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J R Cunningham

Publications and source records attributed to J R Cunningham.

At least 37 records · Page 2Linked to original sources
PubMed1987

Role of fluorescein glucuronide and its metabolism in vitreous fluorophotometry.

Rabbits were given fluorescein or fluorescein glucuronide intravenously. Fluorescein and fluorescein glucuronide concentrations in plasma and vitreous samples were measured by high-performance liquid chromatography. Vitreous fluorophotometry was performed using the Fluorotron Master to compare scans after administration of fluorescein and fluorescein glucuronide, and for comparison of in vivo fluorescence with in vitro high-performance liquid chromatography analysis. Fluorescein glucuronide was shown to enter the vitreous as early as 1 hr after injection. Fluorescein glucuronide was the dominant molecule in both vitreous and plasma of all rabbits at 6 hr. Because fluorescein glucuronide has a lower fluorescence than fluorescein, the fluorophotometer overestimates the vitreous concentration of fluorescein after its administration. Since fluorescein is metabolized rapidly to fluorescein glucuronide in man, entry of fluorescein glucuronide into the eye should be considered in measurements of blood-ocular barrier permeability by vitreous fluorophotometry.

Animals↗
PubMed1985

Effect of excitatory amino acids on gamma-aminobutyric acid release from frog horizontal cells.

The effects of excitatory amino acids, analogues and K on [3H]gamma-aminobutyric acid [3H]GABA) release from horizontal cells of the isolated superfused frog retina were studied. Exposure of the retina to medium containing high concentrations (25-100 mM) of KCl increased the release of [3H]GABA to a maximum which was 40 times the spontaneous resting release. The K-evoked release of [3H]GABA was almost abolished in high-Mg/low-Ca medium. Glutamate, aspartate, kainate and quisqualate also stimulated the release of [3H]GABA from horizontal cells, the maximum evoked release being similar to that produced by KCl. The release of [3H]GABA evoked by glutamate, aspartate, kainate and quisqualate was abolished in high-Mg/low-Ca medium and by Na-free medium. The evoked releases of [3H]GABA were not reduced by tetrodotoxin. N-Methyl-D-aspartate (NMDA) at concentrations up to 10 mM had virtually no effect on [3H]GABA release from horizontal cells. In Mg-free medium, NMDA stimulated [3H]GABA release, but the maximum release was only 10% of that produced by other agonists. Mg-free medium did not significantly affect the evoked release of [3H]GABA by other agonists. NMDA apparently possessed affinity for the kainate receptor, because in normal medium it antagonized the effects of kainate but not glutamate, aspartate or quisqualate. The non-selective antagonist of excitatory amino acids, (+/-)-cis-2,3-piperidine dicarboxylic acid (PDA) antagonized the action of glutamate, aspartate, kainate and quisqualate on horizontal cell [3H]GABA release. D(-)-2-Amino-4-phosphonobutyrate (APB) and D-gamma-glutamylglycine (D-gamma-GG) antagonized the actions of kainate on horizontal cell [3H]GABA release at concentrations which had little affect on quisqualate-evoked responses. Approximate estimates of pA2 values (Schild, 1947) showed that the specificity and potency of the antagonists was low. Nevertheless, the retinal 'non-NMDA' receptors can probably be subdivided into kainate and quisqualate types. Glutamate diethylester (GDEE) did not affect the action of any agonist. We conclude that glutamate (and aspartate) probably stimulate the release of [3H]GABA from frog horizontal cells by activating receptors of the non-NMDA type. This activation may trigger the opening of tetrodotoxin-insensitive Na channels, resulting in the depolarization of the cell membrane and an increase in the conductance of voltage-sensitive Ca-channels. An influx of Ca ions would then trigger the release of [3H]GABA. Our results are not consistent with previous suggestions that GABA release from horizontal cells involves an outwardly directed transport process.

Amino Acids↗
PubMed1985

Effect of excitatory amino acids and analogues on [3H]acetylcholine release from amacrine cells of the rabbit retina.

The pharmacology of cholinergic amacrine cells has been further studied by examining the effects of excitatory amino acids and antagonists on [3H]acetylcholine (ACh) release from the retinas of anaesthetized rabbits. Exposure of the retina to glutamate (5 mM), aspartate (5 mM), kainate (8 microM) and quisqualate (8 microM) abolished the light-evoked release of [3H]ACh but increased the spontaneous resting release four- to fivefold. N-methyl-D-aspartate (NMDA) (5 mM) in normal Krebs bicarbonate medium abolished the light-evoked release of [3H]ACh but did not affect the resting release. However, in Mg-free medium, NMDA (0.5 mM) abolished the light-evoked release of [3H]ACh and increased the resting release fivefold. The effects of other agonists were not altered in Mg-free medium. The amplitude of the electroretinogram (e.r.g.) b-wave was not significantly reduced by glutamate, aspartate or NMDA (in normal or Mg-free medium). Kainate and quisqualate reduced the b-wave amplitude to approximately 50 and 30% of controls respectively. The general excitatory amino acid antagonist, cis-2,3-piperidine dicarboxylic acid (PDA) (2 mM) blocked the light-evoked release of [3H]ACh, but had no significant effect on the e.r.g. b-wave amplitude or on the resting release of [3H]ACh. L(+)-2-amino-4-phosphonobutyrate (L(+)-APB) decreased the light-evoked release of [3H]ACh and the amplitude of the e.r.g. b-wave in parallel (correlation coefficient 0.995). D(-)-APB had similar effects but was fifteen times less potent. Since the L(+)-compound is known to mimic the photoreceptor transmitter on the depolarizing, but not hyperpolarizing, bipolar cells, these results strongly suggest that the [3H]ACh released in response to light originates mainly from the 'on' (displaced) cholinergic amacrine cells. Our experiments give no information on the origin of the spontaneously released [3H]ACh. PDA (2-5 mM) blocked the effects of glutamate, aspartate, kainate, quisqualate and NMDA on the resting release of [3H]ACh. In contrast, D(-)-APB (5 mM), which is a relatively non-specific excitatory amino acid antagonist in the spinal cord, blocked only the actions of kainate and had no blocking effect on the actions of glutamate or aspartate (the putative bipolar cell transmitters) or NMDA. D(-)-2-amino-5-phosphonovalerate (APV) which is a relatively selective NMDA antagonist in the spinal cord failed to discriminate between the effects of kainate and NMDA on the resting release of [3H]ACh. D-alpha-aminoadipate at concentrations up to 5 mM had no effect on any of the agonists.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1985

Hypothesized eye movements of neurolinguistic programming: a statistical artifact.

Neurolinguistic programming's hypothesized eye-movements were measured independently from videotapes of 30 subjects, aged 15 to 76 yr., who were asked to recall visual pictures, recorded audio sounds, and textural objects. chi 2 indicated that subjects' responses were significantly different from those predicted. When chi 2 comparisons were weighted by number of eye positions assigned to each modality (3 visual, 3 auditory, 1 kinesthetic), subjects' responses did not differ significantly from the expected pattern. These data indicate that the eye-movement hypothesis may represent randomly occurring rather than sensory-modality-related positions.

Adolescent↗
PubMed1984

Quality assurance in radiation therapy: clinical and physical aspects. Quality assurance in dosimetry and treatment planning.

The considerations of tissue response to radiation absorbed dose suggest a need for an accuracy of +/- 5% in its delivery. This is very demanding and its regular achievement requires careful quality control. There are three distinct phases to the delivery of the planned treatment: calibration of the radiation beam in a reference situation, calculation of the dose distribution for a patient relative to the reference dose and the delivery of the radiation to the patient as planned. Each has distinctly different quality assurance requirements and must be diligently observed if the desired accuracy is to be achieved.

Humans↗
PubMed1983

Effect of gamma-aminobutyric acid agonists, glycine, taurine and neuropeptides on acetylcholine release from the rabbit retina.

The light-evoked release of [3H]acetylcholine (ACh) from the rabbit retina in vivo was measured and taken as an index of cholinergic amacrine cell activity. The light-evoked release of [3H]ACh was reduced by locally applied gamma-aminobutyric acid (GABA), muscimol and 3-aminopropanesulphonic acid (3-APS). The concentrations of these drugs which reduced the light-evoked release of [3H]ACh by 50% (EC50) were 900, 0.3 and 5 microM respectively. In contrast, (-)-baclofen (5 mM), but not (+)-baclofen, significantly increased the light-evoked release of [3H]ACh. The GABA antagonist, bicuculline increased the resting release of [3H]ACh but abolished the inhibitory action of muscimol on the light-evoked release of [3H]ACh. Glycine and taurine also reduced the light-evoked release of [3H]ACh from the retina, their EC50 values being 1.5 and 0.3 mM respectively. This action was blocked by strychnine, but not by bicuculline. In contrast to the GABA antagonist, strychnine did not affect the spontaneous resting release of [3H]ACh. Retinal [3H]ACh release was not affected by dopamine, 5-hydroxytryptamine (5-HT) morphine, substance P, somatostatin, cholecystokinin sulphate, thyrotropin releasing hormone, luteinizing hormone releasing hormone or angiotensin. Electroretinographic changes produced by amino acids and GABA agonists involved mainly the b-wave and were not correlated with their effects on ACh release. Thus, GABA increased the b-wave amplitude, 3-APS had no effect, whilst muscimol, taurine and glycine either had no effect, or reduced the b-wave amplitude. No obvious changes in the e.r.g. were produced by baclofen, dopamine, 5-HT, morphine or any of the peptides studied with the exception of somatostatin, which reduced the amplitude of the b-wave. It is concluded that cholinergic amacrine cell activity in the rabbit retina may be affected by inputs from other amacrines using GABA or glycine (taurine) as their transmitters, but probably not by inputs from peptidergic or dopaminergic amacrine cells. Our experiments do not provide evidence on the sites of action of GABA, glycine or taurine but the action of bicuculline on the resting release of ACh implies that the activity of the cholinergic amacrine cells is affected by a tonically active GABAergic input.

Acetylcholine↗
PubMed1983

Evidence for a cholinergic inhibitory feed-back mechanism in the rabbit retina.

The effects of muscarine, atropine and nicotinic antagonists on the light-evoked release of radioactivity from rabbit retinas previously exposed to [3H]choline (Ch) was studied. On the basis of previous experiments, this light-evoked release of total radioactivity was taken as a measure of the light-evoked release of [3H]acetylcholine (ACh) from the cholinergic amacrine cells. Atropine (1 microM) in the presence, but not the absence, of eserine more than doubled the light-evoked release of [3H]ACh. Eserine (30 microM) itself had no significant effect on either the spontaneous resting release or the light-evoked release of [3H]ACh. Muscarine (10 microM) in the presence or absence of eserine reduced the light-evoked release of [3H]ACh from the retina by 50%. This effect of muscarine was blocked by atropine used in the absence of eserine. The nicotinic antagonists pempidine, hexamethonium and gallamine had no significant effect on retinal [3H]ACh release. Strychnine (20 microM), which alone had no effect on retinal [3H]ACh release, abolished the effects of both muscarine and atropine on the light-evoked release of [3H]ACh. Bicuculline (5 microM) did not affect the actions of muscarine or atropine on the light-evoked release of [3H]ACh. Previous experiments had shown that glycine and gamma-aminobutyric acid (GABA) reduce the light-evoked release of [3H]ACh from the retina and that these inhibitory effects are selectively blocked by strychnine (20 microM) and bicuculline (5 microM) respectively. These results suggest the presence in the retina of a cholinergic inhibitory feed-back mechanism which involves a neuronal loop, rather than presynaptic or post-synaptic inhibitory muscarinic receptors on the cholinergic amacrine cells themselves. Our experiments do not provide evidence on the nature of the proposed inhibitory loop, except that it apparently includes a glycinergic or taurinergic (amacrine) cell.

Acetylcholine↗
PubMed1981

The effect of 2-amino-4-phosphonobutyrate (APB) on acetylcholine release from the rabbit retina: evidence for on-channel input to cholinergic amacrine cells.

The light-evoked release of acetylcholine (ACh) from the rabbit retina was taken as a measure of cholinergic amacrine cell activity. The glutamate analogue DL-(+/-)-2-amino-4-phosphonobutyric acid (APB) prevented the light-evoked release of ACh and also selectively abolished the ON-responses of ganglion cells and the ERG b-wave. It is concluded that the input to cholinergic amacrine cells involves mainly the depolarizing bipolar cells, which subserve ON-channels. L-(+)-stereoisomer of APB was 15 times more potent than the D-(-)-isomer in suppressing ACh release and the b-wave, suggesting that the mechanism of action of APB does not involve antagonism of excitatory amino acids.

2-Amino-5-phosphonovalerate↗
PubMed1979

The uptake and radioautographical localization in the frog retina of [3H](+/-)-aminocyclohexane carboxylic acid, a selective inhibitor of neuronal GABA transport.

The accumulation of [3H](+/-)-cis-3-aminocyclohexane carboxylic acid ([3H] ACHC) in frog retinae in vitro was highly localized in horizontal cells and their processes. [3H]GABA was also mainly accumulated within horizontal cells, but [3H]L-2,4-diaminobutyric acid ([3H]DABA) was taken up predominantly by the neuroglial Müller cells, whilst [3H]beta-alanine was localised largely within the photoreceptors. The uptake of [3H]ACHC (4.2 microM) was almost linear for 30 min and after 60 min a tissue/medium ratio of 5.25 was achieved. The uptake process was temperature sensitive highly dependent on sodium ions, and appeared to be mediated by a saturable transport process with an IC50 value of 0.83 mM. The accumulation of [3H]ACHC was inhibited by GABA and DABA (IC50 = 0.32 mM and 0.23 mM, respectively) whilst beta-alanine was a relatively weak inhibitor (IC50 = 9 mM) of ACHC uptake. In agreement with these results, the efflux of [3H]ACHC from the retina was increased by exposure to ACHC, GABA and DABA but not beta-alanine. In contrast, the efflux of [3H]DABA from the retina was not increased by GABA or ACHC, although DABA itself and potassium depolarization stimulated the release of [3H]DABA. These results strongly suggest that ACHC is accumulated in the frog retina by the same neuronal transport process as GABA. In contrast, the high affinity sites for DABA are localized mainly in glia, although inhibitor and release studies suggest that, at high concentration, DABA also interacts with the neuronal GABA (ACHC) transport process.

Alanine↗
PubMed1978

Clinical application of a CT based treatment planning system.

An AECL (TP-11) treatment planning system has been modified to allow multiple CT scans to be used directly for dosage calculation and display. This CT/TP-11 system has incorporated the "equivalent tissue-air ratio method" to make corrections for the effects of tissue heterogeneity and the three-dimensional nature of patient shape. In test situations, using an anatomical phantom, an accuracy of ca. 2% has been attained. An investigation has also been made to assess the importance of the reproducibility of patient position and its effect on the validity of such dosage calcualtions. When representing an advance in sophistication of existing facilities, this system has also been designed with practically in mind.

Humans↗