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Biomedical subjects

C Thomson

Publications and source records attributed to C Thomson.

At least 37 records · Page 2Linked to original sources

The molecular structures of 11-methyl and 1,12-dimethylbenz[a]anthracene: purely theoretical semi-empirical AM1 calculations are able to predict accurate structures of these polycyclic hydrocarbons.

Semi-empirical self consistent field calculations are reported on 11-methyl and 1,12-dimethylbenz[a]anthracene using the AM1 method. Comparison of the results of complete geometry optimizations with experimental X-ray structures shows that it is now possible to compute the structure of these large molecules with errors in bond lengths of less than 0.02 A and in bond angles of less than 1.5 degrees.

Benz(a)Anthracenes

The conformations and electrostatic potential maps of phorbol esters, teleocidins and ingenols.

Phorbol esters and the structurally dissimilar teleocidins and ingenols bind to and activate protein kinase C (PKC) during the course of tumour promotion. These compounds are referred to as TPA-like tumour promoters (from 12-O-tetradencanoyl phorbol-13-acetate, the most active of the class) and are amongst the most potent tumour promoters known. Despite their structural dissimilarity, all three groups of molecules have been shown to bind to the diacylglycerol site of PKC with high affinity. It is thought that this binding to and consequent activation of PKC is the crucial step in tumour promotion by these compounds. The aim of this work was to provide a description of the binding site by comparing structural features (in particular the electrostatic potential) with the activity of numerous derivatives of the three classes. Initially the description was obtained by consideration of the phorbol derivatives, and then refined using the teleocidins and ingenols. The activity data were collected from a variety of sources and the structures calculated using the semi-empirical MNDO approximation embodied in the MOPAC program. Where possible, the crystal structure was obtained from the Cambridge Crystallographic Database, and used as a starting point for the calculation. In other cases, a preliminary calculation was carried out using the molecular mechanics program AMBER. Electrostatic potentials were calculated and displayed using an in-house program 3D2, while superpositions of molecules were carried out using CHEM-X.

Diterpenes

Kinetics of cell adhesion to polymer surfaces.

Results of the kinetics of adhesion of granulocytes as well as fresh and glutaraldehyde-fixed erythrocytes, suspended in Hanks Balanced Salt Solution (HBSS; pH 7.2, ionic strength of 0.15) to various polymeric substrates are presented. Cell adhesion increases rapidly initially and reaches a plateau value after approximately 30 minutes. There is no evidence for a lag-time in the onset of cell adhesion, suggesting that electrostatic double-layer forces are negligible under these experimental conditions. For the experiments in which the cells are suspended in HBSS, which has a surface tension larger than that of the cells, the level of cell adhesion increases with decreasing surface tension of the polymeric substrates. An additional experiment with fresh human granulocytes suspended in HBSS containing 10% dimethyl sulfoxide was also performed. The surface tension of the resulting liquid medium is below that of the cells and the pattern of adhesion is reversed, in agreement with the predictions of a thermodynamic model for cell adhesion. The slightly different behavior of siliconized glass as a substrate is discussed in terms of "screening."

Biocompatible Materials

Dipeptidyl peptidases in the soleus muscle of the rat before and after treatment with 5-hydroxytryptamine.

A moderate peptidase activity against L-lysyl-L-proline-4-methoxy-beta-napththylamide was detected histochemically in unfixed sections of soleus muscle fibres of inbred male Wistar rats using two variants of the semipermeable membrane technique. One variant involved simultaneous coupling with tetrazotised 3,3'-dimethoxybenzidine, the other post-coupling. The activity at pH 6 increased approximately three-fold in many fibres showing signs of insult in rats that had been given a single low dose of 5-hydroxytryptamine (10 mg/kg body weight) 48-72 h earlier. The hydroxytryptamine treatment was found to induce a selective myopathy. Some of the increased peptidase activity within insulted muscle fibres appeared to arise from invading mononuclear cells, but the majority seemed endogenous to muscle fibres. The peptidase activity persisted in some fibres 21-28 days after 5-hydroxytryptamine administration, by which time the whole muscle appeared histologically normal. The variation of the activity of the peptidase with pH in the presence of various inhibitors was investigated in both control and insulted muscle fibres. From its sensitivity and behaviour towards Zn2+, Hg2+, Cu2+, puromycin, benzethonium chloride and phenylmethylsulphonyl fluoride and its indifference towards Co2+, Cd2+, Mn2+ and o-phenanthroline, it is concluded that the activity can be attributed to a mixture of at least two peptidases, dipeptidyl peptidase II and an unidentified neutral dipeptidyl peptidase. The possible role of the peptidase(s) in muscle regeneration in discussed.

Animals

Altered platelet lipoxygenase activity in patients with low selenium.

1. Arachidonic acid metabolism through the lipoxygenase pathway in platelets was investigated in 11 patients with low selenium (Se) nutritional status and compared with 14 patients with a normal Se status. 2. Plasma and whole blood Se levels, as well as plasma, whole blood and platelet glutathione peroxidase (GSHPx) activity, were measured in both groups and found to be significantly lower in the group with low Se status. 3. Studies on [14C]arachidonic acid stimulated platelets demonstrated that reduced conversion of the active metabolite 12-hydroperoxyeicosatetraenoic acid to 12-hydroxyeicosatetraenoic acid occurred in patients with low Se nutrition. 4. Changes in [14C]arachidonic acid metabolism are attributed to reduced activity of the seleno-enzyme GSHPx. The effects of other factors cannot be entirely excluded.

Arachidonic Acid

ACTH deficiency: hypothalamic or pituitary in origin?

The level within the hypothalamic-pituitary axis at which isolated ACTH deficiency occurs, can be more clearly identified by assessing this axis with corticotrophin-releasing factor (CRF) and insulin induced hypoglycaemia. We report a case where lack of response to both tests, suggests a pituitary origin for this rare endocrine deficiency.

Adrenal Cortex Function Tests

Inhibitors of glyoxalase I in vitro.

Inhibition in vitro of human red blood cell glyoxalase I activity was measured by the decrease in the rate of formation of S-D-lactoyl-glutathione as determined by the change in absorbance at 240 nm. The percentage activity remaining was determined after addition of various potential inhibitor compounds and the concentration for 50% activity was obtained by graphical interpolation. The inhibitors were selected on the basis of their similarity to a possible transition-state enediol intermediate of methylglyoxal. The most effective inhibitors were dihydroxycoumarins with a 50% inhibition of 0.03 mM. Inhibition of methylglyoxal catabolism suggests possible application as chemotherapeutic agents based on the inhibitor characteristics of methylglyoxal.

Ascorbic Acid

Proving consent.

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