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Biomedical subjects

M J Kresch

Publications and source records attributed to M J Kresch.

26 records · Page 2Linked to original sources

Activities of enzymes of phospholipid and fatty acid synthesis in fetal and adult rat type II pneumocytes.

Although differentiated fetal and adult type II pneumocytes are ultrastructurally similar, it is not known whether there are metabolic differences between them. We measured the activities of selected enzymes of phospholipid and fatty acid synthesis in fetal and adult rat type II cells, in late gestation fetal rat lung explants and in intact lung from rat fetuses of comparable gestational age. The activity of 1-acylglycerophosphocholine acyltransferase was significantly greater in adult type II cells than in fetal type II cells, fetal explants or intact fetal lung. The activity of CDP diacylglycerol:glycerol-3-phosphate 3-phosphatidyltransferase was similar in fetal and adult type II cells, but significantly lower in explants and intact fetal lung. There was a significant positive correlation between the percentage of alveolar epithelial cells in the cultures and tissue studied and CDP diacylglycerol:glycerol-3-phosphate 3-phosphatidyltransferase activity. This suggests that the previously reported correlation between phosphatidylglycerol synthesis and the percentage of alveolar epithelial cells in various lung culture systems may be related to the activity of this enzyme. Phosphatidylglycerol synthesis and CDP diacylglycerol:glycerol-3-phosphate 3-phosphatidyltransferase activity may be metabolic markers of type II cells, whereas the acyltransferase activity may be an indicator of type II cell maturation.

1-Acylglycerophosphocholine O-Acyltransferase↗

Late closure of the ductus arteriosus using indomethacin in the preterm infant.

Several studies have shown a lack of effect of indomethacin therapy for the closure of a patent ductus arteriosus (PDA) in premature infants over 14 days of postnatal age. In this report we describe two cases in which a hemodynamically significant PDA was closed with indomethacin in preterm infants over 20 days of age. The response to indomethacin may be more related to postconceptual age than to actual postnatal age. We suggest that intravenous indomethacin therapy should be attempted before surgical ligation is performed in those premature infants under 34 weeks postconceptual age who have a hemodynamically significant patent ductus arteriosus.

Ductus Arteriosus, Patent↗

Culture of differentiated and undifferentiated type II cells from fetal rat lung.

We have developed a relatively simple and reproducible method for the isolation and culture of both differentiated and undifferentiated type II cells from fetal rat lung. The technique involves an initial period of explant culture in serum and hormone free medium, followed by enzymatic dissociation of the explants, differential adhesion to remove fibroblasts, incubation of the cell pellet to promote aggregation of the type II cells and monolayer culture of the type II cells. The type II cells form clusters which are surrounded by scattered fibroblasts. When the technique was performed with three differential adhesion steps, cultures contained 86.0 +/- 1.4% type II cells. To obtain a higher degree of purity and greater yield, two differential adhesions followed by gentle trypsinization of the cultures which selectively removes the isolated fibroblasts was performed. This resulted in cultures with 89.4 +/- 1.7% type II cells. The differentiated fetal type II cell cultures were prepared from 19-day fetal rat lungs which were initially maintained in explant culture for 48 h. These differentiated cells demonstrated the characteristic morphologic features of type II cells including lamellar bodies and microvilli. Undifferentiated fetal cells were prepared in a similar manner from 18-day fetal rat lung maintained in explant culture for 24 h. These cells did not contain intracellular osmiophilic granules; the appearance of these granules could, however, be induced by hormones. For this reason they are considered to be pre-type II cells. The viability of the cultured cells was 97%. Both the differentiated and undifferentiated fetal type II cells specifically bound the Maclura pomifera lectin, a type II cell surface marker. The phospholipid profile of the fetal cells was similar to that of adult rat type II cells; the differentiated fetal cells, however, synthesized less phosphatidylcholine than the adult cells did, but more than the undifferentiated fetal cells. The differentiated fetal cells secreted phosphatidylcholine at a basal rate of 0.6% +/- 0.1% during a 90-min incubation. There was dose-dependent stimulation of phosphatidylcholine secretion after exposure to terbutaline. Maximum stimulation (76%) was observed at a concentration of 10 microM. This culture system provides a valuable model for studies of the maturation of the undifferentiated fetal type II cell and surfactant metabolism and secretion in the differentiated fetal type II cell.

Acetates↗

The biochemistry of fetal lung development.

Surfactant therapy for RDS is likely to become widespread in the near future. Animal data indicate that this will not preclude a role for hormonal acceleration of lung maturation. In studies with prematurely delivered and ventilated fetal rabbits, Fiascone et al. have shown that the administration of betamethasone antenatally improves lung compliance, as does intratracheal administration of excess amounts of adult rabbit natural surfactant. If the two therapies are combined, however, an additive effect is observed. This suggests that some of the effects of glucocorticoids on lung compliance are not related to surfactant. Prior glucocorticoid therapy may provide a benefit that differs from that of surfactant therapy because steroids mature the lungs anatomically and enhance nonsurfactant-related tissue compliance. It is also possible that surfactant therapy itself may be more effective in the presence of larger and increased numbers of alveoli. It thus seems likely that in the future both hormonal enhancement of lung maturation and surfactant therapy may be used in combination to further reduce the morbidity and mortality from RDS.

Animals↗

Meta-analyses of surfactant replacement therapy of infants with birth weights less than 2000 grams.

OBJECTIVES: We conducted a meta-analysis of surfactant replacement therapy to determine (1) the efficacy of surfactant therapy in the reduction of short-term morbidity and long-term outcome in terms of bronchopulmonary dysplasia (BPD) and mortality; (2) whether there are differences in efficacy between modified natural surfactant and synthetic surfactant; (3) the effectiveness of prophylactic surfactant therapy; and (4) whether there are differences in efficacy between the prophylactic approach and the rescue strategy. STUDY DESIGN: We included studies in which infants with birth weights between 500 and 1500 gm were eligible. Studies were grouped into the following categories: (1) rescue therapy with modified natural surfactant; (2) rescue therapy with synthetic surfactant; (3) prophylaxis with modified natural surfactant; (4) prophylaxis with synthetic surfactant; (5) prophylaxis versus rescue studies; (6) modified natural surfactant versus Exosurf (Burroughs-Wellcome Co., Research Triangle Park, NC) studies. The relative risk ratios, corrected for study size, were calculated for the outcome variables (pneumothorax, incidence of BPD, survival, survival without BPD, prevention of hyaline membrane disease [HMD], and intraventricular hemorrhage [IVH]). RESULTS AND CONCLUSION: Surfactant therapy is efficacious in reducing the risk for pneumothorax and increasing the chance for survival without BPD. Synthetic surfactant is not efficacious in the prevention of HMD. Modified natural surfactant is more effective in reducing the risk of pneumothorax and increasing the chance for survival without BPD than is synthetic surfactant. These data do not support the use of either synthetic or modified natural surfactant for routine prophylaxis.

Bronchopulmonary Dysplasia↗