PubMed Health⌕ Search

Biomedical subjects

D L Shapiro

Publications and source records attributed to D L Shapiro.

At least 37 records · Page 2Linked to original sources
PubMed1988

Changes in pulmonary mechanics after the administration of surfactant to infants with respiratory distress syndrome.

We assessed pulmonary mechanics in 35 premature infants with respiratory distress syndrome just before and one hour after the administration of 90 mg of surfactant to each infant. Transpulmonary pressure was measured between the airway opening and an esophageal balloon with use of a differential transducer, and flow rates were measured by a pneumotachometer. Values for pulmonary mechanics were then calculated by microcomputer processing. The administration of surfactant produced a large decrease (56 percent) in the mean (+/- SEM) ratio of alveolar to arterial oxygen, from 7.1 +/- 0.5 to 3.1 +/- 0.2 (P less than 0.0001)--a change that indicates improvement in gas exchange. Associated changes in pulmonary mechanics were not demonstrable when 10 of the infants were studied during continuous mechanical ventilation. However, in the 25 infants examined during spontaneous breathing with continuous positive airway pressures (identical airway pressures before and after treatment), large and consistent improvements in pulmonary mechanics were found after the administration of surfactant. Tidal volume increased by 32 percent (P less than 0.03), minute ventilation by 38 percent (P less than 0.02), dynamic compliance by 29 percent (P less than 0.004), and inspiratory flow rates by 54 percent (P less than 0.01). We conclude that significant improvement in pulmonary mechanics results from surfactant-replacement therapy for respiratory distress syndrome, but that these mechanical changes are apparent only during spontaneous respiration and can be masked if measurements are made during mechanical ventilation.

Humans↗
PubMed1988

Sequence and properties of the message encoding Tetrahymena hv1, a highly evolutionarily conserved histone H2A variant that is associated with active genes.

hv1 is a histone H2A variant found in the transcriptionally active Tetrahymena macronucleus, but not in the transcriptionally inert micronucleus. hv1 also contains antigenic determinants conserved in the histone complements of representatives of all four eukaryotic kingdoms. A cDNA clone encoding hv1 has been isolated and sequenced. Comparison of the derived protein sequence of hv1 with that of the chicken variant H2A.F and the sea urchin variant H2A.F/Z reveals remarkable homology in all but the extreme amino- and carboxy-termini and a small region in the conserved core. Putative regions of conserved antigenicity are discussed. Evidence is presented that suggests that hv1 is a single-copy, intron-containing gene that encodes a polyadenylated message. Unusual features in the 3' flanking sequence and in codon usage are also described. Evidence is also presented showing that hv1 message amounts are ten-fold greater in growing cells than in starved cells.

Amino Acid Sequence↗
PubMed1988

Diluted formula for beginning the feeding of premature infants.

To evaluate whether there is a preferable mode of advancing feedings in premature infants, 50 infants with birth weights of less than 1500 g were randomized into two groups. Twenty-eight infants were begun on a regimen of full-strength (FS) formula (84 J/30 mL [20 cal/oz]), and the volume of formula was advanced on a daily basis. Twenty-two infants received half-strength formula (equal parts, 84 J/30 mL [20 cal/oz] formula and water) and were advanced at twice the volume per feeding as the FS group. The groups were compared with respect to the amount of time needed to reach an enteral energy intake of 420 J (100 cal)/kg. The half-strength feeding group had fewer residuals and reached the indicated energy intake level earlier than infants in the FS group.

Energy Intake↗
PubMed1988

The development of surfactant replacement therapy and the various types of replacement surfactants.

This overview has been intended to ease the reader who is not familiar with the surfactant replacement field into this area. The discussion of various surfactants should help in the clarification of terminology use by different authors and provides a perspective for the following articles, which deal more completely with many of the issues raised in this article.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1988

Controversies regarding surfactant replacement therapy.

Surfactant replacement therapy for the respiratory distress syndrome is being actively studied in clinical trials. The therapy has great potential for reducing morbidity and mortality in premature infants. Some issues about surfactant replacement therapy are not yet clear, and a number of these are discussed in this article.

Humans↗
PubMed1987

Biophysical activity of synthetic phospholipids combined with purified lung surfactant 6000 dalton apoprotein.

This research studies the biophysical surface activity of synthetic phospholipids combined in vitro with purified lung surfactant apoprotein, having an Mr of 6000. Hydrophobic surfactant-associated protein (SAP-6) was delipidated and purified from both bovine and canine lung lavage, and was combined in vitro with a synthetic phospholipid mixture (SM) of similar composition to natural lung surfactant phospholipids. SM phospholipids were also combined and studied biophysically with another purified surfactant-associated protein, SAP-35. The biophysical activity of synthetic phospholipid-apoprotein combinants was assessed by measurements of adsorption facility and dynamic surface tension lowering ability at 37 degrees C. The SM-SAP-6 combinants had adsorption facility equivalent to natural lung surfactant, and to the surfactant extract preparations CLSE and surfactant-TA used in exogenous surfactant replacement therapy for the neonatal Respiratory Distress Syndrome (RDS). The synthetic phospholipid-SAP-6 combinants also lowered surface tension to less than 1 dyne/cm under dynamic compression in an oscillating bubble apparatus at concentrations as low as 0.5 mg phospholipid/ml. A striking finding was that this excellent dynamic surface activity was preserved as SAP-6 composition was reduced to values as low as 5 micrograms/5 mg SM phospholipid (0.1% SAP-6 protein), an order of magnitude less than the 1% protein content of CLSE and surfactant-TA. Mixtures of SM phospholipids plus SAP-35, the major surfactant glycoprotein, had significantly lower biophysical activity, which did not approach that of a functional lung surfactant. These results suggest that synthetic exogenous surfactants of potential utility for replacement therapy in RDS can be formulated by combining synthetic phospholipids in vitro with specifically purified, hydrophobic surfactant-associated protein, SAP-6.

Animals↗
PubMed1987

Exogenous lung surfactant: effect on radiographic appearance in premature infants.

At birth, premature infants of 25-29 weeks gestation, at high risk for development of neonatal respiratory distress syndrome (RDS), were given a single dose (90 mg) of calf lung surfactant extract (CLSE) by intratracheal instillation. The frequency and severity of RDS were assessed with use of a simple radiographic scoring system in which pulmonary parenchymal densities and the prominence of the air-bronchogram effect were used as indicators of widespread atelectasis. Radiographs were obtained in surfactant-treated and control infants within the first 90 minutes of life as part of an initial evaluation of their pulmonary status. Subsequent examinations were performed at less than 24 hours and less than 48 hours of age. Radiographic assessment of lung disease compared consistently with coordinated data on oxygen and mean airway pressure requirements of the infants. Both indicated a significantly decreased frequency and severity of RDS in the infants treated with surfactant. The results provide supporting evidence of the effectiveness of exogenous lung surfactant replacement in mitigating RDS in very premature infants.

Animals↗
PubMed1987

Lung surfactants for replacement therapy: biochemical, biophysical, and clinical aspects.

This article characterizes and analyzes current concepts of the pulmonary surfactant system, and its actions and importance in respiration. Much of the discussion concerns the fundamental role of lung surfactant in the respiratory distress syndrome (RDS) of premature infants, and the success of exogenous surfactant replacement in clinical therapy for this disease. In addition, basic descriptions of the biophysical and physiological activity of lung surfactant are provided to define mechanisms behind surfactant replacement therapy, and how it might be optimized by the further development of appropriate synthetic lung surfactant substitutes.

Animals↗
PubMed1986

Insulin receptors and insulin effects on type II alveolar epithelial cells.

Type II alveolar epithelial cells (pneumocytes) were isolated to purity from adult rabbits and analyzed for the presence of cell surface insulin receptors and for effects of insulin on cells. Assays were performed on cells cultured for 24 h in Eagle's minimum essential medium. Insulin binding to cells in culture approached a steady-state level by 180 min at 15 degrees C and remained constant for at least 1 h. Competition experiments using native insulin, proinsulin and desoctapeptide supported specificity of binding. Scatchard analysis of binding revealed a class of high-affinity receptors with Kd = 1.5 X 10(-10) M and a low-affinity component with Kd = 4 X 10(-9) M. The number of receptors was estimated at 2000-4000/cell. Insulin added to cell cultures of type II pneumocytes in concentrations from 5 X 10(-11) to 5 X 10(-8) M resulted in a dose-related increase in uptake of 2-deoxyglucose by cells. Insulin also stimulated the incorporation of choline and glucose into phosphatidylcholine and disaturated phosphatidylcholine.

Animals↗
PubMed1986

A quantitative study of the development of type II pneumocytes in fetal lung.

Cell populations dissociated from fetal rabbit lungs were analyzed by laser flow cytometry for the presence of type II pneumocytes. These cells are distinguishable by the staining of their lamellar bodies with the fluorescent lipophilic dye, phosphine-3R and by their intensity of low-angle light scatter. Lung cells were obtained by enzymatic dissociation from fetal rabbits at gestational ages of 24 d, 27 d, and from 2-d newborn rabbits. Flow cytometric analysis was sufficiently sensitive to discriminate between fetuses. Quantitative analysis of type II pneumocytes showed that newborn rabbits had a distinct cell subpopulation in a region of low-angle light scatter and phosphine-3R fluorescence intensity similar to that previously reported on type II cells from adult rabbits. By contrast, 24-d gestation rabbits had a negligible type II cell subpopulation. Fetuses of 27 and 30 d gestation showed a slow but progressive increase in the numbers of cells in the type II region. Mathematical analyses of light scatter and fluorescence intensity distributions were used to define statistically significant (P less than .05) boundaries that characterize the development of the type II cell subpopulation in fetal rabbit lung. The methods employed offer new possibilities for quantification of developing lung cell subpopulations of particular interest to the problem of respiratory distress syndrome in human neonates.

Age Factors↗
PubMed1986

Predictive biochemical assays for late radiation effects.

Surfactant precursors or other products of Type II pneumocytes have the potential to be the first biochemical marker for late radiation effects. This is particularly clinically important in the combined modality era because of the frequent occurrence of pneumonitis and pulmonary fibrosis secondary to radiation or chemotherapy. Accordingly, correlative studies have been pursued with the Type II pneumocyte as a beginning point to understand the complex pathophysiology of radiation pneumonitis and fibrosis. From our ultrastructural and biochemical studies, it is evident that Type II pneumocytes are an early target of radiation and the release of surfactant into the alveolus shortly after exposure persists for days and weeks. Through the use of lavaging techniques, alveolar surfactant has been elevated after pulmonary irradiation. In three murine strains and in the rabbit, there is a strong correlation with surfactant release at 7 and/or 28 days in vivo with later lethality in months. In vitro studies using cultures of type II pneumocytes also demonstrate dose response and tolerance factors that are comparable to the in vivo small and large animal diagnostic models. New markers are being developed to serve as a predictive index for later lethal pneumonopathies. With the development of these techniques, the search for early biochemical markers in man have been undertaken. Through the use of biochemical, histological, and ultrastructural techniques, a causal relationship between radiation effects on type II pneumocytes, pulmonary cells, endothelial cells of blood vessels, and their roles in the production of pneumonitis and fibrosis will evolve.

Animals↗
PubMed1986

Adsorption of natural lung surfactant and phospholipid extracts related to tubular myelin formation.

The microstructure of aqueous dispersions of pulmonary surfactant lipids extracted from bovine lung lavage was investigated by electron microscopic analysis. Following organic solvent extraction (chloroform/methanol) from natural lung surfactant, the mixed lipids (CLL), with 1% residual protein, were dispersed in water by two techniques, probe sonication at 4 degrees C and mechanical vortexing. Surface pressure-time adsorption isotherms were defined for the CLL dispersions, followed by staining with tannic acid, uranyl acetate, and lead citrate for electron microscopy of microstructure. CLL extract dispersions adsorbed in seconds to surface pressures near 45 dynes/cm (surface tension 25 dynes/cm) at low concentrations less than or equal to 0.25 mg/ml after dispersion by sonication of 4 degrees C and by mechanical vortexing. Ultrastructurally, the CLL dispersions were somewhat heterogeneous, but large thin-walled phospholipid vesicles, both intact and fragmented, predominated. No tubular myelin was formed. By contrast, natural lung surfactant (LS) from bronchoalveolar lavage had characteristic regions of tubular myelin when it adsorbed well at low concentrations (less than or equal to 0.25 mg phospholipid/ml). When divalent cations were removed from solution with 5 mM EDTA, this distinctive microstructure was not present and natural LS adsorbed less rapidly; higher concentrations of 0.63 mg phospholipid/ml were necessary for maximal adsorption of natural LS without tubular myelin. These results suggest that while tubular myelin is associated with optimal adsorption for natural LS, it is not a required configuration for rapid adsorption facility at low phospholipid concentrations in general. Specifically, for dispersions of surfactant extracts, other microstructures allow adsorption facility equivalent to that of natural LS with tubular myelin.

Adsorption↗
PubMed1986

Hydrophobic surfactant-associated protein in whole lung surfactant and its importance for biophysical activity in lung surfactant extracts used for replacement therapy.

Hydrophobic protein of 6,000 and 14,000 daltons was isolated from mammalian pulmonary surfactant obtained from canine, human, and bovine alveolar lavage material. Low molecular weight, hydrophobic, surfactant-associated protein (SAP), herein referred to as SAP 6-14, was distinguished from SAP-35, the major glycoprotein in mammalian surfactants (the 35,000 dalton glycoprotein A or apolipoprotein A) by amino acid composition, peptide mapping, and by resistance of SAP 6-14 to digestion by endoglycosidase F, collagenase, trypsin, and other proteases. The amino acid composition of SAP 6-14 was found to be highly enriched in leucine and other hydrophobic amino acids. The characteristics of protein isolated from bovine replacement surfactant extracts utilized for the treatment of hyaline membrane disease in humans were also studied. SAP 6-14 isolated from calf lung surfactant replacement extracts (CLSE) and surfactant-TA were found to be identical to SAP 6-14 isolated from ether/ethanol extracts of various mammalian surfactants. By contrast, SAP-35, the major surfactant-associated glycoprotein of molecular weight = 35,000, and other higher molecular weight proteins were not detected in significant quantities in the CLSE or surfactant-TA replacement surfactants, either by highly sensitive silver stain analysis or by immunoblot using monospecific antisera generated against bovine SAP-35. Biophysical studies of the CLSE replacement surfactant containing only SAP 6-14 and native phospholipids demonstrated full surface activity compared to natural lung surfactant. Dynamic surface tension lowering and adsorption properties of CLSE were essentially identical to those of freshly isolated bovine whole surfactant. Thus, hydrophobic SAP 6-14 is the only protein detected in bovine lung extract surfactants with full biophysical activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Lung surfactant replacement in premature lambs with extracted lipids from bovine lung lavage: effects of dose, dispersion technique, and gestational age.

Extracted bovine calf lung lipids (CLL) with minimal protein (approximately 1%) were instilled prior to ventilation in groups of premature lambs of average gestational ages of 127 and 133 days. Aqueous dispersions of CLL were prepared by two techniques prior to instillation: sonication in an ice bath (S) and mechanical vortexing at room temperature (V). A low surfactant dose (15 mg CLL/kg animal weight) and a high dose (100 mg/kg) were investigated for each dispersion technique. Following tracheal instillation of surfactant, lambs were ventilated with 100% oxygen for 2 h with umbilical circulation intact, and for up to an additional 10 h after separation. A clear improvement in blood oxygenation and lung compliance was found over controls for lambs given 15 mg/kg and 100 mg/kg CLL(V), and 100 mg/kg CLL(S). Lambs treated with 15 mg/kg CLL(S) failed to improve over controls. Experimental groups treated with equal doses of CLL(V) and CLL(S) had similar amounts of lung lavage phospholipid, with values progressively declining during ventilation. Analyses of in vitro surface properties showed that both vortexed and sonicated CLL dispersions adsorbed to equilibrium surface pressures of 45-47 dynes/cm in seconds at concentrations greater than or equal to 0.25 mg CLL/ml. Both dispersions also lowered surface tension to less than 1 dyne/cm under dynamic compression at 37 degrees C in 100% humidity, although CLL(V) showed some enhancement over CLL(S) in dynamic surface activity at low subphase concentration (0.5 mg/ml). Moreover, CLL(V) and CLL(S) differed markedly in their effects on pressure-volume mechanics in a surfactant-deficient excised rat lung model. Instilled CLL(V) dispersions improved excised lung pressure-volume mechanics at significantly lower concentrations than CLL(S) dispersions.

Animals↗
PubMed1985

Double-blind clinical trial of calf lung surfactant extract for the prevention of hyaline membrane disease in extremely premature infants.

A prospective, double-blind, controlled trial was conducted to determine whether instillation of an exogenous surfactant into the lungs before the first breath could prevent hyaline membrane disease. The surfactant is calf lung lipid extracted from saline lung lavage. Entry was limited to infants who were 24 to 28 weeks' gestation, who were born at Children's Hospital of Buffalo, and whose mothers had not received betamethasone for more than 24 hours before birth. Treated infants received 3 mL (90 mg) of calf lung surfactant extract instilled into their trachea before the first breath; control infants received 3 mL of normal saline. A prospective scoring system and respiratory support variables were used to compare the groups. At 48 hours of age, only two of 14 calf lung surfactant extract-treated infants (14%) had hyaline membrane disease compared with seven of 13 control infants (54%) (P = .033). Inspired oxygen, mean airway pressure, ventilator rate and ventilator efficiency index were also lower in the treated group during the first 48 hours of life (P less than .01 to P less than .001). Calf lung surfactant extract instillation at birth appears to be an effective material and method of preventing hyaline membrane disease in extremely premature infants.

Animals↗