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Sökning: WFRF:(Blomberg David)

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1.
  • Cherif, Mariama K., et al. (författare)
  • Is Fc gamma receptor IIA (Fc gamma RIIA) polymorphism associated with clinical malaria and Plasmodium falciparum specific antibody levels in children from Burkina Faso?
  • 2015
  • Ingår i: Acta Tropica. - : Elsevier BV. - 0001-706X .- 1873-6254. ; 142, s. 41-46
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, the influences of Fc gamma RIIA polymorphism on susceptibility to malaria and antibody responses to Plasmodium falciparum antigens were analyzed in children. We recruited 96 healthy children between 3 and 10 years at the beginning of the high transmission season and we followed up for 5 months through the high transmission season to assess the parasitological, immunological and genetic endpoints in relation to clinical malaria status. There was a similar distribution of homozygous and heterozygous individuals carrying the Fc gamma RIIA-131R/R and Fc gamma RIIA-131R/H allele, whereas the number of Fc gamma RIIA-131H/H homozygous individuals was lower. P. falciparum infection frequency was not associated with the Fc gamma RIIa-131R/H polymorphism. Only IgG antibody responses to GLURP R0 showed a significant association between antibody levels and Fc gamma RIIA polymorphism (p = 0.02). IgG levels to MSP2a were significantly higher in children who did not experience any clinical malaria episode compared to those who experienced at least one malaria episode (p = 0.019). Cytophilic and non-cytophylic IgG subclass levels were higher in children without malaria than those who experienced at least one malaria episode. This difference was statistically significant for IgG1 to MSP3 (p = 0.003) and to MSP2a (p = 0.006); IgG3 to MSP2a (p = 0.007) and to GLURP R0 (p = 0.044); IgG2 to MSP2b (p = 0.007) and IgG4 to MSP3 (p = 0.051) and to MSP2a (p = 0.049). In this study, homozygous carriers of the Fc gamma RIIA-131R/R allele had higher malaria-specific antibody levels compare to the heterozygous carriers Fc gamma RIIA-131R/H alleles and to homozygous carriers of Fc gamma RIIA-131H/H alleles. The pre-existing antibodies responses were related to a reduced subsequent risk of clinical malaria.
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2.
  • Jallow, Muminatou, et al. (författare)
  • Genome-wide and fine-resolution association analysis of malaria in West Africa.
  • 2009
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; , s. 657-665
  • Tidskriftsartikel (refereegranskat)abstract
    • We report a genome-wide association (GWA) study of severe malaria in The Gambia. The initial GWA scan included 2,500 children genotyped on the Affymetrix 500K GeneChip, and a replication study included 3,400 children. We used this to examine the performance of GWA methods in Africa. We found considerable population stratification, and also that signals of association at known malaria resistance loci were greatly attenuated owing to weak linkage disequilibrium (LD). To investigate possible solutions to the problem of low LD, we focused on the HbS locus, sequencing this region of the genome in 62 Gambian individuals and then using these data to conduct multipoint imputation in the GWA samples. This increased the signal of association, from P = 4 x 10(-7) to P = 4 x 10(-14), with the peak of the signal located precisely at the HbS causal variant. Our findings provide proof of principle that fine-resolution multipoint imputation, based on population-specific sequencing data, can substantially boost authentic GWA signals and enable fine mapping of causal variants in African populations.
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3.
  • Langrish, Jeremy, et al. (författare)
  • Contribution of endothelin-1 to the vascular effects of diesel exhaust inhalation in humans
  • 2009
  • Ingår i: Hypertension. - Dallas, Tex. : The Association. - 0194-911X .- 1524-4563. ; 54:4, s. 910-915
  • Tidskriftsartikel (refereegranskat)abstract
    • Diesel exhaust inhalation impairs vascular function, and, althoughthe underlying mechanism remains unclear, endothelin (ET) 1and NO are potential mediators. The aim of this study was toidentify whether diesel exhaust inhalation affects the vascularactions of ET-1 in humans. In a randomized, double-blind crossoverstudy, 13 healthy male volunteers were exposed to either filteredair or dilute diesel exhaust (331±13 µg/m3). Plasmaconcentrations of ET-1 and big-ET-1 were determined at baselineand throughout the 24-hour study period. Bilateral forearm bloodflow was measured 2 hours after the exposure during infusionof either ET-1 (5 pmol/min) or the ETA receptor antagonist,BQ-123 (10 nmol/min) alone and in combination with the ETB receptorantagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure hadno effect on plasma ET-1 and big-ET-1 concentrations (P>0.05for both) or 24-hour mean blood pressure or heart rate (P>0.05for all). ET-1 infusion increased plasma ET-1 concentrationsby 58% (P<0.01) but caused vasoconstriction only after dieselexhaust exposure (–17% versus 2% after air; P<0.001).In contrast, diesel exhaust exposure reduced vasodilatationto isolated BQ-123 infusion (20% versus 59% after air; P<0.001)but had no effect on vasodilatation to combined BQ-123 and BQ-788administration (P>0.05). Diesel exhaust inhalation increasesvascular sensitivity to ET-1 and reduces vasodilatation to ETAreceptor antagonism despite unchanged plasma ET-1 concentrations.Given the tonic interaction between the ET and NO systems, weconclude that diesel exhaust inhalation alters vascular reactivityto ET-1 probably through its effects on NO bioavailability.
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4.
  • Liti, Gianni, et al. (författare)
  • Population genomics of domestic and wild yeasts.
  • 2009
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 458:7236, s. 337-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Since the completion of the genome sequence of Saccharomyces cerevisiae in 1996 (refs 1, 2), there has been a large increase in complete genome sequences, accompanied by great advances in our understanding of genome evolution. Although little is known about the natural and life histories of yeasts in the wild, there are an increasing number of studies looking at ecological and geographic distributions, population structure and sexual versus asexual reproduction. Less well understood at the whole genome level are the evolutionary processes acting within populations and species that lead to adaptation to different environments, phenotypic differences and reproductive isolation. Here we present one- to fourfold or more coverage of the genome sequences of over seventy isolates of the baker's yeast S. cerevisiae and its closest relative, Saccharomyces paradoxus. We examine variation in gene content, single nucleotide polymorphisms, nucleotide insertions and deletions, copy numbers and transposable elements. We find that phenotypic variation broadly correlates with global genome-wide phylogenetic relationships. S. paradoxus populations are well delineated along geographic boundaries, whereas the variation among worldwide S. cerevisiae isolates shows less differentiation and is comparable to a single S. paradoxus population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of S. cerevisiae consists of a few well-defined, geographically isolated lineages and many different mosaics of these lineages, supporting the idea that human influence provided the opportunity for cross-breeding and production of new combinations of pre-existing variations.
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5.
  • Mills, Nicholas L, et al. (författare)
  • Exposure to concentrated ambient particles does not affect vascular function in patients with coronary heart disease
  • 2008
  • Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences. - 0091-6765 .- 1552-9924. ; 116:6, s. 709-715
  • Tidskriftsartikel (refereegranskat)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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6.
  • Nunez, Joaquin C B, et al. (författare)
  • Ecological load and balancing selection in circumboreal barnacles.
  • 2021
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719. ; 38:2, s. 676-685
  • Tidskriftsartikel (refereegranskat)abstract
    • Acorn barnacle adults experience environmental heterogeneity at various spatial scales of their circumboreal habitat, raising the question of how adaptation to high environmental variability is maintained in the face of strong juvenile dispersal and mortality. Here we show that 4% of genes in the barnacle genome experience balancing selection across the entire range of the species. Many of these genes harbor mutations maintained across 2 million years of evolution between the Pacific and Atlantic oceans. These genes are involved in ion regulation, pain reception, and heat tolerance, functions which are essential in highly variable ecosystems. The data also reveal complex population structure within and between basins, driven by the trans-Arctic interchange and the last glaciation. Divergence between Atlantic and Pacific populations is high, foreshadowing the onset of allopatric speciation, and suggesting that balancing selection is strong enough to maintain functional variation for millions of years in the face of complex demography.
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7.
  • Arama, Charles, et al. (författare)
  • Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens
  • 2015
  • Ingår i: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 2:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to < 0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig) M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection.
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8.
  • Barath, Stefan, et al. (författare)
  • Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions
  • 2010
  • Ingår i: Particle and Fibre Toxicology. - : BioMed Central. - 1743-8977. ; 7:1, s. 19-
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 mug/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.MEASUREMENTS AND MAIN RESULTS: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).CONCLUSION: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.
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9.
  • Barath, Stefan, 1963- (författare)
  • Respiratory and cardiovascular effects of exposure to oxidative air pollutants
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Background: The negative effects of air pollution on morbidity and mortality have been known since the mid 20th century. The two most well known examples are the Meuse Valley disaster in the 1930’ies and the London black fog in December 1952. Whilst there are numerous epidemiological studies, in which associations between morbidity and mortality and high levels of pollutants have been reported, the underlying mechanisms are not clear. Two of the main air pollutants are particulate matter (PM) mostly emanating from diesel exhaust (DE), and ozone, both of which are highly oxidative. Exposure to DE has resulted in adverse effects both in the respiratory tract and in the cardiovascular system. High ozone levels have also been shown to be associated with increased admissions to hospital for respiratory as well as cardiovascular conditions. The main aim of this thesis was to investigate the respiratory and cardiovascular effects of a combination of exposures to ozone and DE. DE generated during the urban part of the standardized European Transient Cycle (ETC) was compared to DE generated by an idling engine. It was also evaluated whether an acute exposure to ozone would have any effects on the cardiovascular system as assessed by venous occlusion forearm plethysmography and heart rate variability (HRV). In addition, fraction of exhaled nitric oxide (FENO) was evaluated as a potential marker for acute exposure to ozone or DE. Methods: Four double-blind randomized cross-over exposure studies were conducted to investigate the effects of ozone and DE on both the respiratory tract and the vascular function in healthy volunteers. All of the exposures were performed in purposely built “walk-in” chambers with strictly controlled exposures. In the first study, the volunteers were exposed to DE (300µg/m3) generated by an idling engine or to air, for one hour in the morning and to ozone (200 ppb) for two hours in the afternoon. A bronchoscopy with bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed 24 hours after the initial exposure. In study II and III, an assessment of vascular function using venous occlusion forearm plethysmography was performed after an exposure to DE (250 µg/m3) generated under transient running conditions, compared to air exposure (study II) and ozone and air exposure (study III). HRV was assessed under a 24 hour period starting before each exposure (study III). In study IV, FENO measurements were conducted after DE and ozone exposures to investigate whether the previously established airway inflammation would be detectable by this non-invasive method. Results: DE exposure enhanced the established ozone-induced airway inflammation in terms of a pronounced neutrophilia in BW. DE generated under transient running conditions, impaired vascular function in healthy volunteers, whereas exposure to ozone did not. HRV were not altered by exposure to ozone. Exposure to DE caused a significant increase in FENO at the 10  (FENO10) and 50 (FENO50) mL/s flow rates at 6 hours post-exposure, but ozone exposure did not affect FENO at any flow rate or time point. Conclusion: We have tried to mimic real-life exposure to air pollutants. In the first study, an exposure to DE followed by an exposure to ozone in the afternoon resulted in an enhanced airway inflammation, suggesting an additive or synergistic effect, supporting the epidemiological findings of unfavorable effects of the combination of these two air pollutants. DE generated by an engine running at the urban part of the standardized European Transient Cycle impaired two important and complementary aspects of vascular function, the regulation of vascular tone and endogenous fibrinolysis. This has previously been shown with DE generated at idling conditions. This suggests that the mechanisms behind the adverse effects can be found in the properties of the particles and not in the gaseous components. In these studies, exposure to ozone did not impair vascular function in healthy subjects, or cause any alterations in HRV. This suggests that the epidemiological evidence for an increased risk of cardiovascular mortality following acute exposure to ozone might not be totally accurate. Previous controlled exposure studies with ozone have not shown an airway inflammation affecting the endothelium, at least not in the same time-frame as following DE exposure. FENO could possibly be a useful tool for assessing airway inflammation caused by DE, whereas the powerful oxidant ozone did not affect FENO. This suggests that the airway inflammatory effects caused by these two pollutants are regulated via different mechanisms.
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10.
  • Barath, Stefan, 1963-, et al. (författare)
  • Short-Term Exposure to Ozone Does Not Impair Vascular Function or Affect Heart Rate Variability in Healthy Young Men
  • 2013
  • Ingår i: Toxicological Sciences. - : Oxford University Press. - 1096-6080 .- 1096-0929. ; 135:2, s. 292-299
  • Tidskriftsartikel (refereegranskat)abstract
    • Air pollution exposure is associated with cardiovascular morbidity and mortality, yet the role of individual pollutants remains unclear. In particular, there is uncertainty regarding the acute effect of ozone exposure on cardiovascular disease. In these studies, we aimed to determine the effect of ozone exposure on vascular function, fibrinolysis, and the autonomic regulation of the heart. Thirty-six healthy men were exposed to ozone (300 ppb) and filtered air for 75min on two occasions in randomized double-blind crossover studies. Bilateral forearm blood flow (FBF) was measured using forearm venous occlusion plethysmography before and during intra-arterial infusions of vasodilators 2–4 and 6–8h after each exposure. Heart rhythm and heart rate variability (HRV) were monitored during and 24h after exposure. Compared with filtered air, ozone exposure did not alter heart rate, blood pressure, or resting FBF at either 2 or 6h. There was a dose-dependent increase in FBF with all vasodilators that was similar after both exposures at 2–4h. Ozone exposure did not impair vasomotor or fibrinolytic function at 6–8h but rather increased vasodilatation to acetylcholine (p = .015) and sodium nitroprusside (p = .005). Ozone did not affect measures of HRV during or after the exposure. Our findings do not support a direct rapid effect of ozone on vascular function or cardiac autonomic control although we cannot exclude an effect of chronic exposure or an interaction between ozone and alternative air pollutants that may be responsible for the adverse cardiovascular health effects attributed to ozone.
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11.
  • Bergström, Göran, 1964, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • Ingår i: Circulation. - Philadelphia : American Heart Association. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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12.
  • Bergström, Göran, et al. (författare)
  • Prevalence of Subclinical Coronary Artery Atherosclerosis in the General Population
  • 2021
  • Ingår i: Circulation. - : Wolters Kluwer. - 0009-7322 .- 1524-4539. ; 144:12, s. 916-929
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk.
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13.
  • Blomberg, David, et al. (författare)
  • Design, synthesis and biological evaluation of thrombin inhibitors based on a pyridine scaffold
  • 2007
  • Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 5:16, s. 2599-2605
  • Tidskriftsartikel (refereegranskat)abstract
    • A series of 2,4- disubstituted pyridine derivatives has been designed, synthesised and evaluated as thrombin inhibitors. A Grignard exchange reaction was used to introduce various benzoyl substituents in position 4 of the pyridine ring, where they serve as P3 residues in binding to thrombin. In position 2 of the pyridine ring, a para-amidinobenzylamine moiety was incorporated as P1 residue by an SNAr reaction using ammonia as nucleophile followed by a reductive amination. A crystal structure obtained for one of the compounds in the active site of thrombin revealed that the basic amidine group of the inhibitor was anchored to Asp 189 at the bottom of the S1 pocket. A comparison with melagatran, bound in the active site of thrombin, revealed a good shape match but lack of hydrogen bonding possibilities in the S2 - S3 region for the thrombin inhibitors reported in this study.
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14.
  • Blomberg, David, et al. (författare)
  • Synthesis and biological evaluation of leucine enkephalin turn mimetics
  • 2006
  • Ingår i: Organic and biomolecular chemistry. - : Royal Society of Chemistry (RSC). - 1477-0520 .- 1477-0539. ; 4:3, s. 416-423
  • Tidskriftsartikel (refereegranskat)abstract
    • A cyclic Leu-enkephalin mimetic containing a 7-membered ring, and two linear analogues, has been prepared on solid phase. In the cyclic mimetic the intramolecular (1–4) hydrogen bond found in crystalline Leu-enkephalin has been replaced by an ethylene bridge. In addition, the amide bond between Tyr1 and Gly2 has been replaced by a methylene ether isostere and Gly3 has been deleted. The two linear analogues both contain the methylene ether isostere instead of the Tyr1-Gly2 amide bond and the shorter of the two lacks Gly3. The three compounds, and a β-turn mimetic analogous to the 7-membered turn mimetic but with Gly3 included, were evaluated for specific binding to µ- and δ-opioid receptors in rat brain membranes. With the exception of the β-turn mimetic the three other Leu-enkephalin analogues all bound with varying affinity to the µ- and δ-opioid receptors. From the results it could be concluded that Leu-enkephalin binds in a turn conformation to the opiate receptors, but that this conformation is not a (1–4) β-turn.
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15.
  • Blomberg, David, et al. (författare)
  • Synthesis and conformational studies of a β-turn mimetic incorporated in Leu-enkephalin
  • 2004
  • Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 69:10, s. 3500-3508
  • Tidskriftsartikel (refereegranskat)abstract
    • A β-turn mimetic in which the four amino acids of a β-turn have been replaced by a 10-membered ring has been designed, synthesized, and subjected to conformational studies. In the mimetic, the intramolecular COi − HNi+3 hydrogen bond that is often found in β-turns has been replaced by an ethylene bridge. In addition, the amide bond between residues i and i + 1 was exchanged for a methylene ether isoster. Such a β-turn mimetic, based on the first four residues of Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu), was prepared in 15 steps. The synthesis relied on a β-azido alcohol prepared in five steps from Cbz-Tyr(tBu)-OH as a key, i-position building block. tert-Butyl bromoacetate, glycine, and a Phe-Leu dipetide were then used as building blocks for positions i + 1, i + 2, and i + 3, respectively. Conformational studies based on 1H NMR data showed that the β-turn mimetic was flexible, but that it resembled a type-II β-turn at low temperature. This low energy conformer closely resembled the structure determined for crystalline Leu-enkephalin.
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16.
  • Blomberg, David, et al. (författare)
  • Synthesis of a β-strand mimetic based on a pyridine scaffold
  • 2006
  • Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 62:47, s. 10937-10944
  • Tidskriftsartikel (refereegranskat)abstract
    • A synthetic route to a 2,4-disubstituted pyridine as a potential β-strand mimetic has been developed and applied in the synthesis of a tripeptidomimetic of Leu-Gly-Gly. The pyridine scaffold replaces the central glycine, and is substituted with analogues of leucine and glycine in positions 4 and 2, respectively. 2-Fluoro-4-iodopyridine was chosen as the functionalized scaffold and was substituted with protected leucinal in position 4 via a Grignard exchange reaction using iso-propyl magnesium chloride. The glycine moiety was introduced in position 2 via a nucleophilic aromatic substitution reaction (SNAr) facilitated by microwave irradiation. The synthetic sequence involved 12 steps with an overall yield of 7%.
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17.
  • Blomberg, David, 1971- (författare)
  • Synthesis of β-turn and pyridine based peptidomimetics
  • 2007
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Despite the unfavorable pharmacokinetic properties associated with peptides, they are still of great interest in drug development due to a multitude of interesting biological functions. The development of peptidomimetics strives to maintain or improve the biological activity of a peptide concurrently with removing the unwanted properties. This thesis describes two synthetic approaches to peptidomimetics with particular emphasis on secondary structure mimetics. First the design, synthesis and evaluation of two beta-turn mimetics incorporated in the endorphin Leu-enkephalin is presented. The beta-turn mimetics were stabilized by replacement of the intramolecular hydrogen bond with an ethylene bridge, and the amide bond between Tyr and Gly was replaced with an ether linkage. Linear analogues of the two mimetics were also synthesized. The peptidomimetics and their linear analogues were evaluated in a competitive binding assay at two opiate receptors, my and delta. One of the cyclized beta-turn mimetics was found to be a delta receptor antagonist with an IC50 value of 160 nM. Second a synthetic strategy to a beta-strand mimetic using 2-fluoro-4-iodopyridine as scaffold is described. The synthesis involved a Grignard exchange reaction on the pyridine scaffold using an amino acid derivative as electrophile followed by an SNAr reaction using an amine as nucleophile. The synthesis of a tripeptidomimetic of Leu-Gly-Gly and attempts to introduce chiral building blocks at the C-terminal, as well as studies towards elongated mimetics are presented. Two additional studies deal with the synthesis of two classes of potential thrombin inhibitors based on the pyridine scaffold. The first class contain pyridine as central fragment (P2 residue) substituted with a para-amidinobenzylamine group as P1 residue and various benzoyl groups as P3 residues. Three potential thrombin inhibitors were synthesized and found to be microM inhibitors in an enzymatic assay. In the second class, the pyridine ring serves as P3 residue. This class also lacks a strongly basic group in the P1 position. A small library of eight compounds were synthesized and evaluated in the enzymatic assay. Unfortunately, these compounds lacked inhibitory activity.
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18.
  • Blomberg, Eva, et al. (författare)
  • Polymer bilayer formation due to specific interactions between beta-cyclodextrin and adamantane : A surface force study
  • 2004
  • Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 20:24, s. 10449-10454
  • Tidskriftsartikel (refereegranskat)abstract
    • The purposes of this study are to utilize the interactions between an adamantane end-capped poly(ethylene oxide) (PEO) and a cationic polymer of beta-cyclodextrin to build polymer bilayers on negatively charged surfaces, and to investigate the interactions between such layers. The association of this system in solution has been studied by rheology, light scattering, and fluorescence measurements. It was found that the adamantane-terminated PEO (PEC-Ad) mixed with the beta-cyclodextrin polymer gives complexes where the interpolymer links are formed by specific inclusion of the adamantane groups in the beta-cyclodextrin cavities. This results in a higher viscosity of the solution and growth of intermolecular clusters. The interactions between surfaces coated with a cationized beta-cyclodextrin polymer across a water solution containing PEO-Ad polymers were studied by employing the interferometric surface force apparatus (SFA). In the first step, the interaction between mica surfaces coated with the cationized beta-cyclodextrin polymer in pure water was investigated. It was found that the beta-cyclodextrin polymer adsorbs onto mica and almost neutralizes the surface charge. The adsorbed layers of the beta-cyclodextrin polymer are rather compact, with a layer thickness of about 60 Angstrom (30 Angstrom per surface). Upon separation, a very weak attractive force is observed. The beta-cyclodextrin solution was then diluted by pure water by a factor of 3000 and a PEO-Ad polymer was introduced into the solution. Two different architectures of the PEO-Ad polymer were investigated: a four-arm structure and a linear structure. After the adsorption of the PEO polymer onto the beta-cyclodextrin layer reached equilibrium, the forces were measured again. It was found that the weak repulsive long-range force had disappeared and an attractive force caused the surfaces to jump into contact, and that the compressed layer thickness had increased. The attractive force is interpreted as being due to a specific recognition between the hydrophobic adamantane groups on the PEO-Ad polymer and the hydrophobic cavity in the beta-cyclodextrin molecules. Furthermore, the attractive force observed on separation has increased significantly, which is a further indication of a specific interaction between the beta-cyclodextrin polymer and the adamantane groups.
  •  
19.
  • Blomberg, E, et al. (författare)
  • Polymer bilayer formation due to specific interactions between β-cyclodextrin and adamantane: A surface force study
  • 2004
  • Ingår i: Langmuir. - 0743-7463 .- 1520-5827. ; 20, s. 10449-10454
  • Tidskriftsartikel (refereegranskat)abstract
    • The purposes of this study are to utilize the interactions between an adamantane end-capped poly-(ethylene oxide) (PEO) and a cationic polymer of β-cyclodextrin to build polymer bilayers on negatively charged surfaces, and to investigate the interactions between such layers. The association of this system in solution has been studied by rheology, light scattering, and fluorescence measurements. It was found that the adamantane-terminated PEO (PEO-Ad) mixed with the β-cyclodextrin polymer gives complexes where the interpolymer links are formed by specific inclusion of the adamantane groups in the β-cyclodextrin cavities. This results in a higher viscosity of the solution and growth of intermolecular clusters. The interactions between surfaces coated with a cationized β-cyclodextrin polymer across a water solution containing PEO-Ad polymers were studied by employing the interferometric surface force apparatus (SFA). In the first step, the interaction between mica surfaces coated with the cationized β-cyclodextrin polymer in pure water was investigated. It was found that the β-cyclodextrin polymer adsorbs onto mica and almost neutralizes the surface charge. The adsorbed layers of the β-cyclodextrin polymer are rather compact, with a layer thickness of about 60Å(30Å per surface). Upon separation, a very weak attractive force is observed. The β-cyclodextrin solution was then diluted by pure water by a factor of 3000 and a PEO-Ad polymer was introduced into the solution. Two different architectures of the PEO-Ad polymer were investigated: a four-arm structure and a linear structure. After the adsorption of the PEO polymer onto the β-cyclodextrin layer reached equilibrium, the forces were measured again. It was found that the weak repulsive longrange force had disappeared and an attractive force caused the surfaces to jump into contact, and that the compressed layer thickness had increased. The attractive force is interpreted as being due to a specific recognition between the hydrophobic adamantane groups on the PEO-Ad polymer and the hydrophobic cavity in the β-cyclodextrin molecules. Furthermore, the attractive force observed on separation has increased significantly, which is a further indication of a specific interaction between the β-cyclodextrin polymer and the adamantane groups
  •  
20.
  • Blomberg, Jonas, et al. (författare)
  • Increased antiretroviral antibody reactivity in sera from a defined population of patients with systemic lupus erythematosus. Correlation with autoantibodies and clinical manifestations
  • 1994
  • Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 37:1, s. 57-66
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE. The implied role of retroviruses in the pathogenesis of murine systemic lupus erythematosus (SLE) led us to study antiretroviral antibodies in a population-based SLE cohort. METHODS. Immunoassays using whole virus and synthetic peptides were performed on sera from 72 patients with SLE and 88 control subjects. RESULTS. Reactions with whole baboon endogenous virus occurred more frequently in patients with SLE, and correlated with the presence of anti-RNP and anti-Sm. Some retroviral env and gag peptides, several of which were similar to U1 small nuclear RNP, reacted more strongly in patients with SLE, and their presence was correlated with discoid rash, hematologic disorder, and other symptoms. CONCLUSION. These results provide circumstantial evidence for involvement of retroviruses in the pathogenesis of human SLE; further studies should be carried out using other techniques for measurement of retroviral expression.
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21.
  • Blomberg, Jeanette, et al. (författare)
  • Inhibition of cellular FLICE-like inhibitory protein abolishes insensitivity to interferon-α in a resistant variant of the human U937 cell line
  • 2011
  • Ingår i: Apoptosis (London). - : Springer Science and Business Media LLC. - 1360-8185 .- 1573-675X. ; 16:8, s. 783-794
  • Tidskriftsartikel (refereegranskat)abstract
    • Type I interferons constitute a family of pleiotropic cytokines that have a key role in both adaptive and innate immunity. The interferon signalling pathways mediate transcriptional regulation of hundreds of genes, which result in mRNA degradation, decreased protein synthesis, cell cycle inhibition and induction of apoptosis. To elucidate regulatory networks important for interferon induced cell death, we generated interferon resistant U937 cells by selection in progressively increasing concentrations of interferon-α (IFN-α). The results show that IFN-α activates the death receptor signalling pathway and that IFN resistance was associated with cross-resistance to several death receptor ligands in a manner similar to previously described Fas resistant U937 cell lines. Increased expression of the long splice variant of the cellular FLICE-like inhibitor protein (cFLIP-L) was associated with the resistance to death receptor and IFN-α stimulation. Accordingly, inhibition of cFLIP-L expression with cycloheximide or through cFLIP short harpin RNA interference restored sensitivity to Fas and/or IFN-α. Thus, we now show that selection for interferon resistance can generate cells with increased expression of cFLIP, which protects the cells from both IFN-α and death receptor mediated apoptosis.
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22.
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23.
  • Blomberg, Rina, 1974- (författare)
  • Auditory Distraction in ADHD : From Behaviour to the Brain
  • 2022
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • ADHD is a heterogenous disorder encompassing neurodevelopmental deficits in cognitive control. Auditory distraction is a common clinically reported symptom in ADHD, yet empirical research investigating the manifestation of auditory distraction in the disorder is remarkably scarce. Findings from cognitive hearing science highlight the crucial role cognitive control plays in an individual’s ability to gate, attenuate and/or compensate for auditory distraction. However the field is yet to extensively test hypotheses in normal hearing populations with neurodevelopmental deficits in cognitive control such as ADHD. This thesis contributes to narrowing the gap within these two fields of research by studying auditory distraction in this clinical population to a greater extent than previous reports in the literature.Using a combination of both behavioural and neuroimaging methods, the research presented here was able to show that adults and adolescents with ADHD are inherently more susceptible to auditory distraction than their non-ADHD counterparts. At the behavioural level, impaired task performance due to auditory distraction was more likely to manifest in ADHD participants when the working memory system was under high processing load. At the neural level, functional aberrancy in auditory attention was evident at early stages of sensory processing in a variety of tasks, implicating both exogenous and endogenous control systems in ADHD. Furthermore, the distribution of ADHD-symptom severity across participants was shown to correlate with increases in both cortical activity to auditory distractors and intrinsic functional connectivity between auditory and exogenous attention networks.In line with evidence from cognitive hearing science, the general findings of this thesis demonstrate that cognitive control plays an important role in the ability to perceive sound under suboptimal listening conditions and hamper distraction. In addition, findings challenge theories of ADHD that question the extent in which sensory-related attentional control is impaired. More empirical research on the auditory modality in ADHD is therefore encouraged in order to revise models, improve diagnostic tools, and develop evidence-based interventions targeting study/work environments.
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24.
  • Blomberg, Sara, et al. (författare)
  • Bridging the Pressure Gap in CO Oxidation
  • 2021
  • Ingår i: ACS Catalysis. - : American Chemical Society (ACS). - 2155-5435. ; 11:15, s. 9128-9135
  • Tidskriftsartikel (refereegranskat)abstract
    • Performing fundamental operando catalysis studies under realistic conditions is a key to further develop and increase the efficiency of industrial catalysts. Operando X-ray photoelectron spectroscopy (XPS) experiments have been limited to pressures, and the relevance for industrial applications has been questioned. Herein, we report on the CO oxidation experiment on Pd(100) performed at a total pressure of 1 bar using XPS. We investigate the light-off regime and the surface chemical composition at the atomistic level in the highly active phase. Furthermore, the observed gas-phase photoemission peaks of CO2, CO, and O2 indicate that the kinetics of the reaction during the light-off regime can be followed operando, and by studying the reaction rate of the reaction, the activation energy is calculated. The reaction was preceded by an in situ oxidation study in 7% O2 in He and a total pressure of 70 mbar to confirm the surface sensitivity and assignment of the oxygen-induced photoemission peaks. However, oxygen-induced photoemission peaks were not observed during the reaction studies, but instead, a metallic Pd phase is present in the highly active regime under the conditions applied. The novel XPS setup utilizes hard X-rays to enable high-pressure studies, combined with a grazing incident angle to increase the surface sensitivity of the measurement. Our findings demonstrate the possibilities of achieving chemical information of the catalyst, operando, on an atomistic level, under industrially relevant conditions.
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25.
  • Bodvard, Kristofer, 1981, et al. (författare)
  • Continuous light exposure causes cumulative stress that affects the localization oscillation dynamics of the transcription factor Msn2p.
  • 2011
  • Ingår i: Biochimica et biophysica acta. - : Elsevier BV. - 0006-3002. ; 1813:2, s. 358-366
  • Tidskriftsartikel (refereegranskat)abstract
    • Light exposure is a potentially powerful stress factor during in vivo optical microscopy studies. In yeast, the general transcription factor Msn2p translocates from the cytoplasm to the nucleus in response to illumination. However, previous time-lapse fluorescence microscopy studies of Msn2p have utilized a variety of discrete exposure settings, which makes it difficult to correlate stress levels and illumination parameters. We here investigate how continuous illumination with blue light, corresponding to GFP excitation wavelengths, affects the localization pattern of Msn2p-GFP in budding yeast. The localization pattern was analyzed using a novel approach that combines wavelet decomposition and change point analysis. It was found that the Msn2p nucleocytoplasmic localization trajectories for individual cells exhibit up to three distinct and successive states; i) Msn2p localizes to the cytoplasm; ii) Msn2p rapidly shuttles between the cytoplasm and the nucleus; iii) Msn2p localizes to the nucleus. Many cells pass through all states consecutively at high light intensities, while at lower light intensities most cells only reach states i) or ii). This behaviour strongly indicates that continuous light exposure gradually increases the stress level over time, presumably through continuous accumulation of toxic photoproducts, thereby forcing the cell through a bistable region corresponding to nucleocytoplasmic oscillations. We also show that the localization patterns are dependent on protein kinase A (PKA) activity, i.e. yeast cells with constantly low PKA activity showed a stronger stress response. In particular, the nucleocytoplasmic oscillation frequency was found to be significantly higher for cells with low PKA activity for all light intensities.
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26.
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27.
  • Bolad, Ahmed, et al. (författare)
  • Distinct interethnic differences in IgG class/subclass and IgM antibody responses to malaria antigens but not in IgG responses to non-malarial antigens in sympatric tribes living in West Africa
  • 2005
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 61:4, s. 380-386
  • Tidskriftsartikel (refereegranskat)abstract
    • The well-established relative resistance to malaria observed in the Fulani ascompared with other sympatric tribes in West Africa has been attributed totheir higher levels of serum immunoglobulin (Ig) G antibodies to malarialantigens. In this study, we confirm and extend the previous findings by analysesof the levels of IgM, IgG and IgG subclasses of anti-malarial antibodies inasymptomatic individuals of different sympatric tribes in Burkina Faso(Fulani/Mossi) and Mali (Fulani/Dogon). The Fulani showed significantlyhigher median concentrations of anti-malarial IgG and IgM antibodies thanthe sympatric tribes at both locations. Although the overall subclass pattern ofantibodies did not differ between the tribes, with IgG1 and IgG3 as dominant,the Fulani showed consistently significantly higher levels of these subclasses ascompared with those of the non-Fulani individuals. No significant differenceswere seen in the levels of total IgG between the tribes, but the Fulani showedsignificantly higher levels of total IgM than their neighbours in both countries.While the antibody levels to some nonmalarial antigens showed the same patternof differences seen for antibody levels to malaria antigens, no significant suchdifferences were seen with antibodies to other nonmalarial antigens. In conclusion,our results show that the Fulani in two different countries show higherlevels of anti-malarial antibodies than sympatric tribes, and this appears not tobe a reflection of a general hyper-reactivity in the Fulani.
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28.
  • Bråve, Andreas, et al. (författare)
  • Intranasal immunization of young mice with a multigene HIV-1 vaccine in combination with the N3 adjuvant induces mucosal and systemic immune responses
  • 2008
  • Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 26:40, s. 5075-5078
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the major challenges for the development of an HIV vaccine is to induce potent virus-specific immune responses at the mucosal surfaces where transmission of virus occurs. Intranasal delivery of classical vaccines has been shown to induce good mucosal antibody responses, but so far for genetic vaccines the success has been limited. This study shows that young individuals are sensitive to nasal immunization with a genetic vaccine delivered in a formulation of a lipid adjuvant, the Eurocine N3. Intranasal delivery of a multiclade/multigene HIV-1 genetic vaccine gave rise to vaginal and rectal IgA responses as well as systemic humoral and cellular responses. As electroporation might become the preferred means of delivering genetic vaccines for systemic HIV immunity, nasal delivery by droplet formulation in a lipid adjuvant might become a means of priming or boosting the mucosal immunity. © 2008 Elsevier Ltd. All rights reserved.
  •  
29.
  • Courtin, David, et al. (författare)
  • G6PD A-variant influences the antibody responses to Plasmodium falciparum MSP2.
  • 2011
  • Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 11:6, s. 1287-1292
  • Tidskriftsartikel (refereegranskat)abstract
    • High antibody levels directed to Plasmodium falciparum merozoite surface proteins (MSP), including MSP2, as well as genetically related red blood cell defects, have previously been found to be associated with protection against malaria. Here, our main objective was to study the changes in MSP2-specific total IgG, IgG1 and IgG3 responses during a malaria transmission season in order to assess the impact of sickle-cell, α(+)-thalassemia and G6PD variants on antibody kinetics. Repeated parasitological assessments of a cohort of children were conducted during an 8-month period. Antibody responses to recombinant MSP2/3D7 and MSP2/FC27 proteins were measured at the beginning and at the end of transmission season. We found that (i) the period of last Plasmodium falciparum infection during the transmission season was associated with IgG3 anti-MSP2 change. Compared to the IgG3 levels of children infected in January 2003 (end of transmission season), the IgG3 level of children decreased with the length of the period without infection, (ii) G6PD A- carriers had a lower increase of IgG3 levels to MSP2/FC27 and MSP2/3D7 during the transmission season than the noncarriers. This latter finding is suggestive of qualitative and/or quantitative reduction of exposure to malarial antigens related to this genetic variant, leading to weaker stimulation of specific antibody responses. We speculate that cell-mediated immune activity may explain the clinical protection afforded by this genetic trait.
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30.
  • Cullinan, Paul, et al. (författare)
  • Occupational lung diseases : from old and novel exposures to effective preventive strategies
  • 2017
  • Ingår i: The Lancet Respiratory Medicine. - 2213-2600 .- 2213-2619. ; 5:5, s. 445-455
  • Tidskriftsartikel (refereegranskat)abstract
    • Occupational exposure is an important, global cause of respiratory disease. Unlike many other non-communicable lung diseases, the proximal causes of many occupational lung diseases are well understood and they should be amenable to control with use of established and effective approaches. Therefore, the risks arising from exposure to silica and asbestos are well known, as are the means of their prevention. Although the incidence of occupational lung disease has decreased in many countries, in parts of the world undergoing rapid economic transition and population growth-often with large informal and unregulated workforces-occupational exposures continue to impose a heavy burden of disease. The incidence of interstitial and malignant lung diseases remains unacceptably high because control measures are not implemented or exposures arise in novel ways. With the advent of innovative technologies, new threats are continually introduced to the workplace (eg, indium compounds and vicinal diketones). In developed countries, work-related asthma is the commonest occupational lung disease of short latency. Although generic control measures to reduce the risk of developing or exacerbating asthma are well recognised, there is still uncertainty, for example, with regards to the management of workers who develop asthma but remain in the same job. In this Review, we provide recommendations for research, surveillance, and other action for reducing the burden of occupational lung diseases.
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31.
  • Currier, Russell W, et al. (författare)
  • The evolution of infectious agents in relation to sex in animals and humans: brief discussions of some individual organisms.
  • 2011
  • Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 1749-6632 .- 0077-8923. ; 1230, s. 74-107, s. 74-107
  • Forskningsöversikt (refereegranskat)abstract
    • The following series of concise summaries addresses the evolution of infectious agents in relation to sex in animals and humans from the perspective of three specific questions: (1) what have we learned about the likely origin and phylogeny, up to the establishment of the infectious agent in the genital econiche, including the relative frequency of its sexual transmission; (2) what further research is needed to provide additional knowledge on some of these evolutionary aspects; and (3) what evolutionary considerations might aid in providing novel approaches to the more practical clinical and public health issues facing us currently and in the future?
  •  
32.
  • Di, Mengqiao, 1994, et al. (författare)
  • Chasing PtO x species in ceria supported platinum during CO oxidation extinction with correlative operando spectroscopic techniques
  • 2022
  • Ingår i: Journal of Catalysis. - : Elsevier BV. - 0021-9517 .- 1090-2694. ; 409, s. 1-11
  • Tidskriftsartikel (refereegranskat)abstract
    • Industrially relevant, highly dispersed, Pt/ceria and reference Pt/alumina catalysts with narrow Pt particle size distributions have been prepared, characterised ex situ and studied for CO oxidation by operando infrared and X-ray absorption spectroscopy. At high CO conversions, spectator CO ad-species on ionic platinum are observed while the CO oxidation proceeds on Pt particles in a high oxidation state exhibiting significant Pt[sbnd]O coordination. During the protracted catalytic extinction, the CO coverage builds up gradually while the Pt oxidation state and Pt[sbnd]O coordination remain high because of interactions with ceria. The observed CO oxidation at high CO coverage is suggested to involve sites at the platinum-ceria boundary that cannot be CO self-poisoned. This behaviour is in stark contrast to that of Pt/alumina, which shows removal of platinum oxides formed during CO oxidation and the classical drop in catalytic activity caused by rapid CO self-poisoning when reaching a critical temperature.
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33.
  • Ekström, Magnus, et al. (författare)
  • Minimal clinically important differences for Dyspnea-12 and MDP scores are similar at 2 weeks and 6 months : follow-up of a longitudinal clinical study
  • 2021
  • Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 57:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic breathlessness is a dominating symptom that restricts daily life for many people with cardiorespiratory disease [1]. Different dimensions of the symptom, such as the intensity, sensory qualities and emotional responses, can be assessed using the instruments Dyspnea-12 (D-12) [2] and the Multidimensional Dyspnea Profile (MDP) [3], which share similarities in the underlying constructs of what is measured [4] and have emerged as widely used instruments for multi-dimensional measurement of breathlessness
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34.
  • Elmroth Nordlander, Jonas, et al. (författare)
  • Mo3Ni2N Nanoparticle Generation by Spark Discharge
  • 2023
  • Ingår i: Materials. - : MDPI AG. - 1996-1944. ; 16:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Spark ablation is an advantageous method for the generation of metallic nanoparticles with defined particle sizes and compositions. The reaction of the metal particles with the carrier gas during the synthesis and, therefore, the incorporation of those light elements into structural voids or even compound formation was confirmed for hydrides and oxides but has only been suspected to occur for nitrides. In this study, dispersed nanoparticles of Mo3Ni2N and Mo with Janus morphology, and defined particle sizes were obtained by spark discharge generation as a result of carrier gas ionization and characterized using transmission electron microscopy and powder X-ray diffraction. Metal nitrides possess beneficial catalytic and thermoelectric properties, as well as high hardness and wear resistance. Therefore, this method offers the possibility of controlled synthesis of materials which are interesting for numerous applications.
  •  
35.
  • Eriksson, David, et al. (författare)
  • Iodine-131 induces mitotic catastrophes and activates apoptotic pathways in HeLa Hep2 cells
  • 2008
  • Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 23:5, s. 541-549
  • Tidskriftsartikel (refereegranskat)abstract
    • Iodine-131 (131I) has been used both in unconjugated form and conjugated to antibody derivates (i.e., radioimmunotherapy; RIT) to treat malignant diseases. The mechanisms by which 131I-irradiation causes growth retardation are, however, inadequately understood. The aim of this study was to elucidate the sequential molecular and cellular events that initiate cell death in HeLa Hep2 cells exposed to 131I. In this paper, HeLa Hep2 cells were found to display a transient G2-M arrest following irradiation, but then reentered the cell cycle still containing unrepaired cellular damage. An increase of multipolar mitotic spindles, as well as a significant increase in centrosome numbers from 8.8% +/- 1.9% in controls to 54.7% +/- 2.2% in irradiated cells, was observed (p < 0.0001). A subsequent failure of cytokinesis caused the cells to progress into mitotic catastrophe. This was accompanied by the formation of giant cells with multiple nuclei, multilobulated nuclei, and an increased frequency of polyploidy cells. A fraction of the cells also displayed apoptotic features, including the activation of initiator caspases-2, -8, -9, and effector caspase-3, as well as cleavage of poly(ADP-ribose) polymerase, a cell-death substrate for active caspase-3. These findings demonstrate that mitotic catastrophes and the activation of a delayed type of apoptosis might be important mechanisms involved in cell death following the RIT of solid tumors with -emitting radionuclides, such as 131I.
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36.
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37.
  • Gard Timmerfors, Jessica, 1989- (författare)
  • Wood chips for kraft and sulfite pulping : evaluation of novel forest-industrial drum-chipping technology
  • 2020
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Wood chipping and the supply of high-quality wood chips are of critical importance for most forest-industrial processes. The quality of wood chips affects product yield, product quality, and processability. Wood chips from a novel type of forest-industrial drum chipper, with a large drum and specially designed wood-chip channels, were evaluated with regard to wood chips for the Kraft and sulfite processes. Wood chips from a full-scale demonstration version of the drum chipper and from a conventional disc chipper at a Kraft mill were compared. The average bulk density and the fractions of oversized and overthick wood chips were similar, but the demonstration drum chipper produced 51% more large accept chips, 11% more total accept chips, and 74% less pin chips and fines. A pilot-scale drum chipper based on the new technology was used to produce short wood chips designed for acidic processes. When the drum velocity was 30-34 m/s and the average wood-chip length 21-22 mm, the fraction of pin chips and fines was 4.2% and the fraction of total accept was 89-90%. When the average wood-chip length was decreased to 17 mm, the fraction of pin chips and fines increased to 8.5% and the fraction of total accept decreased to 80-82%. The pilot drum chipper was used to investigate the influence of using different tree species (aspen, birch, pine, and spruce), processing of wood with different moisture content, and frozen wood. For hardwood (aspen and birch), the fraction of total accept reached ~90% when the average wood chip length was 17 mm. The pilot drum chipper was also used to generate wood chips of heartwood of pine for a comparison of 15 sulfite-process reaction conditions that differed with regard to impregnation and cooking procedures. The analyses included absorption of liquid in a specially designed impregnation reactor, pulp yield, reject, viscosity, kappa number, brightness, fiber properties, and chemical composition as determined using compositional analysis based on two-step hydrolysis with sulfuric acid and pyrolysis-gas chromatography/mass spectrometry. The results reveal in detail how the individual wood constituents were affected by the different treatments, and demonstrate the benefits of using a pressurized impregnation step prior to sulfite cooking.
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38.
  • Giha, Hayder A., et al. (författare)
  • Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh
  • 2010
  • Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 28:7, s. 1732-1739
  • Tidskriftsartikel (refereegranskat)abstract
    • The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained from a cohort of 136 donors from Daraweesh in Sudan. The cohort was followed for malaria infection for 9 years. After an initial analysis, the immune response to Pf332-C231 antigen was the only one found associated with protection, thus taken for further analysis. The number of previous clinical malaria episodes experienced by the donors was used as an index for relative protection. The number of these episodes was found to be negatively correlated with the levels of pre-existing total IgG, IgG2 and IgG3 to Pf332-C231 (correlation coefficient, CC - 0.215, p=0.012; CC - 0.195, p=0.023 and CC - 0.211, p=0.014, respectively), and also with age (CC - 0.311, p<0.001). Unexpectedly, equal levels of Pf332-C231 antibodies were induced by both patent and sub-patent infections regardless of the number of previous malaria episodes (1-7). Combining the correlation analysis with a multi-linear regression, three variable markers for protection were emerged, two age-dependent, the antibody response to Pf332-C231 and an unidentified marker (likely immune response to other antigens), and the third was an age-independent unidentified marker (possibly gene polymorphisms). In conclusion, this report suggests a protective effect for IgG subclasses to Pf332-C231 antigen against malaria.
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39.
  • Giha, Hayder A., et al. (författare)
  • Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria.
  • 2009
  • Ingår i: Malaria Journal. - : Springer Science and Business Media LLC. - 1475-2875. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • ABSTRACT: BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined. RESULTS: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent. DISCUSSION: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible CONCLUSIONS: The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.
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40.
  • Giha, Hayder A, et al. (författare)
  • Association of a single nucleotide polymorphism in the C-reactive protein gene (-286) with susceptibility to Plasmodium falciparum malaria
  • 2010
  • Ingår i: Molecular Medicine. - : Springer Science and Business Media LLC. - 1076-1551 .- 1528-3658. ; 16:1-2, s. 27-33
  • Tidskriftsartikel (refereegranskat)abstract
    • The role of inflammation in malaria pathogenesis is not fully understood, although C-reactive protein (CRP) may have a negative influence on host immunity to infections. An upstream polymorphism, -286 (C > T > A), in the CRP gene is known to influence CRP levels. In this study, a cohort of 192 Sudanese donors, followed for malaria infection for 9 years, had their CRP -286 gene locus genotyped by pyrosequencing. The number of malaria episodes experienced by each individual over the study period was used as an index for malaria susceptibility. The prevalence of the CRP alleles A, C and T were 21%, 52% and 27%, respectively. Importantly, the A-allele, unlike the C- and T-alleles or CRP genotypes, was significantly associated with an increased number of malaria episodes, P = 0.007. The proportion of A-allele carriers among donors not known to have had malaria during the study period was 18%, whereas it was 43% and 63% among donors who had experienced 1-4 and > or =5 malaria episodes, respectively, over the same period (P = 0.002). Furthermore, the A-allele was associated with higher parasite counts. In conclusion, the CRP -286 A-allele was associated with an increased susceptibility to uncomplicated Plasmodium falciparum malaria.
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41.
  • Giha, Hayder A., et al. (författare)
  • Clustering of malaria treatment failure (TF) in Daraweesh : hints for host genetic susceptibility to TF with emphasis on immune-modulating SNPs
  • 2010
  • Ingår i: Infection, Genetics and Evolution. - : Elsevier BV. - 1567-1348 .- 1567-7257. ; 10:4, s. 481-6
  • Tidskriftsartikel (refereegranskat)abstract
    • In malaria, drug resistance and treatment failure (TF) are not synonymous, although are escalating together. Over 9 years of surveillances for malaria morbidity and TF in Daraweesh village in eastern Sudan (1991-2004), 136 donors (15-78 years) from 43 households, treated for 278 malaria episodes and had experienced 46 incident of TF, were included in this study. Blood obtained from the donors in 2005, was used for measurement of IgG subclasses against Pf332-C231 antigen and GM/KM allotyping and for genotyping of the donors for; FcgammaRIIA 131 (HH, RH, RR), CRP 286 (C
  •  
42.
  • Giusti, Pablo, 1975- (författare)
  • Characterization of antigen-presenting cell function in vitro and ex vivo
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Long-term protective immunity depends on proper initiation of professional antigen-presenting cells (APCs). Autoimmune disorders and certain infections can cause disease through modulation of APCs and thereby affecting the outcome of these diseases. This work aimed to investigate the behaviour of different APC subsets during conditions known to cause improper immune responses. In Paper I, the effects of an anti-inflammatory compound called Rabeximod, intended for treatment of rheumatoid arthritis were investigated on different subsets of APCs. The results showed that Rabeximod affected the differentiation and behaviour of inflammatory subsets of dendritic cells (DCs) and macrophages while no effects were observed on anti-inflammatory subsets. Our findings suggest that Rabeximod acts by inhibiting the functionality of inflammatory subsets of APCs. In Paper II, the effects of different malaria derived stimuli such as hemozoin (Hz) and infected red-blood cells (iRBCs) on monocyte-derived dendritic cells (MoDCs) were investigated. Both stimuli triggered activation and migration of MoDCs. MoDCs exposed to iRBCs induced allogeneic T-cell proliferation while those exposed to Hz did not. These results indicate that different malaria derived stimuli may differently affect DCs and that this could lead to improper and inefficient T-cell activation. In Paper III, innate aspects of malarial immunity were compared in children from two sympatric ethnic groups. We observed decreased activation of APCs and severely supressed TLR responses in Dogon children as compared to Fulani. This may indicate an important role for TLR and APC activation in the Fulani, known to be better protected against malaria than the Dogon. In summary, detailed knowledge of APC activation will be helpful in the understanding of specific effector immune responses. This could in turn, improve treatment of inflammatory disorders as well as the generation of efficient vaccines against infectious diseases.
  •  
43.
  • Golets, Mikhail, 1987-, et al. (författare)
  • A kinetic study of the liquid phase acetoxylation of α-pinene
  • 2012
  • Ingår i: Topics in catalysis. - : Springer. - 1022-5528 .- 1572-9028. ; 55:7-10, s. 649-656
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study introduces kinetic modeling of liquid phase α-pinene acetoxylation with acetic acid over an ion-exchange resin catalyst. The reaction was carried out in a laboratory scale high-pressure autoclave. α-terpinyl (35 wt%) and bornyl (40 wt%) acetates were the primary products. The predominant reaction pathways were identified and evaluated.
  •  
44.
  • Golets, Mikhail, 1987-, et al. (författare)
  • Liquid phase acetoxylation of α-pinene over Amberlyst-70 ion-exchange resin
  • 2012
  • Ingår i: Applied Catalysis A: General. - : Elsevier BV. - 0926-860X .- 1873-3875. ; 435-436, s. 43-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Heterogeneously-catalyzed and solvent-catalyzed liquid phase acetoxylation of α-pinene with acetic acid acting as both a solvent and a reagent was studied. Both solvent-catalyzed and catalytic experiments were carried out and various reaction conditions were studied. The influence of temperature, pressure, solvent and gas milieu were taken into account. Bornyl, fenchyl, verbenyl as well as α-terpinyl acetates, limonene, camphene and γ-terpinene were found among reaction products. The addition of the catalyst allowed for maximization of the yield of bornyl acetate. The predominant products obtained were α-terpinyl, verbenyl and bornyl acetates. The reaction pathways were identified and evaluated. The aim of this work was to study the feasibility of batch acetoxylation of α-pinene. The analysis of the complex product distribution is not trivial and, consequently, resolving the reaction network was important. The optimized reaction conditions were searched for aiming at an efficient conversion of α-pinene to a mixture of valuable products.
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45.
  • Gonzalez, Manuel Cruz, 1969-, et al. (författare)
  • Hyperleptinemia is associated with altered endothelial function
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction The adipocyte-derived hormone leptin has been associated with increased risk of cardiovascular disease but the underlying mechanisms are unclear. Leptin effects on vascular endothelium may be a key mediator although contradictory results have been presented. We aimed to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary heart disease.Methods and Results The vascular effects of leptin were assessed using venous occlusion plethysmography in healthy volunteers (n=17) and in patients with stable coronary heart disease (CHD) (n=83). In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n=10) did not affect forearm blood flow or plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 (PAI-1) concentrations (all P>0.05).  However, during concomitant co-infusion with leptin (800 ng/min; n=10), induced vasodilatation was reduced (P=0.001), and tPA activity increased (P=0.002). In line with this, patients with coronary heart disease included in the highest tertile of plasma leptin concentrations had reduced substance P-induced vasodilatation (P<0.001), and increased tPA antigen and activity release (p<0.001 and p=0.03 respectively) compared to those in the lowest tertile.Conclusions Although leptin does not directly affect basal vascular function, acute local and chronic systemic hyperleptinemia are associated with altered endothelial function in healthy volunteers and patients with coronary heart disease respectively. These results support hyperleptinemia as a link between obesity and cardiovascular disease.
  •  
46.
  • Goodwin, Christopher M., et al. (författare)
  • The Structure of the Active Pd State During Catalytic Carbon Monoxide Oxidization
  • 2021
  • Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 12:18, s. 4461-4465
  • Tidskriftsartikel (refereegranskat)abstract
    • Using grazing incidence X-rays and X-ray photoelectron spectroscopy during the mass transfer limited catalytic oxidation of CO, the long-range surface structure of Pd(100) was investigated. Under the reaction conditions of 50:4 O-2 to CO, 300 mbar pressure, and temperatures between 200 and 450 degrees C, the surface structure resulting from oxidation and the subsequent oxide reduction was elucidated. The reduction cycle was halted, and while under reaction conditions, angle-dependent X-ray photoelectron spectroscopy close to the critical angle of Pd and modeling of the data was performed. Two proposed models for the system were compared. The suggestion with the metallic islands formed on top of the oxide island was shown to be consistent with the data.
  •  
47.
  • Guenot, Marianne, et al. (författare)
  • Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate V gamma 9V delta 2 T Cells
  • 2015
  • Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 83:10, s. 3816-3824
  • Tidskriftsartikel (refereegranskat)abstract
    • Malaria induces potent activation and expansion of the V gamma 9V delta 2 subpopulation of gamma delta T cells, which inhibit the Plasmodium falciparum blood cycle through soluble cytotoxic mediators, abrogating merozoite invasion capacity. Intraerythrocytic stages efficiently trigger V gamma 9V delta 2 T-cell activation and degranulation through poorly understood mechanisms. P. falciparum blood-stage extracts are known to contain phosphoantigens able to stimulate V gamma 9V delta 2 T cells, but how these are presented by intact infected red blood cells (iRBCs) remains elusive. Here we show that, unlike activation by phosphoantigen-expressing cells, V gamma 9V delta 2 T-cell activation by intact iRBCs is independent of butyrophilin expression by the iRBC, and contact with an intact iRBC is not required. Moreover, blood-stage culture supernatants proved to be as potent activators of V gamma 9V delta 2 T cells as iRBCs. Bioactivity in the microenvironment is attributable to phosphoantigens, as it is dependent on the parasite DOXP pathway, on V gamma 9V delta 2 TCR signaling, and on butyrophilin expression by V gamma 9V delta 2 T cells. Kinetic studies showed that the phosphoantigens were released at the end of the intraerythrocytic cycle at the time of parasite egress. We document exquisite sensitivity of V gamma 9V delta 2 T cells, which respond to a few thousand parasites. These data unravel a novel framework, whereby release of phosphoantigens into the extracellular milieu by sequestered parasites likely promotes activation of distant V gamma 9V delta 2 T cells that in turn exert remote antiparasitic functions.
  •  
48.
  • Hunter, Amanda, et al. (författare)
  • Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters
  • 2014
  • Ingår i: Particle and Fibre Toxicology. - : BioMed Central (BMC). - 1743-8977. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.
  •  
49.
  • Johnsson, Åse (Allansdotter), 1966, et al. (författare)
  • Incidental findings and their handling in the Swedish CArdioPulmonary bioimage study (SCAPIS)
  • 2017
  • Ingår i: Incidental Radiological Findings. - Cham : Springer International Publishing. - 0942-5373 .- 2197-4187. - 9783319425818 - 9783319425795 - 9783319826127 ; , s. 91-101
  • Bokkapitel (refereegranskat)abstract
    • The Swedish CArdioPulmonary bioImage Study (SCAPIS) combines the use of new imaging technologies, large-scale proteomics/metabolomics/genomics, and epidemiological analyses to extensively characterize a Swedish cohort of 30,000 men and women aged between 50 and 64 years. Its main aims are to improve risk prediction and to optimize our ability to study mechanisms of cardiopulmonary diseases. SCAPIS is currently recruiting at six sites in Sweden, and a pilot study was conducted in 2012 to test the feasibility of the comprehensive study protocol. In the planning phase, it was recognized that the detailed phenotyping used in SCAPIS would identify a large number of clinical findings in need of medical attention. This was confirmed by evaluation of results from the pilot study. Here we focus on pulmonary nodules and asymptomatic coronary artery stenosis. These clinical features were observed in a large number of participants, and the clinical handing and prognosis related to these observations are unclear. They thus posed great challenges for the study in their practical and ethical handling. This chapter describes how we developed procedures to handle these findings based on existing evidence and expert consensus as well as deliberations on ethical issues.
  •  
50.
  • Langrish, Jeremy, et al. (författare)
  • Exposure to nitrogen dioxide is not associated with vascular dysfunction in man
  • 2010
  • Ingår i: Inhalation Toxicology. - : Informa Healthcare. - 0895-8378 .- 1091-7691. ; 22:3, s. 192-198
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Exposure to air pollution is associated with increased cardiorespiratory morbidity and mortality. It is unclear whether these effects are mediated through combustion-derived particulate matter or gaseous components, such as nitrogen dioxide. Objectives: To investigate the effect of nitrogen dioxide exposure on vascular vasomotor and six fibrinolytic functions. Methods: Ten healthy male volunteers were exposed to nitrogen dioxide at 4 ppm or filtered air for 1 h during intermittent exercise in a randomized double-blind crossover study. Bilateral forearm blood flow and fibrinolytic markers were measured before and during unilateral intrabrachial infusion of bradykinin (100–1000 pmol/min), acetylcholine (5–20 μg/min), sodium nitroprusside (2–8 μg/min), and verapamil (10–100 μg/min) 4 h after the exposure. Lung function was determined before and after the exposure, and exhaled nitric oxide at baseline and 1 and 4 h after the exposure. Results: There were no differences in resting forearm blood flow after either exposure. There was a dose-dependent increase in forearm blood flow with all vasodilators but this was similar after either exposure for all vasodilators (p > .05 for all). Bradykinin caused a dose-dependent increase in plasma tissue-plasminogen activator, but again there was no difference between the exposures. There were no changes in lung function or exhaled nitric oxide following either exposure. Conclusion: Inhalation of nitrogen dioxide does not impair vascular vasomotor or fibrinolytic function. Nitrogen dioxide does not appear to be a major arbiter of the adverse cardiovascular effects of air pollution.
  •  
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