Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 7 de 7
Filter
Add more filters











Database
Publication year range
1.
Rev Neurol ; 66(1): 1-6, 2018 Jan 01.
Article in Spanish | MEDLINE | ID: mdl-29251336

ABSTRACT

AIMS: Simultaneous bilateral implantation of electrodes in the subthalamic nucleus for idiopathic Parkinson's disease (IPD) is associated with long surgery time, language disorders and post-operative confusion. Moreover, there is evidence of ipsilateral improvement after stimulation of the subthalamic nucleus. In order to optimise perioperative management a prospective study is conducted with deep brain stimulation (DBS) in the subthalamic nucleus in two consecutive unilateral procedures. PATIENTS AND METHODS: We conducted a prospective study of 41 patients with bilateral IPD, with DBS implantation in two unilateral surgical phases. Its clinical outcomes are analysed according to the Unified Parkinson's Disease Rating Scale (UPDRS), the Hoehn and Yahr, and the Schwab and England scales, together with their complications. RESULTS: The mean age was 61 ± 7 years old, 23 males. Five patients (12%) did not undergo surgery of the contralateral subthalamic nucleus due to good control. The mean on the motor UPDRS and the Hoehn and Yahr in preoperative pharmacological off was 44 ± 14 and 3, respectively, and 19 ± 8 and 1.8 at six months' follow-up. The mean improvement on the Schwab and England scale in the pre-operative period and at six months was 39%. Two patients suffered post-operative confusion, and one of them had transient dysarthria. CONCLUSIONS: Bilateral DBS in two unilateral stages was an effective option with few complications in our series of patients with IPD. 10% of the patients did not require contralateral electrodes. It would be necessary to conduct a randomised study in patients who underwent bilateral surgery in one and two stages in order to confirm these results.


TITLE: Implantacion bilateral en dos tiempos para estimulacion cerebral profunda en el tratamiento de la enfermedad de Parkinson idiopatica bilateral: resultados clinicos.Objetivo. La implantacion bilateral simultanea de electrodos en el nucleo subtalamico para la enfermedad de Parkinson idiopatica (EPI) se asocia a una duracion elevada de la intervencion, alteraciones del lenguaje y confusion posquirurgica; ademas, existe evidencia de mejoria ipsilateral tras la estimulacion del nucleo subtalamico. Para optimizar el manejo perioperatorio se realiza un estudio prospectivo con estimulacion cerebral profunda (ECP) en el nucleo subtalamico en dos procedimientos unilaterales consecutivos. Pacientes y metodos. Estudio prospectivo de 41 pacientes con EPI bilateral, con implantacion de ECP en dos fases quirurgicas unilaterales. Se analizan sus resultados clinicos segun las escalas Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn y Yahr, y Schwab y England, asi como sus complicaciones. Resultados. La edad media fue de 61 ± 7 años, 23 hombres. Cinco pacientes (12%) no fueron intervenidos del nucleo subtalamico contralateral por buen control. La media en la UPDRS motora y la Hoehn y Yahr en off farmacologico preoperatorio fue de 44 ± 14 y 3, respectivamente, y de 19 ± 8 y 1,8 a los seis meses de seguimiento. La mejoria media en la escala de Schwab y England en el preoperatorio y a los seis meses fue del 39%. Dos pacientes tuvieron confusion postoperatoria, y uno, disartria transitoria. Conclusiones. La ECP bilateral en dos etapas unilaterales fue una opcion eficaz y con escasas complicaciones en nuestra serie de pacientes con EPI. El 10% de los pacientes no preciso electrodos contralaterales. Seria necesario un estudio aleatorizado en pacientes sometidos a cirugia bilateral en uno y dos tiempos para confirmar estos resultados.


Subject(s)
Deep Brain Stimulation/methods , Parkinson Disease/therapy , Female , Humans , Male , Middle Aged , Neurosurgical Procedures/methods , Parkinson Disease/pathology , Prospective Studies , Prosthesis Implantation/methods , Treatment Outcome
2.
Rev Neurol ; 63(12): 537-542, 2016 Dec 16.
Article in Spanish | MEDLINE | ID: mdl-27897304

ABSTRACT

INTRODUCTION: Diffusion tensor imaging (DTI) is a non-invasive technique that can be used to assess the integrity of the white matter in the brain. AIMS: To investigate the usefulness of DTI in patients with temporal lobe epilepsy (TLE) and to observe its relationship with lateralisation of the epileptogenic focus in these patients. PATIENTS AND METHODS: We analysed 11 patients diagnosed with TLE in accordance with the pre-surgical protocol of our epilepsy unit, and who were seizure-free two years after performing a temporal lobectomy plus amygdalohippocampectomy (Spencer technique). As part of their pre-operative study, a 1.5 T magnetic resonance brain scan with diffusion tensor imaging was performed. A voxel-based analysis was then employed to study the differences in connectivity between the hemisphere that underwent surgery and the contralateral hemisphere. RESULTS: Compared with the contralateral hemisphere, a statistically significant reduction in fractional anisotropy (p < 0.05) was observed in the corpus callosum, the cingulate, the superior longitudinal fasciculus, the anterior thalamic radiations, the internal capsule, the ventral lateral and pulvinar nuclei of the thalamus, the inferior frontooccipital fasciculus, the uncinate fasciculus, the inferior longitudinal fasciculus and the parahippocampal gyrus, all ipsilateral to the epileptogenic focus. CONCLUSIONS: The characterisation of the abnormalities in the connectivity of the cerebral white matter, by means of DTI in patients with TLE, can be a valuable aid for the lateralisation of the epileptogenic focus in the pre-surgical evaluation of these patients. Further studies with a higher number of patients would be needed to confirm these results.


TITLE: Papel de la imagen por tensor de difusion en el estudio prequirurgico de la epilepsia del lobulo temporal.Introduccion. La imagen por tensor de difusion (DTI) es una tecnica no invasiva que puede ser utilizada para evaluar la integridad de la sustancia blanca cerebral. Objetivo. Investigar la utilidad de la DTI en pacientes con epilepsia del lobulo temporal (ELT) y ver su relacion con la lateralizacion del foco epileptogeno en estos pacientes. Pacientes y metodos. Se analizan 11 pacientes diagnosticados de ELT segun el protocolo de evaluacion prequirurgica de nuestra unidad de epilepsia, y libres de crisis a los dos años de la realizacion de una lobectomia temporal mas amigdalohipocampectomia (tecnica de Spencer). Como parte de su estudio preoperatorio, se realiza una resonancia magnetica cerebral de 1,5 T con secuencia de tensor de difusion y se estudian, mediante un analisis basado en voxel, las diferencias en la conectividad entre el hemisferio intervenido y el contralateral. Resultados. Comparado con el hemisferio contralateral, se observo una reduccion de la anisotropia fraccional estadisticamente significativa (p < 0,05) en el cuerpo calloso, el cingulo, el fasciculo longitudinal superior, las radiaciones talamicas anteriores, la capsula interna, los nucleos ventral lateral y pulvinar del talamo, el fasciculo frontooccipital inferior, el fasciculo uncinado, el fasciculo longitudinal inferior y el giro parahipocampal ipsilaterales al foco epileptogeno. Conclusiones. La caracterizacion de las anormalidades en la conectividad de la sustancia blanca cerebral, a traves de la DTI en pacientes con ELT, puede tener un valor importante para la lateralizacion del foco epileptogeno en la evaluacion prequirurgica. Serian necesarios estudios con un numero mas elevado de pacientes para confirmar estos resultados.


Subject(s)
Corpus Callosum/diagnostic imaging , Diffusion Tensor Imaging , Epilepsy, Temporal Lobe/diagnostic imaging , White Matter/diagnostic imaging , Anisotropy , Corpus Callosum/pathology , Humans , White Matter/pathology
3.
J Biol Chem ; 275(46): 36358-68, 2000 Nov 17.
Article in English | MEDLINE | ID: mdl-10964924

ABSTRACT

Thrombospondin induces reorganization of the actin cytoskeleton and restructuring of focal adhesions. This activity is localized to amino acids 17-35 in the N-terminal heparin-binding domain of thrombospondin and can be replicated by a peptide (hep I) with this sequence. Thrombospondin/hep I stimulate focal adhesion disassembly through a mechanism involving phosphoinositide 3-kinase activation. However, the receptor for this thrombospondin sequence is unknown. We now report that calreticulin on the cell surface mediates focal adhesion disassembly by thrombospondin/hep I. A 60-kDa protein from endothelial cell detergent extracts has homology and immunoreactivity to calreticulin, binds a hep I affinity column, and neutralizes thrombospondin/hep I-mediated focal adhesion disassembly. Calreticulin on the cell surface was confirmed by biotinylation, confocal microscopy, and by fluorescence-activated cell sorting analyses. Thrombospondin and calreticulin potentially bind through the hep I sequence, since thrombospondin-calreticulin complex formation can be blocked specifically by hep I peptide. Antibodies to calreticulin and preincubation of thrombospondin/hep I with glutathione S-transferase-calreticulin block thrombospondin/hep I-mediated focal adhesion disassembly and phosphoinositide 3-kinase activation, suggesting that calreticulin is a component of the thrombospondin-induced signaling cascade that regulates cytoskeletal organization. These data identify both a novel receptor for the N terminus of thrombospondin and a distinct role for cell surface calreticulin in cell adhesion.


Subject(s)
Calcium-Binding Proteins/metabolism , Focal Adhesions/metabolism , Membrane Proteins/metabolism , Ribonucleoproteins/metabolism , Thrombospondins/metabolism , Amino Acid Sequence , Animals , Antibodies/immunology , Antibodies/pharmacology , Biotinylation , CD36 Antigens/chemistry , CD36 Antigens/immunology , CD36 Antigens/isolation & purification , CD36 Antigens/metabolism , Calcium-Binding Proteins/chemistry , Calcium-Binding Proteins/immunology , Calcium-Binding Proteins/isolation & purification , Calreticulin , Cattle , Cells, Cultured , Chromatography, Affinity , Cytoskeleton/drug effects , Cytoskeleton/metabolism , Endothelium, Vascular/chemistry , Endothelium, Vascular/cytology , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Enzyme Activation/drug effects , Flow Cytometry , Fluorescent Antibody Technique , Focal Adhesions/chemistry , Focal Adhesions/drug effects , Humans , Macromolecular Substances , Membrane Proteins/chemistry , Membrane Proteins/immunology , Membrane Proteins/isolation & purification , Peptide Fragments/chemistry , Peptide Fragments/immunology , Peptide Fragments/metabolism , Peptide Fragments/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Ribonucleoproteins/chemistry , Ribonucleoproteins/immunology , Ribonucleoproteins/isolation & purification , Sequence Homology, Amino Acid , Thrombospondins/antagonists & inhibitors
4.
J Cell Sci ; 111 ( Pt 5): 615-24, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9454735

ABSTRACT

A current model of growth factor-induced cell motility invokes integration of diverse biophysical processes required for cell motility, including dynamic formation and disruption of cell/substratum attachments along with extension of membrane protrusions. To define how these biophysical events are actuated by biochemical signaling pathways, we investigate here whether epidermal growth factor (EGF) induces disruption of focal adhesions in fibroblasts. We find that EGF treatment of NR6 fibroblasts presenting full-length WT EGF receptors (EGFR) reduces the fraction of cells presenting focal adhesions from approximately 60% to approximately 30% within 10 minutes. The dose dependency of focal adhesion disassembly mirrors that for EGF-enhanced cell motility, being noted at 0.1 nM EGF. EGFR kinase activity is required as cells expressing two kinase-defective EGFR constructs retain their focal adhesions in the presence of EGF. The short-term (30 minutes) disassembly of focal adhesions is reflected in decreased adhesiveness of EGF-treated cells to substratum. We further examine here known motility-associated pathways to determine whether these contribute to EGF-induced effects. We have previously demonstrated that phospholipase C(gamma) (PLCgamma) activation and mobilization of gelsolin from a plasma membrane-bound state are required for EGFR-mediated cell motility. In contrast, we find here that short-term focal adhesion disassembly is induced by a signaling-restricted truncated EGFR (c'973) which fails to activate PLCgamma or mobilize gelsolin. The PLC inhibitor U73122 has no effect on this process, nor is the actin severing capacity of gelsolin required as EGF treatment reduces focal adhesions in gelsolin-devoid fibroblasts, further supporting the contention that focal adhesion disassembly is signaled by a pathway distinct from that involving PLCgamma. Because both WT and c'973 EGFR activate the erk MAP kinase pathway, we additionally explore here this signaling pathway, not previously associated with growth factor-induced cell motility. Levels of the MEK inhibitor PD98059 that block EGF-induced mitogenesis and MAP kinase phosphorylation also abrogate EGF-induced focal adhesion disassembly and cell motility. In summary, we characterize for the first time the ability of EGFR kinase activity to directly stimulate focal adhesion disassembly and cell/substratum detachment, in relation to its ability to stimulate migration. Furthermore, we propose a model of EGF-induced motogenic cell responses in which the PLCgamma pathway stimulating cell motility is distinct from the MAP kinase-dependent signaling pathway leading to disassembly and reorganization of cell-substratum adhesion.


Subject(s)
ErbB Receptors/physiology , Isoenzymes/physiology , Signal Transduction/physiology , Tissue Adhesions/physiopathology , Type C Phospholipases/physiology , Animals , Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors , Cell Adhesion/physiology , Cell Line , Cell Movement/physiology , Fibroblasts/physiology , Gelsolin/analysis , Heterozygote , Homozygote , Mice , Phospholipase C gamma
5.
J Biol Chem ; 273(3): 1755-63, 1998 Jan 16.
Article in English | MEDLINE | ID: mdl-9430723

ABSTRACT

Thrombospondin is an extracellular matrix protein involved in modulating cell adhesion. Thrombospondin stimulates a rapid loss of focal adhesion plaques and reorganization of the actin cytoskeleton in cultured bovine aortic endothelial cells. The focal adhesion labilizing activity of thrombospondin is localized to the amino-terminal domain, specifically amino acids 17-35. Use of a synthetic peptide (hep I), containing amino acids 17-35 of thrombospondin, enables us to examine the signaling mechanisms specifically involved in thrombospondin-induced disassembly of focal adhesions. We tested the hypothesis that activation of phosphoinositide 3-kinase is a necessary step in the thrombospondin-induced signaling pathway regulating focal adhesion disassembly. Both wortmannin and LY294002, membrane permeable inhibitors of phosphoinositide 3-kinase activity, blocked hep I-induced disassembly of focal adhesions. Similarly, wortmannin inhibited hep I-mediated actin microfilament reorganization and the hep I-induced translocation of alpha-actinin from focal adhesion plaques. Hep I also stimulated phosphoinositide 3-kinase activity approximately 2-3-fold as measured in anti-phosphoinositide 3-kinase and anti-phosphotyrosine immunoprecipitates. Increased immunoreactivity for the 85-kDa regulatory subunit in anti-phosphotyrosine immunoprecipitates suggests that the p85/p110 form of phosphoinositide 3-kinase is involved in this pathway. In 32Pi-labeled cells, hep I increased levels of phosphatidylinositol (3,4,5)-trisphosphate, the major product of phosphoinositide 3-kinase phosphorylation. These results suggest that thrombospondin signals the disassembly of focal adhesions and reorganization of the actin cytoskeleton by a pathway involving stimulation of phosphoinositide 3-kinase activity.


Subject(s)
Cell Adhesion , DNA-Binding Proteins , Phosphatidylinositol 3-Kinases/metabolism , Saccharomyces cerevisiae Proteins , Signal Transduction , Thrombospondins/physiology , Transcription Factors , Amino Acid Sequence , Androstadienes/pharmacology , Animals , Cattle , Cells, Cultured , Chromones/pharmacology , Enzyme Activation , Enzyme Inhibitors/pharmacology , Humans , Molecular Sequence Data , Morpholines/pharmacology , Oligopeptides/metabolism , Phosphoinositide-3 Kinase Inhibitors , Wortmannin
6.
J Cell Sci ; 109 ( Pt 10): 2499-508, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8923211

ABSTRACT

Focal adhesions are specialized regions of cell membranes that are foci for the transmission of signals between the outside and the inside of the cell. Intracellular signaling events are important in the organization and stability of these structures. In previous work, we showed that the counter-adhesive extracellular matrix proteins, thrombospondin, tenascin, and SPARC, induce the disassembly of focal adhesion plaques and we identified the active regions of these proteins. In order to determine the mechanisms whereby the anti-adhesive matrix proteins modulate cytoskeletal organization and focal adhesion integrity, we examined the role of protein kinases in mediating the loss of focal adhesions by these proteins. Data from these studies show that cGMP-dependent protein kinase is necessary to mediate focal adhesion disassembly triggered by either thrombospondin or tenascin, but not by SPARC. In experiments using various protein kinase inhibitors, we observed that selective inhibitors of cyclic GMP-dependent protein kinase, KT5823 and Rp-8-Br-cGMPS, blocked the effects of both the active sequence of thrombospondin 1 (hep I) and the alternatively-spliced segment (TNfnA-D) of tenascin-C on focal adhesion disassembly. Moreover, early passage rat aortic smooth muscle cells which have high levels of cGMP-dependent protein kinase were sensitive to hep I treatment, in contrast to passaged cGMP-dependent protein kinase deficient cells which were refractory to hep I or TNfnA-D treatment, but were sensitive to SPARC. Transfection of passaged smooth muscle cells with the catalytic domain of PKG I alpha restored responsiveness to hep I and TNfnA-D. While these studies show that cGMP-dependent protein kinase activity is necessary for thrombospondin and tenascin-mediated focal adhesion disassembly, kinase activity alone is not sufficient to induce disassembly as transfection of the catalytic domain of the kinase in the absence of additional stimuli does not result in loss of focal adhesions.


Subject(s)
Cell Adhesion Molecules/pharmacology , Cell Adhesion/drug effects , Cyclic GMP-Dependent Protein Kinases/metabolism , Membrane Glycoproteins/pharmacology , Tenascin/pharmacology , Animals , Aorta , Atrial Natriuretic Factor/pharmacology , Cattle , Cells, Cultured , Colforsin/pharmacology , Cyclic GMP/metabolism , Cyclic GMP-Dependent Protein Kinases/genetics , Endothelium, Vascular , Enzyme Inhibitors/pharmacology , Muscle, Smooth, Vascular , Osteonectin/pharmacology , Penicillamine/analogs & derivatives , Penicillamine/pharmacology , Protein Serine-Threonine Kinases/antagonists & inhibitors , Rats , S-Nitroso-N-Acetylpenicillamine , Thrombospondins , Transfection
7.
J Cell Biochem ; 57(2): 341-50, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7539008

ABSTRACT

SPARC is a one of a group of extracellular matrix proteins that regulate cell adhesion through a loss of focal adhesion plaques from spread cells. We previously reported that SPARC reduced the number of bovine aortic endothelial (BAE) cells positive for focal adhesions [Murphy-Ullrich et al. (1991): J Cell Biol 115:1127-1136]. We have now characterized the effect of SPARC on the cytoskeleton of BAE cells. Addition of SPARC to spread BAE cells caused a dose-dependent loss of focal adhesion-positive cells, that was maximal at approximately 1 microgram/ml (0.03 microM). Consistent with the loss of adhesion plaques as detected by interference reflection microscopy, vinculin appeared diffuse and F-actin was redistributed to the periphery of cells incubated with SPARC. However, the distribution of the integrin alpha v beta 3 remained clustered in a plaque-like distribution. These data, and the observation that SPARC binds to BAE cells but not to the extracellular matrix, indicate that SPARC acts via interactions with cell surface molecules and not by steric/physical disruption of integrin-extracellular matrix ligands. To determine the region(s) of SPARC that mediate a loss of focal adhesions, we tested peptides from the four distinct regions of SPARC. The cationic, cysteine-rich peptide 2.1 (amino acids 54-73) and the Ca(2+)-binding EF-hand-containing peptide 4.2 (amino acids 254-273) were active in focal adhesion disassembly. Furthermore, antibodies specific for these regions neutralized the focal adhesion-labilizing activity of SPARC. These results are consistent with previous data showing that peptide 2.1 and 4.2 interact with BAE cell surface proteins and indicate that the loss of focal adhesions from endothelial cells exposed to SPARC is a receptor-mediated event.


Subject(s)
Calcium/metabolism , Cell Adhesion/drug effects , Extracellular Matrix Proteins/chemistry , Extracellular Matrix Proteins/pharmacology , Glycoproteins/chemistry , Osteonectin/pharmacology , Actins/metabolism , Amino Acid Sequence , Animals , Antibodies , Aorta , Binding Sites , Cattle , Cells, Cultured , Dose-Response Relationship, Drug , Extracellular Matrix Proteins/metabolism , Fluorescent Antibody Technique , Follistatin , Integrins/metabolism , Kinetics , Mice , Microscopy, Interference , Molecular Sequence Data , Osteonectin/chemistry , Peptide Fragments/chemistry , Peptide Fragments/isolation & purification , Protein Conformation , Receptors, Cytoadhesin/metabolism , Receptors, Vitronectin , Vinculin/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL