Abstract:
:A growing body of evidence suggests that neutrophil-derived proteinases play a major role in lung tissue damage in cystic fibrosis (CF). Most previous studies have focused on serine proteinases such as neutrophil elastase, providing no information on the extent to which metalloproteinases participate in proteolytic processes in CF. To address this issue, we evaluated the contribution of one of the major neutrophil metalloproteinases, i.e., 95 kDa gelatinase (type IV collagenase), to the total gelatinolytic activity measured in sputum specimens from 27 patients with CF. Compared with asthmatic children (n = 9), CF patients had a 6.7 times greater level of total gelatinase activity in sputum revealed by zymography. The 95 kDa gelatinase was increased 3.7-fold in the CF subjects (2,441 +/- 411 [SEM] arbitrary units [AU] x 10(6) per ml of sputum versus 665 +/- 201 in asthmatics) and the 88-kDa active form 23.2-fold (2,272 +/- 372 AU x 10(6) per ml of sputum versus 98 +/- 43, respectively). Using radiolabeled 3H-gelatin as the substrate, we demonstrated uninhibited gelatinolytic activity in all CF patients; this activity was significantly correlated to disease severity as assessed by pulmonary function tests. Western blotting using anti-tissue inhibitor of metalloproteinase (anti-TIMP) and anti-95/88-kDa gelatinase antibodies demonstrated a more than 10-fold excess of 95/88 kDa gelatinase over TIMP. Bacterial proteinases from Pseudomonas aeruginosa were shown to contribute little to the gelatinolytic activity measured in sputum supernatants from patients with CF, although culture supernatants from various P. aeruginosa strains expressed gelatinolytic activity in vitro. Finally, lung damage, as assessed by increased type IV collagen degradation products in sputum, was significantly correlated to concentrations of active 88 kDa gelatinase. These data argue for a significant role of 95/88 kDa gelatinase in airway damage in CF.
journal_name
Am J Respir Crit Care Medauthors
Delacourt C,Le Bourgeois M,D'Ortho MP,Doit C,Scheinmann P,Navarro J,Harf A,Hartmann DJ,Lafuma Cdoi
10.1164/ajrccm.152.2.7633740subject
Has Abstractpub_date
1995-08-01 00:00:00pages
765-74issue
2eissn
1073-449Xissn
1535-4970journal_volume
152pub_type
杂志文章abstract:RATIONALE:Systemic sclerosis (SSc)-associated pulmonary arterial hypertension (PAH) portends worse outcome than other forms of PAH. Vasoconstrictive and vascular remodeling actions of endothelin (ET) 1 and angiotensin (Ang) II via endothelin receptor type A (ETAR) and Ang receptor type-1 (AT1R) activation are implicate...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201403-0442OC
更新日期:2014-10-01 00:00:00
abstract::Cyclophosphamide-induced lung toxicity may be difficult to recognize because of the presence of confounding variables such as concomitant use of other cytotoxic drugs, opportunistic infections, diffuse pulmonary malignancy, radiation pneumonitis, and oxygen toxicity. The purpose of this retrospective analysis was to i...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,评审
doi:10.1164/ajrccm.154.6.8970380
更新日期:1996-12-01 00:00:00
abstract:RATIONALE:Asthma commonly originates in early life in association with impaired lung function, which tracks to adulthood. OBJECTIVES:Within the context of a prospective birth cohort study, we investigated the association between single nucleotide polymorphisms (SNPs) in a disintegrin and metalloprotease 33 (ADAM33) ge...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200412-1708OC
更新日期:2005-07-01 00:00:00
abstract:RATIONALE:Sarcoidosis is known as a disease with high heterogeneity in clinical severity and inflammatory activity. On the basis of radiologic criteria, John Guyette Scadding developed a classification system, which is widely used, but is insufficient for clinical decision making. Therefore, biomarkers and genetic mark...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200705-742OC
更新日期:2008-02-01 00:00:00
abstract:RATIONALE:Studies in patients and experimental animals provide compelling evidence of the involvement of the major thrombin receptor, proteinase-activated receptor-1 (PAR(1)), and the potent chemokine, chemokine (CC motif) ligand-2 (CCL2)/monocyte chemotactic protein-1, in the pathogenesis of idiopathic pulmonary fibro...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200712-1827OC
更新日期:2009-03-01 00:00:00
abstract::A variety of substances including human meconium have been found to affect adversely the surface tension-lowering activity of pulmonary surfactants, and this effect may be important in the pathogenesis of a number of human diseases. To find whether inactivation of surfactant could be prevented or reduced by nonionic p...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.5.9808047
更新日期:1999-05-01 00:00:00
abstract:RATIONALE:In cystic fibrosis, abnormal glucose tolerance is associated with decreased lung function and worsened outcomes. Translational evidence indicates that abnormal glucose tolerance may begin in early life. OBJECTIVES:To determine whether very young children with cystic fibrosis have increased abnormal glucose t...
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.201512-2518OC
更新日期:2016-10-15 00:00:00
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:RATIONALE:IL-4 and IL-13 share many biological functions important in the development of allergic airway inflammation and are implicated in the pathogenesis of asthma. AMG 317 is a fully human monoclonal antibody to IL-4Ralpha that blocks both IL-4 and IL-13 pathways. OBJECTIVES:To evaluate efficacy and safety of AMG ...
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.200909-1448OC
更新日期:2010-04-15 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
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:Corticosteroids are the antiinflammatory treatment of choice in asthma. Treatment guidelines are mainly symptom-driven but symptoms are not closely related to airway inflammation. The fraction of nitric oxide in exhaled air (FENO) is a marker of airway inflammation in asthma. OBJECTIVE:We evaluated whether t...
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.200503-458OC
更新日期:2005-10-01 00:00:00
abstract:RATIONALE:Exhaled carbon monoxide (CO) and arterial blood carboxyhemoglobin concentrations (Hb-CO) increase in inflammatory pulmonary diseases. OBJECTIVES:To study whether arterial Hb-CO is useful to monitor disease activity in patients with chronic obstructive pulmonary disease (COPD) who had stopped smoking. METHOD...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.200407-914OC
更新日期:2005-06-01 00:00:00
abstract::Several modalities of ventilatory support have been proposed to gradually withdraw patients from mechanical ventilation, but their respective effects on the outcome of weaning from mechanical ventilation are not known. We conducted a randomized trial in three intensive care units in mechanically ventilated patients wh...
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.150.4.7921460
更新日期:1994-10-01 00:00:00
abstract::Rationale: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma targeting airway smooth muscle (ASM). Observational studies have shown ASM mass reduction after BT, but appropriate control groups are lacking. Furthermore, as treatment response is variable, identifying optimal candidates for BT tre...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201911-2298OC
更新日期:2021-01-15 00:00:00
abstract::We investigated airway responsiveness to mannitol, a new hyperosmolar challenge, in persons hyperresponsive to airway drying. We studied 36 asthmatic subjects, 18 to 40 yr of age, responsive to exercise (n = 23) and eucapnic hyperventilation (n = 28) defined by a 10% fall in FEV1. Fifteen subjects performed both chall...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.158.4.9802087
更新日期:1998-10-01 00:00:00
abstract::Reduced diaphragm contractility has been described in normal subjects after whole body endurance exercise, and it indicates low frequency fatigue (LFF); it is unknown whether LFF is of clinical importance. We therefore studied the effect of treadmill exercise to exhaustion on diaphragm contractility in six patients wi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.3.7663810
更新日期:1995-09-01 00:00:00
abstract::Susceptibility to the development of asthma and other atopic diseases is known to be associated with genetic components, and several candidate genes have been reported to be linked to atopy in Caucasian populations. We conducted a study of linkage between asthma and markers on chromosomes 5q31-q33 and 11q13 in 68 Japa...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.156.5.9702084
更新日期:1997-11-01 00:00:00
abstract::The epithelium of the paranasal sinuses produces nitric oxide (NO), which probably plays a major role in the nonspecific defense of these cavities through its bacteriostatic and cilia motility stimulation properties. Abundant eosinophils of nasal polyps potentially generate superoxide anion (O2-*), but NO and O2-* ina...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.163.1.2002125
更新日期:2001-01-01 00:00:00
abstract::Partial liquid ventilation (PLV) has been shown to be an effective means of improving oxygenation in the injured lung. However, little is known about how approach to ventilation during PLV affects gas exchange and pulmonary mechanics. We hypothesized that gas exchange and pulmonary mechanics would be best with positiv...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.4.9711021
更新日期:1999-04-01 00:00:00
abstract:RATIONALE:Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in asthma. Its role in the disease process before the onset of respiratory symptoms remains unclear. OBJECTIVES:To examine whether elevated NO in newborns with clinically naive airways is associated with subsequent respirator...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200606-782OC
更新日期:2006-12-15 00:00:00
abstract::Rationale: Lumacaftor-ivacaftor is a CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination recently approved for patients with cystic fibrosis (CF) homozygous for the Phe508del mutation.Objectives: To evaluate the safety and effectiveness of lumacaftor-ivacaftor in adolescents (≥12 yr) and a...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201906-1227OC
更新日期:2020-01-15 00:00:00
abstract:RATIONALE:In the absence of active tuberculosis, a positive tuberculin skin test (TST) or interferon-γ release assay (IGRA) result defines latent infection with Mycobacterium tuberculosis, although test results may vary depending on immunodeficiency. OBJECTIVES:This study compared the performance of TST and IGRAs in f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201405-0967OC
更新日期:2014-11-15 00:00:00
abstract:RATIONALE:Increased thickness of the airway smooth muscle (ASM) layer in asthma may result from hyperplasia or hypertrophy of muscle cells or increased extracellular matrix (ECM). OBJECTIVES:To relate ASM hypertrophy, ASM hyperplasia, and deposition of ECM to the severity and duration of asthma. METHODS:Airways from ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201110-1849OC
更新日期:2012-05-15 00:00:00
abstract::Muscle nerve sympathetic activity (MSA), the interval between two R-waves in the ECG, or the interbeat interval (RR-interval), and blood pressure (BP) were recorded in 10 awake patients with obstructive sleep apnea (OSA) and in nine sex- and age-matched controls. Changes in RR-interval and MSA, evoked by sodium nitrop...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/ajrccm.154.5.8912770
更新日期:1996-11-01 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:Severe asthma (SA) remains poorly understood. Mast cells (MC) are implicated in asthma pathogenesis, but it remains unknown how their phenotype, location, and activation relate to asthma severity. OBJECTIVES:To compare MC-related markers measured in bronchoscopically obtained samples with clinically relevant...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201002-0295OC
更新日期:2011-02-01 00:00:00
abstract::Patients in whom acid-fast bacilli smear-positive pulmonary tuberculosis was newly diagnosed were randomized to receive 400 mg moxifloxacin, 300 mg isonaizid, or 600 mg rifampin daily for 5 days. Sixteen-hour overnight sputa collections were made for the 2 days before and for 5 days of monotherapy. Bactericidal activi...
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.200305-682OC
更新日期:2003-12-01 00:00:00
abstract::To determine the usefulness of positron emission tomography with fluoro-2-deoxyglucose (PET-FDG) in assessing mediastinal disease in patients with non-small-cell lung cancer (NSCLC) and to compare its yield to that of computed tomography (CT), we performed a prospective consecutive sample investigation in a university...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.6.8520780
更新日期:1995-12-01 00:00:00
abstract::Acute respiratory distress syndrome (ARDS) is characterized by an extensive alveolar capillary leak, permitting contact between intra-alveolar factors and the endothelium. To investigate whether factors contained in the alveolar milieu induce cell death in human lung microvascular endothelial cells, we exposed these c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.2109004
更新日期:2002-09-01 00:00:00