Abstract:
:We evaluated positron emission tomographic imaging of pulmonary transgene expression, using an enhanced mutant herpes simplex virus-1 thymidine kinase as the reporter gene, in the lungs of normal rats. Sixteen rats were studied 3 days after an intratracheal administration of 5 x 10(9) to 1 x 10(11) viral particles of a replication-incompetent adenovirus containing a fusion gene of the mutant kinase and green fluorescent protein. Three rats infected with adenovirus containing no insert (null vector) served as control subjects. Images were obtained 1 hour after an intravenous injection of 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine, an imaging substrate for the viral kinase. After euthanasia, tissue radioactivity was determined in a gamma counter, and thymidine kinase activity and green fluorescent protein levels were measured in lung tissue samples. Imaging and gamma counting radioactivity measurements were strongly and linearly correlated (r2 = 0.96, p < 0.001). Imaging detected thymidine kinase expression above background (null vector) in 15 of 16 rats, even at low viral doses that produced little to no measurable green fluorescent protein expression. Lung 9-(4-[18F]-fluoro-3-hydroxymethylbutyl)guanine uptake (as assessed by imaging) correlated with in vitro assays of both kinase activity (r(2) = 0.48, p < 0.001) and fluorescent protein (r(2) = 0.46, p < 0.001). We conclude that positron emission tomographic imaging is a sensitive and quantitative method for detecting pulmonary reporter gene expression noninvasively.
journal_name
Am J Respir Crit Care Medauthors
Richard JC,Zhou Z,Ponde DE,Dence CS,Factor P,Reynolds PN,Luker GD,Sharma V,Ferkol T,Piwnica-Worms D,Schuster DPdoi
10.1164/rccm.200210-1217OCkeywords:
subject
Has Abstractpub_date
2003-05-01 00:00:00pages
1257-63issue
9eissn
1073-449Xissn
1535-4970pii
200210-1217OCjournal_volume
167pub_type
杂志文章abstract::Rationale: Recent studies have demonstrated that extracellular vesicles (EVs) released during acute lung injury (ALI) were inflammatory.Objectives: The current study was undertaken to test the role of EVs induced and released from severe Escherichia coli pneumonia (E. coli EVs) in the pathogenesis of ALI and to determ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201812-2296OC
更新日期:2019-11-15 00:00:00
abstract:RATIONALE:S. aureus is the most common respiratory pathogen isolated from patients with cystic fibrosis (CF) in the US. While modes of acquisition and genetic adaptation have been described for Pseudomonas aeruginosa, resulting in improved diagnosis and treatment, these features remain more poorly defined for S. aureus...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.202003-0735OC
更新日期:2020-12-09 00:00:00
abstract:RATIONALE:Platelets may interact with the immune system in tuberculosis (TB) to regulate human inflammatory responses that lead to morbidity and spread of infection. OBJECTIVES:To identify a functional role of platelets in the innate inflammatory and matrix-degrading response in TB. METHODS:Markers of platelet activa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201710-2102OC
更新日期:2018-07-15 00:00:00
abstract::Bacterial lipopolysaccharide (LPS) is known to induce the expression of inducible nitric oxide synthase (iNOS) in the lung and to lead to increased pulmonary nitric oxide (NO) production. The contribution of various pulmonary cells to this phenomenon remains unclear. In this study, we used gadolinium chloride, a block...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.5.9705040
更新日期:1998-05-01 00:00:00
abstract::The present study was designed to examine whether clenbuterol (CLEN) could reduce dexamethasone (DEX)-induced diaphragm dysfunction. We studied four groups of New Zealand white (NZW) rabbits, each receiving one of the following daily injections subcutaneously for 2 wk: saline (control), DEX 3 mg/kg, DEX 3 mg/kg + CLEN...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.154.6.8970370
更新日期:1996-12-01 00:00:00
abstract::We derived reference values for slow vital capacity (VC) and flow-volume curve indexes (FVC, FEV(1), and flows) from the 1,185 tracings provided by 1,039 "normal" subjects who participated in one or both cross-sectional surveys of the Po River Delta study in 1980-1982 and in 1988-1991. Definition of "normal" was based...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.3.9906006
更新日期:2000-03-01 00:00:00
abstract::Hepatocyte growth factor (HGF) has recently been noted to function as a pulmotrophic factor for lung regeneration. The present study was conducted to determine if HGF would be induced in a rat model of pulmonary ischemia-reperfusion (IR) injury, which was established by occlusion of the left lung, and to examine the s...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.162.2.9908064
更新日期:2000-08-01 00:00:00
abstract::The effect of a dental appliance (DA) is usually evaluated in a single mandibular position reached after several weeks and corresponding to either improvement of symptoms or intolerance to any further advancement. The purpose of this study was to test the feasibility of one-night evaluation of the efficacy of a DA. Th...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.165.8.2108056
更新日期:2002-04-15 00:00:00
abstract::Noninvasive and invasive diagnostic techniques have been shown to achieve comparable performances in the evaluation of suspected ventilator-associated pneumonia (VAP). We studied the impact of both approaches on outcome in a prospective, open, and randomized study in three intensive care units (ICUs) of a 1,000-bed te...
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.162.1.9907090
更新日期:2000-07-01 00:00:00
abstract::Lymphangioleiomyomatosis (LAM), a disease that occurs primarily in women, is characterized by cystic lung lesions causing respiratory failure, which may require lung transplantation. Lung diffusion (DLCO) and/or FEV1 are decreased, but frequently not in parallel with each other. Because cardiopulmonary exercise testin...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200206-593OC
更新日期:2003-12-15 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::Chronic beryllium disease (CBD) provides a model system in which to evaluate the antigen-stimulated, cell-mediated, immune response that leads to granulomatous lung disease. We hypothesized that beryllium salts would stimulate bronchoalveolar lavage (BAL) cell release of tumor necrosis factor-alpha (TNF-alpha) and lnt...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.6.9610040
更新日期:1997-12-01 00:00:00
abstract:RATIONALE:The generation of protective secretory IgA relies on the epithelial polymeric immunoglobulin receptor (pIgR). pIgR expression is reduced in chronic obstructive pulmonary disease (COPD), but correlation to disease severity and underlying mechanisms remains unknown. OBJECTIVES:To address the hypothesis that pI...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201311-1971OC
更新日期:2014-09-01 00:00:00
abstract::Ventilation style influences lung injury and the amount of large-aggregate biophysically active surfactant in adult lungs. We asked how positive end-expiratory pressures (PEEP) would influence clinical responses and surfactant pools in surfactant-treated preterm lambs ventilated for 7 h with tidal volumes (VT) of 10 m...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.160.2.9902016
更新日期:1999-08-01 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 prospectively investigated the lower airway response in boilermakers overhauling an oil-powered boiler. We studied 26 male boilermakers with a mean age (SD) of 43.3 (8.6) yr. Pre-exposure spirometry and methacholine challenge tests were performed before beginning the boiler overhaul; postexposure tests were perform...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.5.7582280
更新日期:1995-11-01 00:00:00
abstract::Exaggerated airway narrowing in response to bronchoconstricting stimuli is a characteristic feature of asthmatic subjects. It is unknown whether the site of airway narrowing differs in asthmatic subjects from that observed in normal subjects. Increased airway wall thickness has been suggested as a contributing cause f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.154.5.8912780
更新日期:1996-11-01 00:00:00
abstract:RATIONALE:Spirometric detection of airway obstruction in adults requires separate predictive formulae for each ethnicity and sex for percentage of FEV(1)/FVC (%FEV(1)/FVC) and percentage of FEV(3)/FVC (%FEV(3)/FVC), the major measurements for defining airway obstruction. OBJECTIVES:To eliminate the need for multiple f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200604-517OC
更新日期:2006-09-01 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:Previous studies have demonstrated a high prevalence of sleep apnea (SA) in patients with chronic heart failure (HF), which is associated with higher rates of morbidity, mortality, and health care use. OBJECTIVES:To investigate the reported incidence, treatment, outcomes, and economic cost of SA in new-onset...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201003-0406OC
更新日期:2011-02-15 00:00:00
abstract::The effects of glutathione-S-transferase (GST) M1, GSTT1, and GSTP1 genotypes on lung function growth were investigated in 1,940 children enrolled in the Children's Health Study as fourth graders (aged 8-11 years) in two cohorts during 1993 and 1996 and were followed annually over a 4-year period. Genotypes for GSTM1 ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2112065
更新日期:2002-09-01 00:00:00
abstract:RATIONALE:Serum chitinases may be novel biomarkers of airway inflammation and remodeling, but less is known about factors regulating their levels. OBJECTIVES:To examine serum chitotriosidase activity and YKL-40 levels in patients with asthma and chronic obstructive pulmonary disease (COPD) and evaluate clinically rele...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201504-0760OC
更新日期:2016-01-15 00:00:00
abstract::Neutrophil infiltration is a major feature in the pathogenesis of the common cold, and respiratory viral infection is the major cause of asthma exacerbations. The factors regulating the neutrophil influx are unknown. Interleukin-8 (IL-8) is a potent neutrophil chemoattractant, which has been implicated in several infl...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.4.9105080
更新日期:1997-04-01 00:00:00
abstract:RATIONALE:Neutrophils are key players in chronic obstructive pulmonary disease (COPD), and increased numbers of neutrophils are present in sputum and lung tissue of patients with COPD. Interestingly, immunoglobulin free light chains (IgLC) are able to prolong the life of neutrophils; therefore, IgLC may contribute to t...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201104-0761OC
更新日期:2012-04-15 00:00:00
abstract::Lymphocyte migration from the blood into the lung has been suggested as being responsible for the increase of lymphocytes, in particular CD4 T cells, in the bronchoalveolar lavage (BAL) and bronchial mucosa in human asthma, but so far there has been no direct proof. We studied lymphocyte immigration and lymphocyte sub...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.2.9812021
更新日期:2000-02-01 00:00:00
abstract::Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were sig...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.157.6.9711039
更新日期:1998-06-01 00:00:00
abstract::We evaluated ultrasonic examination as a diagnostic tool for catheter misplacement and pneumothorax after central venous catheter insertion. Physicians in the intensive care unit (ICU) performed the ultrasonic examinations, and the results were compared with those of chest radiography. Eighty-five central venous cathe...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.3.2009042
更新日期:2001-08-01 00:00:00
abstract:RATIONALE:Reactivation tuberculosis (TB) occurs as a result of reactivation of latent TB infection (LTBI), and was reported to occur in the United States at a rate of 0.10 to 0.16 cases per 100 person-years in the 1950s; it has not been measured since. OBJECTIVES:To calculate the rate of reactivation TB in a U.S. comm...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200909-1355OC
更新日期:2010-08-01 00:00:00
abstract::To quantify changes in tissue oxygenation of pathologic lungs, we applied a novel method using near-infrared spectroscopy (NIRs). In in vitro experiments, we assayed the effect of photon scattering on the absorption spectra of an in vitro system simulating structures of lung, which consists of test tube containing air...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.5.97-01112
更新日期:1997-11-01 00:00:00
abstract::The renin angiotensin system plays an important role in the development of pulmonary artery remodeling and right ventricular hypertrophy in hypoxia-induced pulmonary hypertension as may occur in patients with COPD. Several polymorphisms of genes encoding for components of the renin angiotensin system such as the M235T...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9807060
更新日期:1999-06-01 00:00:00