Differential regulation of miR-21 and miR-146a by Epstein-Barr virus-encoded EBNA2.

The discovery of microRNA (miR) represents a novel paradigm in RNA-based regulation of gene expression and their dysregulation has become a hallmark of many a tumor. In virally associated cancers, the host-pathogen interaction could involve alteration in miR expression. Epstein-Barr virus (EBV)-encoded EBNA2 is indispensable for the capacity of the virus to transform B cells in vitro. Here, we studied how it affects cellular miRs. Extensive miR profiling of the virus-infected and EBNA2-transfected B lymphoma cells revealed that oncomiR miR-21 is positively regulated by this viral protein. Conversely, Burkitt's lymphoma (BL) cell lines infected with EBNA2 lacking P3HR1 strain did not show any increase in miR-21. EBNA2 increased phosphorylation of AKT and this was directly correlated with increased miR-21. In contrast, miR-146a was downregulated by EBNA2 in B lymphoma cells. Low miR-146a expression correlates with an elevated level of IRAK1 and type I interferon in EBNA2 transfectants. Taken together, the present data suggest that EBNA2 might contribute to EBV-induced B-cell transformation by altering miR expression and in particular by increasing oncomiR-like miR-21 and by affecting the antiviral responses of the innate immune system through downregulation of its key regulator miR-146a.

Type I interferon and Toll-like receptor expression characterizes inflammatory myopathies.

OBJECTIVES: Juvenile dermatomyositis (JDM), adult dermatomyositis, and polymyositis (PM) are idiopathic inflammatory myopathies (IIMs) characterized by muscle infiltration and specific muscle fiber alterations. They are thought to have an autoimmune etiology, but triggering factors, and how immunologic attack induces muscle weakness, remain unknown. Recent evidence suggests a key role for type I interferon (IFN)-mediated innate immunity in dermatomyositis, which we explored in JDM, dermatomyositis, and PM by gene expression profiling, and other methods. METHODS: Ten IIM and 5 control muscle biopsies were assessed for expression of approximately 16,000 genes by microarray; 37 additional IIM, 10 dystrophinopathic, and 14 nonmyopathic control muscles were studied for type I IFN-dependent genes, and Toll-like receptor (TLR) expression by immunochemistry and PCR. RESULTS: Type I IFN-dependent transcripts were significantly upregulated in IIM muscles compared to controls; in JDM the most expressed were ISG15 (408-fold), IFIT3 (261-fold), MX1 (99-fold), and IRF7 (37-fold). IFN-ß (but not IFN-α) transcripts were upregulated in PM as well as dermatomyositis/JDM. TLR3 was upregulated particularly in JDM, being localized on vascular endothelial cells, muscle infiltrating cells (mainly myeloid dendritic cells), and regenerating myofibers; TLR7 and TLR9 proteins were present in IIM (prominently in PM), mainly on cell infiltrates, particularly plasma cells, and on some injured myofibers. CONCLUSIONS: IFN-ß and type I IFN-induced molecules are involved in PM as well as JDM/dermatomyositis. Endosomal TLRs (effectors of innate immunity) are also involved (but differently) in the 3 conditions, further suggesting viral involvement, although TLR activation could be secondary to tissue damage.

Signos neurológicos blandos: ¿tienen alguna utilidad en la evaluación y diagnóstico del trastorno por déficit de atención/hiperactividad? / Soft neurological signs: are they of any value in the assessment and diagnosis of attention déficit hyperactivity disorder?

Introducción. La asociación entre dificultades en las habilidades motoras, la coordinación visuomanual y el comportamiento sobreactivo fue descrita mucho antes de que se estableciera como categoría diagnóstica el trastorno por déficit de atención/hiperactividad (TDAH). Estas alteraciones se han intentado agrupar bajo diferentes terminologías, siendo una de ellas los signos neurológicos blandos (SNB). Tradicionalmente se ha prestado más atención a los llamados SNB entre la comunidad científica europea que en la americana. En la actualidad, muchos neuropediatras y pediatras del desarrollo continúan considerando que estos déficit, junto con la inatención y la hiperactividad, forman parte de un mismo trastorno. Desarrollo. En este artículo se intenta realizar una revisión neurobiológica del movimiento, de la posible relación entre las alteraciones motoras y los procesos cognitivos desde diferentes perspectivas: neuroanatómica, hallazgos en diferentes test de exploración clínica y modelos experimentales neuropsicológicos. Conclusión. La mayoría de los artículos revisados concluyen que la prevalencia de los SNB es muy superior en los niños con TDAH respecto a los controles, por lo que se recomienda su inclusión en los protocolos de evaluación y diagnóstico de estos trastornos, no sólo para mejorar la sensibilidad y especificidad en el diagnóstico, sino también para poder evaluar cuáles son las necesidades reales de los pacientes con TDAH (AU)

Introduction. The association between difficulties on motor skills, visual-hand coordination and excess motor activity was described previously of being established the attention-deficit/hyperactivity disorder (ADHD) as a diagnostic category. These disorders have been grouped under different terminologies, being one of them the soft neurological signs (SNS). Traditionally, the European scientific community has put more attention on the SNS than the American one. However, nowadays there are a lot of neuropediatrician and community pediatrician that continue to think that those deficits, together with inattention and hyperactivity, form part of the same disorder. Development. In this article we have tried to do a neurobiological revision of the movement and the possible relationship between motor problems and cognitive processes from different points of view: neuroanatomical, findings on different clinical examination tests and neuropsychological experimental models. Conclusion. Most of the revised articles conclude that the SNS prevalence is greater in ADHD children compared with control. Therefore we recommend to include the SNS in the evaluation and diagnosis protocols of these disorders in order to improve the sensitivity and specificity of the diagnosis and to be able to evaluate the real needs of the ADHD patients (AU)

TLR-mediated activation of type I IFN during antiviral immune responses: fighting the battle to win the war.

Toll-like receptors (TLRs) are crucially important in the sensing of viral infections and viral nucleic acids. TLR triggering leads to the induction of specific intracellular signaling cascades that result in the activation of two major families of transcription factors; the IFN-regulatory factors (IRFs) and nuclear factor-kappa B (NF-kappaB). IRFs and NF-kappaB work together to trigger the production of type I interferons (IFNalpha/beta) or inflammatory cytokines leading to the maturation of dendritic cells and the establishment of antiviral immunity. This review will focus on the most recent findings relating to the regulation of IRF activity by TLRs, highlighting the increasing complexity of TLR-mediated signaling pathways.

Sacroileitis. A proposito de un caso en un nino de dos anos. / Sacroleitis.Apropos of a case in a 2-year-old child

La infeccion de la articulacion sacroiliaca es altamente infrecuente y de dificil diagnostico. Su ubicacion y fijeza la alejan de las maniobras clinicas habituales y ademas su patologia plantea una larga lista de diagnosticos diferenciales.Pocos casos de infeccion de la articulacion sacroiliaca son recordados por los medicos ortopedistas del Hospital y, por otra parte, no han quedado registrados como sacroileitis en las historias del archivo hospitalario de los ultimos diez anos, es posible que figuren bajo otros diagnosticos, inespecificos o errados. Es proposito de este trabajo categorizar los datos que pueden orientar hacia el reconocimiento temprano de esta entidad para evitar al paciente examenes inconducentes e internaciones prolongadas

Sacroileitis. A proposito de un caso en un nino de dos anos. / Sacroleitis.Apropos of a case in a 2-year-old child

La infeccion de la articulacion sacroiliaca es altamente infrecuente y de dificil diagnostico. Su ubicacion y fijeza la alejan de las maniobras clinicas habituales y ademas su patologia plantea una larga lista de diagnosticos diferenciales.Pocos casos de infeccion de la articulacion sacroiliaca son recordados por los medicos ortopedistas del Hospital y, por otra parte, no han quedado registrados como sacroileitis en las historias del archivo hospitalario de los ultimos diez anos, es posible que figuren bajo otros diagnosticos, inespecificos o errados. Es proposito de este trabajo categorizar los datos que pueden orientar hacia el reconocimiento temprano de esta entidad para evitar al paciente examenes inconducentes e internaciones prolongadas