Biomedical subjects

D M Mann

Publications and source records attributed to D M Mann.

225 records · Page 13Linked to original sources

PubMedDate not supplied

A quantitative study of the ultrastructure of pyramidal neurons of the cerebral cortex in Alzheimer's disease in relationship to the degree of dementia.

Quantitative morphometric (stereological) methods have been used to measure the number or amount of organelles in pyramidal nerve cells, unaffected by neurofibrillary degeneration, in biopsy specimens of temporal cortex from 11 patients with Alzheimer's disease, and to relate these to the degree of dementia, as measured by psychometric testing. Only areal proportion (AA) and surface area (SA) of rough endoplasmic reticulum were significantly reduced in line with the severity of the degree of dementia. It is suggested that these changes reflect a progressively diminishing requirement for packaging and transport of replacement proteins, particularly in relation to neurotransmitter metabolism in nerve terminals following the loss of synapses which we have shown to occur in these patients.

Aged↗

PubMedDate not supplied

The topographic distribution of senile plaques and neurofibrillary tangles in the brains of non-demented persons of different ages.

The incidence and severity of senile plaques (SP) and neurofibrillary tangles (NFT) were examined in six areas of brain in 60 non-demented patients of age range 6-84 years. Thirty-two patients showed neither SP nor NFT in any region (30 of these were under 65 years of age), 15 patients showed both SP and NFT in one or more regions (14 were over 60 years of age), 11 patients aged 21-84 years showed NFT only in one or more areas and two patients showed SP alone and only in the amygdala. Overall comparison of number and severity showed the greatest severity of SP within the amygdala in most instances, whereas NFT were found in most instances and at greatest severity within the hippocampus. The reason for this apparent vulnerability of these areas of brain to SP and NFT formation may lie with their connections with the outside world via the olfactory bulbs and tract. This pathway may thus provide an entry point to the brain for pathogenic agent(s) that may induce, either directly or indirectly, pathological processes that ultimately lead to SP and NFT formation.

Adolescent↗

PubMedDate not supplied

The progression of the pathological changes of Alzheimer's disease in frontal and temporal neocortex examined both at biopsy and at autopsy.

Brains were obtained at autopsy from five patients with Alzheimer's disease, each of whom had undergone diagnostic craniotomy 3-7 years previously. It was possible, therefore, to examine the number (density) and nucleolar volume of pyramidal nerve cells, and the density of senile plaques and neurofibrillary tangles within the cerebral cortex on two occasions during the progression of their illness, and to assess how these measures might have changed during the period between biopsy and death. In all five patients, at biopsy, the density and the nucleolar volume of pyramidal nerve cells was significantly less than controls and, in general, values for both these measures fell significantly further from biopsy to death. By contrast, in none of the five patients did senile plaque density consistently change from biopsy to death; neurofibrillary tangle density either did not change, or indeed sometimes decreased from biopsy to death. These data show that both the clinical and the pathological progression of Alzheimer's disease is marked by a continuing loss of pyramidal cells from frontal and temporal cortex, although the densities of plaques and tangles within the cortex do not, per se, correlate with the stage of the illness. The usefulness of measurement of plaque and tangle densities as pathological criteria by which the clinical and neurochemical deficits of Alzheimer's disease can be compared in different patients is clearly questionable.

Alzheimer Disease↗

PubMedDate not supplied

An analysis of the morphology of senile plaques in Down's syndrome patients of different ages using immunocytochemical and lectin histochemical techniques.

The morphology of the senile plaque (SP), within the hippocampus and the temporal cortex, has been examined in 21 patients with Down's syndrome (DS), dying between the ages of 13 and 65 years, using immunocytochemical and lectin histochemical methods, as well as with a conventional silver staining technique. The earliest changes detectable within these areas of brain in the younger patients involved a fine diffuse deposition of amyloid (A4) protein and a uniform granular accumulation of an oligosaccharide recognized by the lectin from Canavalia ensiformis (ConA). At this stage, these 'pre-plaque' areas are unrecognizable using silver staining. Later the conventional SP morphology becomes apparent; the A4 protein aggregates into the usual plaque core and neurites appear with silver staining. The fine ConA positive material concentrates into large clumps and becomes recognizable by other lectins such as PSA, WGA and ePHA, which bind to mannose containing structures in an increasingly complex form. It is suggested that the development of the pathological changes of Alzheimer's disease, in patients with DS (and also in AD itself) involves a primary deposition of amyloid protein in conjunction with the accumulation of an as yet unidentified oligosaccharide. These changes precede the neuronal response that is characterized by the formation of neurites and the accumulation of neurofibrillary tangles that ultimately leads to cell death.

Adolescent↗

PubMedDate not supplied

Early senile plaques in Down's syndrome brains show a close relationship with cell bodies of neurons.

A sensitive methenamine silver/Nissl stain was used to study the morphology and relationship of pre-plaques (presumed early senile plaques) in Down's syndrome brains to glial nuclei, capillaries and neuronal perikarya. The larger pre-plaques (greater than 50 microns) usually encompassed all of these tissue elements. However, the smaller pre-plaques (less than or equal to 50 microns) were almost always found immediately adjacent to, or around the cell bodies of neurons (often with associated satellite cells), and they failed to show any consistent, close spatial relationship to the other tissue components. Thus we consider an early stage of pre-plaque formation to be the deposition of amyloid adjacent to the cell body of a morphologically normal neuron. Based on the study of transitional forms, we suggest that the amyloid progressively accumulates around the cell body until the enclosed neuron degenerates. How these pre-plaque lesions might eventually develop into the typical plaque structure is uncertain. Our observations support the theory of a neuronal origin for plaque amyloid.

Adult↗

PubMedDate not supplied

The clinical pathological correlates of lobar atrophy.

Three clinical syndromes associated with fronto-temporal cerebral atrophy, studied in one centre are discussed: dementia of frontal type (DFT), DFT and motor neurone disease (MND) and progressive aphasia (PA). The pathological findings in DFT (13 brains), DFT and MND (5 brains) and PA (5 brains) permit a number of clinical pathological groupings. The nosological status of fronto-temporal atrophy is discussed with reference to the literature and it is suggested that a common underlying pathology, including Picks disease as strictly defined by the presence of inclusion bodies, underlies the clinical syndromes, each being determined by the anatomical distribution of the pathology.

Aphasia↗

PubMedDate not supplied

Photoaffinity labeling of atrial natriuretic factor analog atriopeptin III with [gamma-32P]8N3GTP.

We have determined that atrial natriuretic factor (ANF) analog atriopeptin III (AP III) is a guanosine 5'-triphosphate (GTP) binding protein as shown by photoaffinity labeling with the GTP-analog [gamma-32P]8N3GTP (azido-GTP). The photo-insertion was saturable at 40 microM azido-GTP. Half-maximal protection from photo-insertion was observed using 40-microM concentrations of the native nucleotide GTP. The photolabeling was inhibited approximately 70% by addition of micromolar concentrations of the divalent cations MgCl2, MnCl2 or CaCl2. The related purine-containing nucleotide adenosine 5'-triphosphate (ATP) was able to elicit half-maximal protection of AP III from photo-insertion with 20 microM azido-GTP at a concentration of 120 microM. No significant protection from photoinsertion was observed with other compounds such as GDP, GMP, cGMP, UTP and pyrophosphate. Additionally, a carboxy-terminal F-R-Y deleted analog of ANF, AP I; reduced and carboxymethylated AP III; and resact, a peptide released from sea urchin eggs, were not photolabeled by azido-GTP. These results demonstrate that the AP III analog of ANF contains a functional GTP binding site that would be saturated at physiological concentrations of GTP. At present, the role of this interaction in mediating the biological effects of ANF is unknown, but we speculate that direct GTP interaction with AP III may be involved in the mechanism of action of this peptide.

Affinity Labels↗

PubMedDate not supplied

Changes in Alzheimer's disease in the magnocellular neurones of the supraoptic and paraventricular nuclei of the hypothalamus and their relationship to the noradrenergic deficit.

When compared with those of age-matched control patients the number of nerve cells in the locus caeruleus in 30 patients with Alzheimer's disease is reduced by 65% while nucleolar volume in surviving cells of the locus caeruleus and in those of the paraventricular and supraoptic nuclei of the hypothalamus is reduced by 25%, 48% and 26% respectively. Furthermore the reduction in cell number and nucleolar volume in these 3 cell types are all interrelated, emphasizing the close functional linkage of these cell groups. Similar changes (for age) were seen in a group of 10 patients with a mixed Alzheimer/vascular type dementia and in 6 patients over 50 years of age with Down's syndrome whose brains also showed extensive senile plaque and neurofibrillary tangle formation. This damage to the locus caeruleus and hypothalamic systems is probably responsible for losses of noradrenaline and vasopressin reported in cerebral cortex and hypothalamus; the importance of these changes to the pathogenesis of Alzheimer's disease is emphasized.

Age Factors↗

PubMedDate not supplied

Monoaminergic neurotransmitter systems in presenile Alzheimer's disease and in senile dementia of Alzheimer type.

The number of nerve cells was counted in locus caeruleus, dorsal motor vagus, dorsal tegmental nucleus and substantia nigra and the volume of their nucleolus measured in 30 patients with Alzheimer's disease ranging from 48-92 years of age and in 67 control patients without neurological disease. Loss of nerve cells and reduction in nucleolar volume was greatest in the locus caeruleus and these changes were most severely expressed in the younger patients, falling with age such that by 90 years of age the level of damage approached that of old age alone. Less extensive changes were present in the dorsal tegmental nucleus and these were also age dependent in their severity. Moderate damage to the dorsal motor vagus was not age related. Nucleolar volume alone was altered in substantia nigra and then only significantly so in the younger patients.

Age Factors↗