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C M Wilson

Publications and source records attributed to C M Wilson.

At least 163 records · Page 9Linked to original sources

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↗

Delay in pulmonary glycogen degradation in fetuses of streptozotocin diabetic rats.

The developmental profile of pulmonary glycogen was investigated in fetuses of rats made diabetic before conception with the injection of 40 mg/kg streptozotocin. Lungs of control litters showed increasing pulmonary glycogen concentration from day 16-20, followed by significant decline by term (= 22 days). In contrast, the diabetic litters, which had pulmonary glycogen concentration equal to controls until day 20, showed significantly higher glycogen values (P less than 0.01) on days 21 and 22, consistent with a delay in glycogen degradation. This coincided with the finding of decreased amounts of fetal pulmonary phosphatidylcholine and disaturated phosphatidylcholine on day 21 of the diabetic gestation (P less than 0.05), but not before that time. Pulmonary glycogen phosphorylase A activity was significantly decreased in the diabetic litters on the final days of gestation, at the same time that the delay in glycogen breakdown became evident. Pulmonary glycogen synthase activity did not differ in the control and diabetic fetuses. The delay in pulmonary glycogen degradation seen in the fetus of the diabetic gestation is thus temporally related to the delay in lung maturation seen in this model and may be secondary to a decrease in the activity of the glycogenolytic enzyme phosphorylase A. Decreased availability of pulmonary glycogen stores for surfactant synthesis may be important in elucidating the mechanism of the delayed pulmonic maturation seen in fetuses of diabetic pregnancies.

Animals↗

Fluorescein transport in the anterior uvea.

Rabbit ciliary body-iris preparations accumulate 14C-fluorescein against a concentration gradient when incubated in Tyrode's solution at 37 degrees C and pH 7.4 for 1 hr. Under these conditions, fluorescein metabolism is negligible. This accumulation is depressed by cyanide, dinitrophenol, iodoacetate, by incubation in glucose-free medium, and by incubation at 0 degrees C. This uptake is not inhibited significantly by incubation in sodium-free medium, and relatively high concentrations of ouabain are necessary to cause inhibition. Initial uptake studies show saturation kinetics with half-saturation concentration = 0.12 mM and maximum accumulation rate = 2.3 mmoles/hr/kg wet tissue weight. Fluorescein thus appears to accumulate by a carrier-mediated active uptake process. On the basis of series of competition experiments, it is concluded that fluorescein uptake and p-aminohippurate uptake occur by similar, although not identical, mechanisms.

Animals↗

Genetic and endocrine control of renin activity in the submaxillary gland of the mouse.

Basal activity of submaxillary gland (SMG) renin is high in female mice that carry the Rnrs allele and is induced to higher levels by treatment with dihydrotestosterone (DHT). To determine whether the difference in basal activity between high (Rnrs/Rnrs) and low (Rnrb/Rnrb) strains is due to enhanced sensitivity of Rnrs/Rnrs strains to endogenous androgen, we first studied the effect of several types of endocrine ablation on SMG renin in young female mice, and second, we removed normal androgen receptor protein by introducing the X-linked Tfm gene. Adrenalectomy with or without castration had no effect on basal SMG renin; hypophysectomy decreased basal renin activity 400-fold but did not abolish responsiveness to DHT. Loss of androgen receptor did not affect basal renin activity but did prevent enhancement by DHT. Basal and induced renin activities in L.AKR(Alll)/Cy, a congenic strain homozygous for Rnrs introduced from AKR/J into the background of C57L/J, an Rnrb/Rnrb type strain, are intermediate between levels observed in the original strains. We conclude that (1) the basal level of SMG renin is regulated directly or indirectly by some pituitary hormone(s) but not by androgen, (2) androgen induction of renin activity requires a normal androgen receptor, and (3) major gene(s) that regulate basal as well as induced SMG renin are in a circumscribed region of chromosome 1.

Adrenalectomy↗

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↗

Mechanism of origin of complete hydatidiform moles.

Complete or 'true' hydatidiform mole, an abnormality of human gestation, is characterized by hydropic degeneraton of all placental villi, marked hypertrophy of the trophoblast, absence of a fetus and a propensity to become malignant. The chromosome constitution of complete moles is usually 46,XX, and Kajii et al. reported that the entire genome in seven out of seven cases was paternal in origin, with all centromere markers homozygous for paternal heteromorphisms. These observations, since confirmed, can be explained by the fertilization of an 'empty' egg--no effective genome--by either a haploid sperm that then duplicates without cytokinesis, to restore the diploid number, or by a diploid sperm resulting from failure of the second meiotic division. We report here a study of a series of complete moles that shows the first alternative to be correct in the majority of cases.

Female↗

Cyclophosphamide-induced lung damage in mice: protection by a small preliminary dose.

Cycylphosphamide (Cy) produces an interstitial pneumonitis in CBA mice. The extent of the lung damage has been quantified by measuring the increase in ventilation rate over 6 weeks after an i.p. injection of Cy 200, 250 and 300 mg/kg. A dose-dependent response was found. When a preliminary ("priming") dose of Cy at 50 mg/kg was given 7, 9 or 14 days before a single large dose of 250 mg/kg, lung damage was reduced, as shown by a smaller increase in ventilation rate than in those receiving 250 mg/kg alone, and this difference was significant (P less than 0.01) in the Day-14-and highly significant (P<0.001) in the Day-7-"primed" groups. When primed less than 7 days before, there was a relative increase in ventilation rate, which was statistically significant (P less than 0.01) in the Day-1-primed group. Similar effects were also seen in the survival of the mice.

Animals↗

Plant Nucleases: VI. GENETIC AND DEVELOPMENTAL VARIABILITY IN RIBONUCLEASE ACTIVITY IN INBRED AND HYBRID CORN ENDOSPERMS.

The nuclease activity of developing corn endosperms was found to consist mainly of plant RNase I during the period of major deposition of dry weight. The RNase concentrations in most inbred lines and hybrids increased throughout development, but there were large differences among genotypes in the enzyme levels at all stages. Crosses were made among inbreds classified as containing high or low RNase levels. In most cases, the general patterns of enzyme levels during development of the hybrid endosperms were not changed greatly, or showed intermediate levels of activity compared to the inbred parents. When Oh43 was used as a maternal parent, two contrasting developmental patterns were produced by using two low RNase inbreds as pollen parents. There appear to be genetic controls not only on the gross RNase levels, but also on the timing of RNase synthesis and on its stability after the cells mature. Environmental influences on RNase levels in the endosperm were noted one year.At 18 days after pollination, the RNase levels in the endosperm crown were as much as 10 times higher than in the base. By 35 days after pollination, the enzyme levels were generally uniform; at 50 days, the basal tissue usually contained the highest levels. In some genotypes, however, the enzyme levels fell in the crown while they rose in the base. These changes suggest that RNase may be associated with developmental controls that operate as the different portions of the endosperm cease cell division and begin synthesis of starch and zein.

Journal Article↗

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↗