Scholars@Duke
Stephen Lowe Young

Stephen Lowe Young

Professor Emeritus of Medicine
Medicine, Pulmonary, Allergy, and Critical Care Medicine
stephen.young@duke.edu
2301 Erwin Road, Durham, NC 27710
A5013 VAMC, Durham, NC 27710

Selected Publications

The opprobrium of Big Tobacco.

Journal Article Am J Respir Crit Care Med · May 1, 2012 Full text Link to item Cite

Impact of a winter respiratory virus season on patients with COPD and association with influenza vaccination.

Journal Article Chest · October 2006 BACKGROUND: We assessed the effects of an influenza season on patients with COPD. Data from 2,215 veterans in a multicenter, randomized, double-blind influenza vaccine efficacy study were analyzed for changes in spirometric and functional status, comparing ... Full text Link to item Cite

Physician subsidies for tobacco advertising.

Journal Article Am J Respir Crit Care Med · January 15, 2006 Full text Link to item Cite

Efficacy trial of live, cold-adapted and inactivated influenza virus vaccines in older adults with chronic obstructive pulmonary disease: a VA cooperative study.

Journal Article Vaccine · May 16, 2003 We assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patients with chronic obstructive pulmonary disease (COPD). Subject ... Full text Link to item Cite

Nitric oxide modulates branching morphogenesis in fetal rat lung explants.

Journal Article Am J Physiol Lung Cell Mol Physiol · March 2002 Cells of the developing lung express the constitutive nitric oxide synthases (NOSs) I and III. The developmental importance of these enzymes is largely unknown, although a role for nitric oxide (NO) in the regulation of pulmonary blood flow at birth is est ... Full text Link to item Cite

Incorporation of biotinylated SP-A into rat lung surfactant layer, type II cells, and clara cells.

Journal Article Am J Physiol Lung Cell Mol Physiol · July 2000 The goal of this study was to compare the functions of Clara and type II cells during alveolar clearance and recycling of surfactant protein (SP) A, a secretory product of both cell types. We examined the incorporation of instilled biotinylated SP-A (bSP-A ... Full text Link to item Cite

Ontogeny and localization of TGF-beta type I receptor expression during lung development.

Journal Article Am J Physiol Lung Cell Mol Physiol · June 2000 Transforming growth factor (TGF)-beta is a family of multifunctional cytokines controlling cell growth, differentiation, and extracellular matrix deposition in the lung. The biological effects of TGF-beta are mediated by type I (TbetaR-I) and II (TbetaR-II ... Full text Link to item Cite

Tyloxapol confers durable protection against hyperoxic lung injury in the rat.

Journal Article Exp Lung Res · September 1999 We tested the hypothesis that the nonlipid components of Exosurf, tyloxapol (TY), and cetyl alcohol (CA), protect against hyperoxic lung injury by induction of the animals' endogenous antioxidant defenses. Adult rats were intratracheally instilled with esc ... Full text Link to item Cite

Mechanical ventilation of rat lung: effect on surfactant forms.

Journal Article Am J Physiol · August 1999 Mechanical ventilation of the lung could affect surfactant turnover by alteration of its secretion, recycling, and degradation. In vitro studies of surfactant subfractions recoverable from lavage fluid have led to predictions about surfactant physiology in ... Full text Link to item Cite

Role of surfactant and hyperoxia.

Journal Article J Appl Physiol (1985) · August 1998 Full text Link to item Cite

Induction of tenascin in rat lungs undergoing bleomycin-induced pulmonary fibrosis.

Journal Article Am J Physiol · June 1998 Lung injury induced by bleomycin is associated with early inflammation and subsequent excessive deposition of extracellular matrix. In the present study, we investigated the expression of extracellular matrix glycoprotein tenascin (TN) during pulmonary inj ... Full text Link to item Cite

Expression of transforming growth factor-beta receptors during hyperoxia-induced lung injury and repair.

Journal Article Am J Physiol · August 1997 Lung injury and repair processes involve many cellular activities, including cell growth, differentiation, and remodeling of extracellular matrix components. Transforming growth factor-beta (TGF-beta) is a major class of signaling peptide growth factors re ... Full text Link to item Cite

Changes in the lung after prolonged positive pressure ventilation in normal baboons.

Journal Article J Crit Care · June 1997 PURPOSE: The effects of prolonged positive pressure ventilation on lung ultrastructure are not well defined in primates. This study was designed to measure cardiopulmonary and morphological responses to 4 days of positive pressure ventilation in normal bab ... Full text Link to item Cite

Identification and developmental expression of two activin receptors in baboon lung.

Journal Article Biochem Biophys Res Commun · December 4, 1996 Activins are members of the transforming growth factor-beta (TGF-beta) superfamily that exert their effects through interacting with specific cell surface TGF-beta superfamily receptors (TSRs). To determine whether activins are involved in lung development ... Full text Link to item Cite

VA/Q abnormalities during gram negative sepsis.

Journal Article Respir Physiol · August 1996 Hypoxemia in bacterial sepsis develops by mechanisms which are incompletely understood. In this study, we measured pulmonary gas exchange in eight baboons to determine the causes of hypoxemia after infusion of live Escherichia coli (1 x 10(10) CFU/kg) foll ... Full text Link to item Cite

Requirement of transforming growth factor-beta (TGF-beta) type II receptor for TGF-beta-induced proliferation and growth inhibition.

Journal Article J Biol Chem · February 2, 1996 Growth regulation of fibroblasts is important for lung development and repair of lung injury. In this study, we investigated the role of transforming growth factor-beta (TGF-beta) type II receptor in the TGF-beta-dependent proliferative response of lung fi ... Full text Link to item Cite

Composition of lung lavage in pulmonary alveolar microlithiasis.

Journal Article Respiration · 1996 A case of pulmonary alveolar microlithiasis (PAM) is reported wherein total lung lavage was performed for relief of dyspnea. Characterization of the lavage material and examination of the microliths isolated from the lavage fluid confirmed previous reports ... Full text Link to item Cite

Tenascin in rat lung development: in situ localization and cellular sources.

Journal Article Am J Physiol · October 1995 Tenascin (TN) is a hexameric extracellular matrix glycoprotein that may play an important role during lung development. TN protein is temporally and spatially restricted during lung organogenesis. The temporo-spatial and cellular expression of TN mRNA in l ... Full text Link to item Cite

Expression of transforming growth factor-beta type II receptor in rat lung is regulated during development.

Journal Article Am J Physiol · September 1995 Transforming growth factor-beta (TGF-beta) is an autocrine/paracrine growth factor that regulates cell proliferation, differentiation, extracellular matrix production and various other cell functions in the lung. TGF-beta exerts its effects on cells by bin ... Full text Link to item Cite

Artificial surfactant attenuates hyperoxic lung injury in primates. I. Physiology and biochemistry.

Journal Article J Appl Physiol (1985) · May 1995 Prolonged exposure to O2 causes diffuse alveolar damage and surfactant dysfunction that contribute to the pathophysiology of hyperoxic lung injury. We hypothesized that exogenous surfactant would improve lung function during O2 exposure in primates. Sixtee ... Full text Link to item Cite

Artificial surfactant attenuates hyperoxic lung injury in primates. II. Morphometric analysis.

Journal Article J Appl Physiol (1985) · May 1995 Diffuse lung injury from hyperoxia is accompanied by low compliance and hypoxemia with disruption of endothelial and alveolar epithelial cell layers. Because both function and content of surfactant in diffuse lung injury decrease in animals and in humans, ... Full text Link to item Cite

An age-related difference in hyperoxia lethality: role of lung antioxidant defense mechanisms.

Journal Article Am J Physiol · April 1995 The role of animal age in the lethal response to > 98% oxygen has been extensively studied, with the observation that neonatal rats were resistant while mature animals were sensitive. Antioxidant enzymes increased during the oxygen exposure in neonatal but ... Full text Link to item Cite

TGF-beta regulates expression of tenascin alternative-splicing isoforms in fetal rat lung.

Journal Article Am J Physiol · February 1995 Two distinct mRNA-splice isoforms of tenascin (TN) are expressed differentially during rat lung development. The unique temporal expression pattern of two TN isoforms suggests the expression of tenascin is strictly developmentally regulated in rat lung tis ... Full text Link to item Cite

Pulmonary surfactant - Basic biology and clinical use: Preface

Journal Article Seminars in Respiratory and Critical Care Medicine · January 1, 1995 Cite

Synthetic surfactant scavenges oxidants and protects against hyperoxic lung injury.

Journal Article J Appl Physiol (1985) · September 1994 Injury and mortality after exposure to 100% oxygen can be diminished by surfactants that may operate by mechanisms other than those responsible for surface tension effects. We tested the hypotheses that 1) synthetic surfactant and its components function a ... Full text Link to item Cite

Molecular and cellular processing of lung surfactant.

Journal Article FASEB J · September 1994 Pulmonary surfactant, a complex material that lines the alveolar surface of the lung, is synthesized in the type II pneumocyte. Surfactant consists largely of phospholipids, of which phosphatidylcholine is by far the most abundant component, and is mainly ... Full text Link to item Cite

The stimulation of cellular phospholipid uptake by surfactant apoproteins.

Journal Article Biochim Biophys Acta · June 23, 1994 Surfactant recycling by alveolar cells is influenced by the surfactant apoproteins SP-A, -B and -C (Wright, J.R. and Dobbs, L.G. (1991) Annu. Rev. Physiol. 53, 395-414). Alveolar macrophages and type II cells, but not lung fibroblasts, were reported to acc ... Full text Link to item Cite

Natural surfactant and hyperoxic lung injury in primates. I. Physiology and biochemistry.

Journal Article J Appl Physiol (1985) · March 1994 Surfactant dysfunction contributes to the pathophysiology of adult respiratory distress syndrome (ARDS), and we hypothesized that surfactant treatment would improve experimental ARDS produced by continuous exposure to hyperoxia. Twelve healthy male baboons ... Full text Link to item Cite

Natural surfactant and hyperoxic lung injury in primates. II. Morphometric analyses.

Journal Article J Appl Physiol (1985) · March 1994 Diffuse lung injury is accompanied by low compliance and hypoxemia with histological evidence of endothelial and alveolar epithelial cell disruption. The histological effects of treatment of an acute diffuse lung injury with a natural surfactant product we ... Full text Link to item Cite

Tenascin-C in rat lung: distribution, ontogeny and role in branching morphogenesis.

Journal Article Dev Biol · February 1994 Extracellular matrix is important to organogenesis and may function by modifying cellular adhesion, motility, proliferation, and differentiation. Tenascin-C (TN-C) is a matrix molecule reported to bind some cell lines and to inhibit adhesion of some cell t ... Full text Link to item Cite

Recycling of surfactant lipid and apoprotein-A studied by electron microscopic autoradiography.

Journal Article Am J Physiol · July 1993 Recycling of lipid and apoprotein components by lung epithelium appears to be a key part of the metabolism of surfactant, but many details of this process are poorly understood, including its efficiency and which intracellular pathways participate. We chos ... Full text Link to item Cite

Three-dimensional reconstruction of tubular myelin.

Journal Article Exp Lung Res · 1992 The lipid and protein components of pulmonary surfactant are synthesized by alveolar type II cells and stored in their secretory granules, the lamellar bodies. Tubular myelin is a highly ordered surfactant structure that is lung specific and produced in th ... Full text Link to item Cite

Ontogeny of rat lung type II cells correlated with surfactant lipid and surfactant apoprotein expression.

Journal Article Am J Physiol · June 1991 During the last stages of intrauterine growth, remarkable changes occur in the alveolar epithelium that include cellular differentiation and increased production of surfactant lipid and apoprotein. We made morphometric measurements of type II cell characte ... Full text Link to item Cite

Surfactant apoprotein in adult rat lung compartments is increased by dexamethasone.

Journal Article Am J Physiol · February 1991 The distribution of the major surfactant apoprotein (SP-A) in adult rat lung was determined in order to gain insight into its metabolism, including packaging of SP-A into lamellar bodies. The effect of glucocorticoid treatment on surfactant apoprotein was ... Full text Link to item Cite

Development of type II pneumocytes in rat lung.

Journal Article Am J Physiol · February 1991 At a late stage of fetal development, the mammalian alveolar epithelium undergoes an abrupt differentiation as a part of the preparation of the lung for the postnatal demands of gas exchange. Some of the most striking changes occur in the type II pneumocyt ... Full text Link to item Cite

The pulmonary surfactant system.

Journal Article Hosp Pract (Off Ed) · January 15, 1991 Surfactant's importance is underscored by the severe morbidity of deficiency states--primary, as in neonatal respiratory distress syndrome, or secondary, as in ARDS. Current knowledge of surfactant synthesis and metabolism is reviewed. Clinically, the effe ... Full text Link to item Cite

Alveolar type II cell responses to chronic inhalation of chrysotile asbestos in rats.

Journal Article Am J Respir Cell Mol Biol · December 1990 The effects of chronic exposure to chrysotile asbestos on alveolar type II cells were examined in the lungs of Fischer 344 rats. Morphometric and three-dimensional analyses were used to characterize the alveolar type II cell and to determine the relationsh ... Full text Link to item Cite

Measurement of boundaries using a digitizer tablet.

Journal Article J Microsc · October 1990 The perimeter is the most error prone of the primary measurements (length, perimeter and area) made when using a device such as a digitizer tablet to trace profiles on micrographs. To allow for minimization of this error an expression is developed relating ... Full text Link to item Cite

Neonatal hyperoxia alters the pulmonary alveolar and capillary structure of 40-day-old rats.

Journal Article Am J Pathol · June 1990 High inspired oxygen concentrations during the neonatal period profoundly inhibit rat lung development, an effect that is partly reversed during recovery in air. Persistent effects of neonatal hyperoxia on the size and number of alveoli or the structure of ... Link to item Cite

Postnatal growth of pulmonary acini and alveoli in normal and oxygen-exposed rats studied by serial section reconstructions.

Journal Article Am J Anat · September 1989 Three-dimensional reconstructions from serial sections were used to examine postnatal lung development of rats reared in air (control) or oxygen. From birth to age 21 days, control lung volume increased ninefold, and the average volume of each ventilatory ... Full text Link to item Cite

Cellular uptake and processing of surfactant lipids and apoprotein SP-A by rat lung.

Journal Article J Appl Physiol (1985) · March 1989 The intracellular pathways and the kinetics of metabolism of surfactant apoprotein and lipid, which may be recycled from the alveolar space, are largely unknown. We used a lipid-apoprotein complex made from liposomes of pure lipids in a ratio found in mamm ... Full text Link to item Cite

Alterations of surfactant pools in fetal and newborn rat lungs.

Journal Article Pediatr Res · January 1987 Preparation by the developing alveolar epithelium for the transition to air breathing and surfactant secretion at birth are critical components of neonatal survival. We combined morphometric analysis and biochemical assays of lung phospholipids to measure ... Full text Link to item Cite

Quantitative three-dimensional reconstruction and carbohydrate cytochemistry of rat nonciliated bronchiolar (Clara) cells.

Journal Article Am Rev Respir Dis · May 1986 We have employed three-dimensional reconstructions and cytochemistry to analyze nonciliated bronchiolar epithelial (Clara) cells from rat lungs. We identified a previously unreported ovoid granule type, which was characterized by its relative electron-luce ... Link to item Cite

Dexamethasone increases adult rat lung surfactant lipids.

Journal Article J Appl Physiol (1985) · May 1986 Prenatal administration of glucocorticoids stimulates epithelial cell maturation and induces a precocious development of pulmonary surfactant. The response of the adult lung to steroid administration is less well understood. We administered dexamethasone ( ... Full text Link to item Cite

Three-dimensional reconstruction and quantitative analysis of rat lung type II cells: a computer-based study.

Journal Article Am J Anat · September 1985 The three-dimensional structure of alveolar epithelial type II cells was imaged using a computer-based system designed for reconstruction and quantitative analysis of serially sectioned specimens. Six type II cells were reconstructed from serial ultrathin ... Full text Link to item Cite

Type II cell response to chronic beta adrenergic agonist and antagonist infusions.

Journal Article J Pharmacol Exp Ther · April 1985 Beta adrenergic agonists stimulate the secretion of lamellar bodies by lung alveolar type II cells. Most studies of such stimuli have been for short time periods; we wished to determine the effects of longer infusions of beta adrenergic agonists and antago ... Link to item Cite

Arachidonic acid metabolism in cultured aortic endothelial cells. Effect of cAMP and 3-isobutyl-1-methylxanthine.

Journal Article Biochem Pharmacol · January 1, 1985 To investigate the hypothesis that cyclic AMP (cAMP) regulates arachidonic acid metabolism in vascular tissue, we have studied the effects of forskolin (FSK), an activator of adenylate cyclase, and 3-isobutyl-1-methylxanthine (IBMX), a phosphodiesterase in ... Full text Link to item Cite

Secretion of surfactant by rat alveolar type II cells: morphometric analysis and three-dimensional reconstruction.

Journal Article Exp Lung Res · 1985 Secretion of surfactant by alveolar type II cells occurs by exocytosis and is stimulated by several mechanical and hormonal mechanisms, including beta-agonists. We examined the morphological correlates of this process by electron microscopy and by three di ... Full text Link to item Cite

The role of calcium in the regulation of prostacyclin synthesis by porcine aortic endothelial cells.

Journal Article Lipids · January 1984 Both bradykinin (EC50 = 8 ng/ml) and the ionophore A23187 (EC50 = 3 X 10(-7) M) potently stimulated arachidonate release and prostaglandin synthesis in porcine aortic endothelial cells. The response to each was completely dependent on extracellular Ca2+ (E ... Full text Link to item Cite

Liposome-mediated augmentation of superoxide dismutase in endothelial cells prevents oxygen injury.

Journal Article J Biol Chem · October 25, 1983 Increased intracellular production of oxygen radicals is a major etiology of cell damage from many quinoid antibiotics, environmental toxicants, and hyperoxia. Enhancing the intracellular content of protective enzymes can provide a means of limiting biolog ... Link to item Cite

Morphometric characteristics of cells in the alveolar region of mammalian lungs.

Journal Article Am Rev Respir Dis · August 1983 Morphometric procedures have been used to study the characteristics of cells in the alveolar region of the lungs of rats, dogs, baboons, and humans. Compared with the other species, human lungs were found to contain greater numbers of macrophages and to ha ... Full text Link to item Cite

Role of lymphatics in removal of sheep lung surfactant lipid.

Journal Article J Appl Physiol Respir Environ Exerc Physiol · April 1983 To study the role of lung lymphatics in the removal of surfactant lipid from the sheep lung, we injected [1-14C]palmitate intravenously into six animals previously fitted with a cannula draining the caudal mediastinal lymph node. Lung lymph was collected f ... Full text Link to item Cite

Mechanism of bradykinin-stimulated prostacyclin synthesis in porcine aortic endothelial cells.

Journal Article Biochim Biophys Acta · July 20, 1982 Porcine aortic endothelial cells studied at confluence were found to synthesize both prostacyclin and prostaglandin E2. Addition of arachidonic acid, bradykinin, the calcium ionophore A23187 or thrombin stimulated prostaglandin formation, whereas addition ... Full text Link to item Cite

Chronic beta-agonist stimulation increases rat lung surfactant lipid pools

Journal Article Clinical Research · January 1, 1982 Cite

Rat lung surfactant kinetics biochemical and morphometric correlation.

Journal Article J Appl Physiol Respir Environ Exerc Physiol · August 1981 Biochemical and morphometric techniques were combined to estimate the distribution and flux or rat lung disaturated phosphatidylcholine (DSPC) in surfactant pathways. We found 126 +/- 8 X 10(6) alveolar epithelial type II (AEP II) cells per lung, each cont ... Full text Link to item Cite

Multilamellar bodies in alveolar septal cells.

Journal Article Exp Lung Res · August 1980 Tannic acid was used as a mordant to enhance the preservation of lung phospholipids during fixation and processing for electron microscopy. We found multilamellar bodies within alveolar septa (including type I pneumocytes, capillary endothelial cells, and ... Full text Link to item Cite

Isolated perfused lung--substrate utilization.

Journal Article Fed Proc · February 1977 Lung metabolism has been extremely difficult to determine in vivo primarily because the lung is overwhelmed by a great blood flow that generally makes the Fick principle inadequate. Largely for reasons such as this, investigators have had to rely on in vit ... Link to item Cite

Metabolic activity of the lung.

Journal Article Int Anesthesiol Clin · 1977 Link to item Cite

Glycolysis and adenine nucleotide content of the edematous isolated perfused rat lung

Journal Article Federation Proceedings · January 1, 1977 Cite

An isolated perfused rat lung preparation.

Journal Article Environ Health Perspect · August 1976 An isolated perfused rat lung preparation (IPL) is described and its physiologic status is evaluated. The evaluation includes light and electron microscopy after perfusion and estimations of substrate utilization. ATP content, lactate production, and incor ... Full text Link to item Cite