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Biomedical subjects

B T Smith

Publications and source records attributed to B T Smith.

At least 91 records · Page 5Linked to original sources
PubMed1984

Insulin acts on the fibroblast to inhibit glucocorticoid stimulation of lung maturation.

The effects of insulin and cortisol on saturated phosphatidylcholine synthesis are examined in fetal type II cell cultures and in mixed cell cultures containing type II cells and fibroblasts. In 19-day fetal rat lung type II cell cultures, 100 nM cortisol and 2 nM insulin have no significant effect. Fibroblast-pneumonocyte factor results in enhanced saturated phosphatidylcholine synthesis by fetal type II cells. The significant stimulatory effect of cortisol in mixed-cell cultures is abolished in the presence of insulin or of monoclonal antibodies to fibroblast-pneumonocyte factor. Incubation of type II cells with conditioned media from fibroblasts exposed to cortisol results in increased saturated phosphatidylcholine synthesis. This process is not stimulated when type II cells are incubated with conditioned media from fibroblasts exposed to insulin and cortisol (or to insulin alone). These observations demonstrate that insulin inhibits cortisol induction of lung maturation and suggest that this antagonism results from an inhibitory effect of insulin on the elaboration of fibroblast-pneumonocyte factor by fetal lung fibroblasts.

Animals↗
PubMed1984

Serum somatomedin C concentrations following pneumonectomy.

Because a somatomedinlike substance appears in rabbit serum 9 days after pneumonectomy, which has the capacity to make cultured type II cells incorporate 3H thymidine into DNA, we measured serum immunoreactive somatomedin C concentrations following pneumonectomy, nephrectomy, and sham operation (thoracotomy). We found no striking differences in somatomedin C levels between the 3 groups at 5, 9, 13, 17, and 21 days postsurgery, indicating that somatomedin-C and the serum postpneumonectomy factor are unlikely to be the same. Serum somatomedin-C concentrations, however, rose following surgery in all groups, suggesting that serum somatomedin-C responds to surgical wounding. We speculate that the increase in serum somatomedin-C reflects production of somatomedin-C by the healing tissue.

Animals↗
PubMed1984

Alveolar type II cells isolated from fetal rat lung organotypic cultures synthesize and secrete surfactant-associated phospholipids and respond to fibroblast-pneumonocyte factor.

Alveolar type II cells that were isolated from organotypic cultures of fetal rat lung and maintained in primary monolayer culture were analyzed. Morphologically the cells retained many characteristics of type II cells in vivo. Biochemical analysis revealed that the cells contained and synthesized phosphatidylcholine with a high degree of saturation. Furthermore, the cells released saturated phosphatidylcholine and responded to adrenergic stimulation with increased release. The type II cells retained their ability to proliferate and responded to fibroblast-pneumonocyte factor. These data indicate that primary cultures of fetal type II cells will be useful to elucidate mechanisms modulating type II cell proliferation, surfactant synthesis, and surfactant secretion.

Animals↗
PubMed1984

Influence of the major histocompatibility complex (H-2) on glucocorticoid-stimulated pulmonary surfactant synthesis in two congenic mouse strains.

Mice with different histocompatibility alleles in otherwise identical backgrounds (congenic inbred strains of H-2a and H-2b haplotypes), were used to study the possible influence of the major histocompatibility complex (MHC) upon glucocorticoid-stimulated pulmonary surfactant synthesis during embryonic and fetal stages of mouse lung development. Pregnant C57BL/10SnJ (H-2b) and congenic B10.A/SnSgJ (H-2a) mice were administered single or consecutive intraperitoneal injections of betamethasone during the period of 14 through 17 days gestation. Assays for incorporation of [3H]choline into total lipid and saturated phosphatidylcholine (an index for pulmonary surfactant synthesis) were conducted, 24 hr following the last treatment, on Days 17 or 18 of gestation. Control mice received injections of phosphate-buffered saline. The H-2 genotype appears to influence the relative responsiveness of glucocorticoid-stimulated surfactant synthesis during fetal lung development. The B10.A strain (H-2a haplotype) was more responsive to glucocorticoid-stimulated pulmonary surfactant synthesis than the H-2b haplotype. Whereas both strains were responsive to glucocorticoid-stimulated [3H]choline incorporation into lung surfactant, the differences in responsiveness at specific fetal stages suggest that genes within or closely linked to the H-2 complex might have a role in pulmonary surfactant biosynthesis during mouse lung development. The results also suggest the possibility that relative susceptibility to congenital pulmonary disorders may be influenced by the H-2 complex.

Alleles↗
PubMed1983

Evidence for epithelial-mesenchymal interactions mediating glucocorticoid effects in developing chick liver. Fibroblast-hepatocyte factor.

When trypsin-dissociated liver cells from 17-day chick embryos were grown in regular minimum essential medium, mixed hepatocyte-fibroblast cultures resulted. When D-valine was substituted for L-valine in this medium, fibroblast growth was suppressed, leaving virtually pure hepatocyte cultures. Tyrosine aminotransferase activity is induced by cortisol in mixed cultures. No induction of enzyme activity is observed with cortisol exposure to hepatocytes, grown in D-valine. However, when cortisol-containing medium is conditioned by pre-incubation with mixed cells and then transferred to hepatocytes, tyrosine aminotransferase activity is induced. Enzyme activity is also induced in mixed cells incubated in D-valine medium in the presence of cortisol. It appears that a substance produced in the presence of fibroblasts exposed to cortisol is capable of inducing tyrosine aminotransferase activity in hepatocytes. This activity, which we have termed fibroblast hepatocyte factor, is heat stable, of low molecular weight, and antigenically different from fibroblast pneumonocyte factor, a factor similar to that produced by lung fibroblasts exposed to cortisol.

Animals↗
PubMed1983

Organotypic differentiation of trypsin-dissociated fetal rat intestine.

These studies examined the potential for reorganization and differentiation of dissociated 18-day fetal rat intestine. Cultures of trypsin-dissociated fetal intestine were maintained in vitro for 1 week on a three-dimensional matrix, then transplanted into syngeneic hosts. When harvested after 4 weeks, these transplants consistently demonstrated organotypic differentiation. Spherical structures containing crypts with frequent mitotic figures and villi lined with columnar epithelium had formed. PAS staining demonstrated positive epithelial cell brush borders, goblet cells, and luminal contents. Significant levels of the microvillus membrane enzymes lactase, sucrase, maltase, and alkaline phosphatase were present in the luminal contents. Sucrase-isomaltase, an enzyme characteristic of postweaning small intestine, was demonstrated by immunoprecipitation and SDS-PAGE. Thus, both morphological and biochemical maturation occurred in the transplants.

Animals↗
PubMed1983

Glucocorticoid-thyroid synergism in lung maturation: a mechanism involving epithelial-mesenchymal interaction.

We studied the effects of cortisol and triiodothyronine (T3) on 20-day fetal rat lung cell cultures. Cortisol enhanced the production of surfactant-associated saturated phosphatidylcholine while T3 did not. However, T3 potentiated the cortisol effect. We observed that T3 enhanced the response of cultures enriched with alveolar type H cells to fibroblast-pneumonocyte factor (FPF). Intracellular cAMP was increased by exposure of these cultures to FPF, and T3 potentiated this increase. Unlike cortisol, T3 had no effect on production of FPF by fetal lung fibroblasts, as determined by bioassay of fractions of fibroblast-conditioned medium partially purified by column chromatography. The time course of cortisol action on mixed (fibroblast/epithelial) cultures was in keeping with the proposed mechanism: glucocorticoid induction of FPF in fibroblasts, followed by FPF induction of cAMP in epithelia and, finally, by enhanced production of saturated phosphatidylcholine. Thus, glucocorticoid acting on mesenchyme and thyroid hormone acting on epithelium have a synergistic effect on expression of differentiated epithelial function.

Animals↗
PubMed1982

Influence of corticosteroids on glycogen content and steroid 11-reductase activity in lung and liver of the fetal and newborn rat.

Lung and liver glycogen and corticosteroid 11-reductase activity were studied in fetal and neonatal rats. Glycogen content peaked in the lung on day 20 of gestation, while hepatic glycogen content was generally lower and peaked later. Both pre- and postnatally, betamethasone administration resulted in lowered pulmonary and elevated hepatic glycogen. In both lung and liver, corticosteroid 11-reductase activity showed an inverse developmental pattern to glycogen content. Betamethasone elevated pulmonary corticosteroid 11-reductase activity and lowered hepatic activity. In lung and liver, glycogen content and corticosteroid 11-reductase activity are tightly linked during development and following glucocorticoid therapy.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1981

Effects of reduction of placental size in sheep.

The number of uterine caruncles was reduced by electrocautery in nonpregnancy sheep. Subsequent pregnancies were studied as chronic fetal sheep preparations between 110 days' gestation and term; findings were compared with those for control chronic fetal sheep preparations at a similar gestational age. As a result of decreased weight and reduced number of cotyledons, the placenta in experimental animals was significantly smaller compared with that in controls. The weights of the fetal liver and heart were decreased, fetal PO2 was decreased, and fetal PCO2 and hematocrit levels were increased in the experimental group. Fetal plasma fructose levels were decreased in experimental animals, but fetal blood lactate, pyruvate, and plasma glucose levels were similar in both groups. No differences were demonstrated in fetal plasma or amniotic fluid cortisol levels and amniotic fluid lecithin : sphingomyelin ratios. Fetal respiratory-like activity was significantly depressed in the experimental group.

Animals↗
PubMed1980

Human amniotic fluid contains fibroblast-pneumonocyte factor.

We have studied 41 samples of human amniotic fluid collected at 27-40 wk gestation. After 'stripping' with Florisil, most fluids studied stimulated [3H] choline incorporation into saturated phosphatidylcholine by human fetal alveolar Type II cells. The activity declined with advancing gestation and was inversely related to cell number following incubation. Following acid-ethanol extraction, activity eluted from Sephadex G75 columns in 1 M acetic acid with a Kd of approximately equal to 0.4-0.6, and was greater at earlier gestations (27-31 wk) than at later periods (32-36 or 37-40 wk). In contrast, chromatography at neutral pH without prior extraction resulted in retarded elution. The active material was shown to be heat-stable. Thus, the biochemical features of activity recovered from human amniotic fluid are identical to fibroblast-pneumonocyte factor recovered from supernatant culture media of cortisol-treated human fetal lung fibroblasts.

Amniotic Fluid↗
PubMed1980

Individualised continuous distending pressure applied within 6 hours of delivery in infants with respiratory distress syndrome.

A preliminary study was performed in which a simple clinical technique for estimating appropriate levels of continuous distending pressure (CDP) in infants with respiratory distress syndrome (RDS) was used to compare two groups of infants; one group had CDP started very early in life (3.1 +/- 0.3 hours) while in the other treatment was started at a more conventional age (23 +/- 5.4 hours). Appropriate CDP was identified as the point at which transpulmonary transmission of airways pressure to the oesophagus was seen suddenly to increase, while serial measurements allowed CDP levels to be instituted and varied according to physiological signs during the course of each infant's disease. Oxygen requirements fell to less than 35% more rapidly in the early-treated group (10.6 +/- 1.2 v. 67.4 +/- 5.6 hours; P less than 0.001), as did the requirement for a CDP greater than 4 cmH2O (28.9 +/- 5.3 v. 87.6 +/- 14.2 hours; P less than 0.001). Better (P less than 0.01) values for pH, PaCO2, and A-aDO2 were observed in the early-treated group. We believe that the use of this simple technique has numerous advantages and that very early introduction of CDP can be realised in a manner selective enought for it to be used in those infants in whom intervention is justified.

Age Factors↗
PubMed1980

Influence of oxygen tension and cortisol environment upon growth and cortisone conversion to cortisol by cultured human fetal lung fibroblasts.

Growth and conversion of cortisone to cortisol by human fetal lung fibroblasts in monolayer cell culture have been found to be sensitive to steady-state oxygen concentrations or to acute oxidant stresses. Oxygen-dependent differences are significantly modified by pre-incubation with cortisol. We speculate that cortisol may have an oxygen-protective role, and that the induction of increased conversion of cortisone to cortisol with an increase in oxygen tension, such at that observed at delivery, may be of significance in the prematurely born infant with the respiratory distress syndrome.

Cell Line↗
PubMed1980

Serum from pneumonectomized rabbits stimulates alveolar type II cell proliferation in vitro.

Serum samples collected from pneumonectomized rabbits 9 and 21 days after surgery significantly enhanced the incorporation of [3H]thymidine into DNA by alveolar Type II cells in vitro, but they had no effect on lung or skin fibroblasts. Activity was absent from serums collected 140 days after surgery. Active serums showed a dose-response effect at concentrations between 1% and 10% in the alveolar Type II cell culture system and the activity was heat stable. The active factor eluted from columns of Sephadex G75 at the void volume at neutral pH, but after acid-ethanol extraction and chromatography under acidic conditions, it eluted with a Kd of approximately 0.65. We propose that the active substance is a somatomedin or somatomedin-like peptide.

Animals↗
PubMed1979

Lung maturation in the fetal rat: acceleration by injection of fibroblast-pneumonocyte factor.

Fibroblast-pneumonocyte factor, produced by the fetal lung fibroblast in response to glucocorticoids, was partially purified by column chromatography on Sephadex G-75. The resulting preparation showed two major and two minor bands on sodium dodecylsulfate-polyacrylamide gel electrophoresis. When fetal rats were injected on day 17 of gestation with 1 microgram of this material, they showed on day 20 biochemical evidence of accelerated lung maturation as compared to littermate controls. There were no differences between the two groups in body weights, organ weights, or circulating corticosteroid levels.

Animals↗