| 1. |
- Andersson, Jonas, 1977-, et al.
(författare)
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C-reactive protein is a determinant of first-ever stroke: prospective nested case-referent study.
- 2009
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Ingår i: Cerebrovascular diseases (Basel, Switzerland). - : S. Karger AG. - 1421-9786 .- 1015-9770. ; 27:6, s. 544-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: C-reactive protein (CRP) is a determinant of stroke, but there are no prospective studies on CRP and first ischemic stroke divided into etiologic subtypes. Our primary aim was to study CRP as a determinant of ischemic stroke, classified according to Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, and intracerebral hemorrhage (ICH) in a prospective study. A secondary aim was to study the relationship between the 1444C>T polymorphism, plasma levels of CRP and stroke. METHODS: The study was a prospective population-based case-referent study nested within the Northern Sweden Cohorts. We defined 308 cases of ischemic stroke and 61 ICH. Two controls for each case were defined from the same cohort. RESULTS: The OR for the highest (>3 mg/l) versus lowest group (<1 mg/l) of CRP was 2.58 (95% CI 1.74-3.84) for ischemic stroke and 1.63 (95% CI 0.67-3.93) for ICH. In a multivariate model including traditional risk factors, CRP remained associated with ischemic stroke (OR 2.06; 95% CI 1.29-3.29). Small-vessel disease was associated with CRP in the multivariate model (OR 3.88; 95% CI 1.10-13.7). The CRP 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of CRP but neither with ischemic stroke nor with ICH. CONCLUSIONS: This prospective population-based study shows that CRP is significantly associated with the risk of having a first ischemic stroke, especially for small-vessel disease. No significant associations were found between the CRP 1444C>T polymorphism and any stroke subtype.
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| 2. |
- Hägg, Daniel, 1974, et al.
(författare)
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Expression profiling of macrophages from subjects with atherosclerosis to identify novel susceptibility genes.
- 2008
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Ingår i: International journal of molecular medicine. - 1107-3756 .- 1791-244X. ; 21:6, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- Although a number of environmental risk factors for atherosclerosis have been identified, heredity seems to be a significant independent risk factor. The aim of our study was to identify novel susceptibility genes for atherosclerosis. The screening process consisted of three steps. First, expression profiles of macrophages from subjects with atherosclerosis were compared to macrophages from control subjects. Secondly, the subjects were genotyped for promoter region polymorphisms in genes with altered gene expression. Thirdly, a population of subjects with coronary heart disease and control subjects were genotyped to test for an association with identified polymorphisms that affected gene expression. Twenty-seven genes were differentially expressed in both macrophages and foam cells from subjects with atherosclerosis. Three of these genes, IRS2, CD86 and SLC11A1 were selected for further analysis. Foam cells from subjects homozygous for the C allele at the -765C-->T SNP located in the promoter region of IRS2 had increased gene expression compared to foam cells from subjects with the nonCC genotype. Also, macrophages and foam cells from subjects homozygous for allele 2 at a repeat element in the promoter region of SLC11A1 had increased gene expression compared to macrophages and foam cells from subjects with the non22 genotype. Genotyping of 512 pairs of subjects with coronary heart disease (CHD) and matched controls revealed that subjects homozygous for C of the IRS2 SNP had an increased risk for CHD; odds ratio 1.43, p=0.010. Immunohistochemical staining of human carotid plaques showed that IRS2 expression was localised to macrophages and endothelial cells in vivo. Our method provides a reliable approach for identifying susceptibility genes for atherosclerosis, and we conclude that elevated IRS2 gene expression in macrophages may be associated with an increased risk of CHD.
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| 3. |
- Johansson, Karl-Axel, et al.
(författare)
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The quality assurance process for the ARTSCAN head and neck study - a practical interactive approach for QA in 3DCRT and IMRT.
- 2008
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Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 87:2, s. 290-9
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Tidskriftsartikel (refereegranskat)abstract
- AIM: This paper describes the quality assurance (QA) work performed in the Swedish multicenter ARTSCAN (Accelerated RadioTherapy of Squamous cell CArcinomas in the head and Neck) trial to guarantee high quality in a multicenter study which involved modern radiotherapy such as 3DCRT or IMRT. MATERIALS AND METHODS: The study was closed in June 2006 with 750 randomised patients. Radiation therapy-related data for every patient were sent by each participating centre to the QA office where all trial data were reviewed, analysed and stored. In case of any deviation from the protocol, an interactive process was started between the QA office and the local responsible clinician and/or physicist to increase the compliance to the protocol for future randomised patients. Meetings and workshops were held on a regular basis for discussions on various trial-related issues and for the QA office to report on updated results. RESULTS AND DISCUSSION: This review covers the 734 patients out of a total of 750 who had entered the study. Deviations early in the study were corrected so that the overall compliance to the protocol was very high. There were only negligible variations in doses and dose distributions to target volumes for each specific site and stage. The quality of the treatments was high. Furthermore, an extensive database of treatment parameters was accumulated for future dose-volume vs. endpoint evaluations. CONCLUSIONS: This comprehensive QA programme increased the probability to draw firm conclusions from our study and may serve as a concept for QA work in future radiotherapy trials where comparatively small effects are searched for in a heterogeneous tumour population.
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| 4. |
- Nordberg, Klas, et al.
(författare)
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A flexible runtime system for image processing in a distributed computational environment for an unmanned aerial vehicle
- 2006
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Ingår i: International Journal of Pattern Recognition and Artificial Intelligence. - 0218-0014. ; 20:5, s. 763-780
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Tidskriftsartikel (refereegranskat)abstract
- A runtime system for implementation of image processing operations is presented. It is designed for working in a flexible and distributed environment related to the software architecture of a newly developed UAV system. The software architecture can be characterized at a coarse scale as a layered system, with a deliberative layer at the top, a reactive layer in the middle, and a processing layer at the bottom. At a finer scale each of the three levels is decomposed into sets of modules which communicate using CORBA, allowing system development and deployment on the UAV to be made in a highly flexible way. Image processing takes place in a dedicated module located in the process layer, and is the main focus of the paper. This module has been designed as a runtime system for data flow graphs, allowing various processing operations to be created online and on demand by the higher levels of the system. The runtime system is implemented in Java, which allows development and deployment to be made on a wide range of hardware/software configurations. Optimizations for particular hardware platforms have been made using Java's native interface.
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| 5. |
- Svensson, Per-Arne, 1969, et al.
(författare)
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Regulation and splicing of scavenger receptor class B type I in human macrophages and atherosclerotic plaques
- 2005
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Ingår i: BMC Cardiovasc Disord. - : Springer Science and Business Media LLC. - 1471-2261. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The protective role of high-density lipoprotein (HDL) in the cardiovascular system is related to its role in the reverse transport of cholesterol from the arterial wall to the liver for subsequent excretion via the bile. Scavenger receptor class B type I (SR-BI) binds HDL and mediates selective uptake of cholesterol ester and cellular efflux of cholesterol to HDL. The role of SR-BI in atherosclerosis has been well established in murine models but it remains unclear whether SR-BI plays an equally important role in atherosclerosis in humans. The aim of this study was to investigate the expression of SR-BI and its isoforms in human macrophages and atherosclerotic plaques. METHODS: The effect of hypoxia and minimally modified low-density lipoprotein (mmLDL), two proatherogenic stimuli, on SR-BI expression was studied in human monocyte-derived macrophages from healthy subjects using real-time PCR. In addition, SR-BI expression was determined in macrophages obtained from subjects with atherosclerosis (n = 15) and healthy controls (n = 15). Expression of SR-BI isoforms was characterized in human atherosclerotic plaques and macrophages using RT-PCR and DNA sequencing. RESULTS: SR-BI expression was decreased in macrophages after hypoxia (p < 0.005). In contrast, SR-BI expression was increased by exposure to mmLDL (p < 0.05). There was no difference in SR-BI expression in macrophages from patients with atherosclerosis compared to controls. In both groups, SR-BI expression was increased by exposure to mmLDL (p < 0.05). Transcripts corresponding to SR-BI and SR-BII were detected in macrophages. In addition, a third isoform, referred to as SR-BIII, was discovered. All three isoforms were also expressed in human atherosclerotic plaque. Compared to the other isoforms, the novel SR-BIII isoform was predicted to have a unique intracellular C-terminal domain containing 53 amino acids. CONCLUSION: We conclude that SR-BI is regulated by proatherogenic stimuli in humans. However, we found no differences between subjects with atherosclerosis and healthy controls. This indicates that altered SR-BI expression is not a common cause of atherosclerosis. In addition, we identified SR-BIII as a novel isoform expressed in human macrophages and in human atherosclerotic plaques.
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| 8. |
- Wiklund, Lars, et al.
(författare)
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Neuro- and cardioprotective effects of blockade of nitric oxide action by administration of methylene blue
- 2007
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Ingår i: Neuroprotective agents. - : Wiley. - 9781573316859 ; , s. 231-244
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Konferensbidrag (refereegranskat)abstract
- Methylene blue (MB), generic name methylthioninium (C16H18ClN3 S · 3H2O), is a blue dye synthesized in 1876 by Heinrich Caro for use as a textile dye and used in the laboratory and clinically since the 1890s, with well-known toxicity and pharmacokinetics. It has experimentally proven neuroprotective and cardioprotective effects in a porcine model of global ischemia–reperfusion in experimental cardiac arrest. This effect has been attributed to MB's blocking effect on nitric oxide synthase and guanylyl cyclase, the latter blocking the synthesis of the second messenger of nitric oxide. The physiological effects during reperfusion include stabilization of the systemic circulation without significantly increased total peripheral resistance, moderately increased cerebral cortical blood flow, a decrease of lipid peroxidation and inflammation, and less anoxic tissue injury in the brain and the heart. The last two effects are recorded as less increase in plasma concentrations of astroglial protein S-100β, as well as troponin I and creatine kinase isoenzyme MB, respectively.
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| 9. |
- Wiklund, Lars, 1954, et al.
(författare)
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Neurogenetik.
- 2006
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Ingår i: Neurologi. Fagius J och Aquilonius S-M (ed.). - Stockholm : Liber. - 9789147053131
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Wiklund, Per-Gunnar, et al.
(författare)
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Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of stroke : replicated findings in two nested case-control studies based on independent cohorts.
- 2005
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Ingår i: Stroke. - 0039-2499 .- 1524-4628. ; 36:8, s. 1661-1665
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Impaired fibrinolytic function secondary to elevated plasminogen activator inhibitor-1 (PAI-1) levels has been implicated in ischemic stroke. PAI-1 levels are determined by genetic factors and environmental factors, triglyceride levels in particular. The aim of this study was to investigate the common functional 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene and the risk of stroke. METHODS: A nested case-control study design was applied, using baseline data for 2 independent cohorts obtained at population-based surveys in northern Sweden. In study A, there were 113, and in study B, there were 275 individuals without major concomitant disease at baseline who later experienced a first-ever stroke. Blood samples obtained at baseline were analyzed for potential risk factors, including the 4G/5G polymorphism of the PAI-1 gene. RESULTS: The 4G allele of the PAI-1 polymorphism was associated with an increased risk of future ischemic stroke in both studies (odds ratio [OR] of 4G homozygosity, 1.87; 95% CI, 1.12 to 3.15 in study A; OR of 4G homozygosity, 1.56; 95% CI, 1.12 to 2.16 in study B). Individuals with the combination of hypertriglyceridemia and 4G homozygosity were at the greatest risk of developing stroke. Multiple logistic regression analysis identified 4G homozygosity, systolic blood pressure, and diabetes as independent predictors of ischemic stroke. CONCLUSIONS: Identical findings in 2 independent studies strongly suggest a true and clinically important association between PAI-1 4G/5G genotype and risk of future ischemic stroke. The observed modification of the genotype effect by triglycerides may be interpreted as a gene-environment interaction.
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