Biomedical subjects

E D Bird

Publications and source records attributed to E D Bird.

At least 73 records · Page 4Linked to original sources

PubMed1987

Alzheimer's disease: low cerebral somatostatin levels correlate with impaired cognitive function and cortical metabolism.

Somatostatin-like immunoreactivity in Alzheimer CSF was significantly lower than in that from age-matched controls. The degree of reduction correlated with indices of intellectual impairment and decline in cortical glucose utilization as determined by PET. There was a close association between reduction in CSF somatostatin and glucose hypometabolism in the parietal lobe. In postmortem cortical tissue from Alzheimer patients, somatostatin levels were lower in posterior parietal but not in anterior frontal cortex. Loss of somatostatin-containing neurons, especially in the parietal association cortex, may be a critical determinant for Alzheimer dementia.

Alzheimer Disease↗

PubMed1987

Oxytocin in Alzheimer's disease: postmortem brain levels.

Oxytocin (OXY) injected into the hippocampus is reported to interfere with the formation of memory in experimental animals. Memory impairment is one of the distinguishing features of Alzheimer's disease. We have studied OXY immunoreactivity in postmortem brain tissue from 12 cases of histologically confirmed Alzheimer's disease and 13 controls. OXY concentration was increased 33% in the hippocampus and temporal cortex of Alzheimer brains (p less than 0.05), but normal in all other regions examined. Elevated hippocampal OXY levels may contribute to the memory disturbance associated with Alzheimer's disease.

Adult↗

PubMed1987

The spatial distribution of neurons and glia in human cortex based on the poisson distribution.

A method was devised that employs deviations from the Poisson distribution to analyze the spatial arrangement of neurons and glia in human cerebral cortex. A field of randomly distributed points equal in number of a sample field of neuronal or glial cells is generated by computer, and the proportion of cells in the sample field that are closer to the nearest neighboring cells than to the nearest randomly distributed point is determined. We call this proportion the "Poisson ratio." When the cells are randomly distributed, the Poisson ratio is equal to 0.5. If the Poisson ratio is less than 0.5, the cells are farther away from one another than a random distribution would predict (exclusionary pattern); if the Poisson ratio is greater than 0.5, the cells are closer to one another than a random distribution would predict (clustering). A simple nonparametric statistical test is used to determine the significance of differences in the ratios. This method was applied to samples of human cerebral cortex in order to test the hypothesis that patients with schizophrenic psychosis may have an altered pattern of neuronal clustering. The analysis revealed that there is no difference in the nearest-neighbor distribution of either neurons or glia between psychotic patients and controls. It was found, however, that there is a highly significant difference in the spatial distribution of neurons versus glia in human cerebral cortex. Neurons of layers II to VI in the human cortex show greater-than-expected distances among them and are distributed according to an exclusionary pattern, while neurons in layer I show a clustering pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral Cortex↗

PubMed1986

Topography of enkephalin, substance P and acetylcholinesterase staining in Huntington's disease striatum.

The distribution of Met-enkephalin (Enk) and substance P (SP) was examined in the striatum of Huntington's disease (HD) patients using immunoperoxidase techniques. Both Enk- and SP-like immunoreactivities (ir) were strikingly diminished in the dorsal caudate nucleus and putamen, while patchy staining persisted in the ventral putamen and nucleus accumbens. This was in sharp contrast to the patch-matrix pattern of acetylcholinesterase (AChE) staining which persisted throughout the entire striatum in HD. The regional loss of Enk- and SP-ir parallels the pattern of neuronal depletion in HD. The disparity between AChE staining and Enk- and SP-ir in HD suggests that AChE-positive neurons or fibers are resistant to the destructive process in areas where intrinsic neuronal populations are depleted.

Acetylcholinesterase↗

PubMed1986

Somatostatin-28(1-12)-like immunoreactivity is reduced in Alzheimer's disease cerebral cortex.

A deficiency in somatostatin is the most consistently described neurochemical alteration in Alzheimer's disease (AD) attributable to intrinsic cortical neurons. Somatostatin-28 (SOM-28), an N-terminal-extended form of somatostatin, can be cleaved to form somatostatin-28(1-12)(SOM-28(1-12) ) and somatostatin-14 (SOM-14). We have measured concentrations of SOM-28(1-12)-like immunoreactivity in 8 cortical regions from 12 patients with AD and 13 controls. Significant reductions (P less than 0.001) were found in all cortical regions examined with the largest decrease in temporal lobe. Reductions were significantly correlated with decreases in somatostatin-14-like immunoreactivity in the same regions. The similar reductions of two prosomatostatin-derived peptides in AD cerebral cortex supports the contention that decreased somatostatin immunoreactivity in AD is caused by a degeneration of somatostatin cortical neurons and terminals.

Aged↗

PubMed1986

Brain choline acetyltransferase activity and neuropeptide Y concentrations in Alzheimer's disease.

Choline acetyltransferase (ChAT) activity and neuropeptide Y (NPY) levels in post-mortem tissues from patients with histologically proven Alzheimer's disease were compared with age-matched neurologically normal control individuals. Despite the high NPY concentrations in human cerebral cortex, no significant abnormalities were found. However, ChAT activity was reduced throughout the cortex, without a relationship to areas of functional deficit, as previously identified using fluorodeoxyglucose. These results lend further support to the concept of Alzheimer's disease as a highly selective neurodegenerative disorder.

Alzheimer Disease↗

PubMed1986

Quantitative cytoarchitectural studies of the cerebral cortex of schizophrenics.

Quantitative morphometric determinations of neuronal and glial density, neuron-glia ratios, and neuronal size were performed in the prefrontal, anterior cingulate, and primary motor cortex of ten controls and ten schizophrenics diagnosed by Feighner criteria under blind conditions to assess whether neuronal degeneration had occurred. Stepwise multiple regression and multiple classification analyses were used to evaluate the effect of potential confounding variables such as age, postmortem interval, fixation, hypoxia, and neuroleptic exposure on the measures studied. The neuronal density was significantly lower in layer VI of the prefrontal, layer V of the cingulate, and layer III of motor cortex. There was also a trend toward fewer neurons in most layers of both prefrontal and motor cortex, although by discriminant analysis this generalized pattern was significant only for the prefrontal area. The glial density also tended to be lower throughout most layers of all three cortical regions. There were no differences in the neuron-glia ratios or neuronal size between the two groups. The data do not support the presence of neuronal degeneration in schizophrenic cortex as it is conventionally described by neuropathologists, but do suggest the possibility that cytoarchitectural variations in cortical structure might exist in this group of schizophrenics.

Aged↗

PubMed1986

Distribution of the molecular forms of acetylcholinesterase in human brain: alterations in dementia of the Alzheimer type.

Acetylcholinesterase (AChE), the enzyme that degrades acetylcholine, is a heterogeneous enzyme that can be separated into multiple molecular forms. A tetrameric membrane-bound form (G4) and a monomeric soluble form (G1) are the two predominant enzyme species in mammalian brain. The distribution of AChE molecular forms was defined by sucrose density gradients of 11 anatomical regions of postmortem brains from 10 patients with dementia of the Alzheimer type (DAT) and 14 nondemented controls of similar ages. The results demonstrate an overall loss of protein and enzyme activity in all areas of the DAT brains studied and a selective loss of the G4 form of AChE in Brodmann areas 9, 10, 11, 21, 22, and 40, and the amygdala. There was no change in the G4/G1 ratio in areas 17 and 20, in the hippocampus, or in the cerebellum. There was a high regional correlation of the G4/G1 ratios with published values for choline acetyltransferase activity but lower correlation with total AChE activity. We propose that there is a predominant loss of the G4 form of AChE in DAT and that this loss is correlated with the degeneration of presynaptic elements.

Acetylcholinesterase↗

PubMed1986

Neuropeptide Y immunoreactivity is reduced in cerebral cortex in Alzheimer's disease.

Neuropeptide Y is a 36-amino acid peptide that is found in high concentrations in cerebral cortex and is contained in cortical neurons. We measured concentrations of this peptide in postmortem tissue from patients with Alzheimer's disease and controls using a sensitive and specific radioimmunoassay. High-performance liquid chromatography showed that more than 95% of immunoreactivity co-migrated with synthetic standards in both Alzheimer's disease and control frontal cortex. Significant reductions in neuropeptide Y-like immunoreactivity were found in eleven cortical regions, the hippocampus, and the locus ceruleus. The regions particularly affected included the temporal lobe, frontal lobe, and occipital cortex. As neuropeptide Y is co-localized with somatostatin in a considerable proportion of cortical neurons, the loss of immunoreactivity may in part reflect degeneration of these neurons. Further study of the selective vulnerability of these neurons in Alzheimer's disease cortex may provide clues to the nature of the underlying disease process.

Aged↗

PubMed1986

Widespread reduction of somatostatin-like immunoreactivity in the cerebral cortex in Alzheimer's disease.

Although several studies have documented reduced concentrations of somatostatin-like immunoreactivity (SLI) in the cerebral cortex in Alzheimer's disease, there is controversy concerning the extent and importance of these changes. We measured SLI in brains obtained post mortem from 12 patients with pathologically confirmed Alzheimer's disease and from 13 neurologically normal controls. All major cortical and subcortical regions were examined. Widespread reductions of SLI in Alzheimer's disease cerebral cortex were found, with the most profound changes seen in temporal lobe; but there also were major reductions in both the frontal and occipital cortex. There were no significant reductions in subcortical regions. Characterization of SLI by high-pressure liquid chromatography showed no significant difference in profiles between Alzheimer's disease and control frontal cortex. These results suggest that the reduction in somatostatin immunoreactivity in Alzheimer's disease may be caused by degeneration of intrinsic somatostatin cortical neurons.

Acetylcholinesterase↗

PubMed1986

A postmortem study of amino acid neurotransmitters in Alzheimer's disease.

Concentrations of putative neurotransmitter amino acids were measured in postmortem brains from 10 patients with Alzheimer's disease and 10 controls. Glutamate, aspartate, taurine, gamma-aminobutyric acid (GABA), and alanine levels were examined in 9 cortical regions, hippocampus, thalamus, and basal ganglia using high-performance liquid chromatography with electrochemical detection. There were no significant alterations in aspartate, taurine, or alanine levels in any of the regions examined. Widespread significant reductions in cortical GABA concentrations were observed in the Alzheimer's brains, with the largest decreases in the temporal lobe. Overall values for glutamate concentrations in temporal and frontal cortices showed a significant 12% reduction in Alzheimer's brains, but the only individual cortical region showing a significant reduction in glutamate was the inferior temporal gyrus. These results suggest that gamma-aminobutyric acidergic neurons in Alzheimer's cerebral cortex may be selectively vulnerable to the disease process.

Aged↗

PubMed1986

Vasopressin in Alzheimer's disease: a study of postmortem brain concentrations.

Vasopressin (AVP) and its analogues are reported to improve learning- and memory-related performance in experimental animals, and perhaps also in humans. Memory impairment is a clinical hallmark of the dementing disorder, Alzheimer's disease. We have examined AVP concentrations in postmortem brain tissue from 12 patients with histologically confirmed Alzheimer's disease and 13 control subjects. AVP was measured by a highly specific and sensitive radioimmunoassay, validated by parallel inhibition curves and high-performance liquid chromatography. Alzheimer brains had either normal or slightly increased AVP levels in the neocortex, which does not have AVP cell bodies. Significant reductions in AVP content were found in the hippocampus, nucleus accumbens, and globus pallidus interna. Levels were normal in all other regions studied. Abnormalities of the brain vasopressin system may contribute to the memory deficit associated with Alzheimer's disease.

Adult↗

PubMed1986

HPLC with electrochemical detection to measure chlorpromazine, thioridazine and metabolites in human brain.

Thirteen phenothiazine compounds were separated chromatographically using high performance liquid chromatography with coulometric electrochemical detection. These could be extracted from brain tissue using direct homogenization in tetrahydrofuran followed by one centrifugation, evaporation of supernatant and reconstitution in water. Fluphenazine was used as the internal standard. The absolute lower limit of detection was approximately 50 pg/mg wet tissue, and recovery rates for most standards added to brain homogenates were greater than 85%. Chromatograms from patients receiving chlorpromazine (600 mg) and thioridazine (600 mg) are shown and endogenous brain levels quantified. The results are discussed with respect to their relevance in schizophrenic research.

Brain Chemistry↗

PubMed1986

Elevated postmortem monoamine oxidase B activity in the caudate nucleus in Huntington's disease compared to schizophrenics and controls.

Activity (Vmax) of monoamine oxidase (MAO) B in necropsy samples from the head of the caudate nucleus was 260% higher in patients dying with Huntington's disease (HD) than in controls (P less than 0.05). No differences in MAO A enzyme kinetics were found. MAO B, but not MAO A, was increased (26%) in the frontal cortex from patients dying with HD compared to control subjects. MAO A and B kinetics in caudate nucleus and frontal cortex from a group of schizophrenics did not differ from controls. Postmortem delay, the effect of neuroleptics, or nonspecific degeneration artifacts did not explain these findings. It is suggested that the increase in MAO B activity in the caudate nucleus may reflect neurochemical changes that are responsible for the choreiform movements of Huntington's disease. Lower cortical MAO B activity in the schizophrenic group may reflect the effects of neuroleptics.

Aged↗

PubMed1986

Optimization of freezing, storage, and thawing conditions for the preparation of metabolically active synaptosomes from frozen rat and human brain.

Samples of rat and human cerebral cortex were frozen, stored, and thawed under a variety of conditions to define further the optimal procedure for storing human brain samples for subsequent metabolic and functional studies that use incubated synaptosomes. Tissue samples were best preserved by immersing them in isotonic sucrose prior to slow freezing, but there was no advantage in first chopping up the material. High concentrations of sucrose, rather than exerting a cryoprotective effect, were detrimental to subsequent synaptosomal performance (oxygen uptake, K+ accumulation, stimulus-induced release of amino acid neurotransmitters). However, good activity was observed in preparations from rat brain frozen in the absence of fluid. This result was confirmed by studies on the uptake of gamma-aminobutyrate (GABA) into an osmotically sensitive compartment in synaptosomes prepared from frozen human autopsy material transshipped from the brain tissue collection ("brain bank") at Harvard Medical School, MA, USA, to Sydney, Australia. Although activity was slowly lost over a 3-mo period in rat tissue samples stored at -20 degrees C, there was little or no such loss at -70 degrees C.

Animals↗

PubMed1986

Gilles de la Tourette's syndrome. A postmortem neuropathological and immunohistochemical study.

Immunocytochemical studies of the human forebrain have shown that enkephalin-like, dynorphin-like and substance-P-like immunoreactivity (respectively ELI, DLI, and SPI) normally present in unique pattern (now termed woolly fibers) in the globus pallidus and substantia nigra, in which their concentration is at its densest. Quantitative determinations moreover indicate that the levels of all 3 peptides are higher in the globus pallidus and substantia nigra than in any other region of the brain. We report here the distribution of immunoreactivity of these 3 peptides in the brain of a patient showing the typical clinical manifestations of Gilles de la Tourette's syndrome (TS); a disease for which no characteristic or consistent neuropathological features have been discerned. In the case described here neuropathological examination by means of the usual histopathological methods showed no abnormalities to which the patient's illness could be ascribed. ELI- and SPLI-positive woolly fibers were densely stained and of normal distribution. DLI-staining was, however, considerably less dense throughout the brain than normal. The most striking finding was the total absence of DLI-positive woolly fibers in the dorsal part of the external segment of the globus pallidus; the ventral pallidum showed very faint staining. These observations, which indicate a decrease of dynorphin in striatal fibers projecting to the globus pallidus, are, to our knowledge, the first evidence of a distinct pathological change in the brain in TS.

Acetylcholinesterase↗

PubMed1985

Selective sparing of a class of striatal neurons in Huntington's disease.

A distinct subpopulation of striatal aspiny neurons, containing the enzyme nicotinamide adenine dinucleotide phosphate diaphorase, is preserved in the caudate nucleus in Huntington's disease. Biochemical assays confirmed a significant increase in the activity of this enzyme in both the caudate nucleus and putamen in postmortem brain tissue from patients with this disease. The resistance of these neurons suggests that the gene defect in Huntington's disease may be modifiable by the local biochemical environment. This finding may provide insight into the nature of the genetically programmed cell death that is a characteristic of the disease.

Adult↗

PubMed1985

Reduced numbers of somatostatin receptors in the cerebral cortex in Alzheimer's disease.

Somatostatin receptor concentrations were measured in patients with Alzheimer's disease and controls. In the frontal cortex (Brodmann areas 6, 9, and 10) and temporal cortex (Brodmann area 21), the concentrations of somatostatin in receptors in the patients were reduced to approximately 50 percent of control values. A 40 percent reduction was seen in the hippocampus, while no significant changes were found in the cingulate cortex, postcentral gyrus, temporal pole, and superior temporal gyrus. Scatchard analysis showed a reduction in receptor number rather than a change in affinity. Somatostatin-like immunoreactivity was significantly reduced in both the frontal and temporal cortex. Somatostatin-like immunoreactivity was linearly related to somatostatin-receptor binding in the cortices of Alzheimer's patients. These findings may reflect degeneration of postsynaptic neurons or cortical afferents in the patients' cerebral cortices. Alternatively, decreased somatostatin-like immunoreactivity in Alzheimer's disease might indicate increased release of somatostatin and down regulation of postsynaptic receptors.

Adult↗