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Biomedical subjects

J E Bright

Publications and source records attributed to J E Bright.

At least 19 recordsLinked to original sources

The relationship between the structural mere exposure effect and the implicit learning process.

Three experiments are reported that investigate the relationship between the structural mere exposure effect (SMEE) and implicit learning in an artificial grammar task. Subjects were presented with stimuli generated from a finite-state grammar and were asked to memorize them. In a subsequent test phase subjects were required first to rate how much they liked novel items, and second whether or not they thought items conformed to the rules of the grammar. A small but consistent effect of grammaticality was found on subjects' liking ratings (a "structural mere exposure effect") in all three experiments, but only when encoding and testing conditions were consistent. A change in the surface representation of stimuli between encoding and test (Experiment 1), memorizing fragments of items and being tested on whole items (Experiment 2), and a mismatch of processing operations between encoding and test (Experiment 3) all removed the SMEE. In contrast, the effect of grammaticality on rule judgements remained intact in the face of all three manipulations. It is suggested that rule judgements reflect attempts to explicitly recall information about training items, whereas the SMEE can be explained in terms of an attribution of processing fluency.

Cognition↗

Differences between implicit and explicit acquisition of a complex motor skill under pressure: an examination of some evidence.

Masters (1992) argued that an implicitly acquired motor skill is less likely to fail under pressure than an explicitly acquired skill. He demonstrated this by showing that induced anxiety led to differences in the golf putting performance of groups who had acquired the skill implicitly and explicitly. We replicated Masters' basic findings but our results suggest that the difference in performance under pressure is more readily explained in terms of differences between the learning and testing conditions. Our results are consistent with an explicit learning account of the putting task and we found no support for the claim that implicit and explicit learning of motor skills are differentially affected by anxiety.

Analysis of Variance↗

A histochemical study of changes observed in the mouse diaphragm after organophosphate poisoning.

A sublethal dose of sarin (GB, isopropyl methylphosphonofluoridate) was administered to mice. The animals were killed up to 28 d after dosing and frozen sections were made of the excised diaphragms which were stained using haematoxylin and eosin and a modified Gomori trichrome method. Muscle fibre degeneration and mononuclear infiltration were seen, notably at 24 h and 3 d. A number of histochemical procedures were carried out, including the GBHA procedure for ionized calcium. Calcium accumulation, seen at 4 h, was the earliest abnormality observed. All changes were rapidly regressing by 5 d and histological appearances were normal by 14 d. It was concluded that sarin produced myopathic changes preceded by calcium accumulation.

Acetylcholinesterase↗

The formation of methaemoglobin by 4-aminopropiophenone (PAPP) and 4-(N-hydroxy) aminopropiophenone.

Oral dosing of rats with the cyanide antidote 4-aminopropiophenone (PAPP), brought about peak methaemoglobin levels at 15-40 min, but peak levels were attained at at 15-25 min after intravenous dosing. After both oral and intravenous administration at equimolar doses, 4-(N-hydroxy)aminopropiophenone (PHAPP), the putative methaemoglobin-producing metabolite of PAPP, produced higher peak levels of methaemoglobin than PAPP. Plasma from rats injected with PAPP was capable of forming methaemoglobin when added to naive rat erythrocytes. The identity of the metabolite responsible is discussed.

Administration, Oral↗

Studies of the pharmacokinetics and metabolism of 4-amino-propiophenone (PAPP) in rats, dogs and cynomolgus monkeys.

The pharmacokinetics and metabolism of 4-aminopropiophenone (PAPP), a cyanide antidote, have been studied in rats, dogs and cynomolgus monkeys using 14C-PAPP. Radiolabelled material was rapidly excreted in all three species, mainly in urine. In rats, PAPP was metabolized by N-acetylation, while in dogs, ring and aliphatic hydroxylation occurred. In monkeys, both N-acetylation and oxidation took place. In the latter pathway, PAPP was oxidized to p-aminobenzoic acid which underwent amino acid-conjugation to p-aminohippuric acid. In rat blood in vitro, the PAPP metabolites, p-aminobenzoic, p-aminohippuric and N-acetyl-p-aminobenzoic acid were only weak methaemoglobin producers.

Animals↗

The effect of storage upon cyanide in blood samples.

CDPA blood of human origin was 'spiked' with a solution of potassium cyanide at four different concentrations. When such blood was left in contact with the atmosphere for up to 10 min an appreciable amount of the cyanide was lost. Stoppered tubes containing the 'spiked' blood were stored at -20 degrees C and 4 degrees C for up to 6 months. Most samples, especially those 'spiked' at the highest concentrations, showed a loss of cyanide.

Blood Preservation↗

Evaluation of the efficacy of dimercapto chelating agents for the treatment of systemic organic arsenic poisoning in rabbits.

1 The standard drug for the treatment of arsenic poisoning is BAL (dimercaprol). BAL possesses marked side-effects and a low safety ratio, drawbacks which new BAL analogues, DMPS and DMSA, do not possess. 2 The efficacy of three chelating agents, BAL, DMPS and DMSA, has been evaluated as a treatment for systemic organic arsenic poisoning, induced by intravenous dichloro(2-chlorovinyl)arsine (lewisite) administration to rabbits. Equimolar dosing schedules were used based upon realistic doses for the most toxic agent, BAL. 3 It was concluded that all three dimercapto chelating agents provided significant protection against the lethal systemic effects of lewisite, and, under the test conditions reported here, there was no significant difference between them in therapeutic efficacy. 4 The cause of mortality following intravenous lewisite in treated and untreated rabbits was pulmonary damage. 5 It is considered that DMPS and DMSA are worthy of further study as replacements for BAL in the treatment of systemic poisoning by lewisite.

Animals↗

Histochemical demonstration of calcium accumulation in muscle fibres after experimental organophosphate poisoning.

The LD50 of subcutaneously-injected sarin (GB: isopropyl methylphosphonofluoridate) in mice was 172 micrograms kg-1. Mice were treated with sarin at doses between 25 and 150 micrograms kg-1, administered subcutaneously. After sacrifice of the animals, the diaphragms were removed and stained for acetylcholinesterase activity and the presence of ionized calcium. Calcium was found in the diaphragms of those mice to which sarin had been administered at doses of 50 micrograms kg-1 or above. Calcium accumulation was not present in diaphragms from those animals that had received 25 micrograms kg-1. Calcium accumulation occurred earliest and remained longest in diaphragms from those animals receiving the highest doses. Accumulation of calcium was associated with end-plates, as demonstrated by an acetylcholinesterase histochemical method.

Acetylcholinesterase↗

Methaemoglobin production and reduction by methylene blue and the interaction of methylene blue with sodium nitrite in vivo.

Methylene blue, at high concentrations, interferes with the estimation of methaemoglobin using the IL 282 CO-oximeter: the dye does not interfere with the method of Evelyn & Malloy for determination of methaemoglobin. In beagle bitches methylene blue causes both methaemoglobinogenesis and methaemoglobin reduction, the effect of the former being to delay the decline of methaemoglobin levels, when methylene blue is used to reverse the methaemoglobinaemia produced by sodium nitrite.

Animals↗

Comparative acute systemic toxicity of sodium arsenite and dichloro(2-chlorovinyl)arsine in rabbits.

The acute intravenous toxicity of sodium arsenite and dichloro(2-chlorovinyl)arsine (lewisite) has been compared in rabbits to provide a quantitative and qualitative model for future assessment of treatments of lewisite poisoning. The LD50 of sodium arsenite was 7.6 mg.kg-1; that for lewisite was 1.8 mg.kg-1. On the basis of arsenic content the former was 6.5 times less toxic than the latter. Significant differences in tissue arsenic content and pathology were found between the 2 materials. Histologically, changes were observed in the lungs and gall bladder after lewisite injection but not after sodium arsenite. It was concluded that use of sodium arsenite is not a suitable substitute model for lewisite poisoning.

Animals↗

Pharmacokinetics of intravenous potassium cyanide.

The pharmacokinetics of intravenously injected potassium cyanide have been studied in Beagle bitches. In the period up to about 80 min after dosing, blood levels fell in a manner consistent with first-order elimination kinetics. Thereafter blood cyanide concentrations fell at a slower rate, indicating that a second phase of slower elimination had been entered.

Animals↗

Species differences in methaemoglobin production after addition of 4-dimethylaminophenol, a cyanide antidote, to blood in vitro: a comparative study.

Methaemoglobin production after addition of DMAP to blood of various species, has been studied in vitro. The study was undertaken both with blood, as taken, and after equilibration with atmospheric oxygen. Considerable interspecies variation in methaemoglobin production was found. When the initial rate of methaemoglobin formation was considered only marmoset and human blood showed any marked degree of inhibition by equilibration with atmospheric oxygen.

Aminophenols↗

Methemoglobinogenic potential of primaquine and its mutagenicity in the Ames test.

Single doses of primaquine did not produce methemoglobinemia in beagle bitches. Repeated daily administration for 12 days produced a gradually rising level of methemoglobin over that time period, unaccompanied by depletion of erythrocytic reduced glutathione. Primaquine was mutagenic in the Ames test in Salmonella typhimurium strain TA 1537, with or without S9, using a liquid preincubation assay. Primaquine was non-mutagenic in this assay to strains TA 1535, TA 1538, TA 98 and TA 100, regardless of the presence or absence of S9. In the standard overpour Ames test, the drug was non-mutagenic in all 5 Salmonella strains, both with and without S9 metabolic activation.

Animals↗

Effect on blood and plasma cyanide levels and on methaemoglobin levels of cyanide administered with and without previous protection using PAPP.

Hydrogen cyanide was administered intravenously at doses of 0.67 or 1.34 mg kg-1 to beagle bitches after protection with oral p-aminopropiophenone (0.5 mg kg-1). Hydrogen cyanide was also administered to unprotected bitches at the lower level (0.67 mg kg-1) only. PAPP protection caused sequestration of cyanide inside the red cells. In the case of the lower dose of cyanide this resulted in a lower plasma cyanide in protected than unprotected bitches. In the case of the higher dose it resulted in survival, despite 1.34 mg kg-1 being a known lethal dose. It is concluded that prior administration of PAPP ameliorated the effects of cyanide poisoning.

Animals↗

Sex differences in the production of methaemoglobinaemia by 4-aminopropiophenone.

A methaemoglobin former, 4-aminopropiophenone (p-aminopropiophenone, PAPP), which is active only after metabolic activation in vivo, exhibits a sex difference in male Beagle dogs and bitches. Bitches produced more methaemoglobin for a given dose of PAPP than male dogs. The probable reason for this difference was a lower rate of N-hydroxylation in male dogs.

Animals↗

Kinetics of methaemoglobin production. (1). Kinetics of methaemoglobinaemia induced by the cyanide antidotes, p-aminopropiophenone, p-hydroxyaminopropiophenone or p-dimethylaminophenol after intravenous administration.

Methaemoglobin profiles have been studied by using ISIS, a simulation package, and NONLIN, a non-linear least-squares analysis regression program. A simple kinetic model which satisfactorily describes methaemoglobin profiles after p-aminopropiophenone (PAPP) administration and 4-dimethylaminophenol (DMAP) administration has been developed. The two compounds differed mainly in their effective rates of elimination. The model less satisfactorily described methaemoglobin profiles after p-hydroxyaminopropiophenone (PHAPP) administration.

Aminophenols↗