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P Kao

Publications and source records attributed to P Kao.

7 recordsLinked to original sources

Combining functional and linkage disequilibrium information in the selection of tag SNPs.

UNLABELLED: We have developed an online program, WCLUSTAG, for tag SNP selection that allows the user to specify variable tagging thresholds for different SNPs. Tag SNPs are selected such that a SNP with user-specified tagging threshold C will have a minimum R2 of C with at least one tag SNP. This flexible feature is useful for researchers who wish to prioritize genomic regions or SNPs in an association study. AVAILABILITY: The online WCLUSTAG program is available at http://bioinfo.hku.hk/wclustag/

Algorithms↗

Aging and aldosterone.

We measured urinary and plasma aldosterone in normal subjects, aged 20 to 59 years, during a period of unrestricted sodium intake and after sodium depletion, using furosemide or a 20 meq sodium diet. Before and after sodium depletion, the mean and the upper limit of the range of urinary aldosterone excretion were considerably lower in subjects over 50 years compared with subjects under 30 years. Aging had no effect on plasma aldosterone concentration when the subjects were on an unrestricted sodium diet and blood was sampled while they were recumbent. In contrast, when the subjects were upright, both before and after sodium depletion, the mean and the upper limit of the range of plasma aldosterone concentration were lower in the subjects over 50 years compared with those under 30 years. The metabolic clearance of aldosterone was the same in the younger and the older subjects. Of eight patients over 40 years of age with aldosterone-producing adenoma, four had normal aldosterone excretion rates when the normal range was not age adjusted, but with age adjustment, all of the patients had clearly elevated excretion rates. Similarly, six of seven patients over 40 years of age had normal upright plasma aldosterone concentrations if the normal range of plasma aldosterone concentration was not age adjusted. We conclude that aldosterone secretion declines with advancing age. The effect of age on aldosterone secretion is an important consideration when evaluating older hypertensive patients for primary aldosteronism.

Adenoma↗

The effect of metoclopramide and dopamine on plasma aldosterone concentration in normal man and rhesus monkeys (Macaca mulatta): a new model to study dopamine control of aldosterone secretion.

Metoclopramide, a dopamine receptor antagonist, increases plasma aldosterone concentration in man, suggesting that dopamine regulates the secretion of aldosterone. In the current study, we administered metoclopramide to rhesus monkeys and normal subjects and compared the time-course and dose-response characteristics of plasma aldosterone. We also examined the effect of dopamine on the plasma aldosterone response to metoclopramide in both species. Six male rhesus monkeys and several normal subjects (five women and two men) were studied on diets providing an estimated daily sodium intake of 70 mg/kg. In both species the peak increase in plasma aldosterone occurred 15 min after metoclopramide was injected. The peak plasma aldosterone value was 3-fold higher than control values. There were no significant changes in PRA, cortisol or potassium, whereas plasma PRL increased 7-fold in the monkeys and 11-fold in the normal subjects. After 0.04 mg/kg metoclopramide, there was no change in plasma aldosterone concentration in the monkeys, whereas aldosterone increased significantly (delta = 3.7 +/- 0.68 ng/dl) in the human subjects. The half-maximal dose of metoclopramide was also higher in the monkeys than in the normal subjects. A dopamine infusion at 4.0 to 8.0 micrograms/kg . min partially suppressed the plasma aldosterone response to metoclopramide in both the human subjects and the monkeys. This study demonstrates that metoclopramide produces dose-related increases in plasma aldosterone concentration in the nonhuman primate that are similar to those in normal man and that the increases can be inhibited by dopamine. We conclude that aldosterone secretion may be under dopamine control and that the rhesus monkey should be an excellent model in which to study further the regulation of aldosterone by dopamine.

Adult↗

Effect of metoclopramide on the secretion and metabolism of aldosterone in man.

We performed this study to determine whether metoclopramide increases the concentration of plasma aldosterone in normal man by increasing the secretion rate of aldosterone or by decreasing aldosterone metabolic clearance. On the first day that metoclopramide was administered orally to seven normal subjects, the secretion rate of aldosterone increased significantly (P less than 0.05) from the rate during the preceding placebo period. By the fourth day of treatment, the secretion rate had returned to control values and remained there during an ensuing placebo period. The excretion rate of aldosterone followed a similar pattern. The increase in aldosterone secretion was accompanied by a transient but significant decrease in urinary sodium excretion. Metoclopramide administered iv had no effect on the metabolic clearance of aldosterone. Metoclopramide stimulated aldosterone-producing adenomas and nodular hyperplastic adrenal tissue resected from patients with primary aldosteronism to produce aldosterone in vitro. We conclude that metoclopramide increases the concentration of aldosterone in plasma by stimulating the secretion of aldosterone rather than by decreasing aldosterone metabolic clearance, and that metoclopramide probably stimulates aldosterone secretion by acting directly on adrenal tissue.

Adult↗