Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0476273 (respiratory distress)
 19,632 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary surfactant, a protein-phospholipid mixture, maintains surface tension at the lung epithelium/air interface preventing alveolar collapse during respiration. For mammals appropriate developmental production of surfactant is necessary for adaptation to the air breathing environment. Deficiency of pulmonary surfactant results in respiratory distress syndrome (RDS), a leading cause of death in premature infants. Recently, three lung-specific pulmonary surfactant proteins designated SP-A, SP-B, and SP-C have been described. Cloned sequences for the genes that encode each of these proteins have been partially characterized in humans and other species. Analysis of interspecific backcross mice has allowed us to map the chromosomal locations of these three genes in the mouse. The gene encoding SP-A (Sftp-1) and the gene encoding SP-C (Sftp-2) both map to mouse chromosome 14, although at separate locations, while the gene encoding SP-B (Sftp-3) maps to chromosome 6. The mouse map locations determined in this study for the Sftp genes are consistent with the locations of these genes on the human genetic map and the syntenic relationships between the human and the mouse genomes.
 ...
PMID:Chromosomal localization of three pulmonary surfactant protein genes in the mouse. 134 79

Surfactant-associated protein (SP-A) was measured in tracheal aspirates of ventilated infants with (n = 51) and without (n = 21) respiratory distress syndrome (RDS). SP-A concentrations in samples collected after birth were significantly lower in RDS than in infants ventilated for other reasons than RDS (median 0.03 vs. 1.60 micrograms/ml). As a biochemical test to diagnose RDS early after birth, the sensitivity of measuring SP-A in tracheal aspirates was 87% and specificity 81%. SP-A content in tracheal aspirates of infants with RDS was monitored during the first 7 days of life. A significant (P less than 0.001) increase within the first 4 days was found in those infants who survived, whereas no such change was found in those infants who died.
 ...
PMID:Surfactant protein A in the course of respiratory distress syndrome. 150 80

Neutrophil elastase activity and the concentration of surfactant proteins A and B (SP-A, B) were measured in tracheal aspirate fluid from preterm neonates who were treated with the synthetic surfactant Exosurf Neonatal or air placebo in randomized, placebo-controlled, clinical trials. Elastase activity was transiently reduced in surfactant-treated infants on the second day of life, but the reduction was not sustained. In placebo-treated infants with established respiratory distress syndrome, tracheal aspirate SP-A was low on the first day of life and increased with time as respiratory distress syndrome resolved. In infants with respiratory distress syndrome treated with surfactant, significantly higher levels of SP-A were observed by 2 days after treatment and were maintained through at least the sixth day of life. These data suggest that lung inflammation is not increased and that endogenous surfactant secretion may be stimulated, not suppressed, by treatment with synthetic surfactant.
 ...
PMID:Elastase activity and surfactant protein concentration in tracheal aspirates from neonates receiving synthetic surfactant. 173 50

Human pulmonary surfactant contains four groups of apoproteins, SP-A, B, C and D. We determined the concentration of SP-A in the tracheal aspirate of newborn infants by a two-site simultaneous immunoassay with monoclonal antibodies, and used this assay to assess changes in surfactant in various clinical situations. SP-A concentrations were standardized per milligram of albumin in the aspirate. The ratio of SP-A/albumin (micrograms/mg) in tracheal aspirates of 18 preterm infants with respiratory distress syndrome (RDS), in which samples were obtained within 12 hours of birth, was significantly lower (0.2 +/- 0.1 microgram/mg, mean +/- S.D.) compared to a group of 20 non-RDS preterm infants of similar gestational age (15.8 +/- 7.4 micrograms/mg) (p less than 0.05). None of the RDS infants had a SP-A/albumin ratio above 1 microgram/mg within 12 hours of birth, but the ratio exceeded 5 micrograms/mg in all samples from non-RDS infants. The SP-A/albumin ratio significantly increased, however, at 48 to 72 hours after birth in infants with RDS (15.7 +/- 9.5 micrograms/mg). During the recovery phase of RDS, no difference was evident in the SP-A/albumin ratio in babies treated with artificial surfactant compared to those not treated.
 ...
PMID:Surfactant apoprotein A (SP-A) in tracheal aspirates of newborn infants with RDS. 179 20

The presence of surfactant protein antigenemia and of surfactant protein antibodies was determined in serum from surfactant-treated and control infants with respiratory distress syndrome who were enrolled in a prospective randomized clinical trial. The surfactant used for treatment (surfactant TA) contained surfactant proteins (SPs) B and C and no SP-A. Enzyme-linked immunosorbent assays (ELISAs) that identify surfactant-associated proteins and ELISAs that identify IgG or IgM directed against surfactant proteins were used to investigate sera from these infants obtained prior to treatment, at 1 week of age, and at 2 months of age. There were no significant differences between average values in the surfactant-treated and control groups at each time period. However, in the control group, averaged results from ELISAs that identify SP-A and that identify IgM antibodies to SP-A or to SP-B, C showed significant differences between pretreatment sera and sera obtained at 1 week of age. No significant differences were noted in averaged results for IgG. Positive ELISA values were more frequently found in the control group than in the surfactant-treated group with regard to SP-A, and IgM against SP-A and SP-B, C in sera from neonates at 1 week of age. No positive ELISA values were found in sera from infants at 2 months of age. It is concluded that some patients with severe respiratory distress syndrome presumably leak surfactant proteins into the circulation and that this induces transient low titers of IgM antibody. This occurrence is decreased with surfactant treatment. Surfactant treatment may reduce leak of surfactant proteins into the vascular space by reducing lung damage.
 ...
PMID:Surfactant proteins and anti-surfactant antibodies in sera from infants with respiratory distress syndrome with and without surfactant treatment. 205 77

Congenital pulmonary alveolar proteinosis (CPAP) is a fatal disease of full-term infants that is unresponsive to current medical therapy. It is now recognized that at least some forms of this disorder are associated with a deficiency of SP-B, one of the surfactant-associated proteins, as well as probable aberrations in the surfactant-associated proteins SP-A and SP-C. Given these developments, it is logical to hypothesize that CPAP may be amenable to gene therapy, in which the human SP-B cDNA, and possibly the cDNAs of the other surfactant associated proteins, are transferred to the epithelium of the lower respiratory tract. We constructed replication-deficient, recombinant adenovirus vectors in which a constitutive viral promoter drives the expression of the DNAs for the surfactant-associated proteins, SP-B (AdCMV.SP-B) and SP-A (AdCMV.SP-A). Following infection of the human lung A549 epithelial cell line with these vectors in vitro, the appropriately sized mRNAs for these cDNAs were detected, whereas cells infected with a control virus or uninfected cells produced none. Western blots demonstrated expression of these proteins, including appropriate processing of the hydrophobic protein, SP-B. Following in vivo intratracheal infection of rats with these vectors, Northern analysis of the lungs revealed appropriately sized mRNAs for these cDNAs whereas rats infected with control virus or uninfected rats show no hybridization with the human surfactant-associated protein probes. In the AdCM-V.SP-A-infected rats, Western blots confirmed the overproduction of the human SP-A protein in both the bronchoalveolar lavage and lung homogenates compared to controls. Thus, it is feasible to utilize adenovirus vectors to transfer and express the human surfactant associated protein cDNAs in vitro and in vivo, presenting a possible mode of therapy for CPAP, as well as other surfactant deficiency states such as the neonatal respiratory distress syndrome and possibly the adult respiratory distress syndrome.
 ...
PMID:In vitro and in vivo transfer and expression of human surfactant SP-A- and SP-B-associated protein cDNAs mediated by replication-deficient, recombinant adenoviral vectors. 777 11

Vitamin A (retinol) may play an important role in lung maturation: 1) premature delivery is simultaneously a source of vitamin A deficiency and increased risk of neonatal respiratory distress syndrome and subsequent bronchopulmonary dysplasia (BPD), due to deficit in pulmonary surfactant; 2) neonatal supplementation with retinol reduces the risk of BPD; and 3) fetal rat lung stores retinol in late gestation just before the onset of surfactant synthesis. To test the hypothesis of an implication of retinoids in the control of pulmonary surfactant synthesis, experiments were designed in the pregnant rat, aiming either at enhancing fetal lung vitamin A stores, bringing the active metabolite of vitamin A, retinoic acid (RA), or inhibiting the conversion of retinol to RA with aid of citral. Maternal administration of a single dose of 50,000 IU of retinyl palmitate on day 16 (term 22 days) increased 22 and 29%, respectively, the total phospholipid (TPL) and disaturated fraction of phosphatidylcholine (PC) in extracted fetal surfactant on day 19 but did not change surfactant protein (SP) A concentration. Chronic administration of retinyl palmitate to the mother from day 16 through 20 increased disaturated PC content on day 21 but decreased SP-A concentration. Fetal lung surfactant phospholipids were increased by chronic administration of RA and considerably reduced by citral (-31 and -35% for TPL and PC concns, respectively). RA also enhanced labeled choline incorporation into fetal lung PC on day 20. Given once on day 17, it accelerated the appearance of surfactant precursors on day 18.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Retinoids control surfactant phospholipid biosynthesis in fetal rat lung. 802 60

The structural and functional integrity of pulmonary surfactant depends on several specific proteins. Two of these, SP-A and SP-D, are large and water-soluble, while SP-B and SP-C are small and very hydrophobic. SP-A is an 18-mer of 26 kDa polypeptide chains and contains N-linked oligosaccharides. Structurally, it can be characterized as a collagen/lectin hybrid. Together with SP-B, SP-A is required for conversion of secreted endogenous surfactant to tubular myelin in the alveolar lining. It also regulates surfactant secretion and reuptake of surfactant lipids by type II cells; these functions are probably receptor mediated. SP-D, a 12-mer of 39 kDa polypeptide chains, is a collagenous glycoprotein with structural similarities to C-type lectins. Both SP-A and SP-D stimulate alveolar macrophages. SP-B is a 79-residue polypeptide that contains three intrachain disulphide bridges. It exists mainly as a homodimer, which is strongly positively charged and may selectively remove anionic and unsaturated lipid species from the alveolar surface film, thereby increasing surface pressure. SP-C is a mainly alpha-helical, extraordinarily hydrophobic polypeptide containing 35 amino acid residues and covalently linked palmitoyl groups. Its alpha-helical portion is inserted into surfactant lipid bilayers. SP-C accelerates the adsorption of lipid bilayers to an interfacial monolayer. In babies with respiratory distress syndrome, the clinical response to treatment with surfactant containing SP-B and SP-C is much faster than in babies treated with protein-free synthetic surfactant. We speculate that, in the near future, surfactant preparations based on recombinant hydrophobic proteins will be available for clinical use.
 ...
PMID:The proteins of the surfactant system. 816 91

The failure of some infants with respiratory distress syndrome to respond to therapy with surfactant may be explained in part by inactivation of surfactant caused by leakage of plasma constituents into air spaces. Surfactant-associated proteins (SP-A, SP-B and SP-C) reduce the susceptibility of surfactants to inactivation in vitro. To study this phenomenon further, we used full length synthetic proteins, SP-B [1-78] and SP-C [1-31], mixed with surfactant lipids in different ratios and different concentrations. Equilibrium and minimum surface tensions of these mixtures, with or without serum and calcium, were measured using a pulsating surfactometer. Mixtures containing both SP-B and SP-C had optimal minimum and equilibrium surface tensions of < 5 and < 28 mN/m, respectively. Mixtures with SP-B had optimal minimum surface tensions, but equilibrium surface tensions averaged 35 mN/m. Mixtures with SP-C had high minimal (19 mN/m) and high equilibrium surface tensions (35 mN/m). When serum was added to these mixtures, the least inactivation was found with mixtures containing 3% protein at 1:1 ratio of SP-B/SP-C with 2 mM calcium chloride. These data indicate that SP-B and SP-C, particularly in the presence of calcium, reduce surfactant inactivation that may be caused by plasma constituents. The results lead to the hypothesis that charge interactions among ions, lipids, surfactant proteins, and serum inactivators are a major element in pathophysiological surfactant inactivation.
 ...
PMID:Full length synthetic surfactant proteins, SP-B and SP-C, reduce surfactant inactivation by serum. 832 72

With the advent of surfactant replacement therapy, there is an increasing need for a rapid test of predicting the development of respiratory distress syndrome (RDS). We evaluated the clinical usefulness of the stable microbubble (SM) test in predicting the development of RDS by comparison with other tests in amniotic fluid samples obtained within 12 h before delivery from 40 pregnancies between 23-35 weeks of gestation. These tests included the lecithin/sphingomyelin (L/S) ratio, disaturated phosphatidylcholine/sphingomyelin (DSPC/S) ratio, concentrations of lecithin, DSPC, and surfactant-associated proteins A and B, C (SP-A, SP-B,C). The cut-off value of each test for predicting RDS was determined at a point of maximum diagnostic accuracy. The overall diagnostic accuracy of the SM test was similar to that of other tests. However, both the SM test and the SP-B,C concentration had positive predictive values of 100%. We conclude that the rapid (< 10 min) and reliable information obtained by this test should encourage its use in defining a population of neonates with surfactant deficiency in a multicentre trial of prophylactic surfactant therapy.
 ...
PMID:Stable microbubble test for predicting the risk of respiratory distress syndrome: I. Comparisons with other predictors of fetal lung maturity in amniotic fluid. 844 24


1 2 3 4 5 6 7 8 9 Next >>