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- Villablanca, A, et al.
(författare)
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Involvement of the MEN1 gene locus in familial isolated hyperparathyroidism
- 2002
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Ingår i: European journal of endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 147:3, s. 313-322
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Familial isolated hyperparathyroidism (FIHP) is a hereditary disorder characterised by uni- or multiglandular parathyroid disease. A subset of families are likely to be genetic variants of other familial tumour syndromes in which PHPT is the main feature, for example multiple endocrine neoplasia type 1 (MEN 1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT). OBJECTIVE: To investigate seven families diagnosed with FIHP, each with two to eight affected family members, to clarify the underlying genetic mechanism. METHODS: The entire MEN1 gene was sequenced for germline mutations and, in addition, tumour specimens were analysed in comparative genomic hybridisation and loss of heterozygosity studies. RESULTS: Two families exhibited MEN1 mutations, L112V and 1658delG, which were associated with loss of the wild-type 11q13 alleles in all tumours analysed. In the remaining five families, no MEN1 mutation was identified. CONCLUSION: These results support the involvement of the MEN1 tumour suppressor gene in the pathogenesis of some of the FIHP kindreds. However, loss on chromosome 11 was seen in all tumours exhibiting somatic deletions, although in two families the tumour deletions involved 11q distal to MEN1. We conclude that the altered MEN1 gene function is of importance in the development of FIHP.
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| 4. |
- Carling, K. M., et al.
(författare)
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Vacancy concentration in Al from combined first-principles and model potential calculations
- 2003
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 67:5
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Tidskriftsartikel (refereegranskat)abstract
- We present a comprehensive study of vacancy formation enthalpies and entropies in aluminum. The calculations are done in the framework of the local-density and generalized-gradient approximations in the density-functional formalism. To assess anharmonic contributions to the formation free energies, we use an interatomic potential with parameters determined from density-functional-theory calculations. We find that the binding energy for the nearest-neighbor divacancy is negative, i.e., it is energetically unstable. The entropy contributions slightly stabilize the divacancy but also the binding free energy at the melting temperature is found to be negative. We show that the anharmonic atomic vibrations explain the non-Arrhenius temperature dependence of the vacancy concentration in contrast to the commonly accepted interpretation of the experimental data in terms of the monovacancy-divacancy model.
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| 7. |
- Grundberg, E, et al.
(författare)
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A deletion polymorphism in the RIZ gene, a female sex steroid hormone receptor coactivator, exhibits decreased response to estrogen in vitro and associates with low bone mineral density in young Swedish women
- 2004
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 89:12, s. 6173-6178
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Tidskriftsartikel (refereegranskat)abstract
- Low bone mineral density (BMD) is a major risk factor for osteoporotic fracture, and the trait is under genetic control by a large number of genes. It is recognized that estrogen plays an important role in the maintenance of bone mass by binding to estrogen receptor a (ERa). RIZ1 has previously been shown to be a specific ERa coactivator and strongly enhances its function both in vivo and in vitro. We performed in vitro studies comparing the abilities of RIZ1 P704 polymorphic variants (homozygous presence, P704+; absence, P704-; heterozygosity P704+/- of a proline at position 704) to coactivate the ERa and also examined the polymorphism associated to BMD of 343 Swedish women, aged 20-39 yr. The expression vector containing P704- RIZ1 showed an impaired response in coactivating ERa in a ligand- and dose-dependent manner compared with P704+ RIZ (P < 0.0001). The genotype frequencies were 19% (P704+), 32% (P704-), and 49% (P704+/-) and were in Hardy-Weinberg equilibrium. BMD at the heel was higher in the P704+ genotype group than in the P704+/- group (P = 0.02), which was evident also after corrections for fat and lean mass (P = 0.03). We conclude that RIZ1 may be a new candidate gene for involvement in the variation seen in BMD.
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