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D J Morris

Publications and source records attributed to D J Morris.

220 records · Page 13Linked to original sources

The possible biological role of aldosterone metabolites.

Following the incubation of aldosterone with microsomes from liver of adrenalectomized male rates, a previously unidentified polar neutral metabolite of aldosterone, designated "peak A" material, was isolated and purified using high pressure liquid chromatography. This peak A material, which contains a reduced hydroxylated metabolite of aldosterone, was shown to possess 2% to 3.5% of the mineralocorticoid activity relative to aldosterone. When bovine adrenal glomerulosa cells were incubated with peak A material (3 and 10 micrograms/ml), the binding of 125I-angiotensin II was inhibited by 20% and 36%, respectively. The mineralocorticoid activity of the six possible ring A reduced metabolites was tested. The 5 alpha-reduced metabolites were more potent than the 5 beta-, and the 3 alpha- were more potent than the 3 beta-reduced metabolites. The renal and extrarenal transformations of aldosterone to the polar and nonpolar (reduced) metabolites and their possible role in the accepted mechanism of action of aldosterone is discussed.

Adrenal Glands↗

Study of 30 DNA markers in three southern African populations.

Thirty anonymous DNA markers were investigated in Southern African Caucasoid, Negroid and San populations. Sixteen of these are new markers that were developed in our laboratory; the remainder are closely linked to the cystic fibrosis locus on chromosome 7. Average heterozygosity in the Caucasoid and Negroid populations was calculated at the loci identified by each of the anonymous probes, using two approaches, and was found to be .0020 and .0030 for the Caucasoid population and .0023 and .0025 for the Negroid population. Variation between populations (measured by FST) and between markers was calculated from allele frequency data gathered for all markers in the three populations. Significant differences in allele frequency between the populations were observed for the cystic fibrosis markers MET D, MET H and 7C22, with little or no variation observed in the Negroid and San populations. Mean heterozygosity (D) was found to be considerably lower in San (.250) than in Caucasoid (.373) and Negroid populations (.0320) and possible explanations for this are provided. The smallest genetic distance (60 x 10(-3)) was found between the Negroid and San populations, and the greatest distance between the Caucasoid and San populations (167 x 10(-3)).

Africa, Southern↗

Inhibitors of 11 beta-hydroxysteroid dehydrogenase and 5 beta-steroid reductase in urine from patients with congestive heart failure.

Recently, the current authors reported the presence in normotensive male and female urines of reproducibly measurable levels of naturally occurring substances in partially purified extracts of urine with inhibitory activity like glycyrrhetic acid (GA) towards both 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) and steroid 5 beta-reductase (5 beta-SR) in vitro. Since these substances mimic two known inhibitory activities of GA, they have been named 'Glycyrrhetic Acid-Like Factors', abbreviated as 'GALFs' or, more specifically 11 beta-GALF for substance(s) active against 11 beta-OHSD, and 5 beta-GALF for those inhibitory to 5 beta-SR. Administration of glycyrrhetic acid in man leads to cortisol-dependent mineralocorticoid hypertension, owing to impaired inactivation of cortisol by 11 beta-OHSD, and may be associated with increased sensitivity to mineralocorticoids owing to impaired 5 beta-SR. In this preliminary report, the results are described of a study on the presence of GALF factors in urines collected from patients with congestive heart failure (CHF) and mild essential hypertension. The results show that in such patients there are increased amounts of both 11 beta- and 5 beta- GALFs compared to normotensive. The possible physiological significance of these results is discussed.

11-beta-Hydroxysteroid Dehydrogenases↗