Takashi Dambara

VEGF regulates the proliferation of acid-exposed alveolar lining epithelial cells

Background: Acid induced pneumonitis resulting in acute respiratory distress syndrome (ARDS) is characterised by increased alveolar permeability and accumulation of neutrophils. It is hypothesised that vascular endothelial growth factor (VEGF) is involved in the development of lung oedema. Furthermore, lower levels of VEGF are detected in bronchoalveolar lavage fluid from patients with ARDS than from non-ARDS patients. We hypothesised that VEGF acts cytoprotectively and have investigated this possibility in vitro with A549 cells. Methods: A549 cells were incubated in 24 well culture dishes 24 hours before exposure to acid, then incubated with serum free medium containing various concentrations of HCl for 30 minutes at 37°C in 5% CO2. The acidified medium was changed to normal complete medium; at specified incubation periods the supernatants were collected and the VEGF concentration measured and the number of adherent cells counted. Results: Proliferation of A549 cells and VEGF production were suppressed for at least 48 hours in HCl at a concentration of 50 mM. Restoration of cellular proliferation occurred following exogenous administration of VEGF (concentration of 1–250 ng/ml) and was inhibited by co-incubation with neutralising anti-VEGF antibody, indicating an interaction between VEGF molecules and A549 cells. Control cells were not influenced by administration of exogenous VEGF or anti-VEGF antibody. Treatment with neutralising anti-VEGF receptor (VEGFR) antibodies against VEGFR-1 and VEGFR-2 suppressed proliferation of acid exposed A549 cells but had no effect on control cells. Conclusions: Exogenous VEGF interacts with VEGFR-1 and VEGFR-2 on the surface and regulates the proliferation of injured alveolar lining epithelial cells in an autocrine or paracrine fashion.

Structural organization of pulmonary arteries in the rat lung

The structure of the normal pulmonary arteries in the rat was studied with light and electron microscopy after use of a newly devised technique of perfusion fixation and tissue preparation. We distinguished two main types of artery in the rat lung on the basis of the structure of the media, an elastic artery and a muscular artery. The elastic artery was characterized by an abundance of extracellular matrix in the media and by an oblique arrangement of smooth muscle cells to connect neighboring elastic laminae. It was subdivided into two segments, a classical elastic and a transitional elastic segment. The muscular artery was distinguished by a paucity of extracellular matrix in the media and by a circumferential arrangement of smooth muscle cells (or pericytes) enclosing the lumina, and was subdivided into four segments, a thick muscular, an ordinary muscular, a partially muscular and a nonmuscular segment. The smooth muscle cells in the muscular artery contained well-developed microfilament bundles compared with those in the elastic artery. Structural differences in smooth muscle cells and in extracellular matrix in the media between the elastic and muscular arteries may reflect the functional heterogeneity of pulmonary arteries in response to hypoxic pulmonary vasoconstriction and to vasoactive substances such as endothelium-derived relaxing and hyperpolarizing factors, and endothelin.

Longitudinal follow-up study of 11 patients with pulmonary lymphangioleiomyomatosis: diverse clinical courses of LAM allow some patients to be treated without anti-hormone therapy.

Objective: The purpose of this study is to clarify the existing issues on the clinical diversity, natural history, and mode of disease progression of pulmonary lymphangioleiomyomatosis (LAM).

Increased circulating CD16+ CD14dim monocytes in a patient with pulmonary alveolar proteinosis.

Pulmonary alveolar proteinosis (PAP) is characterized by filling of the alveoli with a periodic acid‐Schiff‐positive proteinaceous material. Although the pathogenesis of primary or idiopathic PAP remains unknown, it has been proposed that a deficiency or loss of responsiveness of the monocyte/macrophage lineage to granulocyte–macrophage colony stimulating factor (GM‐CSF) is involved in PAP. Secondary PAP is associated with haematological malignancies, especially in myeloid disorders. Herein, we report on an adult with PAP associated with myelodysplastic syndrome (MDS). The CD16+ CD14dim monocytes comprise 5–10% of circulating monocytes in healthy volunteers. Flow cytometric analysis of the patient in the present study revealed increased CD16+ CD14dim monocytes in the peripheral blood. It has been demonstrated that the expression of CD16 and CD14 is regulated by macrophage colony stimulating factor (M‐CSF) and GM‐CSF. Hence, serum cytokines were analysed in our patient and the concentration of serum GM‐CSF was found to be less than the lower limit of the assay. In addition, serum M‐CSF and granulocyte colony stimulating factor levels were only slightly increased above the normal range. These results suggest that the increase in the CD16+ CD14dim subpopulation in the circulation of our patient indicates another pathogenetic mechanism for secondary PAP, such as hyperresponsiveness of the monocyte/ macrophage lineage to these cytokines.

Adenovirus vector-mediated transfer of 9 kDa granulysin induces DNA fragmentation in HuD antigen-expressing small cell lung cancer murine model cells

Objective: Granulysin is a tumoricidal molecule secreted by cytotoxic T cells (CTL) and natural killer (NK) cells, that induces apoptotic cell death in tumour cells. It has been demonstrated that small cell lung cancer (SCLC) cell lines are susceptible to NK cells and lymphokine activated killer (LAK) cells, and HuD antigen is assumed to be a target molecule on SCLC cells for host cellular immunity.

Progressive interstitial pneumonia associated with myelodysplastic syndrome: Implication of superoxide hyperproduction by neutrophils

Abstract Interstitial pneumonia and aseptic neutrophilic infiltration in the lung are rare pulmonary manifestations of myelodysplastic syndrome (MDS). We report a patient with progressive interstitial pneumonia associated with MDS. Histological examination of the lung revealed infiltration of atypical haematopoietic cells associated with MDS and diffuse alveolitis with honeycombing. Neutrophils obtained from the patient showed superoxide hyperproduction after stimulation with phagocytosis and phorbol myristate acetate, which might be attributed to the pathogenesis of interstitial pneumonia.

Pancoast's syndrome in a patient with B‐cell lymphoma diagnosed and confirmed with immunoglobulin gene rearrangement

Abstract:  Pancoasts syndrome due to malignant lymphoma is extremely rare. A case of diffuse large B‐cell lymphoma presenting as Pancoasts syndrome is described. A 66‐year‐old man complained of pain and weakness of the right arm, and CXR revealed a right apical lung tumour. Histological findings were consistent with it being a diffuse large cell type lymphoma and Southern blot analysis revealed clonal rearrangement of the immunoglobulin heavy‐chain JH. Thus, the tumour in this patient was diagnosed to be diffuse large B‐cell lymphoma. Malignant lymphoma is an extremely rare cause of Pancoasts syndrome and only five cases have been described. This is the first reported case of Pancoasts syndrome caused by B‐cell lymphoma, which was accurately diagnosed by analysis of gene rearrangement.

Transoesophageal ultrasonography in the staging of lung cancer

In primary lung cancer, tumour extent is generally the most important determinant in the selection of therapy [6,42]. There is a growing tendency to stage this disease with the TNM classification, in which “T” means location and size of the primary lesion, “N”, lymph node involvement of the hilum and mediastinum, and “M”, the presence or absence of distant metastasis [6,35]. Epidemiological surveys based on the TNM classification show an excellent correlation between this staging and survival rate [20,35]. Most patients who have T4, N3 and/or Ml lesions are usually not considered surgical candidates [6,19]. With N2 lesions, it is reported that radical node dissection can cure a significant percentage of patients or prolong their survival rate [19,21,30,39]. T3 patients may be resectable, but surgical management of these lesions is controversial [19,25,30]. In summary, lung resection should not be performed in patients in whom the tumour cannot be completely removed; however, it is also essential not to preclude potentially curative surgery due to overstaging. Therefore the selection of the correct treatment in each patient depends on exact staging [ 13,421. High resolution and real-time sonographic scanning not only permits observation of relative movement of lesions and neighbouring structures, but also provides information about the characteristics of tissues such as differentiation of the vessels from solid masses [11,24,29,33,37,38]. However, the value of ultrasonography for the evaluation of the mediastinum is limited by bones and air. To solve this problem, transoesophageal endoscopic

Do respiratory comorbidities limit the diagnostic usefulness of ultrasound-guided needle aspiration for subpleural lesions?

BACKGROUND The usefulness of ultrasound-guided needle aspiration for subpleural lesions has been reported. However, no reports have evaluated its usefulness and safety in patients with respiratory comorbidities such as chronic obstructive pulmonary disease (COPD) and interstitial pneumonia (IP), which can increase the risk of iatrogenic pneumothorax. In this study, we evaluated the influence of chronic respiratory diseases (CRDs) on the usefulness and safety of ultrasound-guided needle aspiration for subpleural lesions. METHODS Between January 2000 and September 2011, we examined 144 patients with intrapulmonary subpleural lesions. We retrospectively reviewed clinical data, including lesion size on thoracic computed tomography (CT), ultrasound findings, pathological findings obtained by ultrasound-guided needle aspiration, final diagnosis, and complications. RESULTS A positive definitive diagnosis was obtained in 74.3% of all 144 patients; 84.7% patients with malignant diseases, including lung cancer; and 26.9% patients with benign diseases. Of the 144 patients, 64 belonged to the CRD group and 80 to the non-CRD group. The former included 31 patients with COPD, six with emphysematous changes on thoracic CT, 17 with IP, and 10 with other diseases. The positive rate of diagnosis for malignant diseases was 84.7% in the CRD group, which was the same as that in the non-CRD group. With regard to complications related to ultrasound-guided aspiration, there were only two cases of pneumothorax in the CRD group and one in the non-CRD group. CONCLUSION Ultrasound-guided aspiration is safe and useful for subpleural lesions, particularly malignant lesions, even in patients with respiratory comorbidities such as COPD and IP.

Solitary fibrous tumor of the pleura: Ultrasonographic imaging findings of 3 cases

Solitary fibrous tumor (SFT) of the pleura is a rare tumor of mesenchymal origin. Although radiographic findings of thoracic computed tomography and magnetic resonance imaging in the evaluation of SFTs of the pleura have been documented, the value of ultrasonography is uncertain. We presented the ultrasonographic findings of 3 pathologically proven cases of SFTs arising from the visceral pleura. In all the cases, thoracic ultrasonography demonstrated homogeneous, hypoechoic, hemicycle, extrapulmonary lesions, which showed respiratory movement with the adjacent lung, consistent with pedunculated tumors. Preoperative thoracic ultrasonography could be useful in the evaluation of patients with pleural tumors, especially SFTs.