UMLS:C0476273 - FACTA Search

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Query: UMLS:C0476273 (respiratory distress)
19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetuses of mothers with uncontrolled gestational diabetes have an increased risk of developing neonatal respiratory distress syndrome and are frequently hyperinsulinemic, thus it has been proposed that high levels of insulin delay fetal lung maturation. We have shown previously that insulin inhibits the accumulation of mRNA for the surfactant-associated proteins A and B (SP-A and SP-B) in human fetal lung explants maintained in vitro. To test the hypothesis that the inhibitory effects of insulin on the surfactant proteins are the result of a direct action of insulin on the lung epithelial cell, we evaluated the effects of insulin in the H441 cell line, a human pulmonary adenocarcinoma cell line that expresses SP-A and SP-B mRNA. We observed that insulin treatment for 48 h decreased SP-A mRNA and protein levels in a concentration-dependent manner when compared to controls. The inhibitory effect of insulin on SP-A mRNA levels was apparent as early as after 4 h of exposure. SP-B mRNA levels were also significantly decreased by insulin in a concentration-dependent manner. Insulin, at 2.5 microg/ml, inhibited SP-A gene transcription by approx. 67%, and inhibited SP-B gene transcription by about 32%. There was no significant effect of insulin on SP-A or SP-B mRNA stability. Thus, we have observed a pattern of insulin inhibition of SP-A and SP-B gene expression in the H441 lung epithelial cell line similar to that previously observed in human fetal lung explants, which are comprised of both epithelial and mesenchymal cells. Our findings provide further evidence that insulin may delay fetal lung maturation by inhibiting SP-A and SP-B gene expression. Furthermore, our findings suggest that the inhibitory effects of insulin are, at least partially, the result of a direct action on the lung epithelial cell.
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PMID:Insulin inhibits surfactant protein A and B gene expression in the H441 cell line. 976 11

Surfactant protein B is a small homodimeric protein that is found tightly associated with surfactant lipids in the alveolar space. In this review, we discuss the actions of SP-B on phospholipid membranes using information predominantly obtained from model membrane systems. We try to correlate these model actions with current concepts of SP-B structure and proposed biological functions. These functions may include critical roles in the intracellular assembly of surfactant through a role in lamellar body organogenesis, the structural rearrangement of secreted surfactant lipids into tubular myelin, and the subsequent rapid insertion of secreted surfactant phospholipids into the surface film itself. The relevance of SP-B to human biology is emphasized by the fatal respiratory distress that is associated with a genetic deficiency of SP-B and the important role of SP-B in certain exogenous surfactant formulations in wide clinical use.
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PMID:Structure and properties of surfactant protein B. 981 96

Surfactant therapy is an established part of routine clinical management of babies with respiratory distress syndrome. An initial dose of about 100 mg/kg is usually needed to compensate for the well documented deficiency of alveolar surfactant in these babies, and repeated treatment is required in many cases. Recent experimental and clinical data indicate that large doses of exogenous surfactant may be beneficial also in conditions characterized by inactivation of surfactant, caused by, for example, aspiration of meconium, infection, or disturbed alveolar permeability with leakage of plasma proteins into the airspaces. The acute response to surfactant therapy depends on the quality of the exogenous material (modified natural surfactants are generally more effective than protein-free synthetic surfactants), timing of treatment in relation to the clinical course (treatment at an early stage of the disease is better than late treatment, and may reduce the subsequent need for mechanical ventilation), and mode of delivery (rapid instillation via a tracheal tube leads to more uniform distribution and is more effective than slow airway infusion). Treatment with aerosolized surfactant improves lung function in animal models of surfactant deficiency or depletion, but is usually associated with large losses of the nebulized material in the delivery system. Furthermore, data from experiments on immature newborn lambs indicate that treatment response may depend on the mode of resuscitation at birth, and that manual ventilation with just a few large breaths may compromise the effect of subsequent surfactant therapy. The widespread clinical use of surfactant has reduced neonatal mortality and lowered costs for intensive care in developed countries. The hydrophobic surfactant proteins SP-B and SP-C are probably essential for optimal biophysical and physiological activity of exogenous surfactants isolated from mammalian lungs, and the dose-effectiveness (in part reflecting resistance to inactivation) can be further improved by enrichment with SP-A. The development of new artificial surfactant substitutes, based on synthetic analogues of the native surfactant proteins, is an important challenge for future research.
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PMID:Principles of surfactant replacement. 981 84

Natural surfactant preparations containing phospholipids and the hydrophobic surfactant proteins B and C (SP-B and SP-C) are effective in the treatment of respiratory distress syndrome in premature infants. The limited supply, and the risk of infectious agents and immunological reactions have promoted the evaluation of synthetic peptides in surfactant preparations. However, the folding of synthetic SP-C into an alpha-helix is inefficient and alpha-helical SP-C analogues with Val-->Leu substitutions form oligomers. In order to circumvent these problems we have synthesized an SP-C analogue, named SP-C(LKS), which differs from SP-C mainly by the exchange of most of the Val residues in positions 16-28 with Leu residues to promote an alpha-helical conformation, and by the introduction of Lys residues at positions 17, 22 and 27 in order to locate positive charges around the helical circumference and thereby avoid self polymerization. CD spectroscopy showed a spectrum typical for alpha-helical peptides and SDS/PAGE disclosed a single band. The biophysical activity of artificial surfactant preparations containing SP-C(LKS) and phospholipids, with and without native SP-B, was measured using a Wilhelmy balance and a pulsating bubble surfactometer. SP-C(LKS) (3%, w/w) in a mixture of 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/phosphatidylglycerol/palmitic acid (68:22:9, by wt.) suspended in 150 mM NaCl, showed rapid spreading at the air-liquid interface and produced a surface tension of <1 mN/m at minimum bubble size (gammamin) and 42 mN/m at maximum bubble size (gammamax) in the pulsating bubble surfactometer. The addition of 2% (w/w) SP-B to the preparation reduced the maximum surface tension to 33-35 mN/m, i.e. both gammamin and gammamax values were similar to those of natural surfactant preparations. Optimal in vitro characteristics were also obtained from a preparation containing SP-C(LKS), SP-B, DPPC and phosphatidylglycerol, i.e. when palmitic acid was omitted from the lipid mixture. SP-B containing surfactant preparations made up in Hepes buffer at pH 6.9, instead of in 150 mM NaCl, had similar biophysical activity provided that palmitic acid was omitted, but decreased activity in the presence of palmitic acid.
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PMID:Biophysical activity of an artificial surfactant containing an analogue of surfactant protein (SP)-C and native SP-B. 1019 Dec 70

Surfactant treatment in patients with acute respiratory distress syndrome (ARDS) may be a promising treatment strategy. The aim of this study was to investigate whether addition of a recombinant surfactant protein C (rSP-C) to a plain phospholipid (PL) surfactant (PL surfactant) can result in activity comparable to commercially available surfactant preparations (Alveofact and bLES) which contain surfactant protein B and C. In this investigation dose-response comparisons of four surfactants were performed in an animal model of ARDS induced by total lung lavage. The surfactants were given shortly (;10 min) after the last lavage. The effects of surfactant treatment were compared with respect to improve oxygenation and to prevent histopathological changes, such as hyaline membrane formation. The surfactants were compared to lavaged, untreated controls. The surfactants were administered at doses of 25, 50 and 100 mg total amount of phospholipids/kg body weight. At 120 min after early treatment, all three doses of rSP-C surfactant showed statistically significant higher improvements in oxygenation than PL surfactant. This improvement was comparable to bLES and superior to Alveofact. The rSP-C surfactant showed the most prominent effect on preventing hyaline membrane formation. It was again superior to PL surfactant and comparable to bLES. It is concluded that addition of rSP-C enhances the activity of a pure PL surfactant. The rSP-C surfactant showed comparable or even superior activity to bovine-derived surfactant preparations containing both, SP-B and SP-C.
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PMID:Effects of early treatment with rSP-C surfactant on oxygenation and histology in rats with acute lung injury. 1041 39

Surfactant preparations obtained from porcine lungs by extraction with chloroform/methanol followed by chromatography over Lipidex-5000 are used for treatment of respiratory distress syndrome in preterm infants. These preparations contain about 98% phospholipids and 1-2% of the hydrophobic pulmonary surfactant-associated proteins B and C (SP-B and SP-C). Separation of the proteins in the surfactant preparation by reversed-phase high performance liquid chromatography revealed, in addition to SP-B and SP-C, the presence of three peptides derived from the cathelicidin family of antibacterial peptides. The 79-residue proline-rich peptide prophenin (identical to that isolated from leukocytes), an 80-residue prophenin with an N-terminal pyroglutamic acid residue, and a C-terminal 18-residue fragment of prophenin were found in approximate molar ratios of 1:20:5. A synthetic version of the C-terminal 18-residue peptide exhibits salt-dependent antibacterial activity (higher activity in the absence of salt) against the Gram-positive bacterium Bacillus megaterium Bm11 and, to a lesser extent, against Gram-negative Escherichia coli D21 cells. It appears possible that the presence of prophenin peptides may contribute to the antibacterial properties of surfactant preparations.
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PMID:Porcine pulmonary surfactant preparations contain the antibacterial peptide prophenin and a C-terminal 18-residue fragment thereof. 1054 46

We report a case of a full-term female infant who presented with severe respiratory distress shortly after birth and died at 23 d of age with unremitting respiratory failure. Infectious and other known causes of respiratory disease in this clinical setting were excluded. Examination of a lung biopsy showed abnormal lung parenchyma with features reminiscent of desquamative interstitial pneumonitis. Ultrastructural studies revealed that alveolar type II cells lacked cytoplasmic lamellar bodies, while other organelles appeared normal. Histochemical and immunohistochemical investigations indicated normal alveolar type II cell marker expression including surfactant proteins (SP-A, SP-B, pro-SP-B, and pro-SP-C). Mutations in the coding sequences of the SP-B gene were excluded as a cause of disease. This case appears to be a novel congenital defect affecting the pulmonary surfactant system. The cellular abnormality may involve the assembly of cytoplasmic lamellar bodies in alveolar type II cells-the principal storage site of pulmonary surfactant.
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PMID:Deficiency of lamellar bodies in alveolar type II cells associated with fatal respiratory disease in a full-term infant. 1067 7

Several factors have been shown to influence the efficacy of exogenous surfactant therapy in the acute respiratory distress syndrome. We investigated the effects of four different alveolar environments (control, saline-lavaged, N-nitroso-N-methylurethane, and hydrochloric acid) on the metabolic and functional properties of two exogenous surfactant preparations: bovine lipid extract surfactant and recombinant surfactant-associated protein (SP) C drug product (rSPC) administered to each of these groups. The main difference between these preparations was the lack of SP-B in the rSPC. Our results demonstrated differences in the large aggregate pool sizes recovered from each of the experimental groups. We also observed differences in SP-A content, surface area cycling characteristics, and biophysical activities of these large aggregate forms after the administration of the two exogenous surfactant preparations. We conclude that the alveolar environment plays a critical role, influencing the overall efficacy of exogenous surfactant therapy. Thus further preclinical studies are warranted to investigate the specific factors within the alveolar environment that lead to the differences observed in this study.
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PMID:Alveolar environment influences the metabolic and biophysical properties of exogenous surfactants. 1071 Apr 4

Surfactant proteins B and C (SP-B and SP-C), together with phospholipids, are important constituents of pulmonary surfactant and of preparations used for treatment of respiratory distress syndrome (RDS). SP-B belongs to the saposin family of homologous proteins, which include other lipid-interacting proteins, like the membranolytic NK-lysin. SP-B, in contrast to other saposins, is hydrophobic and a disulfide-linked dimer, and its mechanism of action is not known. A model of the three-dimensional structure of one SP-B subunit was generated from the structure of monomeric NK-lysin determined by nuclear magnetic resonance, and the SP-B dimer was formed by joining two subunits via the intersubunit disulfide bond Cys48-Cys48'. After energy minimization, intersubunit hydrogen bonds/ion pairs were formed between the strictly conserved residues Glu51 and Arg52, which creates a central non-polar region located in between two clusters of positively charged residues. The structural features support a function of SP-B in cross-linking of lipid membranes. Mixtures of phospholipids, an SP-C analogue and polymyxin B (which cross-links lipid vesicles but is structurally unrelated to SP-B) exhibit in vitro surface activity which is indistinguishable from that of analogous mixtures containing SP-B instead of polymyxin B. This suggests an avenue for identification of SP-B analogues that can be used in synthetic surfactants for treatment of RDS.
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PMID:Pulmonary surfactant protein B: a structural model and a functional analogue. 1082 41

Mutations in the surfactant protein (SP)-B gene are responsible for SP-B deficiency in congenital alveolar proteinosis (CAP) (Nogee et al. J Clin Invest 1994: 93: 1860-1883; Lin et al. Mol Genet Metab 1998: 64: 25-35; Klein et al. Pediatrics 1998: 132: 244-248; Ballard et al. Pediatrics 1995: 96: 1046-1052). The multigenerational consanguineous pedigree under study does not carry any of the known mutations, although this pedigree had 14 infant deaths following respiratory distress at birth. Immunostaining of the lungs from three such infants revealed decreased or absent SP-B. By sequencing of SP-B exons, exon-intron junctions, and the 5' and 3' flanking regions, nine polymorphisms were found in this pedigree, but none of them could explain the observed SP-B deficiency. Further analysis of SP-B mRNA by reverse transcription-polymerase chain reaction from paraffin-embedded lung tissue of CAP patients showed that SP-B mRNA is not intact. Although the sequence of mRNA from exon 1-exon 7 and from exon 8-exon 10 could be amplified, the region between exons 7 and 8 could not. From fluorescence in situ hybridization of the short arm of chromosome 2p, only 2 signals were identified, eliminating the possibility of translocation as the cause of the SP-B mRNA aberrance. Although the nature of the genetic basis of SP-B deficiency in this family is currently unknown, the existence of aberrant SP-B mRNA may, at least in part, be responsible for the SP-B deficiency in this pedigree.
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PMID:Aberrant SP-B mRNA in lung tissue of patients with congenital alveolar proteinosis (CAP). 1085 70

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