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Biomedical subjects

I Gross

Publications and source records attributed to I Gross.

At least 73 records · Page 4Linked to original sources
PubMed1983

Corticosteroid stimulation of phosphatidylcholine synthesis in cultured fetal rabbit lung: evidence for de novo protein synthesis mediated by glucocorticoid receptors.

To investigate further the mechanism whereby glucocorticoids accelerate the maturation of the pulmonary surfactant system, we studied both binding of glucocorticoids and their effect on phosphatidylcholine synthesis in organ cultures of fetal rabbit lung grown in serum-free medium. The greatest effect of dexamethasone (100 nM for 48 h) occurred at 24 days gestation when there was a 103% increase in the rate of choline incorporation into phosphatidylcholine and a 24% increase in the tissue content of disaturated phosphatidylcholine. Stimulation by corticosteroid was first observed after 12 h of exposure. Choline incorporation increased in a linear fashion for 36 h and then began to plateau; removal of the steroid after 24 h prevented any further increase in stimulation. The presence of other hormones in the culture medium was not a prerequisite for the corticosteroid action. Fetal sex had no influence on dexamethasone-induced phosphatidylcholine synthesis or on nuclear binding of dexamethasone. There was a striking similarity between the Kd values for specific nuclear binding of dexamethasone and cortisol (0.6 +/- 0.1 and 7.3 +/- 0.1 nM, respectively) and the concentrations for half-maximal stimulation of phosphatidylcholine synthesis (0.7 +/- 0.1 and 6.8 +/- 0.5 nM). The relative potencies of a number of steroids (100 nM) for both nuclear binding and stimulation of choline incorporation were the same: dexamethasone greater than cortisol greater than cortisone greater than corticosterone greater than dehydrocorticosterone, with no effect by progesterone, testosterone, or estradiol at this dose. Actinomycin D and cycloheximide blocked dexamethasone-induced phosphatidylcholine synthesis in a dose-dependent fashion. Actinomycin D had a marked effect if added at the initiation of hormone exposure, but little effect when added after 24 h, whereas cycloheximide was primarily effective between 24-48 h. These findings suggest that glucocorticoid stimulation of phosphatidylcholine synthesis in fetal lung is mediated by binding to specific receptors, with subsequent de novo synthesis of RNA and protein.

Animals↗
PubMed1982

Fetal lung in organ culture. IV. Supra-additive hormone interactions.

Corticosteroids, thyroid hormones, and theophylline have previously been shown to accelerate fetal lung maturation. We have examined the interactions between these agents in relation to phospholipid synthesis in explants of 18-day fetal rat lung in organ culture. Maximal stimulation of the rate of incorporation of choline into phosphatidylcholine, the most abundant phospholipid in pulmonary surfactant, was observed at a dexamethasone concentration of 100 nM. Exposure to 100 nM dexamethasone, 1.0 mM theophylline, or a combination of the two agents for 48 h resulted, respectively, in 144, 157, and 508% stimulation of the rate of incorporation of choline into disaturated phosphatidylcholine. Similar supra-additive interactions between dexamethasone and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) were observed, but the effects with caffeine were less striking. The increase in the rate of precursor incorporation was associated with a significant increase in the disaturated phosphatidylcholine content of the cultures. Combination of dexamethasone with 100 nM triiodothyronine (the concn producing maximal effects) also resulted in supra-additive stimulation but to a smaller degree. These findings of interactions in vitro suggest that the agents act on the lung at different biochemical sites, but the mechanisms whereby they interact at the cellular level have yet to be established. The data provide a rationale for in vivo animal studies of the effects of combined hormone administration on fetal lung maturation.

Animals↗
PubMed1981

Gastric antisecretory agents. 2. Antisecretory activity of 9-[(aminoalkyl)thio]-9H-xanthenes and 5-[(aminoalkyl)thio]-5H-[1]benzopyrano[2,3-b]pyridines.

A series of 9-[(aminoalkyl)thio]-9H-xanthenes (3-6) and 5-[(aminoalkyl)thio]-5H-[1]benzopyrano[2,3-b]pyridines (7-10) possessing gastric antisecretory activity in the rat and dog is described Many of the compounds possessed good activity in the pylorus-ligated rat and several inhibited histamine-stimulated gastric acid secretion in the dog. The mechanism of acid secretion inhibition is not related to anticholinergic or histamine (H2) receptor antagonism.

Animals↗
PubMed1981

Organotypic culture of fetal rat lung: evaluation and comparison with organ culture.

Monodispersed suspensions of 19-day fetal rat lung when plated onto gelatin sponges reaggregated to form alveolarlike structures. These structures consisted almost entirely of alveolar type II cells, whereas the whole cultures contained about 65% type II cells. The phospholipid content and composition of the organotypic cultures after 8 days of incubation was very similar to that of explants of 19-day fetal rat lung grown in organ culture of 48 h, as was the pattern of incorporation of choline and acetate into phospholipids. Very little phosphatidylcholine was secreted by the organotypic cultures into the culture medium. Initial observations suggested that the organ cultures are more responsive to hormones. Organotypic cultures do not appear to offer any major advantage over the simpler and quicker organ cultures for studies of hormonal influences on fetal lung maturation. They may be useful for examining the metabolism and sympathetic pathways of the type II cell.

Acetates↗
PubMed1980

Fetal lung in organ culture. III. Comparison of dexamethasone, thyroxine, and methylxanthines.

Exposure of explants of fetal rat lung to dexamethasone, thyroxine, or the methylxanthines, aminophylline and caffeine, resulted in a significant increase in the rate of choline incorporation into all the choline-containing phospholipids. Dexamethasone, aminophylline, or caffeine treatment also resulted in an increase in the percentage of radioactivity from [3H]acetate in the surfactant-associated phospholipids, disaturated phosphatidylcholine, and phosphatidylglycerol and a corresponding decrease in the membrane phospholipids. Exposure to thyroxine had different effects. Only aminophylline and caffeine produced an increase in the rate of incorporation of acetate into phospholipid. Differences were also observed in the activities of enzymes of phospholipid synthesis. The activity of cholinephosphate cytidylyltransferase was increased by dexamethasone and that of choline kinase and lysolecithin acyltransferase by aminophylline. Thyroxine had no effect on any of the enzymes examined. All these agents produced a significant decrease in lung glycogen content and a small decrease in the protein-to-DNA ratio. These data indicate that corticosteroids, thyroxine, and the methylxanthines act directly on the fetal lung, but produce different effects and presumably act via different mechanisms.

Animals↗
PubMed1979

Effects of betamethasone on phospholipid content, composition and biosynthesis in the fetal rabbit lung.

Administration of betamethasone (0.2 mg/kg, intramuscularly) to pregnant rabbits had the following effects on the fetal lung at 26--27 days gestation. It increased the amount of phosphatidylcholine in lung lavage by 70% and almost doubled the phosphatidylcholine/sphingomyelin ratio, it increased the rate of incorporation of choline into phosphatidylcholine in fetal lung slices by up to 90%, it increased the activities of pulmonary cholinephosphate cytidylyltransferase and phosphatidate phosphatase by 50% and it reduced the amount of lung glycogen to 60% of the amount in the controls. Betamethasone had no effect on the activities of pulmonary cholinephosphotransferase or lysolecithin: lysolecithin acyltransferase but it slightly decreased the activity of choline kinase. Betamethasone administration to the doe did not increase the amount of surfactant phospholipid in fetal lung lavage to as great an extent as did direct administration of cortisol to the fetuses. Neither did betamethasone stimulate the activity of pulmonary cholinephosphotransferase. These data suggest that agents other than glucocorticoids mediate the stress-induced acceleration of fetal lung maturation and surfactant production.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1979

Thyrotropin-releasing hormone increases the amount of surfactant in lung lavage from fetal rabbits.

UNLABELLED: Administration of thyrotropin-releasing hormone (TRH) to pregnant rabbits at 25 and 26 days of gestation results in increased pulmonary surfactant production by the fetus at 27 days (full term is 31 days). There was 60% more total phospholipid and 150% more phosphatidylcholine (the major component of surfactant) in the lung lavage from the fetuses in the treated group than in that from the controls. Lung lavage from the fetuses in the treated litters contained 13.4 +/- 1.6 micrograms of total phospholipid phosphorus/g lung dry wt and 5.6 +/- 1.1 micrograms of phosphatidylcholine phosphorus while that from the fetuses in the control litters contained only 8.2 +/- 1.1 micrograms and 2.2 +/- 0.4 micrograms, respectively. The phosphatidylcholine/sphingomyelin ratio increased from 1.0 in the lavage from the controls to 2.2 in that from the treated group. These changes in lung lavage phospholipid content and composition are in the direction of increased lung maturation. TRH administration had no effect on the incorporation of choline into phosphatidylcholine in fetal lung slices. These data suggest that TRH stimulates surfactant release rather than synthesis. SPECULATION: TRH has a physiologic role in fetal lung maturation and surfactant production. It may potentially be used in the prevention of the respiratory distress syndrome in humans.

Animals↗
PubMed1979

Influence of aminophylline and cyclic AMP on glycogen metabolism in fetal rat lung in organ culture.

The glycogen content of fetal rat lung declines coincident with increased pulmonary phospholipid synthesis. Aminophylline, a methylxanthine cyclic adenosine 3',5' monophosphate (AMP) phosphodiesterase inhibitor, and cyclic AMP augment fetal lung phospholipid synthesis. Because lung glycogen breakdown may contribute to pulmonary phospholipid synthesis, the effects of aminophylline and cyclic AMP on glycogen metabolism were studied in explants of 19 day fetal rat lung in organ culture. Treatment with aminophylline or dibutyryl cyclic AMP for 24 hr, resulted in a 25% (P less than 0.025) and 75% (P less than 0.001) decrease, respectively, in the glycogen content of the explants. Glycogen synthase I activity was reduced by 32% in aminophylline treated cultures (P less than 0.025) and 25% in cyclic AMP treated cultures (P less than 0.025). The percent of total synthase in the active form was significantly reduced in all treated cultures. Neither aminophylline nor cyclic AMP treatment resulted in significant changes in glycogen phosphorylase a or total phosphorylase activity.

Aminophylline↗
PubMed1978

Development of glycogen and phospholipid metabolism in fetal and newborn rat lung.

Glucose, a major metabolic substrate for the mammalian fetus, probably makes significant contributions to surface active phospholipid synthesis in adult lung. We examined the developmental patterns of glycogen content, glycogen synthase activity, glycogen phosphorylase activity and glucose oxidation in fetal and newborn rat lung. These patterns were correlated with the development of phosphatidylcholine synthesis, content and the activities of enzymes involved in phosphatidylcholine synthesis. Fetal lung glycogen concentration increased until day 20 of gestation (term is 22 days) after which it declined to low levels. Activity of both glycogen synthase I and total glycogen synthase (I + D) in fetal lung increased late in gestation. Increased lung glycogen concentration preceded changes in enzyme activity. Glycogen phosphorylase a and total glycogen phosphorylase (a + b) activity in fetal lung increased during the period of prenatal glycogen depletion. The activity of the pentose phosphate pathway, as measured by the ratio of CO2 derived from oxidation of C1 and C6 of glucose, declined after birth. Fetal lung total phospholipid, phosphatidycholine and disaturated phosphatidylcholine content increased by 60, 90 and 180%, respectively, between day 19 of gestation and the first postnatal day. Incorporation of choline into phosphatidylcholine and disaturated phosphatidylcholine increased 10-fold during this time. No changes in phosphatidylcholine enzyme activities were noted during gestation, but both choline phosphate cytidylyltransferase and phosphatidate phosphatase activity increased after birth. The possible contributions of carbohydrate derived from fetal lung glycogen to phospholipid synthesis are discussed.

Aging↗
PubMed1978

An organ culture model for study of biochemical development of fetal rat lung.

We have developed a short-term organ culture model for the study of the biochemical and morphological development of late gestation fetal rat lung. Explants (1 mm3) of 19-day lung were cultured in an oxygen enriched environment in the presence of synthetic serum-free medium for 3 days. Morphological maturation continued in culture. The rate of incorporation of choline into disaturated phosphatidylcholine and the content of this phospholipid in the explants increased in vitro in a pattern very similar to that which occurs in vivo. The activities of choline kinase and cholinephosphotransferase were also similar in cultured lung and in vivo. Studies of glucose oxidation to CO2 provided additional evidence that the explants remained viable in culture. The explants retained the sensitivity of fetal lung to hormonal action. This was demonstrated by the stimulation of choline incorporation into phospholipid by cyclic AMP and an increase in the glycogen content after exposure to insulin.

Animals↗
PubMed1978

[Erythropoietin and erythropoiesis inhibitor in neonatal hypoxia and normal conditions].

In 22 healthy newborns and in 31 newborns with transposition of the major arterial vessels (TMAV) erythropoietin and erythropoiesis inhibitor was studied on a model of polycythemic mice. Erythropoietin was not detected, whereas erythropoiesis inhibitor was revealed in the plasma and urine of 5--7-day-old healthy newborns. The newborns with TMAV displayed a rise of erythropoietin level up to the 14th day and its reduction during the period of from 14th to the 56th days. Erythropoiesis inhibitor was also found in the urine concentrates of the newborn with TMAV during the period of 3--4 weeks. The role of erythropoiesis inhibitor as a physiological regulator appearing in the blood of healthy and hypoxic newborns to normalize the erythropoiesis in the course of the initial weeks after birth is discussed.

Erythropoietin↗