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P M Farrell

Publications and source records attributed to P M Farrell.

15 recordsLinked to original sources
PubMed1979

Familial respiratory distress syndrome in three consecutive full-term infants. Case reports and documentation of lung enzyme activities.

Familial respiratory distress syndrome in full-term newborn infants is a rare occurrence. Our patient delivered three consecutive full-term infants who developed findings consistent with respiratory distress syndrome. All three died from autopsy-proven hyaline membrane disease. Analysis of the activities of four enzymes that play an important role in the biosynthesis of lecithin (choline kinase, choline phosphotransferase, phospholipase A and lysolecithin acyltransferase) failed to disclose an abnormality in lung samples in our patient with familial respiratory distress syndrome.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed1978

Evidence for the existence of a single enzyme catalyzing the phosphorylation of choline and ethanolamine in primate lung.

Choline kinase (ATP:choline phosphotransferase, EC 2.7.1.32) has been isolated and purified 1000-fold from adult African Green monkey lung with a yield of 10%. The purified enzyme also phosphorylated ethanolamine (ratio of ethanolamine kinase to choline kinase = 0.30). This ratio remained constant throughout the purification procedure. The Km for choline (3.0 - 10(-5) M) was lower than that of ethanolamine (1.2 - 10(-3) M.) Choline was also found to inhibit ethanolamine kinase activity by 50% at a concentration of 0.005 mM, while ethanolamine inhibited choline only at very high concentrations (100--150 mM). When the enzyme was subjected to inactivation by heat, hemicholinium-3, trypsin digestion, and p-hydroxymercuribenzoate, both ethanolamine kinase and choline kinase activities were destroyed at the same rate. Freezing and thawing in the absence of glycerol also destroyed both activities at the same rate. Based on these findings, we conclude that in adult African Green monkey lung tissue, there is only one enzyme for the phosphorylation of ethanolamine and choline, and that choline phosphorylation predominates.

Animals↗
PubMed1978

Determination of disaturated lecithin in rhesus monkey amniotic fluid as an index of fetal lung maturity.

Although increased concentrations of total lecithin in amniotic fluid allow prenatal assessment of fetal lung maturation, it has become clear that routine use of the L/S index may lead to a substantial number of inaccurate predictions. Since disaturated lecithin (DL) is a more specific marker of pulmonary surfactant than total lecithin, we developed a convenient method for measuring this phospholipid in amniotic fluid, and then evaluated its level in pregnant rhesus monkeys of 120 to 163 days of gestation. The method involves osmic acid destruction of unsaturated lipids, chromatographic isolation of disaturated lecithin, and quantitation by phosphorus assay. It can be performed in approximately 5 hours on 4 ml. of amniotic fluid and yield 67 +/- 3 per cent average recovery of added 14C-dipalmitolyl lecithin. The results of analyzing 36 rhesus amniotic fluid specimens showed the disaturated lecithin and the disaturated lecithin/sphingomyelin ratio (DL/S) increase sharply after 150 days of gestation, consistent with the pattern of lung maturation in this species. We conclude that disaturated lecithin can be readily quantitated in primate amniotic fluid and that its concentration, the DL/S ratio, and percentage of disaturated lecithin are potentially useful indices of fetal lung maturity for the clinical laboratory.

Amniotic Fluid↗
PubMed1978

Lung lecithin synthesis in primates as related to respiratory distress syndrome.

Lecithin is synthesized de novo in the lung by two biochemical pathways, choline incorporation and phosphatidylethanolamine methylation. These studies in the Macaca mulatta fetus and neonate have demonstrated the relative contributions of the two pathways and the timing in monkey gestation of increased pulmonary lecithin production.

Amniotic Fluid↗
PubMed1977

Maternal betamethasone and fetal growth and development in the monkey.

Bethamethasone was administered to pregnant rhesus monkeys of 134 to 150 days' gestation. At operative delivery, umbilical venous plasma cortisol concentrations were significantly lower in the treated group than in the control group, indicating that the agent crossed the placenta. In the treated group, accelerated differentiation was present in several fetal organs including lung, liver, kidney, and adrenal gland. Brain histologic changes suggestive of neuronal injury were found in some instances. There were no differences in the weights of these fetal organs except for liver. It was markedly increased in steroid-treated fetuses and this was accompanied by a fourfold rise in total hepatic glycogen content. These observations suggest that in the subhuman fetal primate, the differentiation of fetal organs in addition to lung is enhanced by short-term corticosteroid treatment while growth is not affected.

Animals↗
PubMed1977

Lung phosphatidylcholine synthesis and cholinephosphotransferase activity in anencephalic rat fetuses with corticosteroid deficiency.

Adrenocortical insufficiency was produced in rat fetuses by surgical decapitation. These animals show low plasma corticosterone levels compared to littermate controls. Lung slices from anencephalic fetuses were found to have reduced incorporation of [14C]choline into phosphatidylcholine, hence diminished choline pathway activity; this abnoramlity was present at 21 days of gestation but not at term. Cholinephosphotransferase (CPT), the terminal catalyst of the choline pathway, also showed diminished activity in lungs of anencephalic fetuses, with a mean of 120 pmol/min/mg protein compared to a control value of 190. Dexamethasone treatment of these animals for 6-12 hr led to enhanced choline incorporation rates. Corticosteroid administration also restored CPT activity and even elevated the enzyme to a mean level (340 pmol/min/mg protein) greater than that found in normal fetuses at 21-22 days of gestation. The early pulmonary biochemical effects of dexamethasone in this model were not accompanied by recognizable ultrastructural changes.

Adrenal Cortex Hormones↗
PubMed1976

Lung lecithin biosynthesis in the nonhuman primate fetus: determination of the primary pathway in vivo.

The two pathways for de novo lecithin (phosphatidylcholine) biosynthesis, choline incorporation (1) and phosphatidylethanolamine methylation (II), were examined simultaneously in lung and other tissues of Rhesus monkey fetuses. Cannulation of interplacental fetal vessels permitted studies on the intrauterine fetus without disruption of fetal-placental-maternal-amniotic fluid anatomic integrity. In contrast to observations with indirect techniques in the same species, direct measurement of the incorporation of isotopic precursors (3H-choline and 14C-ethanolamine) into lecithin indicated that pathway I predominates by 100-fold over PE methylation in pulmonary lecithin synthesis. Fetal liver, brain, and kidney also showed 10--70-gold greater choline incorporation that methylation activity. Measurement of lung phosphatidylcholine production via the two pathways in acidemic fetuses (umbilical venous pH less than 7.20) demonstrated marked inhibition of pathway I, but not II. It is concluded that the choline pathway is the major mechanism of lung lecithin synthesis in fetal primates and that this pathway is pH sensitive in vivo.

Acid-Base Equilibrium↗
PubMed1976

Determination and characterization of ciliary ATPase in the presence of serum from cystic fibrosis patients.

The purpose of this investigation was twofold: (1) to identify and characterize the enzymatic ATP hydrolysis system of epithelial cilia, and (2) to develop a quantitative, biochemical test for the ciliotoxic cystic fibrosis (CF) factor based on inhibition of ATP utilization by ciliary preparations. Our rationale for selecting this system for CF factor analysis relates to the tight and essential mechanochemical coupling of functioning cilia. Using rabbit tracheal epithelium as the source, a high molecular weight (greater than 200,000) ATPase was identified, partially purified, and extensively characterized. The properties of this protein were similar to those observed in previous studies of others with flagellar and ciliary dynein (the motility-associated ATPase) isolated from microorganisms. Analysis of the pH profile revealed a broad range of high enzymatic activity between 6.5 and 9. Studies with potential cation activators showed that the enzyme is activated equally by either Ca2+ or Mg2+ in equimolar concentrations. No activation occurred in the presence of Zn2+, Na+, H+, or Na+ plus K+ and the effect of Mg2+ or Ca2+ was not inhibited by Na+, K+, or Na+ plus K+. The enzyme hydrolyzed Mg2+-containing solutions of UTP, CTP, and ADP at 51-54% the rate of ATP dephosphorylation, whereas Mg-deoxy-ATP was hydrolyzed 79% as effectively as ATP. Using a newly devised, analytical technique with [gamma-32P]ATP as the substrate, the ATP hydrolysis of various ciliary preparations from rabbit trachea and oyster gill (including motile suspensions) was monitored in the presence of sera from CF homo- and heterozygotes. Reproducible rates of ATP dephosphorylation averaging 27 nmol/min/mg protein were demonstrable with homogenates of ciliated epithelium. None of the test systems evaluated, however, were capable of demonstrating CF-related differences in ATPase activity or ATP utilization. Although these attemps have been unsuccessful thus far, the approach described in this report provides an example of an objective, quantitative, biochemical assessment of ciliary function.

Adenosine Triphosphatases↗
PubMed1976

Fetal lung lecithin metabolism in the glucose-intolerant Rhesus monkey pregnancy.

Fetal lung lecithin metabolism was examined in rhesus monkey gestations complicated by glucose intolerance secondary to maternal streptozotocin (STZ) administration. Fetuses of STZ-treated mothers were delivered at 85% to 89% of term and were compared to two control groups of fetuses from normal pregnancies--one group age-matched to the STZ pregnancies, and the other composed of fetuses delivered in the final 10% of gestation. In the glucose-intolerant pregnancies, two measures of fetal lung lecithin biosynthesis--the amniotic fluid lecithin-to-sphingomyelin (L/S) ratio and the rate of 14C-choline incorporation into lecithin in fetal lung slices--were significantly greater than in age-matched normal gestations and were similar to results in late-gestation controls. However, lung lecithin concentrations in the glucose-intolerant group were comparable to the age-matched controls, and both were significantly less than in the late-gestation controls. Since the gestational age, mode of delivery, and fetal acid-base status were the same in the age-matched groups, we conclude that these changes in fetal lung lecithin metabolism are due to the effects of maternal glucose intolerance.

Amniotic Fluid↗
PubMed1976

Diminished pulmonary lecithin synthesis in acidosis: experimental findings as related to the respiratory distress syndrome.

Lung slices from term fetal rats were incubated in vitro at various pH values and the rates of the two de novo pathways for lecithin biosynthesis were determined by measuring the conversion of either 14C-choline (pathway 1) or 14C-methionine (pathway 2) to the phospholipid. It was observed that the choline pathway, but not phosphatidylethanolamine methylation, is pH-sensitive with maximum rates occurring at pH levels between 7.3 and 7.5; significantly less activity was found at pH levels between 7.0 and 7.2 and at pH levels between 7.6 and 8.0. Adjustment of the pH from 7.0 to 7.4 in vitro simulating the clinical correction of acidosis by alkali infusion was found to increase the conversion of choline to lecithin to a rate approximating that observed at pH 7.4. Since lecithins are the principal phospholipid components of pulmonary surfactant, and since pathway 1 is predominantly responsible for lung lecithin synthesis, the demonstration of impaired production with reduced pH offers a biochemical explanation for the pathophysiological effects of acidosis in the respiratory distress syndrome. A comparison of pH effects on choline pathway rate with the pH profiles of pathway enzymes suggests that these effects are mediated by the catalysts of lecithin synthesis.

Acidosis↗