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Biomedical subjects

A Mellors

Publications and source records attributed to A Mellors.

At least 73 records · Page 4Linked to original sources

Nuclear magnetic resonance studies in liposomes: effects of steroids on lecithin fatty acyl chain mobility.

The effects of fourteen sterols on the NMR spectra of liposomes derived from egg yolk phosphatidylcholines were studied by continuous-wave and Fourier-transform measurements at 60 MHz. Sterols were compared for their ability to broaden the acyl methylene resonances of phosphatidylcholine, when incorporated into liposomes at 25% molar ratio. The ratio of the phosphatidylcholine peake heights (acyl methylene: choline N-methyl) was used as a criterion of the relative condensing activity for the different sterols. This ratio was inversely proportional to the molar volume of the incorporated sterol, as measured by the parachor of the compound. Small sterols had little condensing effect, and the larger sterols such as cholesterol and ergosterol had maximum condensing effects. The study confirmed the importance of the sterol side-chain at C-17 as a requirement for sterol-phospholipid interaction.

Glucose↗

Molar volume relationships and the specific inhibition of a synaptosomal enzyme by psychoactive cannabinoids.

The ability of a number of lipophilic compounds to inhibit the mouse-brain synaptosomal enzyme acyl coenzyme A:lysophosphatidylcholine acyltransferase has been measured in vitro. Psychoactive cannabinoids inhibit the enzyme at concentrations much lower than is predicted from their capacity to act as lipid-soluble anesthetics. Nonpsychoactive cannabinoids do not show specific inhibition. Molar volume relationships are used to show that, while all lipid-soluble molecules exert some inhibitory effect in proportion to their ability to dissolve in biological membranes, psychoactive cannabinoids have an inhibitory effect greatly in excess of their anesthetic potency. The isoprenoid convulsant thujone has been suggested to have psychoactivity similar to cannabinoids but does not mimic the cannabinoids in inhibiting the synaptosomal enzyme. Molar volumes and specific interactions are used in structure-activity correlations which yield information on the relative concentrations of biophase in drug-responsive systems and the specificity of membrane-active drugs.

1-Acylglycerophosphocholine O-Acyltransferase↗

The generation of phospholipase A and hemolytic fatty acids by autolysing suspensions of Trypanosoma congolense.

When T. congolense undergoes autolysis there is a concomitant appearance of phospholipase A activity and hemolytic fatty acids. The generation of enzyme activity is exponential, and the appearance of hemolytic activity corresponds to a free fatty acid concentration of 0.02 to 0.03 mg. per ml. The concentration of the trypanosome suspension markedly affected the kinetics of the generation process. In contrast, the autolysis of T. lewisi did not generate hemolytic activity unless exogenous phospholipase A was added to the organisms.

Autolysis↗

Inhibition of a lymphocyte membrane enzyme by delta9-tetrahydrocannabinol in vitro.

Delta-9-tetrahydrocannabinol (delta9-THC) inhibited the activity of lysolecithin acyl transferase, a membrane-bound lymphocyte enzyme, at concentrations above 1.3 muM. Stimulation of acyl transferase activity by concanavalin A, an early response in lymphocyte activation, was entirely abolished in the presence of delta9-THC.

1-Acylglycerophosphocholine O-Acyltransferase↗

The generation and identification of the hemolysin of Trypanosoma congolense.

The hemolytic activity of Trypanosoma congolense appears to be due to the presence of free fatty acids generated by the action of phospholipase A on endogenous phosphatidyl choline. Some lysolecithin also contributes to the lytic activity. Trypanosoma lewisi, being devoid of phospholipase A, does not generate free fatty acids and is therefore non-hemolytic.

Animals↗

Lysosomal membrane labilization by DDT, DDE and polychlorinated biphenyls (PCB).

Incubation of the ubiquitous pollutants, polychlorinated biphenyls (PCB), DDT and DDE with rat liver lysosomes shows that these lipophillic substrates are highly active labilizers of lysosomal membranes. The release of acid phosphatase was used as a marker enzyme and at high PCB, DDT and DDE concentrations (2X10(-3)M) the lytic activity was similar to that of the detergent Triton X-100; at lower concentrations most of the commercial PCB samples, DDT and DDE still retain considerably lytic activity.

Animals↗

Effects of ten steroids on acridine orange uptake and beta-N-acetylglucosaminidase levels in rat liver lysosomes.

Ten steroids have been compared for their ability to modify the rate of uptake of acridine orange by rat liver and by rat liver lysosomes in vivo. The short-term effects of the ten steroids on the specific activity of a lysosomal enzyme, beta-N-acetylglucosaminidase, were also compared. Five of the ten steroids were administered as tritium-labelled compounds and the concentration of steroids or metabolites was measured in rat liver and liver lysosomes at 2.5h and 3.75h after administration. Cortisone acetate, etiocholanolone (5-beta-androstan-3-alpha-01-17-one) and testosterone accelerate and increase the uptake of acridine orange by rat liver lysosomes. Deoxycorticosterone, corticosterone, triamcinolone (9-alpha-fluoro-11-beta, 17, 21-trihydroxy-16-alpha-methyl-pregna-1, 4-diene-3, 20-dione), estradiol-17-beta and progesterone appear to inhibit the uptake of acridine orange by rat liver lysosomes at 2.5 hours. Cortisol and dexamethasone (9-alpha-fluoro-11-beta, 17, 21-trihydroxy-16-alpha-methyl-pregna-1, 4-diene-3, 20-dione) had little effect. All steroids with the exception of etiocholanolone and deoxycorticosterone increase with the specific activity of beta-N-acetylglucosaminidase in the lysosomal fraction at 2.5h. None of the effects at 2.5h are due to lowered protein levels. Lysosomal concentrations of radioactivity following the administration of tritiated steroids were greated for the glucocorticoids, corticosterone and cortisol. Estradiol-17-beta, progesterone and testosterone showed much lower concentrations of radioactivity in isolated lysosomes. Most of the lysosomal radioactivity (73-96%) was associated with the soluble fraction of the disrupted lysosomes.

17-Ketosteroids↗

Evidence for NAD nucleosidase in rabbit-liver lysosomes.

A method is described for the isolation of secondary lysosomes from homogenates of rabbit liver; The uptake of Triton WR-1339 by rabbit-liver lysosomes when administered by intraperitoneal injection was used to decrease the density of secondary lysosomes. Lysosomal fractions prepared by this method contain an NAD nucleosidase (NAD glycohydrolase, EC 3;2.25), an enzyme which has previously been considered to be associated with other subcellular fractions. The enzyme has maximum activity at pH 6 and cleaves both NAD and NADP. It is inhibited by nicotinamide (Ki equals 4.5 mM) and by HgCl2. Both nucleosidase and 2'-nucleotidase show in-vitro latency typical of lysosomal acid hydrolases. Rabbit-liver plasma-membrane fractions were isolated which contained most 5'-nucleotidase but relatively little nucleosidase, whereas rabbit liver lysosomes contain both 5'-nucleotidase and nucleosidase enzymes but little adenyl cyclase.

Animals↗