| 1. |
- Baker, Naomi L., et al.
(författare)
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Molecular consequences of dominant Bethlem myopathy collagen VI mutations
- 2007
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 62:4, s. 390-405
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Dominant mutations in the three collagen VI genes cause Bethlem myopathy, a disorder characterized by proximal muscle weakness and commonly contractures of the fingers, wrists, and ankles. Although more than 20 different dominant mutations have been identified in Bethlem myopathy patients, the biosynthetic consequences of only a subset of these have been studied, and in many cases, the pathogenic mechanisms remain unknown. Methods: We have screened fourteen Bethlem myopathy patients for collagen VI mutations and performed detailed analyses of collagen VI biosynthesis and intracellular and extracellular assembly. Results: Collagen VI abnormalities were identified in eight patients. One patient produced around half the normal amount of alpha 1(VI) messenger RNA and reduced amounts of collagen VI protein. Two patients had a previously reported mutation causing skipping of COL6A1 exon 14, and three patients had novel mutations leading to in-frame deletions toward the N-terminal end of the triple-helical domain. These mutations have different and complex effects on collagen VI intracellular and extracellular assembly. Two patients had single amino acid substitutions in the A-domains of COL6A2 and COL6A3. Collagen VI intracellular and extracellular assembly was normal in one of these patients. Interpretation: The key to dissecting the pathogenic mechanisms of collagen VI mutations lies in detailed analysis of collagen VI biosynthesis and assembly. The majority of mutations result in secretion and deposition of structurally abnormal collagen VI. However, one A-domain mutation had no detectable effect on assembly, suggesting that it acts by compromising collagen VI interactions in the extracellular matrix of muscle.
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| 2. |
- James, M. O., et al.
(författare)
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Properties and regional expression of a CYP3A-like protein in channel catfish intestine
- 2005
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Ingår i: Aquatic Toxicology. - : Elsevier BV. - 0166-445X. ; 72:4, s. 361-371
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Tidskriftsartikel (refereegranskat)abstract
- Biotransformation in the intestine may influence the bioavailability and toxicity of ingested xenobiotics. The objective of this study was to examine the expression and catalytic properties of a constitutive cytochrome P450 (CYP) 3A-like protein along the intestine of channel catfish, Ictalurus punctatus. Fish were maintained on commercial chow or nutritionally complete semi-purified diets. Polyclonal antibodies generated against rainbow trout CYP3A proteins reacted strongly with catfish washed intestinal microsomes on Western blots showing a major protein band with MW of 59 kDa. In catfish maintained on a standard chow diet, the expression of this protein was higher in the proximal segment (0.101 ± 0.031 units/mg protein, mean ± S.D., n = 4) than in the distal part (0.032 ± 0.023 units/mg protein). Microsomal testosterone 6β-hydroxylation activity was monitored as the catalytic indicator of CYP3A, and was higher in proximal than distal catfish intestine (263 ± 80.3 and 88.6 ± 15.6 pmol/min/mg protein for proximal and distal, respectively, mean S.D., n = 4). CYP3A protein levels and testosterone 6β-hydroxylation activities were lower in microsomes from the proximal segment of intestine from catfish maintained on a semi-purified diet, compared with commercial chow, but again the proximal intestine had higher CYP3A and 6β-hydroxylase activities than distal intestine. Testosterone 6β-hydroxylase activities in all samples correlated with the CYP3A protein levels, r(2) = 0.8. Testosterone 6β-hydroxylation was inhibited by specific CYP3A inhibitors, ketoconazole (IC50 = 0.02 μ M) and erythromycin (IC50 = 41 μ M), as well as general CYP inhibitors, metyrapone (IC50 = 2.8 μ M) and SKF-525A (IC50 = 25 μ M). There was evidence for the involvement of CYP3A in the mono-oxygenation of benzo(a)pyrene and of (-)-benzo(a)pyrene-7,8-dihydrodiol in intestinal microsomes from catfish maintained on the semi-purified diet. Mono-oxygenation of both substrates was increased in a concentration-dependent manner by in vitro addition of a-naphthoflavone. Benzo(a)pyrene hydroxylase activities were higher in proximal than in distal intestine; 3.72 ± 0.77 pmol/min/mg protein, mean ± S.D., n = 5 and 1.45 ± 0.42 in these respective segments. The results of this study strongly suggest that CYP3A is important in the first pass metabolism of dietary xenobiotics in untreated fish. © 2005 Elsevier B.V. All rights reserved.
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| 3. |
- Teuten, Emma L, et al.
(författare)
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Transport and release of chemicals from plastics to the environment and to wildlife
- 2009
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Ingår i: PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 364:1526, s. 2027-2045
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Tidskriftsartikel (refereegranskat)abstract
- Plastics debris in the marine environment, including resin pellets, fragments and microscopic plastic fragments, contain organic contaminants, including polychlorinated biphenyls ( PCBs), polycyclic aromatic hydrocarbons, petroleum hydrocarbons, organochlorine pesticides (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane, hexachlorinated hexanes), polybrominated diphenylethers, alkylphenols and bisphenol A, at concentrations from sub ng g(-1) to mg g(-1). Some of these compounds are added during plastics manufacture, while others adsorb from the surrounding seawater. Concentrations of hydrophobic contaminants adsorbed on plastics showed distinct spatial variations reflecting global pollution patterns. Model calculations and experimental observations consistently show that polyethylene accumulates more organic contaminants than other plastics such as polypropylene and polyvinyl chloride. Both a mathematical model using equilibrium partitioning and experimental data have demonstrated the transfer of contaminants from plastic to organisms. A feeding experiment indicated that PCBs could transfer from contaminated plastics to streaked shearwater chicks. Plasticizers, other plastics additives and constitutional monomers also present potential threats in terrestrial environments because they can leach from waste disposal sites into groundwater and/or surface waters. Leaching and degradation of plasticizers and polymers are complex phenomena dependent on environmental conditions in the landfill and the chemical properties of each additive. Bisphenol A concentrations in leachates from municipal waste disposal sites in tropical Asia ranged from sub mu g l(-1) to mg l(-1) and were correlated with the level of economic development.
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