RESUMO
The pulmonary surfactant proteins SP-B (8,000 D) and SP-C (4,000 D) accelerate surface film formation by surfactant phospholipids. We used cDNA probes to examine regulation of these proteins in human fetal lung. The mRNAs were detectable at 13 wk gestation and increased to approximately 50% (SP-B) and approximately 15% (SP-C) of adult levels at 24 wk. The mRNAs were detected only in lung of 11 dog tissues examined. When human fetal lung was cultured as explants without hormones, SP-B mRNA increased and SP-C mRNA decreased. Exposure for 48 h to glucocorticoids, but not other steroids, increased both SP-B mRNA (approximately 4-fold) and SP-C mRNA (approximately 30-fold) vs. controls. Half-maximal stimulation occurred with 1 nM dexamethasone and 300 nM cortisol for SP-B mRNA and at three- to fivefold higher concentrations for SP-C mRNA. Both stimulation and its reversal on removal of hormone were more rapid for SP-B than for SP-C. Terbutaline and forskolin increased SP-B mRNA but not SP-C mRNA. Levels of both mRNAs were much higher in type II cells than fibroblasts prepared from explants. Thus, the genes for SP-B and SP-C are expressed in vivo before synthesis of both SP-A (28,000-36,000 D) and surfactant lipids. Glucocorticoid induction of SP-B and SP-C mRNAs in type II cells appears to be receptor mediated but may involve different mechanisms.
Assuntos
Pulmão/metabolismo , Surfactantes Pulmonares/metabolismo , RNA Mensageiro/metabolismo , Animais , Northern Blotting , Técnicas de Cultura , AMP Cíclico/fisiologia , Dexametasona/farmacologia , Cães , Epitélio/metabolismo , Fibroblastos , Humanos , Pulmão/efeitos dos fármacos , RNA Mensageiro/isolamento & purificaçãoRESUMO
Two years' experience with DNA analysis for the antenatal diagnosis of thalassaemia and haemophilia is described. The advantages of DNA testing, including a first-trimester diagnosis and greater availability, must be considered in relation to the problems that are associated with this procedure. In particular, the risk of recombination in DNA polymorphism studies should be understood and explained fully to the patient.
Assuntos
DNA/análise , Doenças Fetais/diagnóstico , Hemofilia A/diagnóstico , Diagnóstico Pré-Natal/métodos , Talassemia/diagnóstico , Amniocentese , Biópsia , Vilosidades Coriônicas/patologia , Mapeamento Cromossômico , Feminino , Doenças Fetais/genética , Hemofilia A/genética , Heterozigoto , Homozigoto , Humanos , Polimorfismo Genético , Gravidez , Risco , Talassemia/genéticaRESUMO
Prenatal diagnosis by chorionic biopsy was undertaken between the eighth and 12th weeks of pregnancy in 50 patients at risk of chromosomal or genetic abnormalities. Samples from 45 patients were karyotyped. A DNA analysis for the detection of homozygous beta-thalassaemia was undertaken in five patients. The sample from one patient at risk of haemophilia in the fetus was subjected to DNA analysis after a male fetus was confirmed on karyotyping. Abnormal karyotypes were detected in four fetuses while three had homozygous beta-thalassaemia.