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Biomedical subjects

K L Melmon

Publications and source records attributed to K L Melmon.

At least 127 records · Page 7Linked to original sources
PubMed1974

Hemolytic plaque formation by leukocytes in vitro. Control by vasoactive hormones.

Histamine, beta-adrenergic amines, and prostaglandins inhibited hemolytic plaque formation by splenic leukocytes from immunized mice. The same agents had previously been shown to prevent both the IgE-mediated release of histamine from human basophils and the immunologically specific cytolytic activity of murine lymphocytes, through stimulation of the production of cyclic AMP in leukocytes. We therefore tested the hypothesis that cyclic AMP might mediate an inhibitory effect of these drugs by comparing the ability of these agents to inhibit plaque formation with their effects on cyclic AMP accumulation in leukocytes. In splenic cells from three mouse strains, the dose-dependent effects of these agents of cyclic AMP correlated with their inhibition of plaque formation. Beta- but not alpha-adrenergic agonists were effective in both systems, and the effects of isoproterenol were inhibited by propranolol. Histamine was approximately equipotent with isoproterenol in both systems. Two prostaglandins (E(1) and E(2)) were effective in both systems, but prostaglandin F(2alpha) was not. Dibutyryl cyclic AMP, a lipid-soluble analog of the endogenous nucleotide, inhibited plaque formation by cells of all three strains. Theophylline, an inhibitor of cyclic AMP degradation, inhibited plaque formation slightly, but potentiated the effects of histamine, isoproterenol, and the prostaglandins on both cyclic AMP accumulation and plaque formation. Finally, cholera enterotoxin, a potent activator of adenyl cyclase, produced a delayed inhibition of plaque formation and a parallel increase in leukocyte cyclic AMP content; both effects of the toxin were blocked by canine antitoxin. These results suggest that leukocyte cyclic AMP may act as a "second messenger" to suppress plaque formation in vitro. The inhibitory effects of hormones and cyclic AMP on plaque formation are strikingly similar to their effects on in vitro models of immediate and cell-mediated hypersensitivity. The physiologic significance of these findings is not yet known.

Animals↗
PubMed1974

Separation of specific antibody-forming mouse cells by their adherence to insolubilized endogenous hormones.

Spleen cells from mice immunized with sheep red cells were separated by differential adherence to insolubilized histamine, catecholamines, and prostaglandins. The hormones were insolubilized by linking them to Sepharose beads through a protein carrier. We measured hemolytic plaque formation (per million splenic leukocytes) of cells which passed through columns of hormone-carrier-Sepharose beads (i.e., those cells that failed to bind). As compared with control (no column) cells, the number of plaque-forming cells was substantially reduced by passage through histamine, epinephrine, isoproterenol, and prostaglandin-E(2) columns. Plaque-forming cells were not significantly reduced by passage through carrier Sepharose (another control) or norepinephrine- and prostaglandin-F(2alpha)-carrier Sepharose columns. Thus, the ability of an insolubilized hormone preparation to subtract plaque-forming cells roughly correlated with the presence of pharmacologic receptors for the corresponding free hormones, as judged by stimulation of cyclic AMP accumulation in the same cells, reported previously. Both 19S and 7S plaque-forming cells were subtracted by columns prepared from pharmacologically active hormones, but none of the insolubilized hormones stimulated accumulation of intracellular cyclic AMP. The cell membrane phenomenon that allows adherence to a given hormone-carrier-bead column may be identical with the cell receptor.

Animals↗
PubMed1973

Pharmacokinetics of digoxin: interpreting bioavailability.

Three subjects were first given a digoxin tablet in the fasting state and subsequently received the same formulation in the fed state, to simulate a spurious oral bioavailability difference. As expected, when measured by peak serum digoxin concentration as well as by area under the serum digoxin concentration-time curve the bioavailability of digoxin appeared to be higher in the fasting state than in the fed state. However, when measured by cumulative five-day urinary excretion of digoxin bioavailability was identical in both conditions.This simple experiment illustrates the fact that the estimation of bioavailability is subject to considerable methodological error, of which the clinician must be aware when evaluating reports on drug bioavailability in general and of digoxin in particular.

Administration, Oral↗