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Biomedical subjects

R H Perry

Publications and source records attributed to R H Perry.

At least 163 records · Page 9Linked to original sources

Neuropeptides in gliomas: identification of somatostatin 14 in a medulloblastoma.

Forty nine gliomas were analysed for the following neuropeptides: somatostatin (SS), substance P (SP), neurotensin (NT) and vasoactive intestinal polypeptide (VIP) and the pituitary peptide, adrenocorticotrophin (ACTH). A significant amount of authentic SS was found in a medulloblastoma, and low concentrations of SP and NT immunoreactivity in an ependymoma and cerebellar astrocytoma respectively. The majority of the other gliomas did not contain detectable levels of these five neuropeptides. Low levels of neuropeptides were found in some specimens probably due to contamination with cerebral cortex.

Astrocytoma↗

Evidence for the early prenatal development of cortical cholinergic afferents from the nucleus of Meynert in the human foetus.

A combined histochemical and biochemical approach has shown that the cholinergic system in the nucleus of Meynert region of the substantia innominata is well defined both histochemically and neurochemically within the first 3 months of gestation in the human foetus. Thus, at between 12 and 22 weeks of development the most intense acetylcholinesterase (AChE) histochemical reactivity was observed in the neuropil, cell bodies and processes in the nucleus of Meynert. AChE-stained fibres were observed which coursed from the nucleus of Meynert towards the cortical mantle and within the mantle AChE-stained fibres were also present. Micropunch samples from within the nucleus of Meynert contained higher levels of choline acetyltransferase (ChAT) activity than any other area examined including the striatum, while in the cortical mantle the level of ChAT activity was comparable to that found in the adult cerebral cortex. These observations suggest that the cholinergic innervation from the nucleus of Meynert--considered to be the major source of cholinergic afferents in the adult cerebral cortex--may play a key role in the early development of the human neocortex.

Acetylcholinesterase↗

Agonal status affects the metabolic activity of nerve endings isolated from postmortem human brain.

Isolated nerve endings (synaptosomes) that show high rates of metabolic activity have been prepared up to 24 h postmortem from the brains of patients who have died suddenly. In contrast, similar preparations from brains of patients dying after a prolonged terminal illness showed little or no respiration. These data suggest that the agonal state of the patient is of major importance when investigating specific defects in neurotransmitter function in cerebral disorders and effects of neuroactive drugs on human tissue.

Adult↗

Somatostatin immunoreactivity in cortical and some subcortical regions in Alzheimer's disease.

Reverse phase HPLC analysis of somatostatin immunoreactivity in the cerebral cortex in elderly normal individuals revealed that the majority of the immunoreactivity co-eluted with synthetic somatostatin-14. While an immunoreactive peak corresponding to somatostatin-28 was not detected there was a peak of immunoreactivity which eluted after somatostatin-14. In cases of senile dementia of Alzheimer type (SDAT), where abundant neurofibrillary tangles and senile plaques (density greater than 30 per 1.3-mm2 field) were present in the cerebral cortex, somatostatin immunoreactivity was found to be significantly decreased in either the frontal or temporal cortex. Chromatographic analysis, however, revealed that both the major immunoreactive peaks detected in the normal group were reduced in SDAT in the temporal and frontal cortex. Using a punch microdissection technique somatostatin immunoreactivity has been assessed in the nucleus of Meynert and amygdala of SDAT and elderly normal cases. While there was no change in somatostatin immunoreactivity in the nucleus of Meynert in the SDAT group, tissue punches taken from the amygdala revealed a selective decrease in somatostatin immunoreactivity in the basal nucleus, in the SDAT cases.

Aged↗

Blood acetyl- and butyrylcholinesterases in senile dementia of Alzheimer type.

The major neurochemical abnormality described to date in senile dementia of the Alzheimer type (SDAT) is a central cholinergic deficit. To determine whether this central deficit is reflected by changes in the levels of blood cholinesterases, plasma and erythrocyte acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BChE), were measured in SDAT and other psychiatric disorders. Plasma AChE, which has only recently been described in human blood, was significantly elevated (P less than 0.01) in the SDAT group compared with the control and other clinical groups investigated. In contrast there were no significant differences in the activities of either erythrocyte AChE or plasma BChE between any of the clinical groups. Although the source of plasma AChE is unknown the possibility that some portion originates from the central nervous system and that the elevated AChE levels in SDAT reflect increased release from degenerating cholinergic neurons is discussed.

Acetylcholinesterase↗

Cholinergic correlates of cognitive impairment in Parkinson's disease: comparisons with Alzheimer's disease.

Dementia in Parkinson's disease has previously been attributed to the presence in the cerebral cortex of Alzheimer-type neuropathological abnormalities. New evidence suggests, however, that dementia in this disease usually occurs in the absence of substantial Alzheimer-type changes in the cortex and may be related to abnormalities in the cortical cholinergic system. Thus, in Parkinsonian patients with dementia there were extensive reductions of choline acetyltransferase and less extensive reductions of acetylcholinesterase in all four cortical lobes. Choline acetyltransferase reductions in temporal neocortex correlated with the degree of mental impairment assessed by a test of memory and information but not with the extent of plaque or tangle formation. In Parkinson's but not Alzheimer's disease the decrease in neocortical (particularly temporal) choline acetyltransferase correlated with the number of neurons in the nucleus of Meynert suggesting that primary degeneration of these cholinergic neurons may be related, directly or indirectly, to declining cognitive function in Parkinson's disease.

Acetylcholinesterase↗

Neuropeptide localisation in the substantia innominata and adjacent regions of the human brain.

A dense peptidergic innervation has been demonstrated in the substantia innominata region in postmortem specimens of human brain using immunocytochemical techniques. A peptidergic innervation of the nucleus of Meynert - the prominent nucleus of this area containing the cholinergic cell bodies which innervate the cerebral cortex - has been demonstrated by immunostaining with antisera against the following eight neuropeptides: somatostatin, substance P, cholecystokinin octapeptide, vasoactive intestinal polypeptide, met-enkephalin, ACTH, alpha-MSH and oxytocin. Other immunocytochemical features of the substantia innominata region include a dense band of peptide immunoreactivity beneath the medial aspect of the anterior commissure and islands of somatostatin and substance P terminal immunoreactivity in the rostral part of the substantia innominata. Somatostatin immunostained cell bodies have been located in a discrete area of the bed nucleus of the stria terminalis and in the rostral portion of the substantia innominata, nucleus accumbens and the ventral part of the putamen. The dense band of peptide immunoreactivity beneath the medial aspect of the anterior commissure consists of ribbon-like processes stained with antisera against somatostatin, substance P, cholecystokinin octapeptide, vasoactive intestinal polypeptide and met-enkephalin. Less intense immunostaining of ribbon-like elements is also present in the globus pallidus. The presence of a peptidergic innervation to the nucleus of Meynert suggests a possible important modulatory role in cortical cholinergic function.

Adrenocorticotropic Hormone↗

Cortical serotonin-S2 receptor binding abnormalities in patients with Alzheimer's disease: comparisons with Parkinson's disease.

Reductions in the numbers of binding sites for the serotonergic S2-receptor antagonist, ketanserin, are, as previously reported, evident in Alzheimer's disease. New findings indicate that these sites are not affected in the cortex of patients with Parkinson's disease despite the presence of cognitive impairment. In contrast S1-receptor binding sites were reduced to a small but significant extent in both Alzheimer's and Parkinson's disease with cognitive deficit. The S2-receptor binding loss was not related to the cholinergic deficit (decreased choline acetyltransferase) common to both disorders nor to the presence of cortical senile plaques but did relate to the extent of cortical neurofibrillary tangle formation, evident in Alzheimer's but not generally in Parkinson's disease. These observations suggest that S2- but not S1-receptor binding abnormalities may reflect an important intrinsic cortical involvement specifically associated with the Alzheimer disease process.

Aged↗

Studies on neurotransmitter receptor systems in neocortex and hippocampus in senile dementia of the Alzheimer-type.

Ligand binding to alpha 1-, alpha 2- and beta-adrenergic, serotonin, benzodiazepine and GABA receptors was studied in neocortex and hippocampus of controls and patients with senile dementia of the Alzheimer-type. A selective loss of serotonergic binding sites characterised as a loss of both S1 and S2 sites was observed. The reduction in serotonin receptors did not correlate with a clinical assessment of the degree of dementia, or with the extent of Alzheimer-type neuropathological change.

Aged↗

Chromatographic characterization of neuropeptides in post mortem human brain.

Reverse phase high performance liquid chromatography was used to establish the immunoreactive species of five neuropeptides (thyrotropin-releasing hormone, luteinising hormone-releasing hormone, neurotensin, substance-P and somatostatin) in three areas of post mortem human brain--the hypothalamus, amygdala and cortex. In the majority of cases the major immunoreactive peak corresponded to the authentic peptide, although other peaks of immunoreactivity were observed in several instances. It was established that somatostatin-14 was present as the major immunoreactive form and that somatostatin-28 did not occur in any of the three brain areas, although other somatostatin-immunoreactive peaks of unknown structure were detected. In addition to authentic neurotensin in the cortex, a substantial peak of immunoreactivity corresponding to the elution time of neurotensin (1-11) was observed. LH-RH was not detected in the amygdala, but was present in the cortex as a minor component of overall immunoreactivity. The major peak of substance-P immunoreactivity in all three brain areas corresponded to authentic substance-P; in addition immunoreactive material eluting in the region of [Met-O] substance-P, substance-P (5-11) and substance-P (6-11) were detected. TRH occurred as the major peak in all three areas, although minor peaks of immunoreactivity were seen in the amygdala.

Adult↗

Intralaminar neurochemical distributions in human midtemporal cortex: comparison between Alzheimer's disease and the normal.

The intralaminar distributions of transmitter and nontransmitter enzyme activities and amino acid levels were determined in the midtemporal cortices from normal individuals and established cases of Alzheimer's disease. In the normal, choline acetyltransferase (CAT) and acetylcholinesterase (AChE) activities were relatively high in the outer cortical layers, particularly, for CAT, in the two granular layers (II and IV). Both activities were reduced in Alzheimer's disease at all, although generally most extensively in the outer and middle layers of the grey matter whereas activities were near normal in the white matter. Further, the enzyme distribution patterns of these cholinergic activities were also disrupted in Alzheimer's disease and the activity of CAT throughout the cortex was generally reduced to that found in the white matter. No such differences in distribution were found for two other enzymes, pseudocholinesterase and lactate dehydrogenase. Assessment of the gamma-aminobutyric acid (GABA) system in the normal revealed a much more extensive intralaminar variation in the enzyme, glutamate decarboxylase, compared with the level of GABA itself. In contrast with the cholinergic enzymes, neither the levels nor intralaminar patterns of GABA were altered in Alzheimer's disease. From an analysis of free amino acids at the different cortical levels, the cortical pattern of glutamic acid in the normal was different from that for GABA, aspartic acid, or nontransmitter amino acids such as alanine. Neither of the putative amino acids, glutamate or aspartate, was altered in Alzheimer's disease. These findings demonstrate the relatively selective nature of microchemical changes occurring in the cortex in Alzheimer's disease and suggest that a functional abnormality in cholinergic input to the outer neocortical layers (I-IV) with predominantly receptive and associative functions may be an important feature of the disease.

Acetylcholinesterase↗

The substantia innominata and adjacent regions in the human brain: histochemical and biochemical observations.

The substantia innominata was investigated in the adult human brain with particular reference to the cholinergic nature of the nucleus of Meynert. Based on histochemical observations of acetylcholinesterase activity and biochemical estimations of choline acetyltransferase the relations of the Meynert nucleus to adjacent structures in the substantia innominata region were identified precisely. A new dissection procedure is described which permits combined histochemical and histological examination of anatomically complex regions of the human brain, such as the substantia innominata, to be carried out in conjunction with accurate tissue dissection for neurochemical analysis. Using this technique, various acetylcholinesterase-positive and choline acetyltransferase-containing structures are apparent in coronal sections removed from the rostrocaudal length of the substantia innominata. These include, in addition to the prominently stained, putative cholinergic neurons, acetylcholinesterase-positive tracts which contain putative cholinergic projections to the neocortex, and 'islands' of acetylcholinesterase-positive neuropil which presumably reflect a collateral or intrinsic cholinergic innervation in the area. This anatomical complexity of cholinergic structures in the substantia innominata suggests that neurochemical analysis should be conducted on microdissected as opposed to macrodissected tissue samples. Neuropathologically, the present report provides a further basis for optimising quantification of putative cholinergic perikarya. Continued systematic analysis of the nucleus of Meynert at the morphological and biochemical level should thus establish the role of this nucleus in normal brain function and in disease.

Acetylcholinesterase↗

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↗

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↗

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↗

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↗