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Biomedical subjects

E G Spokes

Publications and source records attributed to E G Spokes.

At least 37 records · Page 2Linked to original sources
PubMed1980

Neurochemical alterations in Huntington's chorea: a study of post-mortem brain tissue.

Dopamine, noradrenaline, glutamic acid decarboxylase and choline acetyltransferase were measured in various regions of brain obtained at autopsy from a large series of cases of Huntington's chorea, dying with advanced forms of the disease. Neurochemical values in the choreic cases were compared with those from control and schizophrenic cases. In brain tissue from choreic patients, highly significant increases in dopamine concentrations were found in the corpus striatum, nucleus accumbens and pars compacta of the substantia nigra. This is consistent with the hypothesis that the nigrostriatal dopamine system is spared and may exert a relatively unopposed action on striatal function. Noradrenaline concentrations were raised in the caudate nucleus, lateral pallidum and pars reticulata of the substantia nigra, indicating preservation of central noradrenergic pathways. Glutamic acid decarboxylase activity was reduced in all brain regions examined but, taking ante-mortem factors into account, the depletion was confined to the striatum and lateral pallidum. This is consistent with the view that striatal GABA-containing interneurons degenerate. Significant losses of choline acetyltransferase activity were observed in the striatum, nucleus accumbens, septal nuclei and hippocampus. The development of muscle rigidity in choreic patients did not significantly affect the neurochemical values. The neurochemical alterations in Huntington's chorea could not be attributed to differences in ante-mortem or post-mortem factors between the choreic group and the control and schizophrenic groups.

Adolescent↗
PubMed1979

Antipsychotic drug action in schizophrenic patients: effect on cortical dopamine metabolism after long-term treatment.

In the brains of deceased schizophrenics who underwent long-term treatment with antipsychotic drugs, the concentration of homovanillic acid (a dopamine metabolite) was significantly increased in the orbital frontal, cingulate, and temporal tip areas of the cortex, but not in the putamen or the nucleus accumbens. The concentration of homovanillic acid was normal in the brains of schizophrenics who were not treated with drugs.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

Alterations in [3H]spiperone binding in human caudate nucleus, substantia nigra and frontal cortex in the Shy-Drager syndrome and Parkinson's disease.

[3H]Spiperone binding was investigated in the caudate nucleus, substantia nigra (s. nigra) and frontal cortex of control subjects and of patients with Parkinson's disease and the Shy-Drager syndrome. Binding sites for [3H]spiperone were interpreted as dopamine receptors in caudate and s. nigra, and as 5-hydroxytryptamine (5-HT) receptors in frontal cortex. Scatchard analysis showed that the Bmax (maximal number of binding sites) in caudate was similar in the 3 groups, whereas in s. nigra the Bmax was reduced by approximately 60% in both Parkinsons disease and Shy-Drager syndrome. The dissociation constant (Kd) for [3H]spiperone binding in s. nigra was similar in the 3 groups. In caudate nucleus, the Kd was similar in control and Parkinson groups; however, there was a significant increase in the dissociation constant in the caudate nucleus from cases of Shy-Drager syndrome. No differences in binding characteristics were observed in the frontal cortex. These results are taken to reflect a loss of dopamine receptor sites in the s. nigra in both Parkinson's disease and Shy-Drager syndrome, and a reduced affinity of dopamine receptor sites in the caudate nucleus in Shy-Drager syndrome.

Binding Sites↗
PubMed1979

Multiple system atrophy with autonomic failure: clinical, histological and neurochemical observations on four cases.

Four cases of progressive autonomic failure are described, in all of which there were additional non-autonomic neurological abnormalities, including pyramidal, extra-pyramidal and cerebellar features. Histological examination revealed cell degeneration in the substantia nigra, putamen and intermediolateral columns of the spinal cord as a common pathological finding. In addition, 3 cases showed loss of Purkinje cells in the cerebellum and degeneration of pontine nuclei and inferior olivary nuclei. In one case there was cell loss from the locus coeruleus, caudate nucleus, vestibular nuclei and dorsal vagal nuclei. These were, therefore, cases of multiple system atrophy. Neurochemically, a common feature was a profound depletion in dopamine and noradrenaline from brain regions which are normally rich in these catecholamines. Central cholinergic systems appeared to be involved also, but to a variable degree.

Aged↗
PubMed1979

An analysis of factors influencing measurements of dopamine, noradrenaline, glutamate decarboxylase and choline acetylase in human post-mortem brain tissue.

Measurements have been made of dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetylase (CAT) in a variety of regions from human post-mortem brain tissue, and the results analysed as a function of ante-mortem and post-mortem factors which may influence such measurements. The agonal status of the patient emerged as a major influence on the post-mortem measurement of GAD activity, without significantly affecting the other biochemical parameters. Of the other ante-mortem factors investigated, there appeared to be no differences between male and female, no circadian fluctuations, and few significant age-related changes, in any of the biochemical parameters measured in different brain regions. Moreover, the results indicated that the enzymes GAD and CAT are remarkably stable in human brain during routine post-mortem handling. Similar findings were made for dopamine and noradrenaline, although a substantial loss of both catecholamines probably occurs in the first few hours after death.

Adolescent↗
PubMed1979

Increased dopamine concentration in limbic areas of brain from patients dying with schizophrenia.

Dopamine, noradrenaline, glutamate decarboxylase (GAD) and choline acetyl-transferase (CAT) were measured in post-mortem brain samples from more than 50 patients dying with a hospital diagnosis of schizophrenia and an equal number of controls. GAD was measured in 14 different brain regions, and was significantly lower in both control and schizophrenia patients who died following a protracted illness. If GAD values from patients who died suddenly were compared, no significant differences were observed between the control and schizophrenia groups. There was also no differences between the CAT values measured in 13 different brain regions in the two groups. Noradrenaline values were not different in the two groups in most limbic areas or in the caudate nucleus, but were elevated in the schizophrenic group in nucleus accumbens and in anterior perforated substance. These differences were not, however, statistically significant. On the other hand dopamine concentrations in nucleus accumbens and in anterior perforated substance were significantly elevated (by 34 and 95 per cent, respectively) in the schizophrenia group as compared with controls, although dopamine values were not different in caudate nucleus, putamen, septal nuclei or amygdala. The finding of elevated concentrations of dopamine in certain areas of the limbic forebrain in schizophrenia is discussed in relation to current hypotheses of the involvement of dopamine in this illness, and the difficulties of determining whether the observed changes are related to chronic treatment with antischizophrenic drugs.

Brain Chemistry↗
PubMed1979

Distribution of beta-endorphin in normal and schizophrenic human brains.

beta-Endorphin was measured by radioimmunoassay in post-mortem human brains. Samples of brain were taken from five discrete areas, both from control brains and brains of schizophrenic patients. No difference in beta-endorphin levels was found in these two groups of brains. beta-Endorphin was confirmed to be widely distributed in the brain, but there were considerable differences in the concentrations in different areas.

Brain Chemistry↗
PubMed1978

Angiotensin-converting enzyme in substantia nigra: reduction of activity in Huntington's disease and after intrastriatal kainic acid in rats.

The substantia nigra of Huntington's disease brains shows a 78% reduction in angiotensin-converting enzyme activity in the pars reticulata and a 48% reduction in the pars compacta. The nucleus accumbens shows a 28% reduction in converting enzyme activity. In the rat, after intrastriatal injections of kainic acid (2.5 microgram), an agent which selectively destroys neuronal cell bodies, there is a 55% reduction in angiotensin-converting enzyme activity in the ipsilateral substantia nigra. Both human and animal data suggest that a major part of the angiotensin-converting enzyme in the substantia nigra is localized in nerve terminals whose cell bodies originate in the striatum.

Animals↗