| 1. |
- Wollmer, M Axel., et al.
(författare)
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Association study of cholesterol-related genes in Alzheimer's disease
- 2007
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Ingår i: Neurogenetics. - : Springer Science and Business Media LLC. - 1364-6745 .- 1364-6753. ; 8:3, s. 179-188
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer’s disease (AD) is a genetically complex disorder, and several genes related to cholesterol metabolism have been reported to contribute to AD risk. To identify further AD susceptibility genes, we have screened genes that map to chromosomal regions with high logarithm of the odds scores for AD in full genome scans and are related to cholesterol metabolism. In a European screening sample of 115 sporadic AD patients and 191 healthy control subjects, we analyzed single nucleotide polymorphisms in 28 cholesterol-related genes for association with AD. The genes HMGCS2, FDPS, RAFTLIN, ACAD8, NPC2, and ABCG1 were associated with AD at a significance level of P ≤ 0.05 in this sample. Replication trials in five independent European samples detected associations of variants within HMGCS2, FDPS, NPC2, or ABCG1 with AD in some samples (P = 0.05 to P = 0.005). We did not identify a marker that was significantly associated with AD in the pooled sample (n = 2864). Stratification of this sample revealed an APOE-dependent association of HMGCS2 with AD (P = 0.004). We conclude that genetic variants investigated in this study may be associated with a moderate modification of the risk for AD in some samples.
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| 2. |
- Allan, Ian J., et al.
(författare)
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Evaluation of the Chemcatcher and DGT passive samplers for monitoring metals with highly fluctuating water concentrations
- 2007
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Ingår i: Journal of Environmental Monitoring. ; 9:7, s. 672-681
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Tidskriftsartikel (refereegranskat)abstract
- Passive sampling devices accumulate chems. continuously from water and can provide time weighted av. (TWA) concns. of pollutants over the exposure period. Hence, they offer a no. of advantages over other conventional monitoring techniques such as spot or grab sampling. The diffusive gradient in thin film (DGT) and the Chemcatcher passive samplers can be used to provide TWA concns. of labile metals, but the approaches to their calibration differ. DGT uses diffusion coeffs. of metals in the hydrogel layer, whereas Chemcatcher uses metal specific uptake rates, with both sets of values obtained under controlled lab. conditions with const. aq. metal concns. However, little is known of how such samplers respond to fluctuating concns. We evaluated the responsiveness of these two passive sampling devices to rapidly changing concns. of Cd, Cu, Ni, Pb and Zn in natural freshwater, over a relatively short deployment time. Maximum metal concns. in water were varied between 70 and 140 mg L-1. Expts. were carried out in a tank with a rotating carousel system and filled with Meuse River water, allowing a degree of control over exptl. conditions while using natural river water. Fluctuating concns. were obtained by stepwise addn. of std. solns. of the metals. The reliability and accuracy of the TWA concns. measured by the samplers were assessed by comparison with concns. of the metals in spot samples of water taken regularly over the deployment period. The spot samples of water were either unfiltered (total), filtered (0.45 mm) or ultrafiltered (5 kDa). Predictive speciation modeling using the visual MINTEQ program was also undertaken. There was reasonable agreement between the TWA concns. of Cd and Ni obtained with Chemcatcher and DGT and the total Cd and Ni concns. measured in repeated unfiltered spot samples. For elements (i.e. Cu, Pb, Zn) that assoc. to a significant degree with suspended solids, colloids or dissolved org. carbon, or form complexes with large org. ligands, optimum agreement was with the filtered or ultrafiltered fractions and with the predicted inorg. and inorg.-fulvic acid assocd. fractions. While Chemcatcher-based TWA concn. ranges for Cu and Zn were in best agreement with the total filtered fraction, there was lack of agreement for Pb. The combined use of DGT devices with open pore (OP) and restricted pore (RP) gels allowed the labile fraction of metal assocd. with large org. ligands or DOC to be differentiated and quantified, since this is available to DGT OP but unable to diffuse into the DGT RP. This evaluation of the two sampling devices clearly demonstrated their ability to react reliably to transient peaks in concn. of metal pollutants in water and indicated where future efforts are needed to improve calibration data. Such samplers may prove valuable in responding to the monitoring requirements of the European Union's Water Framework Directive. [on SciFinder (R)]
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| 3. |
- Allan, Ian J., et al.
(författare)
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Strategic monitoring for the European Water Framework Directive
- 2006
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Ingår i: TrAC - Trends in Analytical Chemistry. - : Elsevier BV. - 0165-9936. ; 25:7, s. 704-715
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Tidskriftsartikel (refereegranskat)abstract
- This article first reviews the principal monitoring requirements of the Water Framework Directive (WFD) of the European Union (EU) and assesses how contaminant monitoring may fit into a risk-assessment approach. In this context, we show the limited ability of conventional trace-contaminant-monitoring methods to fulfil all of the WFD requirements. We then clearly define and exemplify the roles and the functions of a new set of monitoring tools, using three case studies based on datasets that we obtained during a field trial in the River Meuse as part of the Screening methods for Water data InFormaTion (SWIFT-WFD) project in support of implementing the WFD.
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| 4. |
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| 5. |
- Holmén, Nathalie, 1979, et al.
(författare)
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Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity.
- 2006
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Ingår i: Inflammatory bowel diseases. - 1078-0998. ; 12:6, s. 447-56
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Factors determining the extension and degree of inflammation in the colonic mucosa of patients with ulcerative colitis (UC) are largely unknown, but CD4+CD25high regulatory T cells (Tregs) have been implicated to play an important role in suppressing inflammation. Therefore, the aims of this study were to determine whether colonic Tregs have suppressive effects on colonic effector T cells in UC and to analyze the association between segmental colonic Treg distribution and disease activity. MATERIALS AND METHODS: The suppressive activity of colonic CD4+CD25high Tregs from patients with active UC was determined in coculture assays measuring proliferation and cytokine production. The frequency of Tregs and the expression of the Treg marker FOXP3 were analyzed with flow cytometry and RT-PCR in isolated cells and the whole mucosa from patients with active and inactive disease, as well as healthy mucosa. RESULTS: Colonic CD4+CD25high T cells from patients with UC suppressed the proliferation and cytokine secretion of colonic effector CD4+ T cells. Healthy controls but not patients with UC had lower Treg frequencies in the sigmoid than in the ascending colon. Patients with UC with active disease had increased frequency of colonic Tregs. The frequency of Tregs was positively correlated with colonic disease activity and serum C-reactive protein. CONCLUSIONS: Colonic CD4+CD25high Tregs are able to suppress colonic effector T cell activity in vitro, and the Treg frequency in the inflamed intestine increases with disease activity in patients with active UC. This suggests that Tregs may be outnumbered by other inflammatory cells or that their suppressive activity may be influenced by the in vivo environment.
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| 6. |
- Leriche, Ludovic, et al.
(författare)
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Positron Emission Tomography Imaging Demonstrates Correlation between Behavioral Recovery and Correction of Dopamine Neurotransmission after Gene Therapy
- 2009
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Ingår i: The Journal of Neuroscience. - 1529-2401. ; 29:5, s. 1544-1553
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Tidskriftsartikel (refereegranskat)abstract
- In vivo gene transfer using viral vectors is an emerging therapy for neurodegenerative diseases with a clinical impact recently demonstrated in Parkinson's disease patients. Recombinant adeno-associated viral (rAAV) vectors, in particular, provide an excellent tool for long-term expression of therapeutic genes in the brain. Here we used the [C-11] raclopride [(S)-(-)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl) methyl)-2-hydroxy6-methoxybenzamide] micro-positron emission tomography (PET) technique to demonstrate that delivery of the tyrosine hydroxylase (TH) andGTPcyclohydrolase 1 (GCH1) enzymes using an rAAV5 vector normalizes the increased [C-11] raclopride binding in hemiparkinsonian rats. Importantly, we show in vivo by microPET imaging and postmortem by classical binding assays performed in the very same animals that the changes in [C-11] raclopride after viral vector-based enzyme replacement therapy is attributable to a decrease in the affinity of the tracer binding to the D-2 receptors, providing evidence for reconstitution of a functional pool of endogenous dopamine in the striatum. Moreover, the extent of the normalization in this non-invasive imaging measure was highly correlated with the functional recovery in motor behavior. The PET imaging protocol used in this study is fully adaptable to humans and thus can serve as an in vivo imaging technique to follow TH + GCH1 gene therapy in PD patientsandprovideanadditionalobjectivemeasuretoapotentialclinicaltrialu singrAAVvectorstodeliverL-3,4-dihydroxyphenylanalineinthebrain.
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