Kazumitsu Ohmori

Activation of human mast cells through the platelet-activating factor receptor

BACKGROUND In human subjects platelet-activating factor (PAF) concentrations are markedly increased in the plasma after anaphylactic reactions, and these correlate strongly with the severity of the response. The mechanism for the systemic spread of mast cell (MC) activation in anaphylaxis is often assumed to relate to the hematogenous spread of allergen, but this is implausible, and amplification mechanisms need to be considered. OBJECTIVE We have investigated the ability of PAF to induce human MC degranulation using skin, lung, and peripheral blood (PB)-derived cultured MCs and the signaling pathways activated in PB-derived MCs in response to PAF. METHODS The expression of PAF receptor was investigated by means of RT-PCR and Western blot analysis. Cell-signaling pathways in PB-derived MCs in response to PAF were investigated by analyzing the effect of various inhibitors and the silencing of phospholipase C (PLC) mRNA on PAF-mediated histamine release. RESULTS We show for the first time that PAF induces histamine release from human lung MCs and PB-derived MCs but not skin MCs. Activation of PAF receptor-coupled G(alphai) leads to degranulation through PLCgamma1 and PLCbeta2 activation in human MCs. PAF-induced degranulation was rapid, being maximal at 5 seconds, and was partially dependent on extracellular Ca(2+). CONCLUSION Our findings provide a mechanism whereby PAF mediates an amplification loop for MC activation in the generation of anaphylaxis.

Hyperexpression of NOD2 in intestinal mast cells of Crohn's disease patients: preferential expression of inflammatory cell-recruiting molecules via NOD2 in mast cells.

NOD2, an intracellular sensor of bacteria-derived muramyl dipeptide (MDP) has been implicated as a key player in intestinal immune health and disease. Mast cells (MCs) have been reported to be increased in the gut of patients with inflammatory bowel disease. However, NOD2 expression and its role in human primary MCs are unknown. The number of NOD2(+) intestinal MCs was significantly increased in the Crohns disease (CD) specimens compared to Ulcerative colitis (UC) specimens and controls. IFN-gamma upregulated NOD2 expression in MCs. CXCL10 and urokinase-type plasminogen activator (uPA) upregulation was specific to MCs activated by MDP compared to MCs activated by LPS and IgE/anti-IgE. MDP-induced upregulation of ICAM-1, VCAM-1, and uPA was specific to MCs compared to mononuclear cells. The number of CXCL10(+)NOD2(+) intestinal MCs was significantly increased in the CD patients. Our results suggest that NOD2(+) MCs have specific pathogenic roles that involve the recruitment of inflammatory cells in CD.

Activation of human synovial mast cells from rheumatoid arthritis or osteoarthritis patients in response to aggregated IgG through Fcγ receptor I and Fcγ receptor II

OBJECTIVE Substantial evidence suggests that human synovial mast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). A plausible pathway for the activation of synovial MCs is through IgG receptors, given the prevalence of circulating IgG isotype autoantibodies and synovial immune complexes in patients with RA. However, IgG receptor expression on human synovial MCs remains uncharacterized. The aim of this study was to identify which IgG receptor(s) on synovial MCs are responsible for MC activation in immune complexes. METHODS Synovial tissue specimens were obtained from patients with RA or patients with osteoarthritis (OA) who were undergoing joint replacement surgery, and synovial MCs were enzymatically dispersed. Cultured synovium-derived MCs were generated by culturing synovial cells with stem cell factor, and receptor expression was analyzed using fluorescence-activated cell sorting. Mediators released from MCs were measured using enzyme immunoassays or enzyme-linked immunosorbent assays. RESULTS Primary synovial MCs and cultured synovium-derived MCs obtained from both patients with RA and patients with OA expressed Fcε receptor I (FcεRI), FcγRI, and FcγRII but not FcγRIII. Cultured synovium-derived MCs induced degranulation and the production of prostaglandin D2 and tumor necrosis factor α (TNFα) through FcγRI. The aggregation of FcγRII caused histamine release from cultured MCs but not from primary MCs. Histamine release induced by aggregated IgG was significantly inhibited by neutralizing anti-FcγRI monoclonal antibody and anti-FcγRII monoclonal antibody. CONCLUSION With regard to the FcR expression profile, synovial MCs from patients with RA and patients with OA were similar. FcγRI was responsible for producing abundant TNFα from synovial MCs in response to aggregated IgG. Immune complexes may activate synovial MCs through FcγRI and FcγRII.

Staple Line Reinforcement with Fleece-Coated Fibrin Glue (TachoComb) After Thoracoscopic Bullectomy for the Treatment of Spontaneous Pneumothorax

BackgroundWe investigated the cause of pneumothorax recurrence after thoracoscopic surgery and the effectiveness of staple line reinforcement with fleece-coated fibrin glue (TachoComb) in the prevention of postoperative pneumothorax recurrence.MethodsFrom April 3, 1992 to the end of December 2005, thoracoscopic bullectomy was performed on 499 patients of primary spontaneous pneumothorax. The causes of recurrence were investigated on 39 patients on the basis of surgical observations, preoperative chest computed tomography, and so on. The most common cause was new bulla formation (37 cases), 19 of which were apparently related to the staple line (within 1 cm of the staple lines) and 15 of which were not related to the staple line. After 2000, we stopped using forceps to grasp lungs and we have reinforced the staple line by applying fleece-coated fibrin glue.ResultsThe staple line reinforced with fleece-coated fibrin glue, or sprayed with fibrin glue solution and the untreated group (bullectomy only with staples) were compared, and the recurrence rates were 1.22%, 7.25%, and 10.00%, respectively (P = 0.0006021).ConclusionsThe recurrence rate after thoracoscopic bullectomy with fleece-coated fibrin glue was significantly lowered and we consider this procedure to be the treatment of choice for the management of spontaneous pneumothorax.

Mature Cystic Teratoma With Malignant Transformation to Adenocarcinoma

An anterior mediastinal tumor had been found in a 65-year-old woman 10 years previously, and she had been followed-up under the diagnosis of a mature cystic teratoma. Changes in the structure of the inside of the mediastinal cystic tumor were observed on a chest computed tomography image, and she was referred to our hospital for surgical intervention. The tumor was removed and was determined to be a mature teratoma. An adenocarcinoma was also observed in part of this cystic lesion. From these findings, the lesion was diagnosed as a malignant change in a mediastinal mature teratoma. Because few if any changes tend to be observed in the cystic wall of such cases, an aggressive resection of such mature cystic teratomas is therefore recommended.

Treatment strategies for chronic expanding hematomas of the thorax

PurposeTo investigate retrospectively the treatment strategies for chronic expanding hematoma (CEH) of the thorax.MethodsWe reviewed the medical records of six patients treated for CEH of the thorax at our institution between October 1996 and October 2006.ResultsAll of the patients had a history of thoracic surgery or tuberculosis with a latent period of 12–55 years before onset. One elderly patient with ischemic heart disease and in poor general health demonstrated a substantial improvement of symptoms after undergoing arterial embolization twice instead of surgery. The remaining five patients underwent either pleuropneumonectomy or a total capsule excision, following which their clinical condition improved remarkably. All six patients were discharged from the hospital. Arterial embolization was performed before surgery, and the amount of intraoperative bleeding ranged from 905 ml to 6 590 ml (average: 2 396 ml).ConclusionChronic expanding hematoma of the thorax may occur after thoracic surgery and a tuberculosis infection; however, considering the risk of massive bleeding during surgery, the decision to perform surgery should be made with extreme care.

Cause and Management of Recurrent Primary Spontaneous Pneumothorax After Thoracoscopic Stapler Blebectomy

BACKGROUND As the number of patients treated by thoracoscopic stapler blebectomy increased, the postoperative recurrence rate had risen unexpectedly. We retrospectively investigated the cause and management of primary spontaneous pneumothorax recurrence after thoracoscopic stapler blebectomy. METHODS From March 1992 to the end of December 2006, thoracoscopic stapler blebectomy was performed in 357 patients with primary spontaneous pneumothorax at the Nihon University Itabashi Hospital. The causes and management of recurrence were investigated in 30 patients with postoperative recurrence based on items such as the resurgical observations, preoperative chest computed tomography findings, previous operative notes. RESULTS Among the patients with bilateral pneumothorax, young patients exhibited a higher tendency for postoperative recurrence. The most common cause was new bulla formation (28 slides, 16 of which were apparently related to the staple line and 12 of which were not related to the staple line). CONCLUSION In thoracoscopic stapler blebectomy for primary spontaneous pneumothorax, the most common cause of recurrence was new bulla formation. It is necessary to establish additional procedures involving either the visceral pleura or the parietal pleura to reduce the recurrence rate.

Surgical Treatment of Catamenial Pneumothorax

OBJECTIVE To discuss the aetiology and determine the optimal surgical treatment of catamenial pneumothorax. METHODS Between January 1980 and December 2007, 17 patients with catamenial pneumothorax were treated at our institution. Regarding the surgical approach, thoracotomy was performed until 1991, and thoracoscopic surgery was performed from 1992 onward. RESULTS Pneumothorax was on the right side in all but two patients. Surgery was performed on 15 of the 17 patients. The surgical procedure was a diaphragm resection plus a partial bleb resection in eight patients, a diaphragm resection in two patients, a diaphragm resection plus an absorbable polyglycolic acid sheet in four patients, and a partial bleb resection in one patient. Five patients demonstrated a postoperative recurrence (33.0%). However, no recurrence has been observed thus far in the four patients with an absorbable polyglycolic sheet placed on the diaphragmatic surface. CONCLUSION Although the postoperative recurrence rate of patients undergoing surgical procedures remains high, there were some patients with no postoperative recurrence. Placement of an absorbable sheet on the diaphragmatic surface may therefore prevent recurrence of catamenial pneumothorax.

Thoracoscopic Resection of Mediastinal Bronchogenic Cysts in Adults

OBJECTIVE The aim of this study was to discuss the diagnosis and determine the optimal thoracoscopic surgical treatment of mediastinal bronchogenic cysts. METHODS From May 1996 to April 2008, 13 consecutive patients with mediastinal bronchogenic cysts underwent thoracoscopic surgery at our institution. There were eight men and five women aged 16-74 years (mean age, 41.5 years). RESULTS In the majority of patients (69.2%), there were no clinical symptoms and the lesions were found incidentally by chest radiography that was performed as part of physical screening. Lesions were found in the posterior mediastinum in five patients (38.5%) and in the upper mediastinum in four (30.8%). In the histopathological examinations, ciliary epithelium was observed in 13 patients (100.0%), bronchial cartilage in 7 patients (53.8%), bronchial glands in 6 patients (46.2%), and smooth muscle in 5 patients (38.5%). No serious postoperative complications were observed. In 3 patients (23.1%), conversion to open thoracotomy was necessary due to major pleural adhesions and intraoperative vascular injury. CONCLUSION Thoracoscopic resection of mediastinal bronchogenic cyst is minimally invasive and has no serious postoperative complications, and should therefore be considered as the primary therapeutic option.

A Case of Giant Atypical Thymoma in the Thoracic Cavity.

症例は47歳, 男性.会社員.既往歴に特記すべきことはない.平成9年11月の検診では異常なかったが, 平成10年11月の胸部X線で異常陰影を指摘された.画像上左胸腔内に小児頭大の腫瘤があり, 肺静脈, 舌区および胸壁浸潤が疑われた.生検でthymomaと診断され化学療法 (ADOC) を2コース施行した.効果は縮小率11%でNCであった.その後胸骨正中切開に後側方開胸を追加して, 拡大胸腺摘出術, 心膜合併切除, 左上葉切除, S6合併切除を行った.切除標本で腫瘍は心膜および左上葉に浸潤し, 正岡III期であった.断端の腫瘍細胞は陰性で, 完全切除であった.免疫組織学的検討ではbc1-2とKi67 (MIB-1) で高い染色性を示し, 高度の細胞増殖能を示した.また013 (MIC2) による染色で腫瘍内浸潤リンパ球は未熟リンパ球と考えられ, 胸腺癌ではなくatypical thymomaと診断された.リンパ球表面マーカーの解析は胸腺腫と胸腺癌の鑑別に有用であった.