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Biomedical subjects

W M Maniscalco

Publications and source records attributed to W M Maniscalco.

49 records · Page 3Linked to original sources

Twin transfusion syndrome causing cutaneous erythropoiesis.

Two cases of twin transfusion syndrome are described in which the donor twin exhibited blueberry muffin-like macules and papules associated with cutaneous erythropoiesis. No evidence was found in either case for intrauterine viral infection, the most common cause of cutaneous erythropoiesis. Cutaneous erythropoiesis is these two cases is considered to be due to persistence or reactivation of fetal dermal erythropoiesis secondary to prolonged, severe intrauterine anemia.

Adult↗

Job satisfaction and stress among neonatologists.

Neonatology is reputed to be a stressful pediatric subspecialty. To quantify objectively this stress and to assess the factors involved, a questionnaire was mailed to neonatologists in the northeastern United States. Ninety-six (70%) replied. A five-point scale was used to determine the level of satisfaction with neonatology as a career and the level and type of stress experienced at work. Almost all neonatologists experienced stress at work: 34% moderately severe and 16% very severe stress. Open-ended questions indicated that the major causes of stress were excessive work load, eg, on call too often or calls at night; problems in patient care, especially dealing with infant death; and staff disagreements, especially nurse or housestaff conflicts. Twenty percent of those surveyed suffered a stress-related illness in the previous 5 years. One sixth of the neonatologists were either moderately or very dissatisfied with their career. Major dissatisfactions were: too much work, especially managing many sick patients; lack of resources, including inadequate salary; too much stress at work; and administrative demands. Job satisfaction was derived from patient care, teaching, intellectual stimulation, and research. Altering subspecialty had been considered at some time by 58% (15% very seriously). This study confirms that neonatology, in the eyes of those who practice it, is a highly stressful career. It also suggests that job stress is a greater problem than job dissatisfaction.

Adult↗

Properties of freshly isolated type II alveolar epithelial cells.

The biochemical characteristics of type II alveolar epithelial cells dissociated from adult rabbit lung by instillation of low concentrations of an elastase trypsin mixture are reported. Cells studied immediately (within 4 h) after isolation were found to incorporate the radioactively labelled precursors [U-14C]glucose, [methyl-3H]choline and [3H]palmitate into cellular phosphatidylcholine at rates 2-10-fold higher than previously reported for cells not subject to short-term cell culture. Secretion of phosphatidylcholine was stimulated by beta-adrenergic agonists. Measurement of specific activities of enzymes of phospholipid biosynthesis in subcellular fractions of isolated lung cells showed a significant enrichment of acyl coenzyme A-lysophosphatidylcholine acyltransferase, an enzyme believed to be involved in pulmonary surfactant phosphatidylcholine remodeling, in the endoplasmic reticulum of type II cells. These observations support the utility of freshly isolated type II cells as a model system for the study of the functions of the alveolar epithelium.

Animals↗

De novo fatty acid synthesis by freshly isolated alveolar type II epithelial cells.

Fatty acid synthesis was studied in freshly isolated type II pneumocytes from rabbits by 3H2O and (U-14C)-labeled glucose, lactate and pyruvate incorporation and the activity of acetyl-CoA carboxylase. The rate of lactate incorporation into fatty acids was 3-fold greater than glucose incorporation; lactate incorporation into the glycerol portion of lipids was very low but glucose incorporation into this fraction was approximately equal to incorporation into fatty acids. The highest rate of de novo fatty acid synthesis (3H2O incorporation) required both glucose and lactate. Under these circumstances lactate provided 81.5% of the acetyl units while glucose provided 5.6%. Incubations with glucose plus pyruvate had a significantly lower rate of fatty acid synthesis than glucose plus lactate. The availability of exogenous palmitate decreased de novo fatty acid synthesis by 80% in the isolated cells. In a cell-free supernatant, acetyl-CoA carboxylase activity was almost completely inhibited by palmitoyl-CoA; citrate blunted this inhibition. These data indicate that the type II pneumocyte is capable of a high rate of de novo fatty acid synthesis and that lactate is a preferred source of acetyl units. The type II pneumocyte can rapidly decrease the rate of fatty acid synthesis, probably by allosteric inhibition of acetyl-CoA carboxylase, if exogenous fatty acids are available.

Acetyl-CoA Carboxylase↗

Necrotizing enterocolitis in premature infants transferred back to community hospitals.

The return of stable premature infants to community hospitals from level III neonatal intensive care units is becoming more common. While these infants usually need only to gain weight, they are still at risk for significant neonatal problems. We report four cases of necrotizing enterocolitis (NEC) in nine stable, growing premature infants who weighed less than 1,300 g and returned to community hospitals. The onset of NEC was within 60 hours of transport, suggesting that transport and early feeding after transport may have been contributory to NEC.

Enteral Nutrition↗

Effects of dexamethasone on beta-adrenergic receptors in fetal lung explants.

The action of beta-adrenergic agonists on pulmonary surfactant secretion requires lung cell membrane beta-adrenergic receptors. In the fetus, the density of beta-adrenergic receptors in lung increases in the latter stages of gestation. The increase in density can also be induced by maternal glucocorticoid treatment. In this study, we measured beta-adrenergic receptors in developing rat lung by (-) [3H]-dehydroalprenalol (DHA) binding and confirmed the increase in beta-adrenergic receptors late in gestation. To determine if glucocorticoids have a direct effect on fetal lung to regulate beta-adrenergic receptors, we cultured fetal lung explants with dexamethasone. Treated explants had increased DHA binding compared with controls (138.0 +/- 8.8 versus 63.2 +/- 5.0 fmole/mg membrane protein). Scatchard analysis revealed that the increased DHA binding was due to an increase in maximum receptor number. There was also a significant difference in the dissociation constant of the treated and control explants (0.85 +/- 0.07 nM versus 0.43 +/- 0.08 nM, respectively; P less than 0.05), suggesting that the receptors induced by dexamethasone were of lower binding affinity. Cyclohexamide, an inhibitor of protein synthesis, completely eliminated the dexamethasone induced increase in DHA binding. These data indicate that glucocorticoids have a direct effect on fetal lung to increase beta-adrenergic receptor density and that new protein synthesis is required for this effect.

Alprenolol↗

De novo fatty acid synthesis in developing rat lung.

The rate of de novo fatty acid synthesis in developing rat lung was measured by the rate of incorporation of 3H from 3H2O into fatty acids in lung slices and by the activity of acetyl-CoA carboxylase in fetal, neonatal and adult lung. Both tritium incorporation and acetyl-CoA carboxylase activity increased sharply during late gestation, peaked on the last fetal day, and declined by 50% 1 day after birth. In the adult, values were only one-half the peak fetal rates. In vitro regulation of acetyl-CoA carboxylase activity in fetal lung was similar to that described in adult non-pulmonary tissues: activation by citrate and inhibition by palmitoyl-CoA. Similarly, incubation conditions that favored enzyme phosphorylation inhibited acetyl-CoA carboxylase activity in lung while dephosphorylating conditions stimulated activity. Incorporation of [U-14 C]glucose into lung lipids during development was influenced heavily by incorporation into fatty acids, which generally paralleled the rate of tritium incorporation into fatty acids. The relative utilization of acetyl units from exogenous glucose for overall fatty acid synthesis was greater in adult lung than in fetal or neonatal lung, suggesting that other substrates may be important for fatty acid synthesis in developing lung. In fetal lung explants, de novo fatty acid synthesis was inhibited by exogenous palmitate. Taken together, these data suggest that de novo synthesis may be an important source of saturated fatty acids in fetal lung but of lesser importance in the neonatal period. Furthermore, the regulation of acetyl-CoA carboxylase activity and fatty acid synthesis in lung may be similar to non-pulmonary tissues.

Acetyl-CoA Carboxylase↗

Factors influencing neonatal autopsy rate.

To determine if common clinical factors are associated with the neonatal autopsy rate, we conducted a retrospective analysis of 117 deaths in a neonatal intensive care unit. The autopsy rate of neonatal deaths was significantly greater than the autopsy rate of adult and non-neonatal pediatric deaths. In the newborn period, the autopsy rate of transported patients was significantly less than that of inborn patients. Among those transported, autopsies were significantly less common in patients of low birth weight or low gestational age. Furthermore, among all newborns dying within two days of admission, transported patients were less likely to undergo autopsies than inborn patients. Other factors, including maternal age, race, and marital status, did not affect the autopsy rate of newborn deaths. These data suggest that early separation of the mother from her infant and the medical team caring for the infant adversely affect the process of autopsy request and consent.

Autopsy↗

Effects of betamethasone on phospholipid content, composition and biosynthesis in the fetal rabbit lung.

Administration of betamethasone (0.2 mg/kg, intramuscularly) to pregnant rabbits had the following effects on the fetal lung at 26--27 days gestation. It increased the amount of phosphatidylcholine in lung lavage by 70% and almost doubled the phosphatidylcholine/sphingomyelin ratio, it increased the rate of incorporation of choline into phosphatidylcholine in fetal lung slices by up to 90%, it increased the activities of pulmonary cholinephosphate cytidylyltransferase and phosphatidate phosphatase by 50% and it reduced the amount of lung glycogen to 60% of the amount in the controls. Betamethasone had no effect on the activities of pulmonary cholinephosphotransferase or lysolecithin: lysolecithin acyltransferase but it slightly decreased the activity of choline kinase. Betamethasone administration to the doe did not increase the amount of surfactant phospholipid in fetal lung lavage to as great an extent as did direct administration of cortisol to the fetuses. Neither did betamethasone stimulate the activity of pulmonary cholinephosphotransferase. These data suggest that agents other than glucocorticoids mediate the stress-induced acceleration of fetal lung maturation and surfactant production.

1-Acylglycerophosphocholine O-Acyltransferase↗

Influence of aminophylline and cyclic AMP on glycogen metabolism in fetal rat lung in organ culture.

The glycogen content of fetal rat lung declines coincident with increased pulmonary phospholipid synthesis. Aminophylline, a methylxanthine cyclic adenosine 3',5' monophosphate (AMP) phosphodiesterase inhibitor, and cyclic AMP augment fetal lung phospholipid synthesis. Because lung glycogen breakdown may contribute to pulmonary phospholipid synthesis, the effects of aminophylline and cyclic AMP on glycogen metabolism were studied in explants of 19 day fetal rat lung in organ culture. Treatment with aminophylline or dibutyryl cyclic AMP for 24 hr, resulted in a 25% (P less than 0.025) and 75% (P less than 0.001) decrease, respectively, in the glycogen content of the explants. Glycogen synthase I activity was reduced by 32% in aminophylline treated cultures (P less than 0.025) and 25% in cyclic AMP treated cultures (P less than 0.025). The percent of total synthase in the active form was significantly reduced in all treated cultures. Neither aminophylline nor cyclic AMP treatment resulted in significant changes in glycogen phosphorylase a or total phosphorylase activity.

Aminophylline↗

Development of glycogen and phospholipid metabolism in fetal and newborn rat lung.

Glucose, a major metabolic substrate for the mammalian fetus, probably makes significant contributions to surface active phospholipid synthesis in adult lung. We examined the developmental patterns of glycogen content, glycogen synthase activity, glycogen phosphorylase activity and glucose oxidation in fetal and newborn rat lung. These patterns were correlated with the development of phosphatidylcholine synthesis, content and the activities of enzymes involved in phosphatidylcholine synthesis. Fetal lung glycogen concentration increased until day 20 of gestation (term is 22 days) after which it declined to low levels. Activity of both glycogen synthase I and total glycogen synthase (I + D) in fetal lung increased late in gestation. Increased lung glycogen concentration preceded changes in enzyme activity. Glycogen phosphorylase a and total glycogen phosphorylase (a + b) activity in fetal lung increased during the period of prenatal glycogen depletion. The activity of the pentose phosphate pathway, as measured by the ratio of CO2 derived from oxidation of C1 and C6 of glucose, declined after birth. Fetal lung total phospholipid, phosphatidycholine and disaturated phosphatidylcholine content increased by 60, 90 and 180%, respectively, between day 19 of gestation and the first postnatal day. Incorporation of choline into phosphatidylcholine and disaturated phosphatidylcholine increased 10-fold during this time. No changes in phosphatidylcholine enzyme activities were noted during gestation, but both choline phosphate cytidylyltransferase and phosphatidate phosphatase activity increased after birth. The possible contributions of carbohydrate derived from fetal lung glycogen to phospholipid synthesis are discussed.

Aging↗

An organ culture model for study of biochemical development of fetal rat lung.

We have developed a short-term organ culture model for the study of the biochemical and morphological development of late gestation fetal rat lung. Explants (1 mm3) of 19-day lung were cultured in an oxygen enriched environment in the presence of synthetic serum-free medium for 3 days. Morphological maturation continued in culture. The rate of incorporation of choline into disaturated phosphatidylcholine and the content of this phospholipid in the explants increased in vitro in a pattern very similar to that which occurs in vivo. The activities of choline kinase and cholinephosphotransferase were also similar in cultured lung and in vivo. Studies of glucose oxidation to CO2 provided additional evidence that the explants remained viable in culture. The explants retained the sensitivity of fetal lung to hormonal action. This was demonstrated by the stimulation of choline incorporation into phospholipid by cyclic AMP and an increase in the glycogen content after exposure to insulin.

Animals↗