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21.
  • Olofsson, Roger, et al. (författare)
  • Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases (the SCANDIUM trial) : study protocol for a randomized controlled trial
  • 2014
  • Ingår i: Trials. - : BioMed Central (BMC). - 1745-6215 .- 1745-6215. ; 15, s. 317-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of patients, with the liver being the most common site for metastases. The median survival for patients with liver metastases is between 6 and 12 months, and no treatment has in randomized trials ever been shown to prolong survival. A previous phase II trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival compared with a historic control group consisting of the longest surviving patients in Sweden during the same time period (26 versus 12 months). Methods/Design: This is the protocol for a multicenter phase III trial randomizing patients with isolated liver metastases of uveal melanoma to IHP or best alternative care (BAC). Inclusion criteria include liver metastases (verified by biopsy) and no evidence of extra-hepatic tumor manifestations by positron emission tomography-computed tomography (PET-CT). The primary endpoint is overall survival at 24 months, with secondary endpoints including response rate, progression-free survival, and quality of life. The planned sample size is 78 patients throughout five years. Discussion: Patients with isolated liver metastases of uveal melanoma origin have a short expected survival and no standard treatment option exists. This is the first randomized clinical trial to evaluate IHP as a treatment option with overall survival being the primary endpoint.
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22.
  • Ramzy, A. G., et al. (författare)
  • Isothiocyanates are important as haptens in contact allergy to chloroprene rubber
  • 2017
  • Ingår i: British Journal of Dermatology. - 0007-0963 .- 1365-2133. ; 177:2, s. 522-530
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Contact allergy to chloroprene rubber products is well known. Thiourea compounds are considered the cause of allergy. Diethylthiourea commonly occurs in this type of product and can decompose to the sensitizer ethyl isothiocyanate. Objectives To investigate the clinical importance of degradation products and metabolites from organic thioureas in contact allergy to chloroprene rubber with a focus on isothiocyanates and isocyanates. Methods Patients with contact allergy to diphenylthiourea were patch tested with phenyl isothiocyanate and phenyl isocyanate. Patients with known contact allergy to diethylthiourea were retested with diethylthiourea, while chemical analyses of their chloroprene rubber products were performed. The stability of diethylthiourea, diphenylthiourea and dibutylthiourea in patch-test preparations was investigated. Liquid chromatography/mass spectrometry and solid-phase microextraction/gas chromatography were used for determination of organic thioureas and isothiocyanates. Results All patients allergic to diphenylthiourea reacted to phenyl isothiocyanate, two of eight reacted to phenyl isocyanate and six of eight reacted to diphenylthiourea. Four patients allergic to diethylthiourea reacted at retest; diethylthiourea was detected in all chloroprene rubber samples, with levels of 2-1200 nmol cm(-2). At 35 degrees C, ethyl isothiocyanate was emitted from all samples. Patch-test preparations of diethylthiourea, diphenylthiourea and dibutylthiourea all emitted the corresponding isothiocyanate, with diethylthiourea showing the highest rate of isothiocyanate emission. Conclusions Thiourea compounds are degraded to isothiocyanates, which are generally strong or extreme sensitizers, thus acting as prehaptens. This process occurs in both chloroprene rubber products and patch-test preparations. Positive reactions to phenyl isocyanate indicate cutaneous metabolism, as the only known source of exposure to phenyl isocyanate is through bioactivation of diphenylthiourea.
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23.
  • Vinnars, Marie-Therese, et al. (författare)
  • Enhanced Th1 and inflammatory mRNA responses upregulate NK cell cytotoxicity and NKG2D ligand expression in human pre-eclamptic placenta and target it for NK cell attack
  • 2018
  • Ingår i: American Journal of Reproductive Immunology. - : John Wiley & Sons. - 1046-7408 .- 1600-0897. ; 80:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ProblemPre-eclampsia (PE), a severe human pregnancy disorder, is associated with exaggerated systemic inflammation, enhanced cytokine production, and increased shedding of microvesicles leading to endothelial dysfunction, coagulopathy, and extensive placenta destruction. The cause of PE is still unclear. Evidence suggests that its origin lies in the placenta and that the maternal immune system is involved. A shift in cytokine production in PE pregnancy promotes NK cell activation, suggested to be important in PE pathogenesis. In line with this suggestion, we studied NK cell cytotoxicity in peripheral blood of PE patients and controls and the mRNA expression of cytokines and of the NKG2D receptor and its ligands MICA/B and ULBP1-3 in PE- and normal placenta. Method of studyThe cytotoxic capacity of peripheral blood NK cells was analyzed using K562 target cells. The cytokine mRNA profiles and the mRNA expression of the NKG2D receptor and its ligands MICA/B and ULBP 1-3 in PE placenta were assessed and compared to those in normal placenta using real-time quantitative RT-PCR. ResultsThe cytotoxicity of peripheral blood NK cells was upregulated in PE cases. Further, we found an enhanced inflammatory cytokine mRNA response combined with a dysregulated regulatory response and a significant mRNA overexpression of NKG2D receptor and its ligands MICA/B and ULBP in PE placenta. ConclusionThe destruction of chorionic villi observed in PE placenta might be conveyed by an enhanced local cytotoxic response through the NKG2D receptor-ligand pathway, which in turn might be promoted by an intense inflammatory response not counteracted by regulatory cytokine responses.
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24.
  • Werner, Mårten, et al. (författare)
  • Autoimmune hepatitis among fertile women : strategies during pregnancy and breastfeeding?
  • 2007
  • Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 42:8, s. 986-991
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective. In published studies there is a lack of data about the risks, management and how women with autoimmune hepatitis (AIH) decide on and are advised about pregnancy. The aim of this study was to investigate how women with AIH consider pregnancies, are advised and pharmacologically treated, as well as the outcome. Material and methods. A questionnaire was mailed to 128 women with AIH diagnosed during their fertile period and data from the Swedish National Birth Register was also used for matched controls. Results. There was an 83% response rate to the questionnaires. Sixty-three pregnancies were reported by 35 women. 48% did not consult their doctors before getting pregnant. More than half of the women reduced or stopped the immune suppression during pregnancy or breastfeeding. Some women were advised to abstain from pregnancy or even to have an abortion. Caesarean sections were performed more frequently in the AIH group (16% compared with 6.5% in the control group p<0.01).There were no significant differences in the number of stillborn infants or infants with malformations. However, 30% of the patients experienced flare-up after delivery. Conclusions. In general, the outcome of pregnancy in women with AIH seems to be good. Current pharmacological treatment appears to be safe, including azathioprine during pregnancy and lactation. After delivery an active preparedness to increase pharmacotherapy should be considered.
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25.
  • Zamora-Ros, Raul, et al. (författare)
  • Dietary flavonoid intake and colorectal cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort
  • Ingår i: International Journal of Cancer. - : John Wiley and Sons. - 0020-7136 .- 1097-0215. ; 140:8, s. 1836-1844
  • Tidskriftsartikel (refereegranskat)abstract
    • Flavonoids have been shown to inhibit colon cancer cell proliferation in vitro and protect against colorectal carcinogenesis in animal models. However, epidemiological evidence on the potential role of flavonoid intake in colorectal cancer (CRC) development remains sparse and inconsistent. We evaluated the association between dietary intakes of total flavonoids and their subclasses and risk of development of CRC, within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. A cohort of 477,312 adult men and women were recruited in 10 European countries. At baseline, dietary intakes of total flavonoids and individual subclasses were estimated using centre-specific validated dietary questionnaires and composition data from the Phenol-Explorer database. During an average of 11 years of follow-up, 4,517 new cases of primary CRC were identified, of which 2,869 were colon (proximal = 1,298 and distal = 1,266) and 1,648 rectal tumours. No association was found between total flavonoid intake and the risk of overall CRC (HR for comparison of extreme quintiles 1.05, 95% CI 0.93–1.18; p-trend = 0.58) or any CRC subtype. No association was also observed with any intake of individual flavonoid subclasses. Similar results were observed for flavonoid intake expressed as glycosides or aglycone equivalents. Intake of total flavonoids and flavonoid subclasses, as estimated from dietary questionnaires, did not show any association with risk of CRC development.
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26.
  • af Sillén, Ulrika, et al. (författare)
  • Self-rated health in relation to age and gender: influence on mortality risk in the Malmö Preventive Project.
  • 2005
  • Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1651-1905. ; 33:3, s. 9-183
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: A study was undertaken to examine whether poor self-rated health (SRH) can independently predict all-cause mortality during 22-year follow-up in middle-aged men and women. Subjects and methods: Data are derived from a population-based study in Malmo¨ , Sweden. This included baseline laboratory testing and a self-administered questionnaire. The question on global SRH was answered by 15,590 men (mean age 46.4 years) and 10,089 women (49.4 years). Social background characteristics (occupation, marital status) were based on data from national censuses. Mortality was retrieved from national registers. Results: At screening 4,261 (27.3%) men and 3,085 (30.6%) women reported poor SRH. Among subjects rating their SRH as low, 1,022 (24.0%) men and 228 (7.4%) women died during follow-up. Corresponding figures for subjects rating their SRH as high were 1801 (15.9%) men and 376 (5.4%) women. An analysis of survival in subjects reporting poor SRH revealed an age-adjusted hazard risk ratio (HR, 95%CI) for men HR 1.5 (1.4–1.7), and for women HR 1.4 (1.2–1.6). The corresponding HR after adjusting for possible social confounders was for men HR 1.3 (1.1–1.4), and women HR 1.1 (0.9–1.4). When additional adjustment was made for biological risk factors the association for men was still significant, HR 1.2 (1.1–1.3). Conclusion: Poor SRH predicts increased long-term mortality in healthy, middle-aged subjects. For men the association is independent of both social background and selected biological variables. The adjustment for biological variables can be questioned as they might represent mediating mechanisms in a possible causal chain of events.
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27.
  • Ali, Ashfaq, et al. (författare)
  • Paranoid potato : phytophthora-resistant genotype shows constitutively activated defense
  • Ingår i: Plant Signaling and Behavior. - : Landes Bioscience. - 1559-2316 .- 1559-2324. ; 7:3, s. 400-408
  • Tidskriftsartikel (refereegranskat)abstract
    • Phytophthora is the most devastating pathogen of dicot plants. There is a need for resistance sources with different modes of action to counteract the fast evolution of this pathogen. In order to better understand mechanisms of defense against P. infestans, we analyzed several clones of potato. Two of the genotypes tested, Sarpo Mira and SW93-1015, exhibited strong resistance against P. infestans in field trials, whole plant assays and detached leaf assays. The resistant genotypes developed different sizes of hypersensitive response (HR)-related lesions. HR lesions in SW93-1015 were restricted to very small areas, whereas those in Sarpo Mira were similar to those in Solanum demissum, the main source of classical resistance genes. SW93-1015 can be characterized as a cpr (constitutive expressor of PR genes) genotype without spontaneous microscopic or macroscopic HR lesions. This is indicated by constitutive hydrogen peroxide (H₂O₂) production and PR1 (pathogenesis-related protein 1) secretion. SW93-1015 is one of the first plants identified as having classical protein-based induced defense expressed constitutively without any obvious metabolic costs or spontaneous cell death lesions.
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28.
  • Ameur, Adam, et al. (författare)
  • SweGen : a whole-genome data resource of genetic variability in a cross-section of the Swedish population
  • 2017
  • Ingår i: European Journal of Human Genetics. - : NATURE PUBLISHING GROUP. - 1018-4813 .- 1476-5438. ; 25:11, s. 1253-1260
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the SweGen data set, a comprehensive map of genetic variation in the Swedish population. These data represent a basic resource for clinical genetics laboratories as well as for sequencing-based association studies by providing information on genetic variant frequencies in a cohort that is well matched to national patient cohorts. To select samples for this study, we first examined the genetic structure of the Swedish population using high-density SNP-array data from a nation-wide cohort of over 10 000 Swedish-born individuals included in the Swedish Twin Registry. A total of 1000 individuals, reflecting a cross-section of the population and capturing the main genetic structure, were selected for whole-genome sequencing. Analysis pipelines were developed for automated alignment, variant calling and quality control of the sequencing data. This resulted in a genome-wide collection of aggregated variant frequencies in the Swedish population that we have made available to the scientific community through the website https://swefreq.nbis.se. A total of 29.2 million single-nucleotide variants and 3.8 million indels were detected in the 1000 samples, with 9.9 million of these variants not present in current databases. Each sample contributed with an average of 7199 individual-specific variants. In addition, an average of 8645 larger structural variants (SVs) were detected per individual, and we demonstrate that the population frequencies of these SVs can be used for efficient filtering analyses. Finally, our results show that the genetic diversity within Sweden is substantial compared with the diversity among continental European populations, underscoring the relevance of establishing a local reference data set.
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29.
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30.
  • Bejerholm, U., et al. (författare)
  • Rasch Analysis of the Profiles of Occupational Engagement in people with Severe mental illness (POES) instrument
  • 2015
  • Ingår i: Health and Quality of Life Outcomes. - : BioMed Central (BMC). - 1477-7525. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: The Profiles of Occupational Engagement in people with Severe mental illness (POES) instrument was developed to study time use profiles of occupations and measure the extent they are characterized by engagement. However, the dimensional factors are not known. The aim of the present study was to establish the internal construct validity of the POES using the Rasch measurement model. Methods: A sample of 192 outpatients in Sweden was administered the POES and data were subjected to Rasch analysis. Results: The POES showed good fit to the Rasch model after accommodation for local dependency. The nine items had high reliability as measured by person separation index, and no threshold disordering was present. Differential item functioning analysis showed no significant differences across groups of age, sex, diagnosis, or country of origin. Conclusion: The POES is a unidimensional scale that represents a continuum of occupational engagement. The transformed POES sum score can be used on an interval scale to measure status and changes in occupational engagement in mental health practice and research.
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