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Biomedical subjects

R H Perry

Publications and source records attributed to R H Perry.

At least 109 records · Page 6Linked to original sources
PubMed1992

Iron and aluminium in relation to brain ferritin in normal individuals and Alzheimer's-disease and chronic renal-dialysis patients.

Ferritin has been isolated and its subunit composition, iron and aluminium content determined in the cerebral cortex and cerebellum of normal individuals and in the cerebral cortex of Alzheimer's-disease and renal-dialysis patients. An e.l.i.s.a. for ferritin has been developed and the ferritin, non-haem iron and aluminium content of the parietal cortex were determined in normal individuals and Alzheimer's-disease patients. It was found that ferritin from the cerebral cortex and cerebellum of normal individuals had a high H-subunit content, similar to that of heart ferritin. The subunit composition of ferritin isolated from the cerebral cortex was not significantly altered in Alzheimer's-disease or renal-dialysis patients. Ferritin from the cerebral cortex of normal individuals had only approx. 1500 atoms of iron per molecule and the iron content of ferritin was not significantly changed in Alzheimer's-disease or renal-dialysis patients. Ferritin isolated from the cerebral cortex of normal, Alzheimer's-disease and renal-dialysis patients had less than 9 atoms of aluminium per molecule. The failure to find increased concentrations of aluminium associated with ferritin in dialysis patients, who had markedly increased concentrations of aluminium in the cerebral cortex, shows that aluminium does not accumulate in ferritin in vivo. This has important implications for the toxicity of aluminium, since it implies that cells are unable to detoxify aluminium by the same mechanism as that available for iron. Comparison of the concentrations of ferritin, aluminium and iron in the parietal cortex from normal and Alzheimer's-disease patients showed that, whereas the concentration of aluminium was not increased, both ferritin and iron were significantly increased in Alzheimer's disease.

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PubMed1992

Hippocampal nerve growth factor receptor immunoreactivity in patients with Alzheimer's and Parkinson's disease.

Using the monoclonal antibody, ME 20.4, against the p75 nerve growth factor (NGF) receptor, NGF receptor-like immunoreactivity has been identified in axonal processes innervating the human hippocampus, where previously a loss of reactivity has been reported in a preliminary study of Alzheimer's disease [10]. In an extended analysis of 15 cases of Alzheimer's disease, the number of NGF receptor positive fibres in the fimbria and alveus was generally decreased compared with age-matched normal groups, in presenile but not senile cases (differentiated by age of onset before or after 65 years). By contrast, in 5 demented Parkinson's disease cases (aged 61-86 years at death) immunohistochemically reactive fibres were consistently minimal or absent. This pattern of NGF receptor loss in the hippocampus most closely reflects the loss of basal forebrain cholinergic neurones, previously reported within the different clinical groups but not by biochemical measures of cholinergic function. It is concluded that even at moderately advanced stages of Alzheimer's disease with onset in the senium, axonal processes and NGF receptor mechanisms may be structurally intact in areas of cholinergic innervation from the basal forebrain, despite evidence of cholinergic dysfunction (decreased choline acetyltransferase (ChAT) and acetylcholinesterase), but that in presenile Alzheimer's and in demented Parkinson's disease cases the receptor declines in conjunction with the loss of subcortical neurones and their processes. The loss of ChAT activity may therefore reflect a dysfunction of the NGF system, in its normal maintenance of the cholinergic phenotype in basal forebrain neurones.

Adult↗
PubMed1992

[3H]MK-801 binding to the NMDA receptor complex, and its modulation in human frontal cortex during development and aging.

[3H]MK-801 binding was found to decline with age in well washed membranes from human frontal cortex taken from an age series from 24 weeks gestation to 100 years old. The decline was significant under basal conditions (no added modulators) (P less than 0.01), and highly significant under stimulation with glutamate, glycine and spermidine alone and in combination (P less than 0.001). Scatchard analysis in the presence of glutamate and glycine showed this decline was due to a loss in the number of [3H]MK-801 binding sites rather than a change in the affinity of the binding site. There was a highly significant age related reduction in the attenuation of [3H]MK-801 binding by zinc (P less than 0.001). In foetal and neonatal cases up to 7 weeks of age spermidine behaved in an antagonistic manner, inhibiting rather than stimulating [3H]MK-801 binding, when alone or in the presence of glutamate and glycine. The changes in influence of glutamate, glycine, spermidine and zinc on [3H]MK-801 binding during development and aging were not due to other pre- or postmortem factors. The reverse effect of spermidine in the foetal and neonatal cases has therapeutic implications in the treatment of neonates with antiischaemic agents whose action involves the polyamine site.

Adolescent↗
PubMed1992

Quantification of beta A4 protein deposition in the medial temporal lobe: a comparison of Alzheimer's disease and senile dementia of the Lewy body type.

The distribution of beta-amyloid protein (beta A4) was examined in the medial temporal lobes from cases of Alzheimer's disease (AD) (n = 13), senile dementia of Lewy body type (SDLT) (n = 12) and age matched controls (n = 9). Using a previously described image analysis technique the extent of beta A4 pathology was determined in ten distinct anatomical sites within the medial temporal lobe. AD and SDLT cases contained very similar amounts of beta A4 in the areas sampled and both contained significantly more beta A4 than the age matched controls, particularly in the dentate and parahippocampal gyri. The similarity of the beta A4 load in the two conditions is in contrast to reported differences in the number of neurofibrillary tangles which can be observed. It is suggested that AD and SDLT represent a spectrum of pathology which centres around the aberrant processing of the beta A4 precursor protein.

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PubMed1992

Operational criteria for senile dementia of Lewy body type (SDLT).

Recent reports have suggested that brain stem and cortical Lewy body formation may identify a neurodegenerative disorder in elderly demented individuals which accounts for up to 20% of cases of senile dementia coming to autopsy. Retrospective analysis of case notes of 21 autopsy patients with neuropathologically proven senile dementia of Lewy body type (SDLT) and 37 cases with neuropathologically proven Alzheimer's disease (AD) identified a characteristic clinical syndrome in SDLT. Fluctuating cognitive impairment; psychotic features including visual and auditory hallucinations, and paranoid delusions; depressive symptoms; falling and unexplained losses of consciousness were all seen significantly more often than in AD. Over half of the SDLT patients in this series who were given neuroleptics in standard dose showed acute and often irreversible adverse reactions indicative of a neuroleptic sensitivity syndrome. The survival time of drug treated patients was reduced by 50%. Operational criteria to aid in the clinical distinction between SDLT and AD patients are proposed and hypotheses regarding possible aetiology and treatment discussed.

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PubMed1992

Prognostic implications of p53 protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours.

The expression of p53 protein, epidermal growth factor receptor (EGFR), and Ki-67 nuclear antigen was examined by immunohistochemistry in biopsies of 16 types of human brain tumours, including 43 astrocytomas. P53 protein, almost certainly its mutant form, was expressed in seven of the 16, and EGFR in 11 of the 16 types of tumours. In astrocytomas both the proportion of tumours which expressed p53 or EGFR increased with grade of malignancy as did the mean Ki-67 labelling index (LI): p53-0% in grade 1, 17% in grade 2, 38% in grade 3, 65% in grade 4; EGFR-0% in grade 1, 33% in grade 2, 85% in grade 3, 95% in grade 4; mean Ki-67 L1-1.1% in grades 1 and 2, 8.3% in grade 3, and 13.4% in grade 4. Astrocytomas which expressed p53 or EGFR had a significantly higher Ki-67 LI at P less than 0.05 (11.8% and 10.7%, resp.) than those that did not (6.2% or 4.1%, resp.). Patients with astrocytomas expressing p53 or EGFR had a significantly reduced survival (P = 0.035 and P = 0.007, resp.): only 11% of the p53 + ve and 13% of the EGFR + ve patients were alive at 100 weeks following diagnosis compared to 36% of p53-ve or 60% of EGFR-ve patients. Patients with Ki-67 LI greater than 5% had a reduced survival (P less than 0.0001)--none survived beyond 86 weeks following diagnosis, whilst 63% of patients with less than 5% positive cells were still alive at 100 weeks. The univariate analysis showed that in astrocytomas expression of p53 mutants, EGFR protein, and Ki-67 greater than 5% are associated with malignant progression and poor prognosis. The multivariate analysis revealed that only tumour grade and Ki-67LI were independent prognostic factors for survival.

Adolescent↗
PubMed1992

Examination of parameters influencing [3H]MK-801 binding in postmortem human cortex.

[3H]MK-801 binding was used as an index of the glutamate receptor N-methyl-D-aspartate-subtype channel to examine the influence of gender, age, mode of death (agonal status), interval between death and autopsy (postmortem delay), and time in storage at -70 degrees C in well washed homogenate preparations from postmortem human frontal cortex. Basal binding and the modulatory effects of glutamate, glycine, spermidine, and zinc were examined with respect to these variables. Basal binding was sensitive to agonal status, being higher in sudden death cases. The effect of added glutamate and glycine was sensitive to age, with a trend toward lower binding with increasing age. The effect of added spermidine alone was sensitive to storage time at -70 degrees C, the binding being higher with longer storage time. The effect of added zinc was also sensitive to postmortem delay, with zinc causing a greater reduction in binding with shorter postmortem delays. Thus, with the exception of gender, all variables examined influenced [3H]MK-801 binding, highlighting the attention that should be given to these factors in postmortem studies in normal and diseased human subjects.

Aged↗
PubMed1992

Nerve growth factor receptor-like immunoreactivity in the human spinal cord.

Nerve growth factor (NGF) receptor-like immunoreactivity has been demonstrated in the normal human adult spinal cord using the monoclonal antibody ME20.4. Intense immunoreactivity was associated with fibres and terminals in the substantia gelatinosa. In lamina IX the neuropil demonstrated punctate staining, the motor neurons themselves being negative. At thoracic levels occasional neurons of the intermediolateral column cell group were NGF receptor positive. Fine axonal and punctate terminal reactivity was observed in the gracile fasciculus, corresponding to axons in transverse section. Similar, though slightly less dense immunoreactivity was observed in the cuneate fasciculus. The demonstration of NGF receptor immunoreactivity may provide a useful marker of sensory innervation in the human spinal cord.

Adolescent↗
PubMed1991

[3H]nitrendipine binding in temporal cortex in Alzheimer's and Huntington's diseases.

Specific [3H]nitrendipine binding which was shown to be calcium- and calmodulin-dependent was found to be significantly reduced in the temporal cortex in Alzheimer's disease compared to age-matched controls. Scatchard analysis revealed that this reduction was due to a loss in the number of cortical [3H]nitrendipine binding sites rather than a change in the affinity of the binding site in the Alzheimer patients. The reduction in cortical [3H]nitrendipine-specific binding was most marked in those Alzheimer's disease cases where the duration of the dementing illness was longer than two years. In contrast, no reduction in cortical [3H]nitrendipine binding was found in Huntington's disease. There was no significant correlation found between age (38-89 years) and [3H]nitrendipine binding in control cases, or between mean overall plaque counts and [3H]nitrendipine binding in the Alzheimer's disease cases. There was a significant correlation found between age (46-88 years) and [3H]nitrendipine binding in the Alzheimer's disease cases where the duration of the dementing illness was greater than two years.

Aged↗
PubMed1991

Neocortical concentrations of neuropeptides in senile dementia of the Alzheimer and Lewy body type: comparison with Parkinson's disease and severity correlations.

Corticotropin releasing hormone (CRH), somatostatin (SRIF), and arginine vasopressin (AVP) concentrations were estimated using radioimmunoassay in the temporal and occipital cortices in postmortem brain from patients clinically and neuropathologically diagnosed as senile dementia of the Lewy body type (SDLT), senile dementia of the Alzheimer type (SDAT), and Parkinson's disease (PD) and from neurologically normal controls. The concentration of temporal and occipital neocortical CRH was diminished in both SDAT and SDLT compared to control values, whereas SRIF was reduced only in temporal cortex in both these conditions. In contrast, the concentrations of both CRH and SRIF were unaltered in PD. The concentrations of AVP in SDLT, SDAT, and PD were similar to those found in the control groups. The decrement in SRIF, but not CRH, was found to be correlated with some indices of severity of illness in SDAT; a similar but nonsignificant trend for SRIF was observed in SDLT.

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PubMed1991

Cortical serotonin-S2 receptor binding in Lewy body dementia, Alzheimer's and Parkinson's diseases.

The binding of the selective 5-HT2 antagonist [3H]ketanserin has been investigated in the temporal cortex of patients with Alzheimer's disease (SDAT), Parkinson's disease (PD), senile dementia of Lewy body type (SDLT) and neuropathologically normal subjects (control). 5-HT2 binding was reduced in SDAT, PD with dementia and SDLT. SDAT showed a 5-HT2 receptor deficit across most of the cortical layers. A significant decrease in 5-HT2 binding in the deep cortical layers was found in those SDLT cases without hallucinations. SDLT cases with hallucinations only showed a deficit in one upper layer. There was a significant difference in cortical layers III and V between SDLT without hallucinations and SDLT with hallucinations. The results confirm an abnormality of serotonin binding in various forms of dementia and suggest that preservation of 5-HT2 receptor in the temporal cortex may differentiate hallucinating from non-hallucinating cases of SDLT.

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PubMed1991

Quantitative neuropathological study of Alzheimer-type pathology in the hippocampus: comparison of senile dementia of Alzheimer type, senile dementia of Lewy body type, Parkinson's disease and non-demented elderly control patients.

A Lewy body dementing syndrome in the elderly has been recently described and designated senile dementia of Lewy body type (SDLT) on the basis of a distinct clinicopathological profile. The pathological changes seen in SDLT include the presence of cortical Lewy bodies (LB) frequently, but not invariably, associated with senile plaque (SP) formation. Whilst neocortical neurofibrillary tangles (NFT) are sparse or absent, a proportion of these cases show involvement of the temporal archicortex by lesions comprising Alzheimer-type pathology (ATP, i.e. NFT, SP and granulovacuolar degeneration [GVD]). Thus the relationship between SDLT and senile dementia of Alzheimer type (SDAT) is complex and controversial. In this study quantitative neuropathology was used to compare the intensity and distribution of ATP in the hippocampus and entorhinal cortex of 53 patients from 3 disease groups (SDLT, SDAT, Parkinson's disease (PD)) and a group of neurologically and mentally normal elderly control patients. For most brain areas examined the extent of ATP between the patient groups followed the trend SDAT greater than SDLT greater than PD greater than control. Statistical comparison of these groups revealed significant differences between the mean densities of NFT, SP and GVD although individual cases showed considerable variability. These results confirm additional pathological differences between SDAT and SDLT regarding the intensity of involvement of the temporal archicortex by ATP. Many patients with Lewy body disorders (LBdis) show a predisposition to develop ATP albeit in a more restricted distribution (e.g. low or absent neocortical NFT) and at lower densities than is found in SDAT. Some cases of SDLT show minimal SP and NFT formation in both neocortex and archicortex supporting previously published data distinguishing this group from Alzheimer's disease.

Aged↗
PubMed1991

Triphenyltetrazolium chloride (TTC) as a marker for ischaemic changes in rat brain following permanent middle cerebral artery occlusion.

Triphenyltetrazolium chloride (TTC) was used to delineate ischaemic lesions in the rat brain at various times following middle cerebral artery occlusion. A comparison was made of TTC staining by immersion and perfusion techniques and conventional light microscopy. The lesions were quantified by measuring the ischaemic area at the sections corresponding to 7 mm in front of the AO line (atlas of Konig and Klippel). In animals examined 24 h after middle cerebral artery occlusion (MCAO), the area of infarction was 17.4 +/- 1.3 mm2 on the TTC perfused slices and 17.6 +/- 1.6 mm2 on the TTC immersed slices (mean +/- SEM). By contrast, there was a marked difference between the two TTC methods when tissues were examined at shorter intervals after artery occlusion. In the TTC-perfused animals, there was no significant difference between the mean areas of infarction measured at 5-20 min, 3-4 h, or 24 h post occlusion. Immersion in TTC, however, failed to reveal any consistent ischaemic damage when applied at the earlier post-occlusion times. Conventional histopathology demonstrated minimal lesions at 5-20 min but at 4 h or more the lesions were not significantly different from those demonstrated by TTC perfusion. TTC immersion staining can, thus, only be used as a reliable marker of cerebral ischaemia damage with post-occlusion survival periods of 24 h. TTC perfusion staining gives results not significantly different from histopathology at 4 h or more post-occlusion but at earlier intervals than 24 h it differs significantly from TTC immersion staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nerve cell loss in the thalamus in Alzheimer's disease and Parkinson's disease.

Serial sections through the thalamus from the fixed right cerebral hemispheres of 15 cases (5 Parkinson's disease, 5 Alzheimer's disease (AD) and 5 controls) were used to obtain quantitative estimates of neuronal loss, neurofibrillary tangle formation and Lewy body inclusions within individual thalamic nuclei. Severe neuronal loss and tangle formation were evident in the anterodorsal nucleus from the AD cases. Nerve cell damage was also present in the centromedian nucleus but was not associated with tangle formation and occurred in all but 2 of the brains examined. It is likely that the anterodorsal neurons are damaged locally by the Alzheimer's disease process whereas the changes in the centromedian nucleus may be related to ageing.

Aged↗
PubMed1990

Cortical concentrations of corticotropin-releasing hormone and its receptor in Alzheimer type dementia and major depression.

Corticotropin-releasing hormone-immunoreactivity (CRH-IR) and CRH receptors (binding capacity and affinity) were measured in postmortem cortical areas from depressed subjects, two groups of senile dementia of the Alzheimer type (SDAT), and age-, sex-, and postmortem-delay-matched controls. No difference in CRH-IR and CRH receptor status between depressed subjects and controls was noted. CRH-IR was decreased in all cortical areas in SDAT, with a corresponding increase in CRH receptor binding capacity (with no change in affinity) in occipital cortex. No effects of postmortem delay were seen. It is suggested that the increase in CRH receptor numbers in SDAT is related to the degree of distribution of pathological involvement in specific regions.

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