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| 4. |
- Griffiths, HR, et al.
(författare)
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Biomarkers
- 2002
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Ingår i: Molecular aspects of medicine. - 0098-2997. ; 23:1-3, s. 101-208
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Tidskriftsartikel (refereegranskat)
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| 13. |
- Guerin, S, et al.
(författare)
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Radiation dose as a risk factor for malignant melanoma following childhood cancer
- 2003
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Ingår i: European Journal of Cancer. - 1879-0852. ; 39:16, s. 2379-2386
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine therapy-related risk factors for the development of melanoma after childhood cancer. Among 4401 3-year survivors of a childhood cancer in eight French and British centres and 25 120 patients younger than 20 years old at first malignant neoplasm (FMN) extracted from the Nordic Cancer Registries, 16 patients developed a melanoma as a second malignant neoplasm (SMN). A cohort study of the French and British cohorts was performed. In a nested case-control study, the 16 patients who developed a melanoma as a SMN (cases) were matched with 3-5 controls in their respective cohort according to gender, age at the first cancer, the calendar year of occurrence of the first cancer and follow-up. Radiotherapy appeared to increase the risk of melanoma for local doses > 15 Gy, Odds Ratio (OR)= 13 (95% Confidence Interval (CI): 0.94-174). Regarding chemotherapy, we observed an increased OR for both alkylating agents and spindle inhibitors, OR 2.7 (95% CI: 0.5-14). Children treated for a gonadal tumour as a FMN were found to be at a higher risk of melanoma, OR 8.7 (95% CI: 0.9-86). The adjusted OR for the local radiation dose was 1.07 (95% CI: 1.00-1.15). In conclusion, radiotherapy may contribute to an increased risk of melanoma as a SMN, but only at very high doses of low linear energy transfer radiation. Common genetic origins between gonadal tumours and malignant melanomas are likely. (C) 2003 Elsevier Ltd. All rights reserved.
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| 15. |
- Hirschfeld, RMA, et al.
(författare)
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Social functioning in depression: a review
- 2000
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Ingår i: The Journal of clinical psychiatry. - : Physicians Postgraduate Press, Inc. - 0160-6689. ; 61:4, s. 268-275
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Hou, M, et al.
(författare)
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Angiotensin II type 1 receptors stimulate protein synthesis in human cardiac fibroblasts via a Ca2+-sensitive PKC-dependent tyrosine kinase pathway
- 2000
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 168:2, s. 301-309
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the proliferative effects of Ang II in human cardiac fibroblasts. The effects of Ang II in human cardiac fibroblasts on the 3H-thymidine incorporation, the cell number, the 3H-leucine incorporation and the total protein content were measured. The expression of receptor mRNA was performed by reverse transcription-polymerase chain reaction (RT-PCR). Ang II increased 3H-leucine incorporation in a concentration-dependent manner but not 3H-thymidine incorporation in primary cultures of human cardiac fibroblasts. The maximum effect (24 +/- 3% over control) was obtained at a concentration of 10 nM. There were no significant alterations of cell number or total protein content, suggesting that Ang II stimulated protein synthesis but did not induce hypertrophy. The accumulation of 3H-leucine was blocked by the AT1 receptor antagonist candesartan but not by the AT2 receptor antagonist PD123319. By using RT-PCR, both AT1 and AT2 receptors mRNA were found to be expressed in human cardiac fibroblasts. The selective MAPKK inhibitor PD098059, the protein kinase C inhibitor K252a or the phospholipase C inhibitor U73122 did not significantly inhibit Ang II augmented 3H-leucine incorporation. However, this was significantly blocked by the Ca2+-dependent protein kinase C inhibitor GO6976, the non-selective protein kinase inhibitor staurosporine and the tyrosine kinase inhibitor tyrphostin 25. The effects of Ang II were unaffected by the Gi-protein blocker pertussis toxin, indicating a Gi-protein-independent pathway. Ang II was synergistic with insulin but showed no significant increase on 3H-leucine incorporation when combined with PDGF or EGF. In summary, Ang II stimulates protein synthesis through AT1 receptors in human cardiac fibroblasts, but has no hypertrophic or hyperplastic effect. The response is mediated by a MAPKK-independent and Ca2+-sensitive PKC-dependent pathway.
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| 17. |
- Hou, M, et al.
(författare)
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Cytokines induce upregulation of vascular P2Y(2) receptors and increased mitogenic responses to UTP and ATP
- 2000
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1524-4636. ; 20:9, s. 2064-2069
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Tidskriftsartikel (refereegranskat)abstract
- P2Y(2) receptors, which mediate contractile and mitogenic effects of extracellular nucleotides in vascular smooth muscle cells (VSMCs), are upregulated in the synthetic phenotype of VSMCs and in the neointima after balloon angioplasty, suggesting a role in the development of atherosclerosis. Because released cytokines in atherosclerotic lesions mediate multiple effects on gene transcription in VSMCs, we speculated that cytokines could be involved in the regulation of P2Y(2) receptor expression. Using a competitive reverse transcription-polymerase chain reaction, we detected that interleukin (IL)-1beta induced a time- and dose-dependent upregulation of P2Y(2) receptor mRNA, which was dramatically enhanced when combined with interferon-gamma or tumor necrosis factor-alpha. Lipopolysaccharide also significantly increased the expression of P2Y(2) receptor mRNA. The upregulation of P2Y(2) receptor mRNA was paralleled at the functional level because IL-1beta significantly increased the UTP-stimulated DNA synthesis and the release of intracellular Ca(2+). Actinomycin D completely blocked the upregulation of P2Y(2) receptor mRNA expression by IL-1beta, indicating de novo mRNA synthesis. There was no cAMP accumulation in the cells stimulated with IL-1beta. The cyclooxygenase inhibitor indomethacin and the protein kinase C inhibitor RO-31-8220 inhibited IL-1beta-induced upregulation of P2Y(2) receptor mRNA expression, whereas rapamycin and PD098059 had no effects. Furthermore, neither P38 mitogen-activated protein kinase inhibitor SB20358 alone nor its combination with PD098059 blocked the effect of IL-1beta on the expression of P2Y(2) receptor mRNA. Our results demonstrate that inflammatory mediators upregulate vascular P2Y(2) receptors at the transcriptional and at the functional level through protein kinase C and cyclooxygenase but not cAMP, extracellular signal-regulated kinases 1 and 2, or P38-dependent pathways. This may result in increased growth-stimulatory or contractile effects of extracellular UTP and ATP, which may be of importance in the development of vascular disease.
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| 20. |
- Moller, T, et al.
(författare)
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Job enlargement and mechanical exposure variability in cyclic assembly work
- 2004
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Ingår i: Ergonomics. - : Informa UK Limited. - 0014-0139 .- 1366-5847. ; 47:1, s. 19-40
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Tidskriftsartikel (refereegranskat)abstract
- Cyclic assembly work is known to imply a high risk for musculoskeletal disorders. To have operators rotate between work tasks is believed to be one way of decreasing this risk, since it is expected to increase variation in mechanical and psychological exposures (physical and mental loads). This assumption was investigated by assessing mechanical exposure variability in three assembly tasks in an electronics assembly plant, each on a separate workstation, as well as in a 'job enlargement' scenario combining all three stations. Five experienced operators worked for 1 h on each station. Data on upper trapezius and forearm extensor muscle activity were obtained by means of electromyography (EMG), and working postures of the head and upper arms were assessed by inclinometry. The cycle-to-cycle variance of parameters representing the three exposure dimensions: level , frequency and duration was estimated using ANOVA algorithms for each workstation separately as well as for a balanced combination of all three. For a particular station, the variability of trapezius EMG activity levels relative to the mean was higher than for extensor EMG: between-cycles coefficients of variation (CV) about 0.15 and 0.10, respectively. A similar relationship between CV applied to the parameter describing frequency of EMG activity. Except for head inclination levels, the between-cycles CV was larger for posture parameters than for EMG. The between-cycles variance increased up to six fold in the job enlargement scenario, as compared to working at only one station. The difference in mean exposure between workstations was larger for trapezius EMG parameters than for forearm extensor EMG and postures, and hence the effect of job enlargement on exposure variability was more pronounced for the trapezius. For some stations, job enlargement even implied less cycle-to-cycle variability in forearm extensor EMG parameters than working at that station only. Whether the changes in exposure variability associated with job enlargement were sufficient to imply a decreased risk for musculoskeletal disorders is not known.
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| 22. |
- Musi, N., et al.
(författare)
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Metformin increases AMP-activated-protein-kinase activity in skeletal of subjects with type 2 diabetes
- 2002
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Ingår i: Diabetes. - Alexandra, VA, USA : American Diabetes Association Inc.. - 0012-1797 .- 1939-327X. ; 51:7, s. 2074-2081
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Tidskriftsartikel (refereegranskat)abstract
- Metformin is an effective hypoglycemic drug that lowers blood glucose concentrations by decreasing hepatic glucose production and increasing glucose disposal in skeletal muscle; however, the molecular site of metformin action is not well understood. AMP-activated protein kinase (AMPK) activity increases in response to depletion of cellular energy stores, and this enzyme has been implicated in the stimulation of glucose uptake into skeletal muscle and the inhibition of liver gluconeogenesis. We recently reported that AMPK is activated by metformin in cultured rat hepatocytes, mediating the inhibitory effects of the drug on hepatic glucose production. In the present study, we evaluated whether therapeutic doses of metformin increase AMPK activity in vivo in subjects with type 2 diabetes. Metformin treatment for 10 weeks significantly increased AMPK α2 activity in the skeletal muscle, and this was associated with increased phosphorylation of AMPK on Thr172 and decreased acetyl-CoA carboxylase-2 activity. The increase in AMPK α2 activity was likely due to a change in muscle energy status because ATP and phosphocreatine concentrations were lower after metformin treatment. Metformin-induced increases in AMPK activity were associated with higher rates of glucose disposal and muscle glycogen concentrations. These findings suggest that the metabolic effects of metformin in subjects with type 2 diabetes may be mediated by the activation of AMPK α2.
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| 23. |
- Narod, SA, et al.
(författare)
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Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers
- 2002
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105. ; 94:23, s. 1773-1779
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Tidskriftsartikel (refereegranskat)abstract
- Background: Oral contraceptive use has been associated with an increase in the risk of breast cancer in young women. We examined whether this association is seen in women at high risk of breast cancer because they carry a mutation in one of two breast cancer susceptibility genes, BRCA1 and BRCA2. Methods: We performed a matched case-control study on 1311 pairs of women with known deleterious BRCA1 and/or BRCA2 mutations recruited from 52 centers in 11 countries. Women who had been diagnosed with breast cancer were matched to control subjects by year of birth, country of residence, mutation (BRCA1 or BRCA2), and history of ovarian cancer. All study subjects completed a questionnaire about oral contraceptive use. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. All statistical tests were two-sided. Results: Among BRCA2 mutation carriers, ever use of oral contraceptives was not associated with an increased risk of breast cancer (OR = 0.94, 95% CI = 0.72 to 1.24). For BRCAI mutation carriers, ever use of oral contraceptives was associated With a modestly increased risk of breast cancer (OR = 1.20, 95 % CI = 1.02 to 1.40). However, compared with BRCA1 mutation carriers who never used oral contraceptives, those who used oral contraceptives for at least 5 years had an increased risk of breast cancer (OR = 1.33, 95% CI = 1.11 to 1.60), as did those who used oral contraceptives before age 30 (OR = 1.29, 95% CI = 1.09 to 1.52), those who were diagnosed with breast cancer before age 40 (OR = 1.38, 95% CI = 1.11 to 1.72), and those who first used oral contraceptives before 1975 (OR = 1.42, 95 % CI = 1.17 to 1.75). Conclusions: Among BRCA1 mutation carriers, women who first used oral contraceptives before 1975, who used them before age 30, or who used them for 5 or more years may have an increased risk of early-onset breast cancer. Oral contraceptives do not appear to be associated with risk of breast cancer in BRCA2 carriers, but data for BRCA2 carriers are limited.
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| 24. |
- Saether, BE, et al.
(författare)
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Time to extinction in relation to mating system and type of density regulation in populations with two sexes
- 2004
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Ingår i: Journal of Animal Ecology. - : Wiley. - 1365-2656 .- 0021-8790. ; 73:5, s. 925-934
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Tidskriftsartikel (refereegranskat)abstract
- 1. Population viability models usually consider only the female segment of the population. However, random variation in sex ratio as well as the mating system may also affect variation in fitness among females. Here we develop population models incorporating demographic stochasticity in both sexes. Furthermore, we consider the effects on the estimated time to extinction and whether density regulation acts only on females or on total population size. 2. We applied these models to two populations of polygynous great reed warblers Acrocephalus arundinaceus L. with differences in population trends to investigate the importance of considering sex in population viability models. 3. Demographic stochasticity was larger in a polygynous than in a monogamous mating system. 4. The estimated time to extinction was considerably shorter for a monogamous than for a polygynous mating system, particularly if density regulation acted only on females than rather on the total population. 5. This study demonstrates that structure of mating system must be included when making population viability analysis based on counts of total population sizes. It is especially important to model the specific effects of density regulation on the two sexes.
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| 26. |
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| 27. |
- Sunde, Peter, et al.
(författare)
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Reversed sexual dimorphism in tawny owls, Strix aluco, correlates with duty division in breeding effort
- 2003
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Ingår i: Oikos. - : Wiley. - 1600-0706 .- 0030-1299. ; 101:2, s. 265-278
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Tidskriftsartikel (refereegranskat)abstract
- Even though most bird species with a raptorial feeding habit express varying extents of reversed sexual dimorphism (RSD: females bigger than males), the evolutionary basis for its maintenance, as well as its possible secondary consequences for the ecological adaptations of the different sexes, is debated. We studied pairs of tawny owls, Strix aluco (females 20% heavier than males), throughout the year by telemetry to test whether any inter-sexual differences in movement patterns, resource partitioning and breeding effort correlated with RSD. Females were larger than males in all body size measures and were 16% heavier than would be expected from the difference in wing length alone. In accordance with predictions from flight economics, males moved longer distances per time unit than females, in particular during the post-fledging season, when they also fed chicks more often than the females. Males had larger home ranges than females during the post-fledging period, whereas the sexes had home ranges of equal size during the non-breeding season. Until 10 days after fledging, females foraged much closer to the offspring than males, apparently balancing their distance to offspring between the needs of offspring guarding and foraging. In males, the parent-offspring distance only increased with decreasing brood condition. The sexes did not differ in habitat use or feeding habits, rendering no indications of food niche partitioning. The study provides further evidence that selection for males to be light and energetically efficient foragers is the main evolutionary force behind RSD in raptorial birds, even when the prey base is confined by territoriality.
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| 28. |
- Tiselius, Peter, 1958, et al.
(författare)
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Functional response of Oikopleura dioica to house clogging due to exposure to algae of different sizes
- 2003
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Ingår i: Marine Biology. - 0025-3162. ; 142:2, s. 253-261
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Tidskriftsartikel (refereegranskat)abstract
- The functional response of the appendicularian Oikopleura dioica was investigated with a unialgal diet (Isochrysis galbana, 0-1,600 mug Cl-1) and with additions of specific concentrations of algae either smaller than the incurrent filter mesh size (Rhodomonas baltica, 90 mug Cl-1; Thalassiosira weissflogii, 60 mug Cl-1) or larger algae (Ceratium lineatum, 8 mug Cl-1; C. tripos, 52 mug C l(-1)). Clearance ranged from 0.13 to 3.3 ml mug C-1 h(-1) and followed a Michaelis-Menten curve corresponding to a maximum filtration rate (particles collected by both animal and house), FRmax = 164 ng C mug C-1 h(-1) and K-m = 64 mug C l(-1). Maximum pellet production was 9 pellets ind(-1) h(-1) and occurred at 100 mugC (-1). Pellet production was proportional to filtration rate below this level, but declined at higher concentrations. House production ranged from 0.5 to 5.5 houses ind(-1) day(-1) and the corresponding curve fit resulted in H-max = 4.6 houses ind(-1) day(-1) and K-m house = 32 mug Cl-1. Addition of edible small algae caused increased internal clogging of the houses, evidenced by significantly higher pigment concentrations in abandoned houses than in houses produced with I.. galbana as a single food. House production was not affected. In contrast, larger algae caused a significantly higher house production, but the algae were not collected on the houses. Increased levels of edible algae will not have negative effects on O. dioica at ecologically realistic concentrations. Ambient bloom concentrations of larger algae may, however, have a negative effect on the growth of O. dioica populations, owing to the compensatory increased house production.
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| 29. |
- Vargas, C. A., et al.
(författare)
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Importance of copepods versus appendicularians in vertical carbon fluxes in a Swedish fjord
- 2002
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Ingår i: Marine Ecology-Progress Series. - 0171-8630. ; 241, s. 125-138
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Tidskriftsartikel (refereegranskat)abstract
- We examined and quantified the contributions of copepods and appendicularians to the vertical flux of carbon during autumn and spring in Gullmar Fjord (west coast of Sweden). Faecal pellet-production rate was determined for major copepod and appendicularian species. In addition, house-production rates were estimated for the appendicularian Oikopleura dioica. Vertical flux of pigments, faecal carbon and appendicularian houses were measured using short-term (24 h) deployments of sediment traps at 2 depths (15 and 30 m). Copepods dominated the community biomass in both spring and autumn and their pellets dominated the faecal carbon flux. O. dioica houses with attached detritus were an important component of the biogenic carbon flux in October (15.3 mg C m(-2) d(-1)), equalling the contribution from copepods at 15 m and 50% of the flux at 30 m. At that time, we observed a loss rate of 70% d(-1) of the houses produced in the water column. In the spring, although Fritillaria borealis dominated the appendicularians, its houses did not appear to contribute to the biogenic flux. Our results suggest that oikopleurids and fritillariids may not operate equivalently in biogeochemical cycles. Because of the significant contribution of appendicularians to carbon fluxes, they should be incorporated in future flow models of coastal oceans.
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