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  • Andersson, P L, et al. (författare)
  • Bioaccumulation of selected PCBs in zebrafish, three-spined stickleback, and arctic char after three different routes of exposure.
  • 2001
  • Ingår i: Arch Environ Contam Toxicol. - 0090-4341. ; 40:4, s. 519-30
  • Tidskriftsartikel (refereegranskat)abstract
    • The uptake and elimination of 20 structurally diverse tetra- to heptachlorinated biphenyls were studied in zebrafish (Danio rerio), three-spined stickleback (Gasterosteus aculeatus), and Arctic char (Salvelinus alpinus). The polychlorinated biphenyls (PCBs) were administered to the fish through food, intraperitoneal injection of peanut oil, or intraperitoneal implantation of silicone capsules. The retention of the PCBs in fish exposed through their diet was related with the substitution patterns of the compounds. Ortho-substituted congeners with no unsubstituted meta-para positions had high biomagnification potential. PCBs with low biomagnification all had adjacent vicinal hydrogens, indicating that congeners with this feature may have been metabolically eliminated. The retention characteristics of the PCBs in the diet-exposed and the injected zebrafish were similar. The pattern of congeners in Arctic char indicates that they have a lower capacity to metabolize PCBs compared to three-spined sticklebacks and zebrafish. The levels in the fish exposed to the PCBs through a silastic implant were negatively correlated with the hydrophobicity of the congeners. Most probably congener-specific release rates of the PCBs from the implants mask their retention characteristics. It is suggested that food, mimicking the natural intake route, should be used in PCB exposure studies to validate extrapolations to natural situations.
  • Andrijevic, Goran, et al. (författare)
  • A fully integrated low-IF DVB-T receiver architecture
  • 2004
  • Ingår i: 2004 INTERNATIONAL SYMPOSIUM ON SYSTEM-ON-CHIP, PROCEEDINGS. - 0-7803-8558-6 ; s. 189-192
  • Konferensbidrag (refereegranskat)abstract
    • We propose a fully integrated DVB-T receiver architecture for low cost CMOS implementation. The receiver uses a dual-IF architecture to cover the receive bands from 170 MHz to 862 MHz and a Low-IF of 4.57 MHz. Key performance values meet the DVB-T requirements with competitive performance (Sensitivity 72.5 dBm, Noise Figure 66 dB, Adjacent Channel Protection Ratio-ACPR=43dB, available SNR=28 dB) and suggest that low cost receivers are realistic in volume for the coming digital broadcasting systems.
  • Andrijevic, Goran, et al. (författare)
  • Multistandard receiver for home networking and digital media
  • 2004
  • Ingår i: 22ND NORCHIP CONFERENCE, PROCEEDINGS. - NEW YORK : IEEE. - 0-7803-8510-1 ; s. 131-134
  • Konferensbidrag (refereegranskat)abstract
    • We propose a fully integrated multistandard receiver architecture that fulfills coming media and networking needs of homes. The receiver uses a dual-IF architecture to cover receive bands from 170 MHz to 920 MHz and the Industrial, Scientific and Medical (ISM) band at 2.4GHz. Key performance values meet the DVB-T, Zigbee, Bluetooth and 802.11b requirements (Sensitivity -72.5dBm. available SNR=28dB. Noise Figure 6.7dB. Adjacent Channel Protection Ratio-ACPR=-44dB, IIP3 = -11 dBm).
  • Attner, Bo, et al. (författare)
  • Cancer among patients with diabetes, obesity and abnormal blood lipids: a population-based register study in Sweden.
  • 2012
  • Ingår i: Cancer Causes and Control. - Springer. - 1573-7225. ; 23:5, s. 769-777
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To study how the incidence of cancer is related to diabetes, obesity or abnormal blood lipids. METHODS: Diagnosis of diabetes, obesity or abnormal blood lipids was studied 0-10 years prior to the diagnosis of cancer in 19,756 cases of cancer and in 147,324 controls matched regarding age, sex and domicile. RESULTS: Diabetes was significantly more common prior to diagnosis in patients with liver, pancreatic, colon and urinary tract/bladder cancer and in patients with breast cancer diagnosed with diabetes 0-4 years prior to the cancer diagnosis. A lower risk of diabetes was seen in patients with prostate carcinoma among individuals with diabetes diagnosed 5-10 years prior to the cancer diagnosis. The findings remained after adjusting for obesity and high blood lipids. Obesity was significantly more common in patients with endometrial, colon and kidney cancer and with breast cancer above the age of 60 years in those where obesity was diagnosed close to the diagnosis of cancer. High blood lipids were significantly more common in patients with ovarian cancer and less common in patients with breast cancer. CONCLUSIONS: The study confirms some previous findings concerning comorbidity and cancer and highlights some new ones.
  • Björner, Sofie, et al. (författare)
  • Epithelial and Stromal MicroRNA Signatures of Columnar Cell Hyperplasia Linking Let-7c to Precancerous and Cancerous Breast Cancer Cell Proliferation.
  • 2014
  • Ingår i: PLoS ONE. - Public Library of Science. - 1932-6203. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Columnar cell hyperplasia (CCH) is the earliest histologically identifiable breast lesion linked to cancer progression and is characterized by increased proliferation, decreased apoptosis and elevated oestrogen receptor α (ERα) expression. The mechanisms underlying the initiation of these lesions have not been clarified but might involve early and fundamental changes in cancer progression. MiRNAs are key regulators of several biological processes, acting by influencing the post-transcriptional regulation of numerous targets, thus making miRNAs potential candidates in cancer initiation. Here we have defined novel epithelial as well as stromal miRNA signatures from columnar cell hyperplasia lesions compared to normal terminal duct lobular units by using microdissection and miRNA microarrays. Let-7c were among the identified downregulated epithelial miRNAs and its functions were delineated in unique CCH derived cells and breast cancer cell line MCF-7 suggesting anti-proliferative traits potentially due to effects on Myb and ERα. MiR-132 was upregulated in the stroma surrounding CCH compared to stoma surrounding normal terminal duct lobular units (TDLUs), and overexpression of miR-132 in immortalized fibroblasts and in fibroblasts co-cultured with epithelial CCH cells caused substantial expression changes of genes involved in metabolism, DNA damage and cell motility. The miRNA signatures identified in CCH indicate early changes in the epithelial and stromal compartment of CCH and could represent early key alterations in breast cancer progression that potentially could be targeted in novel prevention or treatment schedules.
  • Harbst, Katja, et al. (författare)
  • Molecular and genetic diversity in the metastatic process of melanoma.
  • 2014
  • Ingår i: Journal of Pathology. - John Wiley and Sons Inc.. - 0022-3417. ; 233:1, s. 39-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Diversity between metastatic melanoma tumours in individual patients is known; however, the molecular and genetic differences remain unclear. To examine the molecular and genetic differences between metastatic tumours, we performed gene-expression profiling of 63 melanoma tumours obtained from 28 patients (two or three tumours/patient), followed by analysis of their mutational landscape, using targeted deep sequencing of 1697 cancer genes and DNA copy number analysis. Gene-expression signatures revealed discordant phenotypes between tumour lesions within a patient in 50% of the cases. In 18 of 22 patients (where matched normal tissue was available), we found that the multiple lesions within a patient were genetically divergent, with one or more melanoma tumours harbouring 'private' somatic mutations. In one case, the distant subcutaneous metastasis of one patient occurring 3 months after an earlier regional lymph node metastasis had acquired 37 new coding sequence mutations, including mutations in PTEN and CDH1. However, BRAF and NRAS mutations, when present in the first metastasis, were always preserved in subsequent metastases. The patterns of nucleotide substitutions found in this study indicate an influence of UV radiation but possibly also DNA alkylating agents. Our results clearly demonstrate that metastatic melanoma is a molecularly highly heterogeneous disease that continues to progress throughout its clinical course. The private aberrations observed on a background of shared aberrations within a patient provide evidence of continued evolution of individual tumours following divergence from a common parental clone, and might have implications for personalized medicine strategies in melanoma treatment. Published by John Wiley & Sons, Ltd. www.pathsoc.org.uk.
  • Hedström, Erik, et al. (författare)
  • Infarct evolution in man studied in patients with first-time coronary occlusion in comparison to different species - implications for assessment of myocardial salvage
  • 2009
  • Ingår i: Journal of Cardiovascular Magnetic Resonance. - BioMed Central. - 1097-6647. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The time course of infarct evolution, i.e. how fast myocardial infarction (MI) develops during coronary artery occlusion, is well known for several species, whereas no direct evidence exists on the evolution of MI size normalized to myocardium at risk (MaR) in man. Despite the lack of direct evidence, current literature often refers to the "golden hour" as the time during which myocardial salvage can be accomplished by reperfusion therapy. Therefore, the aim of the present study was to investigate how duration of myocardial ischemia affects infarct evolution in man in relation to previous animal data. Consecutive patients with clinical signs of acute myocardial ischemia were screened and considered for enrollment. Particular care was taken to assure uniformity of the patients enrolled with regard to old MI, success of revascularization, collateral flow, release of biochemical markers prior to intervention etc. Sixteen patients were ultimately included in the study. Myocardium at risk was assessed acutely by acute Myocardial Perfusion Single photon emission computed tomography (MPS) and by T2 imaging (T2-STIR) cardiovascular magnetic resonance (CMR) after one week in 10 of the 16 patients. Infarct size was measured by late gadolinium enhancement (LGE) at one week. Results: The time to reach 50% MI of the MaR (T-50) was significantly shorter in pigs (37 min), rats (41 min) and dogs (181 min) compared to humans (288 min). There was no significant difference in T-50 when using MPS compared to T2-STIR (p = 0.53) for assessment of MaR (288 +/- 23 min vs 310 +/- 22 min, T-50 +/- standard error). The transmural extent of MI increased progressively as the duration of ischemia increased (R-2 = 0.56, p < 0.001). Conclusion: This is the first study to provide direct evidence of the time course of acute myocardial infarct evolution in relation to MaR in man with first-time MI. Infarct evolution in man is significantly slower than in pigs, rats and dogs. Furthermore, infarct evolution assessments in man are similar when using MPS acutely and T2-STIR one week later for determination of MaR, which significantly facilitates future clinical trials of cardioprotective therapies in acute coronary syndrome by the use of CMR.
  • Jönsson, Göran B, et al. (författare)
  • The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.
  • 2012
  • Ingår i: Cancer Research. - American Association for Cancer Research Inc.. - 1538-7445. ; 72:16, s. 4028-4036
  • Tidskriftsartikel (refereegranskat)abstract
    • Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter-methylation, but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1 deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1-related hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer, but rarely in BRCA2-hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings demonstrate the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1-status.
  • Lindqvist, Pelle G., et al. (författare)
  • Are active sun exposure habits related to lowering risk of type 2 diabetes mellitus in women, a prospective cohort study?
  • 2010
  • Ingår i: Diabetes Research and Clinical Practice. - Elsevier. - 1872-8227. ; 90:1, s. 109-114
  • Tidskriftsartikel (refereegranskat)abstract
    • Aim An inverse relationship exists between vitamin D levels and diabetes mellitus However, little is known about the correlation of sun exposure habits and type 2 diabetes mellitus (DM) Methods A South Swedish cohort study comprising 1000 women from each age group between 25 and 64 (n = 40,000) drawn from the Southern Swedish population registry 1990-1992 At the inception of the study 74% answered the inquiry (n = 29,518) and provided detailed information on their sun exposure habits and other variables A follow-up inquiry was sent 2000-2002 which 24,098 women answered The mean follow-up time was 11 years Logistic regression analysis was used and the main outcome was the relationship between type 2 DM and sun exposure habits. Results Our findings indicated that women with active sun exposure habits were at a 30% lower risk of having DM, as compared to those with non-active habits. There was an inverse relation between this risk reduction and BMI Conclusion Our investigation gives possible epidemiological explanation to ethnic and seasonal differences in type 2 DM and metabolic control The study supports that sunlight is involved in the glucose metabolism (C) 2010 Elsevier Ireland Ltd All rights reserved.
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