PubMed Health⌕ Search

Biomedical subjects

R H Perry

Publications and source records attributed to R H Perry.

At least 163 records · Page 9Linked to original sources
PubMed1983

Four primary tumors in one child.

A child is described who, following surgery and irradiation for malignant choroid plexus papilloma at the age of 11 months, developed three further tumors: A benign myxofibroma of the cranium at the age of 3 1/2 years, an undifferentiated anaplastic tumor of his clavicle at 7 1/2 years, and a chondroblastic osteogenic sarcoma of his pelvis at the age of 12 years. There was no apparent genetic predispositions to malignancy. The latter three neoplasms may have originated either in, or at the edge of, the original radiotherapy field, suggesting that the child has a particular susceptibility to the oncogenic potential of radiotherapy.

Anaplasia↗
PubMed1983

Human brain neurochemistry - some postmortem problems.

Neurochemical analyses of postmortem human brain tissue is currently a challenging and expanding area of research. Many groups are now concentrating on mapping central neuronal pathways or identifying biochemical abnormalities in neurological and psychiatric diseases. In investigations of this kind a number of more or less obvious problems have to be tackled and this article provides some idea of current, and often controversial, issues associated with sampling postmortem brain material and with some of the variable factors which may influence neurochemical data.

Brain↗
PubMed1983

Molecular forms of acetylcholinesterase in senile dementia of Alzheimer type: selective loss of the intermediate (10S) form.

Using density gradient centrifugation, three molecular forms of acetylcholinesterase have been distinguished in both normal and senile dementia of Alzheimer-type (SDAT) postmortem neocortex. Whilst the levels of the light and heavy forms were unaltered in SDAT there was a selective and extensive loss of the intermediate form. This form is predominantly hydrophobic and its loss from the cerebral cortex in SDAT may reflect degeneration of cholinergic axonal processes. This is the first report of an altered distribution of acetylcholinesterase molecular forms in a disease of the central nervous system.

Acetylcholinesterase↗
PubMed1983

Pathological changes in the nucleus of Meynert in Alzheimer's and Parkinson's diseases.

Combined neuropathological and neurochemical assessment of the nucleus of Meynert in senile dementia of Alzheimer type (SDAT) have demonstrated that the cholinergic biochemical activity, choline acetyltransferase, is more extensively reduced in the nucleus (over 90%) than the loss of putative cholinergic perikarya (35%). Acetylcholinesterase histochemical activity was however substantially retained in individual neurones in the nucleus although virtually absent from the neocortex in SDAT. These abnormalities are consistent with a primary degeneration of cholinergic axons projecting to the cortex and secondary loss of perikarya from the subcortical nucleus. In contrast, preliminary observations on cases of Parkinson's disease suggest that the neuronal loss from the nucleus of Meynert may be greater in this disease than in SDAT, and previous studies have not consistently demonstrated a reduction in cortical choline acetyltransferase activities in Parkinson's disease. These observations, together with major differences in the neuropathology of the nucleus in SDAT and Parkinson's disease (neurofibrillary tangle and Lewy body formation, respectively) suggest that the involvement of the cholinergic system may differ in the two disease processes.

Acetylcholinesterase↗
PubMed1983

Post mortem levels of thyrotropin-releasing hormone and neurotensin in the amygdala in Alzheimer's disease, schizophrenia and depression.

The levels of neurotensin and thyrotropin-releasing hormone (TRH) in normal post mortem human amygdala have been compared with those in cases of schizophrenia, Alzheimer's disease and depression. Amongst various factors which can influence post mortem human brain biochemistry (including age, sex, post mortem delay, time of death, disease status and severity), sex difference appeared to be responsible for the most extensive variation. The levels of both peptides were nearly doubled in males compared with females and this increase was significant in the case of neurotensin. There was also a positive correlation between neurotensin and TRH levels. Although levels of neurotensin and TRH tended to be lower in the disease groups these trends did not reach significance.

Aged↗
PubMed1983

Metabolically active synaptosomes can be prepared from frozen rat and human brain.

Nerve ending particles (synaptosomes) were prepared from pieces of rat and human brain and from brain homogenate that had been frozen and thawed under a variety of conditions. Their purity, as judged by electron microscopy, and performance in terms of a number of metabolic and functional parameters [accumulation of tissue potassium, respiration, release of transmitter amino acids, and the responses on these indices to depolarisation by veratrine (VX)] were compared with those of fresh tissue-derived synaptosomes. It was found that rapid freezing and/or slow thawing severely impaired the subsequent performance of incubated synaptosomes. In contrast, synaptosomes from tissue frozen slowly and thawed rapidly showed relatively good retention of morphology and metabolic performance. It was better to use whole (1-5 g) pieces of tissue than tissue homogenate: the synaptosome fraction from frozen tissue pieces contained 80% of the proportion of identified synaptosomes found in the fresh tissue synaptosome fraction, its respiratory rate was 65%, and its tissue potassium content 70% of that of fresh controls. Moreover, it responded to VX or potassium stimulation by showing increased respiratory rate, decreased tissue potassium, and increased release of neurotransmitter amino acids, to an extent that was comparable to that of fresh tissue fractions. Thus, preparations from frozen rat and human brain were shown to be metabolically and functionally active, and can be used for a variety of neurotransmitter-related studies.

Animals↗
PubMed1983

Decreased imipramine binding in the brains of patients with depressive illness.

The binding of tritiated imipramine was significantly reduced in the hippocampus and occipital cortex from a series of patients with depressive illness compared with age-matched patients with no psychiatric disorder. In contrast there was no change in imipramine binding in established cases of senile dementia of Alzheimer-type. Scatchard analysis indicated normal binding affinity but a reduction in the number of imipramine binding sites in depression. These observations parallel previous findings of decreased binding sites in platelets from depressed patients and suggest there may be an abnormality in the uptake mechanism for serotonin in depression.

Aged↗
PubMed1982

Extensive loss of choline acetyltransferase activity is not reflected by neuronal loss in the nucleus of Meynert in Alzheimer's disease.

Choline acetyltransferase activity in discrete tissue punches from the nucleus of Meynert and in tissue from the temporal cortex was reduced by at least 90% and 75%, respectively, in 5 out of 6 elderly cases of Alzheimer's disease compared with 5 normal cases. In contrast, estimates of neurone density in these same cases revealed that there was only, on average, a 33% neurone loss in the nucleus of Meynert in Alzheimer's disease. These observations suggest that a key pathological change in Alzheimer's disease may be the 'down regulation' of transmitter-specific enzyme production in cholinergic neurones, and that neurone loss itself may be a secondary feature of the disease.

Aged↗
PubMed1982

Use of post-mortem human synaptosomes for studies of metabolism and transmitter amino acid release.

Synaptosomes have been prepared from human brain obtained at autopsies carried out up to 24 h postmortem (p.m.). They showed generally good retention of morphology, as well as accumulation of tissue potassium and linear rates of oxygen uptake. In response to veratrine depolarization they showed increased respiration rate, decreased tissue potassium content and the specific release of transmitter amino acids. Regression analysis indicated that metabolically and functionally active preparations may be obtained up to ca. 25 h p.m. Preparations obtained from patients dying with brain injury were inactive.

Adult↗
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↗
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↗