RESUMEN
Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation.
Asunto(s)
Adenilato Quinasa/genética , Leucopenia/genética , Linfocitos/enzimología , Mitocondrias/genética , Neutrófilos/enzimología , Inmunodeficiencia Combinada Grave/genética , Células Madre/enzimología , Nucleótidos de Adenina/metabolismo , Adenilato Quinasa/deficiencia , Antígenos CD34/genética , Antígenos CD34/metabolismo , Diferenciación Celular , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HL-60 , Humanos , Leucopenia/enzimología , Leucopenia/patología , Linfocitos/patología , Mitocondrias/enzimología , Mitocondrias/patología , Mutación , Neutrófilos/patología , Fosforilación Oxidativa , Cultivo Primario de Células , Inmunodeficiencia Combinada Grave/enzimología , Inmunodeficiencia Combinada Grave/patología , Células Madre/patologíaRESUMEN
A retrospective study of 343 women who lacked prenatal care was conducted to ascertain the effect of recent cocaine abuse on birth weight and gestational age. All pregnant women admitted in labor to a large urban teaching hospital between January 1 and December 31, 1986 who had not received prenatal care were included. The charts of these women were evaluated to obtain information about medical and obstetric complications of pregnancy, labor and delivery, and birth weight and gestational age of the infant. Information about drug use was obtained by urine toxicology at the time of admission. Results of ordinary least-squares multiple regression analyses indicated cocaine abuse to be a significant predictor of low birth weight and early gestational age. No correlation was found between cocaine abuse and abruptio placentae or maternal hypertension.