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Biomedical subjects

B T Smith

Publications and source records attributed to B T Smith.

At least 109 records · Page 6Linked to original sources

Pulmonary epithelial-mesenchymal interactions: beyond organogenesis.

Epithelial-mesenchymal interactions are important regulators of lung growth and organogenesis, but later functional maturation of the fetal lung is though to be primarily under hormonal control. Recent evidence, however, suggests that hormonal effects on pulmonary cellular and biochemical maturation continue to involve intercellular interactions. Communication between cells may have wider importance than has hitherto been appreciated. It should be noted that in addition to organogenesis and biochemical development, mature lung requires an extensive capillary network in close proximity to areas of gas exchange. Recent attempts to isolate and culture pumonary endothelium may be expected to provide new insights into this neglected aspect of lung maturation. The possibility of hormonal or intercellular mediation of the differentiation of airway epithelium might also merit investigation.

Animals↗

Modification of ovine fetal respiratory-like activity by chronic diazepam administration.

Chronic maternal administration of diazepam resulted in a modification of fetal respiratory-like activity (FRLA) in the sheep. An over-all increase in this activity occurred. This increase was probably due to a rebound effect following periods of acute suppression with each administration of diazepam. Loss of central control in the regulation of FRLA was implied. A complete reversal of a circadian rhythm of FRLA was observed in animals receiving diazepam. These changes have implications with respect to the antenatal monitoring of the fetus and sequelae in the newborn infant.

Animals↗

Relation of amniotic fluid lecithin/sphingomyelin ratio and fetal asphyxia to respiratory distress syndrome in premature infants.

In a group of 81 prematurely delivered infants the amniotic fluid lecithin/sphingomyelin ratio was related to functional fetal lung maturity. Intrapartum fetal asphyxia occurred in 33% of the group. An association between fetal asphyxia and the development of respiratory distress syndrome (RDS) in the infant was observed. When pulmonary maturity was borderline according to the amniotic fluid assessment, intrapartum fetal asphyxia was associated with an increased risk for development of RDS in the infant.

Acid-Base Equilibrium↗

The role of pulmonary corticosteroid 11-reductase activity in lung maturation in the fetal rat.

Injection of 11-ketoprogesterone into fetal rats at day 17 of gestation reduced the pulmonary C-11 activation index (an indicator of net gain or loss of glucocorticoid activity) as measured at day 21 (P less than 0.001) and resulted in elevated levels of the inactive hormone 11-dehydrocorticosterone (P less than 0.001), but unchanged corticosterone levels. Adrenal weight was significantly increased (P less than 0.001). 11-Ketoprogesterone-injected fetuses had considerably larger lungs (P less than 0.001) with reduced saturated phosphatidylcholine content (P less than 0.001).

Animals↗

The site of amniocentesis and the lecithin-sphingomyelin ratio.

Simultaneous sampling of amniotic fluid from two sites within the amniotic cavity proximal and distal to the fetal mouth was performed. The lecithin-sphingomyelin (L/S) ratio of amniotic fluid obtained close to the fetal mouth was usually higher than that of amniotic fluid obtained from a site distal to the fetal mouth (20 of 26 cases). Differences of up to 0.7 in the two L/S ratios were measured. This suggested that pooling of amniotic fluid phospholipids occurred and in cases of borderline pulmonary maturity the site of amniocentesis may have influenced the predictive value of the L/S ratio.

Adult↗

Single-step gastric aspirate shake test: bedside predictor of neonatal pulmonary morbidity.

A simplified, single-step shake test has been performed on gastric aspirate samples from 85 preterm infants and a control group of 214 term infants. Respiratory symptoms were seen in 25 of 30 preterm infants with a negative or intermediate test, but in only 2 of 55 infants with a positive test (P less than 0-001). No infant with a positive test developed respiratory distress syndrome (RDS) while RDS developed in 66% of those preterm infants with a negative test. False-negative results were not seen in the preterm group. The gastric aspirate shake test had better sensitivity and selectivity in prediction of clinical outcome than did the amniotic fluid lecithin/sphingomyelin ratio in 37 preterm infants in whom both results were available. Serial shake tests were performed on samples from a number of infants with RDS and the results were seen to change in parallel with clinical recovery. This and other observations suggest that the result of the gastric aspirate shake test depends more upon direct swallowing of fetal lung liquid than on swallowing of amniotic fluid.

Amniotic Fluid↗

Cell line A549: a model system for the study of alveolar type II cell function.

Cell line A549, a continuously cultured line derived from a human pulmonary adenocarcinoma that has morphologic and biochemical features of the pulmonary alveolar type II cell, was studied with regard to saturated phosphatidylcholine synthesis and secretion. Evaluation of a number of culture media showed that those media that supported the most rapid rate of in vitro growth were least optimal for saturated phosphatidylcholine synthesis. Similarly, a labeled precursor (choline labeled with tritium) was most efficiently converted to saturated phosphatidylcholine when growth was slow or arrested, whereas during phases of active cellular proliferation a greater proportion was incorporated into unsaturated (structural) phosphatidylcholine. De novo synthesis of phosphatidylcholine was primarily via the cytidine diphosphate-choline pathway, because no incorporation of labeled methyl groups from S-adenosyl-L-methionine was observed. Cortisol stimulated tritium-labeled choline incorporation into saturated phosphatidylcholine in a manner that likely involed a steroid receptor system, whereas cortisone was inactive. The half-life of cellular saturated phosphatidylcholine was of the order of 100 hours and could be accounted for virtually entirely by release of this phospholipid into the medium unchanged. Both cholinergic and adrenergic agents in high doses modestly stimulated the release of pre-labeled saturated phosphatidylcholine from the cells, and the response to these secretagogues was significantly enhanced by cortisol. Cell line A 549 promises to be a useful model system for studies of the cellular events involved in pulmonary saturated phosphatidylcholine synthesis and secretion.

Cell Differentiation↗

The relationship of cortisol and cortisone to saturated lecithin concentration in ovine amniotic fluid and fetal lung liquid.

Cortisol and cortisone concentrations in ovine amniotic fluid and fetal lung liquid were analyzed with respect to gestational age and fetal lung maturation as reflected by saturated lecithin concentration. In amniotic fluid, the cortisol concentration rises as a function of gestational age while that of cortisone falls (P less than 0.001). The ratio of cortisol/cortisone is significantly related to gestational age (r=0.693, P less than 0.001), and shows an even stronger correlation with saturated lecithin concentration (r=0.832, P less than 0.001). When examined independently of gestational age, the correlation of the cortisol/cortisone ratio to saturated lecithin concentration remains highly significant (r=0.641, P less than 0.001). Similar findings were observed in fetal lung liquid, except that in this fluid both the saturated lecithin concentration and the ratio of cortisol/cortisone are significantly higher than simultaneously determined values in amniotic fluid. These observations provide further evidence that the process of fetal lung maturation is closely linked to the fetal hormonal milieu.

Amniotic Fluid↗

Human amniotic membrane corticosteroid 11-oxidoreductase activity.

The ability of amniotic membrane, obtained with 3 h of delivery of 28 infants, to interconvert 3H-cortisol and 14-C-cortisone has been examined. The conversion of cortisone to cortisol increases as a function of gestational age, being first seen at 29.5 weeks and reaching values of 50--55% at term (n = 28, r = 0.615, P less than 0.01). Furthermore, a net gain of the active hormone (cortisol) resulting from the bidirectional interconversion of cortisol and cortisone ("C-11 activation index") appears at 31 weeks and reaches 40--50% by term (n = 28, r = 0.674, P less than .001). We speculate that this phenomenon could be an important source of active glucocorticoid for the fetus.

Amnion↗

Fetal lung maturity. I. Mode of onset of premature labor. Influence of premature rupture of the membranes.

In a prospective study of 133 spontaneous premature deliveries the relation between premature rupture of the membranes (PRM) and development of respiratory distress syndrome (RDS) in newborn infants is examined. PRM is associated with a significantly decreased incidence of RDS in newborn infants (P less than 0.002). This relation is valid at a gestational age of 28 weeks or more and a birthweight greater than 1000 g. Total respiratory morbidity in newborn infants (transient tachypnea + RDS) is also significantly decreased when labor is associated with PRM (P less than 0.005). Assessment of the influences of sex of the infant, fetal asphyxia, and delivery by cesarian section shows that PRM bears a stronger relation than each of these individual factors to a decreased incidence of RDS. Duration of the latent period has no influence on protection from RDS, and it is suggested that fetal lung maturity occurs before the membranes rupture.

Birth Weight↗

Fetal lung maturation. III. The amniotic fluid cortisol/cortisone ratio in preterm human delivery and the risk of respiratory distress syndrome.

Cortisol and cortisone have been measured in amniotic fluid samples obtained within 24 hours of deliver of 50 premature infants. When expressed as cortisol/cortisone ratios, the ratio tends to rise with advancing gestational age, although statistical significance is not attained. Both cortisol concentration and the cortisol/cortisone ratio are significantly lower in the amniotic fluid of infants who develop respiratory distress syndrome than in those with mature lung function (cortisol ratio: 19.2 +/- 10.3 ng/ml vs 26.1 +/- 9.4, P less than .02; cortisol/cortisone ratio: 1.2 +/- 0.6 vs 2.0 +/- 0.8, P less than .001). These findings also hold in the subgroup of infants less than 32 weeks' gestation but not in those infants at or beyond the 32nd week. The amniotic fluid cortisone concentration is significantly lower in infants born after spontaneous labor beginning with rupture of the membranes as opposed to after contractions or bleeding (13.2 +/- 3.6 ng/ml vs 16.3 +/- 6.1, P less than .05), although the cortisol concentrations and the cortisol/cortisone ratios are not significantly different.

Amniotic Fluid↗

Biogenesis of corticosteroids in monolayer cultures of human foetal adrenal cells.

Human foetal adrenal cells were grown in monolayer culture and their steroidogenic capacity observed for up to a month. The cells produced a complex array of steroids and some of their ester sulphates from endogenous as well as from [14C] and [3H] precursors. ACTH stimulated corticoidogenesis, particularly cortisol secretion, and markedly enhanced the incorporation of progesterone and pregnenolone into cortisol. Following incubation with the same precursors, large amounts of radioactivity remained water soluble. From the butanol extractable material of this fraction, dehydroepiandrosterone sulphate was characterized as the main metabolite of pregnenolone and corticosterone and 11-deoxycorticosterone sulphates as the main metabolites of progesterone. With time in culture there was a decrease in steroidogenesis as well as a steady decline in responsiveness to ACTH, mainly manifested by cortisol secretion. The medium from homologous foetal pituitary cultures stimulated cortisol production by the human adrenal cell monolayer.

Adrenal Glands↗

Preliminary observations of bovine adrenal fasciculata-reticularis cells in monolayer culture: steroidogenesis, effect of ACTH and cyclic AMP.

Bovine adrenocortical cells dispersed by trypsin digestion of fasciculata-reticularis minces were maintained in monolayer culture for up to 6 weeks. During the first week cells grown in medium containing ACTH (1 mU/ml) secreted steroids at a rate 10 to 20-fold greater than control cultures, cortisol accounting for 80-90% of the corticotrophic response. Using tracer amounts of [3H] progesterone and [3H] pregneolone, the major products were cortisol, corticosterone, 11-deoxycortisol and 11-deoxycorticosterone in decreasing order of magnitude. After 10 to 15 days in culture steroidogenesis was no longer enhanced by ACTH. This was concomitant with an apparent loss of 11 beta-hydroxylase activity which was mainly manifested by a sharp increase in the formation of 44-deoxycortisol. Short-term incubations of these cells during the first week in culture provided evidence that steroidogenesis was related to ACTH concentrations (from 0.1 to 100 muU/ml) and stimulated by dibutyryl cyclic AMP, the corticotrophic responses being further enhanced by theophylline (0.5to 50 mumoles/5 ml). Exposure of the cells to ACTH (50 muU/ml) resulted in a rapid increase in intracellular cyclic AMP contractions concomitant with a progressive increase in the corticosteroids released into the medium.

Adrenal Cortex↗