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Biomedical subjects

M Young

Publications and source records attributed to M Young.

At least 451 records · Page 25Linked to original sources
PubMed1973

Net placental transfer of free amino acids against varying concentrations.

1. The patterns of the free plasma amino acids in the pregnant guinea-pig and her foetuses, near term, are described. The concentration of each amino acid was higher in the foetal plasma than in the maternal. The foetal:maternal gradients (F:M) varied for each amino acid; the straight chain amino acids had the highest F:M ratios.2. Net transfer of endogenous plasma amino acids, from the maternal circulation across the placental membrane, was studied. The foetus was removed and the foetal placenta perfused in situ via the umbilical arteries, with an artificial fluid containing varying concentrations of amino acids.3. All the amino acids, both essential and non-essential, could be transferred from the maternal to the foetal circulation against the F:M gradients. With ;closed circuit' perfusion, this transport increased the concentration of total amino N in the perfusate until it was twice that of the normal F:M gradient of 5. The concentrations of the individual amino acids was increased to 1.7-4.2 times those normally present in foetal plasma, and the final values reached were similar to the concentrations of free amino acid found in placental tissue.4. The umbilical vein-artery differences were small, with the placenta perfused ;open circuit' in the steady state, using physiological flow rates and amino acid concentrations. The average net placental transfer of amino N found was 1.14 m-mole min(-1). This is about 60% of the calculated net rate of accumulation of N by the 60 g guinea-pig foetus.5. The influence of foetal placental perfusion concentration on transfer was small but significant. In the steady state, the transfer of amino N, and each individual amino acid, was found to be inversely proportional to the concentrations in the perfusate when the placenta was perfused ;open circuit'. The slopes of the regression of transfer on concentration had an average value of 0.13 n-mole min(-1) g(-1) per mumole. No significant difference in the slopes was found between the three amino acid transport groups.6. Net transfer was independent of perfusate flow, within the physiological range, which suggests a secretory process across the membrane from maternal to foetal circulation.

Amino Acids↗
PubMed1972

Studies on the mechanism of action of nerve growth factor.

In this study, explanted chick-embryo sensory ganglia were treated with nerve growth factor, and cellular concentrations of neurotubule protein were measured chemically by a colchicine-binding assay. Even after brief time periods, ganglia treated with growth factor were enriched in neurotubule protein, as compared with untreated (control) ganglia. Furthermore, studies with ganglia treated with both vincristine and growth factor demonstrated that neurotubule protein synthesis can occur even though neurite outgrowth is abolished. Several lines of evidence indicate that the growth factor stimulates de novo synthesis of neurotubule subunit protein, and that this effect precedes neurite extension. Like nerve growth factor, dibutyryl cyclic AMP also stimulates neurite outgrowth from embryonic sensory ganglia, yet it does not increase neurotubule protein levels. Available information suggests that the ability of growth factor to elicit rapid neurite outgrowth is closely related to its ability to increase cellular neurotubule levels. Cyclic AMP appears to stimulate neurite outgrowth by a different mechanism.

Animals↗
PubMed1972

Studies on the localization of the cardiac glycoside receptor.

The purpose of this study was to see whether the receptor for cardiac glycosides might be localized upon or within the plasma membrane of digitalis-sensitive cells. Ouabain and digoxin were joined covalently to several large protein molecules. These macromolecular conjugates are too large to enter intact cells; consequently, any pharmacologic or biochemical effects which they display should arise from interaction with a cell surface receptor. Conjugates were tested in several cardiac glycoside-sensitive systems: (a), contractility response of isolated cardiac muscle; (b), active (86)Rb(+) uptake by red cells; (c), enzymatic activity of isolated myocardial microsomal (Na(+) + K(+))-activated adenosine triphosphatase (ATPase); and (d), enzymatic activity of solubilized red cell (Na(+) + K(+))-activated ATPase. Results demonstrated that in all of these systems, the macromolecular-glycoside conjugates were 100- to 1000-fold less active than the free glycosides. Careful chromatographic examination of the various conjugates revealed that they contained a small but persistent free cardiac glycoside contaminant. The amount of this species ranged from 0.1 to 1.0% of the total macromolecule-bound glycoside, and its presence fully explains the levels of biologic activity observed with the conjugates. To try to minimize steric factors which could interfere with glycoside-receptor interaction, digoxin and ouabain were also coupled to macromolecule via long, flexible polyamide side-chains. These extended chain conjugates, in which the cardiac glycoside potentially lay some 30 A removed from the surface of the macromolecule, also exhibited negligible digitalis-like effects when tested upon isolated cardiac muscle, red cell (86)Rb(+) uptake, and enzymatic activity of cardiac microsomal (Na(+) + K(+))-ATPase. However, the extended chain conjugates were fully active when examined with the solubilized red cell (Na(+) + K(+))-ATPase system. To further ensure that the chemical reactions used to couple macromolecule to glycoside did not inactivate the drug, all conjugates were subjected to extensive proteolytic digests exhibited full pharmacologic activity. Digoxin was also coupled to the tripeptide alanylglycylglycine, and the resulting conjugate was fully active. Taken together, these results suggest that if the receptor(s) for cardiac glycosides is associated with the plasma membrane, then it may lie deep within it.

Adenosine Triphosphatases↗
PubMed1971

Rapid and complete purification of acetylcholinesterases of electric eel and erythrocyte by affinity chromatography.

Affinity chromatography has been used to purify acetylcholinesterase both from the electric tissue of Electrophorus electricus and from bovine erythrocyte membranes. For this purpose, several specific enzymic inhibitors of each protein were synthesized and joined covalently to an insoluble support resin. AchE is selectively retained by such inhibitor-resins when highly impure solutions are chromatographed upon them. After removal from the resin, both enzymes are electrophoretically homogeneous and they may be recovered in yields of 75% or more.

Acetylcholinesterase↗