Biomedical subjects

B A Williams

Publications and source records attributed to B A Williams.

At least 19 recordsLinked to original sources

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

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↗

PubMed1991

Preference for conditioned reinforcement.

Pigeons were presented with a concurrent-chains schedule in which both choice alternatives led to the same terminal-link stimulus, which was followed by food. Superimposed on the food-reinforced presentations of the terminal-link stimulus was a second schedule of presentations of the same stimulus that were followed by no food. The absolute number of these no-food stimulus presentations was held constant while their relative frequency assigned to one or the other choice alternative was systematically varied. Preference for a given choice alternative tracked the relative frequency of these stimulus presentations, thus demonstrating that they served as reinforcers. These results resolve conflicts in the literature regarding the effect of conditioned reinforcement on choice.

Animals↗

PubMed1991

Choice as a function of local versus molar reinforcement contingencies.

Rats were trained on a discrete-trial probability learning task. In Experiment 1, the molar reinforcement probabilities for the two response alternatives were equal, and the local contingencies of reinforcement differentially reinforced a win-stay, lose-shift response pattern. The win-stay portion was learned substantially more easily and appeared from the outset of training, suggesting that its occurrence did not depend upon discrimination of the local contingencies but rather only upon simple strengthening effects of individual reinforcements. Control by both types of local contingencies decreased with increases in the intertrial interval, although some control remained with intertrial intervals as long as 30 s. In Experiment 2, the local contingencies always favored win-shift and lose-shift response patterns but were asymmetrical for the two responses, causing the molar reinforcement rates for the two responses to differ. Some learning of the alternation pattern occurred with short intertrial intervals, although win-stay behavior occurred for some subjects. The local reinforcement contingencies were discriminated poorly with longer intertrial intervals. In the absence of control by the local contingencies, choice proportion was determined by the molar contingencies, as indicated by high exponent values for the generalized matching law with long intertrial intervals, and lower values with short intertrial intervals. The results show that when molar contingencies of reinforcement and local contingencies are in opposition, both may have independent roles. Control by molar contingencies cannot generally be explained by local contingencies.

Animals↗

PubMed1990

Enduring problems for molecular accounts of operant behavior.

Although the Associative Learner (AL) theory advocated by Shimp, Childers, and Hightower (1990) can simulate several features of human and nonhuman performance in free-operant situations, it fails to account for many of the findings that are theoretically most powerful. It underestimates the sensitivity of behavior to relative reinforcement rate and totally omits any role for incentive variables such as amount and delay of reinforcement. At present, it is not sufficiently comprehensive to serve as an adequate alternative to Herrnstein's (1961, 1970) matching theory as a general account of behavior.

Animals↗

PubMed1990

Conditioned reinforcement versus time to reinforcement in chain schedules.

Pigeons were trained on three-component chain schedules in which the initial component was either a fixed-interval or variable-interval schedule. The middle and terminal components were varied among fixed-interval fixed-interval, variable-interval variable-interval, and an interdependent variable-interval variable-interval schedule in which the sum of the durations of the two variable-interval components was always equal to the sum of the fixed-interval fixed-interval components. At issue was whether the response rate in the initial component was controlled by its time to primary reinforcement or by the temporal parameters of the stimulus correlated with the middle terminal link. The fixed-interval initial-link schedule maintained much lower response rates than the variable-interval initial-link schedule regardless of the schedules in the middle and terminal links. Nevertheless, the intervening schedules played some role: With fixed-interval schedules in the initial links, response rates were consistently highest with independent variable-interval schedules in the middle and terminal links and intermediate with the interdependent variable-interval schedules; these initial-link differences were predicted by the response rates in the middle link of the chain. With variable-interval schedules in the initial links, response rates were lowest with the fixed-interval fixed-interval schedules following the initial link and were not systematically different for the two types of variable-interval variable-interval schedules. The results suggest that time to reinforcement itself accounts for little if any variance in initial-link responding.

Animals↗

PubMed1990

Absence of anticipatory contrast in rats trained on multiple schedules.

Rats were trained on three- and four-component multiple schedules in which two of the components were correlated with identical reinforcement schedules that remained unchanged throughout training. These target components differed in terms of whether their respective following schedules were either higher or lower in value. Unlike corresponding experiments previously reported with pigeons, higher response rates occurred in the target component followed by a higher valued schedule than in the target component followed by the lower valued schedule. Overall contrast effects occurred independently of these sequential effects, but were inconsistent across subjects. The results suggest that the effects of a following schedule of reinforcement are opposite for pigeons and rats, and that one reason previous studies have often failed to show contrast effects with rats is that the effects of the following schedule in rats are in competition with contrast dynamics.

Animals↗

PubMed1990

Role of the carotid chemoreceptors in the respiratory response of newborn lambs to alternate pairs of breaths of air and a hypoxic gas.

We measured the reflex respiratory response to a 2-breath alternation in fractional inspired oxygen in two groups of lambs. Test runs where F(I),O2 was made to alternate (between 0.21 and 0.14) were compared with control runs in which it was held at 0.21. Within 36 h of birth we cut the carotid sinus nerves bilaterally in one group of lambs (n = 5) whilst in a second group (n = 5) sham operations were carried out. The alternating responses in seven respiratory variables were compared between test and control runs in each group of lambs at postnatal days 5-6 and again at postnatal days 10-11. In sham-operated lambs at days 5-6 there was a significant response in most respiratory variables during test runs and by days 10-11 the response was increased, primarily as a consequence of an increase in the tidal volume component of the response, indicating a postnatal maturation of the responses. The time-scale of this maturation is appropriate to that of peripheral chemoreceptor resetting. There was no significant response to the test in the denervated lambs at 5-6 days but by days 10-11 a small response was measured in some variables. Our results therefore indicate that the reflex respiratory response to alternations in FI,O2 is primarily mediated by the carotid chemoreceptors. The development of a response mediated by the aortic chemoreceptors may account for the small alternating response in the denervated lambs at days 10-11.

Animals↗

PubMed1989

Reproductive alterations in female C57BL/Crgl mice exposed neonatally to zearalenone, an estrogenic mycotoxin.

Newborn female mice were injected daily for 5 days with 1 microgram zearalenone (Z, a weakly estrogenic mycotoxin present in cereal grains), resulting in ovary-dependent reproductive tract alterations at 8 months of age. Corpora lutea were absent from 25 of 34 (74%) Z-treated mice, indicating ovarian dysfunction. Fifty-six percent of Z-treated mice had dense collagen deposition in the uterine stroma and lacked uterine glands. Squamous metaplasia of the uterine luminal epithelium was found in 59% of Z-treated mice, and altered vaginal epithelium was found in 32% (2 mice had dysplastic lesions). Ovariectomized Z-treated mice were indistinguishable from ovariectomized controls.

Animals↗

PubMed1989

The effect of chronic hypoxia upon the development of respiratory chemoreflexes in the newborn kitten.

1. We have studied the reflex respiratory responses to two-breath alternations of fractional inspired oxygen (FI,O2) in normoxic (reared in room air) and chronically hypoxic kittens (born into and reared in an FI,O2 of 0.13-0.15) on post-natal days 1, 2-3, 4-8 and 9-14. 2. Respiration was measured non-invasively in the unanaesthetized kittens. Test runs (with alternations of FI,O2 between 0.21 and 0.14) and control runs (with an FI,O2 of 0.21) were carried out during quiet sleep. 3. The degree of alternation in tidal volume, inspiratory time, expiratory time, frequency, drive, timing and instantaneous ventilation components of the respiratory response was compared during control and test runs. 4. There was little response to control runs in either group at any post-natal age. 5. In normoxic kittens we found no significant reflex response in any respiratory variable to test runs before day 4. However significant alternation was found in expiratory time, frequency and ventilation at days 4-8 and in tidal volume at days 9-14. 6. In chronically hypoxic kittens there were no significant differences between control and test runs at any of the ages studied. 7. In the normoxic group increases in the response with post-natal age probably reflect post-natal increases in the sensitivity of the peripheral chemoreceptors. The lack of development in the chronically hypoxic group may indicate abnormal function or delayed maturation of the peripheral chemoreceptor sensitivity to hypoxia. 8. The results suggest that the method can be used to detect developmental and pathological changes in the arterial chemoreflex.

Animals↗