Louis Gluck

The Biochemical Development of Surface Activity in Mammalian Lung: I. The Surface-Active Phospholipids; the Separation and Distribution of Surface-Active Lecithin in the Lung of the Developing Rabbit Fetus

Extract: A simple technique, precipitation with acetone, was described to separate the surface-active lecithin fraction from the nonsurface-active fraction. Surface activity in lung phospholipids was found in the acetone-precipitated fractions of lecithin, sphingomyelin, phosphatidyl dimethylethanolamine and phosphatidyl inositol. Normal surface activity of saline extract of pooled fetal rabbit lung was observed from 28 days of gestation. It was possible to isolate surface-active lecithin from lung parenchyma long before the 29th day of gestation when surface-active lecithin first is found in the alveolar wash. During the nonbreathing fetal state, even at term, only 11% of lecithin from alveolar wash is surface-active increasing after one hours breathing to approximately 50% of the total lecithin. The rabbits delivered prematurely after 28 full days of gestation clinically had respiratory distress and their percentage of surface-active lecithin in alveolar wash increased at a slow rate compared to full-term animals. Good temporal correlation was seen between intracellular storage of surface-active lecithin during the fetal state and the findings with electron microscopy of increasing numbers of osmiophilic inclusion bodies as gestation progresses.Speculation: Surface activity is shared by several phospholipids in lung but is related principally to lecithin. During fetal development there is production of intracellular surface-active lecithin with storage possibly in osmiophilic lamellar inclusion bodies until near term when some (11%) begins to appear in alveolar wash. After breathing, a great release of surface-active lecithin into alveolar wash occurs, with 50% of alveolar lecithin being surface active throughout the life of the animal. Prematurely delivered rabbits take much longer to increase their surface-active alveolar lecithin.

Septicemia of the newborn.

Experience with septicemia in 106 infants over a 25-year period has been reported. An almost 2:1 predominance of males was observed. In the first 10 years of this study, the Group A, beta hemolytic streptococcus was the predominant infecting organism, while in recent years infections with coliform organisms were the most common, although Group A streptococcal infections continue to occur. Significant numbers of those patients observed in the last 15 years were found to be infected with Ps. aeruginosa and with beta hemolytic streptococci of groups other than A. Fever, abdominal distention, icterus, and hepatomegaly were the most common clinical manifestations suggesting sepsis. However, in most patients the clinical picture was one of general, rather vague, systemic illness. Optimal therapy is based on vigorous search for the infecting organism and rapid initiation of intensive antibacterial therapy.

The Biochemical Development of Surface Activity in Mammalian Lung: II. The Biosynthesis of Phospholipids in the Lung of the Developing Rabbit Fetus and Newborn

Extract: In the lung of the rabbit fetus there was a rise in concentration of total lipids before term, the phospholipids constituting the major fraction. The concentrations of phosphatidylethanolamine and lecithin rose concurrently until day 28 when phosphatidylethanolamine concentration dropped, but lecithin continued to rise to term. From day 28 to term in the nonbreathing fetus there was an increase of 300% in acetone-precipitated surface-active lecithin found almost entirely in the residual parenchyma after wash with little increase in this fraction in alveolar wash. After breathing for 1 hour there were increases in total alveolar lecithin 3–5 fold over nonbreathing fetal lung while increases in acetone-precipitated alveolar wash lecithin from nonbreathing to breathing lung were 20–30 fold. Enzymatic reactions were studied in vitro according to the pathways for the de novo synthesis of lecithin and phosphatidylethanolamine as follows:1. CDP-(1,2-14C) choline + D-α, β-diglyceride → cithin2. Phosphatidylethanolamine + 3(14CH3)-S-adenosyl-L-methionine → cithin3. CDP-(1,2-14C) ethanolamine + D-α, β-diglyceride → phosphatidylethanolamine4. Phosphatidylethanolamine + (14C)-L-serine→phosphatidylserine-CO2→phosphatidylethanolamineCDP-choline incorporation declined steadily during gestation, although at term still showed rapid incorporation. The methylation reaction (2) showed peak incorporation on day 28 of gestation, at beginning viability. CDP-ethanolamine incorporation was the most active in vitro pathway studied peaking on days 25–26. Serine incorporation showed little activity, following a pattern of incorporation similar to that of CDP-ethanolamine. Activity of all pathways was found in microsomes. Methylation was also found in mitochondrial fraction of the term fetus and adult and in the cell-free soluble fraction from adult alveolar lavage. Reaction rates were similar from CDP-choline incorporation in both fetal and adult lung homogenate, but fetal lung incorporated methyl groups faster than adult lung. Intermediate compounds of methylation reaction were not found in alveolar wash of fetal lung, but were isolated from adult alveolar wash. Methylation in lung was pH sensitive, peak incorporation was seen at pH 7.8. Addition of ethanol or boiling one minute did not stop methylation. After breathing, those rabbit fetuses delivered by cesarean section after 28 full days of gestation synthesized 100% of surface-active alveolar lecithin by one hour of breathing, 90% of incorporation was with 3H-choline, 10% with (14CH3)-methionine. Much less incorporation into alveolar wash lecithin was seen with the breathing term fetus, but much more surface-active alveolar wash lecithin was isolated than from the fetus of 28 full days of gestation.Speculation: The most important pathway in rabbit fetal development and in the newborn rabbit for the de novo synthesis of surface-active alveolar lecithin is the incorporation of CDP-choline. Although there is good correspondence between the concentrations of lecithin and phosphatidylethanolamine in fetal lung and the enzymatic activities studies in vitro, once breathing begins there is little correspondence between in vivo and in vitro biosynthesis of lecithin by fetuses of the same gestational age. In the rabbit fetus and newborn the methylation reaction appears to be of little significance in the biosynthesis of surface-active alveolar wash lecithin.

EXPERIMENTAL CARDIAC HYPERTROPHY: CONCENTRATIONS OF RNA IN THE VENTRICLES.

Banding of the aorta or pulmonary artery in puppies produces a selectively increased concentration of RNA in the ventricle with the increased hemodynamic load as compared to the opposite side or to normal hearts. The increase in concentration of RNA following distortion of the myocardial cell may represent a fundamental response of growth and the system described mayserve as a useful model for its study.

Effect of an Antiseptic Skin-Care Regimen in Reducing Staphylococcal Colonization in Newborn Infants

IN 1952 Farquharson et al.1 reported the control of an outbreak of staphylococcal skin lesions in their nurseries by washing all infants with a hexachlorophene-containing preparation twenty-four ho...

Effective Control of Staphylococci in a Nursery

IN the last twenty years, the staphylococcus has replaced the streptococcus as the chief cause of infection in maternity units. Sporadic and epidemic staphylococcal infection among newborn infants ...

Staphylococcal Colonization in Newborn Infants with and without Antiseptic Skin Care. A Consideration of Epidemiologic Routes.

RECENT studies at the Yale–New Haven Medical Center1 , 2 have demonstrated that properly performed antiseptic skin and umbilical-cord care brings about a striking decrease in colonization of newbor...

Pulmonary Surfactant and Neonatal Respiratory Distress

With elucidation of the biochemistry of pulmonary surfactant (the substance that normally prevents collapse of the alveoli with each breath) and of the timetable of its maturation in fetal life, th...

RNA: A Marker in Embryonic Differentiation

A modified fluorochrome technique which identifies nucleic acids differentially in tissues permits following production of RNA in the embryo. Compact primordial chick embryo cells show a sequence to RNA production as differentiation begins: First in the nucleus, then in the perinuclear area, then in the cytoplasm. RNA increases in the cytoplasm with cell growth and continues as the cells merge to form an epithelium.

Facility for a Large Center

In seven years the nations first newborn special care unit has succeeded in reducing its infant mortality rate to less than half the national average. The first step was to reject the isolation and fragmentation that conventional concepts of infection control impose on the treatment of problem newborns.