| 1. |
- Gerlofs-Nijland, Miriam E, et al.
(author)
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Toxicity of coarse and fine particulate matter from sites with contrasting traffic profiles.
- 2007
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In: Inhalation Toxicology. - : Taylor & Francis. - 0895-8378 .- 1091-7691. ; 19:13, s. 1055-69
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Journal article (peer-reviewed)abstract
- Residence in urban areas with much traffic has been associated with various negative health effects. However, the contribution of traffic emissions to these adverse health effects has not been fully determined. Therefore, the objective of this in vivo study is to compare the pulmonary and systemic responses of rats exposed to particulate matter (PM) obtained from various locations with contrasting traffic profiles. Samples of coarse (2.5 mu m-10 mu m) and fine (0.1 mu m-2.5 mu m) PM were simultaneously collected at nine sites across Europe with a high-volume cascade impactor. Six PM samples from various locations were selected on the basis of contrast in in vitro analysis, chemical composition, and traffic profiles. We exposed spontaneously hypertensive (SH) rats to a single dose (3 mg PM/kg body weight or 10 mg PM/kg body weight) of either coarse or fine PM by intratracheal instillation. We assessed changes in biochemical markers, cell differentials, and histopathological changes in the lungs and blood 24 h postexposure. The dose-related adverse effects that both coarse and fine PM induced in the lungs and vascular system were mainly related to cytotoxicity, inflammation, and blood viscosity. We observed clear differences in the extent of these responses to PM from the various locations at equivalent dose levels. There was a trend that suggests that samples from high-traffic sites were the most toxic. It is likely that the toxicological responses of SH rats were associated with specific PM components derived from brake wear (copper and barium), tire wear (zinc), and wood smoke (potassium).
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| 2. |
- Lucking, Andrew J, et al.
(author)
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Diesel exhaust inhalation increases thrombus formation in man
- 2008
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 29:24, s. 3043-3051
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Journal article (peer-reviewed)abstract
- AIMS: Although the mechanism is unclear, exposure to traffic-derived air pollution is a trigger for acute myocardial infarction (MI). The aim of this study is to investigate the effect of diesel exhaust inhalation on platelet activation and thrombus formation in men. METHODS AND RESULTS: In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dilute diesel exhaust (350 microg/m(3)) and filtered air. Thrombus formation, coagulation, platelet activation, and inflammatory markers were measured at 2 and 6 h following exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber. Platelet activation was assessed by flow cytometry. Compared with filtered air, diesel exhaust inhalation increased thrombus formation under low- and high-shear conditions by 24% [change in thrombus area 2229 microm(2), 95% confidence interval (CI) 1143-3315 microm(2), P = 0.0002] and 19% (change in thrombus area 2451 microm(2), 95% CI 1190-3712 microm(2), P = 0.0005), respectively. This increased thrombogenicity was seen at 2 and 6 h, using two different diesel engines and fuels. Diesel exhaust also increased platelet-neutrophil and platelet-monocyte aggregates by 52% (absolute change 6%, 95% CI 2-10%, P = 0.01) and 30% (absolute change 3%, 95% CI 0.2-7%, P = 0.03), respectively, at 2 h following exposure compared with filtered air. CONCLUSION: Inhalation of diesel exhaust increases ex vivo thrombus formation and causes in vivo platelet activation in man. These findings provide a potential mechanism linking exposure to combustion-derived air pollution with the triggering of acute MI.
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| 3. |
- Maxwell, Karen L., et al.
(author)
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Protein folding : Defining a "standard" set of experimental conditions and a preliminary kinetic data set of two-state proteins
- 2005
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In: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 14, s. 602-16
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Journal article (peer-reviewed)abstract
- Recent years have seen the publication of both empirical and theoretical relationships predicting the rates with which proteins fold. Our ability to test and refine these relationships has been limited, however, by a variety of difficulties associated with the comparison of folding and unfolding rates, thermodynamics, and structure across diverse sets of proteins. These difficulties include the wide, potentially confounding range of experimental conditions and methods employed to date and the difficulty of obtaining correct and complete sequence and structural details for the characterized constructs. The lack of a single approach to data analysis and error estimation, or even of a common set of units and reporting standards, further hinders comparative studies of folding. In an effort to overcome these problems, we define here a "consensus" set of experimental conditions (25°C at pH 7.0, 50 mM buffer), data analysis methods, and data reporting standards that we hope will provide a benchmark for experimental studies. We take the first step in this initiative by describing the folding kinetics of 30 apparently two-state proteins or protein domains under the consensus conditions. The goal of our efforts is to set uniform standards for the experimental community and to initiate an accumulating, self-consistent data set that will aid ongoing efforts to understand the folding process.
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| 4. |
- Mills, Nicholas L, et al.
(author)
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Exposure to concentrated ambient particles does not affect vascular function in patients with coronary heart disease
- 2008
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In: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 116:6, s. 709-715
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Journal article (peer-reviewed)abstract
- BACKGROUND: Exposure to fine particulate air pollution is associated with increased cardiovascular morbidity and mortality. We previously demonstrated that exposure to dilute diesel exhaust causes vascular dysfunction in humans.OBJECTIVES: We conducted a study to determine whether exposure to ambient particulate matter causes vascular dysfunction. METHODS: Twelve male patients with stable coronary heart disease and 12 age-matched volunteers were exposed to concentrated ambient fine and ultrafine particles (CAPs) or filtered air for 2 hr using a randomized, double-blind cross-over study design. We measured peripheral vascular vasomotor and fibrinolytic function, and inflammatory variables-including circulating leukocytes, serum C-reactive protein, and exhaled breath 8-isoprostane and nitrotyrosine-6-8 hr after both exposures.RESULTS: Particulate concentrations (mean +/- SE) in the exposure chamber (190+/-37 microg/m(3)) were higher than ambient levels (31+/-8 microg/m(3)) and levels in filtered air (0.5+/-0.4 microg/m(3); p<0.001). Chemical analysis of CAPs identified low levels of elemental carbon. Exhaled breath 8-isoprostane concentrations increased after exposure to CAPs (16.9+/-8.5 vs. 4.9+/-1.2 pg/mL, p<0.05), but markers of systemic inflammation were largely unchanged. Although there was a dose-dependent increase in blood flow and plasma tissue plasminogen activator release (p<0.001 for all), CAPs exposure had no effect on vascular function in either group.CONCLUSIONS: Despite achieving marked increases in particulate matter, exposure to CAPs--low in combustion-derived particles--did not affect vasomotor or fibrinolytic function in either middle-aged healthy volunteers or patients with coronary heart disease. These findings contrast with previous exposures to dilute diesel exhaust and highlight the importance of particle composition in determining the vascular effects of particulate matter in humans.
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| 5. |
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| 6. |
- Ceberg, Sofie, et al.
(author)
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RapidArc™ treatment verification using polymer gel dosimetry
- 2009
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In: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 164:1
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Journal article (peer-reviewed)abstract
- The aim of this study was to verify a novel volumetric arc therapy technique, RapidArc". Polymer gel dosimetry system was used to measure the advanced inhomogeneous 3D dose distribution produced using the technique RapidArc". A preclinical installation of the novel beam delivery approach was set up on a linear accelerator at Rigshospitalet in Copenhagen. A prostate treatment plan was delivered to a 1.3 l nPAG gel phantom using one single arc rotation from 200 to 160 degrees, and a target dose of 3.3 Gy. Magnetic resonance imaging of the gel was carried out using the 1.5 T scanner and MATLAB was used for image processing and 3D rendering. The difference in relative absorbed dose between the treatment planning system (TPS) and gel measurement was calculated voxel by voxel within the 80% and the 95% isodose volume, respectively. Measurements agreed well with the TPS within the treated volume. Within both isodose volumes 90% of the voxels showed a deviation less or equal to 5%. This study shows that the 3D gel dosimetry system is a useful tool for dose verification of advanced treatment delivery techniques.
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| 7. |
- Gylvin, T., et al.
(author)
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Functional SOCS1 polymorphisms are associated with variation in obesity in whites
- 2009
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In: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902 .- 1463-1326. ; 11:3, s. 196-203
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Journal article (peer-reviewed)abstract
- The suppressor of cytokine signalling 1 (SOCS1) is a natural inhibitor of cytokine and insulin signalling pathways and may also play a role in obesity. In addition, SOCS1 is considered a candidate gene in the pathogenesis of both type 1 diabetes (T1D) and type 2 diabetes (T2D). The objective was to perform mutation analysis of SOCS1 and to test the identified variations for association to T2D-related quantitative traits, T2D or T1D. Mutation scanning was performed by direct sequencing in 27 white Danish subjects. Genotyping was carried out by TaqMan allelic discrimination. A total of more than 8100 individuals were genotyped. Eight variations were identified in the 5' untranslated region (UTR) region. Two of these had allele frequencies below 1% and were not further examined. The six other variants were analysed in groups of T1D families (n = 1461 subjects) and T2D patients (n = 1430), glucose tolerant first-degree relatives of T2D patients (n = 212) and normal glucose tolerant (NGT) subjects. The rs33977706 polymorphism (-820G > T) was associated with a lower body mass index (BMI) (p = 0.004). In a second study (n = 4625 NGT subjects), significant associations of both the rs33977706 and the rs243330 (-1656G > A) variants to obesity were found (p = 0.047 and p = 0.015) respectively. The rs33977706 affected both binding of a nuclear protein to and the transcriptional activity of the SOCS1 promoter, indicating a relationship between this polymorphism and gene regulation. This study demonstrates that functional variations in the SOCS1 promoter may associate with alterations in BMI in the general white population.
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| 8. |
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| 9. |
- Kjaergaard, Magnus, et al.
(author)
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Solution structure of recombinant somatomedin B domain from vitronectin produced in Pichia pastoris.
- 2007
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In: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 16:9
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Journal article (peer-reviewed)abstract
- The cysteine-rich somatomedin B domain (SMB) of the matrix protein vitronectin is involved in several important biological processes. First, it stabilizes the active conformation of the plasminogen activator inhibitor (PAI-1); second, it provides the recognition motif for cell adhesion via the cognate integrins (alpha(v)beta(3), alpha(v)beta(5), and alpha(IIb)beta(3)); and third, it binds the complex between urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR). Previous structural studies on SMB have used recombinant protein expressed in Escherichia coli or SMB released from plasma-derived vitronectin by CNBr cleavage. However, different disulfide patterns and three-dimensional structures for SMB were reported. In the present study, we have expressed recombinant human SMB by two different eukaryotic expression systems, Pichia pastoris and Drosophila melanogaster S2-cells, both yielding structurally and functionally homogeneous protein preparations. Importantly, the entire population of our purified, recombinant SMB has a solvent exposure, both as a free domain and in complex with PAI-1, which is indistinguishable from that of plasma-derived SMB as assessed by amide hydrogen ((1)H/(2)H) exchange. This solvent exposure was only reproduced by one of three synthetic SMB products with predefined disulfide connectivities corresponding to those published previously. Furthermore, this connectivity was also the only one to yield a folded and functional domain. The NMR structure was determined for free SMB produced by Pichia and is largely consistent with that solved by X-ray crystallography for SMB in complex with PAI-1.
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| 10. |
- Ravnsbaek, Dorthe, et al.
(author)
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A Series of Mixed-Metal Borohydrides
- 2009
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In: Angewandte Chemie (International edition). - : Wiley. - 1521-3773. ; 48:36, s. 6659-6663
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Journal article (peer-reviewed)
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