A5041348182- Chronic Obstructive Pulmonary Disease (COPD) Research
- Protease and Inhibitor Mechanisms
- Neonatal Respiratory Health Research
- Peptidase Inhibition and Analysis
- Asthma and respiratory diseases
- Pulmonary Hypertension Research and Treatments
- Respiratory Support and Mechanisms
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Blood Coagulation and Thrombosis Mechanisms
- Systemic Sclerosis and Related Diseases
- Inhalation and Respiratory Drug Delivery
- Congenital Diaphragmatic Hernia Studies
- Acute Lymphoblastic Leukemia research
- Biochemical and Molecular Research
- Mesenchymal stem cell research
- Lung Cancer Diagnosis and Treatment
- Pleural and Pulmonary Diseases
- Air Quality and Health Impacts
- Pediatric health and respiratory diseases
- Atomic and Subatomic Physics Research
- Endoplasmic Reticulum Stress and Disease
- Medical Imaging and Pathology Studies
- Glutathione Transferases and Polymorphisms
- Rheumatoid Arthritis Research and Therapies
- Pneumonia and Respiratory Infections
Leiden University Medical Center
2016-2025
Leiden University
2006-2024
ERN GUARD-Heart
2020-2024
University of Zurich
2023
Pulmonary Associates
1997-2019
Tohoku University Hospital
2017
Ziekenhuis Gelderse Vallei
2013-2017
Medisch Centrum Leeuwarden
2016
University of Florence
2007
Istituto di Fisiologia Clinica
2007
Phagocytes are able to generate reactive oxygen species by an activatable NADPH oxidase system. We investigated the inhibition of activation a methoxy-substituted catechol, apocynin. Oxygen uptake neutrophils incubated with 300 microM apocynin was completely inhibited at 7 min after addition serum-treated zymosan (STZ), lagtime 2 3 min. The effect in relatively deficient myeloperoxidase about 50% longer when compared normal cells. Inhibition STZ-induced respiratory burst also observed human...
We have investigated whether restoration of the balance between neutrophil elastase and its inhibitor, α1-antitrypsin, can prevent progression pulmonary emphysema in patients with α1-antitrypsin deficiency. Twenty-six Danish 30 Dutch ex-smokers deficiency PI*ZZ phenotype moderate (FEV1 30% 80% predicted) participated a double-blind trial augmentation therapy. The were randomized to either (250 mg/kg) or albumin (625 infusions at 4-wk intervals for least 3 yr. Self-administered spirometry...
Inhalt Seite Zusammenfassung Einleitung 37 Ziele, Organisation des Projektes und Zeitplan der wichtigsten Empfehlungen Arbeitsgruppe zur Diagnose Behandlung Alpha-1-Antitrypsin-Mangel 38 Klinische Erkennung Alpha-1-Antitrypsin-Mangels Genetische Testung auf Lebererkrankungen 39 Andere Erkrankungen 40 Wirksamkeit Substitutionstherapie Allgemeines Management bei obstruktiver Atemwegserkrankung Literatur 41 Lungenerkrankung Erstellung dieses Dokuments Epidemiologie 42 Pathophysiologie...
Cigarette smoking results in oxidative stress and inflammation the lungs, which are involved pathogenesis of chronic obstructive pulmonary disease (COPD). 4-Hydroxy-2-nonenal (4-HNE), a highly reactive diffusible product lipid peroxidation, is key mediator oxidant-induced cell signaling apoptosis. 4-HNE has high affinity toward cysteine, histidine, lysine groups forms direct protein adducts. We investigated presence 4-HNE–modified proteins lung tissue obtained from subjects with without...
Antileukoprotease (ALP), or secretory leukocyte proteinase inhibitor, is an endogenous inhibitor of serine proteinases that present in various external secretions. ALP, one the major inhibitors human lung, a potent reversible elastase and, to lesser extent, cathepsin G. In equine neutrophils, antimicrobial polypeptide has some characteristics ALP been identified (M. A. Couto, S. L. Harwig, J. Cullor, P. Hughes, and R. I. Lehrer, Infect. Immun. 60:5042-5047, 1992). This report, together with...
Chronic airways inflammation is one of the features chronic obstructive pulmonary disease (COPD). We demonstrated previously that bronchiolar epithelium in COPD contains increased numbers macrophages and mast cells. Transforming growth factor β1 (TGF- β1) may be involved this influx because it has chemotactic activity for In study, we examined expression patterns TGF- β1, β receptors type I II RI RII) by immunohistochemistry mRNA situ hybridization peripheral lung tissue 14 current or...
Chronic obstructive pulmonary disease (COPD) is one of the most common causes death, with cigarette smoking among main risk factors. Hallmarks COPD include chronic airflow obstruction and inflammation in airway walls or alveolar septa. An earlier study reported elevated numbers macrophages mast cells within bronchiolar epithelium smokers COPD, compared without. Since specific chemokines may be involved this influx, situ protein mRNA expression monocyte chemoattractant 1 (MCP-1) interleukin 8...
FEV(1) is fundamental to the diagnosis and staging of chronic obstructive pulmonary disease. In emphysema, airflow obstruction usually coexists with impairment gas exchange, but discordance not infrequent. We hypothesized that variations in distribution emphysema would be associated functional differences therefore account for discordant physiology. used quantitative computed tomography assess severity 119 subjects alpha1-antitrypsin deficiency (PiZ phenotype) grouped them according pattern....
Two randomised, double-blind, placebo-controlled trials have investigated the efficacy of IV alpha-1 antitrypsin (AAT) augmentation therapy on emphysema progression using CT densitometry. Data from these similar trials, a 2-center Danish-Dutch study (n = 54) and 3-center EXAcerbations scan as Lung Endpoints (EXACTLE) 65), were pooled to increase statistical power. The change in 15th percentile lung density (PD15) measured by was obtained both trials. All subjects had 1 at baseline least...
Endoplasmic reticulum (ER) stress is increasingly recognized as an important mechanism in a wide range of diseases including cystic fibrosis, alpha-1 antitrypsin deficiency, Parkinson's and Alzheimer's disease. Therefore, there increased need for reliable quantitative markers detection ER human tissues cells. Accumulation unfolded or misfolded proteins the endoplasmic can cause stress, which leads to activation protein response (UPR). UPR signaling involves splicing X-box binding protein-1...
Background: Mesenchymal stromal cells (MSCs) may reduce inflammation and promote tissue repair in pulmonary emphysema. Aim: To study the safety feasibility of bone marrow-derived autologous (BM-) MSC intravenous administration to patients with severe Design: A phase I, prospective open-label registered at ClinicalTrials.gov as NCT01306513. Eligible had lung volume reduction surgery (LVRS) on two separate occasions. During first LVRS marrow was collected, from which MSCs were isolated...
<b>Background:</b> Lung densitometry derived from computed tomographic images offers an opportunity to quantify emphysema non-invasively, but a pathological standard cannot be applied validate its use in longitudinal monitoring studies. Consequently, forced expiratory volume 1 second (FEV<sub>1</sub>) remains the against which new methods must judged. We related progression of (15th percentile point and voxel index, threshold −950 Hounsfield units) disease stage FEV<sub>1</sub> decline two...
There is still controversy about the feasibility and long-term outcome of surgical treatment acquired diaphragm paralysis. We analyzed effects on pulmonary function level dyspnea after unilateral or bilateral plication.Between December 1996 January 2006, 22 consecutive patients underwent plication. Before surgery, spirometry in both seated supine positions a Baseline Dyspnea Index were assessed. The uncut was plicated as tight possible through limited lateral thoracotomy. Patients with...
Chronic obstructive pulmonary disease (COPD) is defined by progressive, irreversible airflow limitation and an inflammatory response of the lungs, usually to cigarette smoke. However, COPD a heterogeneous in terms clinical, physiologic, pathologic presentation. We aimed evaluate whether limitation, airway responsiveness, inflammation are separate entities underlying pathophysiology using factor analysis. A total 114 patients (99 males/15 females, age 62 +/- 8 years, 42 pack-years smoking, no...
Systemic sclerosis (SSc) is a connective tissue disease characterized by vascular inflammation and fibrosis. Visceral involvement, including cardiac manifestations, can lead to severe clinical complications, such as congestive heart failure, arrhythmias, sudden death. Conventional echocardiography parameters have limited sensitivity detect subtle myocardial dysfunction in patients with SSc. The aim of this study was assess, using novel speckle-tracking strain analysis, the presence SSc,...
Genetic factors play a role in chronic obstructive pulmonary disease (COPD) but are poorly understood. A number of candidate genes have been proposed on the basis pathogenesis COPD. These include matrix metalloproteinase (MMP) which tissue remodelling and fit with protease - antiprotease imbalance theory for cause Previous genetic studies MMPs COPD had inadequate coverage genes, reported conflicting associations both single nucleotide polymorphisms (SNPs) SNP haplotypes, plausibly due to...
Palovarotene is an oral γ-selective retinoid agonist. In animal emphysema models, palovarotene reduced inflammation, promoted structural repair and functional improvement. REPAIR (Retinoid treatment of Emphysema in Patients on the α<sub>1</sub>-antitrypsin International Registry), was investigator-initiated, double-blind, placebo-controlled randomised study to assess safety efficacy 5 mg·day<sup>−1</sup> given for 1 year 262 patients with severe deficiency confirmed by computed tomography....
Mesenchymal stromal cells (MSCs) are investigated for their potential to reduce inflammation and repair damaged tissue. Inflammation tissue damage hallmarks of chronic obstructive pulmonary disease (COPD) MSC infusion is a promising new treatment COPD. Inflammatory mediators attract MSCs sites affect immune-modulatory properties, but little known about effect on regenerative properties MSCs. This study investigates the pro-inflammatory cytokines TNF-α IL-1β MSCs, using an in vitro wound...