RESUMEN
The goal of the study reported here was to develop a continuous cell line from the squirrel monkey that expresses the species-specific phenotype of impaired sensitivity to glucocorticoids. Thirty milliliters of blood from a male Bolivian squirrel monkey (Saimiri boliviensis boliviensis) was fractionated, and the buffy coat was obtained and incubated in the presence of B95-8 cell-conditioned medium, an abundant source of Epstein-Barr virus (EBV), and 2 micrograms of cyclosporin A/ml. Cell growth was detected within 8 weeks, after which the cells were cloned by use of the limiting dilution method. One clone (4D8) was characterized in detail. The chromosomal count and G-banding pattern confirmed that the cells were of Bolivian squirrel monkey origin. The B-cell origin of these cells was indicated by electron microscopic analysis and was confirmed by expression of CD20. The cells stained strongly for LMP1, a marker of latent EBV infection, and occasionally for the lytic infection marker ZEBRA (BZLF1). The responsiveness of clone 4D8 cells to glucocorticoids was determined by comparing the effects of dexamethasone on cell growth and the induction of a glucocorticoid-inducible mRNA in 4D8 cells with the effects on a human EBV-transformed B-lymphoblast cell line (HL). Dexamethasone inhibited the growth of HL cells, with IC50 of approximately 9 nM, but had no effect on the growth of 4D8 cells. The induction of FK506-binding protein FKBP51 mRNA by dexamethasone was also significantly blunted in 4D8 cells. Thus, we have developed and characterized a squirrel monkey lymphoblastic cell line derived by transformation of B-lymphocytes with EBV; the cell line has diminished growth and transcriptional responses to glucocorticoids.
Asunto(s)
Linfocitos B/efectos de los fármacos , Resistencia a Medicamentos , Glucocorticoides/farmacología , Saimiri , Animales , Antígenos CD20/análisis , División Celular/efectos de los fármacos , Línea Celular Transformada , Dexametasona/farmacología , Herpesvirus Humano 4 , Humanos , Inmunofenotipificación , Inmunofilinas/genética , Masculino , Microscopía Electrónica , ARN Mensajero/biosíntesis , Especificidad de la Especie , Proteínas de Unión a TacrolimusRESUMEN
We conducted a prospective cohort study of 323 consecutively born very low birth weight infants (< or = 1499 gm) to determine any association between prenatal cocaine exposure and (1) intracranial ultrasonographic abnormalities and (2) other adverse perinatal outcomes. The infants were assigned to either a cocaine-exposed group (n = 86) or a cocaine-nonexposed group (n = 146) on the basis of combined detection methods for prenatal maternal cocaine abuse including maternal history, maternal and infant urine immunoassay (Emit), and meconium analysis (high-performance liquid chromatography and gas chromatography-mass spectrometry). Ninety-one infants were not assigned because of early death before complete testing (n = 80) or missed tests (n = 11). The detected incidence of cocaine exposure in the assigned population was 37% (86/232). Meconium testing with high-performance liquid chromatography and gas chromatography-mass spectrometry was the sole means of detection in 30% (26/86) of cases. The cocaine-nonexposed infants did not differ from the cocaine-exposed infants in the incidence of intraventricular hemorrhage (36% vs 35%), grades III and IV intraventricular hemorrhage (14% vs 14%), or periventricular leukomalacia (4% vs 2%). Adverse outcomes increased by cocaine exposure were abruptio placentae (8% vs 18%; p = 0.046), surgical ligation of a patent ductus arteriosus (1% vs 7%; p = 0.02), and seizures (5% vs 17%; p = 0.004). We conclude that prenatal cocaine exposure does not increase the incidence or severity of intracranial hemorrhage or periventricular leukomalacia but does increase the risk of abruptio placentae, surgical ligation of a patent ductus arteriosus and seizures in very low birth weight infants.
Asunto(s)
Hemorragia Cerebral/epidemiología , Cocaína , Complicaciones del Embarazo , Efectos Tardíos de la Exposición Prenatal , Trastornos Relacionados con Sustancias , Desprendimiento Prematuro de la Placenta/epidemiología , Hemorragia Cerebral/diagnóstico por imagen , Cocaína/análisis , Estudios de Cohortes , Conducto Arterioso Permeable/epidemiología , Conducto Arterioso Permeable/cirugía , Femenino , Humanos , Incidencia , Recién Nacido de Bajo Peso/orina , Recién Nacido , Leucomalacia Periventricular/diagnóstico por imagen , Leucomalacia Periventricular/epidemiología , Embarazo , Complicaciones del Embarazo/orina , Estudios Prospectivos , Factores de Riesgo , Convulsiones/epidemiología , Sensibilidad y Especificidad , Trastornos Relacionados con Sustancias/orina , UltrasonografíaRESUMEN
The fragile-X mental retardation syndrome is the second most common identifiable cause of mental retardation in man. This condition violates many of the expectations for X-linked disorders, including the transmission of the syndrome through men who carry the gene but, for unknown reasons, do not express it. Two new cases of male transmission are presented along with four other cases heretofore unidentified in the literature, bringing the total number of confirmed or probable cases of transmission through normal men to 32. The various unorthodox characteristics of the syndrome are reviewed in light of their influence on genetic counseling. Recommendations for counseling families with fragile-X include evaluating all sons of carrier women psychometrically and cytogenetically, abandoning termination of pregnancies with male fetuses as a means of preventing the fragile-X syndrome, assuming that all mothers of sporadic cases are carriers, and karyotyping at-risk female members at an early age.