Scholars@Duke
Thomas Miles Murphy

Thomas Miles Murphy

Professor Emeritus of Pediatrics
Pediatrics, Pulmonary and Sleep Medicine
murph016@mc.duke.edu
Box 102360 DUMC, Durham, NC 27710
349 Hanes House, 330 Trent Drive, Durham, NC 27710

Selected Publications

Ovalbumin sensitization of guinea pig at birth prevents the ontogenetic decrease in airway smooth muscle responsiveness.

Journal Article Physiol Rep · December 1, 2014 Airway smooth muscle (ASM) displays a hyperresponsive phenotype at young age and becomes less responsive in adulthood. We hypothesized that allergic sensitization, which causes ASM hyperresponsiveness and typically occurs early in life, prevents the ontoge ... Full text Link to item Cite

Airway contractility and remodeling: links to asthma symptoms.

Journal Article Pulm Pharmacol Ther · February 2013 Respiratory symptoms are largely caused by obstruction of the airways. In asthma, airway narrowing mediated by airway smooth muscle (ASM) contraction contributes significantly to obstruction. The spasmogens produced following exposure to environmental trig ... Full text Link to item Cite

Passages: The journal, the editors and the specialty

Journal Article Pediatric Pulmonology · 2013 Full text Cite

Airways smooth muscle: the next generation.

Journal Article Pulm Pharmacol Ther · October 2009 Full text Link to item Cite

Pulmonary manifestations of rheumatoid diseases

Journal Article Pulmonary Manifestations of Pediatric Diseases · 2009 Full text Cite

Barriers to adherence to cystic fibrosis infection control guidelines.

Journal Article Pediatr Pulmonol · September 2008 BACKGROUND: In 2003, the American Cystic Fibrosis (CF) Foundation published revised, evidence-based guidelines for infection control. We sought to assess potential barriers to adherence to these guidelines experienced by health care professionals (HCPs) ca ... Full text Link to item Cite

Trends in the clinical characteristics of the U.S. cystic fibrosis patient population from 1995 to 2005.

Journal Article Pediatr Pulmonol · August 2008 Featured Publication RATIONALE: Respiratory signs and symptoms (cough, sputum production, or crackles) are considered bellwethers of underlying cystic fibrosis (CF) lung disease. If respiratory signs and symptoms predict future lung function loss, then improvements in populati ... Full text Link to item Cite

Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release.

Journal Article Am J Physiol Lung Cell Mol Physiol · May 2008 Featured Publication Airway smooth muscle (ASM) from infant guinea pigs has less spontaneous relaxation during stimulation than ASM from adults. Inhibition of cyclooxygenase (COX), which catalyzes the production of prostanoids, increases this relaxation in infant ASM and aboli ... Full text Link to item Cite

Airway smooth muscle relaxation is impaired in mice lacking the p47phox subunit of NAD(P)H oxidase.

Journal Article Am J Physiol Lung Cell Mol Physiol · January 2008 Featured Publication NAD(P)H oxidase is one of the critical enzymes mediating cellular production of reactive oxygen species and has a central role in airway smooth muscle (ASM) cell proliferation. Since reactive oxygen species also affect ASM contractile response, we hypothes ... Full text Link to item Cite

Three paradigms of airway smooth muscle hyperresponsiveness in young guinea pigs.

Journal Article Canadian journal of physiology and pharmacology · July 2007 Featured Publication Evidence for contributions of airway smooth muscle (ASM) to the hyperresponsiveness of newborn and juvenile airways continues to accumulate. In our laboratory, 3 novel paradigms of hyperresponsiveness of newborn and young ASM have recently emerged using a ... Full text Cite

Nox4 mediates TGF-beta1-induced retinoblastoma protein phosphorylation, proliferation, and hypertrophy in human airway smooth muscle cells.

Journal Article Am J Physiol Lung Cell Mol Physiol · June 2007 Featured Publication Transforming growth factor-beta1 (TGF-beta1) plays a pivotal role in increasing airway smooth muscle mass in severe asthma by inducing proliferation and hypertrophy of human airway smooth muscle. The mechanism(s) for these effects of TGF-beta1 have not bee ... Full text Link to item Cite

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma.

Journal Article Eur Respir J · May 2007 Featured Publication Excessive airway obstruction is the cause of symptoms and abnormal lung function in asthma. As airway smooth muscle (ASM) is the effecter controlling airway calibre, it is suspected that dysfunction of ASM contributes to the pathophysiology of asthma. Howe ... Full text Link to item Cite

The Lung in Sickle Cell Disease

Journal Article · December 1, 2006 Full text Cite

Maturation of guinea pig tracheal strip stiffness.

Journal Article Am J Physiol Lung Cell Mol Physiol · December 2005 Featured Publication Previously, we showed the shortening velocity of guinea pig tracheal strips was the greatest in juvenile (3-wk-old) compared with infant (1-wk-old) and adult animals (3-mo-old). The greatest shortening velocity was associated with the least resistance to s ... Full text Link to item Cite

Length oscillation induces force potentiation in infant guinea pig airway smooth muscle.

Journal Article Am J Physiol Lung Cell Mol Physiol · December 2005 Featured Publication Deep inspiration counteracts bronchospasm in normal subjects but triggers further bronchoconstriction in hyperresponsive airways. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been sugges ... Full text Link to item Cite

A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

Journal Article Can J Physiol Pharmacol · October 2005 Featured Publication It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects ... Full text Link to item Cite

Mechanisms of airway smooth muscle relaxation during maturation.

Journal Article Can J Physiol Pharmacol · October 2005 Featured Publication Greater airway responsiveness in healthy juveniles is considered a factor in the higher asthma prevalence at a young age compared with adults. We have developed a guinea pig maturational model that utilizes tracheal strips from 1-week-, 3-week-, and 3-mont ... Full text Link to item Cite

Ontogenesis of myosin light chain phosphorylation in guinea pig tracheal smooth muscle.

Journal Article Pediatr Pulmonol · February 2005 Featured Publication Increased airway responsiveness occurs in normal young individuals compared to adults. A maturation of airway smooth muscle (ASM) contractility is likely a mechanism of this juvenile airway hyperresponsiveness. Indeed, we showed in guinea pig tracheal smoo ... Full text Link to item Cite

On the terminology for describing the length-force relationship and its changes in airway smooth muscle.

Journal Article J Appl Physiol (1985) · December 2004 Featured Publication The observation that the length-force relationship in airway smooth muscle can be shifted along the length axis by accommodating the muscle at different lengths has stimulated great interest. In light of the recent understanding of the dynamic nature of le ... Full text Link to item Cite

Ontogenesis of myosin light chain kinase mRNA and protein content in guinea pig tracheal smooth muscle.

Journal Article Pediatr Pulmonol · December 2004 Featured Publication We previously reported in guinea pig tracheal smooth muscle that maximal shortening velocity decreases from 3 weeks of age to adulthood. It is not known whether myosin light chain kinase (MLCK), a key enzyme determining the velocity of smooth muscle contra ... Full text Link to item Cite

Maturational changes in airway smooth muscle shortening and relaxation. Implications for asthma.

Journal Article Respir Physiol Neurobiol · September 16, 2003 Featured Publication Greater airway responsiveness in healthy juveniles is considered a factor in the higher asthma prevalence at a young age compared with adults. Several studies on the contractile response of airway smooth muscle (ASM) from birth to adulthood have addressed ... Full text Link to item Cite

Growing up and advancing in airway smooth muscle research.

Journal Article Trends Pharmacol Sci · October 2002 Featured Publication Full text Link to item Cite

Relaxation of guinea pig trachealis during electrical field stimulation increases with age.

Journal Article J Appl Physiol (1985) · May 2002 Featured Publication Our laboratory has previously shown that maturation of airway smooth muscle (ASM) contractility may play a role in the airway hyperresponsiveness displayed by juveniles of many species, including humans (Chitano P, Wang J, Cox CM, Stephens NL, and Murphy T ... Full text Link to item Cite

NADPH oxidase promotes NF-kappaB activation and proliferation in human airway smooth muscle.

Journal Article Am J Physiol Lung Cell Mol Physiol · April 2002 Featured Publication Evidence is rapidly accumulating that low-activity-reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases homologous to that in phagocytic cells generate reactive oxygen species as signaling intermediates in both endothelium and vascular smoo ... Full text Link to item Cite

Different ontogeny of rate of force generation and shortening velocity in guinea pig trachealis.

Journal Article J Appl Physiol (1985) · April 2000 Featured Publication Juveniles of many species, including humans, display greater airway responsiveness than do adults. This may involve changes in airway smooth muscle function. In the present work we studied force production and shortening velocity in trachealis from 1-wk-ol ... Full text Link to item Cite

The lung in sickle cell disease.

Journal Article Pediatr Pulmonol · September 1999 Featured Publication Sickle cell disease is the most common inherited disorder in African-Americans. Although the primary defect is hematological, the changes in the erythrocytes lead to a vasculopathy with multiorgan injury. The pulmonary complications, i.e., acute chest synd ... Full text Link to item Cite

Requirement for reactive oxygen species in serum-induced and platelet-derived growth factor-induced growth of airway smooth muscle.

Journal Article J Biol Chem · July 9, 1999 Featured Publication Reactive oxygen species have been recently identified as important mediators of mitogenic signaling in a number of cell types. We therefore explored their role in mediating mitogenesis of airway smooth muscle. The antioxidants catalase, N-acetylcysteine, a ... Full text Link to item Cite

Dehydroepiandrosterone and analogs inhibit DNA binding of AP-1 and airway smooth muscle proliferation.

Journal Article J Pharmacol Exp Ther · May 1998 Featured Publication The adrenal steroid dehydroepiandrosterone (DHEA) and its analogs reduce growth of immortalized and malignant cell lines. We therefore explored their effects on the growth of airway smooth muscle, whose hyperplasia may lead to fixed airways obstruction and ... Link to item Cite

Ontogeny of dry gas hyperpnea-induced bronchoconstriction in guinea pigs.

Journal Article J Appl Physiol (1985) · March 1994 Featured Publication Adolescent guinea pigs (AGPs) demonstrate dry gas hyperpnea-induced bronchoconstriction (HIB) that shares key features with HIB in humans with asthma. The airways of immature animals exhibit enhanced reactivity to diverse types of stimulation. We tested wh ... Full text Link to item Cite

Physiological mechanisms mediating enhanced force generation during development and immune sensitization.

Journal Article Can J Physiol Pharmacol · April 1992 Featured Publication We examined the development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by acetylcholine (ACh) in a swine model of maturation and a dog model of allergic bronchospasm. Strips of TSM were tethered isometri ... Full text Link to item Cite

Ontogeny of shortening velocity in porcine trachealis.

Journal Article Am J Physiol · March 1992 Featured Publication We examined the effect of maturation on force-velocity (F-V) parameters in porcine tracheal smooth muscle (TSM) to determine the relationship between maximal isometric contractile force (Po) and maximal velocity of shortening (Vmax). Strips of TSM excised ... Full text Link to item Cite

Ontogeny of shortening velocity in porcine trachealis

Journal Article American Journal of Physiology - Lung Cellular and Molecular Physiology · 1992 We examined the effect of maturation on force-velocity (F-V) parameters in porcine tracheal smooth muscle (TSM) to determine the relationship between maximal isometric contractile force (P(o)) and maximal velocity of shortening (V(max)). Strips of TSM exci ... Cite

Ontogenic expression of acetylcholinesterase activity in trachealis of young swine.

Journal Article Am J Physiol · October 1991 Featured Publication Previous investigations have demonstrated that cholinergic contraction of porcine tracheal smooth muscle (TSM) decreases between the second and tenth weeks of life. In this investigation, we hypothesized that the greater contractile response to acetylcholi ... Full text Link to item Cite

Extracellular Ca2+ mobilization in potential-dependent contraction of trachealis of maturing swine.

Journal Article J Appl Physiol (1985) · October 1991 We studied the effect of maturation on potassium-induced parasympathetic activation and Ca2+ entry in tracheal smooth muscle (TSM) from fifteen 2-wk-old (2ws) and sixteen 10-wk-old (10ws) male domestic farm swine. Atropine (10(-7) M) caused inhibition of t ... Full text Link to item Cite

Effect of maturational changes in myosin content and morphometry on airway smooth muscle contraction.

Journal Article Am J Physiol · June 1991 Featured Publication We studied the relationship of airway morphometry, the content of myosin heavy-chain and isoform stoichiometry, and the distribution of bronchoconstrictor responses in the airways of maturing swine. Lungs were excised in 2-wk-old farm swine (2ws; n = 13) a ... Full text Link to item Cite

Effect of maturation on topographic distribution of bronchoconstrictor responses in large diameter airways of young swine.

Journal Article Am Rev Respir Dis · January 1991 We studied the effect of maturation on the topographic distribution of airway constriction in Generations 0 (trachea) through 6 in fourteen 2-wk-old swine (2ws) and sixteen 10-wk-old swine (10ws) in vivo and in excised airways from seven 2ws and seven 10ws ... Full text Link to item Cite

Ontogenic expression of acetylcholinesterase activity in trachealis of young swine

Journal Article American Journal of Physiology - Lung Cellular and Molecular Physiology · 1991 Previous investigations have demonstrated that cholinergic contraction of porcine tracheal smooth muscle (TSM) decreases between the second and tenth weeks of life. In this investigation, we hypothesized that the greater contractile response to acetylcholi ... Cite

Effect of maturational changes in myosin content and morphometry on airway smooth muscle contraction

Journal Article American Journal of Physiology - Lung Cellular and Molecular Physiology · 1991 We studied the relationship of airway morphometry, the content of myosin heavy-chain and isoform stoichiometry, and the distribution of bronchoconstrictor responses in the airways of maturing swine. Lungs were excised in 2-wk-old farm swine (2ws; n = 13) a ... Cite

Maturation of acetylcholinesterase expression in tracheal smooth muscle contraction.

Journal Article Am J Physiol · August 1990 Featured Publication We examined postganglionic development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by cholinomimetic activation and electrical field depolarization in vitro. Epithelium-intact tracheal strips excised from ... Full text Link to item Cite

Maturation of acetylcholinesterase expression in tracheal smooth muscle contraction

Journal Article American Journal of Physiology - Lung Cellular and Molecular Physiology · 1990 We examined postganglionic development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by cholinomimetic activation and electrical field depolarization in vitro. Epithelium-intact tracheal strips excised from ... Cite

Expression of airway contractile properties and acetylcholinesterase activity in swine.

Journal Article J Appl Physiol (1985) · July 1989 We studied the effect of maturation on contractile properties of tracheal smooth muscle from seventeen 2-wk-old swine (2ws) and fifteen 10-wk-old swine (10ws) in situ and in vitro. The response to parasympathetic stimulation was studied in situ in isometri ... Full text Link to item Cite

Evidence for platelet-activating factor secretion during immune activation in dogs.

Journal Article J Appl Physiol (1985) · April 1989 To elucidate the potential physiological significance of platelet-activating factor (PAF) in acute bronchoconstriction, we studied the effect of Ascaris suum antigen on the tachyphylactic response to PAF in 15 natively allergic mongrel dogs in vivo. Active ... Full text Link to item Cite

Effects of vasomotor- and mediator-induced hypotension on bronchomotor tone in swine.

Journal Article J Appl Physiol (1985) · April 1989 We studied the sympathetic neural response on airways to hypotensive stimuli in 19 swine in vivo. The effects of pharmacologically induced hypotension with nitroprusside (NTP) and hypotension elicited by intravenous compound 48/80 (48/80), a mast cell degr ... Full text Link to item Cite

PAF-induced contraction of canine trachea mediated by 5-hydroxytryptamine in vivo.

Journal Article J Appl Physiol (1985) · February 1989 We studied the secretory correlates of tracheal smooth muscle contraction caused by platelet-activating factor (PAF) in nine mongrel dogs in vivo. In five dogs, dose-response curves were generated by rapid intra-arterial injection of 10(-10) to 10(-6) mol ... Full text Link to item Cite

Effect of beta-adrenergic blockade and sympathetic stimulation on canine bronchial mast cell response to immune degranulation in vivo.

Journal Article Am Rev Respir Dis · January 1989 We examined the effect of beta-adrenoceptor blockade and residual alpha-adrenoceptor effects during sympathetic stimulation on mast cell secretion of histamine in 12 natively allergic mongrel dogs. Bronchial mast cell response was measured as the arteriove ... Full text Link to item Cite

Distribution of bronchoconstrictor responses in isolated-perfused rat lung.

Journal Article J Appl Physiol (1985) · January 1989 We studied the effects of bronchoconstrictor stimuli administered selectively through isolated-perfused preparations of the bronchial and pulmonary circulations of 80 Sprague-Dawley rats. Dose-related contraction was elicited with infusion of acetylcholine ... Full text Link to item Cite

Mechanisms of airway hypercontractility in basenji-greyhound dogs.

Journal Article J Appl Physiol (1985) · November 1987 The comparative effects of contractile agonists and physiological stimulation of the tracheal and bronchial smooth muscle (BSM) response were studied isometrically in situ in five Basenji-greyhound (BG) and six mongrel dogs. Frequency-response curves gener ... Full text Link to item Cite

Homeostatic regulation of airway smooth muscle tone by catecholamine secretion in swine.

Journal Article J Appl Physiol (1985) · March 1987 We studied the homeostatic secretory response of catecholamine secretion elicited by progressive bronchoconstriction in 18 swine in vivo. The potential reserve of the sympathetic nervous system (SNS) was first assessed by exogenous nicotinic stimulation wi ... Full text Link to item Cite

Aerosolized ribavirin in the treatment of patients with respiratory syncytial virus disease.

Journal Article Pediatr Infect Dis J · February 1987 Featured Publication Thirty children 1 to 33 months of age were enrolled in a study of aerosolized ribavirin therapy for respiratory syncytial virus lower respiratory tract illness. Twenty patients received ribavirin and 10 received placebo. There were no significant differenc ... Full text Link to item Cite

Potentiation of vagal contractile response by thromboxane mimetic U-46619.

Journal Article J Appl Physiol (1985) · September 1986 We studied the effect of the thromboxane mimetic U-46619 on tracheal smooth muscle contraction caused by bilateral stimulation of the vagus nerves in 14 mongrel dogs in situ. The parasympathetic contractile response was studied isometrically after beta-adr ... Full text Link to item Cite

Effectiveness of continuous positive airway pressure in the treatment of bronchomalacia in infants: a bronchoscopic documentation.

Journal Article Crit Care Med · February 1986 Featured Publication Continuous positive airway pressure (CPAP) was used to treat severe respiratory distress in four infants with bronchomalacia. Fiberoptic bronchoscopy diagnosed the area of bronchomalacia, documented the effects of CPAP on the airway, and helped determine a ... Full text Link to item Cite

Pulmonary function abnormalities in long-term survivors of childhood cancer.

Journal Article Med Pediatr Oncol · 1986 Featured Publication Pulmonary function testing (PFT) was performed on 29 long-term survivors of childhood cancer. The patients, whose mean age was 11.7 years and whose mean age at diagnosis was 3.7 years, included 12 females and 17 males. Original diagnoses included 15 patien ... Full text Link to item Cite

Pseudomonas colonization in cystic fibrosis. A study of 160 patients.

Journal Article JAMA · July 7, 1978 We investigated the role of Pseudomonas aeruginosa colonization in the respiratory tracts of cystic fibrosis (CF) patients to relate the effect of this colonization to progression of bronchial airway pathologic conditions and to the patients' clinical prog ... Link to item Cite