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Biomedical subjects

A Hunt

Publications and source records attributed to A Hunt.

At least 91 records · Page 5Linked to original sources
PubMed1988

Role of thyroid hormone and nerve growth factor in the development of choline acetyltransferase and other cell-specific marker enzymes in the basal forebrain of the rat.

The effects of treatment with L-thyroxine (subcutaneously 0.3 microgram/g body weight daily from birth, i.e., day 1) and 2.5S nerve growth factor (NGF; intraventricularly 2 micrograms on 1, 3, 5, 7, and 9 postnatal days), separately and together, were studied on the biochemical development of different cell types in the basal forebrain of 10-day-old rats. The development of cholinergic, gamma-aminobutyric acid-ergic (GABAergic), and glutamatergic neurons was monitored respectively in terms of choline acetyltransferase (ChAT), glutamate decarboxylase (GAD), and glutaminase activities, whereas glutamine synthetase (GS) and 2',3'-cyclic nucleotide-3'-phosphohydrolase (CNPase) activities were used to judge the maturation of astroglial and oligodendroglial cells. Treatment with either thyroid hormone or NGF from birth significantly increased the expression of ChAT activity in the basal forebrain of neonatal rats. When both agents were administered to the same animal, in agreement with our earlier in vitro findings, the stimulation in ChAT activity was much greater than the sum of the individual effects. In hypothyroid rats, significant effects of NGF at the low doses used were not detectable, although the increase of ChAT activity induced by thyroxine was potentiated by NGF in these animals. Under the present experimental conditions neither thyroxine nor NGF treatment had an appreciable effect on the activities of glutaminase, GS, and lactate dehydrogenase. However, the administration of thyroxine markedly increased CNPase activity in normal rats, whereas in hypothyroid rats the effect on both CNPase and GAD was also significant. Similar elevations in CNPase and GAD activities were not observed after NGF treatment, suggesting that the effect of NGF was specific to the cholinergic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Coronary angioplasty in unstable angina and stable angina: a comparison of success and complications.

One hundred and five patients with unstable angina and 175 with chronic stable angina were treated by primary percutaneous transluminal coronary angioplasty. Patients with unstable angina had had symptoms for a shorter time and were more likely to have angiographically complex lesions and lesions less than 10 mm in length than patients with chronic stable angina. Other baseline variables were not significantly different in the two groups. The overall primary success rate was similar in both groups (87% v 86%). Nine of the 14 unsuccessful procedures in those with unstable angina and nine of the 24 unsuccessful procedures in those with stable angina were the result of acute occlusion. These results led to a 9% frequency of procedure related myocardial infarction in patients with unstable angina and a 5% rate in those with stable angina (NS). The procedure related infarct rate tended to be higher in patients with unstable angina who had coronary angioplasty soon after an episode of unstable angina (mean 10 days) than in those in whom it was delayed (mean 35 days) (12% v 3%) (NS). In patients with unstable angina who had had a previous myocardial infarction procedure related infarction was significantly more common (18%) than in patients with no previous myocardial infarction (3%). The difference between those with and without previous infarction was also significant in patients with stable angina (10% v 3%).

Angina Pectoris↗
PubMed1987

Selective persistent reduction in choline acetyltransferase activity in basal forebrain of the rat after thyroid deficiency during early life.

The effect of thyroid deficiency on the activity of choline acetyltransferase (ChAT; the marker for cholinergic neurons) was studied in different parts of the rat brain at ages 5, 10, 15 and 25 days, and at day 130 following 102 days of rehabilitation. During normal development, the activity of ChAT increased in the cerebral cortex, hippocampus and basal forebrain, and decreased in the cerebellum. Neonatal thyroid deficiency resulted in a marked retardation of the developmental patterns of the enzyme activity. In the hippocampus the effect diminished with age even during the period of thyroid hormone deprivation, while in the cerebral cortex and cerebellum the enzyme activity was restored to normal only after rehabilitation. In contrast, ChAT activity in the basal forebrain remained persistently reduced in comparison with controls. The results indicate that neonatal thyroid deficiency causes selective irreversible biological damage to subcortical cholinergic neurons.

Aging↗
PubMed1987

Effect of thyroid deficiency on the regional development of glutaminase, a glutamatergic neuron marker, in the rat brain.

The effect of thyroid deficiency on the activity of phosphate-activated glutaminase (the marker for glutamatergic neurons) was studied in different parts of the rat brain at ages 5, 10, 15 and 25 days, and at day 130 following 102 days of rehabilitation. The brain regions investigated were the cerebral cortex, basal forebrain, hippocampus and cerebellum. During normal development, the activity of glutaminase increased relatively earlier in the cerebral cortex and hippocampus than in the cerebellum, while the absolute value reached a much higher level in the hippocampus than in other brain regions. In the basal forebrain, the developmental pattern of glutaminase was bimodal, and the rise in enzyme activity after 15 days coincided with the decrease in the cerebral cortex. These regional developmental changes in glutaminase activity correlated well with known information on the formation of glutamatergic cells and pathways in the brain. Neonatal thyroid deficiency had little effect on the developmental patterns of enzyme activity, the exception being a transient decrease in 10-day-old hypothyroid hippocampus. The present results, together with previous findings, indicate that the effect of thyroid hormone on neural maturation is cell-type specific and the glutamatergic neurons are not the main targets of thyroid hormone action.

Aging↗
PubMed1987

Psychiatric disorder among children with tuberous sclerosis.

The psychiatric status of 90 children with tuberous sclerosis was investigated. Over 50 per cent of the sample showed psychotic behaviour, 59 per cent were hyperkinetic and 13 per cent severely aggressive. 57 per cent of the children who had infantile spasms were autistic, as opposed to 13 per cent in a Finnish study of children who had infantile spasms from all causes. The very high incidence of psychiatric disturbance has implications for the advice doctors should give on the management of children diagnosed to have tuberous sclerosis and for the special educational methods that may be needed.

Adolescent↗
PubMed1986

Effect of removal of glutamine and addition of dexamethasone on the activities of glutamine synthetase, ornithine decarboxylase and lactate dehydrogenase in primary cultures of forebrain and cerebellar astrocytes.

The regulation of glutamine synthetase (GS) and ornithine decarboxylase (ODC) was studied in primary cultures of two types of astrocytes derived from either newborn forebrain or 8-day-old cerebellum of the rat. In the 14-day-old cultures the specific activities of both these enzymes were about twice as great in forebrain astrocytes as in cerebellar astrocytes. Treatment with dexamethasone or removal of glutamine from the culture medium caused a marked increase in the specific activity of GS. The glutamine-mediated relative increase in GS activity was similar in both types of astrocytes. Removal of glutamine caused a transient reduction in ODC activity in the forebrain astrocytes, while in cerebellar astrocytes the activity remained markedly decreased throughout the period of glutamine deprivation. The severe reduction in ODC activity had relatively little effect on the cell numbers of protein content of the astrocyte cultures. The increase in GS activities, involving protein synthesis de novo, caused by removal of glutamine and by addition of dexamethasone, were additive and therefore probably mediated by different mechanisms. The induction of GS after glutamine removal was blocked by cycloheximide but not by alpha-amanitin, suggesting regulation at the post-transcriptional level. In contrast, the dexamethasone-mediated induction of GS appeared to be regulated at the transcriptional level, as it was markedly reduced by alpha-amanitin. None of these conditions had any effect on lactate dehydrogenase activity. Treatment with alpha-amanitin resulted in a complete suppression of the activity of ODC (a protein with a very short half life), in both the control and dexamethasone treated cultures. However, this enzyme activity was reduced only partially in astrocytes cultured in glutamine deficient medium, suggesting that under these experimental conditions the mRNA may be markedly stabilized in astroglial cells.

Animals↗
PubMed1986

Immobilization decreases amino acid concentrations in plasma but maintains or increases them in brain.

Immobilization for 2 h significantly decreased plasma concentrations of 13 of 16 amino acids assayed, including the transmitter amine precursors tyrosine and total tryptophan. The level of plasma free tryptophan, however, was increased. Despite the reduced plasma levels, corresponding brain concentrations of many large neutral amino acids (LNAAs) were increased (tryptophan, phenylalanine, valine, leucine, and isoleucine). Brain concentrations of tyrosine and the other amino acids measured were unaltered. The results for the LNAAs were not explained by calculated brain influx rates. Therefore, altered influx kinetics or perhaps altered brain protein metabolism or efflux may be responsible. Comparison of calculated brain influxes and brain concentrations of LNAAs suggests that the rise in level of plasma free tryptophan during immobilization is not responsible for the increase in level of brain tryptophan and that the mechanism responsible for the maintenance of or increase in brain concentrations of the other LNAAs is probably involved. Maintenance of brain concentrations of basic amino acids is explicable by reduced competition for brain uptake.

Amino Acids↗
PubMed1986

Role of Ca 125 as tumor marker in ovarian carcinoma.

Thirty-three healthy women (group 1), 20 patients with a history of ovarian carcinoma but no manifest disease at the time of the study (group 2), and 45 patients with surgically demonstrable ovarian cancer (group 3) were studied to establish guidelines for the use of the ovarian cancer antigen Ca 125 in monitoring the course of ovarian carcinoma. Ninety-nine percent of all Ca 125 titers of patients in groups 1 and 2 were less than or equal to 25 U/mL. By contrast, 96% of patients with manifest ovarian cancer had Ca 125 levels greater than 25 U/mL. Ca 125 values rising from the normal range to greater than 25 U/mL predicted recurrent disease in all of ten patients, provided benign causes (four cases) for titer elevations such as bowel obstruction could be ruled out. Seven of ten patients with recurrent cancer had elevated antigen levels two to five months before the diagnosis could be made clinically. In patients with Ca 125 values greater than 25 U/mL, titer changes of greater than or equal to 50% compared with reference values predicted tumor response or progression in 41 of 43 patients (95%) with antigen positive tumors. Antigen levels less than or equal to 25 U/mL did not exclude the presence of tumor at second look operation in six of 13 patients (46%). It is concluded that the Ca 125 is useful for the detection of persistent and recurrent disease, and for the evaluation of treatment responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1985

Prolonged use of nitrazepam for epilepsy in children with tuberous sclerosis.

A case note study of 90 children with tuberous sclerosis showed that 56 had taken nitrazepam for seizures for from one month to 13 years. In 38 children nitrazepam was withdrawn but only two had immediate major seizures. Given that sleepiness, deterioration in motor skills, or ataxia seems to be associated in some children with treatment with nitrazepam, doctors may wish to review their long term prescriptions of this drug in children with tuberous sclerosis.

Adolescent↗
PubMed1985

Distribution of glutamine synthetase and glial fibrillary acidic protein and correlation of glutamine synthetase with glutamate decarboxylase in different regions of the rat central nervous system.

The concentration of soluble glial fibrillary acidic (GFA) protein and the specific activity of glutamine synthetase (GS) were estimated in 11 central nervous system (CNS) regions of the 90-day-old rat. Marked differences were observed in the regional distribution of these astrocyte marker proteins. The striatum and spinal cord contained the lowest concentration (per g wet weight) of GFA protein and GS activity, respectively, while the olfactory bulbs had the highest level of both astrocytic proteins. Differences between the lowest and the highest values were 3-fold for GS and 4-fold for GFA protein. More significant was the marked variation in the ratio of GS to GFA protein in different CNS regions; the highest and lowest values were in the striatum and the spinal cord respectively, and the difference between the highest and the lowest value was about 5-fold. The spinal cord contained low GS and high GFA protein; on the other hand, the colliculi had high GS and relatively low GFA protein. Immunochemical detection of GS and GFA proteins in whole homogenates of different regions showed that the variation of the specific activities of GS and the concentration of soluble GFA protein were due to the differences in their absolute protein concentrations. In different regions of the brain the activity of GS was significantly correlated with that of glutamate decarboxylase, but not with that of choline acetyltransferase. These observations provide further evidence for differing biochemical properties of astrocytes from various CNS regions and for the involvement of GS in processes associated with amino acid neurotransmission.

Animals↗
PubMed1985

Observations on cell growth and regulation of glutamine synthetase by dexamethasone in primary cultures of forebrain and cerebellar astrocytes.

Cell growth, development of glutamine synthetase and its regulation by glucocorticoids, were studied in primary cultures of two types of astrocytes derived from rat brain, one from newborn forebrain and another from either newborn or 8-day-old cerebellum. Cell number per dish increased linearly following an initial decrease due to removal of non-astrocytic cells, and after the second week reached a stationary phase in both types of cultures at more or less the same time, although the cell number in cerebellar cultures was about 35% lower than in forebrain cultures of the same age. At all ages, irrespective of cell density, the cerebellar astrocytes were larger in size than the forebrain astroglial cells. The developmental curves for glutamine synthetase activity were similar in vitro and in vivo; however, the increase in enzyme activity in vitro was significantly greater than in vivo and this difference was more marked in forebrain than in cerebellar cultures. Throughout the period studied the specific activity of glutamine synthetase was significantly higher in forebrain astrocytes than in cerebellar astroglial cells. Treatment with dexamethasone caused a marked increase in the specific activity of glutamine synthetase. However, in agreement with our previous in vivo findings, the steroid induction in forebrain astrocytes was significantly less than that in cerebellar astrocytes. In culture, both types of astrocytes remain responsive to the hormone for longer than in vivo. The differences in the biochemical properties of the forebrain and cerebellar astrocytes seem to be intrinsic, and not related to the cell density or to the purity of the cultures.

Age Factors↗
PubMed1985

Concentration of free amino acids in primary cultures of neurones and astrocytes.

The cellular distribution of free amino acids was estimated in primary cultures (14 days in vitro) composed principally of cerebellar interneurones or cerebellar and forebrain astrocytes. In cultured neural cells, the overall concentration of amino acids resembled that found in brain at the corresponding age in vivo. In the two neural cell types, there were marked differences in the distribution of amino acids, in particular, those associated with the metabolic compartmentation of glutamate. In neuronal cell cultures, the concentrations of glutamate, aspartate, and gamma-aminobutyric acid were, respectively, about three, four, and seven times greater than in astrocytes. By contrast, the amount of glutamine was approximately 65% greater in astroglial cell cultures than in interneurone cultures. An unexpected finding was a very high concentration of glycine in astrocytes derived from 8-day-old cerebellum, but the concentrations of both serine and glycine were greater in nerve cell cultures than in forebrain astrocytes. The essential amino acids threonine, valine, isoleucine, leucine, tyrosine, phenylalanine, histidine, lysine, and arginine were all present in the growth medium, and small cellular changes in the contents of some of these amino acids may relate to differences in their influx and efflux during culturing and washing procedures. The present results, together with our previous findings, provide further support for the model assigning the "small" compartment of glutamate to glial cells and the "large" compartment to neurones, and also underline the metabolic interaction between these two cell types in the brain.

Amino Acids↗
PubMed1985

Effects of undernutrition and thyroid state on the ontogenetic changes of D1, D2, and D3 brain-specific proteins in rat cerebellum.

Disturbances in metabolic balance brought about by alterations in thyroid state and undernutrition during early life had a marked effect on the concentrations of the brain-specific proteins, D1, D2, and D3 in the developing rat cerebellum. In normal rats, the concentrations of D1 and D3 increased and that of D2 decreased during the first 3 weeks after birth. In the hyperthyroid state a small but consistent advancement was observed in the developmental curves of these proteins. The hypothyroid state caused a marked retardation in the maturational pattern of D1 and D2 but not of D3. In undernutrition, at 6 days the concentrations of D1 and D3 proteins were higher than in controls, but thereafter the developmental increase was markedly delayed for D1 only. The concentration of D2 was normal at 6 days, but after the first week a marked retardation was observed in the maturational pattern of this protein in undernourished rats. In addition, the "anodic-immature" form of D2 predominated in 6-day-old controls, but this was gradually replaced by a "cathodic-mature" form which progressively became the dominant form of D2 in 35-day-old rat cerebellum. The developmental switch in terms of the two forms was also advanced in hyperthyroidism and retarded in thyroid deficiency and undernutrition. Furthermore, daily treatment of hypothyroid rats with physiological doses of thyroxine from birth restored the concentrations of D1 and D2 to normal, but that of D3 was increased above control levels, indicating differences between the proteins in their sensitivity to mechanisms of control by thyroid hormone. Also, the overall effects of undernutrition were markedly different from those of hypothyroidism.

Age Factors↗
PubMed1984

Developmental changes in the amount of glial fibrillary acidic protein in three regions of the rat brain.

Glial fibrillary acidic (GFA) protein, extractable in 50 mM phosphate buffer, pH 8, was measured in the olfactory bulbs, forebrain and cerebellum of the rat during development using a double antibody radioimmunoassay. Each brain region showed a different pattern of development for GFA protein. At birth GFA protein per mg protein was highest in olfactory bulbs followed by forebrain and cerebellum, and these amounted to 15, 10 and 8% of the adult values, respectively. The relative increase in GFA protein was more marked during the first 2 postnatal weeks than in the following 7 weeks after birth. When values were expressed per brain region, the developmental increase in the amount of GFA protein from birth to adulthood was about 100-fold in olfactory bulbs, 85-fold in forebrain and 485-fold in cerebellum. The patterns of developmental increases in GFA protein and in glutamine synthetase activity, another protein enriched in astrocytes, were similar in the forebrain and olfactory bulbs, but differed markedly in the cerebellum. The major increase in content of the GFA protein during development was found to correspond with the maturation of astrocytes rather than with their proliferation; however, a small but significant amount of GFA protein acquired at an early age may be related to increase in astroglial cell numbers in the cerebellum.

Age Factors↗
PubMed1984

Tuberous sclerosis: a new estimate of prevalence within the Oxford region.

Within the counties administered by the Oxford Regional Health Authority (population 2 328 100) the prevalence of tuberous sclerosis was estimated as 1 in 29 900 for persons under 65 years of age. For the population below 30 years of age the prevalence was 1 in 21 500 and for children under 5 years 1 in 15 400. Cases were ascertained through the records of the Department of Medical Genetics at Oxford and the Tuberous Sclerosis Association of Great Britain and also by a questionnaire sent to selected consultants within the region. A previous estimate of prevalence within the region was 1 in 100 000. This study suggests that the prevalence at birth might be even higher than 1 in 15 000.

Adolescent↗