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Biomedical subjects

E Storey

Publications and source records attributed to E Storey.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1987

Stress induced periosteal changes.

The tails of Sprague-Dawley rats of approximately 50 g body mass were either left straight or bent to form a loop containing three or five vertebrae (CV). Subsequent treatment was as follows: (a) in situ: segments were removed at 0, 8, 16, 24 h, 3, 5 and 7 days and examined histologically: (b) transplants: skinned segments were transplanted autologously and examined at the same time intervals; (c) normal saline: skinned segments were placed in a 0.9% solution maintained at (i) 4 degrees C and (ii) 37 degrees C and examined 8, 16 and 24 h later. The results show that on bending a bone in situ the remodelling which occurs reflects the displacement of the soft tissues, and more specifically the periosteum, towards or away from the bone surface. Functionally the developing periosteum consists of three zones and when stressed its fibroelastic component moves away from or towards the osteogenic layer either applying tension to it stimulating bone formation, or pressure eventually inducing bone resorption. These changes are mediated via the mid-zone. The effects on the fibroelastic component alone are best seen in transplants or in normal saline at 37 degrees C where the osteogenic layer dies. The periosteum in growing bones is ideally structured to respond rapidly and sensitively to altered strain by initiating adaptive surface remodelling of bone.

Animals↗
PubMed1986

Remodeling of bone and bones: effects of altered mechanical stress on the regeneration of transplanted bones.

We divided 116 rats weighing 50 gm into four groups with tails either left in situ or transplanted as follows: straight in situ: untreated controls; bent in situ: five caudal vertebrae (CV) in the loop; straight transplants: three CV skinned and transplanted autologously; and bent transplants: five CV skinned, bent to form a loop, and transplanted autologously. Tails were radiographed weekly up to 6 weeks and at 12 weeks, and microradiographic and histological studies were undertaken on selected specimens. At 12 weeks the bones in the apex of the loop of tails left in situ appeared bent with a straight-to-convex shaft on the outer side and a thicker, more concave one on the inner side. In the transplanted bent segments the bone shaft died and initially the reverse occurred: the outer shaft thickened and the inner resorbed completely. A new concave inner diaphysis then formed so that the bones in both instances were essentially similar in final shape. In the bent transplants the surviving osteogenic tissues regenerated and, adapting to the altered forces, formed a new bone shaft. This involved a change in the direction, amount, and nature of endochondral, periosteal, and regenerative growth and subsequent remodeling of bone. The results support previous observations that, within limits, the strain in the osteogenic envelope is an important factor in adaptation of bones to changing stress and that, where the envelope is deficient, the surviving tissues have the capacity to regenerate and repair defects in the bone so that it best resists the changing stresses applied to it.

Animals↗
PubMed1985

Remodelling of bone and bones: effects of altered mechanical stress on caudal vertebrae.

Sprague-Dawley rats weighing 50 g were divided into two groups: (i) control, (ii) rats with tails bent in situ incorporating 7, 5 and 3 caudal vertebrae in the loop. Tails were radiographed weekly up to six weeks and a microradiographic and histological study undertaken on selected specimens. Results showed that the bones in the apex of the loop of the bent tail moved through their investing soft tissues towards the outer side of the bend, the joints became V-shaped and in tails bent acutely the epiphyses and metaphyses tilted. By six weeks the bones appeared bent with a thinner straight to convex shaft on the outer side and a thicker, more concave one on the inner side. The changes observed can be explained by taking into account (i) strain within the bone, (ii) altered growth and (iii) the translation of bones through their investing soft tissues. The results are consistent with the supposition that, on application of a continuous moderate stress, tension induces formation and pressure resorption of bone.

Animals↗
PubMed1984

Remodelling of bone and bones: effects of translation and strain on transplants.

Tail segments, from 4-day-old Sprague-Dawley rats, consisting of caudal vertebrae (CV) approximately 7-9 were impaled on 0.23-mm diameter Elgiloy wire and transplanted subcutaneously into 50-70 g male hosts to study the effects on transplants of (a) impaling (b) strain and (c) translation. The CV were impaled onto straight lengths of wire to serve as controls (a); onto a wire curved to form a loop and exert a bending force (b) and onto the arms of a spring which moved bones through the surrounding tissues, i.e. translation (c). Tissue changes were studied up to 28 days by radiographic and histological techniques. Control bones grow relatively normally along the straight wire. The CV subjected to strain bend initially and then grow in an arc along the curve of the wire. The outer bone shaft usually becomes straighter while the inner one becomes concave and rarefied. In the translated bones remodelling occurs in a direction generally opposite to the direction of movement but this is modified by the influence of soft tissue tension and pressure. Bone resorbs on the outer leading side under continuous pressure and forms on the inner trailing side under continuous tension. The process is essentially the same as that seen in 'cortical drift'; however, since translation is rapid there is an alteration in the shape of the translated bones as formation on the trailing side is faster than resorption on the leading side.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Hepatocellular carcinoma in a patient with sarcoidosis-associated chronic active hepatitis and the MZ alpha-1-antitrypsin phenotype.

A case of primary hepatocellular carcinoma is described in a patient with long-standing sarcoidosis of the liver associated with chronic active hepatitis, and the MZ alpha-1-antitrypsin phenotype. This association appears to be unique. The respective roles of alpha-1-antitrypsin deficiency, sarcoidosis and chronic active hepatitis in the development of hepatocellular carcinoma in this case are uncertain.

Adult↗