Decrease of vascular endothelial growth factor in macrophages from long-term smokers.

Vascular endothelial growth factor (VEGF), a survival factor for endothelial cells and a promoter of angiogenesis, is reportedly expressed in alveolar macrophages (AMs). To investigate whether long-term smoking with age affects VEGF expression in AMs, bronchoalveolar lavage (BAL) was performed on 18 young and 23 older volunteers with various smoking histories. The expressions of VEGF and its functional receptor, fms-like tyrosine kinase (Flt)-1, were quantified in AMs by real-time RT-PCR and, further, the level of VEGF in BAL fluid was determined by ELISA.

Effects of ageing and smoking on SP-A and SP-D levels in bronchoalveolar lavage fluid.

Surfactant protein (SP)-A and SP-D are collagen-like glycoproteins that are synthesised in the distal pulmonary epithelium. This study examined the effects of ageing and long-term smoking on SP-A and SP-D in the lungs. The possible links to the development of pulmonary emphysema were also investigated.

Positional ventricular tachycardia.

A 60-year-old man showed nonsustained repetitive monomorphic VT in the left lateral position, but this was terminated by deep inspiration. Echocardiography and MRI demonstrated a false tendon extending from the apex to the basal septum where the VT could have originated. Spontaneous remission occurred during the 16-year follow-up.

Chemokines in bronchiolar epithelium in the development of chronic obstructive pulmonary disease.

The inflammatory chemokines interleukin-8, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1, are reportedly involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although bronchiolar epithelial cells and macrophages are known to be the cellular sources, the relative contribution of each cell type remains to be elucidated. In the present study, we first quantified cytokine mRNA in human bronchiolar epithelial cells and macrophages obtained using laser-capture microdissection and explored the relationship with early-stage COPD.

Effect of low-dose theophylline on airway inflammation in COPD.

Objective: Recent studies have shown that theophylline may exert anti-inflammatory effects on neutrophils. We undertook to assess the effect of theophylline on airway inflammation in COPD.

Methodology: We performed a 4-week randomized double-blind, placebo-controlled study in 11 theophylline-naive patients with mild to moderate COPD.

Pulmonary Langerhans' cell histiocytosis presenting with an endobronchial lesion.

A 19-year-old man visited our hospital complaining of cough, sputum and low-grade fever. Chest radiograph and computed tomography findings suggested that he was suffering from pulmonary Langerhans' cell histiocytosis (PLCH). Bronchoscopy revealed a whitish elevated lesion at the bifurcation of the right upper lobe bronchus, and a specimen of this lesion showed the same pathological findings as pulmonary parenchymal lesions.

Spontaneous and inducible ventricular arrhythmias after myocardial infarction in mice.

Introduction: Remodeling of gap junctions has been implicated in development of ventricular arrhythmias following myocardial infarction (MI) but the specific contribution of reduced electrical coupling is not known. We addressed this question using hearts from mice heterozygous for a connexin43 null allele (Cx43(+/-)).

Methods: To determine whether Cx43-deficient mice exhibit increased spontaneous ventricular arrhythmias in the setting of chronic ischemic heart disease, radiofrequency transmitters were implanted in wild-type and Cx43(+/-) mice 2 days or 9 weeks after left anterior descending coronary artery ligation or sham operations.

Percutaneous coronary intervention for central sleep apnoea with ischaemic cardiomyopathy.

Central sleep apnoea is often recognized in patients with heart failure. Although the medical treatment to improve cardiac function is effective for sleep apnoea, direct evidence that improved cardiac function ameliorates sleep apnoea has not been reported due to the fact that a particular drug may affect a multitude of organs. We present a chronic heart failure patient with central sleep apnoea whose nocturnal desaturation was improved by percutaneous coronary intervention that resulted in improved cardiac function.

Characterization of hematopoietic progenitor mobilization in protease-deficient mice.

Recent evidence suggests that protease release by neutrophils in the bone marrow may contribute to hematopoietic progenitor cell (HPC) mobilization. Matrix metalloproteinase-9 (MMP-9), neutrophil elastase (NE), and cathepsin G (CG) accumulate in the bone marrow during granulocyte colony-stimulating factor (G-CSF) treatment, where they are thought to degrade key substrates including vascular cell adhesion molecule-1 (VCAM-1) and CXCL12. To test this hypothesis, HPC mobilization was characterized in transgenic mice deficient in one or more hematopoietic proteases.

Laser capture microdissection and mRNA characterization of mouse airway epithelium: methodological considerations.

The use of laser capture microdissection (LCM) to obtain epithelial cells lining the distal airways for gene profiling is described. In the mouse, the distal airways are particularly attractive for LCM as there is very high percentage of a single cell type, Clara cells, lining these airways. It is shown that the RNA from distal airway epithelial cells harvested by LCM is well preserved and that with linear amplification sufficient cRNA for microarray analysis can be attained from small numbers of cells.

[The mechanism of airway obstruction in the development of COPD].

Cigarette smoking is the major cause of chronic obstructive pulmonary disease (COPD) and it is generally accepted that proteinases released from neutrophils and/or macrophages are involved in the development of emphysema. It remained unknown why only a small portion of smokers develops clinically apparent emphysema and which cells and/or proteinases play a key role in the pathogenesis of COPD. Structural cells in the lungs such as epithelial cells and endothelial cells may also be involved in cell death and repair.

Retinoic acid inhibits interleukin-4-induced eotaxin production in a human bronchial epithelial cell line.

Retinoic acid (RA) is known to accelerate wound healing and induce cell differentiation. All-trans RA (ATRA) exerts its effect by binding retinoic acid receptors, which are members of the nuclear receptor family. We investigated whether RA can alter expression of eotaxin, a potent eosinophil chemoattractant that is regulated by the transcription factors signal transducer and activator of transcription 6 (STAT6) and NF-kappaB.

[A case of idiopathic pulmonary upper lobe fibrosis complicated by invasive pulmonary aspergillosis].

A 72-year-old man with idiopathic pulmonary upper lobe fibrosis who had been followed for a year developed a high fever and yellow sputum in July 2001. Chest radiography and chest computed tomography (CT) showed a rapidly enlarging cavity with an internal mass and infiltration in the left upper lung field. Pulmonary aspergillosis was diagnosed by examination of bronchoalveolar lavage fluid (BALF).

Extracellular matrix metalloproteinase inducer is increased in smokers' bronchoalveolar lavage fluid.

Extracellular matrix metalloproteinase inducer (EMMPRIN), also called basigin, is present in the lung during development, but its expression in normal adult lung is minimal. Increases of EMMPRIN have been found in various forms of experimental lung injury. To determine whether EMMPRIN might be involved in alveolar injury/repair associated with smoking, we developed an ELISA for EMMPRIN and applied it to bronchoalveolar lavage fluids from never-smokers (n = 7), former smokers (n = 16), and current smokers (n = 58).

Increased basigin in bleomycin-induced lung injury.

Basigin is expressed in many tissues during development, including lung. It is also found on tumor cells and in wounds where it is thought to stimulate adjacent fibroblasts to produce matrix metalloproteinases. To investigate whether basigin might be expressed in fibro-inflammatory lung processes, we generated bleomycin-induced lung injury in mice.

Role of secretory leukocyte protease inhibitor in the development of subclinical emphysema.

Secretory leukocyte protease inhibitor (SLPI) is a potent inhibitor of human leukocyte elastase. In some chronic airway diseases, the level of SLPI is decreased in sputum, leading to the continuation of neutrophil inflammation. In this study, the role of SLPI in subclinical pulmonary emphysema was examined.

Role of macrophage migration inhibitory factor in bleomycin-induced lung injury and fibrosis in mice.

Macrophage migration inhibitory factor (MIF) is a unique cytokine that reportedly overrides the anti-inflammatory effect of endogenous glucocorticoids. MIF has been demonstrated to be involved in a variety of inflammatory diseases. In this study, we examined the role of MIF in bleomycin (BLM)-induced lung injury and fibrosis.

Echocardiographic evaluation of ventricular remodeling in a mouse model of myocardial infarction.

Gene-targeting in mice is a powerful tool to define molecular mechanisms of ischemic heart disease that determine infarct size, postinfarct left ventricular (LV) remodeling, and arrhythmogenesis. Coronary ligation in mice is becoming a widely used model of myocardial infarction (MI), but the pathophysiologic consequences of MI in mice and its relevance to human MI have not been fully elucidated. To characterize structural and functional changes during evolving MI, we analyzed 2-dimensional-based reconstruction of the left ventricle by noninvasive echocardiography obtained 1 day and 1 week after surgical ligation of the left anterior descending coronary artery in mice.

Increased levels of interleukin-8 in BAL fluid from smokers susceptible to pulmonary emphysema.

Background: It has previously been shown that smokers with computed tomographic (CT) evidence of subclinical emphysema have signs of neutrophil activation, despite having no appreciable increase in the number of neutrophils in their bronchoalveolar lavage (BAL) fluid.

Methods: The levels of the following chemoattractants in BAL fluid from 61 community based older volunteers classified into four groups according to current smoking status and the presence or absence of emphysema were determined: interleukin 8 (IL-8), epithelial neutrophil activating protein 78 (ENA-78) and leukotriene B(4) (LTB(4)) which are primarily chemotactic for neutrophils; monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) which are predominantly chemotactic for mononuclear leucocytes.

Results: Of the five chemoattractants studied, only the level of IL-8 in BAL fluid clearly distinguished between subjects with and without emphysema among current smokers (median values 34.

Redistribution of connexin45 in gap junctions of connexin43-deficient hearts.

Objective: Adult ventricular myocytes express two gap junction channel proteins: connexin43 (Cx43) and connexin45 (Cx45). Cx43-deficient mice exhibit slow ventricular epicardial conduction, suggesting that Cx43 plays an important role in intercellular coupling in the ventricle. Cx45 is much less abundant than Cx43 in working ventricular myocytes.

Cardiac structure and function in young and senescent mice heterozygous for a connexin43 null mutation.

Downregulation of connexin43 (Cx43) in the failing heart has been implicated not only in arrhythmogenesis but in contractile dysfunction as well. Cx43-deficient mice exhibit reduced baseline conduction velocity and increased arrhythmias in response to ischemia. However, it is not known whether Cx43-deficient mice have any abnormalities in contractile function or, furthermore, whether cardiac dysfunction may be manifested in Cx43-deficient mice with advancing age.

Tolerance for ATP-insensitive K(ATP) channels in transgenic mice.

To examine the role of sarcolemmal K(ATP) channels in cardiac function, we generated transgenic mice expressing GFP-tagged Kir6.2 subunits with reduced ATP sensitivity under control of the cardiac alpha-myosin heavy chain promoter. Four founder mice were isolated, and both founders and progeny were all apparently normal and fertile.

Laser capture microdissection and real-time reverse transcriptase/ polymerase chain reaction of bronchiolar epithelium after bleomycin.

Terminal airways are affected in many lung diseases and toxic inhalations. To elucidate the changes in terminal airways in these diverse situations it will be helpful to profile and quantify gene expression in terminal bronchiolar epithelium. We used laser capture microdissection (LCM) to collect terminal bronchiolar epithelial cells from frozen sections of lungs of mice subjected to intratracheal bleomycin.

Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin.

Increased expression of matrix metalloproteinases, particularly gelatinase B (MMP-9), has been described in the lungs in pulmonary fibrosis. Intratracheal bleomycin is often used experimentally to produce lesions resembling human fibrosing alveolitis. To assess the role of gelatinase B in bleomycin-induced fibrosing alveolitis, we instilled bleomycin intratracheally into gelatinase B-deficient mice and gelatinase B+/+ littermates.

[A comparative study of computed tomographic techniques for the detection of emphysema in middle-aged and older patient populations].

Helical-scan computed tomography (CT) is now widely utilized as a mass screening procedure for lung cancer. By adding 3 slices of high-resolution CT (HRCT) to the standard screening procedure, we were able to compare the efficacy of helical-scan CT and HRCT in detecting pulmonary emphysema. Additionally, the prevalence of emphysema detected by HRCT was examined as a function of patient age and smoking history.