| 1. |
- Vasan, Ramachandran S, et al.
(författare)
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Genetic variants associated with cardiac structure and function : a meta-analysis and replication of genome-wide association data
- 2009
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 302:2, s. 168-178
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
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| 2. |
- Lind, Anna-Sara, 1977-
(författare)
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Sociala rättigheter i förändring : En konstitutionellrättslig studie
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation examines the status and role of fundamental social rights in a Swedish context. The point of departure is Chapter 1, Article 2, para. 2 in the Swedish Instrument of Government, where important social rights are articulated as fundamental goals for society: the right to social assistance, the right to shelter and the right to health. As these rights are”goals”, the state and its authorities shall strive to achieve them. They are not formulated as individual rights in the constitution and are not invocable before the courts. In order to analyse the constitutional choice to keep these rights outside the Swedish “Bill of Rights” in Chapter 2 of the Instrument of Government, the constitutions of Canada, Finland and South Africa are studied. The Swedish constitutional context is highly dependant on international obligations in international conventions and the fact that Sweden is a member of the European Union. Changes and trends concerning access to and content of social rights in public international law are traced via the United Nation’s two conventions for human rights, as well as through the conventions of the Council of Europe. The conclusion is that social rights today are being defined in a clearer way than before. Individuals and groups also have wider possibilities to make complaints concerning violations of these rights. A very important factor for this is the evolving view of non discrimination in public international law. Non discrimination is also the point of departure for the strengthening of access to social rights in the European Union. Through the four freedoms of European Community law, the individual has been given individual rights. Today this picture is widened thanks to the citizenship of the European Union and to the EU Charter on Fundamental Rights. We can therefore start considering social human rights in the EU. The conclusion is that the Swedish constitution does not handle the constraints that public international law and the membership in the EU mean for the national welfare state, nor is it equipped to handle that the factual status of social rights as constitutional rights.
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| 3. |
- Andersson, Jessika, et al.
(författare)
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The carotid artery plaque size and echogenicity are related to different cardiovascular risk factors in the elderly : the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study
- 2009
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Ingår i: Lipids. - : Springer. - 0024-4201 .- 1558-9307. ; 44:5, s. 397-403
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Tidskriftsartikel (refereegranskat)abstract
- Carotid plaques can be characterised by ultrasound by size and echogenicity. Both size and echogenicity are predictors of cardiovascular events. The aim of this study was to examine whether traditional risk factors and markers of inflammation and oxidation were associated with plaque size and echogenicity. Computerised analysis of carotid plaque size and echogenicity (grey scale median, GSM) were performed by ultrasound in a population-based health survey in 1,016 subjects aged 70 years (PIVUS study). Information on cardiovascular risk factors was collected, together with markers of inflammation and oxidation. Increased Framingham risk score, systolic blood pressure, higher BMI and decreased HDL, lower glutathione levels were related to echolucent plaques. Previous or present smoking was common with significantly more pack-years related to the echorich plaques. Plaque size was associated with increased Framingham risk score, systolic blood pressure, blood glucose levels, smoking, ApoB/A1 ratio, OxLDL, TNF alpha, HOMA insulin resistance, leucocyte count, decreased BCD-LDL and low levels of l-selectin. Low HDL, increased BMI and decreased glutathione levels were associated with the echolucency of carotid plaques, implying metabolic factors to play a role for plaque composition. Markers of inflammation were related to plaque size alone, implying inflammation to be predominantly associated with the amount of atherosclerosis. These results suggest that plaque size and echogenicity are influenced by different risk factors.
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| 4. |
- Björkqvist, Maria, et al.
(författare)
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A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.
- 2008
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205, s. 1869-1877
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Tidskriftsartikel (refereegranskat)abstract
- Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.
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| 5. |
- Ebeling Barbier, Charlotte, et al.
(författare)
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The exactness of left ventricular segmentation in cine magnetic resonance imaging and its impact on systolic function values
- 2007
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 48:3, s. 285-291
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To evaluate the impact of exactness of the segmentation of the left ventricle (LV), using cine magnetic resonance imaging (MRI). Material and methods: Steady-state free-precession cine MRI was performed on 100 randomly selected subjects. Myocardial borders were outlined on short-axis images using three methods: method 1 was computer assisted, excluding papillary muscles from the left ventricular mass (LVM); method 2 was similar but included papillary muscles; and method 3 was manually traced including papillary muscles. LV end-systolic (ES) and end-diastolic (ED) masses and volumes, ejection fraction (EF), stroke volume (SV), and cardiac output (CO) were calculated from these measurements. The difference between the ES and ED LVM was used to estimate the exactness of the methods. Results: Method 3 was the most exact, and method 1 was the least exact. The three methods generated differing EF, SV, and CO measurements. With an ES-ED LVM difference exceeding 20 g, the mean SV measurement error was 8.83.6 ml. Conclusion: Manual tracing proved more exact than computer-assisted quantification. Exactness had an impact on EF, SV, and CO measurements, and the ES-ED LVM difference can be used to identify assessments that would benefit from more exact segmentation.
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| 6. |
- Forsell, Camilla, 1971-
(författare)
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Perceptually Motivated Constraints on 3D Visualizations
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis addresses some important characteristics of human visual perception and their implications for three-dimensional (3D) information visualization. The effort can be divided into two parts. First, findings from vision science are explored and validated. As a starting point, the compilation of perceptually motivated evidence about what constitutes an effective and efficient method for mapping of data is undertaken. Second, the knowledge obtained is used to create candidate visualizations and to demonstrate the predictive power of the findings.Results indicate a general difficulty to convey metric, i.e. quantitative, information in 3D visualizations. Structure as defined by Euclidean geometry is not perceived with accuracy and information encoded by such distinctions are misunderstood or overlooked. On the other hand, qualitative properties as defined by affine geometry are salient are perceived with accuracy (paper I). These findings are also characteristic of two-dimensional (2D) visualizations when these need to be rapidly examined (paper II). A novel method (3D surface glyphs) for abstract multivariate data sets was developed to investigate the possible merit of encoding information by qualitative distinctions, (paper III). Evaluations showed that the information conveyed was successfully utilized and that these types of glyph have great potential. The study also illustrated the predictive power of the earlier findings. These issues were further demonstrated when investigating how 3D perspective displays are unaffected by distortions in data when the patterns displayed were defined by affine properties (paper IV). In addition, a new metric for measuring the efficiency of visualizations is presented (paper III). It is concluded that as long as visualizations are specified by qualitative properties, they could most probably be effectively and efficiently used. The need for user studies to determine if, when and how to choose a certain visualization technique for a given task is thereby significantly reduced.
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| 7. |
- Hodgson, S., et al.
(författare)
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Bone mineral density changes in relation to environmental PCB exposure
- 2008
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Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 116:9, s. 1162-1166
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Tidskriftsartikel (refereegranskat)abstract
- Background: Bone toxicity has been linked to organochlorine exposure following a few notable poisoning incidents, but epidemiologic studies in populations with environmental organochlorine exposure have yielded inconsistent results. Objectives: The aim of this study was to investigate whether organochlorine exposure was associated with bone mineral density (BMD) in a population 60-81 years of age (154 males, 167 females) living near the Baltic coast, close to a river contaminated by polychlorinated biphenyls (PCBs). Methods: We measured forearm BMD in participants using dual energy X-ray absorptiometry, and we assessed low BMD using age- and sex-standardized Z-scores. We analyzed blood samples for five dioxin-like PCBs, the three most abundant non-dioxin-like PCBs, and p,p'-dichlorophenyldichloroethylene (p,p'-DDE). Results: In males, dioxin-like chlorobiphenyl (CB)-118 was negatively associated with BMD, the odds ratio for low BMD (Z-score less than -1) was 1.06 (95% confidence interval, 1.01-1.12) per 10 pg/mL CB-118. The sum of the three most abundant non-dioxin-like PCBs was positively associated with BMD, but not with a decreased risk of low BMD. In females, CB-118 was positively associated with BMD, but this congener did not influence the risk of low BMD in women. Conclusions: Environmental organochlorine exposures experienced by this population sample since the 1930s in Sweden may have been sufficient to result in sex-specific changes in BMD.
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| 8. |
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| 9. |
- Kalbro, Thomas, 1951-, et al.
(författare)
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Compulsory Purchase - Reasonable and Fair Compensation : An Experimental Study
- 2007
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Ingår i: Nordic Journal of Surveying and Real Estate Research. - Helsinki : Finnish Society of Surveying Sciences. - 1459-5877 .- 2341-6599. ; 4:1
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Tidskriftsartikel (refereegranskat)abstract
- Swedish law provides that compensation for compulsory purchase – in some cases – shall be decided according to the following general principle: The compensation should correspond to the price that could have been expected if it had been a "normal voluntary transaction". However, in those specific situations where compulsory purchase applies, there is always a lack of empirical data of price levels in voluntary agreements. In this article we enlighten the problem through bargaining experiments with buyers and sellers. We provide experimental evidence from Sweden indicating that the price level – or the profit-sharing between buyer and seller – depends on the context and what is judged to be reasonable principles of fair distribution.
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| 10. |
- Kalbro, Thomas, 1951-, et al.
(författare)
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En flexibel och effektiv bostadsmarknad - problem och åtgärder
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Föreliggande rapport är den tredje och avslutande i ett uppdrag från Tillväxtverket (Nutek) till KTHs institution för Fastigheter och byggande. Ett parallellt uppdrag har gått till Institutet för Bostadsforskning vid Uppsala universitet. Den grundläggande frågan har rört hur bostadsmarknaden och bostadsbyggandet i storstadsregionerna kan utvecklas.I rapporten sammanfattas tio års forskning om bostadsmarknadens roll och funktion inkluderat hur nya bostäder kan tillskapas och hur beståndet kan utnyttjas effektivare. Våra observationer och rekommendationer baseras på såväl empiri som teori. De förändringar i regelverk och synsätt som presenteras och diskuteras utgår från bostadskonsumenten och den bostadskarriär som varje hushåll gör.Vår målgrupp är politiker och andra aktörer på bostadsmarknaden. De ska förhoppningsvis finna att rapporten ger nya uppslag och underlag för en intressant och konstruktiv debatt. De slutsatser som dras är våra egna.
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| 11. |
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| 12. |
- Kurland, Lisa, 1960-, et al.
(författare)
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The relationship between the plasma concentration of irbesartan and the antihypertensive response is disclosed by an angiotensin II type 1 receptor polymorphism : results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) Trial
- 2008
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Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 21:7, s. 836-839
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this study was to investigate the effect of the plasma concentration of irbesartan, a specific angiotensin II type 1 receptor (AT1R) antagonist, and the blood pressure response in relation to AT1R gene polymorphisms. Methods Plasma irbesartan was analyzed in 42 patients with mild-to-moderate hypertension and left ventricular hypertrophy from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs. Atenolol (SILVHIA) trial, who were treated with irbesartan as monotherapy for 12 weeks. Blood pressure and irbesartan concentration were measured at trough, i.e., 24 ± 3 h after the last dose. Five AT1R gene polymorphisms were analyzed by minisequencing. Results Neither the plasma concentration of irbesartan, nor any of the AT1R polymorphisms were associated with the blood pressure response to irbesartan treatment. However, the interaction term between the plasma concentration of irbesartan and the AT1R C5245T polymorphism was related to the reduction in systolic blood pressure after 12 weeks of treatment (P = 0.025). Furthermore, the plasma concentration of irbesartan was related to the change in systolic blood pressure in individuals homozygous for the AT1R 5245 T allele (r = -0.56, P = 0.030), but not for other genotypes. Conclusions There was an association between plasma concentrations of irbesartan and the blood pressure response for hypertensive patients with AT1R 5245 TT. Because of the small sample size, this study needs to be viewed as hypothesis generating. This is the first study, to our knowledge, indicating that the concentration–response relationship of an antihypertensive drug may be genotype dependent.
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| 13. |
- Liljedahl, Stefan, et al.
(författare)
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The effects of antihypertensive treatment on the doppler-derived myocardial performance index in patients with hypertensive left ventricular hypertrophy : results from the Swedish irbesartan in left ventricular hypertrophy investigation versus atenolol (SILVHIA)
- 2009
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Ingår i: Echocardiography. - : Wiley. - 0742-2822 .- 1540-8175. ; 26:7, s. 753-758
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the effects of antihypertensive treatment on the Doppler-derived myocardial performance index (MPI) in patients with hypertensive left ventricular hypertrophy. METHODS: The MPI was measured at baseline and after 48 weeks of antihypertensive treatment in 93 participants of the SILVHIA trial, where individuals with primary hypertension and left ventricular hypertrophy were randomized to double blind treatment with either irbesartan or atenolol. RESULTS: Antihypertensive treatment lowered MPI (mean difference -0.03 +/- 0.01, P = 0.04). Changes in MPI by treatment were associated with changes in left ventricular ejection fraction (beta-coefficient -0.35 P = 0.005), stroke volume/pulse pressure (reflecting arterial compliance, beta-coefficient -0.39 P < 0.001) and peripheral vascular resistance (beta-coefficient 0.28 P < 0.04). Furthermore, there was a borderline significant association between changes in MPI and changes in E-wave deceleration time (reflecting diastolic function, beta-coefficient 0.23, P = 0.06). No associations were found between changes in MPI and changes in blood pressure, E/A-ratio, left ventricular mass index, relative wall thickness or heart rate. A stepwise multivariable regression model confirmed the association between changes in MPI and changes in ejection fraction and stroke volume/pulse pressure (all P < 0.05), as well as the trend for E-wave deceleration time (P = 0.08), but not in the case of peripheral vascular resistance. CONCLUSION: The MPI exhibited a modest decrease after 48 weeks of antihypertensive treatment in patients with hypertensive left ventricular hypertrophy. Changes in MPI were associated with changes in left ventricular function and vascular compliance, rather than with changes in left ventricular remodeling or blood pressure.
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| 14. |
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| 15. |
- Lind, Thomas, et al.
(författare)
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Purification of an insect derived recombinant human ADAMTS-1 reveals novel gelatin (type I collagen) degrading activities.
- 2006
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Ingår i: Molecular and Cellular Biochemistry. - : Springer Science and Business Media LLC. - 0300-8177 .- 1573-4919. ; 281:1-2, s. 95-102
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Tidskriftsartikel (refereegranskat)abstract
- ADAMTS-1 (A Disintegrin And Metalloprotease with ThromboSpondin repeats) is a member of a family of secreted proteolytic enzymes with a complex modular structure. These enzymes are characterised by an N-terminal metalloproteinase domain, a disintegrin-like domain and a carboxyl terminal region containing variable numbers of a repeat sequence with homology to thrombospondin-1. The expression of the gene for ADAMTS-1 has been associated with inflammation, ovulation, angiogenesis, cellular proliferation and bone formation. ADAMTS-1 can proteolytically process large proteoglycans indicating a potential role in extracellular matrix turnover. In this study, we have tested ADAMTS-1 activity in gelatin zymogram assays. Since previous data demonstrate that ADAMTS-1 is a matrix metalloproteinase (MMP) substrate and is highly unstable in conditioned medium from eukaryotic cell types, we created an insect cell line expressing human ADAMTS-1. We isolated an epitope tagged full-length recombinant ADAMTS-1 from serum free insect cell conditioned medium. The purified protein had aggrecanase activity and appears as two major bands on the silver stained SDS-PAGE corresponding well to a pro-domain on form of 115 kDa and a pro-domain off form of 90 kDa. Using denatured type I collagen in zymographic analysis we demonstrate that ADAMTS-1 has a previously unreported gelatinolytic activity. Also, we notice that processing of its C-terminal region by an apparently autocatalytic process reveals a 27 kDa species with gelatinolytic activity. Furthermore, we show that MMP2 but not MMP13 remove ADAMTS-1 specific gelatin zymopraphic zones.
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| 16. |
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| 17. |
- Rehn, Anders P, et al.
(författare)
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ADAMTS-1 increases the three-dimensional growth of osteoblasts through type I collagen processing.
- 2007
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Ingår i: Bone. - : Elsevier BV. - 8756-3282 .- 1873-2763. ; 41:2, s. 231-8
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Tidskriftsartikel (refereegranskat)abstract
- The multi-domain neutral endopeptidase, ADAMTS-1 (a disintegrin and metalloprotease with thrombospondin repeats) is induced by parathyroid hormone (PTH) in rat osteoblasts and has therefore been suggested to be involved in initiation of bone remodeling. However, its function(s) in bone cells have not been studied. Here, we first establish that ADAMTS-1 protein is rapidly and transiently produced by human primary osteoblasts in response to PTH (1-34). We also show that ADAMTS-1 is specifically in close proximity to collagen fibrils in bone tissue using ultrastructural immunolabeling. To study the consequence(s) of ADAMTS-1 metalloprotease production in osteoblastic cells, human osteosarcoma cells (SaOS-2), were forced to express either wild-type (wtATS) or a point-mutated (pmATS) metalloprotease dead ADAMTS-1. SaOS-2 cells expressing wtATS had a growth advantage and increased collagenolytic activity when seeded inside a collagen type I gel but exhibited a reduced migration in a scratch wound assay. Immunolabeling of moving cells shows ADAMTS-1 to be located towards the direction of cellular migration. Finally, Western analysis demonstrated excess accumulation of mature collagen type I alpha1 species in the extracellular matrix together with increased release of distinct small collagen fragments into the conditioned media, by cultures of wtATS cells compared to pmATS cells. These results show that ADAMTS-1 has both the opportunity in bone and capability in vitro to induce collagen type I processing, together with a positive influence on osteoblastic three-dimensional growth. Although it is not clear at present if ADAMTS-1 promotes collagen degradation directly or indirectly, it shows that ADAMTS-1 activity can have a profound influence on the osteoblast phenotype, inhibiting migration on a planar substrate but enhancing growth in a collagen scaffold. These findings further establish ADAMTS-1 as a potentially important protein in PTH induced bone remodeling.
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| 18. |
- Sahlén, Anders, et al.
(författare)
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Magnitude, reproducibility, and association with baseline cardiac function of cardiac biomarker release in long-distance runners aged > or =55 years
- 2008
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 102:2, s. 218-222
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac biomarker release after endurance exercise has been described in young athletes. Although older athletes are increasingly active in such sports, they have not previously been studied. Therefore, the aim of this study was to assess the magnitude and reproducibility of biomarker release in athletes aged > or =55 years. Forty-three healthy athletes (mean age 61 +/- 3.6 years) were assessed before and immediately after a 30-km cross-country race and studied with echocardiography at rest. The median N-terminal pro-brain natriuretic peptide (NT-proBNP; normal <194 ng/L) level was 42 ng/L (interquartile range 30 to 95) at baseline and 191 ng/L (interquartile range 114 to 308) after the race. Troponin T (normal <0.03 microg/L) was elevated in 19 subjects (44%) after the race. Twenty-two subjects had also been studied 3 years before at the same race, using an identical test protocol. Between the 2 races, strong correlations were seen for individual runners' postrace biomarker levels (NT-proBNP: r = 0.82, log transformed data; troponin T: Spearman's rho = 0.84; p <0.001 for both). The coefficient of variation for NT-proBNP release was 8.1%. Levels of NT-proBNP after the race were correlated with levels at baseline (r = 0.93, p <0.001) and with left ventricular mass index (r = 0.32, p = 0.03). Moreover, participants with elevated postrace NT-proBNP were significantly older (62.0 vs 59.8 years, p = 0.04). In conclusion, long-distance runners aged > or =55 years released NT-proBNP and troponin T in a reproducible fashion. The magnitude of NT-proBNP release during the race was correlated strongly with NT-proBNP baseline levels and was associated with left ventricular mass and age. These findings may suggest a potential adverse effect of long-distance running on cardiac function in certain participants in this age group.
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| 19. |
- Thelander, Claes, et al.
(författare)
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Development of a Vertical Wrap-Gated InAs FET
- 2008
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Ingår i: IEEE Transactions on Electron Devices. - 0018-9383. ; 55:11, s. 3030-3036
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we report on the development of a vertical wrap-gated field-effect transistor based on epitaxially grown InAs nanowires. We discuss some of the important steps involved in the growth and processing, such as nanowire position control in situ doping, high-kappa dielectric deposition, spacer layer formation: and metal wrap-gate fabrication. In particular, we compare a few alternative methods for deposition of materials onto vertical structures and discuss their potential advantages and limitations. Finally, we also present a comparison of transistor performance for nanowires grown using two different epitaxial techniques.
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