PubMed Health⌕ Search

Biomedical subjects

A W Brown

Publications and source records attributed to A W Brown.

At least 19 recordsLinked to original sources
PubMed1992

A comparison of the acute toxicity, neuropathology, and electrophysiology of N,N-diethyl-m-toluamide and N,N-dimethyl-2,2-diphenylacetamide in rats.

The insect repellent DEET and the structurally related herbicide diphenamid both cause ataxia associated with a spongiform myelinopathy largely confined to the cerebellar roof nuclei. This local myelinopathy was accompanied by the formation of neuronal cytoplasmic clefts and was produced by a single dose of 1 to 3 g/kg N,N-diethyl-m-toluamide (DEET). These dose levels also produced a severe and often fatal prostration and clear electrophysiological signs of prolonged suppressed seizure activity. Diphenamid produced an identical myelinopathy after doses of 0.8 to 1.5 g/kg but without the severe prostration, suppressed seizures, or neuronal clefts. The effects of diphenamid were shown to be reversible over 3 to 7 days by neuropathological, motor, and auditory evoked response indices. Both compounds caused characteristic changes in auditory evoked response which may be useful in clinical diagnosis. Six other alkyl amides, two of which produce signs of CNS excitation, failed to produce myelinopathy at the maximum tolerated doses. Our findings show close parallels with a number of human cases of DEET poisoning and indicate that other amides, like diphenamid, also pose a potential hazard.

Aging↗
PubMed1992

Ubiquitin, PGP 9.5 and dense body formation in trimethyltin intoxication: differential neuronal responses to chemically induced cell damage.

Ubiquitin in normal cells may be important in degrading or transferring short-lived or aberrant proteins to lysosomal dense bodies. To examine its role in degrading proteins produced by a chemical insult, changes in the distribution of ubiquitin and the carboxy-terminal hydrolase, PGP 9.5, have been studied in rat hippocampal neurons and cerebellar Purkinje cells in trimethyltin intoxication. Here tubulovesicular dense bodies (TVBs) form from 12h onwards associated with vacuolation of the Golgi apparatus. Striking accumulations of lysosomal dense bodies follow in hippocampal pyramidal cells but not in cerebellar Purkinje cells; many of the hippocampal neurons later die, while the Purkinje cells generally survive. Ubiquitin immunoreactivity was diffusely increased in hippocampal pyramidal and Purkinje cells 6 h after dosing. By 12 h both diffuse and granular ubiquitin immunoreactivity was present that intensified over 24 and 48 h. Both by light and electron microscopy TVBs showed ubiquitin immunoreactivity, but dense bodies in hippocampal perikarya did not stain with an anti-ubiquitin antibody. PGP 9.5 immunoreactivity was not altered in hippocampal cells at any time, while Purkinje and Golgi cell dendrites and perikarya showed intensified labelling at 3 h that reached a peak of 12 h. At 48 h Western blot analysis of hippocampal homogenates showed significant increases in high molecular weight (HMW) ubiquitin conjugates, while cerebellar homogenates showed an increase in ubiquitin-histone conjugates. Northern blot analyses showed no change in ubiquitin or PGP9.5 gene expression in hippocampus or cerebellum. These findings suggest that the material in the TVBs in hippocampal cells is not being degraded by the ubiquitin system but passes ubiquitinated into the lysosomal system, while material in Purkinje cell TVBs is degraded by the ubiquitin system, suggesting it may have a different composition in each type of neuron.

Animals↗
PubMed1992

Dropout and relapse during diabetes care.

OBJECTIVE: To determine factors associated with dropout and relapse during chronic diabetes care. RESEARCH DESIGN AND METHODS: Private practice outpatient treatment-education program for adult diabetes was surveyed. Retrospective analysis was done, involving 422 patients for up to 3 yr. RESULTS: Of the patients in the study, 12% dropped out after the initial visit, and 33% of the residual cohort dropped out during each subsequent 6-mo period. Factors associated with dropout included distance from home to clinic > 100 miles, lack of insulin treatment, and cigarette smoking. In patients who remained in follow-up, a significant decrease in HbA1C occurred during the first 6 mo, but 40% of the patients relapsed between 6 and 12 mo. Frequency of relapse declined as time passed. Relapse was more frequent in women. CONCLUSIONS: Dropout from treatment and relapse after temporary improvement account for a substantial amount of uncontrolled diabetes, and overcoming the obstacles of dropout and relapse has potential for significant improvement in diabetes care.

Adolescent↗
PubMed1992

Functional/metabolic modulation of the brain stem lesions caused by 1,3-dinitrobenzene in the rat.

To determine whether neuronal activity plays a role in the localisation of brain stem lesions in 1,3-dinitrobenzene intoxication we produced asymmetrical changes in auditory input by rupturing the left tympanic membrane in Fischer rats. This raised the auditory threshold on that side from 57-63 dB to 104-122 dB. It also decreased glucose utilisation in the ipsilateral cochlear nucleus and significantly increased utilisation in the contralateral nucleus, resulting in a relative deficit of 72 +/- 6%. Similarly, tympanic membrane rupture led to decreased glucose utilisation in the contralateral and increased utilisation in the ipsilateral inferior colliculus. Additional exposure to "white noise" prevented the decrease in glucose utilisation in the contralateral inferior colliculus. Dosing with dinitrobenzene (10 mg/kg in 4 doses over 48 hr) to otherwise normal rats produces symmetrical vasculonecrotic lesions in these regions, but in animals with left tympanic membrane rupture the severity of morphological changes in the ipsilateral cochlear nucleus and the contralateral inferior colliculus were substantially reduced. Additional exposure to "white noise" increased the degree of damage in the ipsilateral cochlear nucleus and contralateral inferior colliculus. These findings indicate that altered auditory function in rats, with its associated metabolic consequences exercises a significant role in the development of brain stem damage in auditory pathways following dinitrobenzene intoxication.

Acoustic Stimulation↗
PubMed1991

Food deprivation and hypothalamic neuropeptide gene expression: effects of strain background and the diabetes mutation.

We have used a novel method to identify genes expressed in the hypothalamus which may be potentially involved in controlling food intake and energy metabolism. We assumed that food deprivation, a powerful stimulus of food intake, would stimulate the activity of neural pathways involved in feeding behavior which should be reflected in an increase in the synthesis of any relevant neuropeptide and its messenger RNA. A study of 5 neuropeptides in 5 strains of mice has identified neuropeptide Y (NPY) as a gene whose expression in the hypothalamus is controlled by nutritional status, suggesting that hypothalamic NPY neurons are a link in the neural network regulating feeding behavior and energy metabolism. In addition, we have studied the effect of the diabetes mutation on neuropeptide gene expression during fasting and refeeding. Our findings suggest that abnormal NPY and enkephalin gene expression in the hypothalamus may be two important determinants of the expression of the diabetes mutation.

Animals↗
PubMed1991

Vascular factors in the neurotoxic damage caused by 1,3-dinitrobenzene in the rat.

Using a 3 x 10 mg/kg dose schedule of 1,3-dinitrobenzene (DNB) over two days in Fischer rats, we have found the following changes in vascular function and structure during the early phase of the symmetrical brain stem lesions. 1. Marked increase in cerebral blood flow generally but especially in the inferior colliculi, from 6 h after the final dose of DNB. 2. Increasing incidence of petechial haemorrhages in inferior colliculi, cerebellar roof, vestibular and superior olivary nuclei from 12 h. 3. Focal leakage of horseradish peroxidase and many sleeve-like arteriolar haemorrhages seen in vibratome sections and by scanning electron microscopy (SEM) in these regions from 12 h. 4. Periarteriolar oedema and protein leakage present in step-serial sections in these regions from 12 h, with astrocyte swelling and occasional small infarcts. These changes suggest that the vascular bed may play an important role in the pathogenesis of these lesions, perhaps in parallel with early astroglial damage. They are discussed in relation to (i) the known presence of xanthine oxidase in the vascular bed of the brain and the likelihood of "useless redox cycling' with free radical generation from this enzyme's interaction with nitroheterocyclic compounds, and (ii) the possible role of free radical damage to endothelial cells in this intoxication and in the analogous lesions of natural and experimental Wernicke's encephalopathy.

Animals↗
PubMed1990

Regional variations in nerve cell responses to trimethyltin intoxication in Mongolian gerbils and rats; further evidence for involvement of the Golgi apparatus.

The different responses of neurons with distinctive variations in morphology and function, confirm earlier observations of the lack of uniformity in the reaction of nerve cells to trimethyltin. Thus, hippocampal pyramidal and cortical neurons in both rat and Mongolian gerbil (M. unguiculatus) show abundant lysosomal dense bodies and disorganisation of the protein-synthesising apparatus. Cerebellar Purkinje cells in gerbil, but not in rat, show striking increases in smooth membrane systems, while dense bodies are insignificant in both species; large motor-type neurons in brain stem and spinal cord in both species do not accumulate dense bodies, but their rough endoplasmic reticulum (RER) may undergo intense vacuolation with or without subsequent cell death; and by contrast, spinal ganglion cells of both species may form an excess of dense bodies and, in the gerbil, vacuolation of RER. In contrast with these varied responses to trimethyltin most neurons, large and small, in both species regularly undergo striking vacuolation of the Golgi apparatus in the earliest phase of the intoxication, a constant feature that probably reflects the site of the primary cytotoxic lesion; all other changes we consider are secondary to such damage to the Golgi apparatus, however this may come about. These observations are discussed in relation to earlier reports of the variable effects of trimethyltin and with the metabolic changes reported in trimethyltin intoxication that in general accord with these morphological conclusions.

Animals↗
PubMed1990

Disabled access to information technology--a portable adaptable, multipurpose device.

The technology exists to allow severely physically disabled people to have a far more independent lifestyle than many handicapped people enjoy today. To use an ever increasing range of sophisticated domestic equipment, without special modifications, an individually tailored control system and a universal accessing device are required. A portable multipurpose device allows multiply handicapped, non-speaking people a means of operating a variety of general-purpose or specialized pieces of electronic equipment at home and elsewhere, safely and independently. The device also provides a means of communication through the medium of computer-computer communication over telephone lines and will interface to a powered chair for independent mobility. Various features are provided which are not available from conventional environmental control systems. Through a specialized adjustable multipurpose switch system and a universal control device the handicapped person should be able to enjoy the independence afforded by the intelligent home of the future.

Activities of Daily Living↗
PubMed1990

Selective degeneration of cerebellar cortical neurons caused by cycad neurotoxin, L-beta-methylaminoalanine (L-BMAA), in rats.

Both the racemate and the L-form of BMAA (beta-methylaminoalanine), when injected intraperitoneally into young rats, produced acute signs of cerebellar dysfunction and degeneration of cerebellar stellate, basket, Purkinje and Golgi cells, but not granule cells. Degenerative changes were also occasionally seen in cerebellar roof nuclei which may be secondary in nature. No other changes were found in the remainder of the central nervous system. The doses of the L-form of BMAA producing these changes were from 6 to 14 mumols/g body weight, i.e. the lower and upper levels of the dose range used by Vega and Bell (1967) and equivalent to 75 and 183 mg/rat. Doses of 1 to 4 mg/g body weight of the racemate were given to young rats less than 100 g in weight, but no changes were apparent after daily doses of the racemate of 0.5 mg/g body weight. Damage to cerebellar neurons is considered to be the result of excitotoxic activity. All cells showing degeneration are GABAergic, although not all are known to possess N-methyl-D-aspartate (NMDA) receptors. The present finding of selective cerebellar neuron damage may not conflict with the earlier findings of others, but our results suggest that L-BMAA has unusual glutamate receptor binding properties.

Amino Acids, Diamino↗
PubMed1990

Glial cell intrusions actively remove detritus due to toxic chemicals from within nerve cells.

It has been observed that when neurons are acutely damaged by toxic chemicals leading to accumulations of effete materials, glial supporting cells insert cytoplasmic processes into neuronal cytoplasm and appear to transfer this material into themselves. Essentially the same phenomenon has now been seen in several situations, namely in peripheral nerve axons in a number of experimental peripheral nerve intoxications, especially in spinal roots, as well as occasionally in normal axons in paranodal regions and more frequently above a nerve ligation. It has been seen, too, in cerebellar Purkinje cells after acrylamide intoxication and in hippocampal pyramidal neurons and in neurons of the pyriform cortex after triethyllead and trimethyltin intoxications. A similar process may also be taking place regularly both in normal and chemically damaged spinal ganglion cells through their satellite cell sheath. While probing of neurons by glia has also been noted normally in pre-synaptic regions of mammalian neurons as well as in the perikarya of certain goldfish neurons, the purpose for this is less apparent. Such findings in relation to removal of bulk residual material from neurons raise intriguing questions as to the signals required between cells to enable such evidently cooperative intercellular events to take place, and whether this process, that is apparently so inefficient in removing lipofuscin pigment from ageing neurons, may not, perhaps, be adversely influenced by environmental agents.

Animals↗
PubMed1990

Normal reticulin level in iliac bone marrow.

While the level of marrow reticulin may be a factor that is used when the presence of a hematologic disorder is being considered, to our knowledge no study has graded the amount of reticulin present in normal iliac bone marrow. Grading reticulin stains of bone biopsy specimens from 100 hematologically normal patients documented that the normal amount of reticulin in the marrow is low. Twenty-seven percent of the patients had marrow reticulin grade 0 using the Bauermeister scale, 42% had grade N, 27% had grade 1, and 4% had grade 2; no patient had a Bauermeister grade 3 or 4 reticulin level. Knowledge of the normal range of reticulin is essential when the reticulin level is used as a factor in evaluating the possibility of a hematologic disorder.

Adolescent↗
PubMed1990

Neurochemical changes in hippocampal and caudate dialysates associated with early trimethyltin neurotoxicity in rats.

Following a control period of dialysis of the hippocampus (Hc) or caudate (Cd) of conscious freely-moving rats, a single dose of trimethyltin chloride (TMT, 10 mg/kg) was administered by gavage and dialysis continued for up to 51 hr after dosing. During this time dialysate levels of amino acids, catechols and indoles were continually monitored, GABA A and B and glutamate (Glu) binding was measured at 48 hr, and histological damage was assessed at 24, 48 and 72 hr after dosing. The earliest change to occur was a significant 2-fold increase at 24 hr in Hc and Cd dialysate levels of glutamine (Gln), followed at 48 hr by an almost 4-fold increase in Gln and increases also in Glu, GABA and threonine levels. 5-Hydroxyindoleacetic acid (5-HIAA) levels were also increased in Cd dialysates 24 and 48 hr after dosing. The initial increase in Gln occurred at a time (24 hr) when there was no necrosis, only mild cytoplasmic changes in the CA3b region of the Hc and none in the Cd. By 72 hr cytoplasmic and necrotic changes were well established in both Hc and Cd. GABA A binding was significantly decreased in both Hc and Cd 48 hr after dosing, while Glu binding was unchanged. The results suggest that one component of TMT-induced neurotoxicity may be a consequence of increased extracellular levels of the excitotoxic amino acid, glutamate.

Amino Acids↗
PubMed1987

The relationship between uncoupling of oxidative phosphorylation and neuronal necrosis within the CNS in rats dosed with trihalogenated imidazoles.

The trihalogenated imidazoles, trichloroimidazole (TCI), tribromoimidazole (TBI), and triiodoimidazole (TII), are in vitro uncouplers of oxidative phosphorylation with similar activities. Although TCI and TBI are also uncouplers in vivo, some doubt exists for TII, which is much less toxic and produces atypical signs of poisoning. Dibromo- and monobromoimidazole do not uncouple oxidative phosphorylation either in vitro or in vivo. Dosing of TCI and TBI to rats resulted within 24-48 hr in neuronal necrosis within the CNS involving the vestibular nucleus, red nucleus, and outer parietal neocortex and ataxia of the hindlimbs. However, no neuronal necrosis or ataxia was observed after dosing of TII to rats, even when given at doses four times greater than for either TCI or TBI, resulting in much higher brain concentrations. Although TBI was equitoxic to rats, mice, hamsters, and gerbils, CNS damage and ataxia were observed only in the rat, even though comparable brain concentrations of TBI were found in the gerbil. Measurement of the concentration of TBI in the dissected rat brain gave no indication of localized concentrations of compound in the areas associated with neuronal damage. Doses of TBI and the classical uncoupler 3,5-dinitro-o-cresol (DNOC), matched for whole body O2 consumption, caused comparable changes in rat brain blood flow although DNOC does not cause brain damage. Changes in blood flow were not restricted to those brain areas susceptible to damage. Thus, although we were unable to completely dissociate CNS damage from uncoupling of oxidative phosphorylation produced by TBI and TCI in the rat, it is unlikely that such damage is primarily related to the uncoupling ability of these compounds.

Animals↗
PubMed1986

Insecticide resistance in mosquitoes: a pragmatic review.

Descriptions of the World Health Organization standard methods of assessing susceptibility or resistance in larval and in adult mosquitoes are presented, and the evaluation of their results are discussed. Other susceptibility test methods are also mentioned, including those based on esterase zymograms. Recent work on the biochemical mechanisms of resistance and cross-resistance are reviewed, along with possible countermeasures for the problem of mosquito resistance, now known in 113 species of culicines and anophelines.

Animals↗
PubMed1985

The comparative toxicology of ethyl- and methylmercury.

Neurotoxicity and renotoxicity were compared in rats given by gastric gavage five daily doses of 8.0 mg Hg/kg methyl- or ethylmercuric chloride or 9.6 mg Hg/kg ethylmercuric chloride. Three or 10 days after the last treatment day rats treated with either 8.0 or 9.6 mg Hg/kg ethylmercury had higher total or organic mercury concentrations in blood and lower concentrations in kidneys and brain than methylmercury-treated rats. In each of these tissues the inorganic mercury concentration was higher after ethyl- than after methylmercury. Weight loss relative to the expected body weight and renal damage was higher in ethylmercury-treated rats than in rats given equimolar doses of methylmercury. These effects became more severe when the dose of ethylmercury was increased by 20%. Thus in renotoxicity the renal concentration of inorganic mercury seems to be more important than the concentration of organic or total mercury. In methylmercury-treated rats damage and inorganic mercury deposits were restricted to the P2 region of the proximal tubules, while in ethylmercury-treated rats the distribution of mercury and damage was more widespread. There was little difference in the neurotoxicities of methylmercury and ethylmercury when effects on the dorsal root ganglia or coordination disorders were compared. Based on both criteria, an equimolar dose of ethylmercury was less neurotoxic than methylmercury, but a 20% increase in the dose of ethylmercury was enough to raise the sum of coordination disorder scores slightly and ganglion damage significantly above those in methylmercury-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Selective chromatolysis of neurons in the gerbil brain: a possible consequence of "epileptic" activity produced by common carotid artery occlusion.

Unilateral (50 to 118 minutes) and bilateral (2 to 33 minutes) carotid artery occlusion in gerbils resulted in two distinct types of neuronal alteration: ischemic cell change (ICC) in selectively vulnerable brain regions, and selective chromatolysis (SC) confined to the deeper layers of the cortex, the Sommer sector of zone h-1, and the paramedian region (PM) of the hippocampus. In typical SC the nucleus was eccentric and the Nissl substance was lost in the central eosinophilic cytoplasm. In electron micrographs this area of cytoplasm showed disruption of smooth and rough endoplasmic reticulum with disaggregation of polyribosomes and accumulation of mitochrondria and various dense bodies. SC was identified at 2 to 3 hours and was still recognizable at five days. When bilateral carotid artery occlusion lasted 5 to 6 minutes, SC was seen in the hippocampal Sommer sector and cerebral cortex, while ICC was restricted to the endfolium (h3-5). Unlike ICC, the frequency of SC was not related to the duration of ischemia but probably to the epileptic seizures (overt and subclinical) initiated by ischemia in the gerbil. These changes must be considered when the gerbil is employed as a model of experimental stroke.

Animals↗