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Biomedical subjects

H W Taeusch

Publications and source records attributed to H W Taeusch.

At least 55 records · Page 3Linked to original sources

Primary translation products, biosynthesis, and tissue specificity of the major surfactant protein in rat.

Rat lung tissue was labeled with [35S]methionine and the major surfactant-associated proteins immunoprecipitated using a specific antiserum. The protein pattern obtained was very similar to that seen in rat bronchoalveolar lavage. Rat lung mRNA was subsequently translated in an in vitro rabbit reticulocyte system, and surfactant-associated protein-related polypeptides were immunoprecipitated. A 26-kDa polypeptide was identified and characterized as follows. (a) Unlabeled surfactant proteins added to the immunoprecipitation mixture completely inhibited its immunoprecipitation. (b) Two-dimensional gel electrophoresis of the 26-kDa protein resolved it into 3 isoforms. (c) Inclusion of dog pancreatic microsomes in the translation mixture resulted in the formation of two distinct higher molecular weight groups of isoforms, suggesting that the 26-kDa protein is destined to become a glycoprotein. Immunoprecipitation of [35S]methionine-labeled rat lung tissue proteins after tunicamycin treatment resulted in 3 isoforms, identical to the ones seen in the primary translation products. In addition, expression of the surfactant proteins appears specific to the lung.

Animals↗

Characterization of bovine surfactant for infants with respiratory distress syndrome.

Exogenous surfactant treatment of surfactant-deficient disease states is now under study in a number of centers, using a variety of surfactant preparations. We have chosen one preparation because of its current and potential clinical usefulness, and we have characterized it using selected tests and assays that we thought would be necessary (although not necessarily sufficient) to justify extended clinical use. We found its lipid composition to resemble that of other surfactants derived from lung mince. There is little variation among several batches with regard to lipid composition or surface tension-lowering capability. Morphologic heterogeneity occurs in individual samples of pelleted material studied by electron microscopy. Arterial oxygenation is improved when the material is administered to animals depleted of surfactant. A low molecular weight protein was identified that reacted with antibody that specifically binds nonserum surfactant proteins in a number of animal species (including human and cow). The characteristics of this surfactant preparation should be useful for comparison as newer and simpler products become available.

Animals↗

Biosynthesis and in vitro translation of the major surfactant-associated protein from human lung.

We have characterized a 32,000-36,000-dalton sialoglycoprotein group that is an integral component of the lipoprotein complex called pulmonary surfactant. Our results from the cell-free translation of human lung RNA show that this protein consists of two similarly-sized precursor components of about 29,000-31,000 daltons. Tunicamycin treatment of the lung tissue prevents formation of the normal protein and results in the accumulation of these precursor components which are also seen under normal conditions in very small amounts. Although in vitro translation in the presence of dog pancreatic microsomes suggests that a cleavable signal peptide sequence is present in these precursor molecules, it does not appear that this cleavage occurs in vivo.

Electrophoresis, Polyacrylamide Gel↗

A comparison of the major surfactant-associated proteins in different species.

We examined the major surfactant-associated proteins in a number of species by using two-dimensional gel electrophoresis, protein blotting and immunostaining. All species have a 30,000 to 35,000 mol. wt protein group consisting of multiple isoforms with isoelectric points ranging from pH 4.4 to 5.6. The techniques used in this study have resolved three component subgroups within the 35 K group. A group of proteins at 60,000-65,000 mol. wt has also been consistently identified. We conclude that remarkable similarity exists among the major surfactant-associated proteins from various mammals with regard to isoelectric points, molecular weights and antigenic sites.

Animals↗

Physical, chemical, and physiological characteristics of isolates of pulmonary surfactant from adult rabbits.

Physical and chemical characteristics of two types of preparations of surface active material from adult rabbits were determined. A procedure using multiple centrifugations produced a surface active material (type A) which had 6.6% by weight protein and a phosphorus/protein ratio of 13.1 nmol P/microgram protein. A simpler protocol involving two centrifugations yielded a surface active material (type B) with more protein (10.8%) and a lower phosphorus/protein ratio (8.4 nmol/micrograms). Lipid compositions of both types were similar with phosphatidylcholine being the major phospholipid (80%) and palmitate the major fatty acid in the total lipid (65-71%) and in phosphatidylcholine (80%). Both types exhibited broad thermotropic phase transitions encompassing 37 degrees C. Measurements of aqueous dispersions of surface active material on the surface of a Langmuir-Whilhelmy balance or in a pulsating bubble apparatus indicated that there was variability both between types and between batches of the same type in the capacity to reach low surface tension on the surface balance and in the rates at which low surface tension was achieved on the bubble apparatus. Type A preparations were somewhat more reliable in meeting these ends than were type B. Both types of isolates were effective in normalizing pressure-volume characteristics when instilled into the lungs of immature rabbit fetuses.

Animals↗

An electrophoretic and immunochemical characterization of human surfactant-associated proteins.

We have prepared an antiserum against a serum-free extract of alveolar proteinosis lavage that recognizes the same proteins as an antiserum to human surfactant. Using one and two-dimensional gel electrophoresis, protein blotting and immunostaining we have found proteins with Mr of approx. 35 and 60 kDa to be present in every source of human surfactant we have examined. These proteins are immunologically related to those found in the lavage from alveolar proteinosis patients, have the same electrophoretic characteristics and are not found in serum. The 35 kDa protein is a group of at least eight isoforms ranging in relative molecular mass Mr from 32 to 36 kDa with isoelectric points between 4.8 and 5.5. Neuraminidase digestion studies have shown that at least part of this charge heterogeneity may be due to sialic acid residues. The less abundant form, with a Mr of about 60 kDa is also a sialoglycoprotein with similar isoelectric points.

Amniotic Fluid↗

Localization of pulmonary surfactant protein during mouse lung development.

During lung development type II alveolar epithelial cells produce extracellular pulmonary surfactant. Polyclonal antibodies were produced against nonserum proteins associated with human surfactant. The present studies were designed (i) to determine if mouse surfactant proteins were antigenically cross-reactive with polyclonal antibodies directed against human surfactant proteins; and (ii) to determine surfactant protein localization during fetal, neonatal, and adult mouse lung development. Two-dimensional gel electrophoresis studies in conjunction with immunologic techniques provided evidence that mouse and human surfactant proteins shared antigenic determinants. The major monomeric form of mouse surfactant protein in a glycoprotein of approximately Mr 35,000 under reducing conditions. A less abundant form was identified as a Mr 45,000 polypeptide. Immunohistochemical localization showed that type II cells contain surfactant protein at Theiler stage 26. A gradient of immunostaining was localized within alveolar surfaces. The antigen was not detected in heart, blood vessels, or pulmonary interstitial cells. Surfactant protein was detected lining alveolar surfaces in mature adult lung. The distribution of this protein during fetal and neonatal lung morphogenesis suggests that this extracellular constituent of pulmonary surfactant may be extremely useful as a phenotypic marker with which to evaluate normal and abnormal lung development.

Animals↗

Exogenous surfactant therapy in hyaline membrane disease.

Exogenous surfactant therapy appears to offer promise in the treatment and possible prevention of HMD. Laboratory investigations have begun to reveal the molecular basis for surfactant metabolism and the relationship of this complex process to alveolar stability and pulmonary function. There is every reason to encourage clinical investigation with surfactant therapy in parallel with further basic research. Nevertheless, pediatricians must proceed in small steps with carefully designed studies to address specific questions regarding both efficacy and toxicity. Results from various studies must be shared and discussed and every attempt must be made to eventually provide standardized, readily available preparations of known efficacy and toxicity. Efforts by many investigators make it seem probable that this goal will be achieved in the near future.

Animals↗

Sudden infant death syndrome in infants with bronchopulmonary dysplasia.

The association between bronchopulmonary dysplasia and sudden infant death syndrome was studied retrospectively in low-birth-weight infants discharged from the neonatal program at Harvard Medical School. The incidence of sudden infant death syndrome was seven times greater in infants with bronchopulmonary dysplasia when compared with a group of control infants without bronchopulmonary dysplasia. Confounding factors, including birth weight, sex, multiple birth, socioeconomic status, and apnea were evaluated. The results indicate that there is an association between bronchopulmonary dysplasia and sudden infant death syndrome.

Apnea↗

Suctioning of upper airway meconium in newborn infants.

To compare the efficacy of bulb and catheter suctioning of upper airway meconium in neonates, meconium labeled with technetium Tc 99m sulfur colloid was injected into the trachea and oropharynx of anesthetized kittens. Human birth conditions were simulated by an inflated blood pressure cuff around the thorax and abdomen of the animals and by partial degassing of the lungs before introduction of meconium. Distribution of meconium in the upper airway was determined by scintigraph. Catheter suction brought about a 43% decrease in radioactivity while there was only a 1% decrease after bulb suctioning. Meconium may persist in the trachea for more than 20 minutes after introduction, indicating the desirability of continued suctioning efforts in neonates with meconium aspiration syndrome. The relative safety of the two techniques was not assessed.

Airway Obstruction↗

Magnitude and duration of lung response to dexamethasone in fetal sheep.

Some cases of respiratory distress syndrome (RDS) occur after optimal prenatal exposure to glucocorticoids. To explore whether some of these cases might be due to a transient effect of glucocorticoids on developing fetal lung, we studied nine chronically catheterized sheep fetuses after infusion of 500 micrograms of dexamethasone phosphate. Daily efflux of disaturated phosphatidylcholine (DSPC) from fetal tracheal fluid was measured. Three cases showed no response, two showed an early sustained rise in DSPC, and four showed an unsustained response. We interpret these data as indicating that the fetus may respond in a variety of ways to glucocorticoids, depending possibly on such factors as stage of maturity, sex, dose, and duration of exposure.

Animals↗

Regular fetal breathing induced by pilocarpine infusion in the near-term fetal lamb.

We report that pilocarpine, a cholinergic drug, stimulated regular sustained breathing movements in 10 near-term fetal lambs with chronically implanted catheters in the carotid artery, jugular vein, and trachea. With increasing doses of pilocarpine (0.1-5.9 mg), there was an enhanced respiratory response as measured by the duration of continuous breathing movements (14 +/- 12 min, increasing to 82 +/- 50 min; mean +/- SD), and the mean tracheal pressure per breath at end inspiration during the first 2 min after drug infusion (18 +/- 5, increasing to 38 +/- 12 mmHg). The mean pressure per breath during the control periods was 8 +/- 3 mmHg. There was no significant change in the breath frequency with increasing drug dose. A similar breathing response was not seen with epinephrine, suggesting that pilocarpine does not act by stimulating release of endogenous catecholamines. There was no fetal breathing response to pilocarpine infusion in atropine-pretreated fetal lambs, suggesting tha pilocarpine acts through a muscarinic mechanism. In eight acute experiments on exteriorized fetal lambs, we measured responses to pilocarpine before and after carotid sinus nerve ligation. The response to pilocarpine was abolished by sinus nerve section, suggesting possible mechanisms whereby pilocarpine may stimulate fetal breathing: the drug may increase peripheral chemoreceptor output, may sensitized the central respiratory centers to peripheral chemoreceptor input, of both.

Animals↗

Neonatal pneumopericardium: current management.

Neonatal pneumopericardium (PPC) is a frequently encountered complication of ventilator therapy. However, the appropriate management remains controversial. We describe seven infants who demonstrate the clinical spectrum of PPC. It is apparent that PPC can occur as an asymptomatic finding and may not require invasive therapy. PPC may present also with cardiac tamponade and require immediate diagnosis and therapy. Simple needle pericardiocentesis is appropriate therapy for most cases with tamponade, however a few babies with PPC uncontrolled by needle aspiration required placement of pericardial catheter for continuous drainage of the air. Mortality from PPC with tamponade (86% without therapy) should be much improved with modern management.

Cardiac Catheterization↗