Search PubMed⌕ 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↗
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↗
PubMed1979

An audiovisual teaching model of the muscle spindle.

Students in biology and medicine often have difficulty in visualizing the structure, function and disease of complex integrated body systems. One example in neurophysiology is the muscle spindle and Golgi tendon organ. A model is described which demonstrates the properties of these two muscle receptors. The model combines mechanical elements, which can change their length to represent muscle contraction, with an electronic representation of the passage of action potentials along 'nerves', indicated by light-emitting diodes and loudspeakers. The model has been in use for some years as a supplement to conventional teaching methods. In a recent questionnaire about the model, a group of medical students responded favourably. We suggest that models such as this are valuable teaching aids.

Audiovisual Aids↗
PubMed1979

The behavioral and neuropathologic sequelae of intoxication by trimethyltin compounds in the rat.

Trimethyltin, when given by gavage to rats, has an LD50 of 12.6 mg/kg. Signs of poisoning include tremors, hyperexcitability, aggressive behavior, weight loss, and convulsions. After single (10 mg/kg) or repeated weekly doses (a maximum of four) of 4 mg/kg, rats, up to a survival time of 70 days, were perfusion-fixed for light microscopy. Trimethyltin was assayed in brain and blood in rats after similar treatments. Trimethyltin is cumulative and persistent and binds with high affinity to hemoglobin. Trimethyltin, unlike triethyltin, does not produce white matter edema in rats but does cause bilateral and symmetrical neuronal alterations involving the hippocampus (largely sparing the Sommer sector), pyriform cortex, amygdaloid nucleus, and neocortex. The earliest alteration was loss or dispersal of Nissl substance, then clumping of nuclear chromatin, followed by shrinkage and fragmentation of the nucleus within shrunken eosinophilic cytoplasm. These changes were associated with approximately 1.4 microgram trimethyltin/g wet weight in brain tissue 1 day after the second dose of 4 mg/kg or 2 days after a single dose of 10 mg/kg. Signs of poisoning gradually disappeared, and 4 rats surviving 70 days appeared normal, although their brains had severe damage with cell loss in the hippocampi and each pyriform cortex. Treatment of rats with trimethyltin, therefore, provides a chronic preparation with consistent lesions in the hippocampus of use in other behavioral and neuroanatomic studies. (Am J Pathol 97:59--82, 1979).

Animals↗
PubMed1978

Profound hypoxia in Papio anubis and Macaca mulatta--physiological and neuropathological effects. I. Abrupt exposure following normoxia. II. Abrupt exposure following moderate hypoxia.

Lightly anaesthetized and spontaneously breathing P. anubis (PA) and M. mulatta (MM) inhaled at ambient pressure 3.2% oxygen (identical to 37,500 ft or 11,430 m) from air and also after pre-exposure to 14% oxygen (identical to 10,000 ft or 3,048 m). The EEG, ECG, respiratory rate, arterial and cerebral venous sinus pressures, end-tidal pO2 and pCO2 and body temperature were recorded. Arterial and cerebral venous sinus blood gases, pH and pyruvate and lactate contents were estimated. Before hypoxia, MM showed a relative hyperventilation. Profound hypoxia, from air, ended with the "last breath" at 89--205 sec in PA and at 93--570 sec in MM. Brain damage was restricted to one MM (4 exposures). Profound hypoxia after exposure to 14% oxygen ended with the "last breath" at 87--210 sec in PA and at 120 sec--94 min (including 9 exposures over 5 min) in MM. Brain damage was restricted to one MM ("last breath" at 94 min). In the two MM with brain damage there was evidence of reduction in cerebral perfusion near the end of profound hypoxia. Brain damage in one animal contrasts with the frequent and often severe brain damage in MM after equivalent sub-atmospheric decompressions preceded by exposure to moderate altitude (10,000 ft).

Animals↗