Kazuyoshi Kurashima

Smoking-related changes in the background lung of specimens resected for lung cancer : a semiquantitative study with correlation to postoperative course

Aims:  To assess the pathological findings in lobectomy specimens, to correlate them with smoking history and postoperative course and to compare the findings with those in smoking‐related interstitial lung disease.

The effect of emphysema on lung function and survival in patients with idiopathic pulmonary fibrosis

Background and objective:  In this study the prevalence, lung function and prognosis of IPF combined with emphysema were evaluated.

Bafilomycin A1 induces apoptosis in the human pancreatic cancer cell line Capan‐1

Bafilomycin A1, a specific inhibitor of vacuolar type H+‐ATPase, can inhibit the growth of a variety of cultured cells in a dose‐dependent manner, but its mechanism is unclear. The aim of this study was to examine whether bafilomycin A1 inhibits the growth of Capan‐1 human pancreatic cancer cells through apoptosis. The effect of bafilomycin A1 on tumour growth in vitroand in vivowas examined using an MTT assay and an in vivotumour model. The presence or absence of apoptosis was determined by morphology and DNA analysis of tumour cells. The concentration of bafilomycin A1 for 50 per cent inhibition of cell viability during 72 h by the MTT assay was 5 nm. In DNA analysis, a ladder of fragmented DNA was detected in Capan‐1 cells treated with bafilomycin A1 at concentrations greater than 10 nm for 24 h. Nude mice bearing a xenografted Capan‐1 cell line tumour received 4 weeks of bafilomycin A1 (1·0 mg/kg per day). This treatment significantly inhibited tumour growth compared with controls after 21 days (P<0·05). Histopathological examination of tumour cells in the treated group demonstrated signs of apoptosis with chromatin condensation and cell shrinkage. These observations suggest that bafilomycin A1 inhibits the growth of Capan‐1 human pancreatic cancer cells through apoptosis.

Blockade of eosinophil migration and airway hyperresponsiveness by cPLA2-inhibition

We examined the role of a cytosolic phospholipase A2 (cPLA2) in antigen-induced eosinophil infiltration of airways and in airway hyperresponsiveness to methacholine. Inhibition of cPLA2, or blockade of the platelet-activating factor (PAF) receptor, blocked antigen-induced airway hyperresponsiveness and suppressed eosinophil infiltration. Neither cyclooxygenase nor 5-lipoxygenase inhibition had either effect. We show here that, in antigen-sensitized guinea pigs, cPLA2 inhibition prevents both eosinophilic infiltration and subsequent airway hyperresponsiveness after antigen challenge. We also show that this effect is mediated by first-step hydrolysis of membrane phospholipid into lysophospholipid rather than by prostanoid or leukotriene metabolites of arachidonate.

Increase of chemokine levels in sputum precedes exacerbation of acute asthma attacks.

Basophils and eosinophils can be activated in vitro by several chemokines such as RANTES, monocyte chemotactic and activating factor (MCAF/MCP‐1), macrophage inflammatory peptide‐1α (MIP‐1α), and interleukin‐8 (IL‐8). To explore the clinical relevance of the in vitro observations, we measured here the concentrations of these chemokines in sputa from asthmatic patients during acute attacks. Before the onset of a late‐phase exacerbation, sputum MCAF/MCP‐1, MIP‐1α, and IL‐8 levels transiently but markedly increased from the basal levels in all of the patients with exacerbation, whereas the sputum levels of these chemokines remained unchanged during the course in the patients without a late‐phase exacerbation. These results suggest the involvement of these chemokines in the late‐phase exacerbation of asthma.

Enhanced airway inflammation and decreased subepithelial fibrosis in interleukin 6-deficient mice following chronic exposure to aerosolized antigen.

Background Airway inflammation and remodelling are characteristic features of chronic asthma.

Congenital bronchial atresia : radiologic findings in nine patients

Purpose The purpose of this article is to describe the radiologic findings to diagnose congenital bronchial atresia. Methods Chest radiographs, CT scans, and MRI of nine patients with congenital bronchial atresia were reviewed. Results Six patients (67%) had hilar mass-like shadows and hyperlucency of the peripheral lung field on chest radiographs. On chest CT scans, all patients demonstrated mucocele, occlusion of bronchus central to mucocele, and emphysematous change of the peripheral lung field. On chest MRI, performed in seven patients, all mucoceles demonstrated very high signal intensity on T2-weighted image, indicating that mucoceles were filled with fluid. Conclusion Diagnosis of congenital bronchial atresia can be confirmed based on the findings of chest CT: mucocele, occlusion of bronchus central to mucocele, and emphysematous change of the peripheral lung field.

Effect of surfactant inhalation on allergic bronchoconstriction in guinea pigs

Background In the small airway, surfactant reduces surface tension, prevents liquid filling of bronchioles, thereby maintaining patency in the small airways. Recent reports demonstrated that surfactant dysfunction develops in experimental asthma in immunized guinea pigs. However, there are few reports concerning surfactant and lung function in an experimental asthma model.

Asthma severity is associated with an increase in both blood CXCR3+ and CCR4+ T cells.

Objectives:  A predominance of type 2 helper T cells (Th2) in the bronchoalveolar space and peripheral blood is a well‐accepted feature of bronchial asthma. However, the relationship between peripheral blood Th2 cells and asthma severity has not been thoroughly investigated.

High resolution CT and bronchial reversibility test for diagnosing COPD

Background:  COPD is defined by airflow limitation that is not fully reversible and is associated with relevant risk factors. The diagnosis requires that other causes of chronic airflow limitation (CAL) be excluded. We assessed the diagnostic utility of high resolution thoracic CT (HRCT) and bronchodilator reversibility to assist in making a diagnosis of COPD.