Biomedical subjects

M D Mitchell

Publications and source records attributed to M D Mitchell.

At least 145 records · Page 8Linked to original sources

PubMed1991

Isolation of multiple substances in amniotic fluid that regulate amnion prostaglandin E2 production: the effects of gestational age and labor.

The present study was undertaken to evaluate the effects of whole amniotic fluid (AF) and fractions of AF on amnion cell prostaglandin E2 (PGE2) production. Amnion cells were grown to confluence and then incubated in the presence of AF, or fractions thereof, obtained at 17-19 weeks gestation (MID), at term prior to the onset of labor (NIL), and at term after spontaneous onset of labor (LABOR). All whole AFs were stimulatory to amnion cell PGE2 production (p less than 0.001) but the stimulation by NIL and LABOR AFs was significantly greater (p less than 0.001) than stimulation by the MID AF. Fractionation of the AFs from the three groups (n = 9-10 per group) revealed multiple discernable peaks of stimulatory activity in each group. The majority of peaks had retention times that were similar among the three groups, and peak stimulatory activities were greater in NIL and LABOR samples than in MID samples.

Amnion↗

PubMed1991

Increased production of 15-hydroxyeicosatetraenoic acid by placentae from pregnancies complicated by pregnancy-induced hypertension.

Placentae from pregnancies complicated by pregnancy-induced hypertension (PIH) secrete significantly more 15-hydroxyeicosatetraenoic acid (15-HETE) than gestation-matched controls. 15-HETE and its hydroperoxy precursor can inhibit prostacyclin biosynthesis and may thus contribute to the pathological sequelae of PIH.

Epoprostenol↗

PubMed1991

Epidermal growth factor and the regulation of amnion prostaglandin biosynthesis.

The production of prostaglandins by amnion is a key factor in the mechanism of human parturition yet the regulation of prostaglandin biosynthesis in amnion is poorly understood. Hence, we have investigated the regulation of epidermal growth factor (EGF) stimulation of prostaglandin biosynthesis in human amnion cells. This stimulatory action is inhibited by cycloheximide or actinomycin D at high concentrations, but enhanced at much lower concentrations of these protein synthesis inhibitors. An amnion-produced prostaglandin inhibitor or immediate early gene action may explain these effects. Pretreatment with phorbol esters (inhibition of protein kinase C activity) reduces basal prostaglandin production and attenuates the stimulatory action of EGF on prostaglandin biosynthesis. Hence, amnion prostaglandin biosynthesis is dependent partly on protein kinase C activity.

Amnion↗

PubMed1991

Prostaglandin production by amnion and decidual cells in response to bacterial products.

Media from bacterial cultures have been tested for actions on prostaglandin biosynthesis by human amnion and decidual cells. The bacterial species, which are commonly associated with intrauterine infections, were Group B streptococcus, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis, Gardnerella vaginalis, Neisseria gonorrhea, Mycoplasma hominis and Ureaplasma urealyticum. Overall, low doses of bacterial products were stimulatory of amnion prostaglandin production, whereas high doses were inhibitory. A similar pattern of results was obtained for effects on decidual prostaglandin production, although stimulatory actions at low doses were less pronounced. In all experiments interleukin 1 beta consistently induced a stimulation of prostaglandin production that greatly exceeded that caused by any bacterial product. It is possible that the inhibitory action of high doses of bacterial products on prostaglandin biosynthesis may contribute to the poor course of labor experienced by women with chorioamnionitis. Furthermore, these data lend credence to the view that the host response to infection (i.e. cytokine secretion) is the major mediator of subsequent preterm labor.

Amnion↗

PubMed1991

In vivo correlation of myocardial metabolism, perfusion, and mechanical function during increased cardiac work.

STUDY OBJECTIVE: The aim was to study the in vivo interaction and regulation of myocardial perfusion, metabolism, and pump function in an open chest canine model using a combination of potentially non-invasive and clinically useful techniques. DESIGN: To assess potential regulatory mechanisms and the interaction of myocardial perfusion, metabolism, and contractile function responses during changes in cardiac workload, noradrenaline (1 microgram.kg-1.min-1) was infused and hypoxia was produced by increasing the inspired ratio of nitrogen to oxygen to produce a PaO2 of 2.6-4.0 kPa in separate interventions. SUBJECTS: Nine mongrel dogs of either sex, age 2-5 years, weight 8.5(SD 2.2) kg, were studied in separate interventions. MEASUREMENTS AND MAIN RESULTS: Myocardial perfusion was determined using 2H nuclear magnetic resonance (NMR) measured washout of deuterium oxide from the left ventricle interpreted with a one component Kety-Schmidt exponential model. High energy phosphate bioenergetics were determined by 31P NMR measurements of the phosphocreatine/ATP ratio. Redox state was estimated by nicotinamide adenine dinucleotide fluorometry expressed as percent change from the baseline, normalised to maximum response measured at 100% inspired N2. Mechanical function was evaluated using heart rate X systolic blood pressure and oxygen consumption measurements. During both noradrenaline infusion and hypoxia, mechanical function increased significantly from control values: heart rate X systolic blood pressure = 1.9(SD 0.5), 3.6(0.1), and 2.6(0.4), respectively; oxygen consumption = 0.9(2), 1.6(0.1), and 1.2(0.6) ml.min-1.100 g-1. Myocardial perfusion increased to support the increased workloads, from 87(10) to 131(20), and from 60(12) to 182(14) ml.min-1.100 g-1, respectively. ADP, estimated by the phosphocreatine/ATP ratio, did not change during noradrenaline infusion [2.4(0.2) to 2.4(0.7)], but decreased during hypoxia [2.4(0.4) to 1.7(0.5)]. Redox state decreased during noradrenaline infusion, from 100% to 84(0.7)%, and increased during hypoxia, from 100% to 140(10)%. CONCLUSIONS: Similar changes in workload induced by different physiological stimuli are associated with different biochemical responses even though changes in perfusion are similar. The data suggest that myocardial function is regulated by different biochemical mechanisms under different physiological conditions, ie, there is probably no universal regulator of myocardial function. It is now possible to evaluate potential metabolic regulators of myocardial function in an in vivo animal model.

Animals↗

PubMed1991

The regulation of decidual prostaglandin biosynthesis by growth factors, phorbol esters, and calcium.

The production of prostaglandins by decidua may play a significant part in the mechanisms of human parturition. We have evaluated the regulation of prostaglandin production in human decidual cells in monolayer culture. Both epidermal growth factor and transforming growth factor-alpha induced concentration-related increases in decidual prostaglandin production with significant changes occurring at concentrations of 1 to 10 ng/ml. Two active phorbol esters elicited concentration-related increases in decidual prostaglandin production whereas an inactive phorbol analogue was without effect. The calcium ionophores, ionomycin and A-23187, also stimulated prostaglandin production by human decidual cell cultures. Hence prostaglandin production by human decidua is regulated by hormones and agents in a manner similar to that of other cells including amnion and may play a significant part in the mechanism of parturition.

Calcimycin↗

PubMed1991

Pulmonary hemodynamic reaction to foreign blood in goats and rabbits.

We have found that the goat is extraordinarily sensitive to very small quantities of rabbit or rat blood. As little as 0.004 ml/kg induces transient pulmonary hypertension [maximal rise in pulmonary arterial pressure 32 +/- 10 (SD) cmH2O] in goats. We hypothesized that this reaction may be related to the presence of the resident population of intravascular macrophages that reside in the pulmonary capillaries of goats. If that is so, then rabbits or rats, which have few or no intravascular macrophages, should not be reactive to foreign blood. We compared pulmonary hemodynamics and changes in blood thromboxane B2 concentrations among goats, rabbits, and rats in response to graded doses of foreign blood. The pulmonary reaction to foreign blood was much greater in goats than in rabbits or rats, even though we injected up to 10- or 60-fold larger amounts into the latter species. In goats the pulmonary vascular pressure response to rabbit blood was dose dependent in goats and correlated well with changes in systemic arterial thromboxane B2 concentrations [change in pulmonary arterial pressure = 0.07 (thromboxane B2) + 8.3, r = 0.79]. We also tested the prostaglandin H2 endoperoxide analogue (U-46619) and found that the goats are somewhat more reactive than rabbits. We conclude that the pulmonary hemodynamic reaction to foreign blood is consistent with the concept that the foreign erythrocytes are reacting with the pulmonary intravascular macrophages in goats. The lower reactivity of the rabbit pulmonary circulation to thromboxane may also have a role.

Animals↗

PubMed1991

Cost analysis in health planning and management in Papua New Guinea.

In 1988 a study of the costs of rural health services was carried out in Papua New Guinea. The study collected data from a 16% sample of all health centers and subcenters and was able to determine average staffing patterns, total and average costs, and service levels for different types of facilities. The study methodology and findings have been found to have broad application for both planning and management of health services. The applications of cost analysis for planning and management of health services are discussed, and key recommendations are outlined for improving the efficiency and productivity of rural health facilities in Papua New Guinea.

Cost-Benefit Analysis↗

PubMed1991

Production of interleukin-6 by fetal and maternal cells in vivo during intraamniotic infection and in vitro after stimulation with interleukin-1.

Amniotic fluid samples were obtained by transabdominal amniocentesis from 20 women in preterm labor (less than or equal to 34 wk gestation). Concentrations of IL-6 in culture-positive amniotic fluids (mean 8706 pg/mL, range 5100-14,446 pg/mL) were higher than those in culture-negative fluids (mean 1133 pg/mL, range 15-6534 pg/mL, p less than 0.0001) or fluids from healthy term pregnancies (mean 196 pg/mL, range less than or equal to 5-790 pg/mL, p less than 0.001). To assess possible sources of the Il-6 in amniotic fluid, we tested the ability of a variety of fetal and maternal cells to produce IL-6 in vitro after stimulation with IL-1, a cytokine known to stimulate IL-6 production. Very low concentrations of IL-6 were present in supernatants of cells not stimulated with IL-1; however, high concentrations were observed in supernatants of stimulated umbilical venous endothelial cells, decidual cells, and fetal and maternal blood mononuclear cells. To determine whether cells from adults produce IL-6 with kinetics similar to those of neonates, we incubated mononuclear cells obtained from blood of adults and term and preterm neonates with IL-1. After 6 h, IL-6 was detected in supernatants of adult cells and term neonatal cells, but not in supernatants of preterm cells. Concentrations at 18, 24, and 48 h were similar for adult and term cell supernatants, but were lower in supernatants of preterm cells. We also observed considerably more IL-6 mRNA accumulation in circulating mononuclear cells from adults than in those from neonates.

Amniotic Fluid↗

PubMed1991

Lack of effect of melatonin on myometrial electromyographic activity in the pregnant sheep at 138-142 days gestation (term = 147 days gestation).

A 24-h rhythm has been demonstrated in fetal and maternal melatonin plasma concentrations in pregnant sheep in the last third of gestation. Melatonin in the maternal circulation can cross the placenta and is the major source of melatonin in the fetal circulation. Melatonin has been postulated to act as a prostaglandin (PG) synthetase inhibitor in the uterus. PG synthetase inhibitors decrease myometrial contractility. To assess transplacental passage of melatonin and potential influences of melatonin on uterine contractility, we infused melatonin continuously into the maternal jugular vein in seven pregnant sheep at 138-142 days gestation (term in our instrumented animals is 147 days gestation) at three infusion rates for successive 1-h periods during the late morning to late afternoon. There was no change in the total time during which the myometrium was active, as indicated by myometrial electromyographic activity or the myometrial contracture frequency during the 3 h before and after melatonin infusions and for each hour of the infusions. The MCR for melatonin in the ewe was 4128 +/- 410 ml/min (mean +/- SE; n = 7; weight, 50-70 kg). The resting maternal to fetal melatonin concentration ratio was 0.8; this ratio was maintained at 2.28 during melatonin infusion to the ewe at a wide range of maternal melatonin concentrations. Melatonin concentrations in the range of 3-200 times normal had no effect on the maternal plasma PGF2 alpha metabolite concentration, but caused a 40.4% fall in fetal plasma PGE2 (P less than 0.05). We conclude that changes in maternal and fetal plasma melatonin concentrations within the physiological range observed throughout the day do not alter myometrial contractility, but do alter fetal PGs.

Animals↗

PubMed1991

Renin increases human amnion cell prostaglandin E2 biosynthesis.

Chorionic cells are known to produce several protein hormones; among them is prorenin/renin, whose function is unknown at this time. Amnion is contiguous with chorion and plays a part in the mechanism(s) of parturition through increased prostaglandin (PG) production. The purpose of the present study was to determine whether renin has any action on amnion cell PGE2 biosynthesis. Amnion cells in primary monolayer culture were incubated for 16 h with increasing concentrations of renin. Renin induced a concentration-dependent increase in amnion cell PGE2 production (e.g. in picograms of PGE2 per microgram protein/16 h; mean +/- SEM; n = 4; control, 3.01 +/- 0.15; 0.0001 U/mL renin, 9.66 +/- 2.0; 0.001 U/mL renin, 10.36 +/- 1.91; 0.01 U/mL renin, 10.3 +/- 3.36; 0.1 U/mL renin, 13.82 +/- 2.1). Significant stimulation of amnion cell PGE2 by renin is not observed until 2 h of incubation; stimulation continues a further 6 h, with little change in the following 8 h. We tested the possibility that renin's stimulatory effects were due to angiotensin-I (AI) and angiotensin-II (AII) formation by testing the effects of AI and AII directly and that of renin in the presence of saralasin, a potent antagonist of AII action. Saralasin did not inhibit the effect of renin, nor was AI or AII alone (10(-10)-10(-6) M) stimulatory. Thus, we believe that chorionic renin may have a novel role in the regulation of amnion cell PGE2 production that is independent of angiotensin formation.

Amnion↗

PubMed1991