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E Storey

Publications and source records attributed to E Storey.

At least 37 records · Page 2Linked to original sources
PubMed1994

Movement disorder following excitotoxin lesions in primates.

We previously reported on the histologic and neurochemical features of quinolinic acid lesions in primates which produce many of the characteristic features of Huntington's disease (HD). We now report on the effects of apomorphine in generating a movement disorder in four of these animals. Animals were tested with saline or apomorphine both before and after the lesions. All animals showed few spontaneous abnormal movements after lesioning, but showed marked dyskinetic movements following apomorphine administration. These results show that excitotoxin lesions in primates can produce an apomorphine-inducible movement disorder which closely resembles that of HD.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1994

Patients and the sick building syndrome.

Physicians encounter patients who have complaints related to indoor environments with increasing frequency. Physicians must distinguish between approaches to identify disease in individual patients, characterization of group effects, and analysis of environmental exposure characteristics. Simultaneously they must consider the influence of illness behavior, work stress, and organization function on the presentation of complaints. They must distinguish discomfort and irritation from disabling disease and communicate the implications of pathophysiology and the limits of knowledge to patients. Joint teams with engineers and industrial hygienists, and, at times, organizational analysis is an approach to problem solving for indoor environmental problems.

Air Pollution, Indoor↗
PubMed1993

Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization.

Excitotoxin lesions induced by quinolinic acid (QA) were made unilaterally in the caudate nucleus and putamen of 12 rhesus monkeys. Both acute (2-3 weeks) and chronic (4-6 months) effects were evaluated. Excitotoxin striatal lesions were characterized by a central zone of intense astrogliosis and marked neuronal depletion, which was surrounded by a transition zone in which there was partial neuronal sparing throughout the entire lesioned side. Immunocytochemical and enzyme histochemical markers for both large and medium-sized aspiny- and spiny-striatal neurons clearly demonstrated a selective pattern of neuronal vulnerability to the excitotoxic effects of QA within lesioned striata. Medium-sized spiny neurons containing calbindin Dk28, enkephalin, and substance P were disproportionately lost, while aspiny neuronal subpopulations containing NADPH diaphorase (NADPH-d) and choline acetyltransferase activity (ChAT) were relatively spared. Combined labeling by NADPH-d enzyme histochemistry and Nissl staining, as well as NADPH-d histochemistry and calbindin Dk28 immunocytochemistry, demonstrated significant increases in the ratio of aspiny to spiny neurons within the lesioned striata. Neurochemical measurements confirmed a loss of GABA and substance P-like immunoreactivity yet no significant depletion of somatostatin-like immunoreactivity, neuropeptide Y-like immunoreactivity, or ChAT were seen. The striatal patch-matrix pattern persisted, as demonstrated by acetylcholinesterase activity. The pattern was altered, however, in the chronic animals, such that the matrix zone was significantly reduced, while the total area of patches remained within normal limits. Ultrastructural analysis confirmed axon sparing lesions with neuronal loss and astrogliosis. Pretreatment of 3 monkeys with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, blocked striatal QA neurotoxicity. The present results provide an experimental primate model which closely resembles the neuropathologic and neurochemical features of Huntington's disease. These findings further strengthen the possibility that an NMDA receptor-mediated excitotoxic process plays a role in the pathogenesis of this disorder.

Animals↗
PubMed1993

Neurochemical substrates of rigidity and chorea in Huntington's disease.

Huntington's disease is a progressive degenerative neurological disorder which produces a characteristic movement disorder termed chorea. Although chorea is associated with dysfunction of the basal ganglia, the underlying mechanisms by which dyskinesias such as chorea are produced, are poorly understood. Recent studies in primates have led to experimental models of chorea with postulated involvement of specific neural pathways. In the present study we attempted to determine the validity of the experimental models by measuring concentrations of gamma-aminobutyric acid (GABA), glutamate, substance P and met-enkephalin in the basal ganglia of Huntington's disease patients who manifested either chorea or rigidity/bradykinesia within 6 months of death. We also characterized changes in the Huntington's disease patients according to pathological grade, since this may be a confounding factor. We analysed post-mortem brain tissue from 12 controls, and 11 grade 3 and 12 grade 4 Huntington's disease patients. The grade 3 and 4 cases consisted of eight adult-onset choreic, nine adult-onset rigid and six juvenile-onset rigid patients. We also analysed the putamen and globus pallidus from 11 grade 2 adult onset choreic Huntington's disease patients. A model of chorea based on experimental studies in primates proposes that a loss of striatal GABAergic inhibitory projections to the globus pallidus externa leads to increased activity of the inhibitory globus pallidus externa GABAergic neurons which project to the subthalamic nucleus. It is believed that the loss of GABAergic inputs to the globus pallidus externa precedes a loss of GABAergic input to the globus pallidus interna, which occurs later in the disease and is associated with the development of rigidity and bradykinesia. In the choreic Huntington's disease patients whom we studied, there was a greater loss of GABA in the globus pallidus externa than in the globus pallidus interna, and the globus pallidus interna: globus pallidus externa GABA ratio was significantly increased compared with rigid patients. There were also increases in GABA in the subthalamic nucleus in the choreic patients, although this did not reach significance. A differential loss of met-enkephalin in the globus pallidus externa compared with substance P loss in the globus pallidus interna was not observed in either the choreic patients with advanced disease or the grade II patients. There was a significant increase in GABA concentrations in the ventroanterior nucleus of the thalamus in the choreic patients compared with rigid/bradykinetic patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid.

An impairment of energy metabolism may underlie slow excitotoxic neuronal death in neurodegenerative diseases. We therefore examined the effects of intrastriatal, subacute systemic, or chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid (3-NP) in rats. Following intrastriatal injection 3-NP produced dose-dependent striatal lesions. Neurochemical and histologic evaluation showed that markers of both spiny projection neurons (GABA, substance P, calbindin) and aspiny interneurons (somatostatin, neuropeptide Y, NADPH-diaphorase) were equally affected. Subacute systemic administration of 3-NP produced age-dependent bilateral striatal lesions with a similar neurochemical profile. However, in contrast to the intrastriatal injections, striatal dopaminergic afferent projections were spared. Both freeze-clamp measurements and chemical shift magnetic resonance spectroscopy showed that 3-NP impairs energy metabolism in the striatum in vivo. Microdialysis showed no increase in extracellular glutamate concentrations after systemic administration of 3-NP. The lesions produced by intrastriatal injection or systemic administration of 3-NP were blocked by prior decortication. However, the NMDA antagonist MK-801 did not block the effects of intrastriatal 3-NP, consistent with a non-NMDA excitotoxic mechanism. In contrast to subacute systemic administration of 3-NP, chronic (1 month) administration produced lesions confined to the striatum in which there was relative sparing of NADPH-diaphorase interneurons, consistent with an NMDA excitotoxic process. Chronic administration showed growth-related proliferative changes in dendrites of spiny neurons similar to changes in Huntington's disease (HD). These results are consistent with in vitro studies showing that mild metabolic compromise can selectively activate NMDA receptors while more severe compromise activates both NMDA and non-NMDA receptors. Chronic administration of 3-NP over 1 month produces selective striatal lesions that replicate many of the characteristic histologic and neurochemical features of HD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

The cortical lesion of Huntington's disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex.

Huntington's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma-aminobutyric acid (GABA)-ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N-methyl-D-aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA-induced lesions showed striking sparing of parvalbumin-positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA-induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease.

Age Factors↗
PubMed1992

Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex.

Huntington's disease (HD) is characterized by gradually evolving selective neuronal death. Several lines of evidence suggest that an excitotoxic mechanism may play a role. Tryptophan metabolism leads to production of quinolinic acid, an N-methyl-D-aspartate (NMDA) receptor agonist, and to kynurenic acid, an antagonist at these same receptors. We recently found increased kynurenine to kynurenic acid ratios in HD postmortem putamen and decreased kynurenic acid concentrations in cerebrospinal fluid, consistent with decreased formation of kynurenic acid in HD brain. In the present study we used HPLC with 16 sensor coulometric electrochemical detection to measure kynurenic acid and 18 other electrochemically active compounds in 6 cortical regions, caudate and cerebellum from controls, HD, Alzheimer's disease (AD), and Parkinson's disease (PD) patients. Significant reductions in kynurenic acid concentrations were found in 5 of 6 cortical regions examined. Smaller reductions of kynurenic acid in the caudate, cerebellum and frontal pole were not significant. No significant reductions were found in the AD and PD patients. Both uric acid and glutathionine were significantly reduced in several regions of HD cerebral cortex, which could signify abnormal energy metabolism in HD. Since kynurenic acid is an antagonist of excitatory amino acid receptors, a deficiency could contribute to the pathogenesis of neuronal degeneration in HD.

Aged↗
PubMed1992

1-Methyl-4-phenylpyridinium produces excitotoxic lesions in rat striatum as a result of impairment of oxidative metabolism.

The effects of 1-methyl-4-phenylpyridinium (MPP+) were studied in rat striatum. Using freeze-clamp, microwave, and water-suppressed proton chemical shift magnetic resonance imaging techniques, MPP+ resulted in marked increases in lactate and a depletion of ATP for up to 48 h after the injections. MPP+ produced dose-dependent depletions of dopamine, serotonin, gamma-aminobutyric acid, and substance P that were partially blocked at 1 week by prior decortication or completely blocked by MK-801 at 24 h. The lesions showed relative sparing of somatostatin-neuropeptide Y neurons, consistent with N-methyl-D-aspartate (NMDA) excitotoxicity. MPP+ produces impairment of oxidative phosphorylation in vivo, which may result in membrane depolarization with persistent activation of NMDA receptors and excitotoxic neuronal degeneration. An impairment of energy metabolism may therefore underlie slow excitotoxic neuronal death in neurodegenerative diseases.

1-Methyl-4-phenylpyridinium↗
PubMed1992

Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin change (POEMS) syndrome with IgG kappa paraproteinemia.

The POEMS syndrome is an infrequently reported multisystem disorder which presents usually as an obscure polyneuropathy, with almost all cases reported in Japan. A 64 yr old caucasian man presented with a 12 mth history of a severe sensorimotor neuropathy in association with dermato-endocrine features. Detection of a monoclonal IgG kappa paraprotein and mixed osteosclerotic/lytic bone lesions consistent with a plasma cell dyscrasia led to diagnosis of the POEMS syndrome. Unique ultrastructural features were present on sural nerve biopsy in addition to the unusual association with monoclonal kappa-light chain. This case illustrates that the POEMS syndrome may also occur in caucasian subjects.

Humans↗
PubMed1992

A polyclonal but not a monoclonal antibody to an M(r) 52-kD protein responsible for a punctate fluorescence pattern in Plasmodium falciparum merozoites inhibits invasion in vitro.

A monoclonal antibody, MAb H24, recognized a Plasmodium falciparum antigen with a relative molecular mass (M(r)) of 52 kD that appeared to be a rhoptry component by immunofluorescence microscopy. The antigen is synthesized during both ring and schizont stages, but pulse-chase experiments showed that it is not carried through to the next ring stage after reinvasion. It was not labeled by 3H-glucosamine. The purified MAb failed to inhibit parasite invasion in vitro. The antigen was isolated using affinity chromatography, and used to produce a monospecific polyclonal antibody (PAb H24) in mice. Polyclonal antibody H24 recognized the same antigen as MAb H24 as judged by both immunofluorescence microscopy and immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and was markedly inhibitory in vitro.

Animals↗
PubMed1991

Effects of aging on quinolinic acid lesions in rat striatum.

Several neurologic illnesses in which excitotoxic mechanisms may play a role increase in prevalence with age. In the present study we examined the susceptibility of rats to quinolinic acid striatal lesions at 1, 4 and 20 months of age, and susceptibility to N-methyl-D-aspartate (NMDA) at 1 and 4 months of age. The extent of the lesions was quantitated with measurements of substance P-like immunoreactivity (SPLI) and gamma-aminobutyric acid (GABA). The lesions in the 4- and 20-month-old age groups showed significantly smaller depletions of SPLI and GABA than those in 1-month-old animals. Neuropeptide Y-like immunoreactivity (NPYLI) and somatostatin-like immunoreactivity (SLI) were unchanged in the lesioned striata. NMDA lesions were also attenuated in 4-month- and 12-month-old animals as compared with 1-month-old animals. Uric acid concentrations showed marked dose-dependent increases in the lesioned striatum, and to a lesser extent in the overlying cerebral cortex, in all 3 age groups. There were no changes of SLI, NPYLI or SPLI with aging in the cerebral cortex or hippocampus. Kynurenine and kynurenic acid concentrations showed significant increases with aging in frontal cortex. The present results show a reduced susceptibility of animals to striatal quinolinic acid and NMDA lesions with normal aging. The delayed onset of several neurodegenerative illnesses is therefore unlikely to be due to an increasing susceptibility to excitotoxin lesions with aging.

Aging↗
PubMed1991

Aminooxyacetic acid results in excitotoxin lesions by a novel indirect mechanism.

Aminooxyacetic acid (AOAA) is an inhibitor of several pyridoxal phosphate-depedent enzymes in the brain. In the present experiments intrastriatal injections of AOAA produced dose-dependent excitotoxic lesions. The lesions were dependent on a pyridoxal phosphate mechanisms because pyridoxine blocked them. The lesions were blocked by the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 and by coinjection of kynurenate, a result indicating an NMDA receptor-mediated excitotoxic process. Electrophysiologic studies showed that AOAA does not directly activate ligand-gated ion channels in cultured cortical or striatal neurons. Pentobarbital anesthesia attenuated the lesions. AOAA injections resulted in significant increases in lactate content and depletions of ATP levels. AOAA striatal lesions closely resemble Huntington's disease both neurochemically and histologically because they show striking sparing of NADPH-diaphorase and large neurons within the lesioned area. AOAA produces excitotoxic lesions by a novel indirect mechanism, which appears to be due to impairment of intracellular energy metabolism, secondary to its ability to block the mitochondrial malate-aspartate shunt. These results raise the possibility that a regional impairment of intracellular energy metabolism may secondarily result in excitotoxic neuronal death in chronic neurodegenerative illnesses, such as Huntington's disease.

Aminooxyacetic Acid↗
PubMed1990

The effect of fluoride consumption and social class on dental caries in 8-year-old children.

School dental service data indicate that whilst Melbourne eight-year-old children had worse dental health than similar children in the Geelong area in 1979, the situation in 1985 was the reverse. In order to investigate this, and determine the effects of socio-economic level (SEL), residential history, and fluoride history on dental caries status, 208 eight-year-old children in the Melbourne area and 209 eight-year-old children in the Geelong area were examined for dental caries. A questionnaire was administered to gain details of subjects' exposure to water and supplement fluorides. The SEL of the subjects' school was used in place of individual SEL. A high proportion (46 per cent) of Geelong subjects used a fluoride supplement at some stage, but few continued this for most of their life. Residential history was important, with 2.4 per cent of the Melbourne subjects living most of their life in a nonfluoridated area and 3.4 per cent of Geelong subjects living most of their life in a fluoridated area. There was a significant difference between the dmft in Melbourne and Geelong when only children who had lived all their life in the city in which they were examined and did not use a fluoride supplement were included. A large part of this difference is attributed to water fluoridation in Melbourne. A substantial number of children would benefit from fluoridation of the reticulated water supply in Geelong, particularly those in the lower social classes.

Analysis of Variance↗
PubMed1989

Guillain-Barré syndrome and related conditions in Victorian teaching hospitals 1980-84.

Cases of Guillain-Barré syndrome, its variants, and chronic inflammatory demyelinating neuropathy presenting during the period 1980-84 were identified through computer-based record systems. Case notes were examined, and cases that did not meet standard criteria for diagnosis were excluded. A hundred and ten patients were identified, giving an annual adult incidence rate of 0.9/100,000 and a male:female ratio of 1.3:1. The majority of cases developed severe tetraparesis, but unusual presentations included the Miller-Fisher variant, paraplegia, and bibrachial involvement. There was wide variation in peak disability, ranging from ambulant with weakness (32%), through bedfast but without significant respiratory involvement (29%), to respiratory involvement requiring admission to an intensive care unit (38%). Of those discharged directly home, the average hospital stay for those less than 50 years was 27 days, whilst that for those over 50 was 49 days. CSF protein was measured in 87 patients, and was greater than or equal to 0.6 g/L in 76% of these. Nerve conduction studies were performed in 52 patients, and were abnormal in 90% of these. Guillain-Barré syndrome and allied conditions represent a major drain on health resources, and the need to provide adequate plasmapheresis facilities for patients early in the course of severe disease is stressed.

Adolescent↗
PubMed1988

Pneumoconiosis in carbon electrode workers.

Pneumoconiosis was diagnosed in five workers involved in the manufacture of carbon electrodes. Possible etiologies are discussed. It is generally believed that pneumoconiosis ceased to be a problem in this industry after World War II; however, the reported cases all resulted from exposures after 1940. These findings question the efficacy of recent and current engineering controls and suggest the need for further study of this industry.

Carbon↗