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Biomedical subjects

P Slater

Publications and source records attributed to P Slater.

At least 55 records · Page 3Linked to original sources
PubMed1989

Frontal cortical and left temporal glutamatergic dysfunction in schizophrenia.

Glutamatergic mechanisms have been investigated in postmortem brain samples from schizophrenics and controls. D-[3H]Aspartate binding to glutamate uptake sites was used as a marker for glutamatergic neurones, and [3H]kainate binding for a subclass of postsynaptic glutamate receptors. There were highly significant increases in the binding of both ligands to membranes from orbital frontal cortex on both the left and right sides of schizophrenic brains. The changes are unlikely to be due to antemortem neuroleptic drug treatment, because no similar changes were recorded in other areas. A predicted left-sided reduction in D-[3H]aspartate binding was refuted at 5% probability, but not at 10%. Previously reported high concentrations of dopamine in left amygdala were strongly associated with low concentrations of D-[3H]aspartate binding in left polar temporal cortex in the schizophrenics. The findings are compatible with an overabundant glutamatergic innervation of orbital frontal cortex in schizophrenia. The results also suggest that schizophrenia may involve left-sided abnormalities in the relationship between temporal glutamatergic and dopaminergic projections to amygdala.

Aspartic Acid↗
PubMed1989

Autoradiographic visualization of kappa opioid receptors with labelled dynorphins in guinea pig brain.

The distribution of kappa opioid receptors in guinea pig brain was measured by in vitro receptor autoradiography using [3H]dynorphin A1-9, [3H]dynorphin A1-8 and [3H]bremazocine as ligands. The sites labelled by the two dynorphins had identical, heterogeneous distributions in brain sections. High levels of kappa receptors were seen in striatum, claustrum, nucleus accumbens and laminae V and VI of the cerebral cortex. The substantia nigra and superior colliculus also had high dynorphin binding levels. The [3H]dynorphin autoradiographs were closely similar to those obtained using [3H]bremazocine in the presence of mu and delta receptor displacers. It is concluded that tritiated dynorphin A fragments can be used for autoradiographic studies of kappa opioid receptors in brain.

Animals↗
PubMed1988

Regional changes in [3H]D-aspartate and [3H]TCP binding sites in Alzheimer's disease brains.

The specific binding of [3H]D-aspartate, a marker for the presynaptic glutamate uptake site, and [3H]N-(1-[2-Thienyl]cyclohexyl)-piperidine [( 3H]TCP), a high affinity ligand for the N-methyl-D-aspartate (NMDA)-associated phencyclidine binding site, was measured in homogenates of brain from normal subjects and from subjects with neuropathologically confirmed Alzheimer's disease. Alzheimer's disease was associated with a reduction in [3H]D-aspartate binding density in temporal cortex and caudate nucleus. By contrast, a reduction in the receptor density for [3H]TCP binding was only recorded in the frontal cortex. Thus, glutamate-containing nerve terminals are severely reduced in Alzheimer's disease, whilst the postsynaptic NMDA-phencyclidine receptor complex is much less affected. These findings have implications for theories of glutamate neurotoxicity in Alzheimer's disease.

Aged↗
PubMed1988

The effects of TRH analogues on cerebral ischaemia produced by middle cerebral artery occlusion in the rat.

This study examined the effects of two stabilised analogues of TRH, RX 77368 and CG 3509, in a rat cerebral ischaemia model produced by unilateral occlusion of the middle cerebral artery. The analogues were given intraventricularly after artery occlusion. The extent of the cortical ischaemia was evaluated after 10 days by somatosensory evoked potential (SEP) recording, followed by tetrazolium staining of brain slices for NADH-diaphorase activity. RX 77368 (2 X 10 micrograms; 15 min, 24 h) significantly improved the survival rate, protected the SEP and reduced the area of infarct. In contrast, neither a smaller dose of RX 77368 (2 X 3 micrograms) nor a 4 h delay in the treatment had any significant beneficial effects. Although CG 3509 (2 X 10 micrograms) resulted in an apparent improvement in survival, its overall effects were not statistically significant. The findings indicate that stabilised TRH analogues may have beneficial effects when given to animals with focal cerebral ischaemia.

Animals↗
PubMed1988

Loss of cortical GABA uptake sites in Alzheimer's disease.

[3H]Nipecotic acid bound to membranes of human brain in a saturable, reversible manner which was totally dependent on the presence of sodium ions. The potencies of compounds in inhibiting the specific binding of [3H]nipecotic acid were closely correlated with their potencies in inhibiting the neuronal uptake of [3H]GABA. Compounds selective for GABA receptors were inactive. [3H]Nipecotic acid appears to label neuronal high affinity GABA uptake sites. The binding of [3H]nipecotic acid was substantially reduced in the temporal cortex of brains from subjects with Alzheimer-type dementia, but not in other brain regions. It is concluded that some loss of GABA terminals occurs in this disease.

Aged↗
PubMed1988

Autoradiographic localization of delta opiate receptors in rat and human brain.

In vitro quantitative receptor autoradiography was performed on frozen sections of rat and human brain to visualize delta opiate receptors using the specific ligand [3H][D-Pen2, D-Pen5]enkephalin. For comparison, rat brain sections were also labelled with [3H]D-Ala2, D-Leu5-enkephalin. Compounds which block mu and kappa binding were included to make the [3H]D-Ala2, D-Leu5-enkephalin binding more specific. The two ligands had similar, but not identical, distributions in rat forebrain sections. Sites labelled with [3H][D-Pen2,D-Pen5]enkephalin were distributed heterogeneously within the layers of the frontal and parietal cerebral cortex, with high densities in the superficial and deep cortical layers. The claustrum and striatum had the most delta sites, whereas the globus pallidus had no delta binding. The distribution of [3H]D-Ala2,D-Leu5-enkephalin binding sites was similar to that of [3H][D-Pen2,D-Pen5]enkephalin, except that there was less heterogeneity in the frontal cortex. In the human brain regions studied, the highest delta binding was in caudate, putamen, temporal cortex and amygdala. There was less heterogeneity in the binding of [D-Pen2,D-Pen5]enkephalin in the human cortex than in the rat. No delta binding was seen in the medial and lateral segments of the globus pallidus. In both species, a discrepancy between the high enkephalin content of the globus pallidus and the absence of delta binding was apparent.

Animals↗
PubMed1988

Effects of GABA compounds injected into the subpallidal regions of rat brain on nucleus accumbens evoked hyperactivity.

The effects of administration of gamma-aminobutyric acid (GABA) compounds into the ventral pallidum and substantia innominata on the locomotor hyperactivity induced by the dopamine agonist 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (ADTN) in the nucleus accumbens were investigated in rats. Hyperactivity induced by ADTN was antagonized by the GABA receptor agonists muscimol, isoguvacine, and baclofen. The compounds were equally effective in both subpallidal regions. In contrast, the GABA antagonists picrotoxin and bicuculline injected into subpallidal sites had no effects on accumbens-evoked hyperactivity, although by themselves both antagonists caused a mild and transient locomotor stimulation. It is suggested that GABA receptors in the subpallidal areas are involved in locomotor stimulation elicited from the nucleus accumbens.

Animals↗
PubMed1988

Hostility and the medical student: how a trait measure influences perception of medical specialties.

This paper describes the influence of hostility as a trait on medical students' perception of medicine and its specialties. By means of Repertory Grid analysis, the authors compare the preferences of students having internally and externally directed hostility. The findings suggest that students with low levels of internal hostility are attracted to the popular image of the surgeon as a highly achieving and successful individual who is oriented towards cure. In contrast, those with high levels of internally directed hostility show an interest in specialties which allow for close human contact, particularly within general medicine. A psychological interpretation of these findings is offered.

Attitude of Health Personnel↗
PubMed1987

Fine-needle aspiration biopsy cytology of the breast. A review of the Groote Schuur Hospital experience.

The results of the first 1,500 cytological diagnoses of fine-needle breast aspirates performed at Groote Schuur Hospital Breast Clinic are compared with the histological diagnoses of Tru-cut and excision biopsies of the same lesions. A cytological diagnosis of malignant disease was made in 358 cases, 349 of which were confirmed histologically. The 10 false-positive and 1 false-negative diagnoses are discussed. The reliability of diagnosis in the first 500 cases is compared with that in the second and third 500 cases. There were no false-positive diagnoses in the last 500 cases, and only 3 in the second 500 cases compared with 7 in the first 500 cases. Similarly, the 1 false-negative diagnosis was made in the first 500 cases. The results confirm the reliability of fine-needle aspiration biopsy cytology as a diagnostic technique. The number of incorrect diagnoses decreases as experience with the technique increases.

Biopsy, Needle↗
PubMed1987

Subtraction autoradiography of opiate receptor subtypes in human brain.

Opiate binding sites in sections of human brain were labelled with [3H]etorphine. Many brain areas contained high levels of [3H]etorphine binding sites although the globus pallidus was an exception. Subtraction autoradiography was performed using selective displacement of [3H]etorphine with opioid agonists to visualise mu-, delta- and kappa-opiate receptor subtypes. mu-Receptors were most abundant in the thalamus, caudate nucleus, putamen and the superficial layers of the cerebral cortex. Kappa receptors were concentrated in the deep layers of the cortex, the claustrum and the caudate nucleus. Human brain contained very few delta-receptors. Some brain areas with high concentrations of endogenous opioid peptides have many receptors, but in other areas, for example the globus pallidus, there is a mismatch between peptide concentration and receptor density.

Autoradiography↗
PubMed1987

Sodium dependent D-[3H]aspartate binding in cerebral cortex in patients with Alzheimer's and Parkinson's diseases.

The sodium dependent binding of D-[3H]aspartate to the high-affinity glutamate uptake system was used as a marker of glutamate-releasing terminals in the cerebral cortex of brains from patients with Alzheimer-type dementia (ATD) and Parkinson's disease (PD). Sodium-dependent D-[3H]aspartate binding was reduced in the ATD patients but not in the PD patients. Within the PD patients no association was observed between sodium-dependent D-[3H]aspartate binding and the presence of dementia. In contrast choline acetyltransferase activity was reduced in both the ATD and the PD patients. The present results suggest that changes in the cortical cholinergic system can occur independently of the cortical glutamate system. The glutamatergic deficit in ATD may contribute to some of the clinical differences between the dementia of ATD and PD.

Aged↗
PubMed1987

Changes in limb tone produced by regional injections of opiates into rat brain.

A mechanical apparatus was used to measure the resistance of the hindlegs to flexion in conscious rats. Systemically-administered morphine (7.5-12.5 mg/kg) caused increased muscle tone in the limbs. In rats with intracerebral cannulae, intrastriatal morphine (5-15 micrograms) had no effect on limb tone, whereas in increase in limb tone was induced by morphine (1-30 micrograms) in the globus pallidus. A strong and sustained increase in limb tone developed when morphine (0.2-2.5 micrograms) and the mu opiate receptor agonist DAGO (1.5-2.5 micrograms) were administered into the periaqueductal gray region of the midbrain, whereas the delta opiate receptor agonist DADLE (2.5-8 micrograms) was ineffective. The increased limb tone induced by opiates may be generated by mu-type receptors in at least two areas of brain.

Animals↗
PubMed1987

Rat middle cerebral artery occlusion: use of evoked potentials and tetrazolium staining to assess chronic ischaemia.

This study examined the effects of permanent, unilateral cerebral artery occlusion on the somatosensory evoked potential (SEP) recorded from the ipsilateral cortex in the anaesthetised rat. Ten days after artery occlusion the SEP was absent in the majority of rats tested and in the remainder the wave amplitude was reduced compared to the potential recorded from the normal hemisphere but latency was unaffected. Histochemical staining with Tetrazolium for infarct size has shown that loss of the SEP correlated with ischaemic damage to the cortex. SEP recording can be used to assess the extent of cortical ischaemia in this small animal model.

Animals↗
PubMed1987

Analysis of the brain regions involved in myoclonus produced by intracerebral picrotoxin.

Picrotoxin caused myoclonic jerking of the opposite forelimb when applied to the striatum and the cortical surface of rat brain. Intrastriatal picrotoxin increased [3H]2-deoxyglucose uptake by the ipsilateral frontal cortex, thalamus and subthalamic nucleus. Electrolyte and ibotenic acid lesions made in the globus pallidus prevented striatally evoked myoclonus without affecting the movements elicited from the cortex. Electrolytic lesions in the subthalamic nucleus and thalamus affected striatally evoked myoclonus more than the cortically elicited response. It is concluded that striato-pallidal-thalamic-cortical circuitry is responsible for striatally evoked myoclonus.

Animals↗
PubMed1987

What motivates medical students: how they see themselves and their profession.

This paper describes a repertory grid study of medical students' perceptions of medicine and its specialties. By sampling student attitudes at different stages of training, the authors show that in this sample, final-year medical students have a more vocational out-look than first-year students, in whom concern with relief of suffering is more important than aiming at cure and in whom materialistic success matters less than doing something 'important for mankind.' This is reflected in a shift of interest away from the surgical specialties.

Aspirations, Psychological↗
PubMed1987

Autoradiographic analysis of [3H]kainic acid binding in primate brain.

The distribution of [3H]kainic acid binding sites was studied in the primate brain using semiquantitative autoradiography. The highest levels of binding were observed in the hippocampal area CA3 and the dentate gyrus. The deep layers of pyriform, cingulate and insular cortex, the central nucleus of the amygdala and the caudate nucleus also displayed high levels of [3H]kainic acid binding. Although these areas receive putative excitatory amino acid-containing afferents, other regions containing a similar input displayed low levels of binding. Some similarities were apparent between the distribution of binding sites and pathological changes in human neurodegenerative disorders such as temporal lobe epilepsy.

Animals↗