PubMed Health⌕ Search

Biomedical subjects

F Possmayer

Publications and source records attributed to F Possmayer.

At least 91 records · Page 5Linked to original sources
PubMed1990

Expression of mature pulmonary surfactant-associated protein B (SP-B) in Escherichia coli using truncated human SP-B cDNAs.

The present communication documents attempts to produce the mature form of human surfactant-associated protein B (SP-B) by modification of the 5' and 3' regions of the cDNA and expression of the truncated cDNAs after insertion into the vector pKK223-3. The 5' end of a cDNA for human SP-B (1407 base pairs) was reconstructed through the ligation of synthetic oligonucleotides to an internal PstI site in the 5' region. This construction coded for the initiation of protein synthesis at a Met codon adjacent to a codon for the N-terminal Phe of the mature polypeptide. Variable amounts of the 3' end of the human SP-B cDNA were deleted with mung bean nuclease and exonuclease III. The resulting blunt-ended 3' fragments were then ligated to a synthetic oligonucleotide linker designed to create a stop codon. The modified 5' and 3' ends were ligated to a short PstI-BamHI fragment isolated from the SP-B cDNA and inserted into the expression vector pKK223-3. In vitro translation of sense mRNAs derived from the truncated SP-B cDNAs yielded oligopeptides of appropriate molecular weights, as indicated by urea - sodium dodecyl sulphate - polyacrylamide gel electrophoresis of either intact or immunoprecipitated reaction mixtures. Expression of SP-B in Escherichia coli was confirmed by Northern blot analysis for the mRNAs corresponding to the truncated cDNAs in appropriately transformed bacteria induced with the galactose analog isopropyl-beta-thiogalactoside. Western blot analysis using rabbit antisera prepared against bovine SP-B confirmed the presence of mature SP-B in lipid extracts of transformed E. coli, but the amounts were very small.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1990

Effect of fibrinogen degradation products and lung ground substance on surfactant function.

Acute lung injury syndromes have many characteristics including protein-rich alveolar edema, hyaline membranes, and abnormal surface tension at the alveolar air-liquid interface. Increased surface tension can occur because of a relative surfactant deficiency and/or dysfunction. It has been previously demonstrated that surfactant dysfunction occurs when plasma protein inhibitors leak into the alveolar space during the induction of the lung injury and edema formation. The present study investigated whether inhibitors that would be generated during the stage of repair from lung injury could impair surfactant function. We determined whether fibrinogen degradation products (FDP) which would be released during lysis of the fibrin(ogen)-containing alveolar exudate and hyaline membranes, and components of the lungs' ground substance could inhibit the in vitro function of a lipid extract surfactant preparation. FDP were prepared by incubating human fibrinogen with plasmin or neutrophil elastase for 4 min to 60 h and were characterized by SDS-PAGE. Early (fragment X and Y) and late (fragment D and E) plasmin-derived FDP (MW greater than 40,000) inhibited surfactant function as assessed by a bubble surfactometer. The early elastase-derived FDP also inhibited surfactant, but the later and much smaller fragments (MW less than 15,000) did not affect surfactant function. Laminin also inhibited surfactant in a dose-dependent manner. Neither hyaluronic acid nor heparan sulfate affected surfactant performance in vitro. We conclude that plasmin-induced lysis of intraalveolar fibrinogen and hyaline membranes will result in prolonged generation (i.e. days) of surfactant inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Single- versus multiple-dose surfactant replacement therapy in neonates of 30 to 36 weeks' gestation with respiratory distress syndrome.

To assess the efficacy of a multiple-dose protocol of surfactant replacement therapy in neonates of 30 to 36 weeks' gestation, 75 neonates were randomly assigned to control, single-dose surfactant, or multiple-dose surfactant groups. Neonates at less than 6 hours of age with a diagnosis of respiratory distress syndrome were eligible. Subjects were randomly assigned to receive either 100 mg/kg of bovine surfactant or air placebo. Neonates in the multiple-dose group were eligible to receive up to three additional doses as indicated. Neonates in both surfactant groups showed a positive response to treatment, with marked improvement in oxygenation by 10 minutes postinstillation (P less than .0001). Both surfactant groups had better oxygenation than control subjects at lower ventilatory parameters over the first 24 hours. A deterioration in oxygenation and ventilatory requirements was seen in both treatment groups starting 6 to 12 hours after the first dose. The deterioration in oxygenation could be minimized by the use of multiple doses; however, extra doses had no effect on diminishing ventilatory requirements or time to extubation. It is concluded that surfactant therapy at less than 6 hours of age is effective in acutely reducing oxygen and ventilatory requirements in neonates of 30 to 36 weeks' gestation with respiratory distress syndrome. It appears that multiple doses of surfactant have a greater effect on sustaining improvements in oxygenation than on ventilatory requirements. Further study is required to determine optimal dosage and retreatment strategy.

Apgar Score↗
PubMed1989

Examination of the potential role of the glycerophosphorylcholine (GPC) pathway in the biosynthesis of phosphatidylcholine by liver and lung.

The potential involvement of the glycerophosphorylcholine (GPC) pathway for the synthesis of phosphatidylcholine (PC) has been examined in rat liver and lung and in a human line, the A549 cell which possesses characteristics representative of mature alveolar type II epithelial cells. Although mitochondrial and microsomal fractions from the above sources readily incorporated radioactive glycerophosphate into lipids, the only incorporation observed with radioactive GPC was a small variable labelling with the mitochondrial and microsomal fractions from rat lung. Even with these fractions, no radioactivity from GPC was incorporated into PC or lysoPC. Attempts to increase the incorporation of GPC into lipids by manipulating the incubation conditions were unsuccessful. It was concluded that the occurrence of the GPC pathway in liver and lung is unlikely.

Animals↗
PubMed1989

Structural relationship between the two small hydrophobic apoproteins in bovine pulmonary surfactant.

Lipid extracts of bovine pulmonary surfactant contain two very hydrophobic surfactant-associated proteins (SP) designated SP-B (15 kDa nonreduced) and SP-C (3.5 kDa). These two low molecular weight apoproteins were delipidated and purified on silica SEP-PAK cartridges using various reagents. Dansylation studies revealed that the 15 kDa apoprotein has three N-termini: Phe, Leu and Ile, while the 3.5 kDa apoprotein has two N-termini: Leu and Ile. In either protein, only a very small amount of N-Ile is present. Quantitative N-terminal dansylation analysis of the 15 kDa protein indicated that Phe and Leu (plus Ile) are present in a 1:1 ratio. Carboxy-terminal analysis showed that the 15 kDa protein contains C-terminal Gly, and the 3.5 kDa protein contains C-terminal Leu. Gas-phase amino terminal sequencing of the 15 kDa protein revealed almost exclusively the Phe-polypeptide (SP-B). These results suggest that the 15 kDa apoprotein is not an oligomer of SP-B and SP-C. The reason that analysis of SP-B reveals N-terminal Leu and Ile by dansylation which cannot be confirmed by amino acid sequencing is not known.

Amino Acid Sequence↗
PubMed1989

The effects of Triton X-100 and chlorpromazine on the Mg2+-dependent and Mg2+-independent phosphatidate phosphohydrolase activities of rat lung.

Lung contains both Mg2+-dependent and Mg2+-independent phosphatidate phosphohydrolase activities. Addition of Triton X-100 (0.5%) or chlorpromazine (1 mM) leads to a marked increase in the total phosphatidate phosphohydrolase activity in rat lung microsomes (microsomal fractions), but a decrease in the Mg2+-dependent activity. These observations suggest that the Mg2+-independent activity is stimulated, whereas the Mg2+-dependent activity is inhibited. However, the possibility exists that Triton X-100 could stimulate the Mg2+-dependent enzymic activity in an Mg2+-independent manner. In addition, the positively charged amphiphilic drug could be replacing the enzyme's requirement for Mg2+. These two possibilities were examined by using subcellular fractions in which the Mg2+-dependent phosphatidate phosphohydrolase had been abolished by heat treatment at 55 degrees C for 15 min. Heat treatment does not affect the microsomal Mg2+-independent phosphohydrolase to any great extent. Since the 6-8-fold stimulations due to Triton X-100 and chlorpromazine are retained after heat treatment of this fraction, the Mg2+-independent activity must be involved. Addition of Triton X-100 and chlorpromazine to cytosol virtually abolishes the Mg2+-dependent phosphatidate phosphohydrolase activity and decreases the Mg2+-independent activity by half. Heat treatment also abolishes the Mg2+-dependent activity and decreases the Mg2+-independent activity by over half. The Mg2+-independent phosphatidate phosphohydrolase activity remaining after heat treatment was not affected by Triton X-100 or chlorpromazine. These studies demonstrate that Triton X-100 and chlorpromazine specifically stimulate the heat-stable Mg2+-independent phosphatidate phosphohydrolase activity in rat lung microsomes. In contrast, the heat-labile Mg2+-independent phosphatidate phosphohydrolase activities in cytosol are inhibited by these reagents. Triton X-100 and chlorpromazine inhibit the Mg2+-dependent phosphatidate phosphohydrolase activities in both rat lung microsomes and cytosol. These results are consistent with the view that a single Mg2+-dependent phosphatidate phosphohydrolase present in both microsomes and cytosol is specifically involved in glycerolipid metabolism.

Animals↗
PubMed1989

Effect of surfactant-associated protein-A (SP-A) on the activity of lipid extract surfactant.

The properties of natural bovine surfactant and its lipid extract have been examined with a pulsating bubble surfactometer which assesses the ability of surfactant lipids to adsorb to the air/liquid interface and reduce the surface tension to near 0 dynes/cm during dynamic compression. Studies conducted at 1 mg/ml phospholipid revealed that the surface activity (i.e., the ability to produce low surface tensions) of lipid extracts could be enhanced by incubating the sample at 37 degrees C for 120 min or by addition of CaCl2. In contrast, incubation at 37 degrees C only slightly improved the biophysical activity of natural surfactant and the addition of CaCl2 had a more modest effect than with lipid extracts. With 20 mM CaCl2, the surfactant activity of lipid extract surfactant was similar to that of natural surfactant. Incubation with EDTA reduced the biophysical activity of natural surfactant. Experiments in which increasing amounts of lipid extract were replaced by natural surfactant revealed that small amounts of natural surfactant enhanced the surfactant activity of lipid extract. The biophysical activity of lipid extract surfactant was also increased by the addition of soluble surfactant-associated protein-A (SP-A) (28-36 kDa) purified from natural bovine surfactant. These results indicate that SP-A (28-36 kDa) improves the surfactant activity of lipid extracts by enhancing the rate of adsorption and/or spreading of phospholipid at the air/liquid interface resulting in the formation of a stable lipid monolayer at lower bulk concentrations of either phospholipid or calcium.

Animals↗
PubMed1989

Isolation and characterization of the cDNA for pulmonary surfactant-associated protein-B (SP-B) in the rabbit.

Pulmonary surfactant contains phospholipids including dipalmitoyl-phosphatidylcholine and three surfactant-associated proteins designated SP-A, SP-B and SP-C. A cDNA for rabbit SP-B has been isolated from a fetal (30 days gestation) rabbit lung cDNA library constructed in lambda gt11. The cDNA and deduced amino acid sequences show strong homology with the cDNAs and predicted 40 kDa proproteins for human and canine SP-B. Strong homology is also observed with the amino acid sequences directly determined for the mature 8 kDa bovine and porcine SP-B isolated from lung lavage. SP-B is remarkable for its high cysteine and proline content and for the hydrophobic nature of the organic solvent-soluble, mature protein. In vitro translation of sense but not antisense RNA transcribed from the cDNA led to the production of 40 kDa and 32 kDa proteins. These proteins were immunoprecipitated by an antibody raised against bovine SP-B. Northern blot analysis revealed the mRNA for rabbit SP-B appears in fetal rabbit lung late in gestation and falls slightly in the neonate.

Amino Acid Sequence↗
PubMed1989

Effect of aluminum inhalation on alveolar phospholipid profiles in experimental silicosis.

In the sheep tracheal lobe model of silicosis, we have recently reported that total phospholipid, lecithin, and phosphatidylglycerol levels were elevated in lung lavage. To investigate further this observation, we obtained complete phospholipid profiles of lung lavage in 10 sheep exposed to saline only (Sa group), 10 sheep exposed to aluminum lactate inhalation only (Al group), 10 sheep exposed to 100 mg Minusil-5 in saline followed by monthly saline inhalation (Si group), and 10 sheep exposed to 100 mg Minusil-5 in saline followed by monthly aluminum lactate inhalation (Si-Al group). The following phospholipid components were measured: total phospholipids, phosphatidylglycerol (PG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylcholine, disaturated phosphatidylcholine, sphingomyelin, and lyso-phosphatidylcholine. All values were comparable in the Sa group, Al group, and Si-Al group. In the Si group, there was a significant increase in total phospholipid to approximately 200% of the control values. The phospholipid profile of this group demonstrated an increase in all of the phospholipid components with some enrichment of the fraction of PG, PE, and PI. We concluded that lung exposure to silica dust significantly increases the concentration of phospholipids in the alveoli. This increase is of a large spectrum of alveolar phospholipids and is completely suppressed by aluminum lactate inhalation.

Administration, Inhalation↗
PubMed1989

A captive bubble method reproduces the in situ behavior of lung surfactant monolayers.

We tested a new captive bubble surface tensiometer with films adsorbed from aqueous suspensions of rabbit lung surfactant and a bovine lung surfactant lipid extract and with films of dipalmitoyl-sn-3-glycerophosphorylcholine (DPPC) spread from solvents. The lack of tubes penetrating the bubble surface eliminated potential leakage pathways for the surface film, which was compressed by increasing external pressure. Surface tensions and areas were calculated directly from bubble shapes without the need of pressure measurements. After only one to two compressions, the rabbit surfactant films exhibited the low surface tension, collapse rates, and compressibilities characteristic of the alveolar surface in situ and approached the behavior of spread DPPC films. The bubble "clicking" phenomenon described earlier by Pattle (Proc. R. Soc. Lond. B Biol. Sci. 148: 217-240, 1958) was also reproduced, but only with the bovine extract, which did not perform as well as the rabbit surfactant in surface tests. These findings suggest that surfactant apoprotein SP-A, which was probably present in the rabbit but not the bovine preparations, enhances both adsorption and stability of pulmonary surfactant monolayers.

Animals↗
PubMed1989

The preterm rat: a model for studies of acute and chronic neonatal lung disease.

A preterm rat model has been developed for studies of acute and chronic neonatal lung disease. Premature delivery 24 h before the normal time of delivery is associated with immature pulmonary phospholipid and antioxidant enzyme profiles. The premature lung is more fragile and ruptures at a lower lung vol (172 +/- 8 microL) than the full-term fetal lung (259 +/- 14 microL). Only 7% of premature lungs will float in liquid, after inflation to 85% of the rupture vol, compared with 87% of term fetal lungs. This lung immaturity was reflected in a survival rate of only 6% by 36 h after delivery if the preterm pups were placed in air, which increased to 47% when they were placed in greater than 95% oxygen. Though greater than 95% oxygen enhanced survival of preterm pups during the 1st wk of life, these survivors had a 50% mortality during the 2nd wk of exposure to greater than 95% oxygen. The preterm pup will tolerate intraperitoneal injection of antioxidant enzymes entrapped in liposomes and has a better retention of these liposomes in the lung compared with the term pup. We conclude that the preterm rat is a suitable model for studies of acute and chronic neonatal lung disease.

Acute Disease↗
PubMed1989

Quartz exposure, retention, and early silicosis in sheep.

The purposes of this study were (1) to investigate the chronology of events in cellular and biochemical changes thought to be important in the development of silicosis, (2) to relate these to changes in lung function and radiograph, and (3) to evaluate the relation of quartz exposure and retention to individual response leading to early silicosis. Thirty-six sheep were exposed by repeated intratracheal infusion at 10-day intervals to 100 mg Minusil-5 in 100 ml saline (Si group), and 10 sheep were exposed at the same intervals to 100 ml saline (control). All sheep were investigated at 3-month intervals by chest radiograph, lung function, and lung lavage. At month 9, chest radiograph score of parenchymal opacities was significantly increased at 2.8 +/- 0.6 versus 0.4 +/- 0.4 in the Si group (p less than .05), establishing early radiologic silicosis. Lung function was significantly altered with reduction in lung compliance, vital capacity, and diffusion capacity (p less than .05). Lung lavage cellularity revealed significant increase in total cells (X 2.5), macrophages (X3), and neutrophils (X3). Albumin in BAL remained at the control level. Fibronectin production was significantly increased, as was the fibroblast growth activity, without significant change in procollagen 3 at this early stage of disease. Total phospholipids were significantly elevated in the Si-exposed sheep, and the profile demonstrated an increase in all the phospholipid components. Spontaneous release of hydrogen peroxide by alveolar cells was not increased, but in the presence of phorbol myristate acetate (PMA) higher levels of peroxide were found in the quartz-exposed sheep (p less than .05). The cellular and biochemical alterations of lung lavage preceded other changes. At month 12, there were good correlations (r greater than .49, p less than .001) between parameters evaluating related phenomena but poor correlations between measurements evaluating different aspects of the disorder. To investigate the heterogeneity in the individual response of sheep to the same exposure (susceptibility), individual quartz retention levels at month 12 were measured and found to correlate well with individual parameters of disease activity. We concluded that in early silicosis of sheep, cellular and biochemical changes in lung lavage preceded derangements of pulmonary function and radiographic abnormalities. Thereafter, parameters of lung lavage, lung function, and radiograph were significantly interrelated, but for a given exposure the degree of quartz retention appeared to determine the intensity of the silicotic process.

Animals↗
PubMed1988

Comparative studies on the biophysical activities of the low-molecular-weight hydrophobic proteins purified from bovine pulmonary surfactant.

Two low-molecular-weight hydrophobic proteins with nominal molecular weights Mr = 15,000 and Mr = 3,500 have been isolated from the lipid extracts of bovine pulmonary surfactant by several methods, including (a) dialysis plus silicic acid chromatography, (b) elution from Waters SEP-PAK silica cartridges with a variety of solvent mixtures, and (c) ultrafiltration. As detailed in the text, these proteins have been designated surfactant-associated protein-BC (SP-BC) (15 kDa: nonreduced), and SP-C (3.5 kDa). The biophysical activities of reconstituted surfactant containing these proteins and the phospholipids present in lung surfactant have been compared with the biophysical activities of bovine lipid extract surfactant on a pulsating bubble surfactometer using a phospholipid concentration of 10 mg/ml. At this concentration, unmodified lipid extract surfactant reduces the surface tension of the pulsating bubble to near 0 within 10 pulsations at 20 cycles per min. Similar biophysical properties were observed with modified lipid extract surfactant in which the relative concentration of hydrophobic protein had been reduced from 1 to 0.4% (W/W) of the phospholipids by addition of dipalmitoylphosphatidylcholine (DPPC) or DPPC plus phosphatidylglycerol. Reconstituted surfactants, which contained partially delipidated SP-BC (15 kDa: nonreduced) obtained by method (a) at a relative concentration of 0.1%, were also capable of reducing the surface tension to near 0 mN/m. Preparations of SP-BC (15 kDa: nonreduced) obtained by method (b), which had been subjected to very low pH levels during isolation and were extensively delipidated, exhibited full biophysical activity only at higher protein concentrations and with prolonged pulsation. Extensively delipidated samples of SP-BC obtained by method (c) exhibited impaired biophysical activities, even when prepared with neutral organic solvents. Reconstituted surfactant samples containing SP-C (3.5 kDa) obtained by any of the methods listed above were only able to reduce the surface tension at minimum bubble radius to approx. 20 mN/m. The biophysical activity of SP-C (3.5 kDa) was not significantly affected by low pH or extensive delipidation. Reconstituted samples containing mixtures of SP-BC (15 kDa: nonreduced) and SP-C (3.5 kDa) were more effective than samples containing either protein alone. Furthermore, with samples containing both hydrophobic proteins the final surface tensions at maximum bubble radius were attained within a few bubble pulsations.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Discordant accelerated pulmonary maturation after adrenocorticotropic hormone-induced labor in twin sheep fetuses.

To examine the role of parturition on lung maturation in sheep, we studied parameters of lung development in singleton fetuses treated with pulsatile adrenocorticotropic hormone or saline solution from day 127 or twin pregnancies in which one fetus only received pulsatile adrenocorticotropic hormone from day 127 until labor occurred. These parameters were compared with those of term fetuses (145 days). Pulsatile adrenocorticotropic hormone provoked labor in a mean (+/- SEM) of 102.6 +/- 6.6 and 181.0 +/- 18.0 hours in single and twin pregnancies, respectively. Adrenal/body weight ratios increased similarly in adrenocorticotropic hormone-treated single and twin fetuses at delivery, and basal cortisol levels were two- to threefold higher prepartum in adrenocorticotropic hormone-treated fetuses. Little change in plasma cortisol levels occurred in singletons treated with saline solution or in twins not infused with adrenocorticotropic hormone. The lung weight/body weight was not altered in any group. Lung distensibility and stability were doubled to term values in fetuses treated with pulsatile adrenocorticotropic hormone compared with controls and untreated twins. Mean lavage phosphatidylcholine levels rose from 0.07 to 0.11 mg/gm in saline solution-treated or untreated fetuses to 0.20 to 0.23 mg/gm in pulsatile adrenocorticotropic hormone-treated singletons or twins, compared with 0.63 mg/gm at term. Phosphatidylcholine production increased from 0.51 dpm/gm/hr in saline solution-treated fetuses to 0.73 and 0.89 dpm/gm/hr in the single and twin pulsatile adrenocorticotropic hormone-infused fetuses, respectively; phosphatidylcholine production was 0.62 dpm/gm/hr in the noninfused twin. Lungs of twins treated with pulsatile adrenocorticotropic hormone were morphologically more mature than those of untreated twins. We conclude that fetal endocrine responses to exogenous adrenocorticotropic hormone, rather than the stimuli associated with labor per se, are responsible for lung maturation in the fetal sheep.

Adrenocorticotropic Hormone↗
PubMed1988

Characterization of CDPdiacylglycerol hydrolase in mitochondrial and microsomal fractions from rat lung.

CDPdiacylglycerol pyrophosphatase (E.C. 3.6.1.26) activity has been examined in rat lung mitochondrial and microsomal fractions. While the mitochondrial hydrolase exhibited a broad pH optimum from pH 6-8, the microsomal activity decreased rapidly above pH 6.5. Apparent Km values of 36.2 and 23.6 microM and Vmax values of 311 and 197 pmol.min-1.mg protein-1 were observed for the mitochondrial and microsomal preparations, respectively. Addition of parachloromercuriphenylsulphonic acid led to a marked inhibition of the microsomal fraction but slightly stimulated the mitochondrial activity at low concentrations. Mercuric ions were inhibitory with both fractions. Although biosynthetic reactions utilizing CDPdiacylglycerol require divalent cations, addition of Mg2+, Mn2+, Ca2+, Zn2+, Co2+, and Cu2+ all inhibited the catabolic CDPdiacylglycerol hydrolase activity in both fractions. EDTA and EGTA also produced an inhibitory effect, especially with the mitochondrial fraction. Although addition of either adenine or cytidine nucleotides led to a decrease in activity with both fractions, the marked susceptibility to AMP previously reported for this enzyme in Escherichia coli membranes, guinea pig brain lysosomes, and pig liver mitochondria was not observed. These results indicate that rat lung mitochondria and microsomes contain specific CDPdiacylglycerol hydrolase activities, which could influence the rate of formation of phosphatidylinositol and phosphatidylglycerol for pulmonary surfactant.

Animals↗
PubMed1988

Effect of reconstituted pulmonary surfactant containing the 6000-dalton hydrophobic protein on lung compliance of prematurely delivered rabbit fetuses.

Chloroform:methanol extracts of bovine pulmonary surfactant contain small hydrophobic proteins, designated surfactant-associated apoproteins 6,000 (SAP-6), but do not contain the major surfactant-associated 35,000-dalton glycoprotein, designated SAP-35. Examination of lipid extract surfactant on sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed hydrophobic proteins with apparent molecular masses of 15,000, 7,000, and 3,5000 daltons prior to reduction. After reduction, the 15,000-dalton species largely disappeared and was replaced by a 5,000-dalton species. In addition, the 7000- and 3500-dalton species exhibited a slightly enhanced mobility. Amino acid analysis demonstrated that SAP-6 possesses a more highly hydrophobic profile than SAP-35. Combining the protein-containing fractions from silicic acid chromatography of lipid extract with synthetic dipalmitoylphosphatidylcholine produced a reconstituted surfactant preparation which was just as active as lipid extract surfactant on a pulsating bubble surfactometer. The reconstituted surfactant contained SAP-6 but not SAP-35. Pressure-volume studies revealed that, at the optimal dose, reconstituted surfactant containing half the SAP-6 concentration of lipid extract exhibited similar effectiveness to lipid extract surfactant in promoting lung expansion with prematurely delivered rabbit fetuses of 27 days gestation. Reconstituted surfactant with an identical SAP-6 protein concentration as lipid extract possessed the same biological properties as the preparation with 1% SAP-6 protein. These studies support the view that an artificial surfactant composed of synthetic or semisynthetic lipids plus human SAP-6 produced via biotechnology could be useful for prevention and/or treatment of the neonatal respiratory distress syndrome.

Animals↗