Abdominal aortic aneurysm.
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Biomedical subjects
Publications and source records attributed to J Walston.
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BACKGROUND: The beta-3-adrenergic receptor (beta3AR) stimulates lipolysis and thermogenesis in adipocytes. The Trp64Arg beta3AR variant is associated in some, but not all, studies with an earlier onset of Type 2 diabetes mellitus and features of the insulin resistance syndrome. Functional studies as to the role of the Trp64Arg variant have been inconclusive. Earlier studies screened the beta3AR gene in only ten obese, diabetic Pima Indians. Potentially another yet to be identified polymorphism in the beta3AR gene in linkage disequilibrium with the Trp64Arg polymorphism could explain the findings in the association and functional studies. METHODS: We scanned the beta3AR gene in 20 diabetic Pima subjects and 20 Caucasian subjects using single stranded conformational polymorphism (SSCP) analysis. Variants were sequenced using dideoxy sequence analysis and further characterized using allele specific oligonucleotide hybridization (ASO) and RNA template specific-polymerase chain reaction (RS-PCR) assays. RESULTS: We found a guanine to thymidine substitution in the first intron, 14 bases from the splice donor site in both groups. In virtually all subjects, only two haplotypes were detected, Trp64/g1856 and Arg64/t1856, indicating that the g1856t polymorphism is in linkage disequilibrium with the Trp64Arg polymorphism. The g1856t substitution introduces a new consensus splice donor site which, if used, would encode a truncated protein. RNA levels of the two beta3AR alleles were approximately equal in omental adipose tissue of heterozygotes. No aberrantly spliced beta3AR mRNA was detected, indicating that the new consensus splice donor site is not used in vivo. CONCLUSION: The g1856t polymorphism is in linkage disequilibrium with the Trp64Arg variant, but does not appear to have a functional role.
Measuring functional activity for elderly at very low functional levels remains a challenge because many functional instruments have not been standardized in a frail elderly population. The Frail Elderly Functional Assessment questionnaire (FEFA) is a 19-item, interviewer-administered questionnaire designed to assess function in frail elderly at a very low activity level. The purpose of this study was to determine the reliability and validity of this instrument in a frail elderly population. Two groups of subjects over 65 yr old were selected to test the reliability and validity of this questionnaire. Test-retest reliability was determined by correlating the responses of 29 homebound (including nursing home-bound) subjects who answered the questionnaire on two occasions 2 wk apart. To assess the validity of the FEFA, the questionnaire was administered to 23 frail, homebound (including nursing home-bound) elderly subjects who had a Mini-Mental State Examination score of > or = 18. Validity was determined by correlating patient responses to direct observations by the investigators of tasks addressed in the questionnaire. Correlation was also determined against the Katz's Activity of Daily Living index, Lawton's Instrumental Activity of Daily Living index, and the Barthel index. The reliability coefficient was 0.82. Correlation between the FEFA questionnaire and direct observation of questionnaire task performance was 0.90. Construct validity against the Katz's Activity of Daily Living, Lawton's Instrumental Activity of Daily Living, and the Barthel index showed correlations of 0.86, 0.67 and 0.91, respectively. Initial data indicate that the FEFA is a valid and reliable instrument that may be useful in assessing function in frail elderly people.