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Biomedical subjects

G C Randall

Publications and source records attributed to G C Randall.

At least 19 recordsLinked to original sources

Conformation and dynamics of single DNA molecules in parallel-plate slit microchannels.

The conformation and diffusion of a single DNA molecule confined between two parallel plates are examined using both single molecule experiments and Brownian dynamics simulations accounting for hydrodynamic interactions. The degree of chain stretching and the diffusivity are characterized as a function of the chain confinement and the channel geometry. Good agreement is found between the simulations, experiments, and scaling theory predictions.

Computer Simulation↗

Prostaglandin production by porcine allantochorion in vitro: effect of cortisol infusion in vivo.

The effect of cortisol infusion into the porcine fetus on subsequent prostaglandin (PG) production in vitro by the fetal placenta (the allantochorion) was studied. Also, the possible in vitro effects of glucocorticoids and other steroids on PG production by dispersed cells were examined. Two fetuses in each of 6 sows were catheterized on day 100 or 101 of gestation (normal gestation is 114-116 days); one was infused with cortisol (6 mg/day) and one with saline for 5 days beginning on day 103. On day 108, fetal allantochorionic tissue was aseptically collected from the infused fetuses and 2 uninfused litter mates (controls). Pieces of tissues were cut from the allantochorion (4 sows) and dispersed cell preparations were made from each fetus (4 sows). Each preparation was cultured for 24 h, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha (prostacyclin metabolite) measured. In vivo cortisol infusion had no significant effect on the in vitro production of PGE2 or PGF2 alpha by tissues or dispersed cell preparations. However, tissue from the fetuses infused with cortisol produced significantly less 6-keto-PGF1 alpha than uninfused controls (54% of control, p < 0.05). The dispersed cells from uninfused fetuses and 2 cortisol-infused animals were also incubated for 24 h with 10(-7) and 10(-9) M concentrations of estrone, estradiol, progesterone, cortisol, and dexamethasone, and the production of PGE2, PGF2 alpha, and 6-keto-PFG1 alpha was measured. No significant effect of any of these steroids in vitro on prostanoid production was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Production of prostaglandin by late-gestation porcine placental cells in vitro.

Fifteen sows were assigned to three groups of five each, according to gestational age (109 days, 114 days or labour). Two fetuses per sow were chosen at random, and amnion, allantochorion, amniochorion, amniotic fluid and fetal urine were collected. Tissues were enzymatically dispersed and incubated for 1, 2, 3 or 4 h and the prostaglandin (PG) content of the supernatant medium was measured by radioimmunoassay. In general, all placental cell types produced at least three times more prostaglandin E (PGE) and 6-keto-PGF1 alpha than PGF. Production did not vary across gestational age, except that production of 6-keto-PGF1 alpha was lower in cells collected during labour, resulting in a relative increase in PGF and PGE. Aminochorion cells had a lower de novo capacity to synthesize PG than did allantochorion or amniochorion, whereas treatment of allantochorion with preterm amniotic fluid, preterm or term fetal urine resulted in increased PG output. These results demonstrate that porcine placental cells can synthesize and metabolize prostaglandin in late gestation but suggest that their capacity to produce PGI2 (as measured by 6-keto-PGF1 alpha) is lower than for other prostaglandins during labour.

6-Ketoprostaglandin F1 alpha↗

A morphometric study of lung maturation in the adrenocorticotrophin-infused fetal lamb.

Adrenocorticotrophin (ACTH) effects on lung development were studied in sheep. ACTH was infused into 10 fetal lambs at 129 days of gestation at a rate of 29, 110 or 250 micrograms/day for 72 h, a time course which was independent of the mechanical and hormonal forces associated with labor. Lungs were compared with those of normal fetuses at term (day 147). ACTH accelerates maturation of components of lung structure toward term values. Different components of cytodifferentiation of the type II alveolar cell showed different levels of sensitivity. The degree of acceleration, not the nature of the changes, was influenced by dose.

Adrenal Glands↗

Induction of parturition in pigs: short term effects of prostaglandin F2 alpha on chronically catheterised fetuses at term.

Blood pH and PaO2, and plasma glucose and cortisol concentrations were measured, together with myometrial electromyographic (EMG) activity and fetal heart rate, in eight chronically catheterised gilts and 13 of their fetuses during the induction of parturition with prostaglandin F2 alpha (given as the tromethamine salt). Myometrial EMG activity increased markedly in the first one to two hours after the injection but there was a period of relative quiescence over the next two to three hours. Fetal PaO2 fell significantly after the injection of PGF2 alpha (26.3 vs 21.8 Torr, P less than 0.001) but was unaffected by the injection of saline. Fetal and maternal cortisol concentrations increased significantly (fetal 57.3 vs 92.0 ng/ml, P less than 0.01; maternal 43.1 vs 84.9 ng/ml, P less than 0.001) in response to PGF2 alpha injection. Maternal PaO2 and fetal and maternal pH and plasma glucose concentrations were not altered by the injection of either prostaglandin PGF2 alpha or saline. Mean fetal heart rate increased by 7 to 10 per cent during the first hour after induction but this increase was not significant owing to the wide variations in response. It was concluded that the induction of parturition with prostaglandin F2 alpha resulted in a significant decrease in fetal oxygenation during the period of increased uterine activity but that this effect was transient and would not have an adverse effect in normal pregnancies.

Animals↗

Cytosolic glucocorticoid receptors in the porcine lung during development and after hypophysectomy or thyroidectomy.

The ontogeny of fetal lung glucocorticoid receptors and their regulation by the fetal pituitary, adrenal and thyroid gland during lung maturation were investigated. Sites with a specificity typical of glucocorticoid receptors were detectable in lung cytosol, with the order of potency of steroids being dexamethasone greater than cortisol greater than corticosterone greater than 11-deoxycorticosterone greater than progesterone greater than 17 alpha-hydroxyprogesterone greater than oestradiol-17 beta congruent to testosterone congruent to androstenedione congruent to oestrone. The binding affinity for [3H]dexamethasone was high (Kd = 0.23-0.60 nmol/l) and showed an age-related decrease during the perinatal period when cortisol levels were high. After charcoal treatment of the cytosol, however, a decrease in binding affinity was not as clearly evident. The Kd decreased following hypophysectomy of fetuses; thyroidectomy had no significant effect. The concentration of glucocorticoid receptors was high from day 82 to day 100 of gestation (1437 fmol/mg protein) and declined progressively to a lower value at term and following birth (660 fmol/mg protein). Hypophysectomy, but not thyroidectomy, prevented the age-related decline in receptor concentration. Lung glycogen content declined with fetal ageing in association with increases in plasma concentrations of cortisol and thyroxine and with changes in Kd and Bmax, but appeared to be more closely associated with concentrations of thyroxine. Hypophysectomy of fetuses decreased concentrations of both cortisol and thyroxine and prevented the depletion of lung glycogen content. Preliminary results from thyroidectomized fetuses showed decreases in plasma thyroxine and lung glycogen content compared with day-82 fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effects of hydrocortisone on lung structure in fetal lambs.

The effect of cortisol infusion on fetal lung development was studied in lambs. Changes were compared with those of control groups of saline-infused fetuses of the same age (day 132) and normal late gestation fetuses (142 +/- 4.6 days). Cortisol was infused into five fetal lambs at 129 days of gestation at a rate of 17.0 mg/day. Four fetuses were delivered by hysterotomy at the onset of labour-like uterine activity (58 +/- 3 h). In cortisol-infused fetuses the concentration of cortisol in fetal plasma and tracheal fluid rose to levels similar to those in normal fetuses during the last week of gestation. Progesterone concentration in maternal plasma declined at about 48 h after the start of treatment. Cortisol-infused lambs showed increases in fixed lung volume, specific lung volume, absolute volume of both parenchyma and non-parenchyma and the proportion of the parenchyma which was potential airspace and a decrease in the proportion of parenchyma. For cortisol-infused lambs Type II cell size and the abundance of lamellar bodies, and the volume fraction of cell occupied by the nucleus were similar to the 142 day group, whereas Golgi apparatus and RER were closer to age matched saline-infused (day 132) controls. Glycogen content was midway between the two control groups. We conclude that infusion of cortisol for about 60 h at physiological levels, beginning at 0.85 of gestation, accelerates many, but not all aspects of pulmonary parenchymal maturation, expressed in terms either of morphogenesis of the gas exchange area or differentiation of Type II alveolar cells.

Adrenal Glands↗

Hypophysectomy and porcine fetal lung development.

The effect of hypophysectomy on the development of the lung parenchyma and maturation of pulmonary alveolar type II cells was examined in the fetal pig. In fetuses from four different gilts, hypophysectomy was performed on gestational day 69 or 70. Littermates from the same gilts served as controls. Fetuses were delivered by caesarean section at term (113 +/- 1 days of gestation), and the lungs were fixed by intratracheal instillation. Plasma cortisol and thyroxine concentrations in the umbilical artery were markedly lower for hypophysectomized fetuses compared with control fetuses. Body weight was similar for both groups of fetuses. Total lung volume was 53% smaller in hypophysectomized fetuses compared with control fetuses. However, alveolar septal tissue and capillary luminal volumes were similar in both groups. Total lung alveolar surface area was twice as great in control animals compared with hypophysectomized animals. The volumes of epithelium, interstitium, and endothelium of centriacinar alveolar septa per unit surface area of epithelial basal lamina were 3.7, 4.8, and 2.4 times greater in hypophysectomized fetuses compared with control fetuses. Alveolar type II cell composition also differed significantly between groups. The volume fraction of glycogen in type II cells was 51% for hypophysectomized fetuses and 12% for control fetuses, while lamellar body volume fraction was 8% in hypophysectomized fetuses and 23% in control fetuses. The frequency of alveolar type II cell contact with mesenchymal interstitial cells via foot processes was 5 times greater in the lungs of control animals compared with hypophysectomized animals. These findings demonstrate significant effects of hypophysectomy on the morphogenetic and cytodifferentiation activities of all major tissue compartments of the pulmonary gas exchange area during the final trimester of fetal development.

Animals↗

Form and development of the umbilical cord in pigs and their association with delivery of viable pigs.

Length, extensibility, and absolute strength of umbilical cords were determined in litters of pigs at term. Length was also determined in fetuses earlier in gestation and in hypophysectomized fetuses. Mean cord length at term was 34.6 cm (range, 17 to 50 cm) and its length was correlated with length and birth weight of pigs. Cords were significantly (P less than 0.01) shorter in hypophysectomized fetuses, but cord length was not influenced by sex, position in the uterus, or twisting of the cord. Although the umbilical cord was capable of being stretched considerably, the degree varied among pigs. Tension required to break portions of the cord ranged from 545 to 2,000 g. Variations in length, elasticity, and strength of the cord may influence safe delivery, birth asphyxiation, and perinatal mortality in pigs.

Animals↗

Nontransmission of bluetongue virus by embryos from bluetongue virus-infected sheep.

Donor sheep were infected either by bites of bluetongue virus (BTV)-infected (serotype 11, "Texas Station strain") Culicoides variipennis or by inoculation with 100,000 median chicken embryo intravascular lethal doses of BTV (serotype 11) from a suspension made from infected C variipennis. Fourteen embryos from 4 BTV-infected ewes bred by rams not infected with BTV were transferred to 8 BTV-seronegative recipient ewes, and 35 embryos and 4 unfertilized eggs from 14 BTV-infected ewes bred by BTV-infected rams were transferred to 19 BTV-seronegative recipient ewes. Eleven pregnancies and 12 lambs resulted. None of the recipients or lambs seroconverted, and BTV was not isolated from the pregnant recipient ewes or their lambs at slaughter 30 days after parturition.

Animals↗

Tissue glycogen concentrations in hypophysectomized pig fetuses following infusion with cortisol.

The role of cortisol as a factor controlling the deposition of glycogen in the pig fetus was examined by infusing either a low dose (1 mg/day) or a high dose (3 mg/day) of cortisol into chronically-catheterized hypophysectomized fetal pigs for five days beginning on day 100-104 of gestation. After infusion, liver glycogen was significantly higher (P less than 0.05) and lung glycogen significantly lower (P less than 0.05) than in uninfused hypophysectomized litter mates although concentrations were significantly different from intact litter mates (P less than 0.05). Although skeletal and cardiac muscle content increased after infusion this difference was not significant. Changes in tissue glycogen content were similar for both the low and high rates of infusion. These observations indicate that exogenous cortisol alone is able to stimulate liver glycogen deposition and reverse the effect of hypophysectomy. Although other factors may be necessary for maximal response this suggests that cortisol is an important stimulant for liver glycogen deposition in the fetal pig. The effect of cortisol on muscle glycogen was equivocal suggesting that other hormones may play a more important role in this tissue.

Animals↗

Effect of hypophysectomy on tissue glycogen concentrations in the fetal pig.

The glycogen content was estimated in the liver, lung, cardiac ventricle and skeletal muscle of fetal pigs which had been hypophysectomized between 69-84 days of gestation, decapitated between 35-42 days of gestation or left intact. Comparisons made preterm (103-108 days) or at term (112-114 days) indicated that both liver and skeletal muscle glycogen content were significantly lower in the absence of the fetal pituitary, whereas concentrations in the fetal lungs were significantly higher. There were no significant differences in cardiac glycogen content between hypophysectomized and intact fetuses. Plasma glucose concentrations in both umbilical artery and vein were similar, but plasma arterial fructose concentrations were significantly higher in the hypophysectomized fetuses.

Animals↗

Anatomy of the reproductive tract of the female muskox (Ovibos moschatus).

Reproductive tracts from 23 female muskoxen were collected from the Canadian high arctic during annual native muskox hunts. Twenty tracts were collected during the late breeding season and the last third of pregnancy or anoestrus, with 3 additional specimens taken just before the breeding season in August. The non-gravid muskox uterus was very similar to that of sheep and goats except for two features found in parous muskoxen. The first was endometrial pigmentation found only in the caruncles and associated with a dense collection of lipofuscin granules in the endometrial stroma. The second was a prominent 5 mm deep band of muscular tissue protruding from the antimesometrial border of the uterine horns throughout most of their length. The pregnant uterus and the fetal membranes of the muskox resembled homologous structures in domestic ruminants. However, there was no morphological evidence of a corpus luteum during late pregnancy, apart from a luteal scar in the ovary ipsilateral to the pregnant horn. Of the 4 females collected at the end of the breeding season, 2 lactating females were apparently not cyclic while 2 others had more than one CL, suggesting that they had undergone at least 2 cycles without conceiving or remaining pregnant.

Animals↗

Influence of the fetal pituitary-adrenal axis on fetal and maternal progesterone and unconjugated oestrogen concentrations in the pig.

Fetal and maternal plasma progesterone and unconjugated oestrone and oestradiol-17 beta concentrations were measured in intact pig fetuses and those in which the pituitary had been destroyed. Progesterone concentrations were significantly higher (P less than 0.05) and oestrogen concentrations significantly lower (P less than 0.01) in hypophysectomized fetuses than in intact fetuses. When fetuses in one uterine horn only were hypophysectomized, oestrogen concentrations in the uterine vein draining this horn were lower than those from the contralateral vein. The results indicate that both fetal and maternal oestrogen concentrations are influenced by the fetal pituitary. When dexamethasone was infused (at 27 micrograms/h for 96 h) into 5 chronically-catheterized hypophysectomized fetuses no changes in peripheral fetal progesterone or oestrone were observed.

Animals↗

Attempts to establish congenital bluetongue virus infections in calves.

Three bovine fetuses were inoculated in utero with approximately 10(3) plaque forming units of type 11 bluetongue virus. The gestational ages of the fetuses at the time of inoculation were 106, 113 and 122 days. They were spontaneously aborted 104, 65 and 109 days later, respectively, and the first and third of these fetuses were recovered. There was no grossly normal cerebral tissue, the meninges formed fluid filled sacs, and the cerebellums were reduced in size. Bluetongue virus was not isolated from the fetuses but the older one had neutralizing antibody. The three dams developed neutralizing antibody to bluetongue virus. The present work supports the observation by others that early fetal infections with bluetongue virus normally result in severe central nervous system damage and not in clinically normal, persistently infected calves.

Abortion, Veterinary↗

Heart-rate changes and gasping during intra-partum asphyxiation of a piglet. A case report.

Fetal heart rate and gasping were monitored in a chronically-catheterized fetal piglet which became asphyxiated during delivery. This piglet was the fourth to be delivered in a litter of seven. Prior to delivery of the second piglet in the litter (which was next to the affected piglet in the uterine horn), blood pH and pO(2) values were within normal limits and heart rate changes were restricted to acceleration during uterine contractions. After expulsion of the second piglet in the litter, fetal heart rate became very irregular and fetal gasping became pronounced. Terminally, periods of severe bradycardia (with gasping) which occurred late in or after uterine contractions were observed between periods when the fetal heart rate was increased. These late decelerations followed a pattern similar to those seen in asphyxiated human infants.

Journal Article↗

Changes in the concentrations of corticosteroids in the blood of fetal pigs and their dams during late gestation and labor.

Corticosteroid concentrations were determined in plasma samples obtained from chronically catheterized pig fetuses and their dams during late gestation and parturition. Mean concentrations of 14-20 ng/ml were found in fetal plasma on Days -16 to -10 before delivery and these rose to 40-60 ng/ml between Day -6 and the day of delivery. During the last 8 h of fetal life levels rose rapidly and at birth averaged 168.8 +/- 35.4 ng/ml. Maternal concentrations rose slightly during the last 3 days before delivery but increased significantly during delivery itself. Considerable variation in both the time at which the rise in fetal corticosteroids occurred and the magnitude of the rise was seen both within and between litters. Chromatographic separation indicated that the rise in fetal corticosteroids was associated with increasing cortisol concentrations rather than corticosterone. The data suggest that, while mean fetal corticosteroid concentrations increase in late pregnancy, the role of adrenal maturation of individual fetuses in the initiation of the parturition process in the pig needs further investigation.

Adrenal Cortex Hormones↗

Transfer of embryos from bovine leukaemia virus-infected cattle to uninfected recipients: preliminary results.

One hundred and fifty-one, day 6 or 7, embryos collected from cattle infected with bovine leukaemia virus (BLV) were transferred to uninfected recipients. Thirty-two pregnancies resulted. Two animals aborted at seven months. Three sets of twins and one single calf were still-born. The remaining 26 pregnancies produced 27 live calves which were raised to six months of age. All of the recipients, pregnant and non-pregnant, and all of the calves remained serologically negative for antibodies to BLV-glycoprotein antigen.

Animals↗