RESUMEN
OBJECTIVE: In some 5% of patients with facioscapulohumeral muscular dystrophy (FSHD), no D4Z4 repeat contraction on chromosome 4q35 is observed. Such patients, termed patients with FSHD2, show loss of DNA methylation and heterochromatin markers at the D4Z4 repeat that are similar to patients with D4Z4 contractions (FSHD1). This commonality suggests that a change in D4Z4 chromatin structure unifies FSHD1 and FSHD2. The aim of our study was to critically evaluate the clinical features in patients with FSHD2 in order to establish whether these patients are phenotypically identical to FSHD1 and to establish the effects of the (epi-) genotype on the phenotype. METHODS: This cross-sectional study studied 33 patients with FSHD2 from 27 families, the largest cohort described to date. All patients were clinically assessed using a standardized clinical evaluation form. Genotype analysis was performed by pulsed field gel electrophoresis and PCR; D4Z4 methylation was studied by methylation-sensitive Southern blot analysis. RESULTS: FSHD2 is identical to FSHD1 in its clinical presentation. Notable differences include a higher incidence (67%) of sporadic cases and the absence of gender differences in disease severity in FSHD2. Overall, average disease severity in FSHD2 was similar to that reported in FSHD1 and was not influenced by D4Z4 repeat size. In FSHD2, a small effect of the degree of hypomethylation on disease severity was observed. CONCLUSIONS: Clinically, patients with FSHD2 are indistinguishable from patients with FSHD1. The present data suggest that FSHD1 and FSHD2 are the result of the same pathophysiologic process.
Asunto(s)
Distrofia Muscular Facioescapulohumeral/genética , Distrofia Muscular Facioescapulohumeral/fisiopatología , Proteínas Nucleares/genética , Adolescente , Adulto , Niño , Preescolar , Cromosomas Humanos Par 4 , Estudios de Cohortes , Estudios Transversales , Metilación de ADN/genética , Expansión de las Repeticiones de ADN/genética , Salud de la Familia , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Proteínas de Microfilamentos , Persona de Mediana Edad , Fenotipo , Polimorfismo Genético/genética , Proteínas de Unión al ARN , Adulto JovenRESUMEN
Neurology is a polymorphic discipline, with several subspecialties. In 2006, as in the previous years, a huge amount of scientific work focusing on treatment has been published. However, there has not been a true revolution in any of the current therapeutic strategies; rather, we experienced an improvement in the knowledge about several specific "details". This allows to consider more and more variables when administering a specific treatment, therefore, in each subspecialty a move towards a better patient's care has been made. In this contribution, several specialists analyse and interpret new facts about their respective neurological domain.
Asunto(s)
Enfermedades del Sistema Nervioso/terapia , Trastornos Cerebrovasculares/terapia , Demencia/terapia , Epilepsia/terapia , Humanos , Esclerosis Múltiple/terapia , Enfermedades Neuromusculares/terapia , Enfermedad de Parkinson/terapiaRESUMEN
We report a large family with a mild form of autosomal dominant nemaline myopathy and a new phenotype. Onset of symptoms was in infancy with hypotonia and motor delay. Weakness involved neck flexors, abdominal and proximal limb muscles. There was no bulbar, respiratory or foot dorsiflexion weakness and no slowness in movement. Patients had remarkably good physical endurance and no limitation in daily activities, but were slow runners since childhood. Nemaline rods were seen in less than 5% of muscle fibres. No linkage to the five known nemaline myopathy genes (alpha-tropomyosin-3, nebulin, alpha-actin, troponin T1 and beta-tropomyosin), to the ryanodine receptor gene (associated with core-rod myopathy) or to the 15q21-23 locus was found.
Asunto(s)
Salud de la Familia , Miopatías Nemalínicas , Linaje , Femenino , Humanos , Masculino , Debilidad Muscular/etiología , Músculo Esquelético/patología , Músculo Esquelético/ultraestructura , Miopatías Nemalínicas/genética , Miopatías Nemalínicas/patología , Miopatías Nemalínicas/fisiopatología , FenotipoRESUMEN
The binding characteristics of the prolactin (PRL) receptors present in toad (Bufo marinus) kidneys were investigated and compared to those of PRL receptors present in rabbit mammary glands. The molecular characteristics of the Triton X-100 solubilized renal and mammary PRL receptors were assessed by gel filtration and by migration analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) after affinity labeling of the binding sites with 125I-human growth hormone. Similar results were obtained for both receptors. Partial purification of the toad PRL receptor could be achieved by affinity chromatography. The molecular weight of this purified receptor could be determined by analysis on SDS-PAGE. With the use of a polyclonal antiserum raised against a purified preparation of rabbit mammary PRL receptor, one or several antigenic epitope(s) could be identified on the core of the toad renal PRL receptor. In conclusion, although the structure and the biological role(s) of PRL have substantially changed during evolution, the receptor for this hormone has retained many of its structural features as could be assessed between an amphibian and a mammalian species on functionally different target tissues.
Asunto(s)
Riñón/análisis , Glándulas Mamarias Animales/análisis , Receptores de Prolactina/aislamiento & purificación , Marcadores de Afinidad/metabolismo , Animales , Bufo marinus , Cromatografía en Gel , Sueros Inmunes/inmunología , Riñón/metabolismo , Glándulas Mamarias Animales/metabolismo , Conejos , Receptores de Prolactina/inmunología , Receptores de Prolactina/metabolismo , SolubilidadRESUMEN
The goal of this work was to establish an assay for transformation of epithelial cells. Two epithelial cell lines were obtained after microinjecting transforming genes into primary rabbit mammary secretory cells. The cell lines were analyzed for their oncogenic potential and for the maintenance of a differentiated phenotype. A fully transformed cell line, which retained epithelial cell organization, was obtained by coinjecting simian virus 40 DNA and the activated human c-Ha-ras gene. The proliferation rate of these cells was high, with a doubling time of 16 h. Their growth was anchorage independent, and they had lost contact inhibition. The cells were tumorigenic in nude mice, but had no metastatic potential. Both microinjected DNAs were efficiently transcribed and translated, in contrast to the casein genes, which were expressed in primary cells but not in the transformed cell line. An immortalized cell line established after injection with simian virus 40 DNA alone was characterized by a moderate rate of proliferation with a doubling time of approximately 30 h. The growth of these cells was contact inhibited and anchorage dependent. The cells were not tumorigenic in nude mice. The viral DNA was expressed during early passages, as shown by the presence of the large T antigen in cell nuclei, but not at later passages. A high number of lactogenic hormone receptors were found associated with the cell surface. Despite the presence of these receptors, no induction of genes coding for milk proteins was observed after addition of prolactin. These data demonstrate that this assay system can be used to assess the immortalizing and transforming potential of candidate oncogenes in epithelial cells.
Asunto(s)
Transformación Celular Viral , Glándulas Mamarias Animales/citología , Oncogenes , Animales , Caseínas/genética , Diferenciación Celular , Línea Celular , ADN de Neoplasias/genética , ADN Viral/genética , Células Epiteliales , Regulación de la Expresión Génica , Microscopía Electrónica , Neoplasias Experimentales/genética , Conejos , Virus 40 de los SimiosRESUMEN
Established cell lines (TB-6c and TB-M) obtained by continuous culture of epithelial cells from toad Bufo marinus urinary bladder, which, in culture, maintained a high degree of functional differentiation, exhibited a significant number of high-affinity (KA = 1-2 X 10(10) M-1) binding sites detected both with radioiodinated (125I) ovine prolactin (oPRL) and human growth hormone (hGH). Binding capacity was higher in the case of TB-6c cells (7,573 +/- 581 sites/cell) than with the TB-M cells (1,160 +/- 87). Similarly, binding sites for oPRL were characterized on Xenopus laevis kidney-derived cell line A6. With oPRL used both as tracer and standard, significant cross-reaction was observed with hGH, less with human or rat prolactin (PRL), and none with human chorionic somatomammotropin, bovine growth hormone, and rat luteinizing hormone or follicle-stimulating hormones. B. marinus pituitary extracts completely displaced the binding of 125I-oPRL to toad bladder binding sites. This finding of specific sites for PRL on amphibian bladder and kidney cells confirms that PRL exerts specific biological actions for the control of electrolyte and water metabolism in the amphibians.
Asunto(s)
Prolactina/metabolismo , Receptores de Superficie Celular/metabolismo , Animales , Bufo marinus , Línea Celular , Cinética , Hipófisis/fisiología , Receptores de Superficie Celular/efectos de los fármacos , Receptores de Prolactina , Ovinos , Extractos de Tejidos/farmacología , Vejiga Urinaria , XenopusRESUMEN
In order to examine audience effects when viewing filmed violence, male subjects watched an aggressive or a neutral movie either alone, accompanied by a passive confederate (i.e. mere presence of a co-spectator), or an active one (i.e. reacting to the movie). The subsequent behavioural measures of subjects' aggression were collected via a modified aggression apparatus. The usual instigation effect of filmed violence was found. Furthermore, the type of audience also influenced aggression: subjects accompanied by an active confederate during the violent movie displayed their aggressive behaviour most. These findings stress the importance of the social context when filmed violence is viewed. The results are discussed in terms of social facilitation and disinhibition effects. It is suggested that an active audience may promote a reduction of restraints against aggressing by showing the subject that aggression is permissible.