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Biomedical subjects

G C Liggins

Publications and source records attributed to G C Liggins.

At least 73 records · Page 4Linked to original sources
PubMed1984

The separation of collagen alpha-chains by reversed-phase high-performance liquid chromatography. Comparison of column alkyl stationary phases and temperature effects.

Procedures for the separation of alpha 1(I), alpha 2(I), alpha 1(II) and alpha 1 (III) chains of human collagen by reversed-phase high-performance liquid chromatography are described. The influence of several different chromatographic parameters (stationary phase, mobile phase and temperature) has been examined and procedures to optimise resolution presented. These reversed-phase high-performance liquid chromatographic conditions also permit the separation of collagen alpha 1(I), alpha 2(I), alpha 1(II) and alpha 1(III) monomers from their corresponding dimeric beta- and gamma-components.

Amino Acids↗
PubMed1984

Inhibitory effects of dispersed human amnion cells on production rates of prostaglandin E and F by endometrial cells.

Dispersed cells were prepared from amniotic membranes obtained either by caesarean section near term before labor (CS) or after spontaneous vaginal delivery (SL) and from human endometrial curettings. The cells were maintained separately in primary culture for about 18 h. Production rates (PR) of PGE and PGF during incubation for 1 h in defined medium were determined when the cell-types were separate (n = 60) or combined (n = 27) and when endometrial cells were incubated in medium conditioned by CS amnion cells (n = 13) or SL amnion cells (n = 12). The PR of PGE by CS amnion cells was five times greater than that of PGF and there was a two-fold increase (p less than 0.01) in PGE but not PGF by SL cells. Co-incubation was associated with a 25-32% fall in PR of both PGE and PGF (p less than 0.01) compared to the sum from separately incubated cells when CS cells were used whereas values for co-incubated SL cells did not differ from controls. Conditioned medium from CS but not SL cells inhibited PGE and PGF output by 30% and 40% (p less than 0.01) respectively. These findings suggest that human amnion cells release an inhibitor of prostaglandin synthesis in endometrial cells.

Amnion↗
PubMed1984

Synthesis of prostaglandin F by cultured human endometrial cells.

Human endometrial cells were dispersed with collagenase and maintained in culture overnight. The synthesis of PGF by the dispersed cells incubated at 37 degrees C in serum-free medium was stimulated by estradiol (10(-7)M - 10(-5)M), histamine (5X10(-7)M - 5X10(-5)M), bradykinin (10(-6)M), phorbol myristate (PMA, 3X10(-8)M) and arachidonate (5X10(-6)M). Preincubation of the cells for 3 h with cortisol (5X10(-7)M - 5X10(-5)M), progesterone (10(-6)M) or mepacrine (10(-6)M - 2X10(-4)M) inhibited the response to histamine, bradykinin and PMA but not to arachidonate. Perfusion of the cultured cells in filtration chambers yielded similar results to those obtained in the incubation system but differences in the onset and duration of the responses to stimuli were found. In the perifusion system the responses to histamine and bradykinin were rapid and of short duration (peak response in less than 60 min) while the responses to PMA and arachidonate were of longer duration with a slower onset. We conclude that these observations using dispersed endometrial cells are consistent with previous work showing that histamine, bradykinin and PMA act by stimulating acylhydrolase activity, thereby liberating precursors such as arachidonic acid which are converted to prostaglandins by the cyclo-oxygenase complex.

Arachidonic Acid↗
PubMed1984

Lupus anticoagulant in pregnancy.

In a group of 10 women with circulating lupus anticoagulant 25 intrauterine deaths were previously documented in the nine multigravidae. The presence of lupus anticoagulant activity was confirmed by showing prolongation of the activated partial thromboplastin time and kaolin clotting time with failure of correction of the prolongation on incubation with normal plasma. A clinical diagnosis of systemic lupus erythematosus (SLE) was made in four women. Three had deep vein thrombosis in pregnancy, one chorea gravidarum while two had only recurrent fetal losses. All the women had positive antinuclear antibody tests and blood platelet counts less than 175 X 10(9)/l. Anti-smooth muscle antibody and VDRL tests were each positive in half the patients; anti-DNA antibody was present in two patients with clinically active SLE. In six pregnancies correction of the activated partial thromboplastin and kaolin clotting time was attempted using prednisone (40-60 mg/day); aspirin, 75 mg/day, was added. Five live infants were obtained, four by spontaneous delivery, when the restoration of the clotting abnormalities to normal was achieved. In one woman presenting with extensive deep vein thrombosis a live infant was delivered following therapeutic doses of heparin and low dose aspirin. Maternal lupus anticoagulant activity has major implications for pregnancy and should be excluded in women with a clinical suspicion of SLE, a positive antinuclear antibody test, thrombotic episodes, biologically false-positive VDRL and unexplained late or repetitive early fetal losses.

Aspirin↗
PubMed1984

Growth of the fetal lung.

Pulmonary hypoplasia occurs consistently when thoracic volume is reduced by any of a variety of congenital and acquired disorders and supports the hypothesis that distension of the fetal lung is necessary for normal growth. Many of these disorders also impair fetal breathing movements suggesting that growth is dependent on phasic as well as tonic forces. Results of animal experiments to test the hypothesis by obstructing or facilitating outflow of lung fluid are inconclusive but interrupting breathing movements by upper motor neurone lesions that preserve diaphragmatic tone causes hypoplasia. Episodes of breathing may distend the lungs by retaining secreted lung fluid while single breaths may redistribute fluid within the lungs.

Animals↗
PubMed1983

Fetal survival after prednisone suppression of maternal lupus-anticoagulant.

The presence of the lupus anticoagulant was diagnosed in six pregnant women because they had prolonged activated partial thromboplastin and kaolin clotting times which could not be corrected by dilution of test samples with normal plasma. All previous pregnancies (14) had ended in intrauterine death in the five multigravidas. Three women had had thrombotic episodes during pregnancy. The diagnosis of SLE was established in four. Antinuclear antibody was identifiable in all 6. All were treated with prednisone 40-60 mg/day and aspirin 75 mg/day. Suppression of the lupus anticoagulant activity was achieved in five patients, all of whom gave birth to live infants. In the sixth patient suppression of the anticoagulant activity was demonstrated between pregnancies; a further pregnancy in this patient was lost before she had received sufficient prednisone to suppress the anticoagulant. Since treatment with prednisone and aspirin can lead to successful pregnancies, it is important to screen all women with SLE, thrombotic episodes, recurrent intrauterine deaths, or a biologically false-positive VDRL for the presence of the lupus anticoagulant.

Adult↗
PubMed1983

Inhibition of breathing movements in fetal sheep by prostaglandins.

We studied the effects of infusions (duration 13.4 +/- 2.9 h) of prostaglandins (PG) on fetal breathing movements (FBM) in 12 fetal sheep at 122-141 days gestation. We gave similar doses (1.1 +/- 0.7 microgram . kg-1 . min-1) of PGE2 (8 studies), PGF2 alpha (5 studies), and cyclic endoperoxide analogues (6 studies). During control periods (304 h), incidence of FBM was 41%; this decreased during every infusion. With PGE2, incidence of FBM markedly decreased to 9.8% of control (P less than 0.001). With the other agents the decrease was less profound; incidence of FBM with PGF2 alpha was 63.7% of control and with endoperoxide analogues 69.4% of control (P less than 0.05 for both). During infusions there were no changes in fetal heart rate, arterial blood pressure, pH, or blood gas tensions. In three fetuses (5 infusions) with electrocorticogram recordings, incidence of low-voltage fast activity was unchanged from control values. Inhibition of FBM by PGE2, combined with previous results showing stimulation of FBM by PG synthetase inhibitors, suggests that endogenous PG may inhibit breathing movements in utero and that a change in PG metabolism may contribute to the change in control of breathing at birth.

Animals↗
PubMed1983

Serum somatomedin C concentrations in the fetal sheep increase markedly during gestation.

Serum somatomedin C concentrations in fetal sheep and pregnant ewes from days 51 to 149 of gestation were determined by specific radioimmunoassay. In the fetus (n = 61 samples) serum somatomedin C concentrations, fitted to a regression curve, increased significantly with advancing gestation from 0.44 units/ml at 51 days to 3.99 units/ml at 149 days, an increase of 806% (P less than 0.001). In the pregnant ewes (n = 14 samples), serum somatomedin C did not change during gestation. The temporal relationship between the marked increase in fetal somatomedin C concentrations and the acceleration of fetal growth is consistent with the hypothesis that somatomedin is important in the stimulation of fetal growth.

Animals↗
PubMed1983

The estimation of elastin in fetal tissues by radioimmunoassay of isodesmosine.

A radioimmunoassay was developed for the determination of isodesmosine as the tetraacetyl derivative. Isodesmosine tetraacetate conjugated with bovine albumin was injected into rabbits which developed useful titers of antibodies after five months. The radioligand for the assay was prepared by acetylating isodesmosine with [3H] acetic anhydride. The bound ligand was separated from free ligand by coprecipitation with human gamma-globulin in 46% saturated ammonium sulfate solution. The sensitivity of the assay was 2 ng isodesmosine. The antiserum was specific for isodesmosine tetraacetate and only desmosine tetraacetate gave appreciable cross-reactivity (4%). The assay was found to be suitable for the accurate estimation of elastin in small samples (5 mg dry weight) of rat and ovine fetal lung tissue and for elastin degradation products in amniotic fluid (0.5 ml).

Amino Acids↗
PubMed1983

The effects of hypophysectomy, thyroidectomy, and postoperative infusion of cortisol or adrenocorticotrophin on the structure of the ovine fetal lung.

We studied the effect of in utero hypophysectomy and replacement therapy with cortisol and adrenocorticotropin on maturation of lung structure in ovine fetuses. Twenty-two festuses underwent hypophysectomy in utero at 99-122 days of fetal gestation. At term (148-150 days), ten fetuses received an infusion of ACTH and six fetuses received an infusion of cortisol. The remaining fetuses were untreated. Morphometric analysis of the caudal lobe of the right fetal lung was performed and included measurement of minimum interalveolar wall thickness, numerical density of Type I and Type II pneumocytes in septal tissue, and volume density of septal tissue and air spaces in respiratory lung. The lung of the hypophysectomized animals differed from term controls in that alveolar walls were thicker, numerical density of Type I pneumocytes was less and that of Type II cells greater. Treatment with ACTH or cortisol caused lung structure to appear similar to the lungs of term control animals. We conclude that hypophysectomy impairs structural maturation and that structural maturation can be achieved by a relatively brief infusion of cortisol or ACTH at term.

Adrenocorticotropic Hormone↗
PubMed1982

Free amino acids in the blood of fetal and maternal Weddell seals.

The content of free amino acids in whole blood was measured in near-term gravid female Weddell seals (Leptonychotes weddelli) and compared with fetal amino acid profiles during rest and during experimental diving. With the exception of taurine and glutathione, Ninhydrin-reactive components of acid extracts of blood occurred in higher concentrations on the fetal side of the placenta than on the maternal side. Compared with humans the Weddell seal displayed higher ratios of fetal arterial to maternal arterial levels for aspartate, glycine, alanine, valine, tyrosine, phenylalanine, and total branched-chain amino acids. In the resting state the total free amino acid concentration in maternal blood was only about 70% as large as the total amino acid concentration in fetal blood, compared with a value of over 80% for humans. Only modest changes in the concentrations of specific amino acids occurred during simulated awake diving, but the overall maternal pools of glycine, glutamate, and glutamine were augmented, creating favorable conditions for uptake by the fetus.

Amino Acids↗
PubMed1982

Comparison of the effects of prostaglandin E2, prostacyclin and 1-24 adrenocorticotrophin on plasma cortisol levels of fetal sheep.

The changes in plasma cortisol levels in response to intravenous infusions of prostaglandin E2 (PGE2), prostacyclin and 1-24 ACTH have been studied in chronically catheterized fetal sheep during the last third of gestation. All three drugs increased plasma cortisol levels with prostacyclin being sigificantly more potent than either PGE2 or 1-24 ACTH. No interaction between the steroidogenic actions of 1-24 ACTH and either PGE2 or prostacyclin could be demonstrated. The steroidogenic action of PGE2 was not significantly modified by fetal hypophysectomy. It is concluded that neither PGE2 nor prostacyclin is likely to be involved in the enhanced adrenal responsiveness to 1-24 ACTH observed in fetal sheep in the period immediately before birth.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Special lecture.

Explore the source record for details and available documents.

Animals↗
PubMed1982

Intrathoracic pressures in fetal sheep.

Intrathoracic pressures were investigated in the sheep fetus from 122 to 145 days of gestation. Pressures during fetal apnoea were determined by means of open-ended catheters in the trachea, intrapleural space and amniotic cavity. Measurements made with open water manometers were confirmed by differential water manometry as well as by pressure transducers. During apnoea, the pressure in the trachea exceeded that in the intrapleural space by 2.1-2.6 torr. The pressure was attributable mainly to a positive intratracheal pressure of 1.8-2.0 torr and to a lesser extent to a negative intrapleural pressure of 0.2-0.7 torr. Electronic measurements of intrapleural pressure showed that each breath was accompanied by change in pressure from +10 torr relative to atmospheric pressure to a negative pressure of 2-20 torr. Although tubocurarine hydrochloride (0.8 mg), injected as a bolus into the fetal jugular vein, completely abolished both phasic pressure changes and diaphragmatic electromyographic activity for periods of up to 90 min, curarization did not diminish the positive tracheal pressure. It is postulated that the positive pressure is generated by the continuous production of lung fluid and maintained by a resistance to outflow.

Amniotic Fluid↗
PubMed1981

Development of the fetal lung.

The development of the fetal lung compared to that of other organs is unusual in the degree of its dependence on extrinsic stimuli. When the space available to the growing lung is limited by space-occupying lesions or when the diaphragm is paralysed, lung growth is markedly impaired. The relationship of lung volume to growth may depend on lung distension. Lung hypoplasia associated with experimental procedures causing inhibition or blunting of fetal breathing movements suggests that the distending forces may be generated by these movements. Maturation is less dependent on distension and more dependent on the hormonal environment. Distensibility and stability of the lung in fetal sheep develops rapidly within a few days of birth and correlates strongly with the plasma cortisol concentration. Hypophysectomy retards mutation which is restored by infusing adrenocorticotropin but not cortisol into the fetus. The hormones mainly responsible for controlling the various aspects of maturation probably include cortisol, iodothyronines and catecholamines but the interrelationships of these hormones and the extent of involvement of other hormones is uncertain.

Adrenocorticotropic Hormone↗