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46 results on '"Knook, Dick L."'

3. Total cholesterol and risk of mortality in the oldest old

Author

Weverling-Rijnsburger, Annelies W.E., Blauw, Gerard J., Lagaay, A. Margot, Knook, Dick L., Meinders, A. Edo, and Westendorp, Rudi G.J.

Subjects
Aged -- Patient outcomes, Blood cholesterol -- Health aspects, Cancer -- Patient outcomes, Death -- Risk factors
Published
1997

28. Distributions of retinoids, retinoid-binding proteins and related parameters in different types of liver cells isolated from young and old rats.

Author

Hendriks, Henk F. J., Blaner, William S., Wennekers, Herm M., Piantedosi, Roseann, Brouwer, Adriaan, de Leeuw, A. Margreet, Goodman, DeWitt S., and Knook, Dick L.

Subjects
CARRIER proteins, VITAMIN A, ABDOMEN, BILIARY tract, METABOLISM, RETINOIDS
Abstract

The levels of retinoids, retinol-binding protein, cellular retinol-binding protein, cellular retinoic-acid-binding protein, transthyretin and the activities of retinyl palmitate hydrolase and cholesteryl oleate hydrolase were determined in purified parenchymal, fat-storing, endothelial and Kupifer cell preparations, and in liver homogenates from young adult (6-month-old) and old (36-month-old) rats. Retinoid levels were also determined in the plasma from young and old rats. Retinoid contents were determined by H PLC. The binding proteins and transthyretin were measured by specific radioimmunoassays; retinyl palmitate and cholesterol oleate hydrolases were measured by sensitive microassays. The retinoid content of both the liver homogenates and of the fat-storing, and parenchymal cell preparations increased between 6 months and 36 months of age. The cellular distribution of retinoids was similar for the two age groups analyzed with the fat-storing cells being the main retinoid storage sites in the rat liver. Concentrations of retinol-binding protein and transthyretin were high in parenchymal cell preparations. Cellular retinol-binding protein was enriched both in parenchymal and in fat-storing cell preparations; the highest concentrations of cellular retinoic-acid-binding protein were present in fat-storing cell preparations. No major differences were observed between the two age groups in the cellular concentrations and distributions of any of these binding proteins. High activity of cholesterol oleate hydrolase was measured in parenchymal and in Kupifer cell preparations; end othelial cell preparations also contained considerable activities. The distribution of this activity over the various cell types reflects their role in lipoprotein metabolism. Retinyl palmitate hydrolase activity was specifically enriched in parenchymal and in fat-storing cell preparations, consistent with the roles of these cells in retinoid metabolism. No major differences were observed between the two age groups in the cellular distributions of the two hydrolase activities. This study indicates that no major changes occur in the retinoid- related parameters analyzed with age, suggesting that rat liver retinoid metabolism does not change dramatically with age and that retinoid homeostasis is maintained. [ABSTRACT FROM AUTHOR]

Published
1988
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46. Association of APOE epsilon2/epsilon3/epsilon4 and promoter gene variants with dementia but not cardiovascular mortality in old age.

Author

Heijmans BT, Slagboom PE, Gussekloo J, Droog S, Lagaay AM, Kluft C, Knook DL, and Westendorp RG

Subjects
Age Factors, Aged, Aged, 80 and over, Apolipoprotein E2, Apolipoprotein E3, Apolipoprotein E4, Cardiovascular Diseases genetics, Cohort Studies, DNA genetics, Female, Gene Frequency, Genetic Variation, Genotype, Humans, Male, Risk Factors, Survival Rate, Apolipoproteins E genetics, Cardiovascular Diseases mortality, Dementia genetics, Promoter Regions, Genetic genetics
Abstract

The common apolipoprotein E (APOE) alleles epsilon2, epsilon3, and epsilon4 are associated with the risk of dementia and cardiovascular disease. Recently, two functional variants (- 219G/T and -491A/T) were identified in the promoter of the APOE gene that enable a further characterization of the role of the APOE locus in disease. We investigated the contribution of these APOE gene variants to dementia and cardiovascular mortality in old age using a population-based cohort of 648 subjects aged 85 years and over (Leiden 85-Plus Study). Genotypes containing an APOE epsilon4 allele were associated with a 4.1-fold (95% CI, 2.2-7.7) increased risk of dementia as compared to the epsilon3/epsilon3 genotype in old subjects. Moreover, homozygosity for the -219T allele was found to be associated with a 2.4-fold (95% CI, 1.0-5.8) increased risk independently of epsilon2 and epsilon4; the -491A/T variant was not associated with dementia. Over a 10-year follow-up period, the risk of cardiovascular mortality was not increased among epsilon4 carriers (RR, 0.6; 95% CI, 0.4-1.0) or -219T homozygous subjects (RR, 1.1; 95% CI, 0.7-1.7), nor did it decrease among -491T homozygous subjects (RR, 1.4; 95% CI, 0.6-3.1). In conclusion, both the APOE epsilon2/epsilon3/epsilon4 and the -219G/T variant were identified as risk factors for dementia but not cardiovascular mortality in old age. Our results support the hypothesis that both the isoform and the amount of APOE may influence the risk of dementia. Furthermore, they emphasize that variation at the APOE locus has a higher impact on the risk of dementia than on the risk of cardiovascular disease in old age., (Copyright 2001 Wiley-Liss, Inc.)

Published
2002
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