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| 11. |
- 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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| 15. |
- 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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| 16. |
- 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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| 19. |
- Falkeholm, L, et al.
(författare)
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Xylene-free method for histological preparation : A multicentre evaluation
- 2001
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Ingår i: Laboratory Investigation. - 0023-6837 .- 1530-0307. ; 81:9, s. 1213-1221
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Tidskriftsartikel (refereegranskat)abstract
- The backbone of daily pathological diagnostic work is the paraffin section. Paraffin sections are still prepared by methods largely unchanged for over 150 years. A xylene-free method has been developed that excludes xylene, not only as the intermediate step before the paraffin baths, but also for deparaffinizing of the cut sections, which also eliminates the need for rehydration and dehydration for the staining and mounting steps. Elimination of xylene from tissue processing cuts costs, saves time, and improves the laboratory environment. Experience with xylene-free sections since 1995 at the Vrinnevi Hospital is favorable. Our opinion is that the xylene-free sections are equivalent to conventionally processed sections. To test this hypothesis, nine pathologists from three hospitals participated in an evaluation trial. Paired tissue blocks from 10 consecutively submitted samples each of breast, intestine, and skin were processed by either the xylene-free or the conventional method. Sections from each block were deparaffinized and stained with hematoxylin-eosin (H&E), with periodic acid-Schiff (PAS), and with van Gieson's method. A randomized mix of 180 sections (10 samples x 3 tissues x 3 stains x 2) gave 90 matched pairs. Each section was blindly examined and scored by nine pathologists to give 810 paired observations for statistical evaluation. The xylene-free sections were ranked as good as or better than their conventional counterparts in 74% of the comparisons, and poorer in 26%. The major discriminating factor was the staining method. H&E and PAS sections were equivalent. The xylene-free van Gieson sections, cut from the same blocks and randomly assigned to this stain, tended to be downgraded. This could be traced to a faulty stain solution used for this batch. The overall results have demonstrated professional acceptance for the xylene-free method of processing histological sections.
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| 20. |
- 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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| 22. |
- 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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| 25. |
- Moller, E. F., et al.
(författare)
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Production of DOC by Calanus finmarchicus, C-glacialis and C-hyperboreus through sloppy feeding and leakage from fecal pellets
- 2003
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Ingår i: Marine Ecology-Progress Series. - 0171-8630. ; 262, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- Using C-14-labeled phytoplankton as tracer, we investigated 2 mechanisms of immediate dissolved organic carbon (DOC) release during grazing activity of Calanus spp. - sloppy feeding and leakage from newly expelled fecal pellets. Half of the carbon cleared by Calanus spp. was released as DOC through sloppy feeding. Freshly expelled fecal pellets lost more than 20% of their carbon content within the first hour, corresponding to 6% of the carbon cleared. Thus, copepods should not only be considered as an essential link to higher trophic levels, but also as a feedback link to the microbial food web.
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| 26. |
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| 27. |
- Moller, P., et al.
(författare)
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Genetic epidemiology of BRCA1 mutations in Norway
- 2001
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Ingår i: European Journal of Cancer. - 1879-0852. ; 37:18, s. 2428-2434
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Tidskriftsartikel (refereegranskat)abstract
- Familial breast-ovarian cancer has been demonstrated to be frequent but unevenly distributed in Norway. This was assumed to be caused by the reduced population size created by the medieval Bubonic plague, 25 generations ago, and by the following rapid expansion. We have previously reported that four mutations account for 68% of the BRCA1 mutation carriers. Subsequent analysis has resulted in a total of 100 separate families carrying one of these founder mutations. The four mutations occurred on one specific BRCA1 haplotype each. The 1675delA, 816delGT and 3347detAG families originated from the South-West coast of Norway with a few Families in the north, while the traceable ancestors of the 1135insA families clustered along the historical inland road from the South-East to mid-Norway. The carriers of each of the four mutations today are descendants of one or a few individuals surviving the plagues. We may identify the majority of BRCA1 mutation carriers in Norway by screening for local founder mutations.
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| 28. |
- Moller, P, et al.
(författare)
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Survival in prospectively ascertained familial breast cancer: Analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy
- 2002
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136. ; 101:6, s. 555-559
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Tidskriftsartikel (refereegranskat)abstract
- Dedicated clinics have been established for the early diagnosis and treatment of women at risk for inherited breast cancer, but the effects of such interventions are currently unproven. This second report on prospectively diagnosed inherited breast cancer from the European collaborating centres supports the previous conclusions and adds information on genetic heterogeneity and the effect of oophorectomy. Of 249 patients, 20% had carcinoma in situ (CIS), 54% had infiltrating cancer without spread (CaNO) and 26% had cancer with spread (CaN+). Five-year survival was 100% for CIS, 94% for CaNO and 72% for CaN+ (p = 0.007). Thirty-six patients had BRCA1 mutations, and 8 had BRCA2 mutations. Presence of BRCA1 mutation was associated with infiltrating cancer, high grade and lack of oestrogen receptor (p < 0.05 for all 3 characteristics). For BRCA1 mutation carriers, 5-year survival was 63% vs. 91% for noncarriers (p = 0.04). For CaNO patients, mutation carriers had 75% S-year disease-free survival vs. 96% for noncarriers (p = 0.01). Twenty-one of the mutation carriers had undergone prophylactic oophorectomy, prior to or within 6 months of diagnosis in 13 cases. All but I relapse occurred in the I S who had kept their ovaries, (p < 0.01); no relapse occurred in those who had removed the ovaries within 6 months (p = 0.04) Contralateral cancer was more frequently observed in mutation noncarriers, but this finding did not reach statistical significance. Our findings support the concept that BRCA1 cancer is biologically different from other inherited breast cancers. While current screening protocols appear satisfactory for the majority of women at risk of familial breast cancer, this may not be the case for BRCA1 mutation carriers. The observed effect of oophorectomy was striking.
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| 29. |
- 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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| 31. |
- Nybo, L, et al.
(författare)
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A spurious correlation - Reply
- 2004
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Ingår i: JOURNAL OF APPLIED PHYSIOLOGY. - 8750-7587. ; 97:2, s. 793-793
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 34. |
- Scorilas, A., et al.
(författare)
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Streptavidin-polyvinylamine conjugates labeled with a europium chelate : Applications in immunoassay, immunohistochemistry, and microarrays
- 2000
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 46:9, s. 1450-1455
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Tidskriftsartikel (refereegranskat)abstract
- Background: The favorable properties of lanthanide chelates compared with conventional fluorescent probes have attracted considerable interest. A Eu3+ chelator, 4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA), has been synthesized previously. Methods: We here describe immunoassay, immunohistochemistry, and microarray applications of a new streptavidin-based universal polyvinylamine (PVA) detection reagent that is multiply labeled with the europium chelate of BCPDA. Solid-phase time-resolved immunofluorometric assays for biotinylated mouse IgG and prostate-specific antigen (PSA) were developed using the new conjugate as a detection reagent. The new conjugate was also used for the immunohistochemical localization of PSA expression in paraffin-embedded prostatic tissues. A model microarray with spotted biotinylated antibody as target was also performed. Results: Approximately 50-100 BCPDA moieties were covalently bound to PVA, which was then linked to streptavidin via biotin interaction. The macromolecular complex successfully recognized and bound biotinylated detection reagents, e.g., antibodies. The new reagent enabled measurement of solid phase-immobilized biotinylated mouse IgG with a detection limit of ~1 pg/assay and demonstrated excellent linearity. In an ELISA-type sandwich PSA assay that included two PSA monoclonal antibodies using the new conjugate as detection reagent, we detected 0.001 μg/L PSA (~100 fg or ~3 amol/assay). Serum samples analyzed for PSA by this method and a commercial assay gave highly correlated results. The new reagent enabled excellent immunohistochemical localization of PSA expression in prostate tissues. Using the new reagent in a model microarray experiment with biotinylated mouse IgG as target, we demonstrated excellent spatial resolution of 5-to 10-nL microspots. Conclusions: The new detection reagent may find important applications in biotechnology. (C) 2000 American Association for Clinical Chemistry.
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