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Biomedical subjects

R D Zachman

Publications and source records attributed to R D Zachman.

At least 55 records · Page 3Linked to original sources
PubMed1983

Maternal smoking and respiratory distress syndrome.

Infants of 603 patients on whom information about smoking habits during pregnancy was available were studied for incidence respiratory distress syndrome. Among the 360 patients who did not smoke, the incidence of respiratory distress syndrome in the neonate was 15.1%, whereas among patients who smoked, the incidence was 9.1%. We speculate that smoking produces a condition of chronic stress in the fetus which brings about an acceleration of fetal pulmonary maturation.

Amniocentesis↗
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↗
PubMed1983

Conversion of choline to phosphatidylcholine in the isolated-ventilated-perfused neonatal rabbit lung.

The isolated-ventilated-perfused neonatal rabbit lung model was used to study pulse dosed 14C-choline incorporation into 14C-phosphatidylcholine (PC) and 14C-disaturated phosphatidylcholine (DSPC). 14C-PC and 14C-DSPC synthesis were linearly dependent upon perfusion time to 30 min and upon the pulse dose of 14C-choline of 20-250 nmol at both 10 and 30 min of perfusion. 2-3% of the pulse-dosed choline was taken up by the lung. The water-soluble metabolites of choline found in lung after 10-30 min of perfusion were: choline, 50-60%; betaine 2.4-3.0%; phosphorylcholine, 26-41%, and CDP-choline, trace-10%. 1-day-old perfused lungs incorporated pulse-dosed 14C-choline into 14C-PC and 14C-DSPC at slightly higher rates than at 10 days old. Newborn rabbits receiving an intraperitoneal injection of 0.1 mg dexamethasone/100 g body weight 16 and 22 h prior to perfusion incorporated significantly more 14C-choline into 14C-PC and 14C-DSPC than saline-injected controls.

Animals↗
PubMed1982

Determination of phosphatidylglycerol in amniotic fluid by a simple one-dimensional thin-layer chromatography method.

Phosphatidylglycerol (PG) in amniotic fluid is the second important component of lung surfactant phospholipids and may be clinically useful in assessing fetal lung maturity in utero. Although methods for PG determination are available, there are shortcomings in clinical application. We developed an alternative reliable one-dimensional thin-layer chromatography(TLC) method for separating and quantitating PG in amniotic fluid. A mini-TLC plate (8 X 10 cm) was prepared from silica gel H containing 5% ammonium sulfate. The plate was first developed in tetrahydrofuron/dimethoxymethane/methanol/2N ammonium hydroxide (30.0:20.6:5.6:3.0 v/v) and then in chloroform/methanol (60.9, v/v) in the same direction. PG was clearly separated from other phospholipids and neutral lipids, even when large amounts of other phospholipids were present on the TLC plate. The density of the charred PG was directly proportional to the amount of PG up to 8 nmol. The content of PG in nmol in the specimen can be quantitated by comparing with a standard PG. Up to 10% of blood serum or 3% meconium showed no detectable PG, nor did these substances affect PG quantitation in amniotic fluid. This method is sensitive and accurate. It is also time-saving and economical.

Amniotic Fluid↗
PubMed1980

Pulmonary uptake of liposomal phosphatidylcholine.

Liposomes prepared with phosphatidylcholine (PC) labeled with [1-14C]-dipalmitoyl-PC, dicetylphosphate, cholesterol (molar ratio 7:2:1) were injected into the right ear vein of 2-month-old male rabbits. At 5, 60, and 120 min after injection, organs were removed and analyzed for [14C]-PC. Lung, liver, and spleen took up the [14C]-PC by 5 min. Spleen accumulation of [14C]-PC increased steadily, liver plateaued from 1--2 hr, and lung fell rapidly. The uptake of liposomal [14C]-PC by lung and liver was dependent on the concentration of iv injected liposomal [14C]-PC. All lung subcellular fractions (lamellar bodies, mitochondria, and microsomes) took up [14C]-PC. Lamellar body [14C]-PC was highest at 5 min, and then decreased. Still, on a nmole/mg protein basis, uptake of [14C]-PC by lamellar bodies was higher than other organelle fractions. Of the radioactivity in lung, 95% was [14C]-PC even after 2 hr, whereas by 1 hr, 28% of liposomal PC absorbed by liver had been degraded.

Animals↗
PubMed1979

Effect of diabetes mellitus on amniotic fluid lecithin/sphingomyelin ratio and respiratory distress syndrome.

Ninety-eight insulin-dependent diabetic patients were cared for during 108 pregnancies following an ambulatory program aimed at close control of blood sugar levels. The incidence of respiratory distress syndrome (RDS) in these patients was not different from that in nondiabetic patients. Fetal pulmonary maturity seemed to progress at a normal rate as evidenced by an equal incidence of mature lecithin/sphingomyelin (L/S) ratios at various stages of gestation in diabetic and nondiabetic patients. There was no evidence that Class B and C diabetic patients have delayed fetal lung maturation or that Class E, F, and R patients have accelerated maturation. It is concluded that careful metabolic control of the pregnant diabetic patient results in a normal process of fetal pulmonary maturation without increased risk of RDS.

Amniotic Fluid↗
PubMed1979

Effect of hydrocortisone on the metabolism of phosphatidylcholine in maternal and fetal rabbit lungs and livers.

Administration of hydrocortisone to pregnant rabbits caused a decrease in weights of fetal body and lung and an increase in the incorporation of choline into fetal lung PC. The authors found no induction of the enzymes related to the incorporation of choline into PC in fetal lung. Also, there was no stimulation of any enzymatic activity of CDP-choline pathway or PC-lysoPC cycle pathway in maternal lung and liver or fetal liver. In addition to the acceleration of choline incorporation into fetal lung PC by the cortisol, hydrocortisone also significantly stimulated the secretion of lung PC affected by glucocorticoids may also be related to apparent fetal lung maturation.

Animals↗
PubMed1977

Effect of maternal isoxsuprine on fetal rabbit lung biochemical maturation.

Isoxsuprine was given intramuscularly for 24 hours to pregnant rabbits at 26 to 27 days' gestation. There was no effect on fetal weight within one day of the last injection. Fetuses of isoxsuprine-treated mothers had higher lung lecithin (6.67 micron per gram +/- 2.81) and higher tracheal wash lecithin/sphingomyelin (L/S) ratios (5.85 +/- 4.5) than did untreated fetuses--lung lecithin (5.35 micron per gram 1.23) and tracheal wash L/S (4.08 +/- 2.3). In contrast, phosphorylcholine glyceride transferase activity of the fetal lung was less in isoxsuprine-treated fetal lung tissue.

Animals↗
PubMed1977

Isolated, ventilated, perfused newborn rabbit lung preparation and its assessment.

To achieve an isolated, ventilated, perfused newborn rabbit lung preparation, newborn rabbits are anesthetized and ventilated. The pulmonary vasculature is perfused with a Krebs-Ringer bicarbonate solution containing glucose and plasma expanders, and the lungs are isolated in a 37 degrees C chamber at 100% humidity. The success of a perfusion is evaluated on three levels. 1) Visual. 2)mechanical: a, drop in flow of greater than 20% indicates failure; b, an increase of more than 25% of the initial lung weight indicates fluid accumulation and failure. 3) Biochemical: a, the endogenous ATP concentration after perfusion; b, the level of the enzyme choline phosphotransferase (CPT) after perfusion. Isolated, perfused, ventilated newborn rabbit lungs maintained for 4 h with no changes in the monitored physical and mechanical parameters have an endogenous ATP level of 1.06 +/- 0.06 (2 SD) mumol ATP/mg wet weight and a CPT level of 1.34 +/-0.15 (2 SD nmol [14C]CDP-choline per milligram protein in 30 min. These values are stable at a level lower than observed in intact, hypoxic, newborn rabbit's lungs. In constrast, if perfusion is maintained after any of the monitored criteria indicate failure, the endogenous ATP concentration and CPT activity are significantly depressed.

Adenosine Triphosphate↗
PubMed1977

Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. I. Subcellular localization and properties.

The de novo cytidine-5'-diphosphocholine (CDP-choline) pathway enzymes: choline kinase (CK); phosphorylcholine cytidyltransferase (CyT), and phosphorylcholine glyceride transferase (PCGT), and the phosphatidylcholine-lysophosphatidylcholine (PC-lysolPC) cycle pathway enzymes: lysophospholipase (LPL), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acyl-CoA LAT) were studied in the rabbit lung subcellular fractions. The purity of the fractions was examined by the marker enzymes and electron microscopy. The lamellar bodies had the highest concentration of phospholipids (10.0 mumol/mg protein, 80% of which was phosphatidylcholine (PC), about 10-fold higher than that of mitochondria (0.8) and microsomes (1.0) (50% of which was PC in both fractions). The lamellar bodies contained no enzymic activities of either the CDP-choline pathway or the PC-lysoPC cycle pathway. The enzymic activities of CK, CyT, LPL, and LAT were found mainly in the soluble fraction (about 40% for CK and CyT, and 70% for LPL and LAT); PCGT and acyl-CoA LAT were microsomal enzymes. Some general properties of PC-lysoPC cycle enzymes were also studied. The activities of LPL, LAT, and acyl-CoA LAT were not stimulated by the divalent metal ion Ca+. Their activities were inhibited by 10(-3) M diisopropyl phosphorofluoridate (DFP). The role of the PC-lysoPC cycle pathway enzymes in remodeling the lung PC is discussed.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1977

Phosphatidylcholine-lysophosphatidylcholine cycle pathway enzymes in rabbit lung. II. Marked differences in the effect of gestational age on activity compared to the CDP-choline pathway.

Lysophosphatidylcholine (lysoPC), a breakdown product of phosphatidylcholine (PC), might be important in pulmonary PC synthesis through fatty acid exchange reactions. This study defines the levels of three of the enzymes of the PC-lysoPC cycle pathway (lysophospholipase (LPL) (EC. 3.1.1.5), lysophosphatidylcholine-lysophosphatidylcholine acyltransferase (LAT), and acyl-CoA lysophosphatidylcholine acyltransferase (acryl-CoA LAT) (EC. 2.3.1.23)) in developing fetal rabbit lung and compared them with the enzymes of the CPD-choline synthetic pathway (choline kinase (CK) (EC. 2.7.1.32), phosphorylcholine cytidyl transferase (CyT) (EC. 2.7.7.15), and phosphorylcholine glyceride transferase (PCGT) (EC. 2.7.8.2). Lung homogenates of fetal rabbits of known gestation, newborn, and adult rabbits were used for the enzyme, protein, and phospholipid analyses. Total lung phospholipid, PC, and protein increased with gestational age. Thirty days' gestation, newborn, and maternal lung activities of CK, CyT, and PCGT had decreased to only 50% of their activities at 22-26 days' gestation. In contrast, LPL and LAT activities increased 4-5-fold from 22-26 days to 30 days' gestation, and increased further in the newborn lung, finally to a level matching maternal lung (about 8-10-fold higher than the 22-26 days' gestation activities). The microsomal acyl-CoA LAT also showed a similar increasing activity with gestational age. In fetal lung, enzymic activities for the apparent major PC synthetic pathway decreased. In contrast, the marked increases in LPL, LAT, and acyl-CoA LAT activities with increasing gestational age and at birth suggests importance of the PC lysoPC cycle pathway in regulating synthesis and turnover with maturation.

1-Acylglycerophosphocholine O-Acyltransferase↗