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

Natural surfactant, a mixture of lipids and proteins is potentially immunogenic. Frequent therapeutic and prophylactic use of exogenous lung surfactants necessitates a review of the data on its influence and relation to the immune system. Detection of circulating surfactant-antisurfactant immune complexes in the serum of newborn with respiratory distress syndrome and sporadically of free antisurfactant antibodies was not associated with any other specific symptoms during short term survey. Several studies were unable to detect formation of specific surfactant protein B or C antibodies in response to treatment with bovine surfactants. However further and long term follow up of these neonates especially during newly acquired lung diseases is desirable. In addition to its antigenicity, surfactant participates in a complex manner in the local immune response of the lung. Due to its direct bactericidal effects for some bacteria and various interactions with alveolar macrophages, lymphocytes and monocytes, surfactant is specifically involved in the defense of pulmonary pathogens. Furthermore there is evidence for a modulation and suppression of immune responses in the terminal alveoli by surfactant. These immunological aspects of lung surfactant need further study.
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PMID:[Pulmonary surfactant and the immune system]. 156 9

An artificial pulmonary surfactant prepared from chloroform-methanol extract of bovine pulmonary surfactant (surfactant TA) has been shown to be effective in both the prevention and the treatment of respiratory distress syndrome in premature babies. Recently, two types of protein-free totally synthetic surfactants, artificial lung expanding compound (ALEC) and Exosurf, have been evaluated in clinical trials of surfactant therapy. Artificial lung expanding compound was used initially as a dry powder, but is now prepared as a crystalline suspension in saline at 4 degrees C. In this study we compared the biophysical properties of three different forms of ALEC (dry powder, crystalline suspension at 4 degrees C and 37 degrees C), Exosurf and surfactant TA (Surfacten) using a modified Wilhelmy surface balance and a pulsating bubble surfactometer. Surface activity of a crystalline suspension of ALEC in cold saline was no better than the dry powder of ALEC. Surfactant activity of ALEC was improved by addition of hydrophobic surfactant protein B and C (SP-B, SP-C) which are important constituents of surfactant TA. Surface properties of ALEC in any form and Exosurf were not superior to those of surfactant TA. These results suggest that a surfactant which contains SP-B and SP-C does not necessarily have to be dry or crystalline for an effective exogenous surfactant.
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PMID:Biophysical properties of protein-free, totally synthetic pulmonary surfactants, ALEC and Exosurf, in comparison with surfactant TA. 787 68

The present study was undertaken to determine if a synthetic peptide, KLLLLKLLLLKLLLLKLLLLK (KL4), in which K = lysine and L = leucine, in an aqueous dispersion of phospholipids (DPPC and POPG), would expand pulmonary alveoli and improve gas exchange in premature human infants with respiratory distress syndrome (RDS). The KL4 peptide was synthesized to resemble the amino acid pattern of surfactant protein B (SP-B). Forty-seven infants with RDS were treated within 4 h of birth with the KL4-peptide/phospholipid mixture, called KL4-Surfactant. The average arterial-to-alveolar oxygen tension ratios (a/A O2) of 39 patients included in efficacy analyses rose from pretreatment values of 0.14 +/- 0.02 (mean +/- SEM) to 0.40 +/- 0.04 (normal value > or = 0.40) by 12 h of age. Mean airway pressures and oxygenation index values fell concomitantly, and expansion of the lungs was observed on radiographs. The median duration of mechanical ventilation was 5.0 d. Of the 39 included infants, 29 required only a single dose. Radiographic data indicate that those patients requiring a second instillation of KL4-Surfactant but not showing a sustained rise in a/A O2 ratios did, in fact, exhibit expansion of alveoli in the lung. There were no RDS-related deaths; the incidence of complications was no higher than found in other comparable published studies. The data demonstrate that the synthetic peptide, KL4, which mimics the hydrophobic and hydrophilic pattern of SP-B, when formulated in an aqueous dispersion with the phospholipids DPPC and POPG, creates a strong and durable surfactant activity as judged by expansion of pulmonary alveoli and improvement of gas exchange in infants with RDS.
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PMID:The efficacy and safety of KL4-surfactant in preterm infants with respiratory distress syndrome. 854 50

Since the late 1950s it has been known that the cause of respiratory distress syndrome (RDS) is surfactant deficiency, especially in preterm infants. But surfactant protein B deficiency may cause RDS in term infants as well. Administration of natural surfactant produce is well known to a rapid improvement in oxygenation within 15 to 20 minutes. The effect of synthetic surfactant is less dramatic. Although randomized controlled trials have been done, the majority have been relatively small. Studies on the role of natural surfactant given to infants with established RDS (rescue therapy) have shown a reduction in the incidence of neonatal death and pneumothorax of 40% and 65%, respectively, compared to untreated infants. However, natural surfactant provides no apparent benefits in terms of the incidence of intraventricular hemorrhage (IVH), patent ductus arteriosus (PDA) or bronchopulmonary dysplasia (BPD). The results of synthetic surfactant given as rescue therapy have shown a similar effect with a 40% reduction in mortality and a 48% reduction in pneumothorax. However, synthetic surfactant also led to a 23% reduction in IVH, 27% in PDA, and 32% in BPD. When natural surfactant is given as prophylaxis (i.e. at or soon after birth, before the development of RDS), the reduction in mortality is 45% and the reduction in pneumothorax is 69%, but as with rescue therapy, there is no effect on the incidence of IVH or BPD. The effect on the incidence of PDA is an increase of 27%. When synthetic surfactants are given prophylactically, there is a similar reduction in mortality of 44% and a reduction in pneumothorax of 36%. The incidence of IVH and BPD is unchanged, but as with the natural surfactant, there is a small increase in the incidence of PDA of 27%. The main side effect is pulmonary hemorrhage that has been reported to occur in 4-7% of infants given surfactant. Although the administration of surfactant has had a dramatic effect on neonatal practice, it is likely that further studies will lead to more appropriate use of surfactant.
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PMID:Surfactant and respiratory distress syndrome. 881 19

Studies were conducted to assess the efficacy and safety of a synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome (RDS) in preterm (approximately 80% of normal gestation) infant rhesus monkeys. Surfactant was prepared consisting of the phospholipids dipalmitoylphosphatidyl choline and palmitoyl-oleoyl phosphatidyl glycerol and a synthetic peptide modeled after surfactant protein B (SP-B), "KL4-Surfactant" contained a peptide having the sequence KLLLLKLLLLKLLLLKLLLLK, where "K" is lysine and "L" is leucine. The peptide was selected because it mimics the repeating stretches of hydrophobic residues with intermittent basic hydrophilic residues seen in SP-B. KL4-Surfactant was shown to have biophysical activity assessed as the ability to lower surface tension at an air-liquid interface in a pulsating bubble surfactometer. Thirty premature rhesus monkeys were treated shortly after birth with one dose of KL4-Surfactant. The arterial to alveolar oxygen partial pressure ratio (a/A) was found to rise from a pretreatment level of 0.11 +/- 0.01 (mean +/- SEM), indicative of severe RDS, to 0.40 +/- 0.02 at 12-13 h post-treatment. The improvement in oxygenation persisted throughout the study period, with a mean a/A at 22-23 h of 0.45 +/- 0.07. Chest radiographs and gross and microscopic examination of the lungs all confirmed the reversal of the atelectasis seen before treatment. Animals treated with a dose of 200 mg/kg showed a faster, more consistent, and greater response than did a group treated with an average dose of 127 mg/kg. There was no evidence of toxicity after treatment with the higher dose as demonstrated by physiologic, hematologic, biochemical, and pathologic data. The importance of the peptide in the synthetic surfactant was apparent from the results obtained with a control group of nine premature monkeys treated with a non-peptide-containing surfactant; the a/A of this group was 0.15 +/- 0.03 at nine hours of age as compared with a value of 0.38 +/- 0.02 for 30 comparable animals receiving KL4-Surfactant.
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PMID:Efficacy of synthetic peptide-containing surfactant in the treatment of respiratory distress syndrome in preterm infant rhesus monkeys. 884 50

Variable numbers of composite repetitive motifs are found in different individuals within intron 4 of the surfactant protein B (SP-B) gene (Biochem J. 1995;305:583). This study tests the hypothesis that the distribution of SP-B alleles differs among racial/ethnic groups. A total of 412 SP-B alleles were analyzed: 206 from Caucasian, 68 from African-American, and 138 from Nigerian individuals. Twelve groups of alleles (A-L) carrying 3 to 18 motifs were found. The distribution of the 12 alleles in the Caucasian group differs from that found in the Nigerian (p < .001) and African-American (p < .001) populations. The overall distribution of alleles between the African-American and the Nigerian populations were not statistically different. Specific alleles were also present in different proportions among the groups studied. For example, the most common allele (allele E) in all three populations is present at a significantly higher frequency in Caucasians than in the other two populations, but its frequency does not differ from the Nigerian and African-American groups. A less frequent allele, H, also differs significantly when Caucasians are compared with each of the other two populations, but the frequency of this allele is comparable between the African-American and Nigerian populations. To assess the importance of having comparable racial composition between the control and the case groups, a group of African-Americans with respiratory distress syndrome (RDS) (n = 40) was compared with the African American and the Caucasian groups studied above. No significant difference was observed between the racially matched groups but a significant difference (p = .006) was observed between the racially mixed groups. The results indicate that the distribution of SP-B alleles differs between the racial groups but not between the ethnic groups studied. Thus, racial composition of the groups under study is important when considering whether particular alleles at this locus predispose to inherited disorders.
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PMID:Racial differences in allelic distribution at the human pulmonary surfactant protein B gene locus (SP-B). 887 90

Genetic ablation of the murine SP-B gene in transgenic mice caused lethal perinatal respiratory distress in homozygous offspring, whereas heterozygous SP-B (+/-) mice survived postnatally. In adult SP-B(+/-) mice, surfactant protein B mRNA and the alveolar lavage SP-B protein were reduced by 50% compared with wild-type littermates, consistent with the inactivation of a single SP-B allele. Expression of SP-A, SP-C, and SP-D proteins was not affected in SP-B(+/-) mice. Heterozygous SP-B(+/-) mice reached maturity in numbers expected by Mendelian inheritance of a recessive gene. Lung morphology and both intracellular and extracellular phospholipid pool size and composition were unaltered in the SP-B(+/-) mice. Despite normal survival, pulmonary function studies demonstrated a consistent decrease in lung compliance in SP-B(+/-) mice. Abnormalities of inflation/deflation curves demonstrated airway collapse at low deflation pressures. Residual volumes were increased in the SP-B(+/-) mice. In summary, SP-B mRNA and SP-B protein were reduced by 50% in SP-B(+/-) mice, resulting in abnormalities of lung compliance and air trapping, suggesting a potential susceptibility to pulmonary dysfunction associated with SP-B deficiency.
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PMID:Decreased lung compliance and air trapping in heterozygous SP-B-deficient mice. 899 78

Two infants presenting with respiratory distress in the first 24 h of life are described. Both patients underwent extensive investigation before the diagnosis of surfactant protein B-deficiency was reached. Both children died within 2 months of birth. Parental consanguinity was known to be a feature in the first case, who proved to have a previously unrecognized mutation of the surfactant protein B gene. In the second case, a history of parental consanguinity was not sought from the Caucasian family, but was later volunteered by the parents themselves. Case 2 proved to have the "common" surfactant protein B-deficient genotype. The key to diagnosis is having a high index of suspicion in any term or near-term newborn with severe respiratory distress; parental consanguinity must be excluded. Surfactant protein B-deficiency can be readily diagnosed from bronchoalveolar lavage specimens; a simple, inexpensive procedure which is well tolerated in newborns.
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PMID:Neonatal respiratory distress in near-term infants--consider surfactant protein B deficiency. 917 34

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

We identified an alternatively-spliced surfactant protein B (SP-B) mRNA from normal human lung with a 12 nt deletion at the beginning of exon 8. This deletion causes a loss of four amino acids in the SP-B precursor protein. Sequence comparison of the 3' splice sites reveals only one difference in the frequency of U/C in the 11 predominantly-pyrimidine nucleotide tract, 73% for the normal and 45% for the alternatively-spliced SP-B mRNA (77-99% for the consensus sequence). Analysis of SP-B mRNA in lung indicates that the abundance of the alternatively-spliced form is very low and varies among individuals. Although the relative abundance of the deletion form of SP-B mRNA remains constant among normal lungs, it is found with relatively higher abundance in the lungs of some individuals with diseases such as congenital alveolar proteinosis, respiratory distress syndrome, bronchopulmonary dysplasia, alveolar capillary dysplasia and hypophosphatasia. This observation points to the possibility that the alternative splicing is a potential regulatory mechanism of SP-B and may play a role in the pathogenesis of disease under certain circumstances.
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PMID:An alternatively spliced surfactant protein B mRNA in normal human lung: disease implication. 1049 23


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