RESUMO
A 7-week-old infant presented with persistent noisy breathing and aspirations during swallowing. Neurological examination and brain MRI were normal. His 12-year-old brother underwent pneumonectomy at the age of 10 years due to recurrent aspirations leading to severe lung damage. The older brother developed subsequently ophthalmoplegia and nystagmus along with mild weakness of the neck flexors and proximal muscles. Exome analysis revealed homozygosity for a novel truncating mutation p.G800fs27* in the Myosin Heavy Chain 2 (MYH2) gene in both brothers, while parents and an unaffected sibling were heterozygous. A muscle biopsy from the older brother showed absence of type-2 muscle fibers and predominance of type-1 fibers. The aspirations causing pneumonia likely result from weakness of the laryngeal muscles, normally rich in type-2 fibers. The findings expand the phenotypic spectrum of MYH2 deficiency. MYH2 mutations should be included in the differential diagnosis of infants presenting with recurrent aspirations.
Assuntos
Mutação/genética , Cadeias Pesadas de Miosina/genética , Miotonia Congênita/genética , Pneumonia Aspirativa/genética , Pneumonia Aspirativa/patologia , Criança , Proteínas do Citoesqueleto/genética , Humanos , Lactente , Masculino , Debilidade Muscular/genética , Debilidade Muscular/patologia , Miotonia Congênita/diagnóstico , Miotonia Congênita/patologia , Pneumonia Aspirativa/diagnósticoRESUMO
The human neuroblastoma NMB cell line was found to contain the three types of opioid receptors (60% delta 25% kappa and 15% mu). The opioid receptors were negatively coupled to adenylyl-cyclase. Maximal reduction in cAMP content was achieved by selectively activating single receptor types, indicating the co-presence of the various opioid receptors in the same cells. The opioid receptors in NMB cells were up-regulated following prolonged exposure to the opioid antagonist naloxone and down-regulated following chronic treatment with the opioid agonist etorphine. Down-regulation was time-, dose- and temperature-dependent and was inhibited by colchicine and sodium azide. The NMB culture is presented as an excellent experimental model for studying the selective activation and regulation of the different opioid receptor types when they are co-expressed in the same neuron, as well as for studying interactions between the various opioid receptors.