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Biomedical subjects

B A Williams

Publications and source records attributed to B A Williams.

At least 73 records · Page 4Linked to original sources
PubMed1994

Shortcomings of the behavioral competition theory of contrast: Reanalysis of McLean (1992).

McLean (1992) presented significant data showing that the occurrence of behavioral contrast in a multiple schedule was correlated with shifts in the frequency of reinforcers from a second source between components of the schedule, and interpreted his results as showing that contrast was due to changes in the degree of response competition within the constant component of the multiple schedule. Reanalysis of his data shows that there was an effect of reinforcement in the alternative component of the schedule independent of the shifts in reinforcers between components. Thus, the effect of relative rate of reinforcement cannot be ascribed, at least entirely, to the mechanisms proposed by the behavioral competition theory of contrast.

Journal Article↗
PubMed1994

Context specificity of conditioned-reinforcement effects on discrimination acquisition.

Pigeons were trained on a series of reversals of a simultaneous form discrimination in which the trial outcomes were separated from the choice responses by an 8-s delay interval. Different conditions were defined by the stimuli occurring during the two halves of the delay interval. Discrimination learning was greatly facilitated by having differential stimuli during the delay following correct versus incorrect choices. When the differential stimuli appeared only at the midpoint of the delay, some facilitation occurred relative to when no different stimuli occurred, but there was substantially less facilitation than when the differential stimuli occurred immediately contingent on choice. A reversed-stimulus condition, in which the stimulus at the onset of the delay following a correct choice was the same as that during the last segment of the delay following an incorrect choice, and the stimulus at the onset of the delay following an incorrect choice was the same as that preceding food during the last segment of the delay following a correct choice, also facilitated discrimination learning relative to the nondifferential stimulus conditions.

Journal Article↗
PubMed1993

The effect of 2,4-dinitrophenol on the metabolic rate of bobwhite quail.

Bobwhite quail were exposed to 2,4-dinitrophenol (DNP) in a respirometer designed to continuously monitor exchange of O2 and CO2, from which metabolic rates (MR) were estimated. After 14-16 days of acclimation to the system (temperature 22 degrees C, light cycle 8L:14D), hens received feed amended with 0, 625, or 1250 ppm DNP ad libitum for 8 days, followed by 2-5 days of feed containing no DNP. The 625 ppm treatment produced dark-period MR 31-41% higher than corresponding control values, and light-period MR 23-32% higher than controls. The 1250 ppm treatment produced dark-period MR 48-77% higher than control values, and light-period MR 41-67% higher than controls. Over the 8 days of testing, the 625 ppm treatment hens expended 32% more energy than the control hens. Hens consuming 1250 ppm feed expended 60% more energy than control hens and lost most of their body fat. In general, the risk of being unable to meet energy demands for survival or reproduction would probably be substantially increased by the observed elevation in MR.

2,4-Dinitrophenol↗
PubMed1993

Two types of potassium channel regulated by ATP in pancreatic B cells isolated from a type-2 diabetic human.

Two types of K channel regulated by ATP were observed in pancreatic beta cells from a type-2 diabetic man. One type had a conductance of 67 pS at -70 mV in symmetrical 140 mM KCl and was inhibited by intracellular ATP with a half-maximal concentration of 40 microM. ATP inhibition was antagonised by ADP. Tolbutamide inhibited the whole-cell K currents half-maximally at 25 microM. This channel has properties similar to those found for the ATP-sensitive K channel in rodent and normal human beta cells. The second channel type observed was an ATP-activated K channel. It had a conductance of 37 pS at -70 mV in symmetrical 140 mM KCl and was activated half-maximally by 9 microM intracellular ATP. This channel was unaffected by 1 mM tolbutamide. In cell-attached patches, one beta cell out of four tested responded to 20 mM glucose with depolarization. The role of the ATP-activated K channel with respect to the (patho)physiology of the beta cell is uncertain.

Adenosine Diphosphate↗
PubMed1993

Molar versus local reinforcement probability as determinants of stimulus value.

During one component of a multiple schedule, pigeons were trained on a discrete-trial concurrent variable-interval variable-interval schedule in which one alternative had a high scheduled rate of reinforcement and the other a low scheduled rate of reinforcement. When the choice proportion between the alternatives matched their respective relative reinforcement frequencies, the obtained probabilities of reinforcement (reinforcer per peck) were approximately equal. In alternate components of the multiple schedule, a single response alternative was presented with an intermediate scheduled rate of reinforcement. During probe trials, each alternative of the concurrent schedule was paired with the constant alternative. The stimulus correlated with the high reinforcement rate was preferred over that with the intermediate rate, whereas the stimulus correlated with the intermediate rate of reinforcement was preferred over that correlated with the low rate of reinforcement. Preference on probe tests was thus determined by the scheduled rate of reinforcement. Other subjects were presented all three alternatives individually, but with a distribution of trial frequency and reinforcement probability similar to that produced by the choice patterns of the original subjects. Here, preferences on probe tests were determined by the obtained probabilities of reinforcement. Comparison of the two sets of results indicates that the availability of a choice alternative, even when not responded to, affects the preference for that alternative. The results imply that models of choice that invoke only obtained probability of reinforcement as the controlling variable (e.g., melioration) are inadequate.

Animals↗
PubMed1992

Energetics of lectin-carbohydrate binding. A microcalorimetric investigation of concanavalin A-oligomannoside complexation.

Despite years of study, a comprehensive picture of the binding of the lectin from Canavalia ensiformis, concanavalin A, to carbohydrates remains elusive. We report here studies on the interaction of concanavalin A with methyl 3,6-di-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside, the minimum carbohydrate epitope that completely fills the oligosaccharide binding site, and the two conceptual disaccharide "halves" of the trisaccharide, methyl 3-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside and methyl 6-O-(alpha-D-mannopyranosyl)-alpha-D-mannopyranoside, using titration microcalorimetry. In all cases the interaction of protein and carbohydrate is enthalpically driven, with an unfavorable entropic contribution. The choice of concentration scales has an important impact on both the magnitude and, in some cases, the sign of the entropic component of the free energy of binding. The thermodynamic data suggest binding of the two disaccharides may take place in distinct sites, as opposed to binding in a single high affinity site. In contrast to carbohydrate-antibody binding, delta Cp values were small and negative, pointing to possible differences in the motifs used by the two groups of proteins to bind carbohydrates. The thermodynamic data are interpreted in terms of solvent reorganization. Cooperativity during lectin-carbohydrate binding was also investigated. Significant cooperativity was observed only for binding of the trisaccharide, and gave a Hill plot coefficient of 1.3 for dimeric protein.

Calorimetry↗
PubMed1992

Limb deformity and metaphyseal abnormalities in thalassaemia major.

Regular bone survey radiographs have allowed identification of limb deformity and metaphyseal changes in several patients with thalassaemia major treated at the Adelaide Children's Hospital. Following the progression of limb deformity in five of these patients who were receiving human growth hormone therapy, the records of 25 thalassaemia patients were reviewed. Six patients had evidence of limb deformity, four of whom also had metaphyseal changes. Three additional patients had metaphyseal changes alone. Patients with either type of skeletal change shared similar characteristics, including younger age, earlier commencement of desferrioxamine therapy, better compliance and, in general, lower levels of ferritin. Females predominated in both groups. The frequency of sensorineural hearing loss was similar in affected and nonaffected groups and biochemical parameters, especially plasma calcium, phosphate, alkaline phosphatase, and zinc, which were normal in all patients. The cause of these skeletal changes is not clear; however, several potential factors need to be considered. Among these are focal marrow expansion in the metaphyseal region due to incomplete suppression of erythropoiesis and possible effects of desferrioxamine, including direct interference with bone growth, altered response of bone to inflammation or infection, and altered bone metabolism related to chelation of trace metals. While we can only speculate on aetiological factors, it is clear that human growth hormone therapy has resulted in exaggeration of deformity due to an increased rate of bone growth or decreased rate of mineralization of physeal cartilage. We believe that bone survey radiographs are useful in early identification of skeletal changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Cerebral tumors in children presenting with epilepsy.

The records of 20 children with seizures who had cerebral tumor confirmed histologically between 1979 and 1989 have been reviewed. These patients represented 2.9% of all children presenting with seizures. Forty percent were aged 15 months or younger, all of whom presented with partial seizures. Initial misdiagnosis of seizures occurred in 25% of these infants. Examination was normal in 75% of the study group. Behavior disturbance was present in 50%, with deterioration occurring in 60% of these. Electroencephalograms revealed focal abnormalities in 62% and generalized abnormalities in 25% when performed. Cranial ultrasound was performed in two cases, with false-negative results. Computed tomographic scan findings were not diagnostic of tumor in 40%. Magnetic resonance imaging confirmed the presence of tumor in all children in whom it was performed. Tumors most frequently involved the temporal lobes (55%) and the frontal lobes (40%). Surgical intervention resulted in considerable improvement in seizure control in 75%. Surgery is useful in the control of tumor-related seizures and should be considered early in the treatment of this disorder. Suspicion of tumor should increase when seizures are partial or refractory, particularly if intelligence and physical examination are normal or if there is progressive deterioration in behavior. The most appropriate type of brain imaging is magnetic resonance imaging scan.

Adolescent↗
PubMed1992

Competition between stimulus-reinforcer contingencies and anticipatory contrast.

Procedures used to study anticipatory contrast are conceptually similar to those used to study autoshaping, in that two target stimuli signal either higher or lower rates of reinforcement in the following components of the schedule. Despite this signal contingency, anticipatory contrast entails response rates that are higher to the target stimulus followed by the lower rate of reinforcement. To determine the relation between such effects and autoshaping, different variations of the procedure were used in which the signal contingency was presented in the absence of reinforcement in the target components themselves and in which the reinforcement schedules in the different following components were signaled by the same stimulus. Autoshaping effects of this signal contingency were demonstrated when no reinforcement was available during the target-component signals themselves. Intermediate patterns of behavior occurred when reinforcement was available during the target-component signals and when their different following schedules were correlated with the same stimulus. Attempts to isolate these signal and contrast effects functionally by using the signal-key procedure were unsuccessful. The results demonstrate that Pavlovian stimulus contingencies are in competition with the dynamics of anticipatory contrast, thus reducing its occurrence under some circumstances.

Animals↗
PubMed1992

Inverse relations between preference and contrast.

Pigeons were trained on a multiple schedule in which two target components with identical reinforcement schedules were followed by either the same-valued schedule or by extinction. Response rate increased in both target components but was higher in the target component followed by extinction, replicating previous findings of positive anticipatory contrast. A similar design was used to study negative contrast, in that the two target components were followed either by the same-valued schedule or by a higher valued schedule. Negative contrast occurred equally, on average, in both target components, thus failing to demonstrate negative contrast that is specifically anticipatory in nature. When the stimuli correlated with the two target components were paired in choice tests, the pattern of preference was in the opposite direction. For the positive contrast procedure, no significant preference between the two target stimuli was evident. But for the negative contrast procedure, preference favored the stimulus followed by the higher valued schedule. The results demonstrate a functional dissociation between positive and negative contrast in relation to stimulus value. More generally, the results demonstrate an inverse relation between response rate and preference and challenge existing accounts of contrast in terms of the concept of relative value.

Journal Article↗
PubMed1992

Dissociation of theories of choice by temporal spacing of choice opportunities.

Rats were trained on a discrete-trial version of a concurrent variable-interval (VI) variable-ratio (VR) schedule in which the relative reinforcement rates were varied across conditions. Subjects with the shorter intertrial interval (ITI) had a significant bias toward the VR alternative, as predicted by optimality theory, and were also more likely to choose the VI alternative with longer times since responses to the VI alternative, as predicted by momentary-maximizing theory. Subjects with the longer ITI failed to show either of these effects. Approximation to the matching law was greater with the longer ITI. Thus, matching is not derivative of the processes postulated by optimality or momentary-maximizing theory but instead is in competition with those processes.

Animals↗
PubMed1991

Halothane alters control of intracellular Ca2+ mobilization in single rat ventricular myocytes.

In an attempt to understand the cellular mechanisms underlying volatile anesthetic-induced myocardial depression, halothane-induced negative inotropy was investigated in an animal model through continuous monitoring of intracellular Ca2+ concentration [( Ca2+]i) in rat ventricular myocytes loaded with fura-2. Single cells were stimulated with 15 mM caffeine or 15 mM extracellular K+ (K+O) or were paced by extracellular glass suction pipette electrode. With each stimulus modality, halothane (0.6-1.5%) caused a significant (P less than 0.05) and dose-dependent depression of the Ca2+ transient. Caffeine and electrically stimulated Ca2+ transients were reduced, in 1.5% halothane, to 35 +/- 14 and 42 +/- 8% of control, respectively. Resting or basal [Ca2+]i was unaffected by halothane. Halothane did not elicit spontaneous Ca2+ transients in these cells. Single cells stimulated by trains of electrical stimuli at 1.0, 1.5, and 2.0 Hz showed a change in [Ca2+]i from prestimulus levels to a stimulated baseline steady state that appeared to increase with stimulus frequency. Halothane at 0.7% increased the change in resting to stimulated baseline [Ca2+]i and depressed net transients (P less than 0.05) at 1.0 and 1.5 Hz. In contrast, 0.1 microM ryanodine depressed the Ca2+ transients in myocytes stimulated by trains of stimuli, but did not potentiate the change in stimulated baseline [Ca2+]i at any pacing rate. The results are consistent with the hypothesis that halothane reduces Ca2+i availability by causing a net loss of Ca2+ from the sarcoplasmic reticulum. The results from experiments using onset of pacing to induce a sudden increase in Ca2+i load in previously quiescent myocytes suggest that halothane may act to limit sarcoplasmic reticulum and/or sarcolemmal uptake/extrusion mechanisms, as compared to ryanodine, which depletes sarcoplasmic reticulum Ca2+ stores without affecting reuptake and extrusion.

Animals↗
PubMed1991

Amantadine and sparteine inhibit ATP-regulated K-currents in the insulin-secreting beta-cell line, HIT-T15.

1. The effects of pharmacological agents that potentiate insulin release were studied on ATP-regulated K-currents (K-ATP currents) in the insulin-secreting beta-cell line HIT-T15 by use of patch-clamp methods. 2. The tricyclic drug, 1-adamantanamine (amantadine), reversibly inhibited both whole-cell currents (with a Ki of 120 microM) and single channel currents in inside-out patches. This effect was principally due to an increase in a long closed state which reduced the channel open probability. The related compound, 1-adamantanol, in which the amino group is substituted by a hydroxyl one, did not inhibit K-ATP currents substantially. 3. The alkaloid, sparteine, reversibly inhibited both whole-cell K-ATP currents (Ki = 171 microM) and single channel currents in inside-out patches. 4. The results suggest that sparteine and amantadine can block the K-ATP channel from either side of the membrane and support the idea that at least part of the stimulatory effect of these agents on insulin secretion results from inhibition of this channel.

Adenosine Triphosphate↗
PubMed1991

Development of respiratory chemoreflexes in response to alternations of fractional inspired oxygen in the newborn infant.

1. We studied the reflex respiratory response to breath-by-breath alternations of fractional inspired oxygen (FI,O2) in full-term human infants delivered either vaginally or by caesarian section at 3-10 h (n = 6), 12-24 h (n = 12), 24-48 h (n = 18), 3-4 days (n = 21) and 5-8 days (n = 7) postnatally. 2. Respiration was measured by inductance plethysmography (Respitrace) and respiratory variables for each breath were calculated on-line by a microcomputer. Test runs (with alternations of FI,O2 between 0.21 and 0.16) and control runs (with an FI,O2 of 0.21) of 50-100 breaths were carried out during quiet sleep. For each respiratory variable the magnitude of the reflex breath-by-breath alternation was compared between control and test runs. 3. There was little respiratory response during control runs at any postnatal age. However, there was a significantly greater response to test runs in all infants studied and at all ages. 4. There were no significant differences in the degree of alternation during test runs between infants of similar postnatal ages delivered by caesarean section and those born vaginally. 5. In all infants the magnitude of the respiratory response increased with postnatal age, presumably reflecting postnatal increases in the hypoxic sensitivity of the peripheral arterial chemoreceptors. 6. The results indicate that in human infants the alternate breath method can be used to detect developmental changes in peripheral chemoreflexes between birth and postnatal day 8.

Cesarean Section↗
PubMed1991

Correlation of myocardial necrosis with kinetics of 111In-labeled myosin-specific antibody in isolated rabbit septum.

Radiolabeled monoclonal antibody fragments to myosin, specifically 111In-labeled antimyosin, have been shown to be effective for imaging areas of myocardial infarct. To determine if 111In-labeled antimyosin can be used to assess the extent of necrosis, we compared the tissue retention fraction of 111In-labeled antimyosin with the amount of creatine kinase (CK) released from the isolated, perfused, interventricular rabbit septum after an intervention to induce tissue necrosis. 111In-labeled antimyosin was injected and tissue radioactivity was monitored for a 60-min period under control conditions. Effluent samples were also collected during this period and assayed for CK content. After a period of Ca2+ depletion followed by Ca2+ repletion, 111In-labeled antimyosin was again injected, and washout and CK data were collected. Comparison of the changes in 111In-labeled antimyosin retention fraction from control to intervention with the corresponding increase in CK released during intervention resulted in a correlation coefficient of 0.83. To corroborate the findings of the Ca2+ depletion followed by repletion experiments, further experiments were conducted in which zero-flow ischemia followed by reperfusion was used as a means of introducing necrosis in the septum. The resulting correlation coefficient between CK release and 111In-labeled antimyosin retention fraction was 0.82. The results of these experiments indicate that 111In-labeled antimyosin can be used to quantitatively estimate the extent of necrosis in the rabbit septum, as determined by CK release, and endorse the potential use of tracer kinetics in humans for quantitation of myocardial necrosis in vivo.

Animals↗
PubMed1991

Substitutability between conditioned and primary reinforcers in discrimination acquisition.

Rats and pigeons were trained on a series of reversals of a conditional simultaneous discrimination. The percentage of reinforcement for correct trials was varied across reversals. When nonreinforced correct trials produced the same feedback as incorrect trials, the number of errors to reach an acquisition criterion was greater for smaller percentages of reinforcement, but the number of reinforcers required was either approximately constant or smaller for the smaller percentages. When a stimulus paired with food (the conditioned reinforcer) was added on nonreinforced correct trials, both measures were substantially decreased. When the same stimulus was presented, but without a history of food pairing, learning rate was similar to when no stimulus was presented on nonreinforced trials. The results provide direct evidence that conditioned reinforcers may substitute, although imperfectly, for a primary reinforcer, and that pairing with the primary reinforcer is a necessary condition for such substitutability to occur.

Animals↗