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- Dick, FD, et al.
(författare)
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Gene-environment interactions in parkinsonism and Parkinson's disease : The Geoparkinson study
- 2007
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 64:10, s. 673-680
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To investigate associations of Parkinson's disease (PD) and parkinsonian syndromes with polymorphic genes that influence metabolism of either foreign chemical substances or dopamine and to seek evidence of gene-environment interaction effects that modify risk. Methods: A case-control study of 959 prevalent cases of parkinsonism (767 with PD) and 1989 controls across five European centres. Occupational hygienists estimated the average annual intensity of exposure to solvents, pesticides and metals, (iron, copper, manganese), blind to disease status. CYP2D6, PON1, GSTM1, GSTT1, GSTM3, GSTP1, NQO1, CYP1B1, MAO-A, MAO-B, SOD 2, EPHX, DATl, DRD2 and NAT2 were genotyped. Results were analysed using multiple logistic regression adjusting for key confounders. Results: There was a modest but significant association between MAO-A polymorphism in males and disease risk (G vs T, OR 1.30, 95% C1 1.02 to 1.66, adjusted). The majority of gene-environment analyses did not show significant interaction effects. There were possible interaction effects between GSTM1 null genotype and solvent exposure (which were stronger when limited to PD cases only). Conclusions: Many small studies have reported associations between genetic polymorphisms and PD. Fewer have examined gene-environment interactions. This large study was sufficiently powered to examine these aspects. GSTM1 null subjects heavily exposed to solvents appear to be at increased risk of PD. There was insufficient evidence that the other gene-environment combinations investigated modified disease risk, suggesting they contribute little to the burden of PD.
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| 2. |
- Dick, FD, et al.
(författare)
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Environmental risk factors for Parkinson's disease and parkinsonism : The Geoparkinson study
- 2007
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 64:10, s. 666-672
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the associations between Parkinson's disease and other degenerative parkinsonian syndromes and environmental factors in five European countries. Methods: A case-control study of 959 prevalent cases of parkinsonism (767 with Parkinson's disease) and 1989 controls in Scotland, Italy, Sweden, Romania and Malta was carried out. Cases were defined using the United Kingdom Parkinson's Disease Society Brain Bank criteria, and those with drug-induced or vascular parkinsonism or dementia were excluded. Subjects completed an interviewer-administered questionnaire about lifetime occupational and hobby exposure to solvents, pesticides, iron, copper and manganese. Lifetime and average annual exposures were estimated blind to disease status using a job-exposure matrix modified by subjective exposure modelling. Results were analysed using multiple logistic regression, adjusting for age, sex, country, tobacco use, ever knocked unconscious and family history of Parkinson's disease. Results: Adjusted logistic regression analyses showed significantly increased odds ratios for Parkinson's disease/parkinsonism with an exposure-response relationship for pesticides (low vs no exposure, odds ratio (OR) =1.13, 95% Cl 0.82 to 1.57, high vs no exposure, OR =1.41, 95% Cl 1.06 to 1.88) and ever knocked unconscious (once vs never, OR= 1.35, 95% Cl 1.09 to 1.68, more than once vs never, OR = 2.53, 95% Cl 1.78 to 3.59). Hypnotic, anxiolytic or antidepressant drug use for more than 1 year and a family history of Parkinson's disease showed significantly increased odds ratios. Tobacco use was protective (OR = 0.50, 95% Cl 0.42 to 0.60). Analyses confined to subjects with Parkinson's disease gave similar results. Conclusions: The association of pesticide exposure with Parkinson's disease suggests a causative role. Repeated traumatic loss of consciousness is associated with increased risk.
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| 4. |
- Bauer, D. C., et al.
(författare)
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Classification of osteoarthritis biomarkers: a proposed approach
- 2006
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 14:8, s. 723-727
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Forskningsöversikt (refereegranskat)abstract
- Objective: Osteoarthritis (OA) biomarkers are needed by researchers and clinicians to assist in disease diagnosis and assessment of disease severity, risk of onset, and progression. As effective agents for CA are developed and tested in clinical studies, biomarkers; that reliably mirror or predict the progression or amelioration of CA will also be needed. Methods: The NIH-funded CA Biomarkers Network is a multidisciplinary group interested in the development and validation of CA biomarkers. This review summarizes our efforts to characterize and classify CA biomarkers. Results: We propose the "BIPED" biomarker classification (which stands for Burden of Disease, Investigative, Prognostic, Efficacy of Intervention and Diagnostic), and offer suggestions on optimal study design and analytic methods for use in CA investigations. Conclusion. The BIPED classification provides specific biomarker definitions with the goal of improving our ability to develop and analyze OA biomarkers, and to communicate these advances within a common framework. (C) 2006 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 5. |
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| 6. |
- Delbro, Dick, et al.
(författare)
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Is acetylcholine an autocrine/paracrine growth factor via the nicotinic α-receptor subtype in the human colon cancer cell line HT-29?
- 2009
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 609:1-3, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- We used immunochemistry to demonstrate expression of acetylcholine's nicotinic 7-receptor subtype inhuman colon cancer cell line HT-29. Moreover, RT-PCR and immunochemistry showed that cholineacetyltransferase and acetylcholine esterase, the enzymes responsible for acetylcholine synthesis anddegradation, respectively, localise in HT-29 cells. Bromoacetylcholine bromide, an inhibitor of cholineacetyltransferase, significantly attenuated basal cell growth. Our findings suggest that acetylcholine mightserve as an autocrine/paracrineor speculatively, even intracrinesignalling molecule in cell line HT-29, thuscontributing to carcinogenesis/cancer progression
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| 7. |
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| 8. |
- Dick, G J, et al.
(författare)
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Community-wide analysis of microbial genome sequence signatures
- 2009
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 10:8, s. R85-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Analyses of DNA sequences from cultivated microorganisms have revealed genome-wide, taxa-specific nucleotide compositional characteristics, referred to as genome signatures. These signatures have far-reaching implications for understanding genome evolution and potential application in classification of metagenomic sequence fragments. However, little is known regarding the distribution of genome signatures in natural microbial communities or the extent to which environmental factors shape them. RESULTS: We analyzed metagenomic sequence data from two acidophilic biofilm communities, including composite genomes reconstructed for nine archaea, three bacteria, and numerous associated viruses, as well as thousands of unassigned fragments from strain variants and low-abundance organisms. Genome signatures, in the form of tetranucleotide frequencies analyzed by emergent self-organizing maps, segregated sequences from all known populations sharing < 50 to 60% average amino acid identity and revealed previously unknown genomic clusters corresponding to low-abundance organisms and a putative plasmid. Signatures were pervasive genome-wide. Clusters were resolved because intra-genome differences resulting from translational selection or protein adaptation to the intracellular (pH approximately 5) versus extracellular (pH approximately 1) environment were small relative to inter-genome differences. We found that these genome signatures stem from multiple influences but are primarily manifested through codon composition, which we propose is the result of genome-specific mutational biases. CONCLUSIONS: An important conclusion is that shared environmental pressures and interactions among coevolving organisms do not obscure genome signatures in acid mine drainage communities. Thus, genome signatures can be used to assign sequence fragments to populations, an essential prerequisite if metagenomics is to provide ecological and biochemical insights into the functioning of microbial communities.
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| 10. |
- Edman, Maria C, et al.
(författare)
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Functional expression of the adenosine A1 receptor in rabbit lacrimal gland.
- 2008
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Ingår i: Experimental eye research. - : Elsevier BV. - 0014-4835. ; 86:1, s. 110-7
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Tidskriftsartikel (refereegranskat)abstract
- It has become increasingly clear that purine compounds play a mediator role in exocrine secretion. Therefore, the present study was aimed at examining the presence of the adenosine A1 receptor in rabbit lacrimal gland and to evaluate the role of the A1 receptor in regulated secretion. The expression of the A1 receptor was investigated with reverse transcriptase PCR, cyto- and histochemistry as well as with pharmacological methods. Acinar cells were isolated, cultured in a serum-free medium for 2 days and thereafter treated with purinergic agonists/antagonists and/or carbachol and VIP. Secretory response was assessed by measuring secreted beta-hexosaminidase enzymatic activity. Microscopical evaluation of the immunocyto- and histochemistry specimens indicated that the adenosine A1 receptor is expressed in the rabbit lacrimal gland, which was also supported by reverse transcriptase PCR resulting in a sequence 100% identical with the previously published sequence for the rabbit A1 receptor gene. Incubation of acinar cells with adenosine and the A1 specific agonist N6-cyclopentyladenosine (CPA) resulted in a fourfold increase of secretion at the determined optimal concentrations. Incubation with carbachol alone resulted in a 10- to 15-fold increase. Carbachol combined with either adenosine or CPA increased the secretion 20-fold or more, demonstrating a synergistic effect. Our data provides evidence for the presence of adenosine A1 receptors in both tissue and cultured cells. Even though adenosine and CPA alone had only a moderate effect on secretion, the observed synergistic effect with carbachol suggests a modulatory role for the adenosine A1 receptor in the lacrimal gland.
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