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Biomedical subjects

G M Thompson

Publications and source records attributed to G M Thompson.

44 records · Page 3Linked to original sources
PubMed1983

Regulation of hepatic receptor-dependent degradation of LDL by mevinolin in rabbits with hypercholesterolemia induced by a wheat starch-casein diet.

Rabbits fed a wheat starch-casein diet develop a marked hypercholesterolemia and have a slower rate of removal of rabbit 125I-labeled low density lipoproteins (LDL) from plasma. Treating rabbits with mevinolin, a highly potent competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, at a daily dose of 20 mg per animal prevents the increase in plasma and LDL cholesterol. The mevinolin effect is mediated through an increased rate of removal of rabbit 125I-labeled LDL from plasma. To study the role of mevinolin on the regulation of the hepatic LDL receptor in rabbits, the binding of 125I-labeled LDL and 125I-labeled beta-VLDL (beta-migrating very-low-density lipoproteins) to liver membranes prepared from rabbits fed the wheat starch-casein diet with or without mevinolin was investigated. Liver membranes from wheat starch-casein-fed rabbits have no demonstrable EDTA-sensitive binding activity of 125I-labeled LDL and low (37 ng/mg protein) binding activity of 125I-labeled beta-VLDL. Treatment of the wheat starch-casein fed rabbits with mevinolin results in high levels of specific EDTA-sensitive binding of 125I-labeled LDL (28.7 ng/mg protein) and 125I-labeled beta-VLDL (120 ng/mg protein). To assess the functional role of the hepatic LDL receptor in response to mevinolin, the catabolism of 125I-labeled LDL by perfused rabbit livers was studied. Perfused livers from mevinolin-treated rabbits show a 3.3-fold increase in the rate of receptor-dependent catabolism of 125I-labeled LDL (4.6% X h-1) when compared with that of livers from rabbits not treated with mevinolin (1.4% X h-1). Thus, these studies demonstrate that mevinolin prevents the increase of plasma LDL cholesterol level in rabbits fed a wheat starch-casein diet by regulating the levels of hepatic LDL-binding sites and the rate of receptor-dependent catabolism of LDL by the liver.

Animals↗
PubMed1983

Radiation retinopathy following treatment of posterior nasal space carcinoma.

Posterior nasal space carcinoma has a high mortality and most patients are treated with radiotherapy. Radiation retinopathy was encountered in 7 out of 10 survivors included in this study. Five of the affected patients lost vision as a result of the retinopathy. One patient required laser photocoagulation and responded well to this treatment. There was a variation in the severity of the retinopathy among the patients studied despite the fact that all patients received a similar dose of radiotherapy. We suspect that previously unrecognised factors in the planning of radiotherapy fields may explain this difference.

Adult↗
PubMed1979

Efficacy of acycloguanosine (Wellcome 248U) against herpes-simplex corneal ulcers.

Acycloguanosine (9-[-hydroxyethoxymethyl]guanine) (Wellcome 248U) has a highly specific and potent antiviral action against herpes-simplex virus (H.S.V.) types I and II in cell-culture systems and in animal models of H.S.V. infection in the brain, skin, and eye. Its efficacy in man was tested in twenty-four patients with dendritic corneal epithelial ulcers treated by minimal wiping debridement. Patients were randomly allocated to treatment with 3% acycloguanosine eye ointment or placebo. There were seven recurrences or recrudescences of typical corneal epithelial herpetic lesions within 1 week of debridement in the twelve patients who received placebo, and no recurrences in the twelve who received acycloguanosine. Four further patients with dendritic ulcers have been electively treated with topical acycloguanosine alone. Their ulcers all healed briskly. No adverse effects were seen with the acycloguanosine therapy. These results establish that acycloguanosine is a clinically effective antiviral drug against H.S.V. infection in man.

Administration, Topical↗
PubMed1970

Some central effects in mice of compounds related to nicotine.

1. Some hydroxy-, amino-, and methoxy- phenylalkyltrimethylammonium compounds, beta-pyridylmethyl- dimethylamine and pyrrolidine, and beta-pyridylethyltrimethylammonium, were tested on avoidance learning in mice and their effects were compared with those of (-)-nicotine.2. The o- and m- hydroxybenzyl-, o-hydroxyphenethyl- and m-hydroxyphenylpropyl- trimethylammonium compounds improved performance; (-)-nicotine, in one-quarter of the dose, had similar effects. The m- and p-hydroxyphenethyl-, o-hydroxyphenylpropyl- and o- and p- aminobenzyl, and o-, m-, and p- aminophenethyl-trimethylammonium compounds impaired performance.3. (-)-Nicotine and m-hydroxyphenylpropyltrimethylammonium appeared also to enhance memory consolidating processes.4. The central actions of some of the compounds suggest that the possibility that they can penetrate into the central nervous system should not be ruled out even though they are quaternary salts.5. No correlation was found between the effects of the compounds on avoidance learning and on the frog rectus muscle. Though the differences may be due to differences in access to the central nervous system, it is also possible that the receptors associated with learning processes are different from those in the frog rectus and possibly more specialized.

Animals↗
PubMed1969

The affinity and activity of compounds related to nicotine on the rectus abdominis muscle of the frog (Rana pipiens).

1. Series of pyridylalkyl- and substituted phenylalkyl-trimethylammonium salts, triethylammonium salts, diethylamines and di-n-propylamines have been made. The substituents in the benzene ring were nitro, chloro, bromo, methoxy, hydroxy and amino groups and the alkyl residues had one, two, or three methylene groups separating the aromatic nucleus from the cationic head.2. Most of the trimethylammonium compounds caused a contracture of the frog rectus muscle, but some were partial agonists and a few were antagonists. The di-n-propylamines were all antagonists, as were most of the diethylamines and triethylammonium compounds, though some of these were partial agonists and a few triethylammonium compounds were agonists. The affinities of the antagonists and partial agonists for the receptors stimulated by beta-pyridylmethyltrimethylammonium (and by nicotine) were measured. The equipotent molar ratios of all the agonists were measured relative to beta-pyridylmethyltrimethylammonium.3. The dissociation constants of the pyridylmethyldiethylamines and substituted benzyldiethylamines were measured. The effects of substituents on the pK(a) of benzyldiethylamine were similar to their effects on the pK(a) of aniline, though there were differences with some of the o-substituted compounds, which could be attributed to internal hydrogen-bond formation.4. There is no obvious correlation between the effects of a substituent on the pK(a) of benzyldiethylamine and its effects on affinity. Although increasing the size of the cationic group usually increased affinity, it did not always do so. The compounds with the highest affinity, p-hydroxybenzyldiethylamine (log K, 5.90) had about half the affinity of (+)-tubocurarine (log K, 6.11), but the triethylammonium analogue (log K, 4.17) had only about one-fiftieth of the affinity of the tertiary base. The binding of the drug to the receptor appears to involve many factors which include the size of the groups as well as their electron-releasing or withdrawing nature and other properties, such as their polar and lipophilic or lipophobic character.5. There is no obvious correlation between the effects of a substituent on the affinity of the diethylamino or triethylammonium compounds and its effects on the activity of the trimethylammonium analogue. The most active compounds contain hydroxy- and amino-, phenyl or beta-pyridyl groups, m-hydroxyphenyl-propyltrimethylammonium being about 50 times as active as nicotine, but the corresponding diethylamino or triethylammonium compounds do not have high affinity. There does not seem necessarily to be an inverse relationship between activity and affinity, however, because some m-nitro and m-chloro trimethylammonium compounds have considerable activity and the analogous triethylammonium compounds have considerable affinity.6. It is suggested that ability to activate these receptors is associated with the presence of substituents which can interact with water molecules which may be involved in the action of the drug at the receptor.

Amines↗