Biomedical subjects

Geoffrey Hall

Publications and source records attributed to Geoffrey Hall.

30 records · Page 2Linked to original sources

PubMed2003

Uroplakin gene expression in normal human tissues and locally advanced bladder cancer.

The uroplakins are widely regarded as urothelium-specific markers of terminal urothelial cytodifferentiation. This study investigated the expression of the four uroplakin genes, UPIa, UPIb, UPII and UPIII, in a wide range of normal human tissues to determine tissue specificity and in advanced transitional cell carcinoma (TCC) to examine gene expression in primary and metastatic disease. In the urinary tract, all four uroplakins were expressed by urothelium and UPIII was also expressed by prostatic glandular epithelium. UPIa and UPII appeared to be urothelium-specific, but UPIb was detected in several non-urothelial tissues, including the respiratory tract, where it was associated with squamous metaplasia of tracheal and bronchial epithelia. The ten cases of primary TCC and corresponding lymph node metastases demonstrated that each uroplakin gene could be expressed at the mRNA level. No single uroplakin gene was expressed in all primary tumours or metastases, but 80% of the primary tumours and 70% of the lymph node metastases expressed at least one uroplakin gene. UPIII mRNA was often expressed in the absence of UPIII protein. These results confirm that in human tissues the expression of UPIa and UPII genes is highly specific to urothelium and suggest that the tight differentiation-restricted expression of uroplakin genes in normal urothelium is lost following malignant transformation.

Carcinoma, Transitional Cell↗

PubMed2003

Acquired equivalence and distinctiveness in human discrimination learning: evidence for associative mediation.

In the first stage of Experiments 1-3, subjects learned to associate different geometrical figures with colors or with verbal labels. Performance in Stage 2, in which the figures signaled which of 2 motor responses should be performed, was superior in subjects required to make the same response to figures that had shared the same Stage 1 associate. A third stage of testing showed that the events used as associates in Stage 1 were capable of evoking the motor response trained in Stage 2, an outcome predicted by an associative interpretation of such transfer effects. Experiment 4 provided evidence that the relevant associations can be effective in controlling motor responding even when subjects report an antagonistic relationship between events.

Adolescent↗

PubMed2003

Learned changes in the sensitivity of stimulus representations: associative and nonassociative mechanisms.

Central to associative learning theory is the proposal that the concurrent activation of a pair of event representations will establish or strengthen a link between them. Associative theorists have devoted much energy to establishing what representations are involved in any given learning paradigm and the rules that determine the degree to which the link is strengthened. They have paid less attention to the question of what determines that a representation will be activated, assuming, for the case of classical conditioning, that presentation of an appropriately intense stimulus from an appropriate modality will be enough. But this assumption is unjustified. I present the results of experiments on the effects of stimulus exposure in rats that suggest that mere exposure to a stimulus can influence its perceptual effectiveness -- that the ability of a stimulus to activate its representation can be changed by experience. This conclusion is of interest for two reasons. First, it supplies a direct explanation for the phenomenon of perceptual learning -- the enhancement of stimulus discriminability produced by some forms of stimulus exposure. Second, it poses a theoretical challenge in that it seems to require the existence of a learning mechanism outside the scope of those envisaged by current formal theories of associative learning. I offer some speculations as to how this mechanism might be incorporated into such theories.

Animals↗

PubMed2003

Discrimination between outcomes in instrumental learning: effects of preexposure to the reinforcers.

In two experiments rats received instrumental training with two response levers, one response being reinforced by sucrose solution and the other by sucrose pellets. Prior to a test session, on which both levers were made available in the absence of reinforcement, the rats were given free access to one of the reinforcers, a procedure known to reduce its value. It was found that the rats responded at a lower rate on the lever that had produced the now-devalued reinforcer, but that this effect was substantial only in rats that had received preexposure to the two reinforcers before instrumental training was begun (Experiment 1). Experiment 2 demonstrated that this effect was obtained only when presentations of the two reinforcers were presented according to an inter-mixed schedule during preexposure. It is suggested that this result constitutes an instance of the perceptual learning effect in which intermixed preexposure to similar events enhances their discriminability.

Animals↗

PubMed2003

Changes in stimulus salience as a result of stimulus preexposure: evidence from aversive and appetitive testing procedures.

In two experiments, rats received preexposure to three compound flavor stimuli, AX, BX, and CX, where X represents a saline solution. AX and BX were presented in alternation; CX, on a separate block of trials. The value of X was then modified, being devalued by aversive conditioning in Experiment 1, and rendered valuable by the induction of a state of salt need in Experiment 2. When given a choice between BX and CX, the rats consumed more of BX than of CX in Experiment 1, and more of CX than of BX in Experiment 2, suggesting that B and C differed in their ability to modulate the response governed by the X element. It was suggested that blocked preexposure to CX reduces the salience of the C stimulus but that the salience of B is maintained by preexposure in which BX is alternated with AX. The implications of this result for the phenomenon of perceptual learning are discussed.

Animals↗

PubMed2003

Negative priming and occasion setting in an appetitive Pavlovian procedure.

Rats received training in which two auditory target stimuli, X and Y, were signaled by two visual stimuli, A and B, and followed by food (i.e., A-->X+, B-->Y+). The test consisted of presentations of X and Y preceded either by the same signal as during training (same trials: A-->X, B-->Y) or by the alternative signal (different trials: A-->Y, B-->X). After 8 training sessions, the animals responded less on same trials than on different trials; this effect was significantly reduced after 24 training sessions. In two additional experiments, animals that had also experienced presentations of A and B alone, either before or during training, showed the opposite pattern of results, responding more on same trials than on different trials. These results are interpreted as being due to the interaction between the effects of occasion setting and negative priming (see Wagner, 1981).

Animals↗

PubMed2003

Perceptual learning in flavor aversion: evidence for learned changes in stimulus effectiveness.

Rats were exposed to the compound flavors AX and BX, presented in alternation, and to CX on a separate block of trials. Generalization to BX after aversion conditioning with AX was less than to CX. An equivalent effect was found when the nature of the common element was changed after preexposure but not when the common element was omitted during preexposure, during conditioning and test, or both. Rats conditioned with X alone again showed less aversion to BX than to CX; similarly, rats conditioned with a novel flavor (Y) showed less aversion to BY than to CY. These effects support the proposal that intermixed preexposure to AX and BX enhances the perceptual effectiveness of their unique features, A and B.

Animals↗

PubMed2002

Analysis of the perceptual learning effect in flavour aversion learning: evidence for stimulus differentiation.

Rats received exposure to two compound flavours, AX and BX, where A and B were sucrose and saline and X was acid. For group intermixed (1), exposure consisted of alternating trials with AX and BX; group blocked (B) received a block of AX trials and a separate block of BX trials. Experiment 1 showed that generalization to BX after conditioning with AX was less profound in group 1 than in group B. Separate examination of the elements of the compound showed that the source of this difference lay in the strength acquired by the X element. X acquired less strength in group 1 than in group B (Experiments 1 and 2), whereas for the A element (Experiments 3 and 4) the reverse pattern was obtained. These results support the proposal that the perceptual learning effect (restricted generalization from AX to BX in group 1) depends on a process that enhances the effectiveness of unique stimulus elements (A and B) and reduces that of common elements (such as X).

Animals↗

PubMed2002

Taste aversion after ingestion of lithium chloride: an associative analysis.

In five experiments with rats we examined the aversion established by consumption of a solution of lithium chloride (LiCl). Experiment 1 showed that consumption of LiCl established an aversion to saline (NaCl). Experiment 2 showed that the size of the aversion was reduced in rats given pre-exposure to saline (a latent inhibition effect). Experiment 3 showed that experience of a sucrose-saline compound prior to consumption of LiCl generated an aversion to sucrose (a sensory preconditioning effect). Experiments 4 and 5 examined the effects produced by consumption of a sucrose-LiCl compound and demonstrated reciprocal overshadowing between the two tastes. These results confirm that consumption of LiCl establishes an aversion to the taste of this substance. Their implications for the use of orally consumed LiCl as a technique for the control of predatory behaviour are discussed.

Animals↗

PubMed2002

Postinjection suppression of drinking is modified by the presence of conditioned contextual cues: implications for both anticipatory and posttreatment nausea in humans.

In three experiments, we set out to determine whether the response of rats to an injection of LiCl would be modified by the presence of an environmental context that had previously been paired with LiCl. Experiment 1 confirmed that one feature of the malaise produced by LiCl is a reduced tendency to consume an otherwise palatable flavor. Experiment 2 showed that the size of this response was enhanced if it was measured in the presence of a conditioned context. In Experiment 3, we investigated the possibility that the postinjection response could be modified by an overshadowing treatment given during the conditioning phase. The significance of these findings for the understanding of chemotherapy-induced nausea in the clinical population is discussed.

Animals↗

PubMed2002

Perceptual learning with a sodium depletion procedure.

Rats in a state of salt need prefer a flavor that has previously been paired with saline (Experiment 1). In Experiments 2 and 3, rats exposed to 2 saline concentrations, presented either concurrently or on separate trials, and each paired with a different flavor, showed a preference for the flavor that had been associated with the stronger saline. This effect was substantial, however, only in those rats that had experienced the concurrent exposure schedule. This effect cannot be attributed to a difference in the strength of within-compound associations produced by the 2 preexposure schedules (Experiment 4). It is suggested that concurrent preexposure can engage a learning process that enhances the discriminability of the preexposed stimuli.

Animals↗

PubMedDate not supplied

Latent inhibition of rotation chair-induced nausea in healthy male and female volunteers.

OBJECTIVES: Pre-exposure to an environment in which a nausea-inducing body rotation will subsequently be given constitutes a latent inhibition procedure that might act to reduce anticipatory and postrotation nausea. METHODS: This was tested in 24 healthy subjects randomly assigned to receive no pre-exposure (group 0), a single pre-exposure (group 1), or three pre-exposures (group 3). Rotation was standardized as 5 x 1 minute rotation, but the subjects could terminate it on request. Nausea was determined on a 7-item symptom rating scale before, during, and after rotation on days 3 and 4, whereas anticipatory nausea was measured before presumed rotation on day 5. Saliva cortisol and tumor necrosis factor alpha (TNF-alpha) levels were determined at baseline before, directly, and 15 and 30 minutes after rotation every day, and before presumed rotation on day 5. RESULTS: Pre-exposure significantly reduced the degree of anticipatory nausea on day 5. Cortisol levels increased with rotation and were higher at baseline on days 4 and 5, but subjects habituated from day 3 to day 4; levels were lower in women than in men. In contrast, TNF-alpha decreased with rotation but showed no habituation. For both cortisol and TNF-alpha, no effects on postrotational nausea were found. CONCLUSION: It is concluded that repetitive pre-exposure (latent inhibition) reduces anticipatory but not postrotation nausea; behavioral measures (rotation time) and measures of acute stress (cortisol, TNF-alpha) do not respond to latent inhibition. Thus, Pavlovian conditioning rules are effective in healthy humans with anticipatory nausea but not with postrotation nausea. Hormonal responses--TNF-alpha decrease with stress, compensatory cortisol increase--and gender-related effects on learning and habituation are discussed with regard to psychophysiological and psychoimmunological processes.

Adult↗