Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C-->T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9% vs 41.7%, chi2 = 4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1%) of SP-B1580-18A/C locus is lower than T allele (70.9%) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85% and 15% respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.
Alleles ; China/ethnology ; Genetic Predisposition to Disease/*genetics ; Genotype ; Polymorphism, Genetic/*genetics ; Pulmonary Disease, Chronic Obstructive/*genetics ; Pulmonary Surfactant-Associated Protein B/*genetics ; Pulmonary Surfactant-Associated Protein B/physiology ; Smoking/genetics

<b>OBJECTIVEb>To investigate the effects of maternally administered dexamethasone and ambroxol on the mRNA levels of surfactant proteins (SP-A, SP-B and SP-C) expression in fetal rat lungs at gestational age day 19.

<b>METHODSb>A 19-day fetal rat lung model was employed. In situ hybridization was used to detect the expression of SP-B mRNA in alveolar type II cell, and the levels of SP-A, SP-B and SP-C mRNAs were detected by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).

<b>RESULTSb>(1) SP-B mRNA was detected in situ in alveolar type II cells in fetal rat lung of day 19 gestational age; (2) In the late developmental period of fetal rat lungs, alveolar type II cells were also found around bronchus; (3) Comparing to beta-actin mRNA, the relative values of SP-A, SP-B and SP-C mRNAs were 0.81 +/- 0.26, 0.97 +/- 0.20 and 0.88 +/- 0.11 in fetal lung in the control group. The relative values of mRNAs of SP-A, SP-B and SP-C to beta-actin were 1.04 +/- 0.16, 1.28 +/- 0.29, 1.09 +/- 0.25 in fetal lungs of the ambroxol injected rats, and were 1.08 +/- 0.25, 1.23 +/- 0.35, 1.21 +/- 0.25 in fetal lungs of the dexamethasone injected rats, respectively. Both ambroxol and dexamethasone-treated rats had significantly higher mRNA expression of surfactant proteins compared to the control saline injected animals (P < 0.05). (4) There were no significant differences between ambroxol and dexamethasone in the effects of increasing expressions of surfactant protein mRNAs (P > 0.05).

<b>CONCLUSIONb>Antepartum administration of both ambroxol and dexamethasone can significantly increase fetal lung SP-A, SP-B and SP-C mRNAs expression.

Ambroxol ; pharmacology ; Animals ; Dexamethasone ; pharmacology ; Expectorants ; pharmacology ; Female ; Gene Expression Regulation, Developmental ; drug effects ; Glucocorticoids ; pharmacology ; Lung ; drug effects ; embryology ; metabolism ; Pregnancy ; Pulmonary Surfactant-Associated Protein A ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactant-Associated Proteins ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction

<b>OBJECTIVEb>To review the pathophysiology, evaluation, management, and outcomes of children with inherited disorders of surfactant metabolism due to mutations in the genes encoding surfactant proteins-B or -C (SFTPB, SFTPC), ATP binding cassette member A3 (ABCA3), and thyroid transcription factor (NKX2.1).

<b>DATA SOURCESb>Review of the literature, previous work from the author's and collaborators' laboratories, St. Louis Children's Hospital Lung Transplant Database.

<b>STUDY SELECTIONb>Key articles in the field, author's work.

<b>RESULTSb>Inherited disorders of surfactant metabolism present as acute, severe respiratory dysfunction in the neonatal period (SFTPB, ABCA3, NKX2.1) or as chronic respiratory insufficiency in later infancy and childhood which is of variable onset, severity, and course (SFTPC, ABCA3, NKX2.1). Diagnosis is established with sequencing the relevant genes; lung biopsy with electron microscopy is a useful adjunct. For surfactant protein-B and ABCA3 deficiency presenting with acute neonatal disease, treatment options are limited to lung transplantation or compassionate care. For the more chronic presentations of surfactant protein-C, ABCA3, and NKX2.1 associated disease, the natural history is variable and therefore individualized, supportive care is appropriate,

<b>CONCLUSIONSb>Inherited disorders of surfactant metabolism are rare, but informative diseases that provide unique opportunities for understanding mechanisms of respiratory disease in newborns and children.

ATP-Binding Cassette Transporters ; genetics ; Humans ; Infant, Newborn ; Lung Diseases ; diagnosis ; etiology ; therapy ; Lung Transplantation ; Mutation ; Pulmonary Surfactant-Associated Protein B ; deficiency ; genetics ; Pulmonary Surfactant-Associated Protein C ; genetics ; Pulmonary Surfactants ; metabolism

<b>OBJECTIVEb>Neonatal asphyxia is one of the main causes for the acute respiratory distress syndrome (ARDS) in full-term newborns. Now it is believed that the reduced amount and abnormal function of pulmonary surfactant due to various causes is a major factor leading to acute lung injury. This study aimed at using an intrauterine acute ischemic-hypoxia rat model and investigating the effect of intrauterine acute ischemic-hypoxia on the expression of surfactant protein A (SP-A) and surfactant protein B (SP-B) in neonatal rat lungs.

<b>METHODSb>The rat model of acute intrauterine ischemic-hypoxia was established by ligating the unilateral uterine horn vessels of Wistar rats at the 21st gestational day. While the rat pups from the other side of the uterus, of which the uterine horn vessel was not ligated, were the sham-operation group. Rat pups were delivered by cesarean section at the 20, 30 and 40 min following the ischemic-hypoxia insult. The rat pups delivered by cesarean section from the gestation of 21 days were the normal control group. There were 42 rat pups and 6 pups in each group in this study. The distribution of SP-B protein in the neonatal rat lungs of different period of ischemia was examined by using SABC method. The average gray value of SP-B staining in type II alveolar epithelial cells were measured by Universal Imaging Porporation with Meta Morph software. The reverse transcription polymerase chain reaction (RT-PCR) was performed to quantitate the expression of SP-A and SP-B mRNA.

<b>RESULTSb>Following the intrauterine acute ischemic-hypoxia, the numbers of type II alveolar epithelial cells with the positive SP-B staining were markedly declined. The average gray values at the 20, 30 and 40 min after the ischemia were 78.89 +/- 1.08, 79.69 +/- 0.13 and 80.00 +/- 0.63, respectively, which increased significantly compared with the normal control group (76.13 +/- 0.43, P < 0.01). The expression of SP-A and SP-B mRNA was weak following the ischemic-hypoxia insult. The relative amounts of SP-A (1.16 +/- 0.06, 1.14 +/- 0.01 and 1.13 +/- 0.04, respectively) and SP-B (0.81 +/- 0.02, 0.78 +/- 0.02 and 0.79 +/- 0.04, respectively) at the 20, 30 and 40 min after the ischemia were reduced significantly compared with controls (1.27 +/- 0.09 and 0.89 +/- 0.06, respectively, P < 0.05 and < 0.01) and reduced gradually following the prolongation of the insult. There were no significant differences (P > 0.05) between the normal and sham operation control groups on the expressions of SP-B protein as well as the SP-A and SP-B mRNA.

<b>CONCLUSIONb>The reduced synthesis of SP-B protein and the reduced expression of SP-A and SP-B mRNA might be caused by intrauterine acute ischemic-hypoxia, which may support theoretically the early application of pulmonary surfactant including SP-A and SP-B for treating the lung injuries of asphyxia in newborns.

Animals ; Animals, Newborn ; Female ; Gene Expression ; Hypoxia ; physiopathology ; Ischemia ; physiopathology ; Lung ; metabolism ; Pregnancy ; Pulmonary Surfactant-Associated Protein A ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics ; RNA, Messenger ; genetics ; metabolism ; Rats ; Rats, Wistar ; Reverse Transcriptase Polymerase Chain Reaction ; Uterus ; blood supply

Whether surfactant protein B (SP-B)-18A/C and 1580C/T polymorphism were associated with susceptibility to chronic obstructive pulmonary disease (COPD) in Chinese Han population was investigated. After genomic DNA was isolated from blood of COPD smokers and control smokers, the genotypes of SP-B-18A/C and SP-B1580C/T polymorphism loci were determined by polymerase chain reaction-restriction fragment length polymorphism analysis (PCR-RFLP) respectively. The results showed that there was significant difference in genotypes distribution frequency of SP-B1580C/T polymorphism locus between COPD smokers and control smokers. C-->T mutation rate (including TT homozygote and CT heterozygote) in COPD smokers was higher than in control smokers (57.9% vs 41.7%, chi2 = 4.93, P<0.05), whereas there was no significant difference in genotypes distribution frequency of SP-B1580-18A/C locus between COPD smokers and control smokers. The allele frequency (29.1%) of SP-B1580-18A/C locus is lower than T allele (70.9%) in Chinese Han Population, and the distribution was different from that in Mexican, in which, the A and T allele frequencies were 85% and 15% respectively. It was concluded that SP-B1580 T allele was probably associated with increased susceptibility to COPD in Chinese Han population; The polymorphism of SP-B-18A/C locus maybe varied with race.
Alleles ; China ; ethnology ; Female ; Genetic Predisposition to Disease ; genetics ; Genotype ; Humans ; Male ; Polymorphism, Genetic ; genetics ; Pulmonary Disease, Chronic Obstructive ; genetics ; Pulmonary Surfactant-Associated Protein B ; genetics ; physiology ; Smoking ; genetics

<b>OBJECTIVEb>To detect and analyze the genetic variation in exon 7 of lung surfactant protein B (SP-B), and to investigate the relationship between the genetic variation and the incidence of neonatal respiratory distress syndrome (NRDS) in Han populations in western Inner Mongolia.

<b>METHODSb>In the case-control study, 47 Han infants with NRDS were assigned to case group. All the 47 patients had the last three generations of their ancestors reside in western Inner Mongolia. Forty-seven Han newborns without NRDS were assigned to control group. PCR-based gene analysis was used to determine the mutation in exon 7 of SP-B gene and genotype and allele frequencies of the R236C site in exon 7 of SP-B gene.

<b>RESULTSb>In Han newborns in western Inner Mongolia, there was no mutation in exon 7 of SP-B gene; two genotypes, CC and CT, were identified in the R236C site in exon 7 of SP-B gene. No TT genotype was found in the two groups. There were no significant differences in the genotype frequency of CC or CT as well as the allele frequency of C or T between the case and control groups (CC: 72% vs 85%, P>0.05; CT: 28% vs 15%, P>0.05; C: 85% vs 93%, P>0.05; T: 15% vs 7%, P>0.05).

<b>CONCLUSIONSb>There is no mutation in exon 7 of SP-B gene in Han infants with NRDS in western Inner Mongolia. There is no significant association between the gene polymorphism of the R236C site in exon 7 of SP-B gene and the incidence of NRDS in Han populations in that region.

Case-Control Studies ; China ; Exons ; Female ; Genotype ; Humans ; Infant, Newborn ; Male ; Polymorphism, Genetic ; Pulmonary Surfactant-Associated Protein B ; genetics ; Respiratory Distress Syndrome, Newborn ; genetics

<b>OBJECTIVEb>To study the relationship between pulmonary surfactant-associated protein B (SP-B) gene polymorphisms and their susceptibility to neonatal respiratory distress syndrome (RDS).

<b>METHODSb>Eighty-eight preterm infants with RDS (RDS group) and 103 infants without RDS (control group) were enrolled. The genomic DNA was isolated using DNA kits. Polymerase chain reaction with restriction fragment length polymorphism technique was used to detect the genotype and allele frequency of the SP-B -18A/C and SP-B 1580C/T single nucleotide polymorphisms. The association between the polymorphisms and RDS was analyzed.

<b>RESULTSb>SP-B -18A/C and SP-B 1580C/T were found to be polymorphic in both RDS and control groups. The frequencies of CC genotype (X2=12.26, P<0.01) and C allele (X2=11.97, P<0.01) of SP-B 1580C/T were significantly higher in the RDS group than in the control group. The C allele significantly increased the risk of RDS (OR=2.26, 95%CI: 1.42-3.60). The frequencies of genotype and allele of SP-B -18A/C showed no significant difference between the two groups.

<b>CONCLUSIONSb>SP-B 1580C/T polymorphism contributes to the etiology of RDS and may serve as the susceptibility gene for RDS. The C allele increases the risk of RDS. SP-B -18A/C shows no association with the etiology of RDS.

Genetic Predisposition to Disease ; Genotype ; Humans ; Infant, Newborn ; Polymorphism, Single Nucleotide ; Pulmonary Surfactant-Associated Protein B ; genetics ; Respiratory Distress Syndrome, Newborn ; etiology ; genetics

<b>OBJECTIVEb>To investigate the changes in the pulmonary surface tension and the tissue content of surfactant substance protein B (SP-B) in rabbits during early post-injury stage after smoke inhalation injury.

<b>METHODSb>Thirty-two healthy rabbits inflicted with smoke inhalation injury were employed in the study as injury group, and they were sacrificed at 0.5, 2.0, 6.0, 12.0 post injury hours (PIH), with 8 rabbits at each time point. Another 8 rabbits were assigned to normal control group. The pulmonary tissue samples of the rabbits in each group were harvested for the collection of bronchial-alveolar lavage fluid (BALF). The changes in maximal tension (Tmax), minimal tension (Tmin) and hysteresis square (HS) of BALF were measured after the addition of 0.5, 1.0 and 3.0 ml of SP-B antibody into the BALF of the rabbits in each group. The changes in SP-B and SP-B mRNA contents in rabbit pulmonary tissue of each group were assessed with immunohistochemistry and in situ hybridization techniques, respectively.

<b>RESULTSb>There was no obvious difference in Tmax in BALF of each group or at each time point before and after the action of different concentrations of SP-B antibody in BALF (P > 0.05). But the Tmin in injury group at 2, 6 and 12 PIH was much higher than that before the addition of the antibody (P < 0.05). And the change in HS was similar to that in Tmin. The SP-B content in alveolar type II epithelial cells (AT-II) was decreased significantly at 2, 6 and 12 PIH, whereas the expression in SP-B mRNA exhibited no change.

<b>CONCLUSIONb>There was no obvious change in SP-B synthesis by AT-II in the lung tissue of the rabbits inflicted with smoke inhalation injury during early post injury stage. The increase of SP-B secretion from AT-II cells might be beneficial to the early protection of pulmonary tissue of the rabbits with smoke inhalation injury.

Animals ; Female ; Immunohistochemistry ; Lung ; chemistry ; Male ; Pulmonary Surfactant-Associated Protein B ; analysis ; genetics ; RNA, Messenger ; analysis ; Rabbits ; Smoke Inhalation Injury ; metabolism ; Surface Tension

<b>OBJECTIVEb>To explore dysfunction mechanism of rat alveolar type II (AT-II) injured by bleomycin (BLM).

<b>METHODSb>SD rats were injected with a single intratracheal dose of bleomycin or control saline. On day 7, 14, and 28 following intratracheal bleomycin or saline instillation, animals were killed under overdose of 1.5% sodium pentobarbital (0.25 ml/100 g, i.p.) and bronchoalveolar lavage fluid (BALF) from the lung was tested for the activity of pulmonary surfactant (PS) by the Whihelmy Film Balance. Several concentrations of bleomycin stimulated the culture of rat AT-II cells, and surfactant protein (SP) A, B, and aquaporin-1 (AQP) mRNA were analyzed by fluorescent quantitative polymerase chain reaction (FQ-PCR).

<b>RESULTSb>The activity of PS and hypoxemia significantly decreased on day 7 and improved on day 14 and completely recovered to normal status on day 28. SP-A, B, and AQP-1 mRNA expression in BLM-stimulated group were significantly lower than those in the control group (P<0.001).

<b>CONCLUSIONb>BLM-injured AT-II cells decrease the levels of SP-A, B, and AQP-1 mRNA and cause PS dysfunction, resulting in hypoxemia and pneumonedema.

Animals ; Aquaporin 1 ; biosynthesis ; genetics ; Bleomycin ; administration & dosage ; toxicity ; Cells, Cultured ; Dose-Response Relationship, Drug ; Epithelial Cells ; drug effects ; metabolism ; Hypoxia ; chemically induced ; metabolism ; pathology ; Male ; Pulmonary Alveoli ; cytology ; drug effects ; Pulmonary Surfactant-Associated Protein A ; biosynthesis ; genetics ; Pulmonary Surfactant-Associated Protein B ; biosynthesis ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Time Factors

<b>OBJECTIVEb>To investigate possible relationship between expression of surfactant protein B (SP-B) gene product and neonatal respiratory distress syndrome (NRDS) in Han ethnic group.

<b>METHODb>Unrelated 20 cases with NRDS of Han ethnic group were selected as NRDS group while unrelated 20 diseases cases of Han ethnic group with diseases were selected as control group. The cases in the control group had congenital heart disease or bronchopulmonary dysplasia or persistent pulmonary hypertension. Blood sample was taken from every case. Lung tissues were taken from the patients who died half an hour after death in the two groups. Expression of SP-B in lung tissue was determined with immunohistochemical tecnique. Genetic deficiency variant of SP-B intron IV was screened with polymerase chain reaction (PCR).

<b>RESULTSb>Two cases at gestational age 26 weeks and one case at gestational age 34 weeks and two cases at gestational age 42 weeks of NRDS groups had lower level expression of SP-B in lung tissue than those at the same age of NRDS. Expression of SP-B in lung tissue of control group increased with gestational age, but no such phenomenon was found in NRDS group. Further, two cases at gestational age 42 weeks of NRDS group had genetic deficiency variant of SP-B intron IV with gene analysis of five cases who had lower expression of SP-B. Clinical data suggest that patients at 42 weeks of gestational age had severe illness.

<b>CONCLUSIONSb>Decrease of SP-B expression may participate in occurrence of NRDS, genetic deficiency variant of SP-B intron IV exists in the NRDS cases of Han ethnic group of China.

Bronchopulmonary Dysplasia ; genetics ; China ; Ethnic Groups ; genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Gestational Age ; Humans ; Infant, Newborn ; Introns ; Polymorphism, Genetic ; Pulmonary Surfactant-Associated Protein B ; genetics ; Pulmonary Surfactants ; therapeutic use ; Respiratory Distress Syndrome, Newborn ; genetics ; Wills