Asunto(s)
Regulación Neoplásica de la Expresión Génica , Linfoma de Células B Grandes Difuso/metabolismo , Neoplasias del Mediastino/metabolismo , Factor de Transcripción STAT6/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/genética , Proteína bcl-X/metabolismo , Western Blotting , Ciclo Celular/fisiología , Muerte Celular/fisiología , Humanos , Técnicas para Inmunoenzimas , Linfoma de Células B Grandes Difuso/genética , Linfoma de Células B Grandes Difuso/patología , Neoplasias del Mediastino/genética , Neoplasias del Mediastino/patología , Fosforilación , Regiones Promotoras Genéticas/genética , ARN Interferente Pequeño/farmacología , Factor de Transcripción STAT6/antagonistas & inhibidores , Factor de Transcripción STAT6/genética , Proteína 1 Supresora de la Señalización de Citocinas , Proteínas Supresoras de la Señalización de Citocinas/metabolismo , Células Tumorales Cultivadas , Proteína bcl-X/genéticaAsunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Linfoma de Burkitt/genética , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Linfoma Folicular/genética , Linfoma de Células B Grandes Difuso/genética , Regiones Promotoras Genéticas , Línea Celular Tumoral , HumanosRESUMEN
Activation of the transcription factor NF-kappaB is necessary for full expression of tumor necrosis factor alpha (TNF-alpha)-inducible endothelial chemokines and adhesion molecules. However, a detailed analysis regarding contribution of the different NF-kappaB upstream components to endothelial activation has not been performed yet. We employed a retroviral infection approach to stably express transdominant (TD) mutants of IkappaBalpha, IkappaBbeta, or IkappaBepsilon and dominant negative (dn) versions of IkappaB kinases (IKK) 1 or 2 as well as a constitutively active version of IKK2 in human endothelial cells. TD IkappaBalpha, IkappaBbeta, and IkappaBepsilon were not degraded upon TNF-alpha exposure, and each prevented NF-kappaB activation. These TD IkappaB mutants almost completely inhibited the induction of monocyte chemoattractant protein-1, interleukin-8, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin expression by TNF-alpha, whereas interferon-gamma-mediated up-regulation of intercellular adhesion molecule-1 and HLA-DR was not affected. Expression of dn IKK2 completely blocked TNF-alpha-induced up-regulation, whereas dn IKK1 showed a partial inhibition of expression of these molecules. Importantly, expression of constitutively active IKK2 was sufficient to drive full expression of all chemokines and adhesion molecules in the absence of cytokine. We conclude that the IKK/IkappaB/NF-kappaB pathway is crucial and sufficient for proinflammatory activation of endothelium.
Asunto(s)
Endotelio Vascular/citología , FN-kappa B/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Western Blotting , Células Cultivadas , Quimiocina CCL2/metabolismo , Selectina E/metabolismo , Activación Enzimática , Inhibidores Enzimáticos/farmacología , Citometría de Flujo , Genes Dominantes , Humanos , Quinasa I-kappa B , Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Interferón gamma/metabolismo , Interleucina-8/metabolismo , Mutación , FN-kappa B/genética , Fosforilación , Proteínas Serina-Treonina Quinasas/genética , Retroviridae/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Venas Umbilicales/citología , Regulación hacia Arriba , Molécula 1 de Adhesión Celular Vascular/metabolismoRESUMEN
OBJECTIVES: To assess the individual activity of anaesthetists in paediatric anaesthesia (PA), and collect their wishes about continuing education and recommendations in PA. STUDY DESIGN: Transversal, prospective study. METHODS: A questionnaire of 33 items, sent to 4,360 anaesthetists, spread over 15 health districts, working in a public or private institution. RESULTS: We gathered 1,526 replies (35%) of which 34% university hospitals, 32% public institutions and 31% private institutions. 943 physicians (63%) had no specific structure, and 1,119 (87%) considered a specialized nurse to be essential for PA. 1,127 physicians (74%) had undertaken a specific session during their formation. The practice of PA depends upon age and context. Above 1 year old, the surgery that is performed weekly was ENT (38%), abdominal and urologic surgery (28%). Mask induction was performed by 60% of the physicians in children under 5 years. 63% of the anaesthetists dreaded a laryngospasm during induction. 625 physicians undertook regional anaesthesia in children under 5 years (87% caudal anaesthesia, 48% peripheral nerve blocks). 1,029 physicians (67%) wished for recommendations in PA in children under 12 months. CONCLUSIONS: This survey showed that most of the anaesthetists wished for recommendations in their paediatric anaesthesia practice.