Source:http://linkedlifedata.com/resource/pubmed/id/19589099
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2009-7-10
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pubmed:abstractText |
Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium - containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximately 0.2), HLA-DPB1*0201 (OR approximately 3), and HLA-DPB1*1701 (OR approximately 46). The mouse ear swelling test (MEST) was employed to determine if these different alleles would support a hypersensitivity response to beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p < 0.05). No significant changes were observed in the other transgenic strains for any treatment condition. In addition, inter-strain differences in response to beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the HLA-DPB1*1701 transgene product is an important risk factor for induction of the beryllium-sensitive phenotype. This model should be a useful tool for investigating beryllium sensitization.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1547-6901
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
130-5
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:19589099-Alleles,
pubmed-meshheading:19589099-Animals,
pubmed-meshheading:19589099-Berylliosis,
pubmed-meshheading:19589099-Beryllium,
pubmed-meshheading:19589099-Disease Models, Animal,
pubmed-meshheading:19589099-Genetic Predisposition to Disease,
pubmed-meshheading:19589099-HLA-DP Antigens,
pubmed-meshheading:19589099-HLA-DP beta-Chains,
pubmed-meshheading:19589099-Humans,
pubmed-meshheading:19589099-Hypersensitivity, Delayed,
pubmed-meshheading:19589099-Mice,
pubmed-meshheading:19589099-Mice, Inbred Strains,
pubmed-meshheading:19589099-Mice, Transgenic,
pubmed-meshheading:19589099-Polymorphism, Genetic,
pubmed-meshheading:19589099-Risk Factors,
pubmed-meshheading:19589099-Skin Tests,
pubmed-meshheading:19589099-Species Specificity,
pubmed-meshheading:19589099-Th1 Cells
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pubmed:year |
2009
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pubmed:articleTitle |
Genetic determinants of sensitivity to beryllium in mice.
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pubmed:affiliation |
Department of Environmental Medicine, NYU School of Medicine, Tuxedo, New York 10987, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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