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Previous Volume 328:406-410 February 11, 1993 Number 6 Next

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Congenital pulmonary alveolar proteinosis is an uncommon cause of respiratory failure in full-term newborns^1,2,3,4. Although its histopathological appearance is similar to that of the alveolar proteinosis observed in older children and adults,⁵ the congenital form of the illness follows a different clinical course. All reported infants with congenital alveolar proteinosis have died within the first year of life despite maximal medical therapy. The incidence and cause of congenital alveolar proteinosis are unknown. Familial cases have been reported, and it has been speculated that the cause is an inborn error of surfactant metabolism⁴.

In this report we describe two siblings with the typical course and histopathologic features of congenital alveolar proteinosis. Analysis of their lung tissue by immunologic and molecular biologic methods revealed an absence of one of the surfactant specific proteins, surfactant protein B (SP-B), and its messenger RNA (mRNA). SP-B is important for the proper biophysical function of surfactant, suggesting that the cause of respiratory failure in these infants with congenital alveolar proteinosis was an inherited deficiency of SP-B caused by a pretranslational mechanism (implied by the absence of mRNA).

Case Report

The case patient was a 3600-g boy, the product of a nonconsanguineous marriage, who was delivered by cesarean section at 40 weeks of gestation because of breech presentation, maternal fever, and maternal hypertension. Shortly after birth, respiratory distress developed, and he required intubation and mechanical ventilation with 100 percent oxygen. Chest radiographs demonstrated diffuse granularity and air bronchograms. At 60 hours of life, extracorporeal membrane oxygenation was instituted because of refractory hypoxemia; it was maintained for 14 days without notable improvement in pulmonary function. The patient continued to require mechanical ventilation with 70 to 100 percent oxygen. He was treated with parenteral antibiotics; all bacterial and viral cultures were negative. He received corticosteroids (initially dexamethasone and subsequently methylprednisolone) throughout his course. At two months of age he received two doses of an exogenous surfactant (Survanta, 4 ml per kilogram of body weight) intratracheally. His condition improved slightly after the first dose, but not after the second, and this therapy was not continued. An open-lung biopsy performed when the patient was three months old demonstrated the characteristic findings of pulmonary alveolar proteinosis: eosinophilic, diastase-resistant granular material that was positive on periodic acid-Schiff staining filled the air spaces. In addition, foamy alveolar macrophages and desquamated alveolar epithelial cells were noted within the proteinaceous material, and there was extensive interstitial fibrosis and hyperplasia of alveolar epithelial cells. The patient died of progressive respiratory failure at five months of age. An autopsy was not permitted.

Neither the parents nor the three living siblings had a history of pulmonary disease. Nineteen years earlier, a 3750-g sister born at term had died of respiratory disease at one month of age. After the results of the case patient's biopsy were known, the clinical course and autopsy slides of his sister were reexamined. Signs of respiratory distress had developed shortly after birth and led to progressive respiratory failure. Treatment included 100 percent oxygen; she did not receive mechanical ventilation or corticosteroids. The autopsy revealed alveolar proteinosis, as described above, and changes consistent with bronchopulmonary dysplasia.

Methods

Patients

Control lung tissue was obtained from patients who were undergoing lung transplantation for end-stage pulmonary disease. These included a 2-year-old girl with bronchopulmonary dysplasia who was receiving mechanical ventilation with 100 percent oxygen; a 15-year-old boy and an 11-year-old boy with pulmonary hypertension, neither of whom was receiving supplemental oxygen; a 13-year-old girl with the adult respiratory distress syndrome who was receiving mechanical ventilation with 100 percent oxygen; and a 17-year-old girl with cystic fibrosis who was receiving supplemental oxygen. Only the girl with the adult respiratory distress syndrome was treated with corticosteroids. An unused donor lung specimen from an 18-year-old man without pulmonary disease was also obtained. Specimens were obtained at the time of surgery and immediately frozen in liquid nitrogen. A lung obtained at autopsy from a 19-day-old full-term girl with meconium aspiration syndrome who had received mechanical ventilation with 100 percent oxygen and extracorporeal membrane oxygenation was used as a positive control for immunohistochemical analysis.

Antiserum and Immunohistochemical Studies

Antiserum directed against surfactant protein A (SP-A), SP-B, and surfactant proprotein C (proSP-C) was prepared as described elsewhere^{6,7,8,9,10,11}. Immunostaining was performed on paraffin sections as previously described,¹² with antiserum against SP-A, SP-B, and proSP-C, diluted 1:500 in phosphate-buffered saline. Sections were incubated with nonimmune rabbit serum for negative staining controls.

Protein Analysis

From 15 to 50 mg of lung tissue, frozen at the time of biopsy or removal for transplantation, was homogenized while on ice in TRIS buffer containing proteinase inhibitors, and boiled in loading buffer containing sodium dodecyl sulfate and -mercaptoethanol. Aliquots containing 75 or 150 µg of total protein, as determined by a modified Lowry assay,¹³ were loaded directly onto polyacrylamide gels and underwent electrophoresis with tricine in the cathode buffer for resolution of low-molecular-weight proteins¹⁴. The surfactant proteins were detected by immunoblotting with the antiserum against SP-A, SP-B, and proSP-C, as previously described¹⁵.

RNA Analysis

Frozen lung tissue was pulverized in liquid nitrogen, and RNA was isolated by an acid-phenol extraction method¹⁶. In each sample, 10 µg of total cellular RNA was separated on a 1 percent agarose formaldehyde gel and transferred to a nylon membrane¹⁷. Human complementary DNA (cDNA) probes specific for SP-A,¹⁸ SP-B,¹⁹ and SP-C²⁰ were radiolabeled with [³²P]deoxycytidine triphosphate (ICN Pharmaceuticals) with use of a commercially available random-priming kit (Boehringer-Mannheim Biochemicals). The blots were hybridized, washed in solutions as previously described,¹⁵ and exposed to x-ray film (Kodak). The blots were sequentially probed with SP-C, SP-B, and SP-A cDNAs after stripping off the previously hybridized probe.

Results

Immunoblotting of Surfactant Proteins

SP-B was readily detected in the lung tissue of the control patients with various pulmonary disorders but was absent in the case patient's lung tissue (Figure 1). SP-A was readily detected in all lung samples in roughly comparable amounts. We detected proSP-C in all the patients, but in larger amounts in the case patient. A 6-kd protein identified with the anti-proSP-C antiserum was detected only in the case patient's lung tissue. This molecular weight corresponds to the size of a dimer of SP-C, which is known to form oligomers²¹. Alternatively, this protein could be a partial cleavage product of the proprotein.

View larger version (32K): [in this window] [in a new window]   Figure 1. Protein Blotting for SP-A, SP-B, and SP-C. The top panel shows bands ranging in size from 28 to 36 kd, corresponding to the glycosylated isoforms of SP-A that were present in lung tissue from all the patients (who are identified according to their disorders). In the middle panel, the band corresponding to the 8-kd monomer of SP-B is absent in the lung tissue of the case patient with congenital alveolar proteinosis, but is readily detected in the lung tissue of all the other patients. The bottom panel shows that proSP-C (relative molecular weight, 22,000) is present in the lung tissue of each patient and is increased in the lung tissue of the case patient. A band at 6 kd, corresponding to the molecular weight of a dimer of SP-C, was also observed in the lung tissue of the case patient, but not in the lungs of the other patients. The SP-A and SP-C blots contained 75 µg of total protein per lane; the SP-B blot contained 150 µg per lane. BPD denotes bronchopulmonary dysplasia, and ARDS adult respiratory distress syndrome.

 
Immunohistochemical Studies

In the control patient, abundant immunostaining for SP-B was detected in epithelial cells lining alveolar spaces and lying within alveoli (Figure 2A). In both siblings with congenital alveolar proteinosis immunostaining for SP-B was absent in alveolar epithelial cells and in the intraalveolar proteinaceous material (Figure 2B and Figure 2C). However, the proteinaceous material stained intensely for both SP-C (Figure 3B and Figure 3C) and SP-A (data not shown). In both siblings extensive, intense staining for SP-C was present in the alveolar epithelium, whereas staining was focal and faint in the control patient (Figure 3A). Epithelial-cell SP-A staining was sparse in both siblings and abundant in the control patient (data not shown). The distribution and intensity of immunostaining for SP-A and SP-B in the control patient, including staining in alveolar macrophages and Clara cells, were similar to those observed in other infants¹². No staining was observed with nonimmune serum.

View larger version (132K): [in this window] [in a new window]   Figure 2. Immunohistochemical Analysis for SP-B. In the control patient (Panel A), an infant who died of meconium aspiration syndrome, intense staining for SP-B is present in type II pneumocytes (thin arrows) lining air spaces (stars) and in desquamated type II pneumocytes (thick arrows) within alveoli. No detectable staining for SP-B is observed in the lungs of the case patient (Panel B) or his sibling (Panel C). (Fast-green counterstain; x130.).

 

View larger version (142K): [in this window] [in a new window]   Figure 3. Immunohistochemical Analysis for SP-C. In the control patient (Panel A), sparse staining for SP-C is present in type II pneumocytes (thin arrows) lining air spaces (stars) and in desquamated type II pneumocytes (thick arrows) within alveoli. In the case patient (Panel B) and his sibling (Panel C), intense staining is present in type II pneumocytes (thin arrows) lining air spaces (stars) and in cells and amorphous material within alveoli (thick arrows). (Fast-green counterstain, x130.).

 
RNA Analysis

To investigate the mechanisms underlying the absence of immunoreactive SP-B protein in the case patient's lung tissue, RNA blotting was performed (Figure 4). SP-A and SP-C mRNAs were found in all lung tissues examined. SP-B mRNA was present in all lung samples except that of the case patient, in which no signal was detected even after prolonged exposure. No signal was detected at higher or lower molecular weights to suggest an alternatively processed or degraded message. This result suggests that the lack of SP-B protein in the case patient's lung was due to a pretranslational mechanism -- either a decrease in transcription of the SP-B gene or the production of an unstable SP-B mRNA.

View larger version (91K): [in this window] [in a new window]   Figure 4. RNA Blotting for SP-A, SP-B, and SP-C. SP-A and SP-C mRNAs were readily detectable in the lungs of all the patients. SP-B mRNA was not observed in lung tissue from the case patient with congenital alveolar proteinosis but was readily detectable in all the other samples. Each lane contained 10 µg of total cellular RNA. BPD denotes bronchopulmonary dysplasia; Normal, normal adult lung tissue; and ARDS, adult respiratory distress syndrome.

 
Discussion

Pulmonary surfactant is a complex mixture of lipids and proteins that reduces surface tension at the interface between air and liquid. A lack of pulmonary surfactant is recognized as the principal cause of the respiratory distress syndrome in premature infants²². Specific proteins have been identified that appear to be essential for surfactant function^21,23,24. These include SP-A, a glycoprotein that is likely to be important in surfactant metabolism and that may also play a part in host defense, and SP-B and SP-C, which are hydrophobic proteins of low molecular weight that increase the rate at which surfactant phospholipids are adsorbed to the air-liquid interface^25,26.

Given their importance in the function and metabolism of surfactant, inherited deficiencies of specific surfactant proteins could potentially cause respiratory disease in newborn infants. The two siblings described in this report had the characteristic clinical and histopathologic features of congenital pulmonary alveolar proteinosis and a specific deficiency of SP-B. These observations, and previous studies of SP-B function,^{25,26,27,28,29} support the hypothesis that an inherited deficiency of SP-B was the cause of the respiratory disease in these infants.

Multiple lines of evidence demonstrate the importance of SP-B in surfactant functions. The expression of SP-B is lung-specific and is developmentally regulated^30,31,32. Combinations of surfactant phospholipids and synthetic SP-B peptides exhibited biophysical properties similar to those of native surfactant²⁷. Respiratory failure developed in rabbits treated intratracheally with a monoclonal antibody to SP-B, but not to SP-A^33,34. Synthetic SP-B peptides stimulated the uptake of phosphatidylcholine into alveolar type II cells in primary culture, suggesting that SP-B may be important in surfactant metabolism²⁸. The exact mechanisms by which SP-B deficiency could lead to the histopathological appearance of alveolar proteinosis are unclear, but our observations indicate an essential role for SP-B in the function and metabolism of surfactant.

The absence of SP-B mRNA in the case patient's lungs accounts for the lack of SP-B protein, and it is unlikely to be due to therapy or immaturity of the lungs. The biopsy specimen was obtained at an age when SP-B mRNA should be abundant,³¹ and the deficiency was specific for SP-B, without corresponding decreases in SP-A and SP-C. Glucocorticoid treatment^30,31,35 and exposure to hyperoxia^15,36,37,38 have been associated with increased expression of SP-B. Finally, the immunohistochemical findings in his sibling's lung tissue indicate that she also had SP-B deficiency, which suggests a genetic mechanism.

The respective roles of SP-B and SP-C in surfactant function are unclear. In the infants with SP-B deficiency described in this report, respiratory failure developed despite increased amounts of SP-C, suggesting that SP-B is essential for normal respiratory function. The mechanisms underlying the increased amounts and cellular distribution of SP-C observed in these infants are unknown. The similar patterns of immunostaining in both siblings, and minor variations in SP-C content among the control patients, some of whom were also exposed to oxygen or corticosteroids (or both), suggest that these changes were not secondary to another disease process or therapy.

It is unknown whether infants with congenital alveolar proteinosis from other families are deficient in SP-B. SP-B is necessary to the formation of tubular myelin^39,40. An absence of tubular myelin was noted on ultrastructural examination of the alveolar material in several previously reported cases,^3,4 a finding consistent with the hypothesis that those infants were deficient in SP-B. However, SP-B has been purified from, and tubular myelin has been observed in, the lungs of adults with alveolar proteinosis,^11,41 indicating that the histopathological appearance of alveolar proteinosis can result from conditions other than SP-B deficiency. Whether other infants with congenital alveolar proteinosis have abnormalities of SP-B quantity or function, or possibly deficiencies of other surfactant proteins, remains to be determined.

Finally, the prognosis for infants with congenital alveolar proteinosis has been uniformly poor, even with the use of extracorporeal membrane oxygenation. Therapeutic whole-lung lavage has also been considered⁴. If SP-B deficiency is the basis for congenital alveolar proteinosis in other infants, then replacement therapy (the administration of aerosolized protein, gene therapy, or lung transplantation) may be needed to treat this disorder.

Addendum

Another apparently affected sibling has recently been born to the case family. Severe lung disease has developed in the newborn period; protein-blot analysis of amniotic and lung-lavage fluid showed no detectable SP-B and markedly increased amounts of SP-C.

Supported in part by grants to Dr. Colten (HL-37591) and Dr. deMello (HL-34748) from the National Institutes of Health, and by a grant from the American Lung Association to Dr. deMello.

We are indebted to Dr. Jeffrey A. Whitsett for providing antibodies and cDNA probes to SP-A, SP-B, and SP-C; to Dr. David Phelps for providing antibodies to SP-A and SP-B; to Sarah Heyman for technical assistance in the immunohistochemical studies; to Drs. Thomas Spray, Charles Huddleston, and Michael Crossman and Roberta Mackay, R.N., for assistance in obtaining tissue specimens; and to Drs. Anne Murphy and Arnold Strauss for helpful suggestions.

Source Information

From the Department of Pediatrics, Division of Allergy and Pulmonary Medicine (L.M.N., H.R.C.), and the Department of Pathology (L.P.D.), Washington University School of Medicine; and the Department of Pathology, Cardinal Glennon Children's Hospital (D.E.D.) -- both in St. Louis.

Address reprint requests to Dr. Nogee at the Division of Neonatology, CMSC 210, Johns Hopkins Children's Center, 600 N. Wolfe St., Baltimore, MD 21287-3200.

References

1. Coleman M, Dehner LP, Sibley RK, Burke BA, L'Heureux PR, Thompson TR. Pulmonary alveolar proteinosis: an uncommon cause of chronic neonatal respiratory distress. Am Rev Respir Dis 1980;121:583-586. [Medline]
2. Knight DP, Knight JA. Pulmonary alveolar proteinosis in the newborn. Arch Pathol Lab Med 1985;109:529-531. [Medline]
3. Schumacher RE, Marrogi AJ, Heidelberger KP. Pulmonary alveolar proteinosis in a newborn. Pediatr Pulmonol 1989;7:178-182. [Medline]
4. Moulton SL, Krous HF, Merritt TA, Odell RM, Gangitano E, Cornish JD. Congenital pulmonary alveolar proteinosis: failure of treatment with extracorporeal life support. J Pediatr 1992;120:297-302. [CrossRef][Medline]
5. Rosen SH, Castleman B, Liebow AA. Pulmonary alveolar proteinosis. N Engl J Med 1958;258:1123-1142.
6. Whitsett JA, Hull WM, Ohning B, Ross G, Weaver TE. Immunologic identification of a pulmonary surfactant-associated protein of molecular weight = 6000 daltons. Pediatr Res 1986;20:744-749. [Medline]
7. Weaver TE, Sarin VK, Sawtell N, Hull WM, Whitsett JA. Identification of surfactant proteolipid SP-B in human surfactant and fetal lung. J Appl Physiol 1988;65:982-987. [Free Full Text]
8. Bolling TJ, Mandecki W. An Escherichia coli expression vector for high-level production of heterologous proteins in fusion with CMP-KDO synthetase. Biotechniques 1990;8:488-492. [Medline]
9. Vorbroker DK, Dey C, Weaver TE, Whitsett JA. Surfactant protein C precursor is palmitoylated and associates with subcellular membranes. Biochim Biophys Acta 1992;1105:161-169. [Medline]
10. Phelps DS, Floros J, Taeusch HW Jr. Post-translational modification of the major human surfactant-associated proteins. Biochem J 1986;237:373-377. [Medline]
11. Phelps DS, Floros J. Localization of pulmonary surfactant proteins using immunohistochemistry and tissue in situ hybridization. Exp Lung Res 1991;17:985-995. [Medline]
12. deMello DE, Phelps DS, Patel G, Floros J, Lagunoff D. Expression of the 35kDa and low molecular weight surfactant-associated proteins in the lungs of infants dying with respiratory distress syndrome. Am J Pathol 1989;134:1285-1293. [Abstract]
13. Lees MB, Paxman S. Modification of the Lowry procedure for the analysis of proteolipid protein. Anal Biochem 1972;47:184-192. [CrossRef][Medline]
14. Schagger H, von Jagow G. Tricine-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for the separation of proteins in the range from 1 to 100 kDa. Anal Biochem 1987;166:368-379. [CrossRef][Medline]
15. Nogee LM, Wispe JR, Clark JC, Weaver TE, Whitsett JA. Increased expression of pulmonary surfactant proteins in oxygen-exposed rats. Am J Respir Cell Mol Biol 1991;4:102-107.
16. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987;162:156-159. [Medline]
17. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning: a laboratory manual. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 1989:7.43-7.50.
18. Korfhagen TR, Glasser SW, Bruno MD, McMahan MJ, Whitsett JA. A portion of the human surfactant protein A (SP-A) gene locus consists of a pseudogene. Am J Respir Cell Mol Biol 1991;4:463-469.
19. Glasser SW, Korfhagen TR, Weaver T, Pilot-Matias T, Fox JL, Whitsett JA. cDNA and deduced amino acid sequence of human pulmonary surfactant-associated proteolipid SPL(Phe). Proc Natl Acad Sci U S A 1987;84:4007-4011. [Free Full Text]
20. Glasser SW, Korfhagen TR, Weaver TE, et al. cDNA, deduced polypeptide structure and chromosomal assignment of human pulmonary surfactant proteolipid, SPL (pVAL). J Biol Chem 1988;263:9-12. [Free Full Text]
21. Weaver TE, Whitsett JA. Structure and function of pulmonary surfactant proteins. Semin Perinatol 1988;12:213-220. [Medline]
22. Farrell PM, Avery ME. Hyaline membrane disease. Am Rev Respir Dis 1975;111:657-688. [Medline]
23. Hawgood S, Clements JA. Pulmonary surfactant and its apoproteins. J Clin Invest 1990;86:1-6.
24. Weaver TE, Whitsett JA. Function and regulation of expression of pulmonary surfactant-associated proteins. Biochem J 1991;273:249-264.
25. Whitsett JA, Ohning BL, Ross G, et al. Hydrophobic surfactant-associated protein in whole lung surfactant and its importance for biophysical activity in lung surfactant extracts used for replacement therapy. Pediatr Res 1986;20:460-467. [Medline]
26. Hawgood S, Benson BJ, Schilling J, Damm D, Clements JA, White RT. Nucleotide and amino acid sequences of pulmonary surfactant protein SP 18 and evidence for cooperation between SP 18 and SP 28-36 in surfactant lipid adsorption. Proc Natl Acad Sci U S A 1987;84:66-70. [Free Full Text]
27. Sarin VK, Gupta S, Leung TK, et al. Biophysical and biological activity of a synthetic 8.7-kDA hydrophobic pulmonary surfactant protein SP-B. Proc Natl Acad Sci U S A 1990;87:2633-2637. [Free Full Text]
28. Rice WR, Sarin VK, Fox JL, Baatz J, Wert S, Whitsett JA. Surfactant peptides stimulate uptake of phosphatidylcholine by isolated cells. Biochim Biophys Acta 1989;1006:237-245. [Medline]
29. Yu SH, Possmayer F. Comparative studies on the biophysical activities of the low-molecular-weight hydrophobic proteins purified from bovine pulmonary surfactant. Biochim Biophys Acta 1988;961:337-350. [Medline]
30. Whitsett JA, Weaver TE, Clark JC, et al. Glucocortocoid enhances surfactant proteolipid Phe and pVal synthesis and RNA in fetal lung. J Biol Chem 1987;262:15618-15623. [Free Full Text]
31. Liley HG, White RT, Warr RG, Benson BJ, Hawgood S, Ballard PL. Regulation of messenger RNAs for the hydrophobic surfactant proteins in human lung. J Clin Invest 1989;83:1191-1197.
32. Pryhuber GS, Hull WM, Fink I, McMahan MJ, Whitsett JA. Ontogeny of surfactant proteins A and B in human amniotic fluid as indices of fetal lung maturity. Pediatr Res 1991;30:597-605. [Medline]
33. Kobayashi T, Nitta K, Takahashi R, Kurashima K, Robertson B, Suzuki Y. Activity of pulmonary surfactant after blocking the associated proteins SP-A and SP-B. J Appl Physiol 1991;71:530-536. [Free Full Text]
34. Robertson B, Kobayashi T, Ganzuka M, Grossmann G, Li WZ, Suzuki Y. Experimental neonatal respiratory failure induced by a monoclonal antibody to the hydrophobic surfactant-associated protein SP-B. Pediatr Res 1991;30:239-243. [Medline]
35. Phelps DS, Floros J. Dexamethasone in vivo raises surfactant protein B mRNA in alveolar and bronchiolar epithelium. Am J Physiol 1991;260:L146-L152. [Free Full Text]
36. Minoo P, Segura L, Coalson JJ, King RJ, DeLemos RA. Alterations in surfactant protein gene expression associated with premature birth and exposure to hyperoxia. Am J Physiol 1991;261:L386-L392. [Free Full Text]
37. Wikenheiser KA, Wert SE, Wispe JR, et al. Distinct effects of oxygen on surfactant protein B expression in bronchiolar and alveolar epithelium. Am J Physiol 1992;262:L32-L39. [Free Full Text]
38. Horowitz S, Watkins RH, Auten RL Jr, Mercier CE, Cheng ER. Differential accumulation of surfactant protein A, B, and C mRNAs in two epithelial cell types of hyperoxic lung. Am J Respir Cell Mol Biol 1991;5:511-515.
39. Suzuki Y, Fujita Y, Kogishi K. Reconstitution of tubular myelin from synthetic lipids and proteins associated with pig pulmonary surfactant. Am Rev Respir Dis 1989;140:75-81. [Medline]
40. Williams MC, Hawgood S, Hamilton RL. Changes in lipid structure produced by surfactant proteins SP-A, SP-B, and SP-C. Am J Respir Cell Mol Biol 1991;5:41-50.
41. Hook GER, Gilmore LB, Talley FA. Dissolution and reassembly of tubular myelin-like multilamellated structures from the lungs of patients with pulmonary alveolar proteinosis. Lab Invest 1986;55:194-208. [Medline]

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• Sinha, S. K., Lacaze-Masmonteil, T., Valls i Soler, A., Wiswell, T. E., Gadzinowski, J., Hajdu, J., Bernstein, G., Sanchez-Luna, M., Segal, R., Schaber, C. J., Massaro, J., d'Agostino, R., for the Surfaxin Therapy Against Respiratory Distr, (2005). A Multicenter, Randomized, Controlled Trial of Lucinactant Versus Poractant Alfa Among Very Premature Infants at High Risk for Respiratory Distress Syndrome. Pediatrics 115: 1030-1038 [Abstract] [Full Text]  
• Malcharek, S., Hinz, A., Hilterhaus, L., Galla, H.-J. (2005). Multilayer Structures in Lipid Monolayer Films Containing Surfactant Protein C: Effects of Cholesterol and POPE. Biophys. J 88: 2638-2649 [Abstract] [Full Text]  
• Kandasamy, S. K., Larson, R. G. (2005). Molecular Dynamics Study of the Lung Surfactant Peptide SP-B1-25 with DPPC Monolayers: Insights into Interactions and Peptide Position and Orientation. Biophys. J 88: 1577-1592 [Abstract] [Full Text]  
• Beatty, A. L., Malloy, J. L., Wright, J. R. (2005). Pseudomonas aeruginosa Degrades Pulmonary Surfactant and Increases Conversion In Vitro. Am. J. Respir. Cell Mol. Bio. 32: 128-134 [Abstract] [Full Text]  
• Latzin, P, Tredano, M, Wust, Y, de Blic, J, Nicolai, T, Bewig, B, Stanzel, F, Kohler, D, Bahuau, M, Griese, M (2005). Anti-GM-CSF antibodies in paediatric pulmonary alveolar proteinosis. Thorax 60: 39-44 [Abstract] [Full Text]  
• Brasch, F., Griese, M., Tredano, M., Johnen, G., Ochs, M., Rieger, C., Mulugeta, S., Muller, K.M., Bahuau, M., Beers, M.F. (2004). Interstitial lung disease in a baby with a de novo mutation in the SFTPC gene. Eur Respir J 24: 30-39 [Abstract] [Full Text]  
• Hamvas, A., Nogee, L. M., White, F. V., Schuler, P., Hackett, B. P., Huddleston, C. B., Mendeloff, E. N., Hsu, F.-F., Wert, S. E., Gonzales, L. W., Beers, M. F., Ballard, P. L. (2004). Progressive Lung Disease and Surfactant Dysfunction with a Deletion in Surfactant Protein C Gene. Am. J. Respir. Cell Mol. Bio. 30: 771-776 [Abstract] [Full Text]  
• Ueno, T., Linder, S., Na, C.-L., Rice, W. R., Johansson, J., Weaver, T. E. (2004). Processing of Pulmonary Surfactant Protein B by Napsin and Cathepsin H. J. Biol. Chem. 279: 16178-16184 [Abstract] [Full Text]  
• Inwald, D, Brown, K, Gensini, F, Malone, M, Goldman, A (2004). Open lung biopsy in neonatal and paediatric patients referred for extracorporeal membrane oxygenation (ECMO). Thorax 59: 328-333 [Abstract] [Full Text]  
• Trapnell, B. C., Whitsett, J. A., Nakata, K. (2003). Pulmonary Alveolar Proteinosis. NEJM 349: 2527-2539 [Full Text]  
• Ballard, P. L., Merrill, J. D., Godinez, R. I., Godinez, M. H., Truog, W. E., Ballard, R. A. (2003). Surfactant Protein Profile of Pulmonary Surfactant in Premature Infants. Am. J. Respir. Crit. Care Med. 168: 1123-1128 [Abstract] [Full Text]  
• Cole, F. S. (2003). Surfactant protein B: unambiguously necessary for adult pulmonary function. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L540-L542 [Full Text]  
• Melton, K. R., Nesslein, L. L., Ikegami, M., Tichelaar, J. W., Clark, J. C., Whitsett, J. A., Weaver, T. E. (2003). SP-B deficiency causes respiratory failure in adult mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 285: L543-L549 [Abstract] [Full Text]  
• Foster, C. D., Zhang, P. X., Gonzales, L. W., Guttentag, S. H. (2003). In Vitro Surfactant Protein B Deficiency Inhibits Lamellar Body Formation. Am. J. Respir. Cell Mol. Bio. 29: 259-266 [Abstract] [Full Text]  
• Epaud, R., Ikegami, M., Whitsett, J. A., Jobe, A. H., Weaver, T. E., Akinbi, H. T. (2003). Surfactant Protein B Inhibits Endotoxin-Induced Lung Inflammation. Am. J. Respir. Cell Mol. Bio. 28: 373-378 [Abstract] [Full Text]  
• Guttentag, S., Robinson, L., Zhang, P., Brasch, F., Buhling, F., Beers, M. (2003). Cysteine Protease Activity Is Required for Surfactant Protein B Processing and Lamellar Body Genesis. Am. J. Respir. Cell Mol. Bio. 28: 69-79 [Abstract] [Full Text]  
• Whitsett, J. A., Weaver, T. E. (2002). Hydrophobic Surfactant Proteins in Lung Function and Disease. NEJM 347: 2141-2148 [Full Text]  
• Wang, Z., Baatz, J. E., Holm, B. A., Notter, R. H. (2002). Content-dependent activity of lung surfactant protein B in mixtures with lipids. Am. J. Physiol. Lung Cell. Mol. Physiol. 283: L897-L906 [Abstract] [Full Text]  
• Haczku, A., Atochina, E. N., Tomer, Y., Cao, Y., Campbell, C., Scanlon, S. T., Russo, S. J., Enhorning, G., Beers, M. F. (2002). The late asthmatic response is linked with increased surface tension and reduced surfactant protein B in mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 283: L755-L765 [Abstract] [Full Text]  
• Ikegami, M., Takabatake, N., Weaver, T. E. (2002). Intersubunit disulfide bridge is not required for the protective role of SP-B against lung inflammation. J. Appl. Physiol. 93: 505-511 [Abstract] [Full Text]  
• Seymour, J. F., Presneill, J. J. (2002). Pulmonary Alveolar Proteinosis: Progress in the First 44 Years. Am. J. Respir. Crit. Care Med. 166: 215-235 [Abstract] [Full Text]  
• Klein, J. M., McCarthy, T. A., Dagle, J. M., Snyder, J. M. (2002). Pre- and Postnatal Lung Development, Maturation, and Plasticity: Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro. Am. J. Physiol. Lung Cell. Mol. Physiol. 282: L386-L393 [Abstract] [Full Text]  
• Strayer, M., Savani, R. C., Gonzales, L. W., Zaman, A., Cui, Z., Veszelovszky, E., Wood, E., Ho, Y.-S., Ballard, P. L. (2002). Pre- and Postnatal Lung Development, Maturation, and Plasticity: Human surfactant protein B promoter in transgenic mice: temporal, spatial, and stimulus-responsive regulation. Am. J. Physiol. Lung Cell. Mol. Physiol. 282: L394-L404 [Abstract] [Full Text]  
• Ikegami, M., Weaver, T. E., Conkright, J. J., Sly, P. D., Ross, G. F., Whitsett, J. A., Glasser, S. W. (2002). Deficiency of SP-B reveals protective role of SP-C during oxygen lung injury. J. Appl. Physiol. 92: 519-526 [Abstract] [Full Text]  
• Gupta, M, Hernandez-Juviel, J M, Waring, A J, Walther, F J (2001). Function and inhibition sensitivity of the N-terminal segment of surfactant protein B (SP-B1-25) in preterm rabbits. Thorax 56: 871-876 [Abstract] [Full Text]  
• Bernhard, W., Gebert, A., Vieten, G., Rau, G. A., Hohlfeld, J. M., Postle, A. D., Freihorst, J. (2001). Pulmonary surfactant in birds: coping with surface tension in a tubular lung. Am. J. Physiol. Regul. Integr. Comp. Physiol. 281: R327-R337 [Abstract] [Full Text]  
• Adams, C. C., Alam, M. N., Starcher, B. C., Boggaram, V. (2001). Cell-specific and developmental regulation of rabbit surfactant protein B promoter in transgenic mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L724-L731 [Abstract] [Full Text]  
• Johnson, A. L., Braidotti, P., Pietra, G. G., Russo, S. J., Kabore, A., Wang, W.-J., Beers, M. F. (2001). Post-Translational Processing of Surfactant Protein-C Proprotein . Targeting Motifs in the NH2-Terminal Flanking Domain Are Cleaved in Late Compartments. Am. J. Respir. Cell Mol. Bio. 24: 253-263 [Abstract] [Full Text]  
• Nogee, L. M., Dunbar, A. E., Wert, S. E., Askin, F., Hamvas, A., Whitsett, J. A. (2001). A Mutation in the Surfactant Protein C Gene Associated with Familial Interstitial Lung Disease. NEJM 344: 573-579 [Full Text]  
• Paananen, R., Glumoff, V., Sormunen, R., Voorhout, W., Hallman, M. (2001). Expression and localization of lung surfactant protein B in Eustachian tube epithelium. Am. J. Physiol. Lung Cell. Mol. Physiol. 280: L214-L220 [Abstract] [Full Text]  
• Sherter, C. B., Mark, E. J. (2001). Case 2-2001- A 42-Year-Old Woman with Acute Worsening of Chronic Dyspnea and Cough. NEJM 344: 212-220 [Full Text]  
• Guilbert, T. W., Gebb, S. A., Shannon, J. M. (2000). Lung hypoplasia in the nitrofen model of congenital diaphragmatic hernia occurs early in development. Am. J. Physiol. Lung Cell. Mol. Physiol. 279: L1159-L1171 [Abstract] [Full Text]  
• Haataja, R., Ramet, M., Marttila, R., Hallman, M. (2000). Surfactant proteins A and B as interactive genetic determinants of neonatal respiratory distress syndrome. Hum Mol Genet 9: 2751-2760 [Abstract] [Full Text]  
• Berhane, K., Margana, R. K., Boggaram, V. (2000). Characterization of rabbit SP-B promoter region responsive to downregulation by tumor necrosis factor-alpha. Am. J. Physiol. Lung Cell. Mol. Physiol. 279: L806-L814 [Abstract] [Full Text]  
• Pietschmann, S. M., Pison, U. (2000). cDNA cloning of ovine pulmonary SP-A, SP-B, and SP-C: isolation of two different sequences for SP-B. Am. J. Physiol. Lung Cell. Mol. Physiol. 278: L765-L778 [Abstract] [Full Text]  
• Beers, M. F., Hamvas, A., Moxley, M. A., Gonzales, L. W., Guttentag, S. H., Solarin, K. O., Longmore, W. J., Nogee, L. M., Ballard, P. L. (2000). Pulmonary Surfactant Metabolism in Infants Lacking Surfactant Protein B. Am. J. Respir. Cell Mol. Bio. 22: 380-391 [Abstract] [Full Text]  
• NOGEE, L. M., WERT, S. E., PROFFIT, S. A., HULL, W. M., WHITSETT, J. A. (2000). Allelic Heterogeneity in Hereditary Surfactant Protein B (SP-B) Deficiency. Am. J. Respir. Crit. Care Med. 161: 973-981 [Abstract] [Full Text]  
• Margana, R., Berhane, K., Alam, M. N., Boggaram, V. (2000). Identification of functional TTF-1 and Sp1/Sp3 sites in the upstream promoter region of rabbit SP-B gene. Am. J. Physiol. Lung Cell. Mol. Physiol. 278: L477-L484 [Abstract] [Full Text]  
• Cole, F. S., Hamvas, A., Rubinstein, P., King, E., Trusgnich, M., Nogee, L. M., deMello, D. E., Colten, H. R. (2000). Population-Based Estimates of Surfactant Protein B Deficiency. Pediatrics 105: 538-541 [Abstract] [Full Text]  
• Beck, D. C., Ikegami, M., Na, C.-L., Zaltash, S., Johansson, J., Whitsett, J. A., Weaver, T. E. (2000). The Role of Homodimers in Surfactant Protein B Function in Vivo. J. Biol. Chem. 275: 3365-3370 [Abstract] [Full Text]  
• CUTZ, E., WERT, S. E., NOGEE, L. M., MOORE, A. M. (2000). Deficiency of Lamellar Bodies in Alveolar Type II Cells Associated with Fatal Respiratory Disease in a Full-term Infant. Am. J. Respir. Crit. Care Med. 161: 608-614 [Abstract] [Full Text]  
• Naltner, A., Ghaffari, M., Whitsett, J. A., Yan, C. (2000). Retinoic Acid Stimulation of the Human Surfactant Protein B Promoter Is Thyroid Transcription Factor 1 Site-dependent. J. Biol. Chem. 275: 56-62 [Abstract] [Full Text]  
• Shah, P. L, Hansell, D., Lawson, P. R, Reid, K. B M, Morgan, C. (2000). Rare diseases bullet 6: Pulmonary alveolar proteinosis: clinical aspects and current concepts on pathogenesis. Thorax 55: 67-77 [Full Text]  
• Kotecha, S. (2000). Lung growth: implications for the newborn infant. Arch. Dis. Child. Fetal Neonatal Ed. 82: 69F-74 [Full Text]  
• Tan, R. C., Ikegami, M., Jobe, A. H., Yao, L. Y., Possmayer, F., Ballard, P. L. (1999). Developmental and glucocorticoid regulation of surfactant protein mRNAs in preterm lambs. Am. J. Physiol. Lung Cell. Mol. Physiol. 277: L1142-L1148 [Abstract] [Full Text]  
• Nag, K., Munro, J. G., Inchley, K., Schurch, S., Petersen, N. O., Possmayer, F. (1999). SP-B refining of pulmonary surfactant phospholipid films. Am. J. Physiol. Lung Cell. Mol. Physiol. 277: L1179-L1189 [Abstract] [Full Text]  
• Huddleston, C. B., Sweet, S. C., Mallory, G. B., Hamvas, A., Mendeloff, E. N. (1999). LUNG TRANSPLANTATION IN VERY YOUNG INFANTS. J. Thorac. Cardiovasc. Surg. 118: 796-804 [Abstract] [Full Text]  
• Hickman-Davis, J., Matalon, S. (1999). Surfactant Protein B Deficiency Worsens Hyperoxic Injury to the Alveolar Epithelium. Am. J. Respir. Cell Mol. Bio. 21: 449-450 [Full Text]  
• Tokieda, K., Iwamoto, H. S., Bachurski, C., Wert, S. E., Hull, W. M., Ikeda, K., Whitsett, J. A. (1999). Surfactant Protein-B-Deficient Mice Are Susceptible to Hyperoxic Lung Injury. Am. J. Respir. Cell Mol. Bio. 21: 463-472 [Abstract] [Full Text]  
• Lin, S., Na, C.-L., Akinbi, H. T., Apsley, K. S., Whitsett, J. A., Weaver, T. E. (1999). Surfactant Protein B (SP-B) -/- Mice Are Rescued by Restoration of SP-B Expression in Alveolar Type II Cells but Not Clara Cells. J. Biol. Chem. 274: 19168-19174 [Abstract] [Full Text]  
• Chailley-Heu, B., Chelly, N., Lelièvre-Pégorier, M., Barlier-Mur, A.-M., Merlet-Bénichou, C., Bourbon, J. R. (1999). Mild Vitamin A Deficiency Delays Fetal Lung Maturation in the Rat. Am. J. Respir. Cell Mol. Bio. 21: 89-96 [Abstract] [Full Text]  
• COHEN, A. H., MALLORY, G. B. Jr., ROSS, K., WHITE, D. K., MENDELOFF, E., HUDDLESTON, C. B., KEMP, J. S. (1999). Growth of Lungs after Transplantation in Infants and in Children Younger than 3 Years of Age. Am. J. Respir. Crit. Care Med. 159: 1747-1751 [Abstract] [Full Text]  
• Ghaffari, M., Whitsett, J. A., Yan, C. (1999). Inhibition of hSP-B promoter in respiratory epithelial cells by a dominant negative retinoic acid receptor. Am. J. Physiol. Lung Cell. Mol. Physiol. 276: L398-L404 [Abstract] [Full Text]  
• YUSEN, R. D., COHEN, A. H., HAMVAS, A. (1999). Normal Lung Function in Subjects Heterozygous for Surfactant Protein-B Deficiency. Am. J. Respir. Crit. Care Med. 159: 411-414 [Abstract] [Full Text]  
• HERMANS, C., BERNARD, A. (1999). Lung Epithelium-specific Proteins . Characteristics and Potential Applications as Markers. Am. J. Respir. Crit. Care Med. 159: 646-678 [Full Text]  
• Dirksen, U., Hattenhorst, U., Schneider, P., Schroten, H., Gobel, U., Bocking, A., Muller, K.-M., Murray, R., Burdach, S. (1998). Defective Expression of Granulocyte-Macrophage Colony-Stimulating Factor/Interleukin-3/Interleukin-5 Receptor Common beta  Chain in Children With Acute Myeloid Leukemia Associated With Respiratory Failure. Blood 92: 1097-1103 [Abstract] [Full Text]  
• Yan, C., Ghaffari, M., Whitsett, J. A., Zeng, X., Sever, Z., Lin, S. (1998). Retinoic acid-receptor activation of SP-B gene transcription in respiratory epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 275: L239-L246 [Abstract] [Full Text]  
• Chi, X., Garnier, G., Hawgood, S., Colten, H. R. (1998). Identification of a Novel Alternatively Spliced mRNA of Murine Pulmonary Surfactant Protein B. Am. J. Respir. Cell Mol. Bio. 19: 107-113 [Abstract] [Full Text]  
• CLEMENTS, J. A., AVERY, M. E. (1998). Lung Surfactant and Neonatal Respiratory Distress Syndrome. Am. J. Respir. Crit. Care Med. 157: S59-S66 [Full Text]  
• WHITSETT, J. A., STAHLMAN, M. T. (1998). Impact of Advances in Physiology, Biochemistry, and Molecular Biology on Pulmonary Disease in Neonates. Am. J. Respir. Crit. Care Med. 157: S67-S71 [Full Text]  
• Pryhuber, G. S., Khalak, R., Zhao, Q. (1998). Regulation of surfactant proteins A and B by TNF-alpha and phorbol ester independent of NF-kappa B. Am. J. Physiol. Lung Cell. Mol. Physiol. 274: L289-L295 [Abstract] [Full Text]  
• Strayer, M. S., Guttentag, S. H., Ballard, P. L. (1998). Targeting Type II and Clara Cells for Adenovirus-mediated Gene Transfer Using the Surfactant Protein B Promoter. Am. J. Respir. Cell Mol. Bio. 18: 1-9 [Abstract] [Full Text]  
• Kobayashi, T., Tashiro, K., Yamamoto, K., Nitta, S., Ohmura, S., Suzuki, Y. (1997). Effects of surfactant proteins SP-B and SP-C on dynamic and static mechanics of immature lungs. J. Appl. Physiol. 83: 1849-1856 [Abstract] [Full Text]  
• Tokieda, K., Whitsett, J. A., Clark, J. C., Weaver, T. E., Ikeda, K., McConnell, K. B., Jobe, A. H., Ikegami, M., Iwamoto, H. S. (1997). Pulmonary dysfunction in neonatal SP-B-deficient mice. Am. J. Physiol. Lung Cell. Mol. Physiol. 273: L875-L882 [Abstract] [Full Text]  
• Akinbi, H. T., Breslin, J. S., Ikegami, M., Iwamoto, H. S., Clark, J. C., Whitsett, J. A., Jobe, A. H., Weaver, T. E. (1997). Rescue of SP-B Knockout Mice with a Truncated SP-B Proprotein. FUNCTION OF THE C-TERMINAL PROPEPTIDE. J. Biol. Chem. 272: 9640-9647 [Abstract] [Full Text]  
• DAVIS, A. J., JOBE, A. H., HÄFNER, D., IKEGAMI, M. (1997). Lung Function in Premature Lambs and Rabbits Treated with a Recombinant SP-C Surfactant. Am. J. Respir. Crit. Care Med. 157: 553-559 [Abstract] [Full Text]  
• IKEGAMI, M., WADA, K., EMERSON, G. A., REBELLO, C. M., HERNANDEZ, R. E., JOBE, A. H. (1997). Effects of Ventilation Style on Surfactant Metabolism and Treatment Response in Preterm Lambs. Am. J. Respir. Crit. Care Med. 157: 638-644 [Abstract] [Full Text]  
• DOYLE, I. R., DAVIDSON, K. G., BARR, H. A., NICHOLAS, T. E., PAYNE, K., PFITZNER, J. (1997). Quantity and Structure of Surfactant Proteins Vary Among Patients with Alveolar Proteinosis. Am. J. Respir. Crit. Care Med. 157: 658-664 [Abstract] [Full Text]  
• Margana, R. K., Boggaram, V. (1997). Functional Analysis of Surfactant Protein B (SP-B) Promoter. Sp1, Sp3, TTF-1, and HNF-3alpha TRANSCRIPTION FACTORS ARE NECESSARY FOR LUNG CELL-SPECIFIC ACTIVATION OF SP-B GENE TRANSCRIPTION. J. Biol. Chem. 272: 3083-3090 [Abstract] [Full Text]  
• Lin, S., Akinbi, H. T., Breslin, J. S., Weaver, T. E. (1996). Structural Requirements for Targeting of Surfactant Protein B (SP-B) to Secretory Granules in Vitro and in Vivo. J. Biol. Chem. 271: 19689-19695 [Abstract] [Full Text]  
• Beers, M. F., Beers, M. F. (1996). Inhibition of Cellular Processing of Surfactant Protein C by Drugs Affecting Intracellular pH Gradients. J. Biol. Chem. 271: 14361-14370 [Abstract] [Full Text]  
• Creuwels, L. A. J. M., Boer, E. H., Demel, R. A., Golde, L. M. G. v., Haagsman, H. P. (1995). Neutralization of the Positive Charges of Surfactant Protein C. J. Biol. Chem. 270: 16225-16229 [Abstract] [Full Text]  
• Colin, A. A., Mark, E. J. (1993). Case 49-1993- A 21-Year-Old Woman with Lifelong Progressive Interstitial Lung Disease. NEJM 329: 1797-1805 [Full Text]  
• Glasser, S. W., Burhans, M. S., Korfhagen, T. R., Na, C.-L., Sly, P. D., Ross, G. F., Ikegami, M., Whitsett, J. A. (2001). Altered stability of pulmonary surfactant in SP-C-deficient mice. Proc. Natl. Acad. Sci. USA 98: 6366-6371 [Abstract] [Full Text]