Biomedical subjects

D L Price

Publications and source records attributed to D L Price.

At least 217 records · Page 12Linked to original sources

PubMed1989

Changes in size of motor axons in hereditary canine spinal muscular atrophy.

Hereditary canine spinal muscular atrophy (HCSMA), a dominantly inherited disorder of motor neurons, has three phenotypes: accelerated, intermediate, and chronic. In the accelerated and intermediate phenotypes, axonal sizes in ventral roots were smaller than in controls. Reductions in axonal size occurred primarily in large axons, and the frequency of small-caliber axons was increased. In HCSMA, nerve fiber shape, i.e., circularity, was reduced, and the relative thickness of the myelin sheath as a function of axonal caliber was decreased. The density of fibers in motor nerves was increased, making it unlikely that a selective loss of large-caliber axons explained the increased frequency of small-caliber axons. These observations suggest that, in HCSMA, changes in axonal size in motor nerves are associated with both growth arrest and axonal atrophy.

Age Factors↗

PubMed1988

Developmental changes of neuropeptides and amino acids in baboon cortex.

The pattern of developmental changes in concentrations of substance P, somatostatin and neuropeptide Y immunoreactivity and amino acids was studied in baboon cortex. Samples of occipital or frontal neocortex were obtained from preterm (100-105 days gestation), near-term (170-176 days gestation), and young adult animals. Substance P concentrations were low at preterm, highest at near-term, and then declined to adult levels. Neuropeptide Y and somatostatin immunoreactivity increased steadily across the three age groups. Concentrations of aspartate and gamma-aminobutyric acid (GABA) also increased progressively from preterm to adulthood, whereas glutamate concentrations showed small increases that were not statistically significant. Concentrations of taurine and alanine were highest preterm and declined progressively to adulthood. Levels of neuropeptides and amino acids show distinct patterns of change during development of neocortex in the baboon.

Amino Acids↗

PubMed1988

Topographic, non-collateralized basal forebrain projections to amygdala, hippocampus, and anterior cingulate cortex in the rhesus monkey.

Projections of the basal forebrain magnocellular complex to the limbic telencephalon of the primate were studied by combining double-retrograde tracing with immunocytochemistry. Tracers were injected into anterior cingulate cortex and hippocampus or into hippocampus and amygdala. Retrogradely labeled populations of neurons were topographically arranged but intermingled peripherally. Double-labeled neurons, found only after amygdala-hippocampus injections, were very rare. Approximately 30% of hippocampopetal, 50-70% of amygdalopetal, and 50-90% of cingulopetal neurons were cholinergic; percentages varied among different regions of basal forebrain. These findings further support the concept of a system with a highly organized efferent circuitry.

Amidines↗

PubMed1988

Development of beta 1 and beta 2 adrenergic receptors in baboon brain: an autoradiographic study using [125I]iodocyanopindolol.

[125I]iodocyanopindolol (ICYP) autoradiography was used to investigate the temporal development and distribution of beta 1 and beta 2 receptors in brains of baboons at ages embryonic day 100 (E100), full-term gestation (El80), and 3 years. In all brain regions examined, with the exception of the hippocampus, binding to beta 1 receptors exceeded that to beta 2 receptors. The highest densities of beta 1 receptors were found in the caudate nucleus, putamen, globus pallidus, substantia nigra, and cerebral cortex; intermediate receptor densities were observed in most nuclei of thalamus, and the lowest concentrations were in the hippocampus. At E100, beta receptors were identified in the striatum, globus pallidus, and thalamus. During maturation, the number of beta 1 receptors declined in cortical areas but increased in the head of the caudate and putamen. Significant differences in the developmental distribution of beta receptors during development were also detected: at E100 and E180 beta 1 receptors appeared as patches in the caudate and putamen, but by 3 years of age they were more homogeneously distributed in both regions; changes also occurred in the distribution of binding within cortical layers. Autoradiograms of [125I]ICYP and [3H]mazindol binding show overlapping patches of labeling in the E180 striatum, suggesting a possible developmental association between beta receptors and dopamine high-affinity uptake carrier sites. This study demonstrates that noradrenergic receptors in the primate forebrain undergo significant developmental reorganization with regional variations.

Aging↗

PubMed1988

Levels of neurotransmitter and cytoskeletal protein mRNAs during nerve regeneration in sympathetic ganglia.

The present study examines levels of neurotransmitter messenger RNA (mRNA) at various stages after crush of postganglionic nerves in the superior cervical ganglia. Using complementary DNA (cDNA) probes, we demonstrated a reduction in ganglionic mRNA levels for tyrosine hydroxylase (TH) after axotomy. Concomitantly, actin and tubulin mRNA levels in ganglia were increased. Thus, in neurons of sympathetic ganglia, axotomy appears to be associated with a selective reduction in levels of TH mRNA, and, in turn, alters levels of protein and enzyme activities.

Actins↗

PubMed1988

Reductions in acetylcholine and nicotine binding in several degenerative diseases.

Alzheimer's disease, Parkinson's disease, and progressive supranuclear palsy are all characterized by loss of neurons in the basal forebrain cholinergic system and by associated reductions in cortical presynaptic cholinergic markers, such as choline acetyltransferase. In this report, we identify that a major cortical receptor alteration in these disorders is a reduction in nicotinic receptors measured using both tritiated acetylcholine and levorotatory tritiated nicotine binding.

Acetylcholine↗

PubMed1988

The neuropathology of aminergic nuclei in Alzheimer's disease.

Neuronal loss and the presence of neurofibrillary tangles (NFTs) within aminergic nuclei were examined in a series of patients with Alzheimer's disease (AD). Neuromelanin-containing neurons within the locus ceruleus and large nucleolus-containing neurons within the dorsal raphe nucleus and the central superior (raphe) nucleus were counted in 25 patients with AD and in 12 age-matched control subjects. Numbers of NFTs were quantified in the same regions. Counts were compared with clinical data, including psychiatric evaluations, available for 21 of the patients with AD. Within the locus ceruleus in the patients with AD, abnormalities were more severe at mid level than at caudal or rostral levels (p less than 0.01). Within the dorsal raphe nucleus, neuronal loss was most severe caudally (p less than 0.05). NFTs, but not neuronal loss, were demonstrated within the central superior nucleus. Neuronal and NFT counts did not correlate at individual levels; the relative severity of both pathological processes was consistent from level to level within nuclei but was less consistent between nuclei. Neuronal loss correlated inversely with age, particularly within the locus ceruleus. Duration of disease correlated inversely with counts of NFTs, particularly within the dorsal raphe nucleus, implying a correlation between NFT counts and rate of progression of disease as all but 3 patients had severe dementia. Significantly, patients with AD complicated by major depression had fewer neurons at the mid level of the locus ceruleus and at the rostral level of the central superior nucleus in comparison with nondepressed patients. There was a trend suggesting greater loss of neurons at all levels of the locus ceruleus and dorsal raphe nucleus in depressed individuals.

Adult↗

PubMed1988

Selective silver impregnation of senile plaques: a method useful for computer imaging.

Most silver methods for the demonstration of senile plaques (SP) in Alzheimer's disease (AD) give variable staining of SP and often stain a variety of other structures (including normal axons, neurofibrillary tangles (NFT), blood vessel reticulin, nucleoli of neurons, and nuclei of glia). A newly developed silver method for paraffin sections is described in this report that reliably stains densely arrayed fine processes in SP. Other structures, including NFT, are not darkly stained. The high-contrast staining of SP greatly facilitates the mapping and morphometry of SP using videomicroscopic image analysis systems and provides a new method for other research studies on SP and for diagnostic histopathology.

Aged↗

PubMed1988

Aluminum neurotoxicity: altered expression of cytoskeletal genes.

To better understand perturbations of the neuronal cytoskeleton that occur in several mammalian disorders, we have focused on an animal model in which neurofibrillary pathology follows the administration of aluminum salts. In susceptible species, the injection of aluminum produces accumulations of neurofilaments (NFs) in cell bodies and proximal axons of certain populations of neurons. Mechanisms involved in the production of these abnormalities are unclear; in particular, the role of gene expression in the genesis of this type of neurofibrillary pathology has not been examined. In this study of aluminum-intoxicated rabbits, the expression of genes coding for several cytoskeletal proteins was studied in the spinal cord and dorsal root ganglia (DRG)--tissues with and without neurofibrillary pathology, respectively. In aluminum-treated rabbits, in situ hybridization using a cDNA probe demonstrated the presence of mRNA coding for the 68-kDa NF (NF-L) protein in spinal cord motor neurons with NF accumulations as well in unaffected neurons. On Northern blots, the expression of genes coding for the NF-L protein and tubulin was reduced by approximately 3.5-fold and 3-fold, respectively, in spinal cords of aluminum-intoxicated rabbits as compared to controls. On blots, levels of actin mRNA were not significantly different in spinal cords of aluminum-treated rabbits as compared to controls, but there was a trend for a slight reduction. In DRG of intoxicated animals, the expression of genes coding for these cytoskeletal proteins was not altered.

Aluminum↗

PubMed1988

Innervation of human hippocampus by noradrenergic systems: normal anatomy and structural abnormalities in aging and in Alzheimer's disease.

Immunocytochemical studies, using an antibody directed against human dopamine beta-hydroxylase, identified an extensive plexus of noradrenergic axons/terminals in normal human hippocampus. In hippocampi of individuals with Alzheimer's disease, the density of noradrenergic innervation was reduced and abnormal noradrenergic axons, which exhibited multifocal enlargements, were present in the neuropil. Some of these neurites were clustered around deposits of amyloid (senile plaques), and these abnormalities were most common in CA3-4, a region normally showing a relatively high density of noradrenergic terminals. This investigation provides direct evidence for structural abnormalities of noradrenergic axons/nerve terminals in hippocampi of individuals with Alzheimer's disease.

Aged↗

PubMed1988

Multiple transmitter systems contribute neurites to individual senile plaques.

Senile plaques (SP), which consist largely of abnormal neuronal processes in proximity to deposits of amyloid, are a characteristic neuropathological feature of Alzheimer's disease. In lesser numbers, SP also occur in the brains of nondemented aged humans and nonhuman primates. To date, it is not known whether neurites in individual SP derive from neurons of one or several neurotransmitter systems. In aged monkeys, two strategies were used to test the hypothesis that individual SP can contain abnormal neurites arising from multiple neuronal systems. First, immunocytochemical methods were used to identify somatostatin-immunoreactive neurites in plaques, and these sections were subsequently stained with silver to visualize other neurites. Numerous plaques contained both somatostatin-positive and somatostatin-negative (i.e. argyrophilic only) neurites, suggesting that more than one transmitter system contributed neurites to each of these plaques. Second, two-color immunocytochemical techniques showed, in a small percentage of plaques, that cholinergic neurites coexist with neuropeptide Y (NPY)-containing neurites or catecholaminergic neurites. These results suggest that the formation of SP may result from events that involve abnormalities of neuronal processes arising from multiple transmitter systems.

Alzheimer Disease↗

PubMed1988

Neurofilament antigens in acrylamide neuropathy.

After repeated exposure, acrylamide (AC) produces degeneration of distal axons. Because neurons whose axons have been injured (e.g. by axotomy) show alterations in their structural and chemical properties, the present study was designed to differentiate the direct effects of AC intoxication from neuronal responses secondary to axonal injury caused by AC. Rats were given AC as either a single high dose (75 mg/kg), or as daily intraperitoneal injections (30 mg/kg, six days per week for four weeks). Dorsal root ganglia of the fifth lumbar level, L5, were examined using a variety of monoclonal antibodies directed against nonphosphorylated (2-135) and phosphorylated (03-44, 06-17, 07-05) epitopes of 145 and 200 kilodalton neurofilament proteins. In control rats, antibody 2-135 stained axons and neuronal cell bodies; antibodies against phosphorylated epitopes of neurofilaments stained only axons distal to the glomerulus. Following chronic AC intoxication, all three antibodies directed against phosphorylated epitopes of neurofilaments (particularly 07-05) demonstrated intense immunoreactivity in 20-30% of neuronal cell bodies. In addition, the glomerular region of these axons was stained. Electron microscopy revealed many chromatolytic cells containing few neurofilaments. In contrast, a single high dose of AC produced no abnormal staining of neuronal cell bodies at a time when slow axonal transport was impaired. Our findings are compared to those observed following axotomy and to those occurring in aluminum-intoxicated rabbits, two experimental disorders in which altered distributions of phosphorylated filaments have been documented.

Acrylamides↗

PubMed1988

Neurofilamentous abnormalities in motor neurons in spontaneously occurring animal disorders.

Cytoskeletal proteins have a characteristic distribution within neurons when immunocytochemical techniques are used on conventional paraffin sections. For example, phosphorylated neurofilaments are located within axons but are not normally present in the majority of perikarya of the central nervous system. This pattern can be altered in disease, and neurofilaments that accumulate within perikarya can be phosphorylated inappropriately. To determine whether retained neurofilaments were phosphorylated inappropriately, we used immunocytochemical techniques to examine several diseases in animals in which neurofilaments accumulate within neuronal perikarya. Our investigations of diseases with disparate etiologies show that, whenever neurofilaments are retained within the neuronal perikarya, they are phosphorylated. These results suggest that phosphorylation of neurofilaments in an inappropriate location, i.e. perikarya, may be a nonspecific disease-related response of neurons that can be initiated by a variety of cellular injuries.

Animal Diseases↗

PubMed1988

Neurofibrillary tangles and senile plaques in aged bears.

In aged human beings and in individuals with age-associated degenerative disorders, particularly Alzheimer's disease (AD), neurons develop cytoskeletal abnormalities, including neurofibrillary tangles (NFT) and senile plaques (SP). Senile plaques occur in several nonhuman species; however, NFT, with ultrastructural or immunocytochemical similarities to those occurring in humans, have not been identified in other mammals. In this study of five aged bears (Ursus, 20-30 years of age), we identified cytoskeletal abnormalities similar to those occurring in humans. An aged Asiatic brown bear had NFT, composed of straight 10-16-nm filaments, that were immunoreactive with antibodies directed against: phosphorylated epitopes of neurofilaments (NF); tau; A68 (a protein enriched in AD); and an antigen associated with paired helical filaments (PHF). An aged polar bear had numerous SP; neurites of these plaques were immunoreactive with antibodies against phosphorylated epitopes of NF, but NFT were not identified. These results indicate that nonprimate species develop age-related cytoskeletal abnormalities similar to those occurring in humans. Investigations of the comparative pathology of aged mammals may be useful in elucidating the pathogeneses of these abnormalities.

Alzheimer Disease↗

PubMed1988

Research on Rett syndrome: strategy and preliminary results.

The research strategy presented here involves four assumptions: (1) Rett syndrome exists; (2) a single cause will eventually be found to account for the majority of cases presently assigned to this disease category; (3) it is genetically determined; and (4) it represents a neurodegenerative disorder that can be defined by quantitative studies of nervous system structure and function. The strategy proposed here involves the comprehensive study of 100 patients with the classic Rett syndrome phenotype. Studies include the (1) search for a diagnostic marker; (2) high-resolution cytogenetic banding techniques, (3) quantitative morphologic studies of postmortem brain tissue as well as neurochemical analyses including autoradiographic techniques, radioimmunoassays, and in situ hybridization; and (4) positron emission tomography studies of cerebral glucose metabolism and neurotransmitters.

Adolescent↗

PubMed1988

Gracile tract degeneration in patients with sensory neuropathy and AIDS.

At autopsy, four homosexual men with acquired immunodeficiency syndrome (AIDS) were found to have selective degeneration of the gracile tract, a finding previously unreported in AIDS. Clinically, these patients had progressive lower extremity paresthesias and dysesthesias with reduced or absent ankle jerks, and eventually they developed dementia. Postmortem examination of spinal cords showed a striking loss of both axons and myelin sheaths confined to the fasciculus gracilis, with the most severe involvement in upper thoracic or cervical segments. Lumbar dorsal columns showed only a mild fiber loss, and no fiber loss was observed in lumbar dorsal roots. Lumbar dorsal root ganglia were available from one patient and showed a mild sensory ganglionitis. In all cases examined, microglial nodules were present in the brain. In 23 other individuals with AIDS who had autopsies consecutively with these four subjects, none had sensory neuropathy and the gracile tracts were normal. The combination of distal sensory neuropathy and gracile tract degeneration suggests a "dying-back" process of dorsal root ganglia neurons.

Acquired Immunodeficiency Syndrome↗

PubMed1988

Pathology in brainstem regions of individuals with primary dystonia.

Examination of brains from four individuals with the clinical diagnosis of primary dystonia revealed histopathologic abnormalities in two cases. A 29-year-old man with a 15-year history of dystonia musculorum deformans (DMD) had numerous neurofibrillary tangles (NFT) and mild neuronal loss within the locus ceruleus; occasional NFT were also recognized in the substantia nigra pars compacta, pedunculopontine nucleus, and dorsal raphe nucleus. A 68-year-old man with a 35-year history of Meige syndrome had moderate-to-severe neuronal loss in several brainstem nuclei, including the substantia nigra pars compacta, locus ceruleus, raphe nuclei, and pedunculopontine nucleus. Infrequent NFT were also noted in substantia nigra. An examination of these and other brain regions in a 10-year-old boy with a 6-year history of DMD and a 50-year-old woman with a 3-year history of spasmodic torticollis did not disclose similar abnormalities.

Adult↗

PubMed1988

Reductions in [3H]nicotinic acetylcholine binding in Alzheimer's disease and Parkinson's disease: an autoradiographic study.

In Alzheimer's disease (AD) and Parkinson's disease (PD), dysfunction in the basal forebrain cholinergic system is accompanied by a consistent loss of presynaptic cholinergic markers in cortex, but changes in cholinergic receptor binding sites are poorly understood. In the present study, we used receptor autoradiography to map the distribution of nicotinic [3H]acetylcholine binding sites in cortices of individuals with AD and PD and matched control subjects. In both diseases, a profound loss of nicotinic receptors occurs in all cortical layers, particularly the deepest layers.

Aged↗