Abstract:
RATIONALE:Long-term intermittent hypoxia (LTIH) exposure in adult mice, modeling oxygenation patterns of moderate-severe obstructive sleep apnea, results in lasting hypersomnolence and is associated with nitration and oxidation injuries in many brain regions, including wake-active regions. OBJECTIVES:We sought to determine if LTIH activates inducible nitric oxide synthase (iNOS) in sleep/wake regions, and if this source of NO contributes to the LTIH-induced proinflammatory gene response, oxidative injury, and wake impairments. METHODS:Mice with genetic absence of iNOS activity and wild-type control animals were exposed to 6 weeks of long-term hypoxia/reoxygenation before behavioral state recordings, molecular and biochemical assays, and a pharmacologic intervention. MEASUREMENTS AND MAIN RESULTS:Two weeks after recovery from hypoxia/reoxygenation exposures, wild-type mice showed increased iNOS activity in representative wake-active regions, increased sleep times, and shortened sleep latencies. Mutant mice, with higher baseline sleep times, showed no effect of long-term hypoxia/reoxygenation on sleep time latencies and were resistant to hypoxia/reoxygenation increases in lipid peroxidation and proinflammatory gene responses (tumor necrosis factor alpha and cyclooxygenase 2). Inhibition of iNOS after long-term hypoxia/reoxygenation in wild-type mice was effective in reversing the proinflammatory gene response. CONCLUSIONS:These data support a critical role for iNOS activity in the development of LTIH wake impairments, lipid peroxidation, and proinflammatory responses in wake-active brain regions, and suggest a potential role for inducible NO inhibition in protection from proinflammatory responses, oxidative injury, and residual hypersomnolence in obstructive sleep apnea.
journal_name
Am J Respir Crit Care Medauthors
Zhan G,Fenik P,Pratico D,Veasey SCdoi
10.1164/rccm.200411-1564OCkeywords:
subject
Has Abstractpub_date
2005-06-15 00:00:00pages
1414-20issue
12eissn
1073-449Xissn
1535-4970pii
200411-1564OCjournal_volume
171pub_type
杂志文章abstract:RATIONALE:Pulmonary complications (PCs) cause significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HCT). Shifts in gut microbiota have been linked to HCT outcomes; however, their effect on PCs is unknown. OBJECTIVES:To investigate whether changes in gut microbiota are associate...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201507-1491OC
更新日期:2016-08-15 00:00:00
abstract::We have investigated the influence of the cytokine tumor necrosis factor alpha (TNF alpha), an important mediator of sepsis, on in vitro hamster diaphragm contractility. Costal diaphragm strips were excised and mounted on an experimental apparatus consisting of a force transducer and servomotor. Preparations were rand...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.5.8630610
更新日期:1996-05-01 00:00:00
abstract:RATIONALE:There is consensus on the need to address social determinants of tuberculosis (TB) to achieve TB control, but evidence based on interventions is lacking. OBJECTIVES:We reanalyzed data from the sociomedical experiment performed at the Papworth Village Settlement in England, where the impact of stable employme...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201201-0023OC
更新日期:2012-09-01 00:00:00
abstract::The expression of renin-angiotensin system components and the elevation of angiotensin-converting enzyme (ACE) in a number of fibrotic lung diseases suggests angiotensin II (AII) could play a role in the pathogenesis of pulmonary fibrosis. However, the effect of AII on lung fibroblasts has not previously been assessed...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.6.9907004
更新日期:2000-06-01 00:00:00
abstract:RATIONALE:Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease (ILD) characterized by abnormal extracellular matrix (ECM) remodeling. We hypothesized that ECM remodeling might result in a plasma profile of proteins specific for IPF that could distinguish patients with IPF from other idi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201505-0862OC
更新日期:2016-11-15 00:00:00
abstract:RATIONALE:Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia. OBJECTIVES:To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patien...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201301-0079OC
更新日期:2013-10-15 00:00:00
abstract:RATIONALE:Airway remodeling is an important feature of chronic asthma that causes irreversible airflow obstruction. Although asthma is considered to be a Th2 disease, the role of T-bet and GATA-3, the key transcription factors for differentiation toward Th1 and Th2 cells, in the pathogenesis of airway remodeling is poo...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200601-079OC
更新日期:2006-07-15 00:00:00
abstract:RATIONALE:Activin-A is up-regulated in various respiratory disorders. However, its precise role in pulmonary pathophysiology has not been adequately substantiated in vivo. OBJECTIVES:To investigate in vivo the consequences of dysregulated Activin-A expression in the lung and identify key Activin-A-induced processes th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201105-0784OC
更新日期:2012-02-15 00:00:00
abstract::Systemic inflammation is present in chronic obstructive pulmonary disease (COPD), which has been linked to cardiovascular morbidity and mortality. We determined the effects of oral and inhaled corticosteroids on serum markers of inflammation in patients with stable COPD. We recruited 41 patients with mild to moderate ...
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/rccm.200404-543OC
更新日期:2004-10-01 00:00:00
abstract::We reported that systemic keratinocyte growth factor (KGF) given before bone marrow transplantation (BMT) prevents allogeneic T cell-dependent lung inflammation assessed on Day 7 post-BMT, but the antiinflammatory effects of KGF were impaired in mice injected with both T cells and conditioning regimen of cyclophospham...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.5.2002053
更新日期:2000-11-01 00:00:00
abstract:RATIONALE:S100A12 is overexpressed during inflammation and is a marker of inflammatory disease. Furthermore, it has been ascribed to the group of damage-associated molecular pattern molecules that promote inflammation. However, the exact role of human S100A12 during early steps of immune activation and sepsis is only p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201209-1602OC
更新日期:2013-06-15 00:00:00
abstract::Most patients with cystic fibrosis (CF) are infected by Pseudomonas aeruginosa. Dextran exhibits anti-adhesive effects in preventing attachment of P. aeruginosa to epithelial cells (1). The initial purpose of this study was to evaluate the potential of dextran to alter the rheology and ciliary transportability of CF s...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.3.9703059
更新日期:1998-03-01 00:00:00
abstract:RATIONALE:The effect of early life wheezing on respiratory function and continued symptoms through adolescence has not been fully described. Using data from a population-based birth cohort in Tucson, Arizona, we previously described four phenotypes based on the occurrence of wheezing lower respiratory illnesses before ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200504-525OC
更新日期:2005-11-15 00:00:00
abstract:RATIONALE:Bronchiolitis is the most common lower respiratory infection in infants; however, it remains unclear which infants with bronchiolitis will develop severe illness. In addition, although emerging evidence indicates associations of the upper-airway microbiome with bronchiolitis severity, little is known about th...
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.201701-0071OC
更新日期:2017-10-01 00:00:00
abstract::Epidemiological data indicate that living or working in a moldy building is associated with increased risk of respiratory symptoms and disease related to inflammatory reactions, but biochemical evidence linking cause and effect is still scarce. The staff working in a mold-contaminated school, and a reference group wit...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.6.9903023
更新日期:1999-12-01 00:00:00
abstract::We developed a bronchial provocation test (BPT) with a dry powder preparation of mannitol. The mannitol was inhaled from gelatin capsules containing 5, 10, 20, or 40 mg to a cumulative dose of 635 mg, and was delivered via an inhalator, Halermatic, or Dinkihaler device. We studied the airway sensitivity to inhaled man...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.156.3.9701113
更新日期:1997-09-01 00:00:00
abstract:RATIONALE:FVC has emerged as a standard primary endpoint in clinical trials evaluating novel therapies for patients with idiopathic pulmonary fibrosis (IPF). However, it has recently been proposed that all-cause mortality or a composite comprised of all-cause mortality and all-cause nonelective hospitalization be adopt...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201311-1951OC
更新日期:2014-04-01 00:00:00
abstract:RATIONALE:Improved understanding of the lung microbiome in HIV-infected individuals could lead to better strategies for diagnosis, therapy, and prophylaxis of HIV-associated pneumonias. Differences in the oral and lung microbiomes in HIV-infected and HIV-uninfected individuals are not well defined. Whether highly activ...
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.201501-0128OC
更新日期:2015-12-01 00:00:00
abstract::In normal airways, invasion of small numbers of pathogenic bacteria will not give rise to injury or local colonization. In chronic obstructive pulmonary disease, however, local conditions are changed, which may impair local defense systems and facilitate infection. These include: (1) factors promoting bacterial adhere...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.151.6.7767560
更新日期:1995-06-01 00:00:00
abstract::Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Methods: Patients with Group 1 PAH were included from two national registries wit...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201907-1447OC
更新日期:2020-06-01 00:00:00
abstract::The lungs of newborn rats exposed to 60% oxygen for 14 days develop an injury that shares morphologic similarities to human bronchopulmonary dysplasia (BPD). Neutrophil influx into the lung, as part of an inflammatory response, may play a pivotal role in the development of BPD. A neutrophil chemokine, cytokine-induced...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200402-215OC
更新日期:2004-12-01 00:00:00
abstract::We developed clonal cell lines of human bronchial smooth muscle origin by retroviral transduction of temperature-sensitive simian virus 40 large tumor (T) antigen. These cells show increased growth potential at 33 degrees C, but on shift to the nonpermissive temperature (39 degrees C), they show diminished or arrested...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200307-964OC
更新日期:2004-03-15 00:00:00
abstract:RATIONALE:Plasma transfusions are frequently prescribed for critically ill children, although their indications lack a strong evidence base. Plasma transfusions are largely driven by physician conceptions of need, and these are poorly documented in pediatric intensive care patients. OBJECTIVES:To identify patient char...
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.201503-0450OC
更新日期:2015-06-15 00:00:00
abstract:RATIONALE:Staphylococcus aureus is a major pathogen complicating postsurgical care. OBJECTIVES:To test the effect of sterile laparotomy (LAP) on pulmonary clearance of S. aureus in a murine model. METHODS:Control and LAP mice were infected intranasally with 10(8) cfu of S. aureus. Microbial clearance, pulmonary leuko...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200606-763OC
更新日期:2007-11-01 00:00:00
abstract::Although contraction of human isolated bronchi is mediated mainly by tachykinin NK2 receptors, NK1 receptors, via prostanoid release, contract small-size (approximately 1 mm in diameter) bronchi. Here, we have investigated the presence and biological responses of NK1 receptors in medium-size (2-5 mm in diameter) human...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.5.2002079
更新日期:2001-04-01 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::Men have higher prevalence rates of chronic obstructive pulmonary disease (COPD) than women, which has been attributed to the historically higher rates of cigarette smoking in males. However, the increased rates of cigarette smoking in females within the last several decades have been associated with steadily increasi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.6.2003112
更新日期:2000-12-01 00:00:00
abstract::A noninvasive method to characterize inflammation and infection in the airways of nonexpectorating children with cystic fibrosis (CF) is needed for clinical and research purposes. Accordingly, we performed sputum inductions by administering 3% saline to 11 healthy control children and 20 children with CF, composed of ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.8.2104075
更新日期:2001-10-15 00:00:00
abstract::Pulmonary infections are a significant cause of morbidity and mortality in patients with alcohol abuse and human immunodeficiency virus (HIV) infection, two immunocompromising conditions that frequently coexist. This study examined the separate and combined effects of in vivo lentiviral infection and in vitro alcohol ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.1.9905016
更新日期:2000-01-01 00:00:00
abstract::Recently described surgical approaches to the treatment of emphysema, including buttressed stapled volume reduction and laser coagulation, are associated with variable clinical outcomes. We examined objective preoperative factors as predictors of response to treatment in patients enrolled in a randomized trial of stap...
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.155.4.9105070
更新日期:1997-04-01 00:00:00