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Biomedical subjects

A G Brown

Publications and source records attributed to A G Brown.

At least 19 recordsLinked to original sources
PubMed1992

Direct observations of synapses between L-glutamate-immunoreactive boutons and identified spinocervical tract neurones in the spinal cord of the cat.

Four spinocervical tract cells in lumbosacral spinal cords of adult cats were physiologically characterized and intracellularly labelled with horseradish peroxidase. The neurones were examined with a light microscope and reconstructed. Selected regions were chosen for ultrastructural analysis. Thin sections were treated to reveal the presence of L-glutamate by using the postembedding immunogold method. Two antisera, which specifically recognise the presence of fixed glutamate in tissue, were used in the study. Somata, proximal, and distal dendrites of all four neurones received synaptic contacts from boutons which displayed an obvious immunogold reaction. These boutons formed between 35% and 48% of all synaptic contacts onto spinocervical tract cells. Glutamate-enriched boutons were associated with gold particle densities which were 2-3 times greater than the average densities associated with the surrounding neuropil. Their profiles had a mean diameter of 1.68 microns, contained round agranular synaptic vesicles, and formed asymmetrical synaptic junctions. However, not all boutons displaying these characteristics were enriched with glutamate. Immunogold studies of alternate thin sections, which were incubated with glutamate or GABA antiserum, demonstrated that synaptic boutons on spinocervical tract cells were either enriched with GABA or with glutamate and formed two separate populations which had distinct morphological characteristics. GABA-containing boutons contained irregularly shaped agranular vesicles and formed symmetrical synaptic junctions, whereas glutamate-enriched boutons corresponded to those described above. A further population of boutons, containing highly flattened vesicles, was not immunoreactive for GABA or glutamate. The evidence supports the idea that much of the excitatory transmission into the SCT is mediated by L-glutamate.

Animals↗
PubMed1992

The upgraded Finapres 2300e. A clinical evaluation of a continuous noninvasive blood pressure monitor.

Measurements from the upgraded Finapres 2300e continuous noninvasive blood pressure monitor, the Finapres 2300 and Colin oscillometric noninvasive blood pressure monitor were compared with invasive arterial line blood pressure readings. Fifteen young Chinese patients undergoing elective spinal surgery of more than 2 h duration had contemporaneous blood pressure measurements digitally recorded every minute. Data were analysed using methods described by Bland and Altman to assess agreement of noninvasive devices with an arterial line. Results showed that although the Finapres 2300e was significantly more accurate than the Finapres 2300 and Colin noninvasive blood pressure monitors it could not be recommended as a substitute for continuous arterial line blood pressure monitoring. Both Finapres devices demonstrated reductions in accuracy related to time (drift) and over-read diastolic and mean pressures by 5-8 mmHg throughout the range of mean arterial line pressures (bias). The Colin was consistently less accurate than the Finapress monitors and performed worst at low mean arterial line pressures.

Adolescent↗
PubMed1992

An evaluation of prolonged oximetric data acquisition.

Data derived from pulse oximetry has inherent limitations, one of which is artifactual desaturation caused by patient movement. Perioperative patterns of oxygen desaturation were studied for a mean duration of 67 hours in eight young patients following corrective spinal surgery. Pulse oximetry data were relayed to a computer using Satmaster, a program which permits storage, retrieval, signal evaluation and statistical analysis of oximetry data. Desaturation episodes were mild, of short duration and their infrequent occurrence was not increased during intravenous morphine infusion. Retrospective identification of contemporaneous artifactual changes in signal amplitude permitted the removal of artifactual desaturations from our statistical data analysis. This decreased the average time desaturated from 5.4% (220 minutes) to 4.2% (162 minutes) of the monitored period representing a 25% reduction in absolute incidence and a 35% reduction in episodic incidence of desaturation. Acquired data should be validated and inferences drawn from non-validated data must be assessed with caution.

Adolescent↗
PubMed1991

Relationships between hair-follicle afferent axons and glycine-immunoreactive profiles in cat spinal dorsal horn.

In order to identify synapses between hair-follicle afferent axons and glycine-containing structures in cat spinal cord, semithin sections containing physiologically identified primary afferent boutons which had been filled with horseradish peroxidase (HRP) were reacted with anti-glycine antiserum, while adjacent ultrathin sections were examined for synaptic contacts. Four axodendritic synapses between hair-follicle afferent boutons and glycine-immunoreactive dendrites and 4 axoaxonic synapses in which HRP-filled boutons were postsynaptic to immunoreactive axons were identified. These results suggest that glycine is involved in the spinal processing of input from A beta hair-follicle afferent axons.

Animals↗
PubMed1991

Direct observations of synapses between GABA-immunoreactive boutons and identified spinocervical tract neurons in the cat's spinal cord.

Three spinocervical tract neurons in adult cats were physiologically characterized and intracellularly labelled with horseradish peroxidase. The neurons were reconstructed and examined with the light microscope and were prepared for postembedding immunochemical analysis by using an antiserum which specifically recognizes GABA in glutaraldehyde-fixed tissue. Semithin sections were tested and examined with the light microscope. Somata, proximal, and distal dendrites of all three cells were associated with numerous punctate GABA-immunoreactive structures. Immunoreactive perikarya of small neurons in the vicinity of spinocervical tract cells were also observed. Ultrastructural analysis, with the immunogold technique, revealed that somata and proximal dendrites of all three neurons received synaptic contacts (about 37% of total synapses) from GABA-immunoreactive boutons and that distal dendrites were also associated with substantial numbers of immunoreactive structures (about 27% of synapses). Immunoreactive boutons were small (about 1 micron in diameter), contained irregularly shaped agranular vesicles, and formed symmetrical synaptic junctions with identified neurons. An additional group of immunoreactive boutons was observed to be associated with one of the cells only; these contained many large dense-core vesicles in addition to small agranular vesicles. Boutons containing round agranular vesicles and flattened agranular vesicles were not observed to be immunoreactive. The evidence supports the idea that much of the postsynaptic inhibition observed in spinocervical tract neurons is mediated by GABA and that even the most distal dendrites of these neurons receive inhibitory inputs.

Animals↗
PubMed1991

Responses of the L5178Y mouse lymphoma forward mutation assay: V. Gases and vapors.

A new protocol for testing vapors and gases in the L5178Y mouse lymphoma assay is presented. Four chemicals, propylene, 1,2-propylene oxide, 1,3-butadiene, and vinylidene chloride, were tested for their mutagenic potential. Cultures were exposed to the chemicals, which were delivered as vapors or gases, for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 microgram/ml. Each chemical was tested at least twice. Significant responses were obtained with 1,2-propylene oxide and vinylidene chloride, but neither cytotoxicity nor mutagenicity was induced by 1,3-butadiene; propylene could not be classified as either mutagenic or non-mutagenic in the assay. Rat liver S9 mix was not a requirement for the mutagenic activity of 1,2-propylene oxide, whereas the liver preparation markedly enhanced both the cytotoxicity and mutagenicity of vinylidene chloride.

Air Pollutants↗
PubMed1991

Responses of the L5178Y mouse Lymphoma cell forward mutation assay. V: 27 coded chemicals.

Twenty-seven chemicals were tested for their mutagenic potential in the L5178Y tk+/tk- mouse lymphoma cell forward mutation assay using procedures based upon those described by McGregor et al. (McGregor DB, Martin R, Cattanach P, Edwards I, McBride D, Caspary WJ (1987): Environ Mol Mutagen 9:143-160). Cultures were exposed to the chemicals for 4 hr, then cultured for 2 days before plating in soft agar with or without trifluorothymidine (TFT), 3 micrograms/ml. The chemicals were tested at least twice. Statistically significant responses were obtained with acid orange 10, aniline, benzaldehyde, o-chloroaniline, chlorodibromomethane, cytembena, 1,2-dibromo-4-(1,2-dibromomethyl) cyclohexane, dieldrin, lithocholic acid, oxytetracycline, phenazopyridine HCl, 1-phenyl-3-methyl-5-pyrazolone, sodium diethyldithiocarbamate, solvent yellow 14, tetraethylthiuram disulfide (disulfiram), 2,4-toluene diisocyanate, and 2,6-toluene diisocyanate. Apart from phenazopyridine HCl, acid orange 10, and solvent yellow 14, rat liver S9 mix was not a requirement for the mutagenic activity of these compounds. Chemical not identified as mutagens were N-4-acetylaminofluorene, chlorpheniramine maleate, chloropropamide, 1,4-dioxane, endrin, ethylene glycol, iron dextran, methapyrilene, sodium(2-ethylhexyl)alcohol

Animals↗
PubMed1990

Direct observations of synapses between GABA-immunoreactive boutons and muscle afferent terminals in lamina VI of the cat's spinal cord.

Single group Ia muscle afferent fibres in the lumbar spinal cord of the cat were impaled with microelectrodes and labelled with horseradish peroxidase. Two collateral axons were prepared for combined light and electron microscopy. Arbors selected from lamina VI were processed by the postembedding immunogold technique with antiserum which specifically recognizes GABA in glutaraldehyde-fixed tissue. Twelve Ia boutons were examined through series of thin sections with the electron microscope and all of them were associated with presynaptic axon terminals which were positively labelled for GABA. Some Ia boutons received synaptic contacts from several GABAergic terminals. The present study establishes that a GABA-like substance is present in axon terminals presynaptic to Ia afferent boutons in lamina VI of the spinal cord. This evidence provides a morphological basis for presynaptic inhibition of Ia afferent input into lamina VI.

Animals↗
PubMed1990

L5178Y mouse lymphoma cell mutation assay results with 41 compounds.

Forty-one chemicals were tested for their abilities to induce trifluorothymidine resistance in L5178Y mouse lymphoma (MOLY) cells. These chemicals were included in the National Toxicology Program's evaluation of four in vitro short-term toxicity assays for predicting carcinogenicity in the rodent bioassay. Of the 41 chemicals examined for this report, 8 were equivocal in the rodent bioassay, and 7 were questionable in- the MOLY assay. If these chemicals are eliminated from an analysis of concordance, the remaining 26 chemicals lead to a concordance of 69% with a sensitivity of 71%. The specificity could not be determined because only two non-carcinogens were detected.

Animals↗
PubMed1990

Afferent inhibition and facilitation of transmission through the spinocervical tract in the anaesthetized cat.

1. Extracellular microelectrode recordings were made from single spinocervical tract (SCT) neurones in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralysed with gallamine triethiodide. 2. Pairs of air-jet stimuli, 60 ms in duration, were used to investigate in-field afferent inhibition in SCT cells. One jet was used to condition the responses to another jet located at a different position within the excitatory receptive field and occurring at times from 100 to 1800 ms later. Fifteen neurones were tested and significant in-field inhibition was observed in all of them. 3. The in-field afferent inhibition was organized spatially in the sense that inhibition was generally strongest when conditioning and testing stimuli were close together and became weaker as they were moved apart. There was also a weak effect due to the strength of the conditioning response; when conditioning produced a strong response, from near the most excitable part of the receptive field, there was often a weak reduction in the test response from distant sites. The inhibitory areas defined in these experiments were generally less than 100 mm in length in units with excitatory receptive fields much longer than this. 4. The in-field afferent inhibition had a time course that lasted from 300 to about 1000 ms. 5. Afferent inhibition was also evoked by applying either air-jet stimuli to hairy skin outside, but close to, the excitatory receptive field or by applying a vibratory stimulus from a piezoelectric transducer (200 Hz) to glabrous skin of the toe pads or the central foot pad. These conditioning stimuli had durations of 20 or 60 ms. For convenience we call this inhibition 'out-of-field' afferent inhibition. 6. Out-of-field afferent inhibition was evoked from both glabrous and hairy skin areas outside the excitatory receptive field. It was common in neurones with receptive fields on the toes and of twenty-eight such neurones tested it was observed in twenty-four. This inhibition had a short latency (usually about 10 ms or less but occasionally up to 30 ms) and lasted for about the duration of the test stimulus (30 or 80 ms when the test stimulus was 20 or 60 ms respectively). It was often followed by a further period of inhibition, with a latency of between 50 and 100 ms and lasting for 60 up to 130 ms. 7. In thirteen SCT neurones more complex effects were seen.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1989

TFT and 6TG resistance of mouse lymphoma cells to analogs of azacytidine.

5-Azacytidine (5-aza-CR) and six of its analogs were examined for their ability to induce trifluorothymidine (TFT) and/or 6-thioguanine (6TG) resistance in L5178Y mouse lymphoma cells. These analogs were 5-aza-2'-deoxycytidine (5-aza-CdR), 5-fluoro-2'-deoxycytidine (5-FCdR), 5,6-dihydro-5-azacytidine (dH-aza-CR), 6-azacytidine (6-aza-CR), cytidine (CR) and 1-b-D-arabinofuranosylcytosine (ara-C). 5-Aza-CR and 6-aza-CR were examined for their ability to induce 6TG-resistant colonies and results demonstrated no effect. At least a 5-fold increase in TFT resistance was observed for 5-aza-CR, 5-aza-CdR, 5-FCdR, dH-aza-CR and ara-C. The concentration at which these compounds induced TFT resistance correlated well with the potential of the nucleoside analogs to induce differentiation in C3H10T1/2 cells as determined by Constantinides et al. (Nature, 267, 364-366, 1977). In L5178Y mouse lymphoma (MOLY) cells, 5-aza-CR induced TFT resistance and produced both small and large colonies. Previous studies using mammalian cells showed the absence of mutagenic activity with 5-aza-CR and some of its analogs at the ATPase and hgprt loci. However, the different spectrum of DNA lesions detected at the tk locus may be responsible for the response of MOLY cells to 5-aza-CR.

Animals↗
PubMed1989

Receptive fields and in-field afferent inhibition of neurones in the cat's lateral cervical nucleus.

1. Extracellular microelectrode recordings were made from projection neurones of the lateral cervical nucleus (LCN) in cats anaesthetized with chloralose and paralysed with gallamine triethiodide. 2. The receptive fields of eight-five units were analysed. Most units had excitatory receptive fields similar in size and shape to those of spinocervical tract (SCT) cells. A few (14%) had either very large fields or 'stocking-like' fields. The majority of the LCN neurones (fifty-five, 65%) were excited by hair movement and, in addition, by noxious mechanical stimulation within the skin area responding to hair movement. Twenty-five units (29%) were excited by hair movement alone. For seven of these twenty-five neurones, noxious mechanical stimulation within the excitatory receptive field produced inhibition of the background discharge. One unit was excited by noxious mechanical stimulation and for the remaining four units no receptive field could be found. In six units inhibitory receptive fields outside the excitatory field were found. 3. Air-jet stimuli were used to define the excitatory profiles of the units' receptive fields to hair movement. In general, receptive fields had single regions of greatest sensitivity usually at or near the centre of the field, where that was oval in shape, with the sensitivity declining towards the field's circumference. In some units with very large fields that included parts of one or two limbs and the trunk there could be more than one highly sensitive region. 4. Pairs of air-jet stimuli were used to investigate in-field afferent inhibition in LCN cells. One jet was used to condition the responses to another jet located at a different position within the excitatory receptive field and occurring 200 ms later. Sixteen units were tested and significant in-field inhibition was observed in all sixteen. 5. The in-field afferent inhibition was organized spatially in the sense that inhibition was generally strongest when the conditioning and testing stimuli were close together and became weaker as they were moved apart. The afferent inhibition was not simply a function of the response produced by the conditioning stimulus. Furthermore, increasing the strength of the stimuli did not in general lead to larger areas from which the inhibition could be produced. The inhibitory areas defined in these experiments were generally less than 120 mm in length in units with receptive fields much longer than 100 mm.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1988

MM 42842, a new member of the monobactam family produced by Pseudomonas cocovenenans. I. Identification of the producing organism.

A bacterial soil isolate designated 326-32B produces a new member of the monobactam series of antibiotics, MM 42842, and the bulgecins. Identification studies show isolate 326-32B to be a strain of Pseudomonas cocoveneans which is a species previously noted for the production of toxoflavin. A description of P. cocovenenans does not appear to have been previously published and the identify of strain 326-32B was established by means of a direct comparison with the deposited organism P. cocovenenans NCIB 9450. The properties of strain 326-32B, and P. cocovenenans NCIB 9450 were compared with those of the monobactam and bulgecin producing organisms Pseudomonas acidophila ATCC 31363 and Pseudomonas mesoacidophila ATCC 31433. The four organisms were found to share certain properties, including the ability to grow at pH 4.0.

Monobactams↗
PubMed1987

Fine structure of synapses associated with characterized postsynaptic dorsal column neurons in the cat.

Fourteen dorsal horn neurons with axons projecting through the dorsal columns were identified either by electrophysiological methods (and subsequently injected with horseradish peroxidase) or by retrograde labelling with horseradish peroxidase in cats. All neurons were contacted by small (less than 2 micron) boutons containing spherical or elongated agranular vesicles. One neuron with its soma located in lamina III received additional contacts from central elements of glomerular complexes. Neurons with somata located more ventrally (deep lamina IV and V) were also postsynaptic to large (greater than 2 microns) electron lucent profiles which formed multiple synapses with the labelled cells. Some boutons presynaptic to postsynaptic dorsal column neurons were themselves postsynaptic to profiles containing pleiomorphic agranular vesicles at axoaxonic synapses. They also occasionally participated in triadic complexes. It is concluded that the synaptic arrangements formed by boutons in association with postsynaptic dorsal column neurons differ significantly from those associated with spinocervical neurons. Such differences might provide the anatomical substrate for the observed receptive field characteristics of these neurons.

Animals↗
PubMed1987

Excitatory actions of single impulses in single hair follicle afferent fibres on spinocervical tract neurones in the cat.

1. In cats under chloralose anaesthesia single dorsal root ganglion cells with axons innervating hair follicles were stimulated intracellularly to produce single impulses. At the same time single spinocervical tract (s.c.t.) neurones were recorded extracellularly, from their axons in the upper lumbar cord. 2. When the receptive field of the afferent fibre was contained within the impulse firing zone of the s.c.t. cell, a single afferent impulse increased the probability of firing of the neurone. In thirty-nine pairs of units, where the afferent fibre had a group II conduction velocity, coupling was very efficient and for seventeen pairs the single afferent impulse produced one or more impulses in the s.c.t. cell in at least 90% of trials. The mean number of impulses evoked in s.c.t. cells by a single group II afferent impulse was 1.47. The latencies of the impulses ranged from 1.5 to 14.0 ms, with times to peak and total durations of 2.5-17.5 ms and 4.5-28.0 ms respectively. For two pairs of units where the afferent fibre had a group III conduction velocity the effectiveness of single afferent impulses was much less and the latencies, but not the durations, of the impulses were longer (12 and 17 ms). 3. When the receptive field of the hair follicle afferent fibre was outside, but close to, the firing zone of the s.c.t. neurone there was no indication that single afferent impulses affected the probability of neuronal discharge for thirteen of fifteen pairs of units. Weak excitation was observed in two pairs and this was clear only when two or more afferent impulses were employed. 4. There was a tendency for hair follicle afferent fibres with their receptive fields at or near the centre of the s.c.t. cell's firing zone to be most effective, producing shorter latency responses with more impulses at higher frequencies. When the afferent's field was peripherally located in the s.c.t. neurone's firing zone there was a wide range of responses but these included those with the longest latencies and very few impulses. 5. The results are discussed with reference to previous work on the spinocervical tract and to the known actions of single impulses on other neuronal types. Suggestions are made for the possible excitatory neuronal circuits linking hair follicle afferent fibres to the s.c.t. neurones.

Action Potentials↗
PubMed1987

Actions of trains and pairs of impulses from single primary afferent fibres on single spinocervical tract cells in cat.

1. In cats under chloralose anaesthesia single lumbosacral dorsal root ganglion cells of hair follicle afferent fibres were stimulated intracellularly to produce trains or pairs of impulses. At the same time, single spinocervical tract (s.c.t.) neurones were recorded extracellularly, from their axons in the upper lumbar spinal cord. Afferent fibre-neurone pairs were chosen in which the receptive field of the fibre was contained within the excitatory receptive field (firing zone) of the neurone. 2. Trains of impulses of 2.0 Hz were less effective in increasing the probability of s.c.t. cell firing than trains at 0.67 Hz, and this latter rate was usually less effective than trains at 0.33 Hz. 3. Successive responses to individual members of a train of hair follicle afferent impulses were variable. In some pairs of units succeeding responses declined until a fairly consistent plateau was reached. In others there was no decline and the responses remained irregular. 4. Pairs or short trains of impulses revealed two phenomena: over the first 5 ms or so following an impulse in a group II hair follicle afferent fibre, a second or small group of impulses produced a greater response from the s.c.t. neurone but at intervals of 25-200 ms there was a profound depression of the responses evoked by the second member of a pair of impulses. For A delta afferent fibres the early facilitation lasted for at least 25 ms. 5. It is concluded that a single impulse in a single hair follicle afferent fibre from within the excitatory receptive field of a s.c.t. neurone has complex actions on transmission through that neurone. An initial excitatory influence is followed by a long-lasting depression that influences transmission through the system for at least 1500 ms. Possible mechanisms underlying this depression are discussed.

Action Potentials↗