| 1. |
- Emerging Risk Factors, Collaboration, et al.
(författare)
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The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases
- 2007
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Ingår i: Eur J Epidemiol. - 0393-2990. ; 22:12, s. 839-69
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Tidskriftsartikel (refereegranskat)abstract
- Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
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| 2. |
- Elsik, Christine G., et al.
(författare)
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The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
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Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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| 3. |
- Newton-Cheh, Christopher, et al.
(författare)
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Genome-wide association study identifies eight loci associated with blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:6, s. 666-676
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N <= 71,225 European ancestry, N <= 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 x 10(-24)), CYP1A2 (P = 1 x 10(-23)), FGF5 (P = 1 x 10(-21)), SH2B3 (P = 3 x 10(-18)), MTHFR (P = 2 x 10(-13)), c10orf107 (P = 1 x 10(-9)), ZNF652 (P = 5 x 10(-9)) and PLCD3 (P = 1 x 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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| 4. |
- Vasan, Ramachandran S, et al.
(författare)
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Genetic variants associated with cardiac structure and function : a meta-analysis and replication of genome-wide association data
- 2009
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 302:2, s. 168-178
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. OBJECTIVE: To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. DESIGN, SETTING, AND PARTICIPANTS: Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nucleotide polymorphisms (SNPs; imputed to the HapMap CEU panel) and echocardiographic traits. In stage 2, SNPs significantly associated with traits in stage 1 were tested for association in 2 other cohorts (n = 4094 people of European ancestry). Using a prespecified P value threshold of 5 x 10(-7) to indicate genome-wide significance, we performed an inverse variance-weighted fixed-effects meta-analysis of genome-wide association data from each cohort. MAIN OUTCOME MEASURES: Echocardiographic traits: LV mass, internal dimensions, wall thickness, systolic dysfunction, aortic root, and left atrial size. RESULTS: In stage 1, 16 genetic loci were associated with 5 echocardiographic traits: 1 each with LV internal dimensions and systolic dysfunction, 3 each with LV mass and wall thickness, and 8 with aortic root size. In stage 2, 5 loci replicated (6q22 locus associated with LV diastolic dimensions, explaining <1% of trait variance; 5q23, 12p12, 12q14, and 17p13 associated with aortic root size, explaining 1%-3% of trait variance). CONCLUSIONS: We identified 5 genetic loci harboring common variants that were associated with variation in LV diastolic dimensions and aortic root size, but such findings explained a very small proportion of variance. Further studies are required to replicate these findings, identify the causal variants at or near these loci, characterize their functional significance, and determine whether they are related to overt cardiovascular disease.
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| 5. |
- Walker, M. D., et al.
(författare)
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Plant community responses to experimental warming across the tundra biome
- 2006
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 103:5, s. 1342-1346
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Tidskriftsartikel (refereegranskat)abstract
- Recent observations of changes in some tundra ecosystems appear to be responses to a warming climate. Several experimental studies have shown that tundra plants and ecosystems can respond strongly to environmental change, including warming; however, most studies were limited to a single location and were of short duration and based on a variety of experimental designs. In addition, comparisons among studies are difficult because a variety of techniques have been used to achieve experimental warming and different measurements have been used to assess responses. We used metaanalysis on plant community measurements from standardized warming experiments at 11 locations across the tundra biome involved in the International Tundra Experiment. The passive warming treatment increased plant-level air temperature by 1-3 degrees C, which is in the range of predicted and observed warming for tundra regions. Responses were rapid and detected in whole plant communities after only two growing seasons. Overall, warming increased height and cover of deciduous shrubs and graminoids, decreased cover of mosses and lichens, and decreased species diversity and evenness. These results predict that warming will cause a decline in biodiversity across a wide variety of tundra, at least in the short term. They also provide rigorous experimental evidence that recently observed increases in shrub cover in many tundra regions are in response to climate warming. These changes have important implications for processes and interactions within tundra ecosystems and between tundra and the atmosphere.
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| 6. |
- Richards, Stephen, et al.
(författare)
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The genome of the model beetle and pest Tribolium castaneum.
- 2008
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Ingår i: Nature. - 1476-4687. ; 452:7190, s. 949-55
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Tidskriftsartikel (refereegranskat)abstract
- Tribolium castaneum is a representative of earth’s most numerous eukaryotic order, a powerful model organism for the study of generalized insect development, and also an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved an ability to interact with a diverse chemical environment as evidenced by large expansions in odorant and gustatory receptors, as well as p450 and other detoxification enzymes. Developmental patterns in Tribolium are more representative of other arthropods than those found in Drosophila, a fact represented in gene content and function. For one, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, and some are expressed in the growth zone crucial for axial elongation in short germ development. Systemic RNAi in T. castaneum appears to use mechanisms distinct from those found in C. elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.
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| 7. |
- Wolever, Thomas M S, et al.
(författare)
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Measuring the glycemic index of foods: interlaboratory study.
- 2008
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Ingår i: The American journal of clinical nutrition. - 0002-9165 .- 1938-3207. ; 87:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Many laboratories offer glycemic index (GI) services. OBJECTIVE: We assessed the performance of the method used to measure GI. DESIGN: The GI of cheese-puffs and fruit-leather (centrally provided) was measured in 28 laboratories (n=311 subjects) by using the FAO/WHO method. The laboratories reported the results of their calculations and sent the raw data for recalculation centrally. RESULTS: Values for the incremental area under the curve (AUC) reported by 54% of the laboratories differed from central calculations. Because of this and other differences in data analysis, 19% of reported food GI values differed by >5 units from those calculated centrally. GI values in individual subjects were unrelated to age, sex, ethnicity, body mass index, or AUC but were negatively related to within-individual variation (P=0.033) expressed as the CV of the AUC for repeated reference food tests (refCV). The between-laboratory GI values (mean+/-SD) for cheese-puffs and fruit-leather were 74.3+/-10.5 and 33.2+/-7.2, respectively. The mean laboratory GI was related to refCV (P=0.003) and the type of restrictions on alcohol consumption before the test (P=0.006, r2=0.509 for model). The within-laboratory SD of GI was related to refCV (P<0.001), the glucose analysis method (P=0.010), whether glucose measures were duplicated (P=0.008), and restrictions on dinner the night before (P=0.013, r2=0.810 for model). CONCLUSIONS: The between-laboratory SD of the GI values is approximately 9. Standardized data analysis and low within-subject variation (refCV<30%) are required for accuracy. The results suggest that common misconceptions exist about which factors do and do not need to be controlled to improve precision. Controlled studies and cost-benefit analyses are needed to optimize GI methodology. The trial was registered at clinicaltrials.gov as NCT00260858.
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| 8. |
- Bjornvold, M., et al.
(författare)
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FOXP3 polymorphisms in type 1 diabetes and coeliac disease
- 2006
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Ingår i: J Autoimmun. - : Elsevier BV. - 0896-8411. ; 27:2, s. 140-4
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Tidskriftsartikel (refereegranskat)abstract
- The FOXP3 gene encodes a transcription factor thought to be essential for the development and function of T regulatory cells. Two previous studies have tested common polymorphisms in FOXP3 for association with type 1 diabetes (T1D) with conflicting results. The aim of our study was to see whether there is any evidence of association between the FOXP3 polymorphisms previously reported to be associated with T1D, in a Caucasian population regarding T1D and coeliac disease (CD). We further looked for evidence of interaction between FOXP3 polymorphisms and HLA-DR3 in conferring susceptibility to T1D. Initially, we analysed two microsatellites in the FOXP3 gene in 363 T1D nuclear families. Our results indicated an association between FOXP3 and T1D (global p=0.004) and a possible interaction between FOXP3 and the HLA-DR3-DQ2 susceptibility haplotype. We then genotyped an additional independent set of 826 T1D patients and 1459 controls as well as one CD dataset consisting of 325 families. A similar tendency was revealed in the CD family material (pnc=0.055 for the associated allele). On the other hand, we were unable to reproduce our initial findings in the T1D case-control dataset (global p=0.6). Our results suggest that the tested FOXP3 markers do not have any major impact on susceptibility for these diseases.
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| 9. |
- Soranzo, Nicole, et al.
(författare)
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A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:11, s. 38-1182
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Tidskriftsartikel (refereegranskat)abstract
- The number and volume of cells in the blood affect a wide range of disorders including cancer and cardiovascular, metabolic, infectious and immune conditions. We consider here the genetic variation in eight clinically relevant hematological parameters, including hemoglobin levels, red and white blood cell counts and platelet counts and volume. We describe common variants within 22 genetic loci reproducibly associated with these hematological parameters in 13,943 samples from six European population-based studies, including 6 associated with red blood cell parameters, 15 associated with platelet parameters and 1 associated with total white blood cell count. We further identified a long-range haplotype at 12q24 associated with coronary artery disease and myocardial infarction in 9,479 cases and 10,527 controls. We show that this haplotype demonstrates extensive disease pleiotropy, as it contains known risk loci for type 1 diabetes, hypertension and celiac disease and has been spread by a selective sweep specific to European and geographically nearby populations.
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| 10. |
- Amundsen, S. S., et al.
(författare)
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Association analysis of MYO9B gene polymorphisms with celiac disease in a Swedish/Norwegian cohort
- 2006
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Ingår i: Hum Immunol. - : Elsevier BV. - 0198-8859. ; 67:4-5, s. 341-5
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Tidskriftsartikel (refereegranskat)abstract
- Association between myosin IXB (MYO9B) gene variants and celiac disease (CD) has been reported in a study of a Dutch cohort. Six single nucleotide polymorphisms (SNPs) within the 3' part of the MYO9B gene showed significant genetic association and formed an associated haplotype. The current study aimed to replicate these findings in a Swedish/Norwegian cohort. Genotyping of the three SNPs which tagged the associated haplotype was performed in a CD family dataset (n = 326) and in an additional set of healthy controls (n = 562). Although our material provided reasonable power to detect the previously observed association, we were unable to replicate association with these SNPs. Lack of reproducibility could be explained by no or negligible contribution of MYO9B to the genetic predisposition to CD in the Swedish/Norwegian population. Alternatively, it might be due to variable linkage disequilibria in distinct populations in the tested SNPs and a causative mutation yet to be identified or to false positive findings (type I error) in the Dutch study.
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| 11. |
- Bombelli, A., et al.
(författare)
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An outlook on the Sub-Saharan Africa carbon balance
- 2009
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Ingår i: Biogeosciences. - 1726-4189. ; 6:10, s. 2193-2205
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Tidskriftsartikel (refereegranskat)abstract
- This study gives an outlook on the carbon balance of Sub-Saharan Africa (SSA) by presenting a summary of currently available results from the project CarboAfrica (namely net ecosystem productivity and emissions from fires, deforestation and forest degradation, by field and model estimates) supplemented by bibliographic data and compared with a new synthesis of the data from national communications to UNFCCC. According to these preliminary estimates the biogenic carbon balance of SSA varies from 0.16 Pg C y(-1) to a much higher sink of 1.00 Pg C y(-1) (depending on the source data). Models estimates would give an unrealistic sink of 3.23 Pg C y(-1), confirming their current inadequacy when applied to Africa. The carbon uptake by forests and savannas (0.34 and 1.89 Pg C y(-1), respectively,) are the main contributors to the resulting sink. Fires (0.72 Pg C y(-1)) and deforestation (0.25 Pg C y(-1)) are the main contributors to the SSA carbon emissions, while the agricultural sector and forest degradation contributes only with 0.12 and 0.08 Pg C y(-1), respectively. Savannas play a major role in shaping the SSA carbon balance, due to their large extension, their fire regime, and their strong interannual NEP variability, but they are also a major uncertainty in the overall budget. Even if fossil fuel emissions from SSA are relative low, they can be crucial in defining the sign of the overall SSA carbon balance by reducing the natural sink potential, especially in the future. This paper shows that Africa plays a key role in the global carbon cycle system and probably could have a potential for carbon sequestration higher than expected, even if still highly uncertain. Further investigations are needed, particularly to better address the role of savannas and tropical forests and to improve biogeochemical models. The CarboAfrica network of carbon measurements could provide future unique data sets for better estimating the African carbon balance.
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| 12. |
- Fiessinger, J. N., et al.
(författare)
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Ximelagatran vs low-molecular-weight heparin and warfarin for the treatment of deep vein thrombosis: a randomized trial
- 2005
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Ingår i: Jama. - 1538-3598. ; 293:6, s. 681-9
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Ximelagatran, an oral direct thrombin inhibitor with a rapid onset of action and predictable antithrombotic effect, has the potential to be a simple therapeutic alternative to current standard treatment of acute venous thromboembolism. OBJECTIVE: To compare the efficacy and safety of ximelagatran with standard enoxaparin/warfarin treatment for the prevention of recurrent venous thromboembolism. DESIGN, SETTING, AND PATIENTS: Randomized, double-blind, noninferiority trial (Thrombin Inhibitor in Venous Thromboembolism [THRIVE] Treatment Study) of 2489 patients with acute deep vein thrombosis, of whom approximately one third had concomitant pulmonary embolism. The study was conducted at 279 centers in 28 countries from September 2000 through December 2002. INTERVENTIONS: Patients were randomized to receive 6 months of treatment with either oral ximelagatran, 36 mg twice daily, or subcutaneous enoxaparin, 1 mg/kg twice daily, for 5 to 20 days followed by warfarin adjusted to maintain an international normalized ratio of 2.0 to 3.0. MAIN OUTCOME MEASURES: Recurrent venous thromboembolism, bleeding, and mortality. RESULTS: Venous thromboembolism recurred in 26 of the 1240 patients assigned to receive ximelagatran (estimated cumulative risk, 2.1%) and in 24 of the 1249 patients assigned to receive enoxaparin/warfarin (2.0%). The absolute difference between ximelagatran and enoxaparin/warfarin was 0.2% (95% confidence interval [CI], -1.0% to 1.3%). This met the prespecified criterion for noninferiority. Corresponding values for major bleeding were 1.3% and 2.2% (difference, -1.0%; 95% CI, -2.1% to 0.1%), and for mortality were 2.3% and 3.4% (difference, -1.1%; 95% CI, -2.4% to 0.2%). Alanine aminotransferase levels increased to more than 3 times the upper limit of normal in 119 patients (9.6%) and 25 patients (2.0%) receiving ximelagatran and enoxaparin/warfarin, respectively. Increased enzyme levels were mainly asymptomatic. Retrospective analysis of locally reported adverse events showed a higher rate of serious coronary events with ximelagatran (10/1240 patients) compared with enoxaparin/warfarin (1/1249 patients). CONCLUSIONS: Oral ximelagatran administered in a fixed dose without coagulation monitoring, was as effective as enoxaparin/warfarin for treatment of deep vein thrombosis with or without pulmonary embolism and showed similar, low rates of bleeding. Increased levels of liver enzymes in 9.6% of ximelagatran-treated patients require regular monitoring; the mechanism requires further evaluation. Prospective assessment of coronary events in future studies is warranted.
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| 13. |
- Kamiyama, S., et al.
(författare)
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Extremely high quantum efficiency of donor-acceptor-pair emission in N-and-B-doped 6H-SiC
- 2006
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Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 99:9
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Tidskriftsartikel (refereegranskat)abstract
- High-efficiency visible light emission in N-and-B-doped 6H-SiC epilayers was observed in photoluminescence measurements at room temperature. The orange-yellow light emission due to the recombination of donor-acceptor pairs (DAPs) has a broad spectrum with a peak wavelength of 576 nm and a full width at half maximum of 110 nm at 250 K. The high B concentration of more than 1018 cm-3 improves the emission efficiency of the DAP recombination at a high temperature. Compared with the photoluminescence spectrum of GaN at 10 K, a high quantum efficiency of 95% was estimated for the highly B-doped sample. From time-resolved photoluminescence measurements, a DAP recombination time of 5.0 ms was obtained, which is in good agreement with the calculated value by the rate equation with the assumption of a 95% internal quantum efficiency. This is quite promising as a light-emitting medium by optical pumping, as well as monolithic light sources combined with nitride-based light-emitting diodes grown on the DA-doped SiC epilayer. © 2006 American Institute of Physics.
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| 14. |
- Perry, H E, et al.
(författare)
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A novel study of association between Neisseria gonorrhoeae and the human carbohydrate blood groups.
- 2007
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Ingår i: Immunohematology / American Red Cross. - 0894-203X. ; 23:3, s. 100-4
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of association of ABO blood groups with gonorrhea have shown contradictory results. Despite the interdependencies of ABO, Lewis, and secretor systems, none of the previous studies examined the combined effect of these systems on their proposed association with gonorrhea. This study attempted to redress that and used genotyping in addition to RBC phenotyping to determine correct tissue phenotypes. Samples from 131 gonorrhea-positive individuals and from 175 gonorrhea-negative individuals were typed for ABO and Lewis using routine antisera. Secretor and Lewis genotyping was performed to ensure accurate determination of ABO and Lewis phenotypes. Chi-square and probability values were used to examine whether there is an association of ABO, Lewis, and secretor systems with gonorrhea infection. Neither single nor combined statistical analysis of data sets yielded a significant association of ABO, Lewis, and secretor phenotypes with Neisseria gonorrhoeae. Nevertheless, this study is an example of the approach that should be taken when examining microbial associations with ABO antigens, in turn influenced by coexpression and modification by the interdependent systems of Lewis and secretor, in mucosal tissues.
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| 15. |
- Adamovic, Svetlana, 1965, et al.
(författare)
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Fine mapping study in Scandinavian families suggests association between coeliac disease and haplotypes in chromosome region 5q32.
- 2008
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Ingår i: Tissue Antigens. - : Wiley. - 1399-0039 .- 0001-2815. ; 71:1, s. 27-34
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Tidskriftsartikel (refereegranskat)abstract
- The previous genome-wide scan in Scandinavian families supported earlier evidence for linkage of a region on chromosome 5 (5q31–33) to coeliac disease. This study deals with further genetic mapping of an 18 cM region, spanning from marker GAh18A (131.87 Mb) to D5S640 (149.96 Mb). Linkage and association analyses were performed in a two-step approach. First, seven microsatellites were added. Strong evidence for linkage was obtained with a Zlr score of 3.96, Pnc = 4 × 10−5 at marker D5S436. The strongest association was with a haplotype consisting of the markers D5S2033 and D5S2490 (Pnc < 0.001). In the second step, we added 17 microsatellites and 69 single nucleotide polymorphisms (SNPs) to the analysis. These markers were located close to or within candidate genes across the region of approximately 7 Mb beneath the linkage peak marked by D5S2017 and D5S812. A substantial increase of the linkage signal with a maximum Zlr score of 4.6 at marker rs1972644 (Pnc = 2 × 10−6) was obtained and several SNPs showed association. Seven SNPs that individually showed the strongest association were genotyped in a second independent family sample set (225 trios). In the trio family sample as well as in the multiplex family sample, the strongest association was found with SNPs within the region flanked by the associated microsatellites D5S2033 and D5S2490 at 5q32.
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| 16. |
- Bennett, N. S., et al.
(författare)
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Enhanced n-type dopant solubility in tensile-strained Si
- 2008
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Ingår i: Thin Solid Films. - : Elsevier BV. - 0040-6090 .- 1879-2731. ; 517:1, s. 331-333
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Tidskriftsartikel (refereegranskat)abstract
- The creation of highly conductive ultrashallow-doped regions in strained Si is a key requirement for future Si based devices. It is shown that in the presence of tensile strain, Sb becomes a contender to replace As in strain-engineered CMOS devices due to advantages in sheet resistance. While strain reduces resistance for both As and Sb; a result of enhanced electron mobility, the reduction is significantly larger for Sb due to an increase in donor activation. Differential Hall measurements suggest this is a consequence of a strain-induced Sb solubility enhancement following solid-phase epitaxial regrowth, increasing Sb solubility in Si to levels approaching 10(21) cm(-3). Experiments highlight the importance of maintaining substrate strain during thermal annealing to maintain this high Sb activation.
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| 17. |
- Raval, Aparna, et al.
(författare)
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Downregulation of death-associated protein kinase 1 (DAPK1) in chronic lymphocytic leukemia
- 2007
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Ingår i: Cell. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 129:5, s. 879-890
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Tidskriftsartikel (refereegranskat)abstract
- The heritability of B cell chronic lymphocytic leukemia (CLL) is relatively high; however, no predisposing mutation has been convincingly identified. We show that loss or reduced expression of death-associated protein kinase 1 (DAPK1) underlies cases of heritable predisposition to CLL and the majority of sporadic CLL. Epigenetic silencing of DAPK1 by promoter methylation occurs in almost all sporadic CLL cases. Furthermore, we defined a disease haplotype, which segregates with the CLL phenotype in a large family. DAPK1 expression of the CLL allele is downregulated by 75% in germline cells due to increased HOXB7 binding. In the blood cells from affected family members, promoter methylation results in additional loss of DAPK1 expression. Thus, reduced expression of DAPK1 can result from germline predisposition, as well as epigenetic or somatic events causing or contributing to the CLL phenotype.
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| 18. |
- Svensson, Lola, 1948, et al.
(författare)
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Novel glycolipid variations revealed by monoclonal antibody immunochemical analysis of weak ABO subgroups of A.
- 2005
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Ingår i: Vox sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 89:1, s. 27-38
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: The chemical basis of the subgroups of A is largely unknown. We used thin-layer chromatography immunochemical staining techniques together with a range of characterized monoclonal reagents to analyse glycolipids isolated from a variety of weak subgroups. MATERIALS AND METHODS: Glycolipids isolated from red cells collected from nine genetically defined individuals of the rare subgroups of A, including a novel A(3) allele (A(2) 539G>A) not described previously, were subjected to a highly sensitive thin-layer chromatographic immunochemical analysis. RESULTS: Semicharacterized monoclonal antibodies revealed that, in addition to the expected quantitative differences between common phenotypes and the weak subgroups, qualitative glycolipid differences (or at least an apparent qualitative basis), caused by major changes in the ratios of different structures exist. Specifically it was found that the weakest A-expressing samples (A(el) phenotype) appeared to express an unusual A structure in the 8-12 sugar region. Variable expression of several structures in one of the A weak samples were suggestive of novel blood group A structures. CONCLUSIONS: Although no structural characterization could be undertaken, the results are clearly indicative that the variant glycosyltransferases of the rare ABO subgroups are not only inefficient, but they may potentially synthesize novel ABO structures.
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| 19. |
- Abdi, Y., et al.
(författare)
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Light-emitting nano-porous silicon structures fabricated using a plasma hydrogenation technique
- 2005
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Ingår i: Materials Science and Engineering B: Solid-State Materials for Advanced Technology. - : Elsevier BV. - 0921-5107. ; 124-125:SUPPL., s. 483-487
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Tidskriftsartikel (refereegranskat)abstract
- The preparation of porous silicon films by DC-plasma hydrogenation and subsequent annealing of amorphous silicon films on silicon and glass substrates is reported for the first time. The effects of varying plasma power and annealing temperatures have been investigated and characterized by scanning-electron microscopy, transmission-electron microscopy, and photoluminescence. A plasma density of about 5.5 W/m2 and hydrogenation-annealing temperatures of about 400 °C was found to be suitable for the formation of nano-crystalline silicon films with grain diameters of the order of 3-10 nm. The intensity and wavelength of the emitted visible light were found to depend on the hydrogenation and annealing conditions, and patterning of the silicon films using standard lithography allowed the creation of light-emitting patterns.
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| 20. |
- Bernstein, Henry H., et al.
(författare)
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Comparison of the safety and immunogenicity of a refrigerator-stable versus a frozen formulation of ProQuad (measles, mumps, rubella, and varicella virus vaccine live)
- 2007
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 119:6, s. 1299-1305
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Tidskriftsartikel (refereegranskat)abstract
- Objective. A refrigerator-stable formulation of ProQuad has been developed to expand the utility of ProQuad to areas in which maintenance of a frozen cold chain (- 15 degrees C or colder) during storage and transport may not be feasible. The objective of this study was to demonstrate that the immunogenicity and safety profiles of a refrigerator-stable formulation of ProQuad are similar to the recently licensed frozen formulation. Methods. In this double-blind, randomized, multicenter study, healthy 12- to 23-month- old children with negative vaccination and clinical histories for measles, mumps, rubella, varicella, and zoster were vaccinated with either the refrigerator-stable formulation of ProQuad (N = 1006) or the frozen formulation of ProQuad (N = 513). Patients were followed for 42 days after vaccination for adverse experiences. Immunogenicity was evaluated 6 weeks after vaccination. Results. The refrigerator-stable formulation of ProQuad was generally well tolerated. The incidence of adverse experiences was similar between groups. No vaccine-related serious adverse experiences were reported. For both groups, the response rate was >= 97.7% for measles, mumps, and rubella, and the percentage of patients with a varicella zoster virus antibody titer of >= 5 U/mL glycoprotein antigen-based enzyme-linked immunosorbent assay after vaccination was >= 88.8%. The geometric mean titers for all antigens were numerically slightly higher in patients who received the refrigerator-stable formulation. Conclusions. The refrigerator-stable formulation of ProQuad is generally well tolerated, highly immunogenic, and noninferior in terms of postvaccination antibody responses. This refrigerator-stable formulation may improve ease of vaccine administration, increase use of the vaccine throughout the world because of its improved storage conditions, and replace the frozen formulation of ProQuad or any dose of M-M-RII and Varivax in routine practice.
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| 21. |
- Cullberg, M., et al.
(författare)
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Pharmacokinetics of ximelagatran and relationship to clinical response in acute deep vein thrombosis
- 2005
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Ingår i: Clin Pharmacol Ther. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 77:4, s. 279-90
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Our objective was to characterize the pharmacokinetics of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, and the relationship between melagatran exposure and clinical outcome in patients with acute deep vein thrombosis. METHODS: A population pharmacokinetic analysis was performed on samples from patients with deep vein thrombosis participating in a randomized dose-finding study (THRombin Inhibitor in Venous thrombo-Embolism [THRIVE I]). Patients received fixed doses of oral ximelagatran (24, 36, 48, or 60 mg twice daily) for 12 to 16 days. Thrombus size was evaluated by venography before and after treatment. Exposure-response curves were characterized for the probability of regression, no change, and progression of the thrombus extension and of having a bleeding-related event, by use of logistic regression models. RESULTS: The pharmacokinetics of melagatran (1836 samples in 264 patients) was predictable, without significant time or dose dependencies. Clearance after oral administration (population mean, 27.3 L/h) was correlated with creatinine clearance (P < 10(-6)), and volume of distribution (population mean, 176 L) was correlated with body weight (P = 2 x 10(-5)). Gender, age, or smoking did not significantly influence melagatran pharmacokinetics after the influence of renal function and body weight was accounted for. Unexplained interpatient variability values in total plasma clearance and bioavailability were 19% and 21%, respectively. The median area under the plasma melagatran concentration versus time curve across all patients and dose levels was 3.22 h x micromol/L (5th-95th percentiles, 1.35-7.69). There was no significant relationship between area under the plasma concentration versus time curve and change in thrombus extension (P = .59) or bleeding-related events (P = .77), and the estimated exposure-response curves were relatively flat. CONCLUSIONS: The pharmacokinetics of melagatran in patients with acute deep vein thrombosis was predictable after oral ximelagatran administration. Shallow exposure-response curves for efficacy and bleeding indicate that there is no need for individualized dosing or therapeutic drug monitoring in the patient population studied.
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| 22. |
- Donfield, Sharyne M., et al.
(författare)
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Delays in maturation among adolescents with hemophilia and a history of inhibitors
- 2007
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 110:10, s. 3656-3661
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Tidskriftsartikel (refereegranskat)abstract
- Inhibitory antibodies to factors VIII or IX have the potential to affect a broad range of outcomes among people with hemophilia; however, their possible effect on growth and maturation has not been explored. We evaluated skeletal maturation (bone age), pubertal progression, serum testosterone levels, height velocity, and stature in the multicenter Hemophilia Growth and Development Study. A total of 333 children and adolescents (mean age, 12.4 years) were enrolled from 1989 to 1990 and followed for 7 years. Of these, 18% (n = 60) had a history of inhibitors. Bone age among HIV- adolescents with a history of inhibitors lagged 9 or more months behind those without inhibitors at every age from 12 to 15 years. Those with a history of inhibitors were older at every Tanner stage transition, attained a lower maximum growth velocity, and their serum testosterone levels were significantly lower compared with those without inhibitors. Delays were greater among HIV+ patients with a history of inhibitors compared with those without inhibitors; however, the differences were generally small and not statistically significant. The results of this investigation underscore the importance of monitoring the growth and maturation of children and adolescents with hemophilia, particularly those with inhibitors.
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| 23. |
- Erichsen, Martina M, et al.
(författare)
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Clinical, Immunological, and Genetic Features of Autoimmune Primary Adrenal Insufficiency: Observations from a Norwegian Registry.
- 2009
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 94, s. 4882-4890
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Primary adrenal insufficiency [Addison's disease (AD)] is rare, and systematic studies are few, mostly conducted on small patient samples. We aimed to determine the clinical, immunological, and genetic features of a national registry-based cohort. Design: Patients with AD identified through a nationwide search of diagnosis registries were invited to participate in a survey of clinical features, health-related quality of life (HRQoL), autoantibody assays, and human leukocyte antigen (HLA) class II typing. Results: Of 664 registered patients, 64% participated in the study. The prevalence of autoimmune or idiopathic AD in Norway was 144 per million, and the incidence was 0.44 per 100,000 per year (1993-2007). Familial disease was reported by 10% and autoimmune comorbidity by 66%. Thyroid disease was most common (47%), followed by type 1 diabetes (12%), vitiligo (11%), vitamin B12 deficiency (10%), and premature ovarian insufficiency (6.6% of women). The mean daily treatment for AD was 40.5 mg cortisone acetate and 0.1 mg fludrocortisone. The mean Short Form 36 vitality scores were significantly diminished from the norm (51 vs. 60), especially among those with diabetes. Concomitant thyroid autoimmunity did not lower scores. Anti-21-hydroxylase antibodies were found in 86%. Particularly strong susceptibility for AD was found for the DR3-DQ2/ DRB1*0404-DQ8 genotype (odds ratio, 32; P = 4 x 10(-17)), which predicted early onset. Conclusions: AD is almost exclusively autoimmune, with high autoimmune comorbidity. Both anti-21-hydroxylase antibodies and HLA class II can be clinically relevant predictors of AD. HRQoL is reduced, especially among diabetes patients, whereas thyroid disease did not have an impact on HRQoL. Treatment modalities that improve HRQoL are needed.
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| 24. |
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| 25. |
- Isoya, J, et al.
(författare)
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Pulsed EPR studies of phosphorus shallow donors in diamond and SiC
- 2006
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Ingår i: Physica B, Vols. 376-377. - : Elsevier BV. ; , s. 358-361
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Konferensbidrag (refereegranskat)abstract
- Phosphorus shallow donors having the symmetry lower than T-d are studied by pulsed EPR. In diamond:P and 3C-SiC:P, the symmetry is lowered to D-2d and the density of the donor wave function on the phosphorus atom exhibits a predominant p-character. In 4H-SiC:P with the site symmetry of C-3v, the A(1) ground state of the phosphorus donors substituting at the quasi-cubic site of silicon shows an axial character of the distribution of the donor wave function in the vicinity of the phosphorus atom. (c) 2005 Elsevier B.V. All rights reserved.
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| 26. |
- Koliopoulou, S, et al.
(författare)
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Metal nano-floating gate memory devices fabricated at low temperature
- 2006
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Ingår i: Microelectronic Engineering. - : Elsevier BV. - 0167-9317 .- 1873-5568. ; 83:4-9, s. 1563-1566
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Tidskriftsartikel (refereegranskat)abstract
- In this communication, we report on the realization of low-temperature processed Electrically Erasable Programmable Read-Only Memory (EEPROM) like device with embedded gold nanoparticles. The realization is based on the fabrication of a V-groove SiGe Metal Oxide Semiconductor Field Effect Transistor (MOSFET), the functionalization of a gate oxide followed by self-assembly of gold nanoparticles and finally, the deposition of an organic insulator by Langmuir-Blodgett (LB) technique. Such structures were processed at a temperature lower than 400 degrees C. The electrical characteristics of the final hybrid Metal Insulator Semiconductor FET (MISFET) memory cells were evaluated in terms of memory window and program/erase voltage pulses. A model describing the memory characteristics, based on the electronic properties of the gate stack materials, is presented.
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| 27. |
- Lindh, Rebecka, et al.
(författare)
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Multisite phosphorylation of adipocyte and hepatocyte phosphodiesterase 3B.
- 2007
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Ingår i: Biochimica et Biophysica Acta: Molecular Cell Research. - : Elsevier BV. - 0167-4889. ; 1773:4, s. 584-592
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Tidskriftsartikel (refereegranskat)abstract
- Phosphodiesterase 3B (PDE3B) is an important component of insulin and cAMP-dependent signalling pathways. In order to study phosphorylation of PDE3B, we have used an adenoviral system to express recombinant flag-tagged PDE3B in primary rat adipocytes and H4IIE hepatoma cells. Phosphorylation of PDE3B after treatment of cells with insulin, cAMP-increasing agents, or the phosphatase inhibitor, calyculin A was analyzed by two-dimensional tryptic phosphopeptide mapping and mass spectrometry. We found that PDE3B is multisite phosphorylated in adipocytes and H4IIE hepatoma cells in response to all these stimuli. Several sites were identified; serine (S)273, S296, S421, S424/5, S474 and S536 were phosphorylated in adipocyte as well as H4IIE hepatoma cells whereas S277 and S507 were phosphorylated in hepatoma cells only. Several of the sites were phosphorylated by insulin as well as cAMP-increasing hormones indicating integration of the two signalling pathways upstream of PDE3B, maybe at the level of protein kinase B.
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| 28. |
- Martin, Thomas N., et al.
(författare)
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ST-Segment deviation analysis of the admission 12-lead electrocardiogram as an aid to early diagnosis of acute myocardial infarction with a cardiac magnetic resonance imaging gold standard
- 2007
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 50:11, s. 1021-1028
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study was to validate existing 12-lead electrocardiographic (ECG) ST-segment elevation myocardial infarction (STEMI) criteria in the diagnosis of acute myocardial infarction (AMI) and the application of similar ST-segment depression (STEM I-equivalent) criteria with contrast-enhanced cardiac magnetic resonance imaging (ceMRI) as the diagnostic gold standard. Background The admission ECG is the cornerstone in the diagnosis of AMI, and ceMRI is a new diagnostic gold standard that can be used to validate existing and novel 12-lead ECG criteria. Methods One hundred fifty-one consecutive patients with their first hospital admission for chest pain underwent ceMRI. The 116 patients without ECG confounding factors were included in this study, and AMI was confirmed in 58 (50%). The admission ECG was evaluated on the basis of the lead distribution of ST-segment deviation according to current American College of Cardiology/European Society of Cardiology (ACC/ESC) guidelines. Results A sensitivity of 50% and specificity of 97% for AMI were achieved with the currently applied ST-segment elevation criteria. Consideration of ST-segment depression in addition to elevation increased sensitivity for detection of AMI from 50% to 84% (p < 0.0001) but only decreased specificity from 97% to 93% (p = 0.50). There were no significant differences in AMI location or size between patients meeting the 12-lead ACC/ESC ST-segment elevation criteria and those only meeting the ST-segment depression criteria. Conclusions In patients admitted to hospital with possible AMI, the consideration of both ST-segment elevation and depression in the standard 12 lead-ECG recording significantly increases the sensitivity for the detection of AMI with only a slight decrease in the specificity.
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| 29. |
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| 30. |
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| 31. |
- Svensson, Lola, 1948, et al.
(författare)
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Blood group A(1) and A(2) revisited: an immunochemical analysis.
- 2009
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Ingår i: Vox sanguinis. - : Wiley. - 1423-0410 .- 0042-9007. ; 96:1, s. 56-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVE: The basis of blood group A(1) and A(2) phenotypes has been debated for many decades, and still the chemical basis is unresolved. The literature generally identifies the glycolipid chemical differences between blood group A(1) and A(2) phenotypes as being poor or no expression of A type 3 and A type 4 structures on A(2) red cells, although this assertion is not unanimous. MATERIALS AND METHODS: Using purified glycolipids and specific monoclonal antibodies, we revisited the glycolipid basis of the A(1) and A(2) phenotypes. Purified glycolipids were extracted from four individual A(1) and four individual A(2) blood units. One blood unit from an A weak subgroup was also included. Monoclonal anti-A reagents including those originally used to define the basis of A(1) and A(2) phenotypes were used in a thin layer chromatography - enzyme immunoassay to identify the presence of specific glycolipids. RESULTS: A type 3 glycolipid structures were found to be present in large amounts in all phenotypes. In contrast, the A type 4 glycolipid structure was virtually undetectable in the A(2) phenotype, but was present in the A(1) and A subgroup samples. CONCLUSION: The major glycolipid difference between the A(1) and A(2) phenotypes is the dominance of A type 4 glycolipids in the A(1) phenotype.
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| 32. |
- Vesikari, Timo, et al.
(författare)
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Safety and efficacy of a pentavalent human-bovine (WC3) reassortant rotavirus vaccine.
- 2006
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Ingår i: N Engl J Med. - 1533-4406. ; 354:1, s. 23-33
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Rotavirus is a leading cause of childhood gastroenteritis and death worldwide. METHODS: We studied healthy infants approximately 6 to 12 weeks old who were randomly assigned to receive three oral doses of live pentavalent human-bovine (WC3 strain) reassortant rotavirus vaccine containing human serotypes G1, G2, G3, G4, and P[8] or placebo at 4-to-10-week intervals in a blinded fashion. Active surveillance was used to identify subjects with serious adverse and other events. RESULTS: The 34,035 infants in the vaccine group and 34,003 in the placebo group were monitored for serious adverse events. Intussusception occurred in 12 vaccine recipients and 15 placebo recipients within one year after the first dose including six vaccine recipients and five placebo recipients within 42 days after any dose (relative risk, 1.6; 95 percent confidence interval, 0.4 to 6.4). The vaccine reduced hospitalizations and emergency department visits related to G1-G4 rotavirus gastroenteritis occurring 14 or more days after the third dose by 94.5 percent (95 percent confidence interval, 91.2 to 96.6 percent). In a nested substudy, efficacy against any G1-G4 rotavirus gastroenteritis through the first full rotavirus season after vaccination was 74.0 percent (95 percent confidence interval, 66.8 to 79.9 percent); efficacy against severe gastroenteritis was 98.0 percent (95 percent confidence interval, 88.3 to 100 percent). The vaccine reduced clinic visits for G1-G4 rotavirus gastroenteritis by 86.0 percent (95 percent confidence interval, 73.9 to 92.5 percent). CONCLUSIONS: This vaccine was efficacious in preventing rotavirus gastroenteritis, decreasing severe disease and health care contacts. The risk of intussusception was similar in vaccine and placebo recipients. (ClinicalTrials.gov number, NCT00090233.) Copyright 2006 Massachusetts Medical Society.
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| 33. |
- Yin, Henry H, et al.
(författare)
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Ethanol reverses the direction of long-term synaptic plasticity in the dorsomedial striatum.
- 2007
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Ingår i: The European journal of neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 25:11, s. 3226-32
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Tidskriftsartikel (refereegranskat)abstract
- The striatum is a critical structure for the control of voluntary behaviour, and striatal synaptic plasticity has been implicated in instrumental learning. As ethanol consumption can cause impairments in cognition, learning, and action selection, it is important to understand the effects of this drug on striatal function. In this study we examined the effects of ethanol on long-term synaptic plasticity in the dorsomedial striatum (DMS), a striatal subregion that plays a central role in the acquisition and selection of goal-directed actions. Ethanol was found to impair N-methyl-d-aspartic acid receptor (NMDAR)-dependent long-term potentiation (LTP) dose-dependently in the DMS, and to promote long-term depression (LTD) at the highest concentration (50 mm) used. These results suggest that ethanol, at a concentration usually associated with mild intoxication, could significantly change experience-dependent modification of corticostriatal circuits underlying the learning of goal-directed instrumental actions.
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