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Biomedical subjects

José Prados

Publications and source records attributed to José Prados.

7 recordsLinked to original sources

The Espinet and the perceptual learning effects in flavour aversion conditioning: do they depend on a common inhibitory mechanism?

In three experiments rats were given short or long preexposure (4 or 10 sessions) to two compound flavours, AX and BX, according to an intermixed or a blocked schedule. Following preexposure, aversion conditioning trials were given with AX as the conditioned stimulus (CS). In Experiments 1 and 2, retardation and summation tests were then carried out to assess the inhibitory properties of B (an Espinet procedure). In Experiment 3, test trials evaluated generalization from AX to BX (the standard perceptual learning procedure). The results showed that B performed as an inhibitor of the unconditioned stimulus (US; an Espinet effect) only after long intermixed preexposure, whereas a reliable perceptual learning effect was observed both after short and after long preexposure. The observation that B had no detectable inhibitory properties after short preexposure casts doubt on the suggestion that inhibitory learning is responsible for perceptual learning after brief exposure to AX and BX.

Animals↗

Prognostic value of RT-PCR tyrosinase detection in peripheral blood of melanoma patients.

Malignant melanoma (MM) prognosis has been related to tumour thickness and clinical stage and metastasis risk has been associated with presence of tumour cells in peripheral blood. The aim of this study was to determine the relationship between presence of tyrosinase in peripheral blood of MM patients and their clinical prognosis. Blood samples from 58 MM patients (stage I-IV) were analysed, using RT-PCR assay to detect tyrosinase mRNA. The results showed that positive RT-PCR assay for tyrosinase were significantly associated with clinical status and tumour thickness. After a median follow-up of 24 months, RT-PCR results were found to be significant correlated with recurrence (p<0.05) and clinical stage III (p<0.05). Separate analysis of stage III tumours to determine the prognostic value of tyrosinase presence in peripheral blood showed an overall 24-month survival rate of 70% in the RT-PCR negative group versus 10% in the positive group (p<0.02). These results suggest that detection of circulating melanoma cells may be especially relevant in stage III patients, in whom RT-PCR positivity defines a subpopulation at high risk of recurrence.

Adult↗

Modulation of the effective salience of a stimulus by direct and associative activation of its representation.

In 2 experiments, rats received exposure to presentations of a footshock preceded by a given cue. In the PRf (partial reinforcement) condition, this cue also occurred in the absence of the shock; in the CRf (continuous reinforcement) condition, it did not. Subsequent testing in which a new stimulus was used to signal the shock (Experiment 1) showed that the shock was more effective as a reinforcer for the PRf than for the CRf group. In Experiment 2, the shock was used as a conditioned stimulus signaling food delivery, and it was found that conditioning occurred more readily in the PRf than in the CRf group. These results accord with the hypothesis that preexposure to the shock results in a decline in its effective salience but that experience of a cue that signals shock in the absence of the shock itself attenuates this effect and helps maintain stimulus salience.

Analysis of Variance↗

Dissociation between the Espinet and perceptual learning effects in flavour aversion conditioning.

In three experiments rats were given pre-exposure to two compound flavours, AX and BX, the two compounds being presented for some subjects on alternate trials (the intermixed schedule) and, for others, in separate blocks of trials (the blocked schedule). After aversion conditioning with A (in Experiments 1 and 2), the inhibitory properties of B were tested using both retardation (Experiment 1) and summation tests (Experiment 2). The results failed to support the proposal [Anim. Learn. Behav. 23 (1995) 361] that B should acquire inhibitory properties in the intermixed condition (the "Espinet effect"). Experiment 3 demonstrated that generalisation to BX after conditioning with AX was attenuated by intermixed pre-exposure (a perceptual learning effect). This pattern of results challenges the hypothesis that inhibitory learning during intermixed pre-exposure to AX and BX can account for both the Espinet and the perceptual learning effects.

Animals↗

Growth inhibition, G(1)-arrest, and apoptosis in MCF-7 human breast cancer cells by novel highly lipophilic 5-fluorouracil derivatives.

In this study we evaluate the antitumour activity, the cell cycle arrest and apoptotic properties of novel lipophilic benzene-fused seven-membered 5-fluorouracil (5-FU) analogs in comparison to 5-FU on MCF-7 human breast cancer cells. The lipophilicities of ESB-786B, ESB-252A and ESB-928A were predicted by using the CDR option of the PALLAS 2.0 program. Cytotoxic assays were evaluated in MCF-7 cells treated with the sulforhodamine B colorimetric method. Cell cycle perturbations were studied by flow cytometry. Apoptosis was determined by both DNA fragmentation and annexin V-FITC and propidium iodide staining. The novel derivatives were more lipophilic than 5-FU and induced a marked growth inhibition, in a dose-dependent manner. After treatment with IC(50) value (ranged from 2.5 to 22 microM) for each compound, light microscopy observation showed modifications in the morphology of MCF-7 cells. In addition, the 5-FU analogs arrest cells in the G(0)/G(1) phase of the cell cycle whereas 5-FU induced arrest in S-phase. Moreover, induction of apoptosis was demonstrated by the annexin-V-based assay and confirmed using DNA fragmentation analysis on MCF-7 cells, a cell line in which the induction of DNA laddering is very difficult. The novel benzannelated seven-membered 5-FU analogs can be considered as specific apoptotic inducers. These experimental findings provide support for the use of these novel compounds as new weapons in the fight against breast cancer.

Animals↗

Transfection of MS-36 melanoma cells with gef gene inhibits proliferation and induces modulation of the cell cycle.

The gef gene, found in Escherichia coli DNA, encodes a small (50 amino acids) protein which is related to cell-killing functions. We used the MS-36 melanoma cell line as an experimental model to examine the usefulness of the gef gene as a new strategy for cancer therapy. We transfected MS-36 cells using the pMAMneo vector, and induced gef gene expression with dexamethasone. This decreased the proliferation rate of MS-36TG by as much as 85% in comparison with MS-36 parental cells. The decrease in cell growth was accompanied with significant modifications of the cell cycle and morphology. The G1-phase gradually disappeared, with accumulation in the S-phase. However, studies with annexin V-FITC and 7-aminoactinomycin D failed to demonstrate induction of apoptosis. Morphological changes were an increase in cell size and the number of filopodia, and especially the appearance of pore-like alterations in the cell membrane which were not seen in parental cells. Our results demonstrate that the gef gene, a system independent of the administration of a prodrug, significantly reduces the proliferation of MS-36 cells. This gene may therefore be considered a new candidate for cancer gene therapy.

Apoptosis↗

Recovery effects after extinction in the Morris swimming pool navigation task.

In three experiments in which rats were used as subjects, we developed an extinction procedure using a Morris pool. The animals were trained to find a hidden platform located at a fixed position and were then given extinction trials in which the platform was removed from the pool. When training and extinction were carried out in the same context and time was allowed to elapse between extinction and test, spontaneous recovery of learning was observed. On the other hand, those rats that received extinction in a context different from the one used for training failed to show spontaneous recovery of learning when tested in the extinction context after an interval of 96 h. However, they did show renewal of spatial learning when tested in the training context. These results show that extinction in the spatial domain behaves like extinction in standard conditioning preparations.

Animals↗