Biomedical subjects

J Piedra

Publications and source records attributed to J Piedra.

7 recordsLinked to original sources

PubMed2001

Regulation of beta-catenin structure and activity by tyrosine phosphorylation.

beta-Catenin plays a dual role as a key effector in the regulation of adherens junctions and as a transcriptional coactivator. Phosphorylation of Tyr-654, a residue placed in the last armadillo repeat of beta-catenin, decreases its binding to E-cadherin. We show here that phosphorylation of Tyr-654 also stimulates the association of beta-catenin to the basal transcription factor TATA-binding protein. The structural bases of these different affinities were investigated. Our results indicate that the beta-catenin C-terminal tail interacts with the armadillo repeat domain, hindering the association of the armadillo region to the TATA-binding protein or to E-cadherin. Phosphorylation of beta-catenin Tyr-654 decreases armadillo-C-terminal tail association, uncovering the last armadillo repeats. In a C-terminal-depleted beta-catenin, the presence of a negative charge at Tyr-654 does not affect the interaction of the TATA-binding protein to the armadillo domain. However, in the case of E-cadherin, the establishment of ion pairs dominates its association with beta-catenin, and its binding is greatly dependent on the absence of a negative charge at Tyr-654. Thus, phosphorylation of Tyr-654 blocks the Ecadherin-beta-catenin interaction, even though the steric hindrance of the C-tail is no longer present. These results explain how phosphorylation of beta-catenin in Tyr-654 modifies the tertiary structure of this protein and the interaction with its different partners.

Cytoskeletal Proteins↗

PubMed1999

Regulation of E-cadherin/Catenin association by tyrosine phosphorylation.

Alteration of cadherin-mediated cell-cell adhesion is frequently associated to tyrosine phosphorylation of p120- and beta-catenins. We have examined the role of this modification in these proteins in the control of beta-catenin/E-cadherin binding using in vitro assays with recombinant proteins. Recombinant pp60(c-src) efficiently phosphorylated both catenins in vitro, with stoichiometries of 1.5 and 2.0 mol of phosphate/mol of protein for beta-catenin and p120-catenin, respectively. pp60(c-src) phosphorylation had opposing effects on the affinities of beta-catenin and p120 for the cytosolic domain of E-cadherin; it decreased (in the case of beta-catenin) or increased (for p120) catenin/E-cadherin binding. However, a role for p120-catenin in the modulation of beta-catenin/E-cadherin binding was not observed, since addition of phosphorylated p120-catenin did not modify the affinity of phosphorylated (or unphosphorylated) beta-catenin for E-cadherin. The phosphorylated Tyr residues were identified as Tyr-86 and Tyr-654. Experiments using point mutants in these two residues indicated that, although Tyr-86 was a better substrate for pp60(c-src), only modification of Tyr-654 was relevant for the interaction with E-cadherin. Transient transfections of different mutants demonstrated that Tyr-654 is phosphorylated in conditions in which adherens junctions are disrupted and evidenced that binding of beta-catenin to E-cadherin in vivo is controlled by phosphorylation of beta-catenin Tyr-654.

Animals↗

PubMed1994

Stereotactic retransplantation in Parkinson's disease: clinical, imaging and electrophysiological evidence of adrenal brain graft viability.

In March 1993, a patient with idiopathic Parkinson disease who had received an adrenal brain autograft 6 years before underwent bilateral stereotactic transplantation of a mesencephalic cell suspension into the striatum, in order to prevent further deterioration in his neurological condition. During the CT-guided surgical planning and the transplantation procedures, electrophysiological evidence of the adrenal graft viability was assessed. Based on these findings, we drew the preliminary conclusion that the chromaffin tissue implanted in April 1987 is still functional, which explains the clinical evolution of this patient during the postoperative long-term follow-up.

Adrenal Medulla↗

PubMed1994

CT-oriented microrecording guided selective thalamotomy.

A further trial of CT-oriented microrecording guided stereotactic selective thalamotomy was conducted at the Centro Internacional de Restauración Neurológica, Havana City as treatment of resting tremor in 11 patients with idiopathic Parkinson's disease (PD), and in 3 other patients with intentional tremor associated with multisystemic atrophy and cerebral palsy. Three of the parkinsonian patients had undergone fetal mesencephalic tissue transplantation with significant improvement of the most debilitating symptoms of PD and stabilization of the motor state, but predominantly unilateral tremor had impaired them progressively despite increased levodopa doses. A Leksell frame was used with a novel surgical planning system and electrophysiological recordings to identify the optimal target point inside the ventralis intermedius. In all but 1 case, the tremor was totally arrested. No persistent complications were observed.

Case-Control Studies↗

PubMed1994

Neurotransplantation in Parkinson's disease: from open microsurgery to bilateral stereotactic approach: first clinical trial using microelectrode recording technique.

This paper summarizes the results of three controlled clinical trials related to the transplantation of embryonic ventral mesencephalic tissue into the striatum of 46 idiopathic parkinsonian patients exhibiting motor complications on standard levodopa therapy. From January 1988 to April 1990, 30 subjects with fluctuating Parkinson's disease received fetal dopaminergic tissue implants by the open microsurgical technique. In March 1992 the stereotactic approach was adopted for successive fetal mesencephalic cell suspension transplants (7 unilateral and 9 bilateral) into the caudate and putamen of parkinsonian patients with levodopa-induced complex fluctuations and dyskinesias. The neurological assessment performed 12 months before and 3-18 months after transplantation demonstrated a reduction of both the daily time spent in the 'off' condition and the number of daily 'off' periods, and a significant improvement of the motor scale. The stereotactic selective thalamotomy with microelectrode recording was introduced in January 1993, in order to provide a further potential treatment strategy; i.e., the combination of the two surgical trends in Parkinson's disease, the restorative neurotransplantation technique, and the selective lesional approach. In addition to that, microelectrode recording is also used for implantation site selection and functional characterization.

Adrenal Medulla↗

PubMed1994

Computer-assisted CT-guided stereotactic biopsy and brachytherapy of brain tumors.

From March 1991 to September 1993, 26 patients (aged 4-78 years) with brain tumors (4 glioblastoma multiforme, 10 nonglioblastoma multiforme, 1 mixed oligoastrocytoma, 2 carniopharyngiomas, 2 meningiomas and 7 metastases) were treated with stereotactic techniques at the Centro Internacional de Restauración Neurológica, La Habana, Cuba. A total of 28 stereotactic surgical procedures were performed with no operative mortality; they included biopsies in all cases, 1 stereotactic microsurgical resection and 12 permanent implants of 192Ir, followed by external beam fractionated radiation therapy (40-60 Gy). The present paper shows that the combined use of a stereotactic approach, a comprehensive and reliable stereotactic dosimetric planning system, stereotactic brachytherapy with 192Ir and complementary percutaneous radiation treatment constitutes a promising strategy for brain tumor management.

Adolescent↗

PubMedDate not supplied

[Stereotaxic biopsy and 192Ir implant in intracranial tumors. A review of 7 years of experience].

INTRODUCTION: The combination of stereotaxic techniques, advances in neuroimaging and the creation of continually improving software has permitted stereotaxic biopsy of cerebral lesions at the most varied sites. Improvement in the method of permanent interstitial radiation (brachytherapy) improves the precision with which the radioactive sources may be inserted, releasing a maximum dose of radiation to the tumour with minimum radiation to the surrounding tissue. PATIENTS AND METHODS: We treated 237 patients (aged 1 to 78 years) with intracranial lesions, all included in the protocol of our centre. Stereotaxic systems of Leksell, Riechert-Mundinger, Micromar and Estereoflex were used. The procedure was in three stages: acquisition of the image, surgical planning and surgical operation. The imaging guide was the computerized axial tomography (CAT). RESULTS: Stereotaxic biopsy guided by CAT images was done in 153 patients. These were divided into three groups, taking the biopsy findings as the reference: group A (primary tumors, 128), group B (metastatic tumors, 15) and group C (non-malignant lesions, 10). Ninety six permanent implants of 192Ir were inserted, with a low dose of 4-7 cGy/h and a total dose of 80-120 Gy. CONCLUSIONS: Stereotaxic biopsy is a very effective procedure with a significantly low range of complications. The permanent implant with a low dose rate, well situated and using a source of 192Ir is a safe, simple, effective method for the treatment of primary and recurrent glial tumours, and non-glial tumours which fulfil criteria for this type of brachytherapy.

Adolescent↗