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Biomedical subjects

K M Shaw

Publications and source records attributed to K M Shaw.

At least 73 records · Page 4Linked to original sources
PubMed1979

Properties of malate dehydrogenase isolated from Methanospirillum hungatii.

A NADH-linked oxygen-tolerant malate dehydrogenase was purified 270-fold from cell extracts of Methanospirillum hungatii. Inhibitors of the enzyme included ADP, alpha-ketoglutarate, and excess NADH. Inhibition patterns for ADP were competitive with respect to NADH and non-competitive with respect to oxalacetate. Inhibition by alpha-ketoglutarate was non-competitive with oxalacetate as variable substrate and uncompetitive with respect to NADH. alpha-Ketoglutarate is surmised to function as an end-product inhibitor of the enzyme in reactions converting oxalacetate to alpha-ketoglutarate. No enzyme activity was detected in the direction of malate conversion to oxalacetate, in keeping with a strictly biosynthetic function of the enzyme. An analysis of variance of intial rate data fit to sequential and ping-pong equations showed that a sequential mechanism was perferred. The malate dehydrogenase of M. hungatii resembles those of many other bacteria and eucaryotic cells respect to molecular weight (61,700) and reaction mechanism, but may be regulated differently.

Enzyme Activation↗
PubMed1978

Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the 'cheese effect'.

After pretreatment with the selective monoamine oxidase B inhibitor, (-)-deprenyl, in doses sufficient for complete inhibition of the platelet enzyme, 4 normal and 6 parkinsoniam volunteers (2 receiving levodopa and 2 levodopa plus carbidopa) suffered no adverse pressor reaction ('cheese effect') after challenge with oral tyramine in amounts considerably greater than those likely to be encountered in a normal diet. Nor did the levodopa-deprenyl combination itself result in a pressor response. Normal human intestinal mucosa was shown predominantly to contain the deprenyl-insensitive A form of the enzyme, which presumably degraded administered tyramine in the deprenyl-treated volunteers; even those receiving the drug for prolonged periods manifested no 'cheese effect', suggesting that the A form remained uninhibited. Intestinal monoamine oxidase A was able to oxidise dopamine, whereas in human platelet or striatum the amine is a monoamine oxidase B substrate. Like tyramine, oral phenylethylamine challenge with amounts greater than those known to be present in a normal diet similarly gave rise to no adverse reaction in (-)-deprenyl-treated subjects; the reasons for this remain to be determined.

Adult↗
PubMed1978

Bromocriptine in parkinsonism. A long-term study.

Bromocriptine was given in a controlled trial to 86 parkinsonian patients. Eight of 30 previously untreated patients with early and mild disease showed sustained benefit for two years and did not develop "on-off" effects or dyskinesias. Only two of 23 patients unable to tolerate or failing to respond to levodopa benefited from bromocriptine. Thirty-three patients with residual disabilities despite maximum tolerated doses of levodopa were also given bromocriptine: although benefit accrued, treatment was abandoned because of unacceptable side effects, and there was no improvement in the 11 with severe "on-off" disabilities. Although it was found that benefit from 70 mg daily of bromocriptine was comparable to that from 750 mg of levodopa with carbidopa, bromocriptine seems to offer no advantage to the majority of patients who have received or are receiving levodopa and/or carbidopa.

Anorexia↗
PubMed1978

Endocrine aspects of bromocriptine therapy in Parkinsonism.

Plasma growth hormone (GH) concentrations in Parkinsonian patients following 3 months optimum therapy with bromocriptine showed no significant change from pretreatment values, whilst plasma prolactin concentrations were uniformly suppressed. Pretreatment GH and prolactin levels were unrelated to clinical disability, and no correlation between hormonal changes and therapeutic response was found. These results suggest the presence of different dopaminergic receptor mechanisms for GH and prolactin release as well as between the extrapyramidal and neuroendocrine systems.

Bromocriptine↗
PubMed1978

Baclofen in Parkinson's disease.

In a controlled trial, baclofen (mean dose 45 mg daily) signficantly increased disability from Parkinsonism in 12 patients with the long-term levodopa syndrome. Peak dose choreoathetosis was not improved but benefit was observed in all four patients with "off period dystonia." Adverse side effects were common and severe, and included visual hallucinations, vomiting, and dizziness.

Aged↗
PubMed1977

Deprenyl in Parkinson's disease.

In a double-blind crossover trial, (-)-deprenyl, a fast-acting selective monoamine-oxidase-B inhibitor without a "cheese effect", was given to 41 patients with idiopathic Parkinson's disease who were receiving maximum tolerated doses of levodopa either alone or combined with carbidopa ("Sinemet"). In a dose of 10 mg, daily or on alternate days, (-)-deprenyl prolonged the therapeutic effect of levodopa and was effective in mild "on-off" disabilities with end-of-dose akinesia; the majority of patients with nocturnal and early-morning akinesia also improved. No statistically significant improvement occurred in diurnal akinesia, and there was no improvement in patients with severe on-off disabilities with freezing and rapid oscillations ("yo-yo" effect). Levodopa-induced dyskinesias were aggravated in 14 patients. In 5 previously untreated patients, (-)-deprenyl alone gave no benefit, but when it was used with levodopa and carbidopa a mean dosage reduction of 200 mg levodopa daily was possible. Depression, present in 15 patients, was unchanged. (-)-Deprenyl in combination with smaller total daily doses of levodopa and a peripheral decarboxylase inhibitor may prove useful in reducing the frequency and severity of some types of on-off effect with overall benefit comparable to that obtained with larger doses of levodopa.

Adult↗