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P D Coleman

Publications and source records attributed to P D Coleman.

At least 19 recordsLinked to original sources
PubMed1995

[Differential neuronal loss in the hippocampus in normal aging and in patients with Alzheimer disease].

The causal relationship between the neurodegenerative changes that accompany normal ageing and those that characterize Alzheimer's disease is unclear. The high incidence of Alzheimer's disease associated with old age and the presence of its neuropathological signs in non-demented older individuals suggest that these two phenomena involve the same neurodegenerative processes and mechanisms and that Alzheimer's disease is an extension of normal ageing. On the other hand, the identification of environmental and genetic risk factors associated with Alzheimer's disease suggests the involvement of a specific disease process that is not related to normal ageing. The resolution of this fundamental issue is of importance in the design of investigative and therapeutic strategies. In this report, we describe differences in the regional patterns of neuronal loss, in the hippocampal region of the brains of Alzheimer's patients and normal ageing subjects, that indicate that Alzheimer's disease is not the manifestation of accelerated ageing, but the expression of a distinct pathological process.

Aged↗
PubMed1994

Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease.

The distinction between the neurodegenerative changes that accompany normal ageing and those that characterise Alzheimer's disease is not clear. The resolution of this issue has important implications for the design of therapeutic and investigative strategies. To this end we have used modern stereological techniques to compare the regional pattern of neuronal cell loss in the hippocampus related to normal ageing to that associated with Alzheimer's disease. The loss related to normal ageing was evaluated from estimates of the total number of neurons in each of the major hippocampal subdivisions of 45 normal ageing subjects who ranged in age from 13 to 101 years. The Alzheimer's disease related losses were evaluated from similar data obtained from 7 cases of Alzheimer's disease and 14 age matched controls. Qualitative differences were observed in the regional patterns of neuronal loss related to normal ageing and Alzheimer's disease. The most distinctive Alzheimer's disease related neuron loss was seen in the CA1 region of the hippocampus. In the normal ageing group there was almost no neuron loss in this region (final neuron count in the CA1 region: 4.40 x 10(6) neurons for the Alzheimer's disease group vs 14.08 x 10(6) neurons in the normal ageing group). It is concluded that the neurodegenerative processes associated with normal ageing and with Alzheimer's disease are qualitatively different and that Alzheimer's disease is not accelerated by ageing but is a distinct pathological process.

Adolescent↗
PubMed1993

Altered phosphorylation of growth-associated protein B50/GAP-43 in Alzheimer disease with high neurofibrillary tangle density.

The growth-associated phosphoprotein B50/GAP-43, associated with axonal proliferation and regeneration, was isolated from superior temporal gyrus (area 22) of seven control and eight Alzheimer disease (AD) postmortem human brains. Membrane and cytoplasmic proteins were fractionated and B50/GAP-43 was isolated by reverse-phase HPLC and gel electrophoresis. B50/GAP-43 was identified with rabbit polyclonal antibodies 4P3 (generated against the calmodulin binding domain of B50/GAP-43) and 1B5 (generated against whole bovine B50/GAP-43). B50/GAP-43 protein was further separated into phosphorylated and dephosphorylated species by calmodulin-Sepharose chromatography. The amounts of phosphorylated and dephosphorylated B50/GAP-43 forms were determined by electrophoresis, protein staining, and densitometry. Data on the relative phosphorylation of B50/GAP-43 protein in membrane and cytoplasmic fractions show a 10-fold difference in the ratio of cytoplasmic/membrane phosphorylation of B50/GAP-43 in AD brains with high neurofibrillary tangle (NFT) density compared to AD brains with low NFT density. This difference is due to a decreased percentage of phosphorylated B50/GAP-43 in the membrane fraction relative to that in the cytosolic fraction from high NFT density. No analogous relationship was found between the phosphorylation of B50/GAP-43 and the density of neuritic plaques in the brains examined. These data indicate differential distribution of phosphorylated and dephosphorylated B50/GAP-43 in normal and AD brains is related to NFT density but not to neuritic plaque density.

Aged↗
PubMed1992

Caregiver support groups: factors affecting use of services.

Use of time-limited psychoeducational support groups by family caregivers to help frail elderly people in the community reflects a mixture of predisposing, enabling, and need factors. Using multivariate regression methods that control for dependent-variable censoring, the authors found that attendance in support groups by primary caregivers was greater for those who were older, who had a secondary informal caregiver involved in providing care, or who had significant health problems. Attendance was greater also for those caring for Alzheimer's victims and for those experiencing higher levels of burden in their caregiving role. In English-language groups, Mexican American caregivers showed markedly lower attendance than Anglo American caregivers, but in Spanish-language groups attendance by Mexican American caregivers was essentially the same as that of the Anglo Americans in English-language groups. Data for this study are from a federally funded support group demonstration project conducted in a southwestern metropolitan area.

Age Factors↗
PubMed1990

Hippocampal plasticity in normal aging and decreased plasticity in Alzheimer's disease.

Different patterns of age-related dendritic change have been reported in different zones of the human hippocampal region in the normal and Alzheimer's disease (AD) brain. In normal aging there is an increase in average (net) dendritic extent (which we interpret as plasticity) in the parahippocampal gyrus and dentate gyrus. There is net stability of dendritic extent in CA2-3, CA1, and subiculum. In regions that show plasticity in normal aging, dendrites in AD show reduced or aberrant plasticity. In regions that show stability in normal aging, dendrites either are stable or regress in AD, depending upon how severely involved the region is with the pathology of AD.

Aged↗
PubMed1988

Estimating the number of granule cells in the dentate gyrus with the disector.

A practical example is given of how a newly developed stereological estimator of particle number, the disector, can be used to make estimates of neuron number in the dentate gyrus of rats. The estimates are free of biases related to lost caps, overprojection and assumptions about size, shape and orientation of the objects that are counted. The disector principle and the practical considerations relating to histological preparations and sampling are presented.

Animals↗
PubMed1987

Volumes of the components of the hippocampus in the aging F344 rat.

Much of the recent data on cells, synapses, and other structures in the dentate gyrus and hippocampus as a function of age are packing density or volume fraction data. In order to estimate total numbers, volumes, or surface areas of cells, synapses, vessels, etc., as a function of age, the total volumes of the subregions of the dentate gyrus and hippocampus must be known. The volumes of these subregions, visualized with the Timm stain, have been determined in 24 F344 rats from 4 to 37 months of age. Volumes of the various structures showed age-related increases which were statistically significant for the perforant path zone of the dentate gyrus molecular layer, as well as the total molecular layer, the hilus, and regio inferior and total mossy fiber systems. If the 4-month age group is eliminated from consideration, only the ratio of the volume of the mossy fiber zones to the volume of the perforant path zones of the dentate molecular layer increases significantly with age. Our general finding of lack of volumetric reorganization of the subdivisions of the hippocampal region between 12 and 37 months suggests that studies of the packing densities of structures in most of these zones may be considered comparable across ages, assuming comparability of sampling regions.

Aging↗
PubMed1987

Dendritic extent in human CA2-3 hippocampal pyramidal neurons in normal aging and senile dementia.

The extent of dendritic trees of pyramidal neurons of the CA2-3 field of the hippocampus of 20 human brains obtained at autopsy was quantified in Golgi Cox-stained tissue. Fifteen cases were neurologically and psychiatrically normal and ranged in age from 43 to 95 years. Five cases had a progressive, dementing disease consistent with the diagnosis of senile dementia (SD) of the Alzheimer's type. Dendritic extent of both the apical and basal trees of CA2-3 pyramidal neurons was found to be unchanged from middle age to very old age. This finding of net stability of dendritic extent is in contrast to previous quantitative reports of either continued dendritic growth in human parahippocampal gyrus or of dendritic growth followed by regression in human dentate gyrus. This finding is consistent with the suggestion that changes in dendritic extent in normal aging are a function of the balance between regressive and proliferative influences and are region specific. In cases with SD, dendritic extent of both the apical and basal trees was found to be similar to that of the normal age-matched cases. These data are consistent with those of others suggesting relative sparing of the CA2-3 field from the degenerative changes in senile dementia.

Adult↗
PubMed1987

Dendritic extent in human dentate gyrus granule cells in normal aging and senile dementia.

Granule cells of the hippocampal dentate gyrus of 22 human brains obtained at autopsy were studied in Golgi-Cox stained tissue. Seventeen cases were cognitively normal and ranged from 43 to 95 years of age. Five cases had a progressive, dementing disease consistent with the diagnosis of senile dementia (SD) of the Alzheimer's type. Dendritic extent of granule cells was found to increase in normal aging between middle age (fifties) and early old age (seventies). However, dendritic regression was found in the oldest old (nineties). This finding of dendritic regression following growth is in contrast to previous quantitative reports of continued dendritic growth in parahippocampal gyrus of normal aging human brain and suggests that changes in dendritic extent in normal aging are region and age specific. In cases with SD, dendritic extent was greatly reduced when compared with the normal cases of the same age (seventies) and slightly reduced when compared with middle-aged cases. The very old normal and SD cases were similar in dendritic extent, suggesting that the functional and memory deficits characteristic of SD cannot be explained solely on the basis of the static status of dendritic extent of single neurons.

Aged↗
PubMed1986

Failed compensatory dendritic growth as a pathophysiological process in Alzheimer's disease.

In normal human aging the remaining neurons of two areas of the hippocampal region have been found to compensate for age-related neuronal loss by proliferating new dendrites. In Alzheimer's disease (AD) the layer II pyramidal neurons of the parahippocampal gyrus fail to show this compensatory response, in spite of a probable, exaggerated disease-related loss of neurons. In AD the dentate gyrus granule cells of the hippocampus also show a reduced amount of the compensatory response. This failure of the AD brain to show the normal compensatory plastic response, seen in normal aging as dendritic growth, may be viewed as one of the pathophysiological processes of the disease.

Aged↗
PubMed1986

Acid phosphatases of Sporothrix schenckii.

Sporothrix schenckii cells were grown on a medium containing yeast extract, neopeptone and glucose at 20 degrees C to obtain a mixture of mycelia and conidia, and at 35 degrees C to obtain yeast-like cells. The organism was maintained in the mycelial form, and its transformation to yeast at the higher temperature proceeded via conidia and 'intermediate cells' that then gave rise to yeast by a blastic mechanism. Cell-free extracts were analysed by PAGE at pH 8.0 and acid phosphatases (EC 3.1.3.2) were revealed by a sensitive detection reagent at pH 5.0. Mycelial, conidial and yeast extracts all had some acid phosphatase activity (M-I, C-I and Y-I) at the origin, although the proportion was highest for the yeast extracts. All of the bands that penetrated the gels had different electrophoretic mobilities. Mycelial and conidial extracts each had one other isoenzyme (M-II and C-II), while the yeast extracts had a total of five electrophoretically distinct acid phosphatases. Isoenzyme Y-II was further resolved into five closely related bands (Y-IIa to Y-IIe), the relative intensities of which varied with the phosphate nutrition of the yeast cells and the history of the extracts. The acid phosphatase isoenzymes were inhibited to various extents by sodium fluoride, L(+)-tartrate and phosphate, and showed interactions with citrate as opposed to acetate as the background buffer at pH 5.0.

Acid Phosphatase↗