RESUMEN
The effects of the combination of a 'lowest' lung ventilation with extracorporeal elimination of carbon dioxide by interventional lung assist are described in a patient presenting with severe acute respiratory distress syndrome due to fulminant pneumonia. Reducing tidal volume to 3 ml.kg(-1) together with interventional lung assist resulted in a decrease in severe hypercapnia without alveolar collapse or hypoxaemia but with a decrease in serum levels of interleukin-6. This approach was applied for 12 days with recovery of the patient, without complications. Extracorporeal removal of carbon dioxide by interventional lung assist may be a useful tool to enable 'ultraprotective' ventilation in severe acute respiratory distress syndrome.
Asunto(s)
Oxigenación por Membrana Extracorpórea/métodos , Hipercapnia/terapia , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/terapia , Dióxido de Carbono/sangre , Humanos , Hipercapnia/sangre , Hipercapnia/etiología , Masculino , Persona de Mediana Edad , Oxígeno/sangre , Presión Parcial , Síndrome de Dificultad Respiratoria/sangre , Volumen de Ventilación PulmonarRESUMEN
Gephyrin is essential for both the postsynaptic localization of inhibitory neurotransmitter receptors in the central nervous system and the biosynthesis of the molybdenum cofactor (Moco) in different peripheral organs. Several alternatively spliced gephyrin transcripts have been identified in rat brain that differ in their 5' coding regions. Here, we describe gephyrin splice variants that are differentially expressed in non-neuronal tissues and different regions of the adult mouse brain. Analysis of the murine gephyrin gene indicates a highly mosaic organization, with eight of its 29 exons corresponding to the alternatively spliced regions identified by cDNA sequencing. The N- and C-terminal domains of gephyrin encoded by exons 3-7 and 16-29, respectively, display sequence similarities to bacterial, invertebrate, and plant proteins involved in Moco biosynthesis, whereas the central exons 8, 13, and 14 encode motifs that may mediate oligomerization and tubulin binding. Our data are consistent with gephyrin having evolved from a Moco biosynthetic protein by insertion of protein interaction sequences.
Asunto(s)
Empalme Alternativo , Proteínas Portadoras/genética , Coenzimas , Variación Genética , Proteínas de la Membrana/genética , Filogenia , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Encéfalo/metabolismo , Proteínas Portadoras/química , Proteínas del Citoesqueleto/química , Proteínas del Citoesqueleto/genética , Exones , Biblioteca Genómica , Humanos , Intrones , Queratinas/química , Queratinas/genética , Proteínas de la Membrana/química , Metaloproteínas/metabolismo , Ratones , Ratones Endogámicos BALB C , Datos de Secuencia Molecular , Cofactores de Molibdeno , Especificidad de Órganos , Pteridinas/metabolismo , Ratas , Alineación de Secuencia , Homología de Secuencia de AminoácidoRESUMEN
The peripheral membrane protein gephyrin is essential for the postsynaptic localization of the inhibitory glycine receptor and is thought to anchor the receptor complex to the subsynaptic cytoskeleton. Since gephyrin transcripts are also found in non-neuronal tissues, we analyzed the 5'-flanking region of the gephyrin gene to identify its promoter region. This region contains several SP1 consensus sites, which may account for the widespread expression of gephyrin mRNA. Indeed, reporter gene constructs encompassing at least the two SP1 consensus sites upstream from the transcription start site were efficiently transcribed in both a fibroblast and a neuronal cell line. Our data are consistent with the widespread expression of the gephyrin gene in most mammalian tissues.
