Search PubMed⌕ Search

Biomedical subjects

M K Johnson

Publications and source records attributed to M K Johnson.

At least 271 records · Page 15Linked to original sources
PubMed1972

Properties of purified pneumococcal hemolysin.

With a purified preparation of pneumococcal hemolysin, a sigmoid relationship was found to exist between lysin concentration and hemolytic activity. Hemolysis was inhibited by a high ratio of erythrocytes to lysin, suggesting a multi-hit mechanism of action. Reaction rate decreased rapidly with time, possibly due to competition between ghosts and unlysed erythrocytes for fixation of lysin. The effects of pH and various agents on the processes of lysin adsorption and hemoglobin release were determined. The pneumococcal preparation did not possess nicotinamide adenine dinucleotide glycohydrolase activity.

Animals↗
PubMed1971

Side effects of organophosphorus compounds: delayed neurotoxicity.

Many organophosphorus compounds produce a chronic toxicity that has been classified as a dying-back process in which the long axons are particularly affected. Recent evidence indicates that an essential first step in the production of the lesion is the phosphorylation of a protein that is able to hydrolyse substrates such as phenyl phenylacetate. The esterase activity of the protein is inhibited by this phosphorylation, presumably at the active site. However, the toxic effect is related only to phosphorylation and not to loss of esterase activity.

Animals↗
PubMed1970

Organophosphorus and other inhibitors of brain 'neurotoxic esterase' and the development of delayed neurotoxicity in hens.

1. The delayed neurotoxic effects of some organophosphorus compounds are associated with phosphorylation of the active site of a nervous-tissue enzyme capable of hydrolysing phenyl phenylacetate. 2. Neurotoxic organophosphorus compounds and some carbamates and sulphonyl fluorides progressively inhibit the enzyme, attaching a substituent covalently at the active site. 3. Prolonged inhibition of the enzyme by phenyl N-benzyl-N-methylcarbamate or phenylmethane-sulphonyl fluoride does not lead to neurotoxic effects. 4. Prior inhibition of the enzyme by carbamates or sulphonyl fluorides in vivo prevents the neurotoxic effects of several organophosphorus compounds. 5. After dosage of hens with protective compounds, protection lasts until about 70% of the enzyme site again becomes available for phosphorylation. 6. Reaction of all the inhibitors at the active site of the enzyme leads to the same inhibitory effect with respect to hydrolysis of phenyl phenylacetate but does not in all cases lead to delayed neurotoxicity. It is concluded that the nature of the group substituted at the enzyme active site determines the toxic response.

Animals↗
PubMed1969

A phosphorylation site in brain and the delayed neurotoxic effect of some organophosphorus compounds.

1. It is proposed that part of a neurotoxic dose of di-isopropyl phosphorofluoridate will be covalently bound in vivo to a specific component in the brain and spinal cord as the initial biochemical event in the genesis of the lesion. 2. A test system in vitro was devised that removes many di-isopropyl phosphorofluoridate-binding sites and indicates that the specific component may be a protein present in brain at a concentration comparable with that of the cholinesterases. 3. The site was found to be present and capable of binding di-isopropyl phosphorofluoridate in vitro in brain samples taken from either normal hens or those dosed with organophosphorus esterase inhibitors that are not neurotoxic. 4. Very little of the specific binding activity was found in brain samples from hens pre-dosed with a variety of neurotoxic organophosphorus compounds. 5. A solubilized preparation of the active brain component was obtained, suitable for further purification and study.

Animals↗
PubMed1969

The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase.

1. Organophosphorus compounds that produce a delayed neurotoxic effect in hens phosphorylate a specific site in the brain soon after administration. 2. Phosphorylation of the specific site by di-isopropyl [(32)P]phosphorofluoridate in vitro is blocked by the prior addition of phenyl phenylacetate. 3. A small proportion of the total activity of hen brain hydrolysing phenyl phenylacetate in vitro was shown to be due to an enzyme different from two others previously described. 4. This enzyme is only slightly inhibited in vitro by concentrations of tetraethyl pyrophosphate and paraoxon (diethyl 4-nitrophenyl phosphate) up to 64mum and is completely inhibited by 6mum-di-isopropyl phosphorofluoridate and 128mum-mipafox. 5. It is also inhibited in vivo by effective doses of neurotoxic organophosphorus compounds but not by high doses of non-neurotoxic analogues. 6. It is deduced that the active site of this enzyme is the phosphorylation site associated with the genesis of delayed neurotoxicity.

Amides↗