PubMed Health⌕ Search

Biomedical subjects

M J Engle

Publications and source records attributed to M J Engle.

At least 37 records · Page 2Linked to original sources
PubMed1986

Changes in surfactant phospholipids in fetal rat lungs from normal and diabetic pregnancies.

The purposes of this study were to adapt and evaluate further a pulmonary surfactant isolation method applicable to unperfused fetal rat lung, to quantitate key phospholipids phosphatidylcholine (disaturated phosphatidylcholine, and phosphatidylglycerol) of the isolated material during the last 3 days of gestation, and to determine if abnormalities in surfactant phospholipids were present in fetuses of diabetic pregnancies. A simplified scheme of sucrose gradient centrifugation proved useful for small scale preparations of material enriched in the phospholipids most characteristic of pulmonary surfactant. It was shown that fetal blood phospholipids did not contaminate the surfactant fraction and therefore would not produce artifacts in assessment of lung maturational changes. Analyses of subcellular fractions isolated at 19.5, 20.5, and 21.5 days revealed that the percentages of disaturated phosphatidylcholine relative to total phospholipids were 23-44% in the surfactant preparations and 14-21% in the residual (nonsurfactant) fractions, while the disaturated phosphatidylcholine/phosphatidylcholine ratios were 0.62 +/- 0.06 and 0.41 +/- 0.03, respectively. Summation of the amounts of individual phospholipids in the two fractions yielded data that were nearly identical to the concentrations of these compounds in whole fetal lung samples analyzed independently, implying that losses during the surfactant isolation technique were negligible. The concentrations of phosphatidylcholine, disaturated phosphatidylcholine, phosphatidylglycerol, and total phospholipids increase markedly (more than 10-fold) and progressively in surfactant fractions prepared from normal fetal rat lung at 19.5, 20.5, and 21.5 days of gestation. In contrast, the residual fractions showed no changes from 19.5 to 20.5 days and then relatively modest increases from 20.5 to 21.5 days, except for phosphatidylglycerol, which increased markedly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Fetal lung development in male and female nonhuman primates.

Indices of lung maturation were assessed in 58 rhesus fetuses at five gestational ages during the last trimester of nonhuman primate pregnancy to determine whether fetal sex influences lung maturation. In addition to analysis of whole lung phospholipids, glycogen, protein, DNA, and pressure-volume curves surfactant fraction phosphatidylcholine (PC) was quantitated following isolation by sucrose gradient centrifugation and a combination of predictors were assessed by all possible subsets regression to attain a composite "maturity index." For the total population, there was a uniform progression in physical growth characteristics, lung destensibility and stability and phospholipids with advancing gestation. The quantitative change in surfactant fraction PC concentration for both sexes was considerably greater than that observed for whole lung PC between 135 days gestation and term. Further, the increase in surfactant PC occurred in association with improving lung destensibility and deflation stability prior to maximum changes in the whole lung PC or disaturated PC concentration. There were no statistically discernible differences in biochemical or physiological assessment between sexes at any gestational age. These data in nonhuman primates suggest that documented differences in survival from the respiratory distress syndrome between males and females do not result from a discordance in lung maturation as a function of time throughout the last trimester of gestation.

Animals↗
PubMed1985

Developmental aspects of lung lipids.

From this review, it is evident that multiple maternal/fetal endogenous or completely exogenous factors have been associated with the complex process regulating fetal lung development. Recent in vitro experiments with human fetal lung explants are especially noteworthy and may establish a perspective for future research. Snyder et al (108) and Medelson et al (74) have found that lung explants from 16-22-week abortuses show differentiated type II cells and augmented PC synthesis within 4 days of culture, rather than the minimum 10- to 15-week period expected in utero. Such a phenomenon is reminiscent of the usual time for clinical recovery from uncomplicated RDS (34). Thus, although expression of the genes influencing lung surfactant phospholipid synthesis and related biochemical processes normally occurs relatively late in gestation, the potential for biochemical differentiation is clearly present in earlier stages. It appears then that the "programming" of the fetal lung for maturation is not absolute but may be altered under certain influences. Whether the advent of lung biochemical maturation occurs as a result of release from inhibition, as the human lung explant data imply, or occurs in response to stimuli, as suggested by exogenous corticosteroid effects, remains to be clarified and is a very challenging scientific problem. It will also be of great interest to define further other biochemical regulators, such as fibroblast pneumocyte factor, that may play an important role in fetal lung maturation.

Androgens↗
PubMed1985

Fatty acid abnormalities in cystic fibrosis.

Fatty acids were measured by gas chromatography in lipid extracts of plasma and tissues obtained from three categories of 46 patients with cystic fibrosis. Low levels of the major essential fatty acid linoleate were found in plasma total lipids of patients who had malabsorption but not in those without evidence of steatorrhea. Circulating arachidonic acid was only slightly decreased, and the unusual triene reflecting pathologically altered fatty acid metabolism (20:3 omega 9) was generally not detected, nor was the triene/tetraene ratio abnormal except for in two patients. There was no correlation between plasma linoleate and age, clinical severity score, or vitamin E status. Decreased linoleate did correlate with two indices of malabsorption, namely plasma carotene (r = 0.64) and fecal fat excretion (r = 0.76). Our data therefore indicate that the abnormality in linoleate is associated with (secondary to) malabsorption of dietary fat despite pancreatic enzyme replacement therapy and consumption of a regular diet. The frequency of this alteration was determined to be quite high in 40 patients with steatorrhea, 85% of whom showed values below the lower limit of normal for plasma linoleate. It was of interest to find markedly decreased levels of linoleate in adipose tissue, cardiac muscle, and lung and lesser reductions in liver and psoas muscle taken at autopsies. Tissue arachidonic acid percentage was normal, however, and 20:3 omega 9 was rarely present. Thus, the physiological significance of this common abnormality in CF patients with malabsorption remains to be determined.

Adipose Tissue↗
PubMed1984

Changes in food intake during menstrual cycles and pregnancy of normal and diabetic rhesus monkeys.

Food intake of control and streptozotocin-diabetic rhesus monkeys was measured during menstrual cycles and pregnancy. Intake of control monkeys was lower at the time of ovulation than during other phases of the menstrual cycle. Intake of control monkeys was also low during most of pregnancy, but this was accompanied by normal fetal growth and net maternal weight gain. Diabetic monkeys ate more than controls in all conditions and their intake did not vary reliably according to reproductive status. It is suggested that (1) oestrogen normally inhibits food intake during menstrual cycles and pregnancy, (2) food energy is utilized more efficiently during pregnancy than during non-pregnant states, and (3) the influence of oestrogen on food intake is either attenuated by insulinopenia or is obscured by the hyperphagia typically exhibited by the diabetic monkeys.

Animals↗
PubMed1984

Relationship between the severity of experimental diabetes and altered lung phospholipid metabolism.

Glucose intolerance was induced in rats by iv infusion of streptozotocin (STZ) in doses of 30, 40, 50, and 100 mg/kg. Serum glucose concentrations were elevated versus controls and weight gains were reduced in a dose-dependent fashion up to 50 mg/kg. Urine outputs and blood urea nitrogen (BUN) values were higher than control values in the animals treated with 40 and 50 mg/kg and serum albumin concentrations were decreased after infusion with 50 mg STZ/kg. Lung phosphatidylcholine (PC) concentrations and dry-to-wet weight ratios were unchanged by STZ treatment, while lung protein and disaturated phosphatidylcholine (DSPC) concentrations were depressed in the 50-mg/kg group. Animals surviving treatment with 100 mg/kg demonstrated increased fasting blood glucose levels, BUN values, and 48-hr urine outputs, and decreased lung protein levels. However, these alterations were less than those found in the 50-mg/kg animals. Pulmonary concentrations of PC, DSPC, and lung dry-to-wet weight ratios were unchanged. It was found advantageous to express the results relative to fasting blood glucose levels. This demonstrated that urine output and BUN values increased and weight gain decreased with rising glucose concentrations, but serum albumin decreased only in moderate and severe hyperglycemia. Fasting glucose concentrations greater than 400 mg/dl were associated with reduced lung DSPC and protein levels, while pulmonary PC and dry-to-wet weight ratios demonstrated no change with increasing hyperglycemia.

Animals↗
PubMed1984

Saturated phospholipids in amniotic fluid of normal and diabetic pregnancies.

To assess fetal lung maturation in normal and diabetic pregnancies, the authors studied two phospholipids that are more specific for pulmonary surfactant than total phosphatidylcholine (lecithin), namely saturated phosphatidylcholine and phosphatidylglycerol. Results indicated that saturated phosphatidylcholine concentrations normally increase from 10 to 20 nmol/mL before 34 weeks to as high as 150 nmol/mL at term. Although the absolute concentration of saturated phosphatidylcholine could not be used to reliably identify pregnancies leading to respiratory distress syndrome, a saturated phosphatidylcholine level greater than 50% of total phosphatidylcholine was associated with satisfactory neonatal pulmonary function, whereas RDS often occurred in premature infants when less than half the phosphatidylcholine was saturated. Carefully regulated diabetic pregnancies at 36 to 42 weeks of gestation were not different from matched control subjects with respect to total phosphatidylcholine, its ratio to sphingomyelin, saturated phosphatidylcholine, or phosphatidylglycerol. Respiratory distress syndrome did not occur in any infant of the 40 diabetic mothers studied, nor were there any congenital anomalies or cases of symptomatic hypoglycemia.

Amniotic Fluid↗
PubMed1983

The effects of insulin and hyperglycemia on surfactant phospholipid synthesis in organotypic cultures of type II pneumocytes.

Organotypic cultures of fetal type II epithelial cells were incubated in media containing insulin at concentrations ranging from 10 to 400 microunits/ml. Exposure to insulin resulted in increased glucose uptake from the media and in the rate of glucose conversion to CO2. Furthermore, both glucose uptake and CO2 production were dependent on the glucose concentration in the media. Surfactant and residual phosphatidylcholine fractions were isolated from the organotypic cultures by sucrose density centrifugation. The presence of low doses of insulin (10-25 microunits/ml) caused a significant increase in the incorporation of glucose into both surfactant and residual phosphatidylcholine. Insulin at levels of 100 microunits/ml or higher resulted in a significant decrease in glucose incorporation into both phosphatidylcholine fractions. Increasing the media glucose concentration from 5.6 to 20 mM caused a 2- to 2.5-fold increase in glucose utilization for surfactant and residual phospholipid synthesis, but did not produce any significant changes in choline incorporation into either surfactant or residual phosphatidylcholine. The addition of 400 microunits/ml of insulin to media containing 20 mM glucose, however, resulted in a 20% decrease in choline incorporation into surfactant phosphatidylcholine but had no effect on choline incorporation into residual phosphatidylcholine. These results suggest that insulin is an important hormone regulating fetal lung maturation and that hyperinsulinemia may be responsible for the delayed lung development in infants of diabetic mothers.

Animals↗
PubMed1983

Amniotic fluid phospholipids after maternal administration of dexamethasone.

The administration of corticosteroids to pregnant women in premature labor can accelerate fetal lung development and potentially prevent neonatal respiratory distress syndrome (RDS). Controversy exists, however, as to whether amniotic fluid phospholipid indices of lung maturation are influenced by such treatment. Without a suitable test for evaluating the fetal response to corticosteroids, there is no method of recognizing whether and when lung development has been stimulated. In an attempt to resolve this issue, we carried out a study of amniotic fluid phospholipids as part of the National Institutes of Health multicenter trial of prenatal corticosteroids. Amniocenteses were performed before the administration of either steroid hormone or placebo and approximately 1 week after a series of four injections was initiated. Analysis of the ratio of lecithin (phosphatidylcholine) to sphingomyelin (L/S ratio) revealed nearly identical values initially and no significant difference in the posttreatment means when 25 steroid-treated pregnancies were compared to 20 control pregnancies. Although there were significant increases in both groups during the interval between amniocenteses, no statistical difference was found in the extent of change in L/S ratios between the two groups, when pretreatment values were compared with those obtained an average of 1 week later. In addition to evaluating L/S ratios, we performed an assessment of phospholipid concentrations in 17 pregnancies before and after administration of dexamethasone. This revealed no detectable phosphatidylglycerol. There were increases in the absolute concentrations of phosphatidylcholine and disaturated phosphatidylcholine, but these changes were relatively modest in magnitude and could be attributable to either advanced gestational age or dexamethasone. Our results demonstrate that current tests of fetal lung maturity do not provide a routine means for prenatal detection of pulmonary maturational responses to corticosteroids.

Amniotic Fluid↗
PubMed1982

Comparative analysis of four methods for rapid glucose determination in neonates.

As an important aspect of newborn care, the rapid assessment of glucose homeostasis is often accomplished by a glucose oxidase-peroxidase chromagen test strip method, either alone or with a reflectance colorimeter. The precision of these techniques has been established, but few studies have determined accuracy in an intensive care setting. We performed the following study. During the time of routine heelstick blood sampling, the nurses collected 90 complete study sets for glucose analysis from 43 neonates. Dextrostix, Ames Meter, Chemstrip bG, and Stat Tek Meter determinations were performed according to manufacturers' instructions. Concurrent determination of blood glucose level by a glucose analyzer (Beckman) served as a standard for comparison. There was no significant difference in estimation of true blood glucose concentration among the rapid methods tested. The marked variability of results suggests only modest accuracy in estimating whole blood glucose concentration when employed in the routine neonatal clinical setting. These data indicate that the results from rapid blood glucose estimation techniques require confirmation by conventional laboratory methods prior to therapeutic intervention.

Blood Glucose↗
PubMed1982

Biochemical and physiological development of fetal rhesus lung.

Study of 17 fetal rhesus monkeys (Macaca mulatta) revealed a sequential rise in lung phosphatidylcholine (PC) concentration due to elevations in both disaturated (DSPC) and unsaturated constituents. The % DSPC in lung tissue clinical abruptly at 145 days of gestation prior to significant increases in PC or DSPC concentration but in association with improved lung deflation stability (% V10). This suggests that the DSPC-to-PC ratio may be a sensitive biochemical indicator of surfactant phospholipid production in lung parenchyma. Phosphatidyl-glycerol content did not increase significantly until after 155 days gestation, which was coincident with maximizing pulmonary distensibility (V max). Declining levels of phosphatidylethanolamine and sphingomyelin in lung tissue at 162 days support the hypothesis that preferential synthesis of PC occurs during late gestation. A serial decline in lung glycogen content with advancing gestation may reflect glycogen utilization as a substrate for lung phospholipid production. Comparison of biochemical and physiological data confirms the impression that discordances occur among lung maturational events. Lastly, a relationship between rising fetal blood cortisol levels and indices of fetal lung development was not demonstrated.

Animals↗
PubMed1982

Complications of pregnancy and fetal development.

Although the outcome of pregnancy for women with diabetes mellitus has improved in recent years, the infant of the diabetic mother has an increased risk of major clinical problems, particularly in the early neonatal period. These include birth injury due to macrosomia, neonatal hypoglycemia, respiratory distress syndrome, and serious congenital anomalies. Because of the great difficulties encountered during attempts to investigate these problems in clinical research protocols, there is a continuing need to establish appropriate animal models of the diabetic pregnancy. Studies carried out over the past decade, primarily with chemically-induced diabetes have suggested techniques which might be useful. In general, the choice of the animal to be studied will depend on the hypotheses being addressed. For instance, small animals such as rabbits and rats made diabetic with streptozotocin have been successfully used for investigation of fetal lung development. Furthermore, the rat model has been helpful for evaluation of fetal anomalies associated with maldevelopment of the spine and central nervous system. Larger animals, such as the nonhuman primate, are more appropriate for studying placental function and amniotic fluid composition in diabetic pregnancies. The task group on pregnancy and fetal development recommends that animal models of diabetes mellitus be used for a more extensive hormonal and metabolic characterization of diabetic mothers during pregnancy, for investigation of placental physiology with respect to the transfer of substrates from mother to fetus, for systematic and comprehensive study of mechanisms controlling fetal lung development, and for delineation of the pathophysiology of neonatal hypoglycemia. It is further recommended that animal models of spontaneous diabetes such as the BB/W rat be used in future studies dealing with pregnancy and fetal development. Because females with spontaneous diabetes show reduced conception rates, there is a pressing need to enhance the fertility of these animals in order to intensify studies on fetal development.

Alloxan↗
PubMed1981

The stability of phospholipids in amniotic fluid.

A systematic study of amniotic fluid phospholipids including phosphatidylcholine (PC, lecithin), saturated phosphatidylcholine, and phosphatidylglycerol was undertaken to evaluate the stability of these surfactant indices as a function of temperature and time. The purpose of the study was to determine optimum conditions for storage and for transport of specimens to centralized laboratories performing comprehensive analyses of amniotic fluid phospholipids for improved assessment of fetal lung development. Remarkable stability was found for the above phospholipids, as well as for the more commonly employed ratio of lecithin to sphingomyelin. We determined that room temperature more commonly employed ratio of lecithin to sphingomyelin. We determined that room temperature storage is acceptable for periods up to 24 hours; however, when longer delays before lipid extraction are anticipated, it is essential that specimens be frozen or that refrigeration or wet-ice storage (4 degrees C) be employed. Results of this study indicate that when amniotic fluid samples are stored frozen and strict quality control is maintained in analytic procedures, only minimal changes occur in phospholipid concentrations over 12 months.

Amniotic Fluid↗
PubMed1981

Effect of dexamethasone upon surfactant phosphatidylcholine and phosphatidylglycerol synthesis in organotypic cultures of type II cells.

Organotypic cultures of pulmonary type II epithelial cells were treated with dexamethasone at concentrations between 10(-10) and 10(-5) M for 48 h followed by a 3 h incubation in 5.6 mM [U-14C]glucose. A surfactant and a residual fraction was isolated from the cultures by discontinuous sucrose gradient centrifugation. Phosphatidylcholine and phosphatidylglycerol were purified from each fraction and analyzed for total content. The specific activity of each phospholipid was measured as an index of the rate of synthesis. Dexamethasone treatment produced a dose-dependent increase in synthesis and content of surfactant phosphatidylcholine, with a maximum response occurring at 10(-6) M dexamethasone. At concentrations of 10(-5) M, dexamethasone ceased to produce a significant stimulation. Dexamethasone produced an increase in surfactant phosphatidylglycerol synthesis only at a concentration of 10(-8) M and higher. There was not a significant effect upon the content or rate of synthesis of phosphatidylcholine or phosphatidylglycerol in the residual fraction at any of the dexamethasone concentrations tested.

Animals↗