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Biomedical subjects

A Dickinson

Publications and source records attributed to A Dickinson.

At least 91 records · Page 5Linked to original sources
PubMed1991

Instrumental judgment and performance under variations in action-outcome contingency and contiguity.

The intentional theory of instrumental performance proposes that performance of an action is determined in part by a belief about its causal effectiveness in producing a desired outcome. At variance with this notion, previous implicit learning experiments appear to have yielded dissociations between subjects' performance and beliefs. In two experiments, subjects were given an opportunity to perform an action--pressing a key on a computer keyboard--which was associated with an outcome on the computer screen according to a free-operant contingency. The subjects in one group were asked to judge the effectiveness of the action in causing the outcome, while those in a second group were asked to maximize their points score under a payoff schedule. In the first study, the effect of varying the contingency between the action and outcome was examined by keeping the probability of an outcome contiguous with an action constant and varying the probability of an outcome in the absence of an action. Performance and judgments showed a comparable sensitivity to variations of the instrumental contingency. In the second study, the delay between the action and the resultant outcome was varied. Increasing the action-outcome delay from 0 sec up to 4 sec produced a systematic decline in both causal judgments and performance relative to noncontingent, control conditions. These results are in accord with the intentional theory of performance, but they present difficulties for the notion of implicit learning.

Adult↗
PubMed1990

The conditioning connection.

In 1948 Konorski argued that conditioning reflects the strengthening of a connection between elements representing the signal and the reinforcer, as a result of the coincidence of activity in the signal element with a rise in activity in the reinforcer element. This Konorskian process represents one way of implementing an error-correcting learning rule and thus, unlike a simple Hebbian process, anticipates selective conditioning, such as that observed in Kamin's blocking procedure. However, the Konorskian process, in common with other error-correcting learning rules, fails to explain why blocking is attenuated by 'surprising' changes in reinforcement conditions that should not augment activity in the reinforcer element. Rather, the reinforcer-specificity of such unblocking suggests the operation of an associability process by which stored information about the past predictive history of the signal is expressed at the connection between signal and reinforcer elements to modulate changes in the connection weight.

Animals↗
PubMed1990

Performance on ratio and interval schedules with matched reinforcement rates.

In the first study, rats were trained to pull a chain on a schedule (RPI) that regulates the probability of reinforcement to maintain a constant average reinforcement rate without differentially reinforcing long inter-response times (IRTs). Although the response rate was sensitive to the overall rate of reinforcement, performance was unaffected by variations between 1 and 50 in the IRT memory size used in programming the schedule. In the second study, two groups of animals performed on either a random-interval (RI) schedule or a RPI schedule, with reinforcement rates determined by those generated by a third group performing on a random ratio (RR) 20 schedule. The RI group responded at a lower rate than the RPI group, which, in turn, responded at a lower rate than the RR group, even though the three groups experienced comparable rates of reinforcement. The fact that the RPI group responded at a lower rate than the RR group suggests that the standard response rate difference observed between ratio and interval schedules, which have been matched for reinforcement rate, cannot be attributed solely to the fact that conventional interval schedules differentially reinforce long IRTs.

Animals↗
PubMed1990

Motivational control of instrumental performance following a shift from thirst to hunger.

Thirsty rats were trained to press a lever for either a sucrose solution or saline before performance was tested in extinction while the animals were either hungry alone or experiencing both hunger and a sodium appetite. Reinforcer-specific motivational control was observed in that the animals trained with the sucrose solution pressed more than those trained with the saline when they were tested hungry, but not when they were tested under combined hunger and sodium appetite. In order to assess the role of a Pavlovian incentive process in this effect, thirsty animals received non-contingent pairings of one stimulus with the sucrose solution and another with saline in the second experiment. In an extinction test the sucrose stimulus augmented lever pressing relative to the saline stimulus when the animals were hungry, but not when they were thirsty. In the subsequent experiments the contribution of the Pavlovian process was equated by giving concurrent training with both incentives. Lever pressing and chain pulling were reinforced concurrently, one with the sucrose solution and the other with saline, while the animals were thirsty. Once again, the animals pressed more in extinction if this action had been trained with the sucrose solution rather than the saline, but only if they were hungry rather than thirsty. Thus, instrumental performance across a thirst-to-hunger shift can also be controlled by an instrumental incentive process. The direct engagement of the instrumental process by this motivational shift contrasts to the absence of such control following a hunger-to-thirst transition (Dickinson & Dawson, 1987a), a fact attributed to the asymmetrical motivational interactions produced by water and food deprivation.

Animals↗
PubMed1989

A phase I study of immunostimulation and toxicity in patients with colorectal carcinoma using the immunomodulator 3,6-bis(2-piperidinoethoxy) acridine trihydrochloride (CL 246738).

Seventeen patients with residual or recurrent colorectal carcinoma were given a new synthetic immunomodulator [3,6-bis(2-piperidinoethoxy) acridine trihydrochloride CL246738) as part of a phase I clinical trial. No patients had undergone previous immunotherapy or chemotherapy. Detailed immunological studies including interferon levels, interleukin 2 levels, natural killer cell function, mitogen responses of lymphocytes, immunoglobulin levels and lymphocyte subpopulation levels were analysed in the patients who received this drug in an attempt to find out whether there was any biological activity identifiable in humans. None of the subjects showed any significant increases in post treatment values of the immunological parameters studied. Toxic effects of the drug at high doses included nausea, diarrhoea and decreased levels of consciousness. In conclusion, no immunological effects were identified following the administration of CL 246738 in human subjects with recurrent or residual colorectal cancer.

Acridines↗
PubMed1987

The thyroid microenvironment in autoimmune thyroid disease: effects of TSH and lymphokines on thyroid lymphocytes and thyroid cells.

Thyroid lymphocytes synthesize thyroid autoantibodies in close proximity to thyroid cells and consequently soluble mediators such as TSH and interleukins (IL) 1 and 2 may have unforeseen effects on lymphocytes and thyrocytes, respectively. Investigations of thyroid autoantibody synthesis by thyroid lymphocytes in vitro showed that TSH did not affect microsomal (Mic) antibody production, but thyroglobulin (Tg) antibody synthesis was decreased, probably as a result of complexing between Tg antibody and Tg secreted by small numbers of thyrocytes in the cell suspension. IL-1 and IL-2 partially mimicked the inhibitory effects on spontaneous autoantibody synthesis induced by Pokeweed mitogen (PWM) in cultures of thyroid lymphocytes. This inhibition may require a number of soluble mediators released by T cells in response to the mitogen; however, depletion studies indicated that the cell type responsible for PWM inhibition is unlikely to be a suppressor T cell and may be an NK cell. IL-1 and IL-2 had little effect on the viability of thyrocyte monolayers in an 18 h assay, but antibody dependent cells cytotoxicity (ADCC) using blood lymphocytes and thyroid autoantibody positive sera was demonstrated; further, the cytotoxicity appeared to be due to Mic antibodies. It is possible that IL-1 and/or IL-2 (as well as other cytokines) may affect thyroid cells after longer periods of exposure, either by altering them functionally or by direct damage. However, assuming that NK cells are present in sufficient numbers in the gland, ADCC could play a major role in the development of hypothyroidism in Hashimoto's disease.

Cells, Cultured↗
PubMed1986

Subpopulations of thyroid autoantibody secreting lymphocytes in Graves' and Hashimoto thyroid glands.

Lymphocytes isolated from Graves' and Hashimoto thyroid tissue by enzymatic (dispase) digestion or mechanical disaggregation were markedly different in terms of their ability to synthesize thyroid autoantibodies in culture. Dispase digestion, followed by removal of thyroid follicular cells, gave a lymphocyte population with a high T:B cell ratio (6:1). However, the ability of these cell suspensions to synthesize microsomal (Mic) and thyroglobulin (Tg) antibodies spontaneously was significantly increased compared with lymphoid suspensions isolated by mechanical means. Spontaneous synthesis of thyroid autoantibodies was not markedly enhanced in cell suspensions prepared from patients' lymph node tissue by digestion compared with mechanical disaggregation. Further, Mic and Tg antibody production by thyroid lymphocytes prepared using dispase was inhibited by pokeweed mitogen (PWM) whereas in most cases suspensions prepared from the same tissues by mechanical dispersion synthesized low or undetectable levels of autoantibodies whether PWM was present or absent. Digestion of tissue debris remaining after mechanical removal of lymphocytes gave suspensions which had an increased proportion of suppressor/cytotoxic T cells compared with suspensions produced mechanically or by digestion alone; however, in terms of spontaneous autoantibody synthesis and PWM induced inhibition, these suspensions were similar to these obtained by digestion alone. It would therefore seem that enzymatic digestion of thyroid tissue resulted in the isolation of a lymphoid population which was different from that extracted by mechanical disaggregation. The digestion process appears to permit the recovery of lymphocytes closely associated with thyroid follicular cells and our studies suggest that it is this population which makes the major contribution to autoantibody synthesis.

Adult↗
PubMed1985

Acute lymphoblastic leukaemia in adults in the northern region of England--a study of 75 cases.

Over a ten-year period we have studied 75 cases of adult acute lymphoblastic leukaemia (ALL). Sixty of the cases were seen from 1979 to 1984 and represent an unselected series of all known cases in a region of 3 000 000 people. Study of these patients has given further insight into the heterogeneous, clinical and cytological nature of adult ALL. Three protocols have been used and results are presented indicating that conventional approaches to treatment in this disease are unsatisfactory. Not all patients could be entered on protocols but these patients are included to give the overall perspective of this disease in clinical practice. A new strategy is proposed which envisages abandoning traditional maintenance chemotherapy in favour of either allogeneic marrow transplant or autologous transplant in first remission in the post-consolidation phase. Preliminary results of this flexible approach are given.

Acute Disease↗
PubMed1985

Thyroid autoantibody synthesis by lymphocytes from different lymphoid organs: fractionation of B cells on density gradients.

Lymphocytes from thymus, blood, lymph nodes and thyroid tissue of patients with autoimmune thyroid disease have been assessed for their ability to synthesize thyroid autoantibodies spontaneously or following stimulation by Pokeweed mitogen (PWM). Blood and thymic lymphocytes synthesized IgG and microsomal or thyroglobulin antibodies of IgG class in response to PWM (and were therefore probably B-memory cells), while thyroid lymphocytes frequently secreted autoantibodies spontaneously. Lymph node lymphocytes resembled blood lymphocytes in terms of increased production of IgG in response to PWM; however, spontaneous secretion of thyroid autoantibodies was observed in some lymph node suspensions, and the magnitude of the increment in thyroid autoantibodies synthesized in response to PWM was lower than that observed for blood lymphocytes. Fractionation of B-cell enriched populations on density gradients and subsequent incubation of the fractions with T cells and PWM demonstrated that, whereas blood B cells capable of synthesizing autoantibody were found in both medium and low density fractions, lymph node precursors of thyroid autoantibody-secreting cells were associated almost exclusively with the light fractions. The presence in lymph nodes of small numbers of low density B cells, compared with a much higher proportion of the heterogeneous population capable of secreting IgG, could account for the discrepancy between the IgG and autoantibody response to PWM. Further, it seems likely that the density difference in the autoantibody precursor population of lymph nodes and blood is related to the difference in the state of activation of B cells in these lymphoid organs.

Adult↗
PubMed1985

Therapeutic exercise.

Physical activity provides the biologic stimulus for a number of body adaptive mechanisms and therefore is a potent force in both prevention and treatment of sports injury. It has been shown, however, that therapeutic exercise must be prescribed with precision and care if it is to be of optimal value. There are no "general" effects of exercise. The effects of exercise on the cellular structure of muscle, connective tissue, and the nervous system are specific to the intensity, duration, and frequency of exercise and dependent on the length of time after injury.

Athletic Injuries↗
PubMed1984

Coccidioidomycosis with cutaneous involvement.

Coccidioidomycosis is a fungal disease endemic in the southwestern United States and northern Mexico. Disseminated disease is often associated with a variety of skin lesions, including ulcerating or intact nodules with underlying sinus tracts. We have reported a case demonstrating that the diagnosis of coccidioidomycosis may be accomplished by histopathologic examination and culture of skin lesions, even when cultures from other sites are negative.

Adult↗
PubMed1984

The dilemma of mild hyperprolactinaemia.

Ninety-eight women with mild hyperprolactinaemia (less than 4N) were followed for a mean duration of 5.5 years. Where pregnancy was desired treatment with bromocriptine (+/- clomiphene) was effective in 87%. Following cessation of bromocriptine therapy almost one-third had a 'spontaneous' resolution of hyperprolactinaemia and resumed cyclical menstrual activity and fertility. Pituitary tumours were identified on coned-view assessment in 9% of patients at the time of presentation and a further 10% during follow-up. Although some of these latter tumours may have been diagnosed earlier had CAT scans been performed routinely in all hyperprolactinaemic patients, such a policy would be hard to justify for those with mild hyperprolactinaemia as the tumours were small, produced no harmful effects, and would almost certainly have responded to bromocriptine should this have been administered. All patients found to have pituitary tumours and given bromocriptine, showed no evidence of tumour progression subsequently, even where pregnancy occurred and the bromocriptine therapy was ceased. In addition, patients without pituitary tumours who were given bromocriptine to achieve pregnancy, were less likely to develop tumours during follow-up even when pregnancy had occurred. Bromocriptine therapy can thus be justified in mildly hyperprolactinaemic patients to reduce troublesome galactorrhoea, achieve pregnancy, improve the chance of 'spontaneous' resolution of the menstrual problem and infertility, control or reduce tumour growth where a pituitary tumour has been identified, and reduce the risk of tumour development in patients with normal radiographs at the time of presentation.

Bromocriptine↗
PubMed1983

Enrichment and depletion of thyroglobulin autoantibody synthesizing lymphocytes.

Lymphocyte populations enriched for (or depleted of) a receptor for thyroglobulin (Tg) have been prepared from Hashimoto peripheral blood mononuclear cells (PBM) by rosetting with Tg coated erythrocytes. Removal of Tg binding cells from PBM or B cell preparations resulted in greater than 85% reduction in their ability to synthesize Tg antibody when stimulated with pokeweed mitogen (PWM) or EB virus (EBV); the depletion was specific since the ability of Tg receptor negative cells to secrete microsomal antibody and total IgG was unimpaired. Hashimoto lymphocytes (PBM or B cells) enriched for Tg binding cells produced only small amounts of Tg antibody when cultured with PWM even in the presence of irradiated T cells and monocytes; exposure to autoantigen followed by mitogen appeared to be inhibitory. However, the Tg receptor positive fraction was readily activated by EBV to synthesize Tg antibody with a specific activity 4-10 times higher than that secreted by unfractionated lymphocytes. The ability to isolate Tg specific B cells from peripheral blood will facilitate the development of EBV transformed cell lines secreting monoclonal Tg antibody and such antibodies will provide invaluable probes in the investigation of autoimmune thyroid disease.

Aged↗
PubMed1983

Giant molluscum contagiosum of the sole.

Molluscum contagiosum is usually diagnosed on the basis of clinical findings. However, when this common lesion is present in an unusual location, such as the sole of the foot, diagnosis may be more difficult. The following case demonstrates that molluscum contagiosum infection should be considered in the differential diagnosis of lesions of the soles.

Adult↗