Search PubMed⌕ Search

Biomedical subjects

E K Perry

Publications and source records attributed to E K Perry.

At least 163 records · Page 9Linked to original sources
PubMed1982

The influence of agonal status on some neurochemical activities of postmortem human brain tissue.

The number of general biochemical and specific neurochemical activities have been investigated in postmortem human brain tissue in relation to the terminal state of the patient. Cases were broadly divided into those dying after a period of normal or near normal health (Category A) and those dying after a prolonged period of severe illness (Category B). Whilst most of the metabolic and transmitter-related enzymes, amino acids and neuropeptides investigated were not significantly different between the two groups, there were in Category B highly significant reductions in glutamate decarboxylase, phosphofructokinase and tissue pH, and increases in several amino acids including, most extensively, tryptophan. The possible use of such activities as 'markers' of agonal status in the selection of normal material and in the matching of control and pathological material in postmortem human brain studies is discussed.

Amino Acids↗
PubMed1982

Angiotensin converting enzyme in Alzheimer's disease increased activity in caudate nucleus and cortical areas.

The activity of the dipeptidyl carboxypeptidase, angiotensin converting enzyme, was assayed in several brain regions of patients dying with Alzheimer's disease and compared to that of appropriately age-matched controls. Enzyme activity was found to be elevated by 44% and 41% in the medial hippocampus and parahippocampal gyrus, respectively, and by 27% and 29% in the frontal cortex (area 10 of Brodman) and caudate nucleus, respectively, in Alzheimer's disease patients. Converting enzyme activity did not differ from controls in the nucleus accumbens, substantia nigra, temporal cortex, anterior or posterior hippocampus, amydgala, and septal nuclei.

Alzheimer Disease↗
PubMed1981

A rapid method for preparing synaptosomes: comparison, with alternative procedures.

A method for the rapid (1-1.5 h) preparation of nerve ending particles (synaptosomes) from rat cerebral cortex is described. The synaptosome fraction has been characterized by quantitative electron microscopy and enzyme distribution studies. By these criteria, the fraction showed a degree of enrichment in synaptic structures which was comparable to that of the standard (4-5 h) preparation, and substantially better than an alternative fast (2-2.5 h) method. On incubation, synaptosomes obtained by the new procedure accumulated a high tissue concentration of potassium and showed a high, linear rate of oxygen uptake. Depolarization by veratrine caused a significant increase in the rate of respiration and in the release of the physiologically active amino acids; glutamate, aspartate and GABA, as well as a significant reduction in tissue potassium. Thus, the new procedure compared favourably with alternative methods as judged by these indices of metabolic and functional performance. The new preparation method has been found to be of value in metabolic studies of synaptosomes prepared from human post-mortem brain.

Amino Acids↗
PubMed1981

Properties and possible significance of substance P and insulin fibrils.

The neuropeptide substance P forms polymeric fibrils similar to those previously reported for the hormone, insulin. Structural and chemical aspects of these two fibrillary forms have been compared and their possible existence in vivo considered. Numerous substance P fibrils are readily formed in vitro in mM solutions under conditions which are physiological with respect to salt concentration, pH and temperature, whereas more severe conditions (heat and acid) are apparently required for the rapid formation of numerous insulin fibrils. Morphologically, both fibrils appear to be relatively long and unbranched and the neuropeptide fibrils are similar in size to such naturally occurring structures as neurofilaments. Disaggregation of the neuropeptide fibril follows dilution (1000-fold) whilst more stringent (alkaline) treatment is apparently necessary for insulin fibril dissociation. These observations are discussed in relation to the role of an insulin-like peptide in the formation of certain types of amyloid and the possibility that fibrillary of similar polymeric forms of substance P may exist in normal tissue.

Insulin↗
PubMed1981

Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease.

The activity of the noradrenergic marker enzyme dopamine-beta-hydroxylase was measured in brains removed postmortem from control patients and patients with Alzheimer's disease. Enzyme activity was decreased in the frontal and temporal cortices and hippocampus in patients with Alzheimer's disease, but was within the normal range in patients with depression, multiinfarct dementia, and terminal coma.The decrease in enzyme activity in Alzheimer's disease may reflect an abnormality of cortical noradrenergic fibres in some patients with the disease.

Aged↗
PubMed1981

Neuropathological and biochemical observations on the noradrenergic system in Alzheimer's disease.

Abnormalities of the noradrenergic system in Alzheimer's disease have been investigated by comparing quantitative histological and biochemical components of this transmitter system (locus coeruleus neuron counts and cortical dopamine beta-hydroxylase (DBH) activity, respectively) in a series of demented and non-demented cases. Cortical activities of the noradrenergic enzyme, DBH, did not correlate significantly with the number of locus coeruleus neurons, a finding which contrasts with the previous observations in animal brains of reductions in cortical DBH following locus coeruleus lesions. The extent of Alzheimer-type abnormalities, assessed from either morphological measures (mean plaque counts) or clinical measures (Mental Test Scores) of severity, was not significantly related to the cortical activity of DBH in the present series of cases, although non-significant trends were apparent. In contrast the activity of the cholinergic enzyme choline acetyltransferase did, as previously reported, correlate significantly with the extent of Alzheimer-type abnormalities, suggesting that abnormalities of the cholinergic system are more closely associated with specific aspects of the Alzheimer disease process than those of the noradrenergic system.

Alzheimer Disease↗
PubMed1981

Neuropeptides in Alzheimer's disease, depression and schizophrenia. A post mortem analysis of vasoactive intestinal peptide and cholecystokinin in cerebral cortex.

Vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) have been measured, by radioimmunoassay, in cerebral cortex obtained at autopsy from patients without neurological or psychiatric disease and from patients with Alzheimer's disease, depression and schizophrenia. Sephadex gel filtration indicated that over 90% of the CCK immunoreactivity was associated with the octapeptide in extracted material from the different clinical groups investigated. There were no significant differences from the normal in the overall concentrations of either VIP or CCK in any of the psychiatric groups examined, although differences in Alzheimer's disease were apparent when cases were grouped according to postmortem delay.

Alzheimer Disease↗
PubMed1981

Neurochemical activities in human temporal lobe related to aging and Alzheimer-type changes.

Activities relating to 3 neurotransmitter and 4 neuropeptide systems have been examined in human temporal lobe (post mortem) for their relationships with age and Alzheimer-type changes (senile plaques and cognitive function). Significant alterations with increasing age (from 61 to 92 years) in a series of non-demented cases included a reduction of the cholinergic enzyme, choline acetyltransferase, and an increase in vasoactive intestinal peptide immunoreactivity. In cases of alzheimer's disease the only neurochemical activity investigated which correlated significantly with cognitive impairment (assessed from a Mental Test Score obtained shortly before death) and with the severity of Alzheimer-type abnormalities (senile plaques density) was choline acetyltransferase. Further analyses of the data in relation to the severity of plaque formation suggest that alterations in other neurochemical activities including reductions in dopamine-beta-hydroxylase activity, cholecystokinin octapeptide (aqueous extracted) and somatostatin immunoreactivities and an increase in substance P immunoreactivity, may occur at later stages of the disease process. These comparative data suggest that biochemical changes in this brain area associated with age and earlier stages of Alzheimer's disease may be relatively selective.

Aged↗
PubMed1980

Coenzyme A-acetylating enzymes in Alzheimer's disease: possible cholinergic 'compartment' of pyruvate dehydrogenase.

In the mammalian central cholinergic system the precise mechanism for the production of acetyl-CoA used in acetylcholine synthesis has not yet been identified. As a possible means of investigating this problem the relationship between the activities of several enzymes which can synthesize acetyl-CoA and the cholinergic defect of Alzheimer's disease has been examined. Small, but significant reductions in the activities of pyruvate dehydrogenase, ATP-citrate lyase and acetoacetyl-CoA thiolase were found in post mortem brain tissue from cases of Alzheimer's disease, and the decrease in pyruvate dehydrogenase appeared to be related to the extent of the cholinergic defect (as indicated by loss of choline acetyltransferase). Furthermore, the regional distribution of choline acetyltransferase was similar to that of pyruvate dehydrogenase but not to the distribution of the other enzymes investigated in normal human brain tissue. These observations tend to support a recent suggestion that there may be a particular form of pyruvate dehydrogenase associated with cholinergic neurones.

ATP Citrate (pro-S)-Lyase↗
PubMed1980

The cholinergic system in old age and Alzheimer's disease.

Activities relating to the cholinergic system in post-mortem brain tissue have been examined in relation to ageing and Alzheimer-type pathology. As senile plaque numbers increased in non-demented and demented old people, activities of choline acetyltransferase and acetylcholinesterase decreased, butyrylcholinesterase increased and muscarinic receptor binding remained unchanged. The behaviour of these biochemical activities was further examined in relation to the ageing process in mentally normal people. Loss of choline acetyltransferase also occurred, to a lesser extent, with increasing age and muscarinic binding decreased but there was no age-related loss in acetylcholinesterase. These biochemical findings are discussed in relation to the possible involvement of the cholinergic system in 'normal' ageing and in Alzheimer's disease and are compatible with an extension of age-related nerve terminal changes to abnormalities of cholinergic processes in the disease itself.

Acetylcholine↗
PubMed1980

Histochemical observations on cholinesterase activities in the brains of elderly normal and demented (Alzheimer-type) patients.

The extent and distribution of acetylcholinesterase staining in the hippocampus has been compared in normal elderly cases and patients with Alzheimer's disease. In both groups some senile plaques and neurofibrillary tangles stain positively with acetylcholinesterase and in Alzheimer's disease there is a reduction in acetylcholinesterase staining of nerve processes. The positive staining of processes in senile plaques suggests that they are, at least partly, derived from cholinergic, axonal fibres and the decrease in acetylcholinesterase staining of nerve processes may indicate a diminution in cholinergic, afferent input fibres to the hippocampus in Alzheimer's disease.

Acetylcholinesterase↗
PubMed1980

Hippocampal free amino acids in Alzheimer's disease.

The free amino acid content of the hippocampus, obtained at postmortem, has been analysed in cases of Alzheimer's disease and compared with normal cases. There were no significant differences in the levels of 23 amino acids including the transmitter candidates gamma-aminobutyric, glutamic or aspartic acids. This finding is interpreted in relation to present knowledge of transmitter pathways in the region of the hippocampus. A tendency for some amino acids to be increased in the Alzheimer group reached statistical significance for arginine. This observation is consistent with increased proteolytic or peptidase activity in Alzheimer's disease.

Aged↗
PubMed1978

Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia.

Necropsy brain tissue from normal (control) patients and patients with depression and dementia was examined for activities of various cholinergic components, and these related to the degree of senile plaque formation and extent of intellectual impairment. Choline acetyltransferase and acetylcholinesterase activities decreased significantly as the mean plaque count rose, and in depressed and demented subjects the reduction in choline acetyltransferase activity correlated with the extent of intellectual impairment as measured by a memory information test; muscarinic cholinergic receptor binding activity remained unchanged with increasing senile plaque formation but butyrylcholinesterase activity increased. The results suggest a close relation between changes in the cholinergic system and Alzheimer's dementia, but the precise role of the system in this disease remains to be elucidated.

Acetylcholinesterase↗