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Biomedical subjects

H W Taeusch

Publications and source records attributed to H W Taeusch.

At least 37 records · Page 2Linked to original sources
PubMed1991

Surfactant protein B: lipid interactions of synthetic peptides representing the amino-terminal amphipathic domain.

The mechanisms by which pulmonary surfactant protein B (SP-B) affects the surface activity of surfactant lipids are unclear. We have studied the peptide/lipid interactions of the amino-terminal amphipathic domain of SP-B by comparing the secondary conformations and surface activities of a family of synthetic peptides based on the native human SP-B sequence, modified by site-specific amino acid substitutions. Circular dichroism measurements show an alpha-helical structure correlating with the ability of the peptides to interact with lipids and with the surface activity of peptide/lipid dispersions. Amino acid substitutions altering either the charge or the hydrophobicity of the residues lowered the helical content and reduced the association of the aminoterminal segment with lipid dispersions. Surface activity of peptide/lipid mixtures was maximally altered by reversal of charge in synthetic peptides. These observations indicate that electrostatic interactions and hydrophobicity are important factors in determining optimal structure and function of surfactant peptides in lipid dispersions.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

Inhibition of mixtures of surfactant lipids and synthetic sequences of surfactant proteins SP-B and SP-C.

The respiratory distress syndrome of premature infants is caused by both surfactant deficiency and surfactant inhibition by capillary-alveolar leakage of serum factors. Dispersions of a standard surfactant lipid mixture, with and without various synthetic peptides, modeled on human surfactant proteins SP-B (residues 1-25, 49-66, 1-78) and SP-C (residues 1-10), were evaluated for inhibition by serum and by plasma constituents using a pulsating bubble surfactometer. Inhibition was derived from the changes in surface properties of these mixtures after addition of human serum or plasma constituents. Modified bovine surfactant (TA) containing native SP-B and SP-C was used as a control. In the absence of serum inhibitors, mixtures with synthetic peptides gave results similar to surfactant TA. However, inhibition was more evident in the dispersions with synthetic peptides when compared with surfactant TA. The peptide/phospholipid mixture with the entire sequence of SP-B and the first 10 residues of SP-C were more resistant to inhibition than mixtures with synthetic peptides containing fewer domains. Addition of calcium reduced the inhibitory effects of serum both in mixtures containing synthetic peptides and in surfactant TA. Therefore, synthetic SP-B and SP-C peptides in surfactant lipids, in cooperation with calcium, permit resistance to inhibition by several plasma constituents that probably inactivate surfactant by a variety of different mechanisms.

Adult↗
PubMed1991

Antibodies against synthetic amphipathic helical sequences of surfactant protein SP-B detect a conformational change in the native protein.

Synthetic peptides based on the native human sequence of surfactant protein B have been used to generate polyclonal monospecific antibodies against specific segments of the native SP-B protein. Circular dichroism analysis of the synthetic peptides shows they have a dominant helical content in structure promoting environments and tensiometric measurements indicate these peptides lower surface tension at air-water interfaces implying that they contain amphipathic alpha helical motifs. Antibodies directed against the C-terminal segment of SP-B react with the native protein in the oxidized and reduced state. Antibodies directed against the N-terminal sequence of SP-B react with the native protein only in the reduced state suggesting that this domain has a conformation dependent on disulfide bond formation.

Amino Acid Sequence↗
PubMed1991

Radiographic findings associated with surfactant treatment.

Radiographs of the chest (CXR) were evaluated in 35 of 41 infants enrolled in a randomized controlled trial of modified bovine surfactant extract (Surfactant-TA Tokyo-Tanabe) treatment. Infants between birthweight 1000 and 1500 gm with respiratory distress syndrome requiring mechanical ventilation and an inspired oxygen concentration 0.4 or greater were randomly assigned to either a single intratracheal dose of saline or surfactant-TA prior to 8 hours of age. Radiographs obtained prior to treatment and 24 hours after treatment were reviewed by a radiologist (N.T.G.) without knowledge of treatment group. Evaluation consisted of a score including criteria for inflation of the lungs, density of the lungs, and extent of air bronchograms. Pneumothorax, pulmonary interstitial emphysema, and asymmetric parenchymal involvement were noted as well. No significant difference in CXR scores were noted in the two groups, before or after treatment. There was a greater incidence of pneumothorax and pulmonary interstitial emphysema in the control infants, which supports the role of surfactant in preventing barotrauma. Increased incidence of asymmetric parenchymal involvement was noted in the surfactant-treated infants. Further study of the possibility of drug maldistribution is warranted.

Female↗
PubMed1991

Surfactant proteins and anti-surfactant antibodies in sera from infants with respiratory distress syndrome with and without surfactant treatment.

The presence of surfactant protein antigenemia and of surfactant protein antibodies was determined in serum from surfactant-treated and control infants with respiratory distress syndrome who were enrolled in a prospective randomized clinical trial. The surfactant used for treatment (surfactant TA) contained surfactant proteins (SPs) B and C and no SP-A. Enzyme-linked immunosorbent assays (ELISAs) that identify surfactant-associated proteins and ELISAs that identify IgG or IgM directed against surfactant proteins were used to investigate sera from these infants obtained prior to treatment, at 1 week of age, and at 2 months of age. There were no significant differences between average values in the surfactant-treated and control groups at each time period. However, in the control group, averaged results from ELISAs that identify SP-A and that identify IgM antibodies to SP-A or to SP-B, C showed significant differences between pretreatment sera and sera obtained at 1 week of age. No significant differences were noted in averaged results for IgG. Positive ELISA values were more frequently found in the control group than in the surfactant-treated group with regard to SP-A, and IgM against SP-A and SP-B, C in sera from neonates at 1 week of age. No positive ELISA values were found in sera from infants at 2 months of age. It is concluded that some patients with severe respiratory distress syndrome presumably leak surfactant proteins into the circulation and that this induces transient low titers of IgM antibody. This occurrence is decreased with surfactant treatment. Surfactant treatment may reduce leak of surfactant proteins into the vascular space by reducing lung damage.

Animals↗
PubMed1990

Structure-function relationships of bovine pulmonary surfactant proteins: SP-B and SP-C.

Pulmonary surfactant contains at least three unique proteins: SP-A, SP-B and SP-C. SP-B and SP-C from bovine surfactant are markedly hydrophobic and have molecular masses between 3 and 26 kDa. We identify surfactant proteins under nonreducing conditions on polyacrylamide gels with approximate molecular mass of 5, 14, 26 kDa (SP-5, 14, 26) when organic solvent-soluble material is eluted from a Sephadex LH-20 size exclusion column followed by separation on a high-performance reverse-phase chromatography system. These bands correspond to monomeric SP-C, oligomeric SP-C and oligomeric SP-B, respectively. Computer analysis (Eisenberg-hydrophobic moment) of sequences for these proteins suggests that SP-B contains surface-seeking amphiphilic segments. In contrast, SP-C resembles a more hydrophobic transmembrane anchoring peptide. Dispersions containing dipalmitoylphosphatidylcholine, phosphatidylglycerol, palmitic acid and multimeric SP-B and SP-C duplicate the surface activity of natural surfactant when assayed in a pulsating bubble surfactometer. We speculate that oligomers of SP-B and monomers and oligomers of SP-C may act cooperatively in affecting surfactant function. An important function of SP-B and SP-C may be to affect the ordering of surfactant lipids so that rates of transport of surfactant lipids to the hypophase surface in the alveoli are enhanced.

Amino Acid Sequence↗
PubMed1990

Health and developmental outcomes of a surfactant controlled trial: follow-up at 2 years.

Several randomized clinical trials have shown that surfactant therapy improves the pulmonary status of infants with respiratory distress syndrome and has the potential to reduce morbidity and mortality in these infants. Relatively little is known, however, about the long-term consequences of surfactant treatment. In this report, the results of health and developmental assessment are described at 1 and 2 years of age of 32 survivors of an initial group of 41 infants enrolled in a randomized clinical trial of bovine surfactant therapy. The frequencies of abnormal findings were comparable in the two groups although there was a trend toward a greater frequency of allergic manifestations in the control group (6 of 16 (38%) vs 1 of 15 (7%), P = .08). Similarly, no differences were seen in the mental and motor scores of the Bayley Scales of Infant Development at either 1 or 2 years of age. This study and other recently published reports of follow-up studies of infants treated with surfactant provide encouraging evidence that major long-term side effects do not result from surfactant therapy.

Animals↗
PubMed1990

Defining quality of care indicators for neonatal intensive care units independent of maternal risk factors.

Observed and birthweight-specific neonatal mortality rates have been used for assessing quality of neonatal care, but these are crude and affected by risk characteristics of the population served. Even when neonatal mortality rate is corrected for four risk factors, race, sex, birthweight, and multiple births, (California Data Research Facility, Santa Barbara, CA) it is possible that the corrected neonatal mortality rate is not comparable among institutions because of population differences not corrected for, eg, prenatal care. To analyze whether our high neonatal mortality rate is primarily dependent on population risk or quality of neonatal care, we used contemporaneous data collection by senior physicians and a microcomputer database system to construct indices of quality of care that are based on diagnoses graded according to disease severity. For the 1987/1988 academic year, we found: neonatal intensive care unit nosocomial infection rate, 20%; severe intraventricular hemorrhage per 100 very low birthweight infants (1500 g), 20%; bronchopulmonary dysplasia per 100 cases of severe respiratory distress syndrome, 27%; necrotizing enterocolitis per 100 neonatal intensive care unit discharges, 5%; air leak per 100 cases of severe respiratory distress syndrome, 21%; and neonatal mortality rate per very low birthweight delivery rate, 0.4. We propose that microcomputer, hospital-based analyses will improve comparisons of neonatal intensive care unit quality of care if appropriate indices can be sufficiently well-defined and shared.

Black or African American↗
PubMed1988

Surfactant-associated proteins in tracheal aspirates of infants with respiratory distress syndrome after surfactant therapy.

We have developed enzyme-linked immunoassays (ELISAs) that measure major proteins that are associated with pulmonary surfactant. Using these ELISAs, we tested sequential tracheal aspirates from infants severely ill with respiratory distress syndrome (RDS) who had been treated either with exogenous surfactant or with placebo within 8 h of birth. On average, we found low concentrations of surfactant proteins in tracheal aspirates on Day 1 of life, with increases evident by Day 3. The surfactant used in this study (TA surfactant) contains only the low molecular weight (6 kDa) surfactant proteins and not the 35 kDa surfactant protein. As we expected, those who were treated with TA surfactant more frequently had detectable concentrations of low molecular weight surfactant protein on the second day of life when compared with control infants. No differences were evident in the concentrations of surfactant proteins between the 2 groups by Day 3, nor were differences evident between the 2 groups evident for 35 kDa surfactant protein during the first 3 days of life. Increased low molecular weight surfactant proteins in tracheal aspirates 1 to 2 days after surfactant therapy may occur either because of persistence of exogenous surfactant proteins and/or enhanced surfactant protein production. Comparisons with measurements from other groups of patients with RDS confirm that absence of both surfactant proteins reflects alveolar surfactant deficiency.

Enzyme-Linked Immunosorbent Assay↗
PubMed1988

Mixtures of low molecular weight surfactant proteins and dipalmitoyl phosphatidylcholine duplicate effects of pulmonary surfactant in vitro and in vivo.

Pulmonary surfactant proteins SP-B and SP-C were isolated from lavage fluids of bovine lungs and recombined (lipid/proteins, 9/1, wt/wt) with dipalmitoyl phosphatidylcholine for testing in vitro and in surfactant-deficient adult rats. Using a pulsating bubble surfactometer, we found that inflation pressures of bubbles at minimum radii in these mixtures were 0.34 +/- 0.05 cm H2O (+/- SD, n = 24) after 1 min. These values were not affected by increasing amounts of surfactant protein relative to dipalmitoyl phosphatidylcholine (DPPC). Minimum inflation pressures were similar to those of modified bovine surfactant, surfactant Tokyo Akita (TA) (0.33 +/- 0.05 cm H2O, n = 7). In vivo testing was carried out in adult rats made surfactant deficient by repeated lavage and ventilated with 100% oxygen. Rats received tracheal instillations of either air, DPPC, DPPC/SP-B,C (9:1), or surfactant TA at 50 mg/kg body weight. Surfactant TA and DPPC/SP-B, SP-C mixtures resulted in similar immediate and sustained improvements in arterial oxygenation (308 +/- 66 torr, n = 10 and 312 +/- 101 torr, n = 6 at 30 min posttreatment) that were significantly greater than those of sham (76 +/- 24 torr, n = 17) and DPPC-treated rats (64 +/- 32 torr, n = 7). Rats treated with either DPPC/SP-B,C mixtures or surfactant TA showed similar postmortem static lung compliances (2.3 +/- 0.8 ml/cm H2O/kg, n = 8 and 1.9 +/- 0.4 ml/cm H2O/kg, n = 5, respectively) that were significantly larger than sham (1.3 +/- 0.3 ml/cm H2O/kg, n = 14) and DPPC-treated rats (1.2 +/- 0.2 ml/cm H2O/kg, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1987

Isolation of a cDNA clone encoding a high molecular weight precursor to a 6-kDa pulmonary surfactant-associated protein.

Mammalian surfactant is an incompletely defined mixture of lipids and associated proteins of molecular mass 35,000 Da and approximately 6,000 Da. Surfactant preparations which are highly effective in treating respiratory distress syndrome in premature infants lack the 35-kDa proteins, but contain the 6-kDa proteins. We isolated and partially sequenced one of these low molecular weight proteins from the lung lavage material of an alveolar proteinosis patient. Oligonucleotides deduced from the sequence were used as probes to isolate a human cDNA clone. The clone codes for a 42-kDa protein which contains the sequence of the 6-kDa protein. Messenger RNA coding for the 42-kDa protein was identified in human lung RNA by in vitro translation and immunoprecipitation of the translation products with an antiserum against purified bovine surfactant 6-kDa proteins. Immunoprecipitation of the 42-kDa primary translation product is inhibited by the presence of the bovine 6-kDa protein. These observations suggest a precursor-product relationship of the 42-kDa protein to one of the 6-kDa proteins.

Amino Acid Sequence↗
PubMed1987

Characterization and partial amino acid sequence of a low molecular weight surfactant protein.

Chloroform:methanol (2:1) extracts of bovine surfactant were subjected to LH-20 Sephadex chromatography in order to isolate a 6,000-dalton surfactant protein. The 6,000-dalton protein eluted in the void volume and was shown to be homogeneous by protein sequencing, although SDS gel electrophoresis revealed bands of 6, 14, and 18 kDa. The N-terminal sequence obtained was very hydrophobic, as was the amino acid composition of the 6,000-dalton protein. An antiserum raised against the low molecular weight protein fraction from TA surfactant recognized the 6,000-dalton bovine and human proteins in addition to protein bands at 14,000 and 18,000 daltons. These bands appear to be aggregates of the 6,000-dalton protein. No cross-reactivity of the 6,000-dalton protein antiserum could be demonstrated with the 35,000-dalton surfactant-associated protein. These studies strongly suggest that the 35,000- and 6,000-dalton surfactant proteins do not have a precursor-product relationship.

Amino Acid Sequence↗
PubMed1987

Surfactant sufficiency for immature infants--prenatal induction vs. postnatal treatment.

The prenatal and postnatal therapeutic management of surfactant insufficiency are reviewed. Prenatal maternal glucocorticoid therapy promotes lung maturation and enhances lung surfactant levels in the neonate, but a minimum of 24 hr treatment is required and the therapy is of limited effectiveness even under optimal conditions. Relatively few women in premature labour are good candidates for glucocorticoid therapy. Research into combinations of glucocorticoids with hormones (e.g. thyroid), and adrenergic agents in progress. The authors are studying the effects of fibroblast-pneumonocyte factor (FPF) on the fetal lung surfactant system. Postnatal therapy with insufflated natural and artificial surfactants has been studied in several centres with varying degrees of success. Currently, the risk:benefit ratios favour attempts to reduce the risks of respiratory distress syndrome (RDS) by both prenatal surfactant induction and postnatal replacement therapy. Greater understanding of the underlying mechanisms should permit the establishment of more satisfactory treatment.

Female↗
PubMed1987

Randomized controlled trial of exogenous surfactant for the treatment of hyaline membrane disease.

We conducted a prospective, randomized, unblinded, controlled trial of exogenous bovine surfactant (surfactant TA) in premature infants requiring ventilator support for the treatment of severe hyaline membrane disease. Forty-one low birth weight infants with severe hyaline membrane disease were randomly assigned to saline or surfactant therapy and treated within eight hours of birth. Significant improvements in oxygenation (increased arterial/alveolar PO2) and respiratory support (decreased mean airway pressure) were seen in the group receiving surfactant within four hours after treatment. These improvements were maintained in the surfactant-treated infants, who also had fewer pneumothoraces and fewer number of days in environments of fractional inspiratory oxygen greater than 0.4 mm Hg. No problems were associated with administration of surfactant, and no acute side effects were detected. We conclude that exogenous surfactant, administered early in the course of severe hyaline membrane disease, is an effective therapy that can diminish the amount of respiratory support required during the first 48 hours of life.

Animals↗
PubMed1986

Post-translational modification of the major human surfactant-associated proteins.

The major protein in human pulmonary surfactant is a sialoglycoprotein of 32-36 kDa (PSP-A) that has been shown by translation of lung mRNA in vitro to be derived from precursor molecules of 29-31 kDa [Floros, Phelps & Jaeusch (1985). J. Biol. Chem. 260, 495-500]. We show here that two-dimensional gel patterns of PSP-A similar to that of the primary translation products are obtained by incorporation of [35S]methionine in the presence of tunicamycin or by N-glycanase digestion of the 32-36 kDa group. Additional gel patterns are also observed in which the isoelectric-point heterogeneity is similar to that of either tunicamycin-treated tissue or primary translation products, but with higher molecular masses. The gel patterns showing higher-molecular-mass components are obtained when terminal sialic acid addition is prevented by the incubation of lung tissue with monensin or when terminal sialic acids are digested from the fully processed protein with neuraminidase. The 32-36 kDa forms have been shown to contain [14C]mannose. Pulse-chase experiments indicate that the acidic isoforms in the protein group arise from basic isoforms that are detectable within 10 min.

Electrophoresis, Polyacrylamide Gel↗
PubMed1986

Isolation and characterization of cDNA clones for the 35-kDa pulmonary surfactant-associated protein.

A group of 35,000-dalton sialoglycoproteins is the major non-serum protein component of pulmonary surfactant. Tryptic fragments of these proteins were sequenced, and oligonucleotide probes were synthesized based on the amino acid sequences. A human lung cDNA library was then screened using the oligonucleotide probes, and clones coding for these proteins were identified and characterized. By in vitro transcription-translation experiments we have associated individual clones with particular proteins. The data suggest that co-translational modifications of two primary translation products account for many of the isoforms observed by two-dimensional gel electrophoresis in the precursors of 35,000-dalton sialoglycoproteins.

Amino Acid Sequence↗