Biomedical subjects
Publications and source records attributed to A N Davison.
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Loss of neurons from the ageing human brain is accompanied by reduction in biochemical markers. Compared with age-matched controls about one third of nerve cell components are lost from the temporal lobe of patients with senile dementia of Alzheimer's type. There is marked loss of choline acetyltransferase activity, especially in the hippocampus. This alteration parallels the intensity of neuropathological damage and relates to prior mental impairment. Smaller changes in other neurotransmitter synthesizing enzymes are generally found.
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Peripheral blood lymphocytes from 24 out of 26 patients with clinically well-defined multiple sclerosis in remission showed sensitisation to multiple sclerosis brain extracts as assayed by enhancement of the early erythrocyte rosette test. Such an increase in the number of early rosettes was not found when the lymphocytes of multiple sclerosis patients were exposed to extracts of control brains. In contrast the sensitised cells were found in the circulation in only two of 11 patients with multiple sclerosis in acute relapse. The percentage of circulating T-lymphocytes which formed early rosettes was lower in the group of patients suffering a relapse than in patients in remission. A longitudinal study of one patient who was tested before, during and after a relapse revealed the disappearance from the blood of the sensitised T-cells during the relapse and their subsequent reappearance after recovery. Of 36 patients with other neurological diseases, two responded solely to multiple sclerosis brain, two responded to both multiple sclerosis and control brain, and three responded only to control brain. No healthy controls showed sensitisation to any brain extract.
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Extensive biochemical analysis of whole temporal lobe from cases of dementia and controls suggests that Alzheimer's disease is a primary degenerative nerve-cell disorder and not the result of accelerated ageing. There is selective loss of neocortical cholinergic neurones. Transmitter systems apart from the cholinergic system appears to be affected, but to a lesser extent, and there are no significant changes in the caudate nucleus. The change in cholinergic neurones has been confirmed in biopsy samples.
Further examination of the neutral lipid fractions derived from brain tissue of two patients afflicted with adrenoleukodystrophy has demonstrated the presence not only of free cholesterol and cholesteryl ester, but also of appreciable free fatty acid and triglyceride. Using a gas--liquid chromatographic system normally employed for the analysis of long-chain fatty acids of galactolipids and spingomyelin, it was possible to establish the presence of long-chain (greater than C20) fatty acids in the cholesteryl ester, free fatty acid and triglyceride fractions. Long-chain fatty acids were most abundant in the cholesteryl esters. Fatty acids identified by gas--liquid chromatography and gas chromatography--mass spectroscopy included normal saturated and monounsaturated fatty acids as large as C34. Several unknown fatty acyl compounds, of as yet undetermined structure, were also observed. All investigations thus far would indicate that the pathogenesis of adrenoleukodystrophy is closely related to the aberrant metabolism of these long-chain fatty acids.
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Material has been examined from eighteen brains, postmortem and from 3 cortical biopsies. The case were classified on clinical and morphological criteria and include cases of dementia and of nonneurological disease. Fractions were isolated from homogenates of neocortex and caudate nucleus by means of discontinuous sucorse density gradient centrifugation. The fractions were analysed for protein content. The mean protein content of fraction 1, at the interphase between 0.32 M and 0.8 M sucrose, from the cortex of the 6 Alzheimer cases was reduced. (P less than 0.005) by 25%. This deficit in protein content represents less than 5% of the total tissue protein. There were no significant differences in the protein content between other fractions from the control and Alzheimer cases.
Upon stimulation by immune complexes, the polymorphonuclear (PMN) blood secretes lysosomal hydrolases, including neutral proteinase, which is concentrated in the PMN cell. Neutral and acid proteinase activity were increased and decreased, respectively, in the circulating white cells of patients with multiple sclerosis during an exacerbation of the disease, but there was no correlation with serum immune complex levels. Neutral proteolytic activity in the cellular fraction of the cerebrospinal fluid was also found to be elevated in acute multiple sclerosis, as monitored by digestion of myelin basic protein.
The in vitro synthesis of myelin proteins has been studied by measuring the incorporation of [3H] lysine in developing rat brain slices. This incorporation system has been used to assay potentially gliotoxic and myelinolytic agents. A reduced incorporation of the labelled amino acid into myelin proteins occurs in the presence of anti-myelin anti-serum and anti-basic protein anti-serum. Diphtheria toxin has been found to inhibit the synthesis of myelin basic and proteolipid protein in the white matter slices of developing rats. Recent experiments with serum samples from multiple sclerosis patients in exacerbation suggest the presence of a factor which interferes with the synthesis of myelin in white matter slices.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The passage of orally administered taurine across the intestinal wall to the blood plasma and target sites of neuromuscular excitability has been studied. This has been correlated with the effect of repeated oral dosing on the manifestations of cobalt-induced epilepsy in the rat. The blood-brain barrier and the organ distribution of taurine uptake have important implications in testing its effect on hyperexcitability phenomena.