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Sökning: WFRF:(Rönmark E) > Medicin och hälsovetenskap

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  • Thorgeirsson, T. E., et al. (författare)
  • A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences
  • 2016
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:5, s. 594-600
  • Tidskriftsartikel (refereegranskat)abstract
    • Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P = 1.2 x 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P = 4.0 x 10(-4)), chronic obstructive pulmonary disease (COPD; P = 9.3 x 10(-4)), peripheral artery disease (PAD; P = 0.090) and abdominal aortic aneurysms (AAAs; P = 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49, P = 2.2 x 10(-4)), COPD (OR = 3.22, P = 2.9 x 10(-4)), PAD (OR = 3.47, P = 9.2 x 10(-3)) and AAA (OR = 6.44, P = 6.3 x 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P = 6.8 x 10(-5)), particularly for early-onset cases (P = 2.1 x 10(-7)). Our results are in agreement with functional studies showing that the human alpha 4 beta 2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.
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  • Wilson, Jeffrey M., et al. (författare)
  • α-Gal specific-IgE prevalence and levels in Ecuador and Kenya : Relation to diet, parasites, and IgG4
  • 2021
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 147:4, s. 1393-1401.e7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: IgE to α-Gal is a cause of mammalian meat allergy and has been linked to tick bites in North America, Australia, and Eurasia. Reports from the developing world indicate that α-Gal sensitization is prevalent but has been little investigated. Objective: We sought evidence for the cause(s) of α-Gal sensitization and lack of reported meat allergy among children in less developed settings in Ecuador and Kenya. Methods: IgE to α-Gal and total IgE were assessed in children from Ecuador (n = 599) and Kenya (n = 254) and compared with children with (n = 42) and without known (n = 63) mammalian meat allergy from the southeastern United States. Information on diet, potential risk factors, and helminth infections was available for children from Ecuador. IgG4 to α-Gal and antibodies to regionally representative parasites were assessed in a subset of children. Results: In Ecuador (32%) and Kenya (54%), α-Gal specific IgE was prevalent, but levels were lower than in children with meat allergy from the United States. Sensitization was associated with rural living, antibody markers of Ascaris exposure, and total IgE, but not active infections with Ascaris or Trichuris species. In Ecuador, 87.5% reported consuming beef at least once per week, including 83.9% of those who had α-Gal specific IgE. Levels of α-Gal specific IgG4 were not high in Ecuador, but were greater than in children from the United States. Conclusions: These results suggest that in areas of the developing world with endemic parasitism, α-Gal sensitization is (1) common, (2) associated with Ascaris exposure, and (3) distinguished by a low percentage of specific/total IgE compared with individuals with meat allergy in the United States.
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4.
  • Ställberg, Björn, et al. (författare)
  • Living with asthma in Sweden - The ALMA study
  • 2003
  • Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 97:7, s. 835-843
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Recently performed studies have found a number of limitations in the daily lives of asthmatics, and a large disparity between the perception of the sufferers and what health care professionals believe matters to asthmatics. Aim: What matters to Swedish asthma patients, what medicines do they use, and are they compliant with given prescriptions? A further aim was to compare perceptions about asthma and asthma management in asthmatics and among Swedish general practitioners (GP). Design: A structured telephone interview of a representative sample of Swedish asthmatics, and a mailed questionnaire survey among GPs from different parts of Sweden. Methods: Screening by telephone of a random sample of 10,350 subjects aged 18-45. Of those, 240 were subsequently selected for a detailed structured telephone interview about their asthma. A mailed structured questionnaire containing similar questions to those asked of the asthmatics was sent to 600 GPs, and 139 returned completed answers. Results: 16% of the asthmatics reported (asthma) symptoms occurring every day during the previous month. Nocturnal symptoms at least twice per week were reported by 19%. Both these were reported by considerably higher proportions of the asthmatics than the GPs had expected. A large majority classified their disease as mild or very mild, although great majority reported frequent symptoms. Activities or situations which caused symptoms of asthma often or "now and then" were physical exertion, 67%, bad weather, 59%, contact with animals/pets, 58%, and visits to cafés or restaurants, 36%, and several asthmatics avoided these activities due to their asthma. Conclusion: A great majority of asthmatics report a large number of symptoms and limitations in their daily living in proportions which were roughly expected by the GPs. © 2003 Elsevier Science Ltd. All rights reserved.
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  • Commins, Scott P, et al. (författare)
  • Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma.
  • 2012
  • Ingår i: American journal of respiratory and critical care medicine. - 1535-4970 .- 1073-449X. ; 185:7, s. 723-30
  • Tidskriftsartikel (refereegranskat)abstract
    • IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) are common in the southeastern United States. These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract.
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9.
  • Allinson, James P, et al. (författare)
  • Changes in lung function in European adults born between 1884 and 1996 and implications for the diagnosis of lung disease: a cross-sectional analysis of ten population-based studies.
  • 2022
  • Ingår i: The Lancet. Respiratory medicine. - : Elsevier. - 2213-2619 .- 2213-2600. ; 10:1, s. 83-94
  • Tidskriftsartikel (refereegranskat)abstract
    • During the past century, socioeconomic and scientific advances have resulted in changes in the health and physique of European populations. Accompanying improvements in lung function, if unrecognised, could result in the misclassification of lung function measurements and misdiagnosis of lung diseases. We therefore investigated changes in population lung function with birth year across the past century, accounting for increasing population height, and examined how such changes might influence the interpretation of lung function measurements.In our analyses of cross-sectional data from ten European population-based studies, we included individuals aged 20-94 years who were born between 1884 and 1996, regardless of previous respiratory diagnoses or symptoms. FEV1, forced vital capacity (FVC), height, weight, and smoking behaviour were measured between 1965 and 2016. We used meta-regression to investigate how FEV1 and FVC (adjusting for age, study, height, sex, smoking status, smoking pack-years, and weight) and the FEV1/FVC ratio (adjusting for age, study, sex, and smoking status) changed with birth year. Using estimates from these models, we graphically explored how mean lung function values would be expected to progressively deviate from predicted values. To substantiate our findings, we used linear regression to investigate how the FEV1 and FVC values predicted by 32 reference equations published between 1961 and 2015 changed with estimated birth year.Across the ten included studies, we included 243465 European participants (mean age 51·4 years, 95% CI 51·4-51·5) in our analysis, of whom 136275 (56·0%) were female and 107190 (44·0%) were male. After full adjustment, FEV1 increased by 4·8 mL/birth year (95% CI 2·6-7·0; p<0·0001) and FVC increased by 8·8 mL/birth year (5·7-12·0; p<0·0001). Birth year-related increases in the FEV1 and FVC values predicted by published reference equations corroborated these findings. This height-independent increase in FEV1 and FVC across the last century will have caused mean population values to progressively exceed previously predicted values. However, the population mean adjusted FEV1/FVC ratio decreased by 0·11 per 100 birth years (95% CI 0·09-0·14; p<0·0001).If current diagnostic criteria remain unchanged, the identified shifts in European values will allow the easier fulfilment of diagnostic criteria for lung diseases such as chronic obstructive pulmonary disease, but the systematic underestimation of lung disease severity.The European Respiratory Society, AstraZeneca, Chiesi Farmaceutici, GlaxoSmithKline, Menarini, and Sanofi-Genzyme.
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10.
  • Matsson, H., et al. (författare)
  • Targeted high-throughput sequencing of candidate genes for chronic obstructive pulmonary disease
  • 2016
  • Ingår i: Bmc Pulmonary Medicine. - : Springer Science and Business Media LLC. - 1471-2466. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Reduced lung function in patients with chronic obstructive pulmonary disease (COPD) is likely due to both environmental and genetic factors. We report here a targeted high-throughput DNA sequencing approach to identify new and previously known genetic variants in a set of candidate genes for COPD. Methods: Exons in 22 genes implicated in lung development as well as 61 genes and 10 genomic regions previously associated with COPD were sequenced using individual DNA samples from 68 cases with moderate or severe COPD and 66 controls matched for age, gender and smoking. Cases and controls were selected from the Obstructive Lung Disease in Northern Sweden (OLIN) studies. Results: In total, 37 genetic variants showed association with COPD (p < 0.05, uncorrected). Several variants previously discovered to be associated with COPD from genetic genome-wide analysis studies were replicated using our sample. Two high-risk variants were followed-up for functional characterization in a large eQTL mapping study of 1,111 human lung specimens. The C allele of a synonymous variant, rs8040868, predicting a p.(S45=) in the gene for cholinergic receptor nicotinic alpha 3 (CHRNA3) was associated with COPD (p = 8.8 x 10(-3)). This association remained (p = 0.003 and OR = 1.4, 95 % CI 1.1-1.7) when analysing all available cases and controls in OLIN (n = 1,534). The rs8040868 variant is in linkage disequilibrium with rs16969968 previously associated with COPD and altered expression of the CHRNA5 gene. A follow-up analysis for detection of expression quantitative trait loci revealed that rs8040868-C was found to be significantly associated with a decreased expression of the nearby gene cholinergic receptor, nicotinic, alpha 5 (CHRNA5) in lung tissue. Conclusion: Our data replicate previous result suggesting CHRNA5 as a candidate gene for COPD and rs8040868 as a risk variant for the development of COPD in the Swedish population.
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