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Biomedical subjects

A Hunt

Publications and source records attributed to A Hunt.

At least 109 records · Page 6Linked to original sources

Regulation of in vivo glutamine synthetase activity by glucocorticoids in the developing rat brain.

Induction of glutamine synthetase in vivo by glucocorticoids was studied in different brain regions of the rat during development. Corticosterone treatment resulted in an age-dependent increase in glutamine synthetase activity. In 11-day-old rats, in comparison with controls, the increase was about 80% in the cerebellum, 50% in the olfactory bulbs and 20% in the forebrain. During development the effect diminished markedly and at day 20 a marked increase was detectable only in the cerebellum, suggesting that the elevation of glutamine synthetase was dependent on the maturational state of the region at the time of hormone treatment. The increase in enzyme activity was dose-dependent, and was also observed after treatment with dexamethasone but not with testosterone, estradiol or progesterone. Pre-treatment with the protein synthesis inhibitor anisomycin blocked the hormonal response. Also, immunochemical detection of glutamine synthetase in brain homogenates fractionated by SDS-polyacrylamide gel electrophoresis and transferred to diazobenzyloxymethyl paper showed that the increase in enzyme activity was due to induction of protein synthesis. This may be the first report showing a regulation by glucocorticoids of mammalian brain glutamine synthetase in vivo, and it is in good agreement with previous findings with chick retina in vivo and various avian and mammalian cells in vitro.

Age Factors↗

Tuberous sclerosis: a survey of 97 cases. II: Physical findings.

Physical signs, excluding epilepsy, were studied in 97 individuals with tuberous sclerosis. While the red facial rash (adenoma sebaceum) is taken to be one of the classic symptoms, depigmented skin macules were more common. The depigmented patches and raised areas (shagreen patches) appeared in early childhood, and sometimes were present at birth. Other skin problems were common. Although the tuberous sclerotic lesions are known also to cause kidney problems, few individuals had been examined thoroughly to detect these difficulties.

Adolescent↗

Tuberous sclerosis: a survey of 97 cases. III: Family aspects.

Although tuberous sclerosis is transmitted through a dominant gene, less than half the parents and siblings of the 97 individuals surveyed had received genetic counseling. There was no apparent difference in severity of handicaps in relation to whether the gene was transmitted by the father or the mother. The majority of the sample were mentally retarded, and speech was more affected than gross motor development. Behaviour problems were of more concern to parents than their children's seizures or worries about the future.

Adolescent↗

The activities in different neural cell types of certain enzymes associated with the metabolic compartmentation glutamate.

The cellular distribution of certain enzymes associated with the metabolic compartmentation of glutamate was estimated in ultrastructurally preserved and metabolically competent perikarya fractions that were enriched in astrocytes, granule cells and Purkinje cells and derived from 8-day-old rat cerebellum, and in monolayer cultures (14 days in vitro) composed principally of interneurones or astrocytes. The neuronal activities of glutamine synthetase and glutamate dehydrogenase were respectively about 4- to 8-fold and 2- to 5-fold lower than in astrocytes, depending upon the class of neurone and the type of preparation used for comparison. By contrast glutaminase activity was about 3- to 12-fold higher in neuronal than in astroglial preparations. Estimations of the specific activity of succinate dehydrogenase differed less between cell types, indicating that the differences in glutamate dehydrogenase and glutaminase were not simply related to variations in the concentration of mitochondria relative to the other cellular constituents. The findings presented provide direct evidence in support of our model assigning the 'small' glutamate compartment, where most of the labelled glutamine is synthesized, to glial cells, and the 'large' compartment to neurones, and also underline the metabolic interaction between these two cell types in the brain.

Animals↗

Brief marital therapy outcome: personality correlates.

The purpose of the study was to investigate with regression analyses the relationship between personality and background variables and outcome of brief marital therapy. Twenty personality dimensions from the Personality Research Form and data on age, education, number of previous unions, number of children and number of sessions were used as independent variables. The dependent variable was provided by ratings of over-all improvement in affective communication: sexual, verbal, and social, provided by clinical records of 30 couples. The main result was that only the husband's traits were found to be important correlates of improvement in affective communication of both husbands and wives. The important traits involved husband's cognitive efficiency in the area of reflection and accurate judgement of situations, submissiveness, and sensitivity to social approval of his behaviour. The number of individual therapy sessions given to wives was also a notable predictor of improvement. Other personality and background variables were not significantly related to outcome.

Adult↗

Indolic substances in plasma, cerebrospinal fluid, and frontal cortex of human subjects infused with saline or tryptophan.

Psychiatric patients undergoing the psychosurgical operation of stereotactic subcaudate tractotomy were infused intravenously with either saline or L-tryptophan (15 mg/kg/h). Plasma, lumbar cerebrospinal fluid (CSF), ventricular CSF and a specimen of frontal cortex were collected. The relationships of plasma concentrations of substances claimed to influence brain tryptophan concentration (total tryptophan, free tryptophan, large neutral amino acids) with the concentration of tryptophan in the cortex and CSF were investigated. Tryptophan infusion resulted in plasma tryptophan values comparable to those found after oral doses used in treating depression or insomnia, and about sixfold increases of tryptophan in the cerebral cortex. Increased brain 5-hydroxytryptamine synthesis was indicated by significant rises of CSF 5-hydroxyindoleacetic acid. The concentration of plasma free tryptophan was a better predictor than plasma total tryptophan of cortex tryptophan concentration. As all correlation coefficients of plasma versus brain or plasma versus ventricular CSF tryptophan concentrations were decreased when allowance was made for differences of concentration of large neutral amino acids, the results suggest that the role of these substances within their physiological range as inhibitors of tryptophan transport to the brain may previously have been overemphasised.

Cerebral Cortex↗

Effects of thyroid state on brain development: beta-adrenergic receptors and 5'-nucleotidase activity.

The effect of thyroid status on beta-adrenergic receptor binding and 5'-nucleotidase activity was studied in the forebrain and the cerebellum of the rat during the first 5 postnatal weeks. The developmental increase in beta-adrenergic receptor binding was significantly depressed in thyroid deficiency in both the forebrain and the cerebellum. The effect was more pronounced in the cerebellum, where at day 35 the concentration and the total number of beta-adrenergic receptor sites were reduced by 35% and 50% respectively. In contrast, hyperthyroidism had no significant effect on the development of beta-adrenergic receptors in the brain. On the other hand, hyperthyroidism led to a sustained increase in the forebrain in the activity of 5'-nucleotidase, an enzyme which is also associated with plasma membranes and has been proposed to play some role in neurotransmission. In thyroid deficiency the enzyme activity was markedly depressed. The effect was significant from day 12 in the cerebellum and from day 21 in the forebrain, the maximal depression, at day 21, being 55% and 45% respectively. In comparison with these plasma membrane markers, the accretion of membranous proteins was less affected: although this was retarded in hypothyroidism and advanced in hyperthyroidism there was no residual effect at 35 days except those attributable to changes in organ size. The results indicated, therefore, that the biochemical specialization of cells, as reflected in certain plasma membrane constituents, are chatacteristically influenced in the developing brain by thyroid disorders.

Aging↗

Effects of thyroid state on brain development: muscarinic acetylcholine and GABA receptors.

A study was made of the effects of age, neonatal hypothyroidism and hyperthyroidism on the development in rat brain of muscarinic cholinergic and GABA receptors. The former receptors were estimated by the binding of [3H]quinuclidinylbenzilate and the latter by binding of [3H]muscimol to crude membrane preparations from the forebrain and the cerebellum. In the normal forebrain, the density of muscarinic cholinergic receptors (in terms of unit membrane proteins) doubled during the period 6-35 days after birth. Thyroid state had relatively little effect on this development. In contrast, in the normal cerebellum the peak of the density of the receptors was attained in the early neonatal period followed by a progressive decline reaching about half of the maximum at day 35. Furthermore, in the cerebellum this development was significantly influenced by thyroid disorders: the rate of decrease in receptor density was accelerated by hyperthyroidism and retarded in thyroid deficiency. In comparison with euthyroid rats, the density of muscarinic receptors in the cerebellum was 30% lower in the hyperthyroidism (at day 21) and 40% higher in thyroid deficiency (at day 35). The increase in the density of GABA receptors with age was very small in the normal forebrain relative to the marked rise in the cerebellum. In the forebrain, thyroid state had no significant effect on this development. In contrast, in the cerebellum the ontogenesis of GABA receptors was advanced by thyroid hormone treatment and retarded in thyroid deficiency. However, by day 35 receptor density was normal in both conditions. Thyroid state had no significant influence on the affinity of either [3H]muscimol or the [3H]quinuclidinylbenzilate binding. The results suggest that thyroid hormone disorders during early life may lead to distortions rather than synchronized shifts in the relative development of several central transmitter systems.

Acetylcholine↗

Studies on the mechanism of shock. Central serotoninergic neuron activity after trauma in the rat.

An attempt has been made to assess the effect of injury (limb ischaemia, scald) on the central serotoninergic system of the rat by studying the effect of these injuries on the tryptophan concentration, the tryptophan hydroxylase activity and the metabolism of serotonin in the hypothalamus, mid-brain and hind-brain. The effects of a serotonin uptake inhibitor and an antagonist on the survival time and mortality rate after limb ischaemia have been examined as well as the effects of central lesions produced by the injection of 5.6- and 5.7-dihydroxytryptamine into a lateral cerebral ventricle and the i.p. injection of (+/-)-4-chloroamphetamine. A few changes indicative of increased activity in the central serotoninergic system were found--an increase in tryptophan hydroxylase activity after 4 h bilateral hind-limb ischaemia, better survival of fed rats pre-treated with 5,6-dihydroxytryptamine--but for the most part the changes were not as great as those produced by starving or exposure to cold. Hence the effect of trauma on this system seems small.

5,6-Dihydroxytryptamine↗