturstudie om nanopartiklar genomförts.Litteraturstudierna omfattade fysiokemisk information, begränsningar och förbud som berör ämnena, toxikologiska och ekotoxikologiska data, hantering och emissioner av ämnena, spridning och omvandling i naturen, förekomst i miljö och människa, en PBT bedömning (dvs. en bedömning av ämnenas motstånd mot nedbrytning, ämnenas bioackumulationspotential och ämnenas toxicitet), en bedömning av möjliga matriser där ämnena kan återfinnas samt möjliga metoder för analys av ämnena.För att förbättra överskådligheten presenteras detaljerad information om de olika ämnena i ämnesrapporter som bifogas huvudrapporten. I själva rapporten redovisas varje ämnesgrupp i översiktliga tabeller där en del av informationen om varje ämne återfinns.En rad olika informationskällor har använts. Dessa innefattar olika ämnesdatabaser, rapporter från statliga och överstatliga organ, vetenskapliga databaser där nyare information återfinns och olika tillverkares/importörers/exportörers information om de olika ämnena.De studerade ämnesgrupperna är, med en kortfattad beskrivning:Aminer är en grupp alifatiska eller aromatiska ämnen där minst en amingrupp ingår. Alla ämnen i gruppen är faroklassificerade och tillgången på toxikologiska och ekotoxikologisk data är förhållandevis god. Ämnena inom gruppen används bl.a. som smörjmedelstillsatser och tre ämnen i gruppen är högvolymsprodukter. Några av ämnena bedöms vara något intressanta för screening pga. de påträffats i miljön och kan ha negativa hälso- och miljöeffekter.Biocider är en liten grupp ämnen som bl.a. används i färger. Alla ämnena i gruppen är faroklassificerade som mycket giftiga för vattenlevande organismer och tillgången på toxikologiska och ekotoxikologisk data är förhållandevis god. Ett av ämnena i gruppen bedöms vara något intressant för screening pga. de förhållandevis låga ekotoxikologiska effekthalterna och den icke försumbara mängden som registreras.Estrar innefattar både estrar med enkla och polyaromatiska substituenter och alifatiska estrar. Två ämnen i gruppen är faroklassificerade som mycket giftiga för vattenlevande organismer och tillgången på ekotoxikologiska data är förhållandevis god. Ämnena ingår i olika industriella kemikalieprodukter och de flesta är högvolymskemikalier i EU. Två av ämnena i gruppen bedöms vara något intressanta för screening pga. de förhållandevis låga ekotoxikologiska effekthalterna och den icke försumbara mängden som registreras.Heterocykliska ämnen innefattar fyra ämnen vars enda strukturella likhet är att de innehåller minst en aromatisk ring. Flera ämnen i gruppen är faroklassificerade som mycket giftiga för vattenlevande organismer och tillgången på ekotoxikologisk data är begränsad. Ämnena ingår i olika industriella kemikalieprodukter och inga är högvolymskemikalier i EU. Ämnena i gruppen bedöms vara mindre intressanta för screening. Framförallt för att förhållandevis små mängder registreras årligen.Organiska fosfater och svavelföreningar innefattar tre ämnen utan strukturella likheter. Alla tre ämnen är högvolymsprodukter i EU och används som tillsatsämnen i kemikalie/plast -industrin. Ett av ämnena i gruppen är något intressant för screening eftersom registreringen ökar samtidigt som ämnet är misstänkt cancerframkallande. Dock är registreringen av detta ämne i Sverige förhållandevis låg (20 ton/år).Organiska halogener innefattar åtta ämnen. Samtliga är faroklassificerade som mycket giftiga för vattenlevande organismer och tillgången på ekotoxikologiska data är god. Fyra ämnen är dessutom misstänkt cancerogena. De flesta ämnen i gruppen är bekämpningsmedel och fyra ämnen är högvolymsprodukter. Flera ämnena i gruppen bedöms vara intressanta för screening pga. mycket hög giftighet gentemot vattenlevande organismer. Extra intressant i denna grupp är cypermetrin vars användning förväntas öka för att skydda timmerupplag mot skadedjurangrepp.Organiska jonföreningar innefattar sexton anjoniska ämnen som alla innehåller minst en bensenring. Flera av ämnena är alkylbensensulfonater och några av dessa har linjära alkylgrupper vilket innebär att de är s.k. linjära alkylbensensulfonater (LAS). Inga av ämnena i gruppen är faroklassificerade. Ämnen förekommer främst i olika rengörings- och ytbehandlingsprodukter och elva ämnen i gruppen är högvolymsprodukter i EU. Tillgången på ekotoxikologiska data är varierande men flera av ämnena tycks vara relativt giftiga för vattenlevande organismer. Flera ämnen i denna grupp bedöms vara intressanta för screening främst för att stora mängder registreras årligen samtidigt som den huvudsakliga användningen är i sådana produkter där en spridning till omgivningen via t.ex. reningsverk är möjlig.Pigmentämnen innefattar 10 gula, 3 orange, 13 röda, 3 lila, 1 blå och 2 gröna pigmentämnen. Hela gruppen är mycket heterogen vad gäller molekylstruktur, egenskaper, farlighet förr människa och miljö samt registrerade mängder. I denna studie är detta den grupp av ämnen som det finns minst information om i förhållande till den mängd som registreras. Trots bristen på information bör inte denna grupp uteslutas från screening. Däremot kan det viktigaste kriteriet för urval av pigmentämnen till screening tänkas vara den registrerade mängden. Ur detta hänseende framstår det enda blå pigmentämnet som en lämplig kandidat med en registrerad mängd av 1250 ton år 2004 samtidigt som det finns förhållandevis mycket information om detta ämne.Betongtillsatser innefattar 7 ämnen vars enda gemensamma nämnare är att de alla används som tillsatsämnen vid betongtillblandning. Flertalet av dessa ämnen är faroklassificeradeoch alla ämnen är högvolymsprodukter inom EU samtidigt som mycket stora mängder registreras i Sverige årligen (100 – 12000 ton). Tillgången på ekotoxikologisk data är varierande men flera av ämnena tycks vara relativt giftiga för vattenlevande organismer. Flera ämnen i denna grupp bedöms vara intressanta för screening främst för att mycket stora mängder registreras årligen samtidigt som deras miljöfarlighet inte är obetydlig.Nanopartiklar är inte en ämnesgrupp i egentlig mening. Istället är detta en materialkategori som kännetecknas av rymdstrukturer på en skala < 100 nm. I denna rapport behandlas främst nanopartiklar vilket innefattar både linjära och partikulära nanomaterial men inte nanoytor (ytbeläggningar). Nanopartiklar kemiska sammansättning varierar mellan helt oorganiska nanopartiklar, kolnanopartiklar och nanokompositer. Pga. av sin storlek kan nanopartiklar passera en rad biologiska barriärer inklusive cellmembran och blod-hjärn barriären. Nanopartiklars speciella egenskaperna (t.ex. hög reaktivitet) beror bl.a. på den extremt stora ytan i förhållande till volymen vilket innebär att en stor andel av alla atomer befinner sig på ytan av strukturer, där de har en större möjlighet till att interagera med andra abiotiska eller biologiska material. Nanopartiklar har i laboratorieförsök visat sig kunna ha negativa hälsoeffekter. Trots detta finns det endast begränsad kunskap om i vilken grad som exponering för nanopartiklar leder till faktiska hälsoeffekter. Det går inte i nuläget att kvantifiera varken import, export eller mängden nanopartiklar som används i Sverige. Orsakerna är att det i nuläget inte finns några krav på att material eller produkter som innehåller nanopartiklar skall rapporteras till någon myndighet, varken i Sverige eller på EU-nivå. Dessutom finns det en mycket lång rad användningsområden för nanopartiklar, vilket gör att det kan vara besvärligt att sammanställa statistik som på ett tillförlitligt sätt kvantifierar användning, export och import. Det faktum att mycket stora mängder nanopartiklar (framförallt kolpulverbaserade nanopartiklar) använts i en lång rad år före begreppet nanopartiklar uppmärksammades, försvårar statistiksammanställningen ytterligare. 
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46.
  •  
47.
  • Vandenput, Liesbeth, 1974, et al. (författare)
  • Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men.
  • 2007
  • Ingår i: J Bone Miner Res. - : Wiley. ; 22:2, s. 220-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Androgens are important regulators of bone and prostate health in elderly men. The role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in men is unclear. We show that specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Introduction: Androgens are important regulators of bone and prostate health in elderly men. Local synthesis and degradation of androgens are likely to be important parameters of biological action of androgens in androgen-responsive tissues. The aim of this study was to determine the role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in elderly men. Materials and Methods: A subsample of the population-based Swedish part of the MrOS study (n = 631, average age = 75.9 years) was investigated. Bone parameters were measured using DXA. Serum levels of total testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography/mass spectroscopy (GC-MS); androstane-3α,17β-diol-3glucuronide (3G) and androstane-3α,17β-diol-17glucuronide (17G) were measured by liquid chromatography/mass spectroscopy. Prostate volume (n = 159) was measured by transrectal ultrasound. Results: The general pattern is that two of the glucuronidated androgen metabolites, namely 17G and 3G, are stronger positive predictors of BMD than the bioactive androgens (T and DHT). In addition, 17G is a clear positive predictor of prostate volume, explaining 4.5% of the variance in prostate volume, whereas the bioactive androgens do not display any association with prostate volume. Conclusions: Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Future studies should determine if the glucuronidated androgen metabolites also reflect other biological correlates of androgenic activity, including prostate cancer, and if low levels might be a marker of general androgen deficiency in men.
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48.
  • Vandenput, Liesbeth, et al. (författare)
  • Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men
  • 2007
  • Ingår i: Journal of Bone and Mineral Research. - : Wiley. - 0884-0431 .- 1523-4681. ; 22:2, s. 220-227
  • Tidskriftsartikel (refereegranskat)abstract
    • Androgens are important regulators of bone and prostate health in elderly men. The role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in men is unclear. We show that specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men.Introduction: Androgens are important regulators of bone and prostate health in elderly men. Local synthesis and degradation of androgens are likely to be important parameters of biological action of androgens in androgen-responsive tissues. The aim of this study was to determine the role of serum levels of glucuronidated androgen metabolites as predictors of BMD and prostate volume in elderly men.Materials and Methods: A subsample of the population-based Swedish part of the MrOS study (n = 631, average age = 75.9 years) was investigated. Bone parameters were measured using DXA. Serum levels of total testosterone (T) and dihydrotestosterone (DHT) were measured by gas chromatography/mass spectroscopy (GC-MS); androstane-3,17-diol-3glucuronide (3G) and androstane-3,17-diol-17glucuronide (17G) were measured by liquid chromatography/mass spectroscopy. Prostate volume (n = 159) was measured by transrectal ultrasound.Results: The general pattern is that two of the glucuronidated androgen metabolites, namely 17G and 3G, are stronger positive predictors of BMD than the bioactive androgens (T and DHT). In addition, 17G is a clear positive predictor of prostate volume, explaining 4.5% of the variance in prostate volume, whereas the bioactive androgens do not display any association with prostate volume.Conclusions: Serum levels of specific glucuronidated androgen metabolites predict BMD and prostate volume in elderly men. Future studies should determine if the glucuronidated androgen metabolites also reflect other biological correlates of androgenic activity, including prostate cancer, and if low levels might be a marker of general androgen deficiency in men.
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49.
  • Wallerstedt, Susanna Maria, 1970, et al. (författare)
  • Haplotype association analysis of the polymorphisms Arg16Gly and Gln27Glu of the adrenergic beta2 receptor in a Swedish hypertensive population.
  • 2005
  • Ingår i: Journal of human hypertension. - : Springer Science and Business Media LLC. - 0950-9240 .- 1476-5527. ; 19:9, s. 705-8
  • Tidskriftsartikel (refereegranskat)abstract
    • The Arg16Gly and the Gln27Glu polymorphisms in the gene for the beta2-adrenergic receptor (beta2AR) have been linked to an increased risk for cardiovascular disease. The aim of the present study was to evaluate the significance of these haplotypes for development of myocardial infarction (MI) as well as other cardiovascular phenotypes. In a prospective study cohort (CAPPP), 522 hypertensive patients (174 MI and 348 matched controls) were analysed for the Arg16Gly and the Gln27Glu polymorphisms by dynamic allele-specific hybridisation. The haplotype could successfully be determined in 516 patients. Haplotype was not significantly associated with MI. Systolic blood pressure (SBP) was higher in patients with Arg16Gly+Gln27Gln and lower in patients with Arg16Gly+Gln27Glu as compared with the other haplotypes. Haplotype was not associated with body mass index, diastolic blood pressure, cholesterol, LDL, HDL triglycerides or a diagnosis of diabetes mellitus. The present study found no evidence that haplotype for the two most common polymorphisms in the beta2AR are associated with development of MI in a Swedish hypertensive population, but haplotype may be associated with SBP.
  •  
50.
  • Windahl, Sara H, 1971, et al. (författare)
  • Identification of Target Cells for the Genomic Effects of Estrogens in Bone
  • 2007
  • Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 148:12, s. 5688-95
  • Tidskriftsartikel (refereegranskat)abstract
    • Estrogen has bone protective effects, but the exact mechanism behind these effects remains unclear. The aim of the present study was to identify the primary target cells in bone for the classical genomic effects of estrogens in vivo. For this purpose we have used reporter mice with a luciferase gene under the control of three estrogen-responsive elements (EREs), enabling detection of in vivo activation of gene transcription. Three-month-old ovariectomized mice were treated with a single dose (50microg/kg) 17beta-estradiol (E2). Luciferase activity was analysed in several tissues and in different bone marrow-derived lymphocyte enriched/depleted preparations using MacsMouse CD19 (for B lymphocytes) or CD90 (for T lymphocytes) MicroBeads. Histological characterization of cells with high luciferase content was performed using immunohistochemistry. Both cortical bone and bone marrow displayed a rapid (within 1h) and pronounced E2-induced increase in luciferase activity. The luciferase activity in total bone marrow and in bone marrow depleted of lymphocytes was increased 6-8 times more than in either B lymphocyte and T lymphocyte enriched cell fractions 4h after the E2-injection, demonstrating that mature lymphocytes are not major direct targets for the genomic effect of estrogens in bone. Immunohistochemistry identified clear luciferase staining in hypertrophic growth plate chondrocytes, megakaryocytes, osteoblasts and lining cells, while no staining was seen in proliferative chondrocyte. Although most of the osteocytes did not display any detectable luciferase staining, a subpopulation of osteocytes both in cortical and trabecular bone stained positive for luciferase. In conclusion, hypertrophic growth plate chondrocytes, megakaryocytes, osteoblasts, lining cells and a subpopulation of osteocytes were identified to respond to estrogen via the classical ERE-mediated genomic pathway in bone. Furthermore, our findings indicate that possible direct estrogenic effects on the majority of osteocytes, not staining positive for luciferase, on proliferative chondrocytes and on mature lymphocytes are mediated by non-ERE actions.
  •  
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