Abstract:
RATIONALE:Donor mesenchymal stromal/stem cell (MSC) expansion and fibrotic differentiation is associated with development of bronchiolitis obliterans syndrome (BOS) in human lung allografts. However, the regulators of fibrotic differentiation of these resident mesenchymal cells are not well understood. OBJECTIVES:This study examines the role of endogenous and exogenous prostaglandin (PG)E2 as a modulator of fibrotic differentiation of human lung allograft-derived MSCs. METHODS:Effect of PGE2 on proliferation, collagen secretion, and α-smooth muscle actin (α-SMA) expression was assessed in lung-resident MSCs (LR-MSCs) derived from patients with and without BOS. The response pathway involved was elucidated by use of specific agonists and antagonists. MEASUREMENT AND MAIN RESULTS:PGE2 treatment of LR-MSCs derived from normal lung allografts significantly inhibited their proliferation, collagen secretion, and α-SMA expression. On the basis of pharmacologic and small-interfering RNA approaches, a PGE2/E prostanoid (EP)2/adenylate cyclase pathway was implicated in these suppressive effects. Stimulation of endogenous PGE2 secretion by IL-1β was associated with amelioration of their myofibroblast differentiation in vitro, whereas its inhibition by indomethacin augmented α-SMA expression. LR-MSCs from patients with BOS secreted significantly less PGE2 than non-BOS LR-MSCs. Furthermore, BOS LR-MSCs were found to be defective in their ability to induce cyclooxygenase-2, and therefore unable to up-regulate PGE2 synthesis in response to IL-1β. BOS LR-MSCs also demonstrated resistance to the inhibitory actions of PGE2 in association with a reduction in the EP2/EP1 ratio. CONCLUSIONS:These data identify the PGE2 axis as an important autocrine-paracrine brake on fibrotic differentiation of LR-MSCs, a failure of which is associated with BOS.
journal_name
Am J Respir Crit Care Medauthors
Walker NM,Badri LN,Wadhwa A,Wettlaufer S,Peters-Golden M,Lama VNdoi
10.1164/rccm.201105-0834OCsubject
Has Abstractpub_date
2012-01-01 00:00:00pages
77-84issue
1eissn
1073-449Xissn
1535-4970pii
201105-0834OCjournal_volume
185pub_type
杂志文章abstract:RATIONALE:Venous thromboembolism is difficult to diagnose in critically ill patients and may increase morbidity and mortality. OBJECTIVES:To evaluate the cost-effectiveness of strategies to reduce morbidity from venous thromboembolism in critically ill patients. METHODS:A Markov decision analytic model to compare wee...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201106-1059OC
更新日期:2011-12-01 00:00:00
abstract::Collections of sputum from 105 patients with newly diagnosed pulmonary tuberculosis were made before and at 1 and 2 d after the start of chemotherapy with isoniazid (INH) alone given to groups of patients in doses of 600 mg, 300 mg, 150 mg, 75 mg, 37.5 mg, 18.75 mg, and 9 mg daily, as well as from an untreated group. ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.156.3.9609132
更新日期:1997-09-01 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) is a highly prevalent disorder in children, in which enlarged adenotonsillar tissues (AT) play a major pathophysiologic role. Mechanisms leading to the proliferation and hypertrophy of AT in children who subsequently develop OSA remain unknown, and surgical extirpation of AT is a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200909-1398OC
更新日期:2010-05-15 00:00:00
abstract::We have recently demonstrated the development of systemic hypertension in a canine model of obstructive sleep apnea (OSA), but the underlying physiological mechanisms were not identified. Therefore, the purpose of this study was to examine the effect of OSA on arterial baroreceptor control of heart rate (HR) in this c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.4.9806114
更新日期:1999-04-01 00:00:00
abstract::Chronic obstructive pulmonary disease (COPD) is a condition in which continuous bronchodilation may have clinical advantages. This study evaluated salmeterol, a beta-agonist bronchodilator with a duration of action substantially longer than that of short-acting beta-agonists, compared with ipratropium, an anticholiner...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1164/ajrccm.163.5.9903053
更新日期:2001-04-01 00:00:00
abstract::Exposure to fine airborne particulate matter (PM(2.5)) is associated with cardiovascular events and mortality in older and cardiac patients. Potential physiologic effects of in-vehicle, roadside, and ambient PM(2.5) were investigated in young, healthy, nonsmoking, male North Carolina Highway Patrol troopers. Nine troo...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200310-1463OC
更新日期:2004-04-15 00:00:00
abstract::Mechanical ventilation may promote overdistension-induced pulmonary lesions in patients with acute respiratory distress syndrome (ARDS). The static pressure-volume (P-V) curve of the respiratory system can be used to determine the lung volume and corresponding static airway pressure at which lung compliance begins to ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.1.7599810
更新日期:1995-07-01 00:00:00
abstract::In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the inju...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.4.2005127
更新日期:2001-08-15 00:00:00
abstract::To determine the factors contributing to tuberculosis incidence in the U.S.-born and foreign-born populations in San Francisco, California, and to assess the effectiveness of tuberculosis control efforts in these populations, we performed a population-based molecular epidemiologic study using 367 patients with strains...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.6.9804029
更新日期:1998-12-01 00:00:00
abstract:RATIONALE:Acute lung injury (ALI) acts as a complex genetic trait, yet its genetic risk factors remain incompletely understood. Large-scale genotyping has not previously been reported for ALI. OBJECTIVES:To identify ALI risk variants after major trauma using a large-scale candidate gene approach. METHODS:We performed...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.201005-0701OC
更新日期:2011-05-15 00:00:00
abstract::Despite extensive research into the etiology and treatment of severe sepsis, little is known about its epidemiology in children. We sought to determine the age- and sex-adjusted incidence, outcome, and associated hospital costs of severe sepsis in United States children using 1995 hospital discharge and population dat...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200207-682OC
更新日期:2003-03-01 00:00:00
abstract::A group of male amateur cyclists was studied in the summer of 1991 in the east of the Netherlands. Lung function was measured before and after training sessions or competitive races on a number of occasions. Continuous heart rate monitors were employed to document exercise levels. Heart rate averaged 161 beats/min dur...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.150.4.7921470
更新日期:1994-10-01 00:00:00
abstract:RATIONALE:Clinical benefits of fixed-dose 100-mg subcutaneous (SC) mepolizumab in prednisone-dependent patients are modest when sputum eosinophilia is not adequately controlled. OBJECTIVES:This study compared treatment response of weight-adjusted intravenous (IV) reslizumab in patients previously treated with 100-mg S...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201707-1323OC
更新日期:2018-01-01 00:00:00
abstract:RATIONALE:Bronchial remodeling, including increased bronchial smooth muscle (BSM) mass, contributes to bronchial obstruction in asthma. However, its mechanisms are complex and remain controversial. Recently, a role of the chitinase 3-like 1 protein (YKL-40) has been evoked in asthma. Indeed, YKL-40 concentration was in...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201105-0915OC
更新日期:2012-04-01 00:00:00
abstract::Infection of the cystic fibrosis (CF) airways elicits an exaggerated, interleukin-8 (IL-8) mediated, neutrophil inflammatory response. Necrosing neutrophils release DNA and actin into the airways, increasing the viscoelasticity of airway secretions. Mucolytics aim to improve airway clearance by reducing this viscoelas...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.5.9908107
更新日期:2000-11-01 00:00:00
abstract::To elucidate which cells are synthesizing tenascin in usual interstitial pneumonia (UIP) we have analyzed thoracoscopic or open lung biopsies from 30 patients with UIP by mRNA in situ hybridization, using (35)S-labeled tenascin RNA probes. The phenotype of the cells expressing tenascin mRNA was confirmed by immunohist...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.3.9809115
更新日期:2000-03-01 00:00:00
abstract::Rationale: Recent retrospective evidence suggests the efficacy of early norepinephrine administration during resuscitation; however, prospective data to support this assertion are scarce. Objectives: To conduct a phase II trial evaluating the hypothesis that early low-dose norepinephrine in adults with sepsis with hyp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.201806-1034OC
更新日期:2019-05-01 00:00:00
abstract::Induced sputum using hypertonic saline (HS) is a useful research tool to study airway inflammation (AI). HS provocation testing can also be used to measure airway hyperresponsiveness (AHR). A combined HS challenge and sputum induction procedure has been developed to permit assessment of AI and AHR in a single test. Th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.7.2103015
更新日期:2001-10-01 00:00:00
abstract::DNA fingerprinting of Mycobacterium tuberculosis is used to study the epidemiology of tuberculosis, but the specificity of the widely used IS6110 technique has not been validated. Isolates from Denver, Colorado from December 1988 through June 1994 were fingerprinted with the IS6110 technique. Available records were re...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.3.9117000
更新日期:1997-03-01 00:00:00
abstract::The inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta), have been associated with accelerated metabolism and protein turnover following exogenous administration in normal humans. We hypothesized that these inflammatory cytokines might contribute to the weight-losing proc...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.2.8564110
更新日期:1996-02-01 00:00:00
abstract:RATIONALE:Data on hemoptysis of unknown origin (i.e., "cryptogenic") are scarce and the outcome of patients affected is controversial. OBJECTIVES:To describe the clinical spectrum and course of patients with cryptogenic hemoptysis, as well as pathologic findings when surgery is performed. METHODS:A cohort of 81 patie...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200609-1362OC
更新日期:2007-06-01 00:00:00
abstract:RATIONALE:Although frequent, little is known about early-onset pneumonia that occurs in the postresuscitation period. Although induced hypothermia is recommended as a method of improving neurological outcome, its influence on the occurrence of early-onset pneumonia is not well defined. OBJECTIVES:To describe the incid...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究
doi:10.1164/rccm.201102-0331OC
更新日期:2011-11-01 00:00:00
abstract:RATIONALE:The airway surface liquid, the thin layer of liquid covering the airways, is essential for mucociliary clearance and as a barrier against microbial and other noxious agents. Proteins secreted into the airway surface liquid by epithelial and nonepithelial cells may be important in innate immunity and to improv...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200409-1185OC
更新日期:2005-11-01 00:00:00
abstract::To gain insight into the source of exhaled nitric oxide (NO) in normal humans, we examined the effects of respiratory pattern on the concentration of NO in exhaled air while subjects were wearing a noseclip and then under endotracheal intubation, using a specially designed gas sampling system to separate exhaled air i...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.5.8912750
更新日期:1996-11-01 00:00:00
abstract::The development of sensitization to inhaled allergens is determined by the interaction of multiple genetic and environmental influences. Occupational sensitization to low-molecular-weight chemicals allows a specific immunological response to an inhaled hapten to be studied in a well-defined population with characteriz...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.2.9807065
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:The clinical utility of bronchoalveolar lavage fluid (BAL) cell analysis for the diagnosis and management of patients with interstitial lung disease (ILD) has been a subject of debate and controversy. The American Thoracic Society (ATS) sponsored a committee of international experts to examine all relevant l...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,实务指引
doi:10.1164/rccm.201202-0320ST
更新日期:2012-05-01 00:00:00
abstract:RATIONALE:Th2 cytokines play an important role in allergic diseases. These cytokines activate signal transduction pathways, including Janus kinase/signal transducer and activator of transcription (STAT) signaling. Although the suppressor of cytokine signaling (SOCS) family protein, a negative regulator of the Janus kin...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200806-992OC
更新日期:2009-06-01 00:00:00
abstract::Large pleural effusions are typically associated with dyspnea and potential respiratory compromise. Experimental evidence suggests that with large effusions, increased intrapleural pressure may be transmitted to the pericardial space, resulting in impaired cardiac filling and reduced stroke volume. We report two cases...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm/151.3_Pt_1.904
更新日期:1995-03-01 00:00:00
abstract::Little is known about the anti-asthmatic effects of powerful anti-inflammatory agents such as aspirin-like drugs. We compared the effects of two aspirin-like drugs with different pharmacologic activities, sodium salicylate (SSA) and indomethacin, with the effect of lysine acetylsalicylate (LASA), inhaled 30 min before...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.159.4.9709045
更新日期:1999-04-01 00:00:00
abstract::Previous studies suggest that lung function tests using monodisperse aerosols can help to identify early stages of lung diseases. We investigated intrapulmonary particle loss and aerosol bolus dispersion-a marker of convective gas transport-in 32 women with asymptomatic nonspecific bronchial hyperresponsiveness (BHR) ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.3.9805036
更新日期:1999-03-01 00:00:00