No abstract

Arrestin was identified in ciliary photoreceptors of Pecten irradians, and its role in terminating the light response was established electrophysiologically. Downstream effectors in these unusual visual cells diverge from both microvillar photoreceptors and rods and cones; the finding that key regulatory mechanisms of the early steps of visual excitation are conserved across such distant lineages of photoreceptors underscores that a common blueprint for phototransduction exists across metazoa. Arrestin was detected by Western blot analysis of retinal lysates, and localized in ciliary photoreceptors by immunostaining of whole-eye cryosections and dissociated cells. Two arrestin isoforms were molecularly identified by PCR; these present the canonical N-and C-arrestin domains, and are identical at the nucleotide level over much of their sequence. A high degree of homology to various ␤-arrestins (up to 70% amino acid identity) was found. In situ hybridization localized the two transcripts within the retina, but failed to reveal finer spatial segregation, possibly because of insufficient differences between the riboprobes. Intracellular dialysis of anti arrestin antibodies into voltage-clamped ciliary photoreceptors produced a gradual slow-down of the photocurrent falling phase, leaving a tail that decayed over many seconds after light termination. The antibodies also caused spectrally neutral flashes to elicit prolonged aftercurrents in the absence of large metarhodopsin accumulation; such aftercurrents could be quenched by chromatic illumination that photoconverts metarhodopsin back to rhodopsin. These observations indicate that the antibodies depleted functionally available arrestin, and implicate this molecule in the deactivation of the photoresponse at the rhodopsin level.

The Wiedemann-Rautenstrauch syndrome (WRS, OMIM: 264090) characterizes a premature aging syndrome in which several features of aging are apparent at birth. We did not find mutations in Lamin A/C (LMNA) gene in four WRS patients, and in particular, we did not find the G608G mutation (GGC > GGT transition) which is associated with most cases with Hutchinson-Gilford progeria (OMIM 176670). These findings suggest that WRS represents a distinct progeroid entity that may be caused by recessive mutations of a different gene.

Introduction: In recent decades, hemophilia A treatment has been focused on body weight, without taking pharmacokinetic parameters into account. Previous research has shown that the individual pharmacokinetic response is more effective in predicting the required dose of clotting factor. We want to evaluate the impact on reducing the frequency of bleeding in patients treated with recombinant factor VIII, based on a personalized comprehensive management program.   Objective: Our aim was to compare the results of a standard comprehensive treatment program (stage I) vs. a personalized pharmacokinetic - based treatment program (stage II) in a cohort of 60 patients with severe hemophilia without inhibitors.   Results:The median age was 15.5 years (3 - 68). The ABR was 1.03 (62 episodes) in the first stage and 0.58 (35 episodes) in the second one, (p = 0.004). By type of bleeding, the impact of the intervention differs significantly in spontaneous bleeding (p = 0.007) and a 73% reduction in the first stage. There were no significant differences in traumatic bleeding.   Conclusions: The use of pharmacokinetics for personalized dosing of patients with severe hemophilia A, significantly reduces ABR and spontaneous bleeding, improving the patient's quality of life and costs for the health system.

Introduction. Free trisomy 21 is responsible for 95% of Down syndrome cases. Advanced maternal age and susceptible recombination patterns are recognized risk factors associated to Down syndrome. Maternal origin of trisomy occurs in approximately 90% of cases; paternal and mitotic origin share the remaining 10%. However, the recombination events that serve as a risk factors for trisomy 21 have not been carefully characterized. Objective. To analyze and validate observations in a sample of Colombian trysonomy 21 cases. Materials and methods. Twenty-two Colombian families were selected, each with one affected Down syndrome (free trisomy 21) child. Microsatellite polymorphisms were used as DNA markers to determine the parental/stage origin of non-disjunction and recombination events. Nonparametric tests were used to compare our results with those reported. Multiple correspondence analysis was used to outline different groups and their associations. Results. Distribution of trisomy 21 was 90.9% maternal, 4.5% paternal and 4.5% from mitotic origin, similar to distributions reported previously. However, we found differences in the frequency of maternal meiotic stage errors between the present study (46.1% meiosis I and 53.9% meiosis II) compared to those reported previously (70% meiosis I and 30% meiosis II). Multiple correspondence analyses showed association of either local recombination events or absence of recombination with specific non-disjunction stages. Conclusions. Recombination patterns found in this study support the hypothesis that susceptible chiasmate configurations are associated to maternal meiosis I and meiosis II errors. Nondisjunction frequencies between maternal meiotic stages need to be clarified in our population.Key words: Down syndrome; nondisjunction, genetic; trisomy; meiosis; recombination, genetic; microsatellite repeats.Origen parental, estado de no disyunción y recombinación meiótica del cromosoma 21 extra en el síndrome de Down: estudio en una muestra de población colombiana Introducción. La trisomía 21 libre es responsable del 95% de los casos de síndrome de Down. La edad materna y la recombinación son los principales factores de riesgo asociados con la concepción de estos individuos. El origen materno de la trisomía ocurre en el 90% de los casos, mientras que los casos de origen paterno y mitótico comparten un 10%. Por otra parte, la recombinación como factor de riesgo para la trisomía 21 no ha sido comprobada completamente. Objetivo. Analizar y validar estas observaciones en una muestra colombiana de casos con trisomía 21 libre. Materiales y métodos. Se estudiaron 22 afectados con síndrome de Down (trisomía libre) y sus respectivos padres. Se usaron marcadores microsatélites de ADN para determinar el origen en los progenitores, el estado de no disyunción y los eventos de recombinación. Por COMUNICACIÓN BREVE 142 Biomédica 2007;27:141-8 Ramírez NJ, Belalcazar HM, Yunis JJ et al medio de pruebas no paramétricas se compararon los resultados con los reportados en la literatura. Se re...

Recently, mutations in the RNA polymerase III subunit 3A (POLR3A) have been described as the cause of the neonatal progeria or Wiedemann-Rautenstrauch syndrome (WRS). POLR3A have important roles in the regulation of transcription of small RNAs, including tRNA, 5S rRNA and U6 snRNA. We aim to describe cellular and molecular features of WRS fibroblasts. Cultures of primary fibroblasts from one WRS patient [monoallelic POLR3A variant c.3772_3773delCT (p.Leu1258Glyfs*12)] and one control were grown. Mutation in POLR3A causes a decreased in the expression of POLR3A mRNA and protein and a sharp increased of mutant protein.In addition, there was an increased in its nuclear localization. These changes were associated to an increase number and area of nucleoli, a significantly larger nuclear area, and a high increased in the expression of pP53 and pH2AX. All these changes were associated to premature senescence. The present observations add to our understanding of the differences between HGPS and WRS, and opens new alternatives to study cell senesce and human aging.

Durante el periodo federal (1857-1886) en el Estado Soberano de Santander se presentaron permanentes alteraciones del orden público por cuenta de los grupos armados de filiación conservadora que desafiaron la legitimidad del Estado en manos de los liberales radicales. Esa amenaza los obligó a crear un ejército permanente para la defensa del proyecto político, mantener el poder del Estado, garantizar el funcionamiento de las instituciones, controlar la población civil, y mantener el orden público.La existencia del ejército demandó nuevas partidas presupuestales para su funcionamiento en tiempos de paz, y en tiempos de guerra las operaciones eran financiadas a través de los empréstitos, unos voluntarios y otros forzosos. Estos los utilizaron los gobiernos del orden nacional, regional, departamental y local como arma política contra sus adversarios. Las cuatro guerras civiles que enfrentaron los radicales en Santander las financiaron de esa forma.

ObjetivoIdentificar factores de riesgo, genéticos, clínicos y ambientales, para el desarrollo de demencias, movimientos anormales y trastornos afectivos, en población adulta mayor de tres barrios de la Localidad Cuarta de Bogotá.MetodologíaEstudio Piloto, analítico de tipo transversal, diseñado para la identificación clínica y de factores de riesgo en una muestra intencional con participación voluntaria de 250 individuos, realizado en dos etapas: primera, de tamización, con base en diagnóstico interdisciplinario (Medicina, Enfermería y Psicología); segunda, de confirmación diagnóstica por especialistas (Neurología y Psiquiatría). Diferentes instrumentos neuro-psicológicos y pruebas de genética molecular y bioquímicas fueron realizadas a los participantes.ResultadosSe estudiaron individuos de ambos sexos, con edad promedio de 68,3 años, y también algunos de sus familiares. El 65,5% de la población de estudio está afectada por alguna de las entidades valoradas, con una mayor frecuencia de los trastornos afectivos (35,0%), seguida por alteración de las funciones cognitivas (23,3%). Los estudios genéticos permitieron identificar varios polimorfismos en genes, que pueden estar influyendo en la aparición de estas enfermedades.ConclusionesEstudio poblacional interdisciplinario en una de las localidades de Bogotá, D.C, de estratos uno y dos, para identificar trastornos cognitivos, afectivos y de movimientos anormales, con instrumentos clínicos y de biología molecular, lo que permite avanzar en la caracterización de perfiles genéticos de nuestra población y sus aplicaciones en programas de Salud Pública.