| 1. |
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| 2. |
- Speliotes, Elizabeth K., et al.
(författare)
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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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| 3. |
- Heid, Iris M, et al.
(författare)
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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
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Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
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| 4. |
- Marouli, Eirini, et al.
(författare)
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Rare and low-frequency coding variants alter human adult height
- 2017
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
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Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
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| 5. |
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| 6. |
- Ashar, Foram N., et al.
(författare)
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A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 39:44, s. 3961-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
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| 7. |
- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
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| 8. |
- Stitziel, Nathan O., et al.
(författare)
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Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease
- 2016
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 374:12, s. 1134-1144
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets. METHODS Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes. RESULTS We confirmed previously observed significant associations between coronary artery disease and low-frequency missense variants in the genes LPA and PCSK9. We also found significant associations between coronary artery disease and low-frequency missense variants in the genes SVEP1 (p.D2702G; minor-allele frequency, 3.60%; odds ratio for disease, 1.14; P = 4.2x10(-10)) and ANGPTL4 (p.E40K; minor-allele frequency, 2.01%; odds ratio, 0.86; P = 4.0x10(-8)), which encodes angiopoietin-like 4. Through sequencing of ANGPTL4, we identified 9 carriers of loss-of-function mutations among 6924 patients with myocardial infarction, as compared with 19 carriers among 6834 controls (odds ratio, 0.47; P = 0.04); carriers of ANGPTL4 loss-of-function alleles had triglyceride levels that were 35% lower than the levels among persons who did not carry a loss-of-function allele (P = 0.003). ANGPTL4 inhibits lipoprotein lipase; we therefore searched for mutations in LPL and identified a loss-of-function variant that was associated with an increased risk of coronary artery disease (p.D36N; minor-allele frequency, 1.9%; odds ratio, 1.13; P = 2.0x10(-4)) and a gain-of-function variant that was associated with protection from coronary artery disease (p.S447*; minor-allele frequency, 9.9%; odds ratio, 0.94; P = 2.5x10(-7)). CONCLUSIONS We found that carriers of loss-of-function mutations in ANGPTL4 had triglyceride levels that were lower than those among noncarriers; these mutations were also associated with protection from coronary artery disease.
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| 9. |
- Sugihara, Yutaka, et al.
(författare)
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A New Look at Drugs Targeting Malignant Melanoma – An Application for Mass Spectrometry Imaging
- 2014
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Ingår i: Proteomics. - : Wiley. - 1615-9861 .- 1615-9853. ; 14:17-18, s. 1963-1970
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Forskningsöversikt (refereegranskat)abstract
- Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors (PKI) has been highly effective for certain subsets of MM patients. Vemurafenib, a PKI targeting BRAF mutated protein, has shown significant efficacy in slowing disease progression. In this paper we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of personalized medicine drugs within tumor compartments. In this study, we have introduced matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MSI was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using mass spectrometry fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment.
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| 10. |
- Turcot, Valerie, et al.
(författare)
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Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:1, s. 26-41
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are similar to 10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed similar to 7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
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| 11. |
- Webb, Thomas R., et al.
(författare)
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Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 69:7, s. 823-836
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.OBJECTIVES This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.METHODS In discovery analyses involving 42,335 CAD cases and 78,240 control subjects we tested the association of 29,383 common (minor allele frequency >5%) single nucleotide polymorphisms available on the exome array, which included a substantial proportion of known or suspected single nucleotide polymorphisms associated with common diseases or traits as of 2011. Suggestive association signals were replicated in an additional 30,533 cases and 42,530 control subjects. To evaluate pleiotropy, we tested CAD loci for association with cardiovascular risk factors (lipid traits, blood pressure phenotypes, body mass index, diabetes, and smoking behavior), as well as with other diseases/traits through interrogation of currently available genome-wide association study catalogs.RESULTS We identified 6 new loci associated with CAD at genome-wide significance: on 2q37 (KCNJ13-GIGYF2), 6p21 (C2), 11p15 (MRVI1-CTR9), 12q13 (LRP1), 12q24 (SCARB1), and 16q13 (CETP). Risk allele frequencies ranged from 0.15 to 0.86, and odds ratio per copy of the risk allele ranged from 1.04 to 1.09. Of 62 new and known CAD loci, 24 (38.7%) showed statistical association with a traditional cardiovascular risk factor, with some showing multiple associations, and 29 (47%) showed associations at p < 1 x 10(-4) with a range of other diseases/traits.CONCLUSIONS We identified 6 loci associated with CAD at genome-wide significance. Several CAD loci show substantial pleiotropy, which may help us understand the mechanisms by which these loci affect CAD risk.
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| 12. |
- Welinder, Charlotte, et al.
(författare)
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Analysis of Alpha-Synuclein in Malignant Melanoma - Development of a SRM Quantification Assay.
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM) assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light) versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.
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| 13. |
- Welinder, Charlotte, et al.
(författare)
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Feasibility Study on Measuring Selected Proteins in Malignant Melanoma Tissue by SRM Quantification.
- 2014
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 13:3, s. 1315-1326
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Tidskriftsartikel (refereegranskat)abstract
- Currently there are no clinically recognized molecular biomarkers for malignant melanoma (MM) for either diagnosing disease stage or measuring response to therapy. The aim of this feasibility study was to develop targeted selected reaction monitoring (SRM) assays for identifying candidate protein biomarkers in metastatic melanoma tissue lysate. In a pilot study applying the SRM assay, the tissue expression of nine selected proteins [complement 3 (C3), T-cell surface glycoprotein CD3 epsilon chain E (CD3E), dermatopontin, minichromosome maintenance complex component (MCM4), premelanosome protein (PMEL), S100 calcium binding protein A8 (S100A8), S100 calcium binding protein A13 (S100A13), transgelin-2 and S100B] was quantified in a small cohort of metastatic malignant melanoma patients. The SRM assay was developed using a TSQ Vantage triple quadrupole mass spectrometer that generated highly accurate peptide quantification. Repeated injection of internal standards spiked into matrix showed relative standard deviation (RSD) from 6% to 15%. All nine target proteins were identified in tumor lysate digests spiked with heavy peptide standards. The multiplex SRM peptide assay panel was then measured and quantified on a set of frozen MM tissue samples obtained from the Malignant Melanoma Biobank collected in Lund, Sweden. All nine proteins could be accurately quantified using the new SRM assay format. This study provides preliminary data on the heterogeneity of biomarker expression within MM patients. The S100B protein, which is clinically used as the pathology identifier of MM, was identified in 9 out of 10 MM tissue lysates. The use of the targeted SRM assay provides potential advancements in the diagnosis of MM that can aid in future assessments of disease in melanoma patients.
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| 14. |
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| 15. |
- Ericsson, Anette, 1975, et al.
(författare)
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Hormonal regulation of glucose and system A amino acid transport in first trimester placental villous fragments.
- 2005
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Ingår i: American journal of physiology. Regulatory, integrative and comparative physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 288:3
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Tidskriftsartikel (refereegranskat)abstract
- Alterations in placental nutrient transfer have been implicated in fetal growth abnormalities. In pregnancies complicated by diabetes and accelerated fetal growth, upregulations of glucose transporter 1 (GLUT1) and amino acid transporter system A have been shown in the syncytiotrophoblast of term placenta. In contrast, intrauterine growth restriction is associated with a downregulation of placental system A transporters. However, underlying mechanisms of transporter regulation are poorly understood, particularly in early pregnancy. In this study, hormonal regulation of placental glucose and system A transporters was investigated. The uptake of 3-O-[methyl-(14)C]-d-glucose was studied in villous fragments isolated from first trimester (6-13 wk of gestation) and term human placenta. Villous fragments were incubated in buffer containing insulin, leptin, cortisol, growth hormone (GH), prolactin, IGF-I, or under hypo/hyperglycemic conditions for 1 h. Subsequently, 3-O-[methyl-(14)C]-D-glucose uptake was measured with and without phloretin for 70 s in first trimester tissue and 20 s in term tissue. Methylaminoisobutyric uptake was measured with and without Na+ for 20 min. Glucose uptake was unaltered by hormones or hypo/hyperglycemia. GH decreased system A activity by 31% in first trimester (P < 0.05). The uptake of glucose was 50% higher in term compared with first trimester fragments and increased markedly between 6 and 13 wk of gestation (P < 0.05). We conclude that placental glucose transporter activity is not regulated by short exposures to the hormones or glucose concentrations tested. In contrast to term placental villous fragments, system A activity was not regulated by insulin or leptin in first trimester but was downregulated by GH.
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| 16. |
- Jansson, Nina, 1976, et al.
(författare)
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Activation of Placental mTOR Signaling and Amino Acid Transporters in Obese Women Giving Birth to Large Babies.
- 2013
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 98:1, s. 105-13
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Tidskriftsartikel (refereegranskat)abstract
- Context: Babies of obese women are often large at birth, which is associated with perinatal complications and metabolic syndrome later in life. The mechanisms linking maternal obesity to fetal overgrowth are largely unknown. Objective: We tested the hypothesis that placental insulin/IGF-I and mammalian target of rapamycin (mTOR) signaling is activated and amino acid transporter activity is increased in large babies of obese women. Design and Setting: Pregnant women were recruited prospectively for collection of placental tissue at a university hospital and academic biomedical center. Patients or Other Participants: Twenty-three Swedish pregnant women with first trimester body mass index ranging from 18.5 to 44.9 kg/m(2) and with uncomplicated pregnancies participated in the study. Interventions: There were no interventions. Main Outcome Measures: We determined the phosphorylation of key signaling molecules (including Akt, IRS-1, S6K1, 4EBP-1, RPS6, and AMPK) in the placental insulin/IGF-I, AMPK, and mTOR signaling pathways. The activity and protein expression of the amino acid transporter systems A and L were measured in syncytiotrophoblast microvillous plasma membranes. Results: Birth weights (range, 3025-4235 g) were positively correlated to maternal body mass index (P < 0.05). The activity of placental insulin/IGF-I and mTOR signaling was positively correlated (P < 0.001), whereas AMPK phosphorylation was inversely (P < 0.05) correlated to birth weight. Microvillous plasma membrane system A, but not system L, activity and protein expression of the system A isoform SNAT2 were positively correlated to birth weight (P < 0.001). Conclusions: Up-regulation of specific placental amino acid transporter isoforms may contribute to fetal overgrowth in maternal obesity. This effect may be mediated by activation of insulin/IGF-I and mTOR signaling pathways, which are positive regulators of placental amino acid transporters.
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| 17. |
- Jansson, Nina, 1976, et al.
(författare)
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Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet.
- 2006
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Ingår i: The Journal of physiology. - : Wiley. - 0022-3751. ; 576:Pt 3, s. 935-46
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Tidskriftsartikel (refereegranskat)abstract
- Intrauterine growth restriction (IUGR) represents an important risk factor for perinatal complications and for adult disease. IUGR is associated with a down-regulation of placental amino acid transporters; however, whether these changes are primary events directly contributing to IUGR or a secondary consequence is unknown. We investigated the time course of changes in placental and fetal growth, placental nutrient transport in vivo and the expression of placental nutrient transporters in pregnant rats subjected to protein malnutrition, a model for IUGR. Pregnant rats were given either a low protein (LP) diet (n = 64) or an isocaloric control diet (n = 66) throughout pregnancy. Maternal insulin, leptin and IGF-I levels decreased, whereas maternal amino acid concentrations increased moderately in response to the LP diet. Fetal and placental weights in the LP group were unaltered compared to control diet at gestational day (GD) 15, 18 and 19 but significantly reduced at GD 21. Placental system A transport activity was reduced at GD 19 and 21 in response to a low protein diet. Placental protein expression of SNAT2 was decreased at GD 21. In conclusion, placental amino acid transport is down-regulated prior to the development of IUGR, suggesting that these placental transport changes are a cause, rather than a consequence, of IUGR. Reduced maternal levels of insulin, leptin and IGF-1 may link maternal protein malnutrition to reduced fetal growth by down-regulation of key placental amino acid transporters.
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| 18. |
- Jansson, Nina, 1976, et al.
(författare)
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Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments.
- 2003
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 88:3, s. 1205-11
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Tidskriftsartikel (refereegranskat)abstract
- The activity and expression of placental nutrient transporters are primary determinants for the supply of nutrients to the fetus, and these nutrients in turn regulate fetal growth. We developed an experimental system to assess amino acid uptake in single primary villous fragments to study hormonal regulation of the amino acid transporter system A in term human placenta. Validation of the method, using electron microscopy and studies of hormone production, indicated that fragments maintained ultrastructural and functional integrity for at least 3 h. The activity of system A was measured as the Na(+)-dependent uptake of methylaminoisobutyric acid (MeAIB), and the effect of 1 h incubation in various hormones was investigated. Uptake of MeAIB into villous fragments in the presence of Na(+) was linear up to at least 30 min. Insulin (300 ng/ml, n = 14) increased system A activity by 56% (P < 0.05). This effect was also present at insulin concentrations in the physiological range (+47% at 0.6 ng/ml, n = 10, P < 0.05). Leptin (500 ng/ml, n = 14) increased Na(+)-dependent MeAIB uptake by 37% (P < 0.05). System A activity increased in a concentration-dependent fashion in response to leptin (n = 10). However, neither epidermal GF (600 ng/ml), cortisol (340 ng/ml), nor GH (500 ng/ml) altered system A activity significantly (n = 14). We conclude that primary single isolated villous fragments can be used in studies of hormonal regulation of nutrient uptake into the syncytiotrophoblast. These data suggest that leptin regulates system A, a key amino acid transporter.
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| 19. |
- Jansson, Nina, 1976, et al.
(författare)
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Maternal hormones linking maternal body mass index and dietary intake to birth weight.
- 2008
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Ingår i: American Journal of Clinical Nutrition. - Bethesda, USA : American Society for Nutrition. - 0002-9165 .- 1938-3207. ; 87:6, s. 1743-9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Obese women often give birth to large-for-gestational age infants (typically defined as a birth weight greater than the 90th percentile), who are at risk of birth injuries and of developing metabolic syndrome later in life. The mechanisms underlying increased fetal growth remain to be established. OBJECTIVE: We aimed to identify maternal hormones that can explain the link between dietary intake, body mass index (BMI), and birth weight. DESIGN: Pregnant women with BMIs (in kg/m(2)) ranging from 17 to 44 (n = 49) were recruited in gestational weeks 8-12. Serum hormone concentrations were measured and dietary history interviews were performed in the first and third trimesters. Multiple regression models were produced to identify hormones that correlate with birth weight and are influenced by BMI or dietary factors. RESULTS: We found a strong positive correlation between BMI and first- and third-trimester insulin and leptin concentrations and a negative correlation between BMI and first-trimester adiponectin and first- and third-trimester insulin-like growth factor binding protein-1 (IGFBP-1). Maternal total fat intake in the first trimester was positively correlated with maternal leptin and inversely correlated with adiponectin. In addition, third-trimester total fat intake was positively correlated with circulating resistin concentrations. First-trimester maternal serum resistin was positively correlated with birth weight, whereas third-trimester maternal IGFBP-1 was negatively correlated with birth weight. CONCLUSIONS: High first-trimester maternal serum resistin and low third-trimester IGFBP-1 were correlated with increased birth weight. We propose that low serum concentrations of IGFBP-1 represent a link between high BMI and increased fetal growth by increasing the bioavailability of insulin-like growth factor-I, which up-regulates placental nutrient transport.
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| 20. |
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| 21. |
- Jonsson, Thomas, et al.
(författare)
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Limb ischemia after EVAR : an effect of the obstructing introducer?
- 2008
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Ingår i: Journal of Endovascular Therapy. - Phoenix, AZ : International Society of Endovascular Specialists. - 1526-6028 .- 1545-1550. ; 15:6, s. 695-701
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To evaluate the splanchnic and limb metabolic effects of open repair (OR) of abdominal aortic aneurysms (AAA) versus endovascular aneurysm repair (EVAR) in a pilot study utilizing microdialysis. METHODS: Nine AAA patients (8 men; mean age 74 years, range 61-85) were treated with EVAR and 9 had an OR (5 men; mean age 70 years, range 55-85). In the EVAR cases, which were performed percutaneously, the external iliac artery was obstructed by the introducer to a mean functional stenosis of 70% (52%-100%). Catheters for microdialysis were placed subcutaneously above the ankle of the right leg and freely in the abdominal cavity to measure the levels of lactate and pyruvate. The lactate/pyruvate ratio was calculated as a measure of ischemia. Measurements started at the end of surgery and continued for 2 days. Mean values were compared using the Mann-Whitney U test. RESULTS: The mean value of intraperitoneal lactate during the first day after EVAR was 1.5+/-0.7 mM versus 2.6+/-0.8 mM after OR (p = 0.019). The lactate/pyruvate ratio was 10.2+/-2.2 after EVAR and 12.3+/-2.6 after OR (p = 0.113). Leg lactate mean values were 4.2+/-2.0 mM after EVAR versus 1.8+/-0.6 mM after OR (p<0.001). The lactate/pyruvate ratio was 20.1+/-8.3 for EVAR and 13.7+/-3.3 for OR (p = 0.040). These differences between EVAR and OR continued for the second day. CONCLUSION: Intraperitoneally, metabolism was slightly increased after OR; however, it was not suggestive of splanchnic ischemia. Leg findings reflected a more extensive ischemia after EVAR over 48 hours, which was a somewhat unexpected finding that may be related to the introducer's impact on blood flow to the limb during the intervention. Although no clinical consequences were recorded, the finding suggests some benefit of minimizing as much as possible the time of reduced perfusion to the limb.
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| 22. |
- Lager, Susanne, 1978, et al.
(författare)
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Effect of IL-6 and TNF-α on fatty acid uptake in cultured human primary trophoblast cells.
- 2011
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Ingår i: Placenta. - : Elsevier BV. - 1532-3102 .- 0143-4004. ; 32:2, s. 121-7
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Tidskriftsartikel (refereegranskat)abstract
- Maternal obesity and gestational diabetes (GDM) are conditions associated with fetal overgrowth and excessive fat accumulation in the fetus, implicating an increased placental nutrient transfer in these pregnancies. Obese and GDM mothers have altered metabolism and hormone levels, including elevation of maternal circulatory lipids and pro-inflammatory cytokines. We tested the hypothesis that interleukin (IL)-6 and tumor necrosis factor (TNF)-α stimulate placental fatty acid transport, as these pro-inflammatory cytokines have been shown to affect lipid metabolism in other tissues. In cultured primary human trophoblast cells IL-6, but not TNF-α, stimulated fatty acid accumulation, as measured by BODIPY fluorescence. The increased fatty acid accumulation could not be explained by an increased expression of key components in placental fatty acid transport, such as adipophilin, fatty acid transport protein (FATP)1, FATP4, or lipoprotein lipase. In a cohort of lean and overweight/obese pregnant women, increasing maternal third trimester IL-6 plasma concentrations correlated with decreasing placental lipoprotein lipase activity. However, as no effect on lipoprotein lipase activity was observed in cultured trophoblast cells after exposure to either IL-6 or TNF-α, the correlation between maternal circulatory IL-6 levels and placental lipoprotein lipase activity at term is unlikely to represent a cause-and-effect relationship. In conclusion, high levels of IL-6 stimulate trophoblast fatty acid accumulation, which could contribute to an excessive nutrient transfer in conditions associated with elevated maternal IL-6 such as obesity and gestational diabetes.
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| 23. |
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| 24. |
- Roos, Sara, 1979, et al.
(författare)
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Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth.
- 2007
-
Ingår i: The Journal of physiology. - : Wiley. - 0022-3751. ; 582:Pt 1, s. 449-59
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Tidskriftsartikel (refereegranskat)abstract
- Pathological fetal growth is associated with perinatal morbidity and the development of diabetes and cardiovascular disease later in life. Placental nutrient transport is a primary determinant of fetal growth. In human intrauterine growth restriction (IUGR) the activity of key placental amino acid transporters, such as systems A and L, is decreased. However the mechanisms regulating placental nutrient transporters are poorly understood. We tested the hypothesis that the mammalian target of rapamycin (mTOR) signalling pathway regulates amino acid transport in the human placenta and that the activity of the placental mTOR pathway is reduced in IUGR. Using immunohistochemistry and culture of trophoblast cells, we show for the first time that the mTOR protein is expressed in the transporting epithelium of the human placenta. We further demonstrate that placental mTOR regulates activity of the l-amino acid transporter, but not system A or taurine transporters, by determining the mediated uptake of isotope-labelled leucine, methylaminoisobutyric acid and taurine in primary villous fragments after inhibition of mTOR using rapamycin. The protein expression of placental phospho-S6K1 (Thr-389), a measure of the activity of the mTOR signalling pathway, was markedly reduced in placentas obtained from pregnancies complicated by IUGR. These data identify mTOR as an important regulator of placental amino acid transport, and provide a mechanism for the changes in placental leucine transport in IUGR previously demonstrated in humans. We propose that mTOR functions as a placental nutrient sensor, matching fetal growth with maternal nutrient availability by regulating placental nutrient transport.
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| 25. |
- Sarwar, Nadeem, et al.
(författare)
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Interleukin-6 receptor pathways in coronary heart disease : a collaborative meta-analysis of 82 studies
- 2012
-
Ingår i: The Lancet. - New York, NY, USA : Elsevier. - 0140-6736 .- 1474-547X. ; 379:9822, s. 1205-1213
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Tidskriftsartikel (refereegranskat)abstract
- Background: Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling. Methods: In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125 222 participants. We also compared the frequency of Asp358Ala in 51 441 patients with coronary heart disease and in 136 226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6. Findings: The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele >= 0.04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34.3% (95% CI 30.4-38.2) and of interleukin 6 by 14.6% (10.7-18.4), and mean concentration of C-reactive protein was reduced by 7.5% (5.9-9.1) and of fibrinogen by 1.0% (0.7-1.3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3.4% (1.8-5.0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes. Interpretation: Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.
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| 26. |
- Végvári, Ákos, et al.
(författare)
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Experimental Models to Study Drug Distributions in Tissue Using MALDI Mass Spectrometry
- 2013
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:12, s. 5626-5633
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Tidskriftsartikel (refereegranskat)abstract
- Requirements for patient safety and improved efficacy are steadily increasing in modern healthcare and are key drivers in modern drug development. New drug characterization assays are central in providing evidence of the specificity and selectivity of drugs. Meeting this need, matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is used to study drug localization within micro-environmental tissue compartments. Thin sections of human lung tumor and rat xenograft tissues were exposed to pharmaceutical drugs by either spotting or submerging. These drugs, the epidermal growth factor receptor antagonists, erlotinib (Tarceva™) and gefitinib (Iressa™), and the acetylcholine receptor antagonist, tiotropium were characterized by microenvironment localization. Intact tissue blocks were also immersed in drug solution followed by sectioning. MALDI-MSI was then performed using a Thermo MALDI LTQ Orbitrap XL instrument to localize drug distribution patterns. We propose three MALDI-MSI models measuring drug disposition that have been used to map the selected compounds within tissue compartments of tumors isolated from lung cancer patients.
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| 27. |
- Welinder, Charlotte, et al.
(författare)
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A protein deep sequencing evaluation of metastatic melanoma tissues.
- 2015
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Malignant melanoma has the highest increase of incidence of malignancies in the western world. In early stages, front line therapy is surgical excision of the primary tumor. Metastatic disease has very limited possibilities for cure. Recently, several protein kinase inhibitors and immune modifiers have shown promising clinical results but drug resistance in metastasized melanoma remains a major problem. The need for routine clinical biomarkers to follow disease progression and treatment efficacy is high. The aim of the present study was to build a protein sequence database in metastatic melanoma, searching for novel, relevant biomarkers. Ten lymph node metastases (South-Swedish Malignant Melanoma Biobank) were subjected to global protein expression analysis using two proteomics approaches (with/without orthogonal fractionation). Fractionation produced higher numbers of protein identifications (4284). Combining both methods, 5326 unique proteins were identified (2641 proteins overlapping). Deep mining proteomics may contribute to the discovery of novel biomarkers for metastatic melanoma, for example dividing the samples into two metastatic melanoma "genomic subtypes", ("pigmentation" and "high immune") revealed several proteins showing differential levels of expression. In conclusion, the present study provides an initial version of a metastatic melanoma protein sequence database producing a total of more than 5000 unique protein identifications. The raw data have been deposited to the ProteomeXchange with identifiers PXD001724 and PXD001725.
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| 28. |
- Welinder, Charlotte, et al.
(författare)
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Establishing a Southern Swedish Malignant Melanoma OMICS and Biobank Clinical Capability
- 2013
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Ingår i: Clinical and Translational Medicine. - : Wiley. - 2001-1326. ; 2:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The Southern Swedish Malignant Melanoma (SSMM) research team is a truly cross functional group with members from oncology, clinical, surgery, bioinformatics, proteomics, and genomics initiatives. The SSMM’s objectives and goals are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits. The science output in these resulting study outcomes further strengthens the build of healthcare benefit in the complex challenges of malignant melanoma pathophysiology that is addressed by the novel personalized medicines entering the market. These patient biobank archives will be fully automated with novel ultralow temperature biobank storage units and used as a clinical resource. Methods: Clinical materials from patients before, during and after treatments, with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. We are developing standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community. Results: An IT-infrastructure using a laboratory information management system (LIMS) has been established, that will be the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund will form the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are being associated with the biobank materials, including pathology reports on disease diagnosis on the MM patients. Conclusions: We provide data on the developments of protein profiling and targeted protein target assays on isolated melanoma tumors, as well as reference blood standards that is used by the team members in the respective laboratories. These pilot data show biobank access and feasibility of performing quantitative proteomics in MM biobank repositories collected in southern Sweden.
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| 29. |
- Wendt, Fabian, et al.
(författare)
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Ocean energy systemswave energy modelling task: Modelling, verification and validation ofwave energy converters
- 2019
-
Ingår i: Journal of Marine Science and Engineering. - : MDPI AG. - 2077-1312. ; 7:11
-
Tidskriftsartikel (refereegranskat)abstract
- The International Energy Agency Technology Collaboration Programme for Ocean Energy Systems (OES) initiated the OES Wave Energy Conversion Modelling Task, which focused on the verification and validation of numerical models for simulating wave energy converters (WECs). The long-term goal is to assess the accuracy of and establish confidence in the use of numerical models used in design as well as power performance assessment of WECs. To establish this confidence, the authors used different existing computational modelling tools to simulate given tasks to identify uncertainties related to simulation methodologies: (i) linear potential flow methods; (ii) weakly nonlinear Froude-Krylov methods; and (iii) fully nonlinear methods (fully nonlinear potential flow and Navier-Stokes models). This article summarizes the code-to-code task and code-to-experiment task that have been performed so far in this project, with a focus on investigating the impact of different levels of nonlinearities in the numerical models. Two different WECs were studied and simulated. The first was a heaving semi-submerged sphere, where free-decay tests and both regular and irregular wave cases were investigated in a code-to-code comparison. The second case was a heaving float corresponding to a physical model tested in a wave tank. We considered radiation, diffraction, and regular wave cases and compared quantities, such as the WEC motion, power output and hydrodynamic loading.
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| 30. |
- Abdellah, Tebani, et al.
(författare)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 31. |
- Abraham-Nordling, Mirna, et al.
(författare)
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Incidence of hyperthyroidism in Sweden
- 2011
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:6, s. 899-905
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100000 inhabitants per year. This extended study has evaluated the incidence for similar to 40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. Methods:All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows:clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. Results:A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. Conclusion:The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.
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| 32. |
- Agrell, Beata, et al.
(författare)
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Ett laglöst tillstånd
- 2012
-
Annan publikation (populärvet., debatt m.m.)
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| 33. |
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| 34. |
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| 35. |
- Ahlberg, Erik, et al.
(författare)
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"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 36. |
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| 37. |
- Allegrini, Elisa, et al.
(författare)
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Quality and generation rate of solid residues in the boiler of a waste-to-energy plant
- 2014
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Ingår i: Journal of Hazardous Materials. - : Elsevier. - 0304-3894 .- 1873-3336. ; 270, s. 127-136
-
Tidskriftsartikel (refereegranskat)abstract
- The Danish waste management system relies significantly on waste-to-energy (WtE) plants. The ash produced at the energy recovery section (boiler ash) is classified as hazardous waste, and is commonly mixed with fly ash and air pollution control residues before disposal. In this study, a detailed characterization of boiler ash from a Danish grate-based mass burn type WtE was performed, to evaluate the potential for improving ash management. Samples were collected at 10 different points along the boiler's convective part, and analysed for grain size distribution, content of inorganic elements, polychlorinated dibenzo-. p-dioxins and dibenzofurans (PCDD and PCDF), and leaching of metals. For all samples, PCDD and PCDF levels were below regulatory limits, while high pH values and leaching of e.g. Cl were critical. No significant differences were found between boiler ash from individual sections of the boiler, in terms of total content and leaching, indicating that separate management of individual ash fractions may not provide significant benefits.
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| 38. |
- Antonsson, Kjell, et al.
(författare)
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Occurrence of the hermit beetle (Osmoderma eremita), in Sweden.
- 2003
-
Ingår i: Entomologisk tidskrift. - 0013-886X. ; 124:4, s. 225-240
-
Tidskriftsartikel (refereegranskat)abstract
- We have compiled data on the occurrence of a threatened beetle, Osmoderma eremita, in Sweden. The species inhabits tree hollows with wood mould. The data were compiled from field surveys conducted in 1993-2003, using pitfall traps at 401 localities and using wood mould sampling at 104 localities. We have also gone through published data and all larger Swedish museums and registered old records. O. eremita was recorded at about 30% of the field surveys. In Sweden, oak is by far the most important host tree species, but the beetle has also been found in other deciduous trees, such as beech, alder, ash and lime. Currently, 270 localities with Osmoderma eremita, defined as records of living adults, larvae, fragments of adult body parts, or excrements situated at least 1 km from each other, are known in Sweden. 129 of these localities are records of live beetles or larvae made after 1990. The species is found in the southern third of Sweden only, and there are more localities in the eastern part compared to the western. The great majority of the localities have been discovered during the last ten years. At some of the localities only excrements or fragments have been recorded, and the species might actually be extinct at some of these localities. Due to low search intensity historically, it is impossible to use these data to discover any changes in the distribution or occurrence over time. Because old, hollow oaks were much more frequent 200 years ago, we suggest that the species has decreased severely in Sweden since that time. Today, old oaks are rarely cut down but instead lack of grazing cattle is a threat because many sites regrow with dense tree stands which outcompete the old hollow trees. Many local extinctions could also be expected during the next few decades, because many of the localities have too few hollow trees and are too isolated. At many localities, lack of younger trees which can take over the role as host trees when the present trees die will also be a problem in the future.
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| 39. |
- Aramrattana, Maytheewat, 1988-, et al.
(författare)
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Team Halmstad Approach to Cooperative Driving in the Grand Cooperative Driving Challenge 2016
- 2018
-
Ingår i: IEEE transactions on intelligent transportation systems (Print). - Piscataway, N.J. : Institute of Electrical and Electronics Engineers Inc.. - 1524-9050 .- 1558-0016. ; 19:4, s. 1248-1261
-
Tidskriftsartikel (refereegranskat)abstract
- This paper is an experience report of team Halmstad from the participation in a competition organised by the i-GAME project, the Grand Cooperative Driving Challenge 2016. The competition was held in Helmond, The Netherlands, during the last weekend of May 2016. We give an overview of our car’s control and communication system that was developed for the competition following the requirements and specifications of the i-GAME project. In particular, we describe our implementation of cooperative adaptive cruise control, our solution to the communication and logging requirements, as well as the high level decision making support. For the actual competition we did not manage to completely reach all of the goals set out by the organizers as well as ourselves. However, this did not prevent us from outperforming the competition. Moreover, the competition allowed us to collect data for further evaluation of our solutions to cooperative driving. Thus, we discuss what we believe were the strong points of our system, and discuss post-competition evaluation of the developments that were not fully integrated into our system during competition time. © 2000-2011 IEEE.
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| 40. |
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| 41. |
- Backman, Helena, et al.
(författare)
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Eosinophilic inflammation and lung function decline in a long-term follow-up of a large population-based asthma cohort
- 2018
-
Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The relationship between lung function decline and airway inflammation among asthmatics has important therapeutic implications, but has rarely been studied in large samples or in population-based asthma cohorts.A population-based adult asthma cohort (n=2055) was recruited during 1986-2001 and clinically examined including spirometry. In 2012-2014, all still eligible subjects (n=1425) were invited to a clinical follow-up including spirometry, blood sampling, and a structured interview, and n=1006 participated (55% women, mean age 59y, 32-92y). Linear regression was performed with age, sex, smoking habits, year of first examination, family history of asthma, socioeconomic status, eosinophils (EOS)>=0.3x109/L, and neutrophils (NEUT)>=5.0x109/L as independent variables and pre-bronchodilator FEV1 decline/year (ml and % of predicted [pp], respectively) as dependent. In secondary models, both ICS use at baseline and ICS use at follow-up were also included.The mean annual FEV1 decline in ml (pp) among asthmatics with EOS<0.3, 0.4>EOS>=0.3 and EOS>=0.4x109/L, respectively, was 26ml (0.03pp), 29ml (0.10pp) and 34ml (0.27pp) (p<0.001). In adjusted analyses, EOS>=0.3 was significantly associated with FEV1 decline, both in terms of ml (4ml excess annual decline vs EOS<0.3) and pp. The association between EOS and FEV1 decline in pp, but not ml, remained when additionally adjusted for ICS use. The association with NEUT>=5.0x109/L was less clear.On group level, adult asthmatics with higher levels of eosinophils in blood have a history of excess FEV1 decline compared to asthmatics with lower levels of eosinophil inflammation, independent of other factors such as ICS use.
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| 42. |
- Backman, Helena, et al.
(författare)
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FEV1 decline in relation to blood eosinophils and neutrophils in a population-based asthma cohort
- 2020
-
Ingår i: World Allergy Organization Journal. - : Elsevier. - 1939-4551. ; 13:3
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The relationship between lung function decline and eosinophils and neutrophils has important therapeutic implications among asthmatics, but it has rarely been studied in large cohort studies.Objective: The aim is to study the relationship between blood eosinophils and neutrophils and FEV1 decline in a long-term follow-up of a population-based adult asthma cohort.Methods: In 2012-2014, an adult asthma cohort was invited to a follow-up including spirometry, blood sampling, and structured interviews, and n = 892 participated (55% women, mean age 59 y, 32-92 y). Blood eosinophils, neutrophils and FEV 1 decline were analyzed both as continuous variables and divided into categories with different cut-offs. Regression models adjusted for smoking, exposure to vapors, gas, dust, or fumes (VGDF), use of inhaled and oral corticosteroids, and other possible confounders were utilized to analyze the relationship between eosinophils and neutrophils at follow-up and FEV1 decline.Results: The mean follow-up time was 18 years, and the mean FEV 1 decline was 27 ml/year. The annual FEV1 decline was related to higher levels of both blood eosinophils and neutrophils at follow-up, but only the association with eosinophils remained when adjusted for confounders. Further, the association between FEV1 decline and eosinophils was stronger among those using ICS. With EOS <0.3 × 109/L as reference, a more rapid decline in FEV1 was independently related to EOS ≥0.4 × 109/L in adjusted analyses.Conclusions and clinical relevance: Besides emphasizing the importance of smoking cessation and reduction of other harmful exposures, our real-world results indicate that there is an independent relationship between blood eosinophils and FEV1 decline among adults with asthma.
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| 43. |
- Backman, Helena, et al.
(författare)
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Severe asthma : A population study perspective
- 2019
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Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 49:6, s. 819-828
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSevere asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.ObjectiveTo describe characteristics and estimate the prevalence of severe asthma in a large adult population‐based asthma cohort followed for 10‐28 years.MethodsN=1006 subjects with asthma participated in a follow‐up during 2012‐14, when 830 (mean age 59y, 56% women) still had current asthma. Severe asthma was defined according to three internationally well‐known criteria: the ATS workshop definition from 2000 used in the US Severe Asthma Research Program (SARP), the 2014 ATS/ERS Task force definition and the GINA 2017. All subjects with severe asthma according to any of these criteria were undergoing respiratory specialist care, and were also contacted by telephone to verify treatment adherence.ResultsThe prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS Taskforce), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma according to the asthma control test. Severe asthma was related to age >50 years, nasal polyposis, impaired lung function, sensitization to aspergillus, and tended to be more common in women. Further, neutrophils in blood significantly discriminated severe asthma from other asthma.Conclusions and clinical relevanceSevere asthma differed significantly from other asthma in terms of demographic, clinical and inflammatory characteristics, results suggesting possibilities for improved treatment regimens of severe asthma. The prevalence of severe asthma in this asthma cohort was 4‐6%, corresponding to approximately 0.5% of the general population.
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| 44. |
- Backman, Helena, et al.
(författare)
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Severe asthma among adults : Prevalence and clinical characteristics
- 2018
-
Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Severe asthma is a considerable challenge for patients, health care professionals and society. Few studies have estimated the prevalence of severe asthma according to modern definitions of which none based on a population study.Methods: We estimated the prevalence and studied characteristics of severe asthma in a large adult population-based asthma cohort followed for 10-28 years in northern Sweden: 1006 subjects participated in a follow-up during 2012-14, when 830 (82.5%) still had current asthma (mean age 59y, 32-92y, 56% women). Severe asthma was defined according to three internationally well-known criteria: the US SARP, ATS/ERS and GINA. All subjects with severe asthma were undergoing respiratory specialist care, and were also contacted by telephone to verify adherence to treatment.Results: The prevalence of severe asthma according to the three definitions was 3.6% (US SARP), 4.8% (ERS/ATS), and 6.1% (GINA) among subjects with current asthma. Although all were using high ICS doses and other maintenance treatment, >40% had uncontrolled asthma and <10% had controlled asthma according to the ACT. Severe asthma was related to age >50 years, nasal polyposis, decreased FEV1, not fully reversible airway obstruction, sensitization to aspergillus, elevated neutrophils and partly to eosinophils, and tended to be more common in women.Conclusion: The prevalence of severe asthma in this asthma cohort was 4-6%, corresponding to approximately 0.5% of the population in northern Sweden. A substantial proportion of those with severe asthma had uncontrolled disease, and severe asthma differed significantly from other asthma in terms of both clinical and inflammatory characteristics.
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| 45. |
- Bag, Pushan, 1993-, et al.
(författare)
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An atlas of the Norway spruce needle seasonal transcriptome
- 2021
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Ingår i: The Plant Journal. - : John Wiley & Sons. - 0960-7412 .- 1365-313X. ; 108:6, s. 1815-1829
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Tidskriftsartikel (refereegranskat)abstract
- Boreal conifers possess a tremendous ability to survive and remain evergreen during harsh winter conditions and resume growth during summer. This is enabled by coordinated regulation of major cellular functions at the level of gene expression, metabolism, and physiology. Here we present a comprehensive characterization of the annual changes in the global transcriptome of Norway spruce (Picea abies) needles as a resource to understand needle development and acclimation processes throughout the year. In young, growing needles (May 15 until June 30), cell walls, organelles, etc., were formed, and this developmental program heavily influenced the transcriptome, explained by over-represented Gene Ontology (GO) categories. Later changes in gene expression were smaller but four phases were recognized: summer (July–August), autumn (September–October), winter (November–February), and spring (March–April), where over-represented GO categories demonstrated how the needles acclimated to the various seasons. Changes in the seasonal global transcriptome profile were accompanied by differential expression of members of the major transcription factor families. We present a tentative model of how cellular activities are regulated over the year in needles of Norway spruce, which demonstrates the value of mining this dataset, accessible in ConGenIE together with advanced visualization tools.
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| 46. |
- Baguma, Yona, et al.
(författare)
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Expression patterns of the gene encoding starch branching enzyme II in the storage roots of cassava (Manihot esculenta Crantz)
- 2003
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Ingår i: Plant Science. - 0168-9452 .- 1873-2259. ; 164:5, s. 833-839
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Tidskriftsartikel (refereegranskat)abstract
- Spatial and temporal expression patterns of the sbeII and sbeI genes, encoding starch branching enzyme II and I, respectively, in cassava (Manihot esculenta Crantz) were studied at different phenological stages of the crop. A partial cDNA for sbeII in cassava was cloned and used along with a cDNA-specific fragment of sbeI. As the cassava plant aged, the transcriptional activity of the sbeII and sbeI genes in the underground storage roots increased, whereas the activity in other organs remained the same or declined. At 180 days after planting (d.a.p.), levels of sbeII and sbeI transcripts in storage roots were very low, whereas at 360 d.a.p., the levels had increased dramatically. The 360 d.a.p. old storage roots also accumulated gbssII and gbssI transcripts, as well as a longer gbssI transcript, gbssI′. The difference between the gbssI and gbssI′ transcripts was shown to be due to differential splicing, whereby the gbssI′ transcript retained the first three introns. Unexpectedly, expression of sbeII and sbeI in the 360 d.a.p. storage roots exhibited fluctuations during the 24 h cycle, both under the normal light/dark regime and under continuous light or continuous dark conditions.
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| 47. |
- Basnet, Shyam Kumar, et al.
(författare)
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A Bayesian econometrics and risk programming approach for analysing the impact of decoupled payments in the European Union*
- 2021
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Ingår i: Australian Journal of Agricultural and Resource Economics. - : Wiley. - 1364-985X .- 1467-8489. ; 65:3, s. 729-759
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Tidskriftsartikel (refereegranskat)abstract
- We estimate a risk-based programming, individual farm model and apply it to study the wealth effects of crop-related, decoupled direct payments under the European Union (EU) Common Agricultural Policy. The model expands on previous work on estimating risk-based programming models by applying a robust Bayesian econometric framework. The results indicate that the wealth effect varies greatly between individual farms, but that its impact on aggregate crop production is small. For larger farms, in particular, removing the decoupled payments, while keeping total land constant, increases the diversity of the cropping plan.
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| 48. |
- Benrick, Anna, 1979, et al.
(författare)
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A non-conservative polymorphism in the IL-6 signal transducer (IL6ST)/gp130 is associated with myocardial infarction in a hypertensive population.
- 2008
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Ingår i: Regulatory peptides. - : Elsevier BV. - 0167-0115. ; 146:1-3, s. 189-96
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation is a key component in the development of atherosclerosis, and myocardial infarction (MI); therefore we investigated the association between an interleukin-6 signal transducer (IL6ST)/gp130 polymorphism, gp130 function and risk of MI. Structural modeling suggested that a non-conservative single nucleotide polymorphism in the gp130, Gly148Arg, can change the stability and functional properties of the molecule. In vitro studies were done with BAF/3 cells lacking endogenous gp130. Cells stably transfected with the gp130 148Arg variant proliferated less and showed slightly lower STAT-3 phosphorylation in response to gp130 stimulation as compared to cells transfected with gp130 148Gly. In a prospectively followed hypertensive cohort we identified 167 patients who suffered a MI during the study and compared them to matched controls (mean age 57 years, 73% males, n=482). Carriers of the 148Arg variant (f(Arg)=0.12) of the gp130 receptor had decreased odds ratio for MI in univariate analysis (0.56, 95% CI 0.34-0.91, p=0.02). In conclusion, a genetically determined structural variant of the IL-6 receptor subunit gp130 is, independently of other known risk factors, associated with decreased risk of MI. The variant is also associated with decreased IL-6 responsiveness and could lead to a configuration change in the gp130 receptor.
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| 49. |
- Bergqvist, David, et al.
(författare)
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Inga dödsfall/slaganfall efter kirurgi vid asymtomatisk karotisstenos : femårsresultat redovisat i riksstäckande register
- 2006
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 103:5, s. 301-302
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Tidskriftsartikel (refereegranskat)abstract
- In the Swedish vascular registry 7473 carotid endarterectomies are registered, in 10% the indication being a symptomatic stenosis. There are great variations in indication for carotid endarterectomy within Sweden. During the last five years the combined postoperative mortality and/or postoperative permanent stroke has varied between 3% in 1999 and 1.5% in 2003. During the same period not a single patient operated on for a symptomatic carotid stenosis experienced these complications.
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| 50. |
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