A Lobulated Mass with Extensive Ecchymosis in the Epigastrium.


Potential of fluoropyrimidine to be an immunologically optimal partner of immune checkpoint inhibitors through inducing immunogenic cell death for thoracic malignancies.

Our findings indicate that fluoropyrimidine can be an immunologically optimal partner of ICIs through the induction of ICD for thoracic malignancies.

5-FU induced cell surface expression of CRT and ATP secretion most efficiently among the several chemotherapeutic agents. This effect was enhanced when it was combined with platinum. In the antitumor vaccination assay in vivo, we found that vaccination with dying-AB1-HA (a murine malignant mesothelioma cell line) cells treated with 5-FU, but neither PEM nor PTX, reduced the tumor growth of living-AB1-HA cells inoculated 1 week after vaccination by recruiting CD3


Antipodoplanin antibody enhances the antitumor effects of CTLA-4 blockade against malignant mesothelioma by natural killer cells.

-f enhanced the antitumor effects of CTLA-4 blockade. Combination therapy with anti-PDPN Ab and anti-CTLA-4 Ab increased tumor-infiltrating natural killer (NK) cells. The depletion of NK cells inhibited the synergistic effects of PMab-1-mG

-f and CTLA-4 blockade in vivo. These findings indicated the essential role of NK cells in novel combination immunotherapy targeting PDPN and shed light on the therapeutic strategy in advanced MPM.


An increased relative eosinophil count as a predictive dynamic biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

We retrospectively reviewed all 151 patients diagnosed with NSCLC and treated with ICI monotherapy and blood test data between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University.

ICI-treated NSCLC patients with an increased REC after 4 weeks of treatment had a better DCR and prognosis than the other patients examined.


A multicenter, open-label, phase II trial of pemetrexed plus bevacizumab in elderly patients with previously untreated advanced or recurrent nonsquamous non-small cell lung cancer.

Combination chemotherapy with PEM plus Bev in elderly patients with previously untreated advanced non-squamous NSCLC exhibited favorable antitumor activity and tolerability, suggesting that a combination of PEM plus Bev might be a promising treatment option for this population.

The median age at initiating chemotherapy was 80 years old. Almost all patients (92.6%) had adenocarcinoma histology. The median number of cycles administered was 6, and the objective response rate was 40.7%. The median progression-free survival, overall survival and 1-year survival were 8.8 months, 27.2 months and 79%, respectively. The treatment was well-tolerated, and no treatment-related death was observed.


Pretreatment eosinophil counts as a predictive biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors.

We retrospectively reviewed all patients diagnosed with NSCLC and treated with ICI monotherapy between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University.

OS was significantly longer in ICI-treated NSCLC patients with a pretreatment eosinophil count of 100 ≤ Eo <500 than in the other patients and, thus, has potential as a new predictive biomarker.


Prostatic lymphangitis carcinomatosis with massive bilateral pleural effusion.

The American Journal of the Medical Sciences


Slowly Expanding 18 F-FDG PET-Positive Irregular Opacities in the Lung Due to Diffuse Lymphoid Hyperplasia Preceding Rheumatoid Arthritis.

Pulmonary diffuse lymphoid hyperplasia (DLH), a nonneoplastic lymphoproliferative disorder (LPD), is extremely rare, and no PET/CT findings have been reported for pulmonary DLH. We observed slowly expanding irregular opacities with 18 F-FDG accumulation (SUV max , 3.64) in the right lower lobe of a 51-year-old asymptomatic man. The patient underwent video-assisted thoracoscopic biopsy on suspicion of malignant lesions. Histologically, no neoplastic cells were present, and the lesion was consistent with DLH. Six months later, the patient developed rheumatoid arthritis. DLH should be considered in the differentiation of PET-positive irregular opacities, even in the absence of known immune abnormalities.


Identification of fibrocyte cluster in tumors reveals the role in antitumor immunity by PD-L1 blockade.

fibrocytes do not. Tumor-infiltrating fibrocytes acquire myofibroblast-like phenotypes through transforming growth factor β (TGF-β)/small mothers against decapentaplegic (SMAD) signaling. Thus, TGF-βR/SMAD inhibitor enhances the antitumor effects of dual VEGF and PD-L1 blockade by regulating fibrocyte differentiation. Fibrocytes are highlighted as regulators of the response to programmed death 1 (PD-1)/PD-L1 blockade.

fibrocytes is enhanced by anti-PD-L1 antibody. Peritumoral implantation of fibrocytes enhances the antitumor effect of PD-L1 blockade in vivo; CD86


当院で経験した新型コロナウイルス感染症による死亡例の検討

当院で経験した新型コロナウイルス感染症による死亡例の検討


Non-small cell lung cancer with EGFR (L858R and E709X) and CNNB1 mutations responded to afatinib.

Lung cancer with complex epidermal growth factor receptor (EGFR) and CTNNB1 comutations is rare, and the efficacy of tyrosine kinase inhibitors (TKIs) is generally poor. Here, we encountered a lung cancer patient with complex EGFR (L858R and E709X) and CTNNB1 comutations who successfully responded to afatinib. A 78-year-old woman visited our hospital with a cough and bloody sputum that had worsened over the past year. She had multiple mass shadows in both lungs and nodular shadows in the bronchi. The patient was diagnosed with lung adenocarcinoma cT4N3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx target test multi-CDx system revealed positivity for EGFR (L858R and E709X) and CTNNB1 mutations. The expression of programmed death ligand 1 (22C3 clones) in tumor cells was negative by immunostaining. The patient was treated with afatinib as first-line therapy and achieved clinical improvement and a partial response and is continuing treatment 1 year later. Case reports of lung cancer patients with EGFR/CTNNB1 comutations are rare, and TKIs are not considered to be effective. We herein present the first case report of lung cancer with the co-occurrence of uncommon and complex EGFR (L858R and E709X) and CTNNB1 mutations that was successfully treated with afatinib.


Late-onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer.

Immune-related adverse events (irAEs) occur in rare cases, even after the completion of immune checkpoint inhibitor (ICI) therapy. We encountered a lung cancer patient diagnosed with acute-onset type 1 diabetes mellitus (DM) 7 months after the cessation of ICI. A 68-year-old woman was referred to our hospital for chest abnormalities. She was diagnosed with lung adenocarcinoma cT4N2M1c, stage IVB. Immunostaining showed that the expression of programmed death ligand 1 in tumor cells was negative. A genetic analysis using the Oncomine Dx Target Test Multi-CDx System revealed that the primary tumor was positive for ERBB2. Combined immunotherapy with carboplatin, pemetrexed, and pembrolizumab was performed as first-line therapy, followed by maintenance therapy with pemetrexed plus pembrolizumab, which was successful. After the seventh course, maintenance therapy was stopped because only the primary tumor showed local enlargement. Local chest radiotherapy (66 Gy/33 Fr) was performed, and the patient was followed up. HbA1c was 4.9% 3 months after the completion of pembrolizumab, and dry mouth and polyuria occurred after 5 months. Seven months later, the patient developed diabetic ketoacidosis with a blood glucose of 348 mg/dL and an HbA1c of 11.3%. Antiglutamic acid decarboxylase antibodies were negative and urinary C-peptide was 9.3 μg/day. The patient was diagnosed with acute-onset type 1 diabetes and received insulin therapy. There has been no case report of type 1 diabetes diagnosed 7 months after the last administration of an ICI. These results indicate that irAE needs to be considered even after the cessation of ICI.


Transient and Recurrent Pulmonary Infiltrations Associated with Familial Mediterranean Fever.

Chest symptoms and pleural effusion due to serositis in familial Mediterranean fever (FMF) are occasionally misdiagnosed as acute pneumonia. However, the actual pulmonary involvement of FMF is extremely rare. A 67-year-old man was referred to our hospital due to repeated and transient anterior chest pain. Chest images revealed a moderate amount of pericardial fluid, slight bilateral pleural effusion, and infiltrations in both lower lung lobes. Colchicine treatment without antibiotics rapidly improved these symptoms and findings. Pericarditis, pleurisy and the response to colchicine indicated FMF. FMF should be considered as a causative disease of pulmonary infiltrations, especially if it occurs repeatedly.


Usefulness of bronchoalveolar lavage (BAL) in the diagnosis of pulmonary alveolar proteinosis.

QJM : Monthly Journal of the Association of Physicians


S-1 eliminates MDSCs and enhances the efficacy of PD-1 blockade via regulation of tumor-derived Bv8 and S100A8 in thoracic tumor.

Myeloid-derived suppressor cells (MDSCs) have been known to play a pivotal role in the induction of immune tolerance, which limits the benefits of immune checkpoint inhibitors (ICIs). Recent studies revealed that several chemotherapeutic agents decreased tumor-infiltrating MDSCs. Therefore, combination therapy with cytotoxic chemotherapeutic agents and ICIs was approved for first-line treatment for lung cancer. However, the impact of chemotherapeutic agents on MDSCs and an optimal partner of ICIs has not been fully investigated in thoracic tumors, including lung cancer and malignant pleural mesothelioma. In the present study, we found that treatment with 5-FU and its oral formulation, S-1, suppressed tumor progression and inhibited the accumulation of MDSCs in thoracic tumor-bearing mice. Tumor-infiltrating T cells and dendritic cells were significantly expanded in S-1-treated mice. 5-FU suppressed the ability of tumor cells to recruit MDSCs, while it did not suppress the survival and differentiation of mouse MDSCs in vitro. We also revealed that 5-FU or S-1 significantly downregulated the expression of tumor-derived Bv8 and S100A8. The knockdown of Bv8 or S100A8 in tumor cells suppressed tumor growth and MDSC recruitment in vivo. Furthermore, in comparison with pemetrexed, administration of S-1 improved the synergistic therapeutic efficacy of anti-PD-1 antibodies with or without carboplatin. Our findings revealed a novel mechanism wherein S-1 primed a favorable tumor microenvironment to provide the rationale for combination therapy with S-1 and ICIs as the optimal therapy for thoracic cancer.


Surgical resection combined with perioperative chemotherapy for a patient with locally recurrent, previously stage IV thymic small-cell carcinoma: A case report.

An 83-year-old Japanese man visited our hospital with dyspnea and general fatigue. Computed tomography (CT) revealed a tumor in the anterior mediastinum, bilateral pleural effusion, pericardial fluid, and multiple liver nodules. We performed a CT-guided tumor biopsy, and the patient was diagnosed with thymic small-cell carcinoma, Masaoka-Koga stage classification IVb. The patient received four cycles of carboplatin and etoposide, and all lesions disappeared on CT. However, after 6 months, CT revealed a recurrent tumor in the anterior mediastinum. After one cycle of rechallenge chemotherapy, we performed extended total thymectomy followed by another three cycles of chemotherapy. More than 2.5 years after the last chemotherapy session, the patient's carcinoma did not recur. Thus, this case suggests that salvage surgery may be a treatment option for local recurrence of thymic carcinoma after complete remission with chemotherapy, even in patients with stage IV cancer.


Pulmonary nocardiosis caused by Nocardia pneumoniae mimicking non-tuberculous mycobacterial disease.


Solitary Ground-Glass Nodule Mimicking Lung Cancer due to Focal Progression of Usual Interstitial Pneumonia.

Idiopathic pulmonary fibrosis is often associated with lung cancer, but early malignant lesions mixed with fibrous lesions are not always easy to diagnose. A 78-year-old woman was referred to our hospital due to a ground-glass nodule in the left upper lobe detected on chest high resolution computed tomography during follow-up of chronic idiopathic interstitial pneumonia. Pathological examination of the resected specimen revealed that the ground-glass nodule was locally progressed usual interstitial pneumonia (UIP). It should be noted that focal progression of UIP may occur and present with ground-glass nodule mimicking lung cancer, even if lesions in other areas remain unchanged. Moreover, in such cases, recognition of nodular lesions by the gross findings on the pleural surface and palpation during surgical resection are difficult and require precise marking.

International Journal of Surgical Pathology


Early mortality factors in immune checkpoint inhibitor monotherapy for advanced or metastatic non-small cell lung cancer.

Immune checkpoint inhibitors (ICI) are a promising treatment, but may cause hyperprogressive disease and early death. The present study investigated early mortality factors in ICI monotherapy for lung cancer.

Liver metastases, ECOG PS score ≥ 2, and a non-smoking history are early mortality factors in ICI monotherapy for advanced or metastatic NSCLC.

Journal of Cancer Research and Clinical Oncology


Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study).

, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes.

Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).


Cardiopulmonary arrest due to bronchoscopy-induced Takotsubo syndrome in a patient with antineutrophil cytoplasmic autoantibody-associated lung disease: a case report.

This case indicates that bronchoscopy can cause severe TTS, especially in patients with systemic inflammation.


Type A thymoma: a rare cause of neoplastic cardiac tamponade with long-term survival.

This case indicates that neoplastic cardiac tamponade, even in elderly patients, should not necessarily be regarded as a terminal cancer and requires a systematic investigation for underlying causes.


Massive eosinophilia despite severe aplastic anemia.


An 18 F-FDG-PET-Positive Mucoid Impaction With Ring Enhancement on CT Mimicking Lung Cancer.

We encountered a case of an 18 F-FDG PET-positive solitary nodule with ring enhancement on CT mimicking lung cancer in the left S6 region of an 80-year-old woman. Since transbronchial biopsy by endobronchial ultrasonography with a guide sheath could not obtain sufficient material, despite the guide sheath being placed within the lesion, the patient underwent thoracoscopic partial left S6 resection. The nodule was diagnosed as acquired cystic bronchiectasis and mucoid impaction associated with chronic inflammation. The ring-shaped enhancement and the 18 F-FDG uptake may reflect angiogenesis in the cystic wall and accumulation of viable inflammatory cells in the wall and inner space, respectively.


18FDG PET-Positive Congenital Pulmonary Airway Malformation Mimicking Lung Cancer.

Adult cases of type 2 congenital pulmonary airway malformation (CPAM) are extremely rare, and no PET/CT findings have been reported for CPAM. We encountered a case of 18FDG PET-positive CPAM mimicking lung cancer in a 45-year-old asymptomatic man. CT revealed a large cavitary mass in the left lower lobe. SUVmax measured by 18FDG PET was 3.5. The patient underwent video-assisted thoracoscopic lobectomy on suspicion of CPAM with/or lung cancer. Histologically, no neoplastic cells were present, and the lesion was consistent with type 2 CPAM. An adenomatoid proliferative pattern and granulomatous lesions may have contributed to a PET/CT false-positive result.


Angioedema of the Eyelids Induced by a Ketoprofen Adhesive Patch.


A Case of Arc-welders' Pneumoconiosis Improved by Reduction of Dust Exposure

粉じん曝露の低減により改善した溶接工肺の1例

The Journal of the Japanese Society of Internal Medicine


A single dose of pembrolizumab treatment causing a profound and durable response in lung cancer.

Profound and durable responses to a single dose of pembrolizumab in lung cancer are rare. We encountered a non-small cell lung cancer patient showing a deep and durable response with a single dose of pembrolizumab. A 79-year-old man reported bloody sputum for several weeks and visited a general physician. A chest x-ray revealed a tumor shadow in the right middle lung field at that time, and the patient was referred to our hospital. He was diagnosed with adenocarcinoma of the lung by transbronchial biopsy. The expression of programmed death ligand 1 in tumor cells was 100% by immunostaining. Based on the above, immunotherapy with pembrolizumab was performed as first-line therapy. Cancer cells had significantly shrunk at the end of the first cycle. The patient had grade-3 immune-related hepatitis at the end of the first cycle. Pembrolizumab treatment was stopped and prednisolone (80 mg/body) was initiated. Subsequently, liver function normalized, and prednisolone was tapered and discontinued. Since then, no tumor recurrence has been detected for 1.5 years without treatment. There have been few reports of profound and durable responses to a single dose of pembrolizumab in lung cancer. The results indicate that a single dose of pembrolizumab alone may be sufficient to cause durable response and serious immune-related adverse events in some cases.


Dramatic response to immunochemotherapy followed by salvage surgery in an elderly lung cancer patient.

F-fluorodeoxyglucose (FDG) on FDG-positron emission tomography/computed tomography before chemotherapy almost disappeared after pembrolizumab-based immunochemotherapy, left upper lobectomy and lymph node dissection were performed. No cancer cells were pathologically detected from the resected tissue. Therefore, ICIs combined with chemotherapy may enable inoperable advanced lung cancer patients to undergo surgery and achieve a complete response.


Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab.

Pembrolizumab may be used as a treatment option for pulmonary LCNEC.

A 65-year-old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD-L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3-positive T cells and CD138-positive plasma cells. Second-line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing.


Multiple tumors on the pleura with pleural effusion mimicking malignant mesothelioma.


Programmed death (PD)-1/PD-ligand 1 blockade mediates antiangiogenic effects by tumor-derived CXCL10/11 as a potential predictive biomarker.

Immune checkpoint inhibitor (ICI) programmed death (PD)-1/PD-ligand 1 (PD-L1) blockade has been approved for various cancers. However, the underlying antitumor mechanisms mediated by ICIs and the predictive biomarkers remain unclear. We report the effects of anti-PD-L1/PD-1 Ab in tumor angiogenesis. In syngeneic mouse models, anti-PD-L1 Ab inhibited tumor angiogenesis and induces net-like hypoxia only in ICI-sensitive cell lines. In tumor tissue and serum of ICI-sensitive cell line-bearing mice, interferon-γ (IFN-γ) inducible angiostatic chemokines CXCL10/11 were upregulated by PD-L1 blockade. In vitro, CXCL10/11 gene upregulation by IFN-γ stimulation in tumor cell lines correlated with the sensitivity of PD-L1 blockade. The CXCL10/11 receptor CXCR3-neutralizing Ab or CXCL11 silencing in tumor cells inhibited the antiangiogenic effect of PD-L1 blockade in vivo. In pretreatment serum of lung carcinoma patients receiving anti-PD-1 Ab, the concentration of CXCL10/11 significantly correlated with the clinical outcome. Our results indicate the antiangiogenic function of PD-1/PD-L1 blockade and identify tumor-derived CXCL10/11 as a potential circulating biomarker of therapeutic sensitivity.


Human metapneumovirus-associated community-acquired pneumonia in adults during the first wave of COVID-19.

hMPV infection may be considered in the differential diagnosis of COVID-19 and CAP in Japan under the preventive measures for SARS-CoV-2 infection, at least during the epidemic season of hMPV infection.


Eosinophilic pleural effusion due to lung cancer has a better prognosis than non-eosinophilic malignant pleural effusion.

Lung cancer patients with EPE have a better prognosis than those with non-EPE.

A total of 152 patients were included: 89 were male (59%). The median age was 74.4 years (range 37-101), and all patients were pathologically shown to have MPE. Most patients (140; 92%) had an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0/1. Twenty patients had EPE. The median overall survival (OS) of all 152 lung cancer patients with MPE was 298 days. The median OS of the patients with EPE was 766 days, and the median OS of the patients with non-EPE was 252 days. Kaplan-Meier univariate analysis showed that lung cancer patients with EPE had a significantly better prognosis than patients with non-EPE (P < 0.05). Cox proportional regression analysis showed that EPE, ECOG PS, sex, and the neutrophil-to-lymphocyte ratio in the serum (sNLR) may be independent prognostic factors affecting survival in patients with MPE.


Tracheobronchopathia Osteochondroplastica Complicated with Mycobacteroides abscessus Pulmonary Disease.


PCR検査が3回陰性だが,抗体検査で陽性であった新型コロナウイルス感染症(COVID-19)と思われる1例


Mycobacterium Shinjukuense Pulmonary Disease Progressed to Pleuritis after Iatrogenic Pneumothorax: A Case Report.

infection should be considered in the differential diagnosis of mycobacterial pulmonary disease with effusion.

Journal of Clinical Tuberculosis and Other Mycobacterial Diseases


Pulmonary tuberculosis misdiagnosed as extensively drug-resistant tuberculosis due to selection of a nontuberculous mycobacterial colony from a preculture dish used for a drug-susceptibility test.

Drug-susceptibility test (DST) is important for tuberculosis care; however, there are several pitfalls with the procedure. A 70-year-old woman was diagnosed with extensively drug-resistant tuberculosis based on the result of a DST using microdilution method. Because she had no history of medication for tuberculosis and the sputum acid-fast bacillus smear test turned negative during standard treatment, identification of the strain used for DST was performed. Consequently, the strain was found to be M. intracellulare. It was assumed that a colony of M. intracellulare that had existed in the preculture solid medium was selected and used for the DST.


Distinct improvement of pulmonary function, ground-glass opacity, hypoxia and physical findings in an idiopathic pulmonary fibrosis patient after pirfenidone treatment : a case report with a review of the literature.

Background : Pirfenidone (PFD), an anti-fibrosis drug for idiopathic pulmonary fibrosis (IPF), suppresses disease progression and delays decline of forced vital capacity. However, this drug rarely makes marked improvement of pulmonary function, chest high-resolution computed tomography (HRCT) findings and hypoxia. Case presentation : A 59 year-old-man, who was a former smoker and had a history of alcoholic liver cirrhosis, developed exertional dyspnea and was referred to our hospital. HRCT showed honeycomb changes with surrounding ground-glass opacity (GGO) in a predominantly basal and subpleural distribution. He was diagnosed with IPF and the treatment with PFD was started. At 16 months after the start of treatment, the predicted forced vital capacity value markedly improved from 82.9% to 98.6%. His resting-state partial pressure of arterial oxygen while breathing room air increased from a minimum of 54.7 mmHg (at 2 months treatment) to 72.5 mmHg. The GGO observed at diagnosis disappeared in HRCT. But after 32 months of treatment, his general condition got worse gradually, and he died from chronic progression of IPF after 48 months of treatment. Conclusion : Our case suggests that a complication of chronic liver disease and the existence of GGO may be characteristics of super-responder to PFD treatment for IPF patients. J. Med. Invest. 67 : 358-361, August, 2020.

The Journal of Medical Investigation : JMI


左右脚の片脚立位時間と歩行自立度の関連-運動器疾患のない高齢入院患者における検討


Mycobacterium abscessus ssp. abscessus infection progressing to empyema from vertebral osteomyelitis in an immunocompetent patient without pulmonary disease: a case report.

VO of the thoracic spine due to non-tuberculous mycobacterial infection should be considered as a cause of pleuritis or empyema without pulmonary disease, especially in patients with back pain.

A 63-year-old woman was admitted to our hospital with back pain persisting for 4 months and a 2-day history of fever and right chest pain. The patient was initially treated as right-sided empyema due to general bacteria. However, after removal of the chest tube, a previously overlooked paravertebral lesion was observed on CT. MRI confirmed VO at T7/8. Mycobacterium abscessus ssp. abscessus was detected in both the thoracic cavity and the paravertebral lesion. Both VO and the paravertebral abscess were improved by antimycobacterial treatment.


A lobulated mass in the left lower lobe: not what it seems.


悪性気道狭窄に対してAEROステント留置が有効であった1例

悪性気道狭窄に対してAEROステント留置が有効であった1例


Pneumocystis jirovecii pneumonia in an HIV-infected patient mimicking acute eosinophilic pneumonia: a case report with a review of the literature.


Atypical pulmonary alveolar proteinosis presenting as a mixed nodular ground-glass opacity with focal mucinosis mimicking lung cancer.


Elevated Levels of Intelectin-1, a Pathogen-binding Lectin, in the BAL Fluid of Patients with Chronic Eosinophilic Pneumonia and Hypersensitivity Pneumonitis.

Objective Human intelectin-1 (hITLN-1) binds to galactofuranosyl residues, which are present in the microbial cell wall, but which are absent in mammalian tissues, and has been suggested to play an immunological role against microorganisms. However, the involvement of hITLN-1 in the pathogenesis of diffuse pulmonary diseases remains unknown. The aim of this study was to compare the hITLN-1 concentrations in the bronchoalveolar lavage (BAL) fluid of patients with diffuse pulmonary diseases. Methods The cell components and concentrations of hITLN-1 were analyzed in the BAL fluid of 8 patients with idiopathic chronic eosinophilic pneumonia (ICEP), 3 patients with drug-induced eosinophilic pneumonia, 4 patients with hypersensitivity pneumonitis (HP), 11 patients with sarcoidosis, 9 patients with cryptogenic organizing pneumonia, and 5 patients with idiopathic fibrosing interstitial pneumonia (fibrosing nonspecific interstitial pneumonia or usual interstitial pneumonia). Results The hITLN-1 concentrations in the BAL fluid of patients with ICEP and HP were higher than in those with other diseases. In the ICEP group, no significant difference was observed in the hITLN-1 concentrations of patients with or without a history of bronchial asthma. Conclusion The results of the present study suggest that hITLN-1 may be involved in the pathogenesis of ICEP and HP, and that an increase in the hITLN-1 concentration in the BAL fluid may represent a new biomarker for these diseases.


Clinical outcomes after initial treatment of methicillin-resistant Staphylococcus aureus infections.

In this observational study reflecting real-world conditions, vancomycin was associated with higher 30-day mortality and incidence of kidney dysfunction than other anti-MRSA agents. The significance of the differences observed among antimicrobials other than vancomycin is uncertain.


Goodpasture's disease in a patient with advanced lung cancer treated with nivolumab: An autopsy case report.

Nivolumab, an anti-programmed death-1 immune checkpoint inhibitor (ICI), is now widely used to treat numerous cancers. Although most adverse effects related to ICIs are controllable, fulminant immune-related adverse events can occur. A 74-year-old patient with non-small-cell lung cancer was treated with nivolumab as a second-line treatment. After 8 cycles, acute kidney injury with macroscopic hematuria appeared, followed by diffuse ground-glass opacities with hemoptysis. Since the clinical course suggested Goodpasture's disease, methylprednisolone pulse therapy and plasma exchange were started. Later, it was confirmed that the serum anti-glomerular basement membrane antibody was positive. However, the patient died 35 days after admission due to respiratory failure, and an autopsy showed crescentic glomerulonephritis and massive alveolar hemorrhage which were compatible with Goodpasture's disease. Our case provides a possible link between nivolumab and lethal Goodpasture's disease.


Fan-shaped ground-glass opacity (GGO) as a premonitory sign of pulmonary infarction: a case report.

Radiological findings of pulmonary infarction have been well characterized mainly in established infarction. However, the early course CT appearance of patients who develop pulmonary infarction has not yet been fully elucidated. A 50-year-old female with a history of postmenopausal hormone replacement therapy (HRT) presented with dry cough and high-resolution computed tomography (HRCT) findings of fan-shaped segmental ground-glass opacity (GGO) in the right lower lobe. As the parenchymal density in the GGO gradually enlarged over a period of 4 weeks in spite of antibiotic treatment, the patient was referred to our hospital on clinical suspicion of bronchioloalveolar cell carcinoma. However, the pathological findings of a transbronchial biopsy of the lesion were compatible with pulmonary infarction. After an endoscopic examination, the typical CT appearance of established pulmonary infarction was observed. Moreover, enhanced CT detected an intraluminal filling defect in the right lower lobe artery suggesting peripheral pulmonary emboli. Our case was a peripheral pulmonary infarction probably induced by HRT, and suggested that fan-shaped GGO may be a premonitory sign of pulmonary infarction.


MAC症診断における液体培地の有用性,および液体培地のみ陽性患者の臨床的特徴についての検討


Solitary costal plasmacytoma mimicking lung cancer metastasis.

A clinical diagnosis of metastatic bone tumors is usually based on radiological findings without bone biopsy. Plasmacytoma can present as a single osteolytic lesion as described in this case. Early bone biopsy should be considered in unusual clinical settings for a differential diagnosis of primary bone tumors.


歩行速度と下肢荷重率および等尺性膝伸展筋力の関係-高齢入院患者における検討

歩行速度と下肢荷重率および等尺性膝伸展筋力の関係-高齢入院患者における検討


Non-Hodgkin's lymphoma involving a femur bone and bilateral adrenal glands alone with adrenal insufficiency.

Primary bone lymphoma and primary adrenal lymphoma are rare clinicopathological entities of non-Hodgkin's lymphoma (NHL). We present the first case of diffuse large B-cell lymphoma with the involvement of a single bone and both adrenal glands alone with adrenal insufficiency. As primary extranodal NHL may have other unusual extranodal lesions, which may present unexplained clinical findings, patients with primary extranodal NHL require careful systemic examination, even when lymphadenopathy is absent.


Diffuse 18F-fluorodeoxyglucose accumulation in the bone marrow of a patient with haemophagocytic lymphohistiocytosis due to Hodgkin lymphoma.


Cavitary lung cancer with cartilage tissues in the wall mimicking aspergilloma.


有瘻性膿胸に対してEWS を用いた気管支充填術と瘻孔内フィブリン糊注入 の併用が有効であった1例


肺アスペルギローマ術後肺瘻に対してPushampSlide法とロープウェイ法を応用したEWS による気管支充填術が有用であった1例


Overlapping lung parenchymal and bronchial lesion and hilar lymphadenopathy in pulmonary actinomycosis mimicking lung cancer.


Disseminated tuberculosis after pregnancy progressed to paradoxical response to the treatment: report of two cases.

Physicians should recognize PR in tuberculosis patients with postpartum and then evaluate treatment efficacy.

We present two sequential cases (Patient 1: 26-year-old; Patient 2: 29-year-old) of postpartum tuberculosis with pulmonary and extrapulmonary lesions (Patient 1: peritonitis; Patient 2: psoas abscess secondary to spondylitis). Both cases progressed to PR (worsening of pre-existing lung infiltrations (Patients 1, 2) and new contralateral effusion (Patient 2)) in a relatively short time after initiation of treatment (Patient 1: 1 week; Patient 2: 3 weeks), suggesting that immune modulations during pregnancy and delivery may contribute to the pathogenesis of both disseminated tuberculosis and its PR. The pulmonary lesions and effusion of both cases gradually improved without change of chemotherapy regimen.


Miliary pulmonary nodules due to Mycobacterium xenopi in a steroid-induced immunocompromised patient successfully treated with chemotherapy: a case report.

Even when clinical and radiological disease manifestations are similar to those of miliary tuberculosis, M. xenopi infection should be considered in the differential diagnosis of miliary nodules.


Acute respiratory distress syndrome caused by Mycoplasma pneumoniae without elevated pulmonary vascular permeability: a case report.

Sporadic patients with acute respiratory distress syndrome (ARDS) caused by Mycoplasma pneumoniae have been reported. However, knowledge about the pathophysiology and pharmacological treatment of this condition is insufficient. Moreover, the pulmonary vascular permeability in ARDS related to M. pneumoniae infection has not been reported. We report a case of ARDS caused by Mycoplasma pneumoniae without elevated pulmonary vascular permeability, which was successfully treated using low-dose short-term hydrocortisone, suggesting that pulmonary infiltration in ARDS caused by Mycoplasma pneumoniae does not match the criteria of permeability edema observed in typical ARDS.


喘息管理におけるクイックチェックの有用性

喘息管理におけるクイックチェックの有用性


Effect of Isometric Knee Extension Strength on the One-leg Standing Time of Elderly Inpatients

等尺性膝伸展筋力が片脚立位保持時間に及ぼす影響


Kikuchi-Fujimoto disease associated with community acquired pneumonia showing intrathoratic lymphadenopathy without cervical lesions.

KFD should be considered in the differential diagnosis of massive mediastinal and hilar lymphadenopathy, even when there are no superficial lesions. In addition, we need to bear in mind that unexpected disorders occasionally coexist with common diseases.


Primary Gingival Tuberculosis Diagnosed Based on Genetic Identification.

A case of primary gingival tuberculosis in a 71-year-old Japanese woman is herein presented. A serous saliva culture was positive for tuberculosis, and we recognized that the origin of the tuberculosis infection was the gingiva based on the genetic identification in gingival biopsy tissue. The definitive diagnosis was facilitated by the genetic identification, a useful modern tool for diagnosing infectious diseases. The location and clinical presentation of this lesion were unusual, which underlines the importance of considering tuberculosis in the differential diagnosis of oral lesions that affect the gingiva.


Extensive rhabdomyosarcomatous differentiation in recurrent low-grade urothelial carcinoma of the bladder after transurethral resection: a case report.

Urothelial carcinoma of the urinary bladder with extensive rhabdomyosarcomatous differentiation is rare, but it should be considered in the differential diagnosis even when urothelial carcinoma coexisting with a rhabdomyosarcomatous component is low-grade and non-invasive.


Asymptomatic tracheal MALT lymphoma discovered on spirometric findings presenting with elevated respiratory resistance.

The addition of impulse oscillometry to spirometry may be useful for screening CAO in routine health examinations.


Relationship between Standing Balance and Walking Independence of Elderly Inpatients: Examination of the Weight-bearing Ratio and One-leg Standing Time

高齢入院患者における歩行自立と立位バランスの関係


The Relationship between the Weight-bearing Ratio and Isometric Knee Extension Strength of Elderly Inpatients

高齢入院患者における下肢荷重率と等尺性膝伸展筋力の関係


Improvement in idiopathic nonspecific interstitial pneumonia after smoking cessation.

Although cigarette smoking has been recognized as a risk factor for the development of several interstitial lung diseases, the relationship between smoking and nonspecific interstitial pneumonia (NSIP) has not yet been fully elucidated. We here present a case of fibrotic NSIP with mild emphysema in an elderly male with normal pulmonary function, whose symptoms, serum KL-6 level, and high-resolution computed tomography findings of interstitial changes markedly improved without medication following the cessation of smoking. Our case suggests that smoking may be an etiological factor in some patients with NSIP and that early smoking cessation before a clinically detectable decline in pulmonary function may be critical for smokers with idiopathic NSIP.


Hepatosplenic Hodgkin lymphoma without lymphadenopathy following reversible methotrexate-associated lymphoproliferative disorder.

Lymphoproliferative disorders (LPDs) occur more frequently in rheumatoid arthritis (RA) patients treated with immunosuppressive agents than in the non-RA population. However, the various forms of disease progression have not yet been elucidated in detail. We encountered a case of Epstein-Barr virus (EBV)-positive atypical polymorphous LPD in the cervical and intraabdominal lymph nodes with hepatosplenomegaly in an 88-year-old female with RA who had taken infliximab and methotrexate (MTX) for six years. Although spontaneous remission occurred following the withdrawal of infliximab and MTX, reversible LPD evolved into hepatosplenic Hodgkin lymphoma without lymphadenopathy presenting as a cholestatic febrile illness. Our findings suggest that the recurrent lesions of MTX-associated LPDs may not always coincide with the primary lesion and may present unexplained findings based on various extranodal diseases.


BCG-induced pneumonitis with lymphocytic pleurisy in the absence of elevated KL-6.

We speculate that the pathogenesis of our case may be a hypersensitive reaction to the proteic component of BCG entering the lung and pleural space, which is different from the etiology of the common type of HP.


Thallium-201-scintigraphy-positive recurrent pulmonary hyalinising granuloma with elevated IgG4.

The International Journal of Tuberculosis and Lung Disease


Bronchopleural fistula following M. abscessus infection 11 years after lobectomy for lung cancer.

Bronchopleural fistula (BPF) is a potentially fatal complication of lung cancer resection surgery that occurs during the healing process of the bronchial stump. However, the vulnerability of the healed surgical wound to overlapping acquired airway destruction has not yet been determined in detail. We herein present a case of fatal BPF following Mycobacterium abscessus (M. abscessus) infection, which occurred 11 years after right upper lobectomy for lung cancer. The findings of the present study suggest that patients with M. abscessus pulmonary disease in which airway destruction is progressing towards the bronchial stump of previous lobectomy should be considered for early completion pneumonectomy to prevent fatal BPF.


Asymptomatic primary tuberculous pleurisy with intense 18-fluorodeoxyglucose uptake mimicking malignant mesothelioma.

FDG PET/CT imaging may be useful for evaluating disease activity in tuberculous pleurisy patients with an unknown time of onset.


Cholera toxin induces a shift from inactive to active cyclooxygenase 2 in alveolar macrophages activated by Mycobacterium bovis BCG.

Intranasal vaccination stimulates formation of cyclooxygenases (COX) and release of prostaglandin E(2) (PGE(2)) by lung cells, including alveolar macrophages. PGE(2) plays complex pro- or anti-inflammatory roles in facilitating mucosal immune responses, but the relative contributions of COX-1 and COX-2 remain unclear. Previously, we found that Mycobacterium bovis BCG, a human tuberculosis vaccine, stimulated increased release of PGE(2) by macrophages activated in vitro; in contrast, intranasal BCG activated no PGE(2) release in the lungs, because COX-1 and COX-2 in alveolar macrophages were subcellularly dissociated from the nuclear envelope (NE) and catalytically inactive. This study tested the hypothesis that intranasal administration of BCG with cholera toxin (CT), a mucosal vaccine component, would shift the inactive, NE-dissociated COX-1/COX-2 to active, NE-associated forms. The results showed increased PGE(2) release in the lungs and NE-associated COX-2 in the majority of COX-2(+) macrophages. These COX-2(+) macrophages were the primary source of PGE(2) release in the lungs, since there was only slight enhancement of NE-associated COX-1 and there was no change in COX-1/COX-2 levels in alveolar epithelial cells following treatment with CT and/or BCG. To further understand the effect of CT, we investigated the timing of BCG versus CT administration for in vivo and in vitro macrophage activations. When CT followed BCG treatment, macrophages in vitro had elevated COX-2-mediated PGE(2) release, but macrophages in vivo exhibited less activation of NE-associated COX-2. Our results indicate that inclusion of CT in the intranasal BCG vaccination enhances COX-2-mediated PGE(2) release by alveolar macrophages and further suggest that the effect of CT in vivo is mediated by other lung cells.


Role of PPARγ in COX-2 activation in mycobacterial pulmonary inflammation.

Preliminary studies show that intranasal (i.n.) administration of BCG in mice induces M1 activation of alveolar macrophages (M) that increase TNF-α production and cyclooxygenase-2 (COX-2) expression but reduce constitutive peroxisome proliferator-activated receptor gamma (PPARγ) expression. However, COX-2 is catalytically inactive for prostaglandin E(2) release, unlike COX-2 that is active in M1 activation in vitro by BCG. In this study, we determined the role of PPARγ for BCG-induced M1 activation in vivo and in vitro. We found that treatment of mice with GW9662, a PPARγ antagonist, prior to i.n. BCG, partially restored PPARγ expression, and decreased TNF-α production and COX-2 expression. But COX-2 was still inactive. The decreased effects on TNF-α and COX-2 were also observed when alveolar M were treated in vitro with GW9662/BCG, but COX-2 was still active. Our results indicate that PPARγ upregulates M1 activation of alveolar M, but inactive COX-2 formation is independent of PPARγ in mycobacterial pulmonary inflammation.


Extragonadal seminoma presenting as a large mass in the pelvic cavity without c-kit-activating mutations.

Extragonadal germ cell tumors are relatively rare tumors, which usually occur in the mediastinum or retroperitoneum. In this report, we present a case of primary seminoma arising in the pelvic cavity. A 58-year-old man with urinary retention and abdominal distension was admitted to our hospital. Computed tomography and magnetic resonance imaging demonstrated a large mass in the pelvic cavity. Histological examination of the specimens obtained by open biopsy revealed seminomatous malignant cells. Immunohistochemical studies detected vimentin, placental alkaline phosphatase and c-kit. Taking these results together with the patient's other clinical manifestations, this case was diagnosed as extragonadal seminoma without c-kit-activating mutations, and chemotherapy followed by radiation therapy was successful. Primary seminoma in the pelvic cavity is extremely rare, but should be considered a cause of pelvic mass formation.


肋骨発生の線維性骨異形成症の1例

肋骨発生の線維性骨異形成症の1例

The Japanese Journal of Thoracic Surgery


Exacerbation of cranial nerurological symptoms by platelet transfusion before the diagnosis of thrombotic thrombocytopenic purpura

確定診断前の血小板輸血により神経症状が顕性化したと考えられる血栓性血小板減少性紫斑病

The Japanese Journal of Clinical Hematology


A Case of Lung Aspergilloma in Which Endobronchial Watanabe Spigot (EWS) Was Not Effective for Hemoptysis

喀血に対してendobronchial Watanabe spigot (EWS)による気管支充填術が有効でなかった肺アスペルギローマの1例

The Journal of the Japan Society for Respiratory Endoscopy


CD5-positive diffuse large B cell lymphoma infiltrating the central nervous system presenting Guillain-Barré-like syndrome after chemotherapy.

An 83-year-old woman was admitted to our hospital with abdominal pain. Examination revealed mediastinal lymphoadenopathy, hepatosplenomegaly, and infiltration of abnormal cells into the bone marrow with hemophagocytosis, and CD5-positive diffuse large B cell lymphoma was diagnosed. Chemotherapy was administered and progressive weakness of the limbs, resembling a Guillain-Barré-like syndrome, subsequently appeared. Cerebrospinal fluid examination indicated lymphoma cell infiltration. Although immune globulin and steroid therapies were not effective, intrathecal injection of methotrexate, predonisolone, and cytarabine improved these symptoms. Subsequent to chemotherapy, cell surface antigen changes were observed in the cerebrospinal fluid relative to those in bone marrow.

Journal of Clinical and Experimental Hematopathology


Acute myeloid leukemia with myelodysplasia-related changes mimicking acute promyelocytic leukemia.

We describe a patient with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) that clinically resembled acute promyelocytic leukemia (APL). The karyotype of his leukemic cells was 46, XY, del (3) (q?) and did not include a chromosomal translocation involving the retinoic acid receptor-α gene. However, retinoic acid syndrome developed, and partial remission was achieved after treatment with all-trans retinoic acid (ATRA) followed by chemotherapy. Our case might provide new insights into the mechanism of the growth inhibitory effect of ATRA on APL-like cells.


汎血球減少を呈し血液培養で結核菌陽性であった粟粒結核の1例

汎血球減少を呈し血液培養で結核菌陽性であった粟粒結核の1例

医療 : 国立医療学会誌 :Japanese journal of National Medical Services


Chylothorax, the accumulation of fatty fluid within the chest cavity, is associated with multiple etiologies including surgical injuries. A rare complication of acupuncture in a 37-year-old woman who developed left pneumothorax and pleural fluid collection after acupuncture was performed on the neck and upper back is described. Chest tube drainage resulted in complete lung expansion, and analysis of the milky fluid revealed chyle leakage. Conservative treatment with a diet low in lipids and rich in medium-chain triacylglycerols allowed extubation. Acupuncture-induced thoracic duct injury, although extremely rare, should be considered as a cause of chylothorax.


Immunoglobulin D-lambda type multiple myeloma presenting with FDG-PET/CT negative bone marrow involvement.

We here report a rare case of a patient with IgD-lambda-positive multiple myeloma presenting with FDG-PET/CT negative bone marrow involvement. A 72-year-old man was admitted to our hospital for evaluation of a paravertebral tumor of the chest. Thoracotomy was performed and a histopathological evaluation of resected intrathoracic tumor demonstrated a plasmacytic neoplasma. Initially we thought that this case was a solitary plasmacytoma because there were no positive findings on postoperative FDG-PET/CT. However, bone marrow aspiration study demonstrated massive infiltration of myeloma cells (72%). It is necessary to recognize that IgD-lambda type myeloma cells may not be sufficiently metabolically active to form high uptake on FDG-PET/CT.


Two cases of drug-induced intrathoracic lesions caused by mesalazine in patients with ulcerative colitis

Mesalazine による薬剤性胸郭内病変を呈した潰瘍性大腸炎の2例

The journal of the Japanese Respiratory Society


抗酸菌感染症との鑑別を要した肺サルコイドーシスの1例

抗酸菌感染症との鑑別を要した肺サルコイドーシスの1例

日本胸部臨床 = The Japanese journal of chest diseases


Chitin particles induce size-dependent but carbohydrate-independent innate eosinophilia.

Murine M that phagocytose CMP develop into M1; this response depends on the size and the chemical composition of the particles. In contrast, recent studies concluded that chitin particles induce M2 and eosinophil migration, promoting acquired Th2 immune responses against chitin-containing microbes or allergens. This study examined whether these apparently inconsistent responses to chitin could be induced by variation in the size and chemical composition of the chitin particles. We compared the responses of M with CMP, LCB, and Sephadex G-100 beads (>40 μm). Beads were given i.p. to WT mice and to mice deficient in a CRTH2, a receptor for the eosinophil chemoattractant PGD(2). In contrast to the M1 activation induced by CMP, i.p. administration of LCB or Sephadex beads induced within 24 h a CRTH2-dependent peritoneal eosinophilia, as well as CRTH2-independent activation of peritoneal M that expressed Arg I, an M2 phenotype. LCB-induced M exhibited elevated Arg I and a surface MR, reduced surface TLR2 levels, and no change in the levels of CHI3L1 or IL-10 production. Our results indicate that the effects of chitin in vivo are highly dependent on particle size and that large, nonphagocytosable beads, independent of their chemical composition, induce innate eosinophilia and activate M expressing several M2, but not M1, phenotypes.


Safety of Adjuvant Chemotherapy with Carboplatin and Weekly Paclitaxel for Pathological Stage IB-IIIB Non-small Cell Lung Cancer

病理病期IB∼IIIB期非小細胞肺癌に対するcarboplatin+weekly paclitaxel併用術後化学療法の安全性に関する検討


A Case of Pulmonary Nontuberculous Mycobacteriosis Induced by Tocilizumab Treatment for Rheumatoid Arthritis

トシリズマブによる関節リウマチ治療中に発症した非結核性抗酸菌症の 1 例


内痔核による出血が原因となった著明な鉄欠乏性貧血の1例

内痔核による出血が原因となった著明な鉄欠乏性貧血の1例


一般診療所における潜在的COPD患者の疫学調査

一般診療所における潜在的COPD患者の疫学調査


Capture of heat-killed Mycobacterium bovis bacillus Calmette-Guérin by intelectin-1 deposited on cell surfaces.

Intelectin is an extracellular animal lectin found in chordata. Although human and mouse intelectin-1 recognize galactofuranosyl residues included in cell walls of various microorganisms, the physiological function of mammalian intelectin had been unclear. In this study, we found that human intelectin-1 was a serum protein and bound to Mycobacterium bovis bacillus Calmette-Guérin (BCG). Human intelectin-1-binding to BCG was inhibited by Ca(2+)-depletion, galactofuranosyl disaccharide, ribose, or xylose, and was dependent on the trimeric structure of human intelectin-1. Although monomeric, mouse intelectin-1 bound to BCG, with its C-terminal region contributing to efficient binding. Human intelectin-1-transfected cells not only secreted intelectin-1 into culture supernatant but also expressed intelectin-1 on the cell surface. The cell surface intelectin-1 was not a glycosylphosphatidylinositol-anchored membrane protein. Intelectin-1-transfected cells captured BCG more than untransfected cells, and the BCG adherence was inhibited by an inhibitory saccharide of intelectin-1. Intelectin-1-preincubated cells took up BCG more than untreated cells, but the adhesion of intelectin-1-bound BCG was the same as that of untreated BCG. Mouse macrophages phagocytosed BCG more efficiently in medium containing mouse intelectin-1 than in control medium. These results indicate that intelectin is a host defense lectin that assists phagocytic clearance of microorganisms.


Persistent inactivation of macrophage cyclooxygenase-2 in mycobacterial pulmonary inflammation.

The induction of cyclooxygenase-2 (COX-2) in tissue macrophages (MØ) increases prostaglandin E(2) (PGE(2)) release, potentially down-regulating granulomatous inflammation. In response to Mycobacteria, local MØ express COX-2, which is either nuclear envelope (NE)-associated or NE-dissociated. Persistent mycobacterial pulmonary inflammation is characterized by alveolar MØ expressing NE-dissociated (inactive) COX-2 without release of PGE(2). In this study, we examined COX-2 in alveolar MØ after intranasal exposure to heat-killed Mycobacterium bovis BCG (HK-BCG). After administration, whole lungs of C57Bl/6 mice were lavaged with saline; COX-2 expression and PGE(2) release by alveolar MØ and tumor necrosis factor (TNF)-alpha and nitric oxide levels in the lung lavage were monitored. Normal alveolar MØ had undetectable levels of COX-2 on Western blots. However, 1 day after intranasal administration, almost all alveolar MØ had phagocytosed HK-BCG and expressed NE-dissociated COX-2 without any increase in the release of PGE(2). At 28 days after intranasal administration, 68% of alveolar MØ still contained both BCG and the NE-dissociated form of COX-2. NE-associated (active) COX-2 was not observed in alveolar MØ. In contrast, 7 days after intraperitoneal injection of HK-BCG, peritoneal MØ containing HK-BCG were no longer detected. At 28 days after intranasal administration, TNF-alpha and nitrite levels in the lung lavage fluid were significantly higher than those in controls. Our results indicate that mycobacterial pulmonary inflammation is associated with suppressed PGE(2) production by alveolar MØ, with expression of COX-2 dissociated from the NE.

American Journal of Respiratory Cell and Molecular Biology


Depletion of cellular cholesterol enhances macrophage MAPK activation by chitin microparticles but not by heat-killed Mycobacterium bovis BCG.

When macrophages phagocytose chitin (N-acetyl-d-glucosamine polymer) microparticles, mitogen-activated protein kinases (MAPK) are immediately activated, followed by the release of Th1 cytokines, but not IL-10. To determine whether phagocytosis and macrophage activation in response to chitin microparticles are dependent on membrane cholesterol, RAW264.7 macrophages were treated with methyl-beta-cytodextrin (MBCD) and stimulated with chitin. These results were compared with the corresponding effects of bacterial components including heat-killed (HK) Mycobacterium bovis bacillus Calmette-Guèrin (BCG) and an oligodeoxynucleotide (ODN) of bacterial DNA (CpG-ODN). The MBCD treatment did not alter chitin binding or the phagocytosis of chitin particles 20 min after stimulation. At the same time, however, chitin-induced phosphorylation of cellular MAPK was accelerated and enhanced in an MBCD dose-dependent manner. The increased phosphorylation was also observed for chitin phagosome-associated p38 and ERK1/2. In contrast, CpG-ODN and HK-BCG induced activation of MAPK in MBCD-treated cells at levels comparable to, or only slightly more than, those of control cells. We also found that MBCD treatment enhanced the production of tumor necrosis factor-alpha (TNF-alpha) and the expression of cyclooxygenase-2 (COX-2) in response to chitin microparticles. In neither MBCD- nor saline-treated macrophages, did chitin particles induce detectable IL-10 mRNA synthesis. CpG-ODN induced TNF-alpha production, and COX-2 expression were less sensitive to MBCD treatment. Among the agonists studied, our results indicate that macrophage activation by chitin microparticles was most sensitive to cholesterol depletion, suggesting that membrane structures integrated by cholesterol are important for physiological regulation of chitin microparticle-induced cellular activation.

American Journal of Physiology, Cell Physiology


Meaning of Pulmonary Function Test in Physical Checkup

健康診断における肺機能検査の意義

Japanese Journal of National Medical Services


Catalytically inactive cyclooxygenase 2 and absence of prostaglandin E2 biosynthesis in murine peritoneal macrophages following in vivo phagocytosis of heat-killed Mycobacterium bovis bacillus Calmette-Guérin.

Over 25 years ago, it was observed that peritoneal macrophages (Mphi) isolated from mice given heat-killed Mycobacterium bovis bacillus Calmette-Guérin (HK-BCG) i.p. did not release PGE(2). However, when peritoneal Mphi from untreated mice are treated with HK-BCG in vitro, cyclooxygenase 2 (COX-2), a rate-limiting enzyme for PGE(2) biosynthesis, is expressed and the release of PGE(2) is increased. The present study of peritoneal Mphi obtained from C57BL/6 mice and treated either in vitro or in vivo with HK-BCG was undertaken to further characterize the cellular responses that result in suppression of PGE(2) release. The results indicate that Mphi treated with HK-BCG in vivo express constitutive COX-1 and inducible COX-2 that are catalytically inactive, are localized subcellularly in the cytoplasm, and are not associated with the nuclear envelope (NE). In contrast, Mphi treated in vitro express catalytically active COX-1 and COX-2 that are localized in the NE and diffusely in the cytoplasm. Thus, for local Mphi activated in vivo by HK-BCG, the results indicate that COX-1 and COX-2 dissociated from the NE are catalytically inactive, which accounts for the lack of PGE(2) production by local Mphi activated in vivo with HK-BCG. Our studies further indicate that the formation of catalytically inactive COX-2 is associated with in vivo phagocytosis of HK-BCG, and is not dependent on extracellular mediators produced by in vivo HK-BCG treatment. This attenuation of PGE(2) production may enhance Mphi-mediated innate and Th1-acquired immune responses against intracellular infections which are suppressed by PGE(2).


Differential structure and activity between human and mouse intelectin-1: human intelectin-1 is a disulfide-linked trimer, whereas mouse homologue is a monomer.

Human intelectin-1 (hITLN-1) is a 120-kDa lectin recognizing galactofuranosyl residues found in cell walls of various microorganisms but not in mammalian tissues. Although mouse intelectin-1 (mITLN-1) has been identified previously, its biochemical properties and functional characteristics have not been studied. Therefore, we have compared structures and saccharide-binding specificities of hITLN-1 and mITLN-1 using recombinant proteins produced by mammalian cells. Recombinant hITLN-1 is a trimer, disulfide-linked through Cys-31 and Cys-48, and N-glycosylated at Asn-163. Despite 84.9% amino acid identity to hITLN-1, recombinant and intestinal mITLN-1 are unglycosylated 30-kDa monomers. Recombinant hITLN-1, as well as recombinant and intestinal mITLN-1 were purified by Ca(2+)-dependent adsorption to galactose-Sepharose. In competitive binding studies, hITLN-1 was eluted from galactose-Sepharose by 100 mM 2-deoxygalactose, a galactofuranosyl disaccharide, d-xylose, and both d- and l-ribose. In contrast, mITLN-1 was partially eluted by the galactofuranosyl disaccharide, and only minimally by the other saccharides indicating that the two intelectins have different saccharide-binding specificities. When the N- and C-terminal regions of hITLN-1 were replaced, respectively, with those of mITLN-1, galactose-Sepharose binding was associated with the C-terminal regions. Finally, hITLN-1 binding to galactose-Sepharose was not affected by the substitution of the Cys residues in the N-terminal region that are necessary for oligomer formation, nor was it affected by the removal of the N-linked oligosaccharide at Asn-163. Although both hITLN-1 and mITLN-1 recognize galactofuranosyl residues, our comparative studies, taken together, demonstrate that these intelectins have different quaternary structures and saccharide-binding specificities.


Squamous Cell Carcinoma of the Lung in a 17-year-old Boy

17歳で発症した低分化型肺扁平上皮癌の1例


軟性気管支鏡と耳鼻科用鉗子を併用して摘出し得た気道異物(義歯)の1例

軟性気管支鏡と耳鼻科用鉗子を併用して摘出し得た気道異物(義歯)の1例


A Case of Pulmonary Epithelioid Hemangioendothelioma

肺類上皮血管内皮腫の1例


糖尿病教育入院中に発見された睡眠時無呼吸症候群を合併した2型糖尿病5例の臨床的検討

徳島赤十字病院医学雑誌 = Tokushima Red Cross Hospital Medical Journal


Typical Pulmonary Carcinoid With Mediastinal Lymph Node Metastasis

縦隔リンパ節に転移を認めた末梢型定型的肺カルチノイドの1例


Gemcitabine reduced the size of tumor and improved QOL in a case of malignant pericardial mesothelioma

ゲムシタビンにて腫瘍縮小効果とQOL改善が得られた心膜悪性中皮腫の1例


三尖弁感染症心内膜炎および化膿性脊椎炎に併発した敗血症性肺塞栓症の1例(症例報告)

The journal of the Japanese Respiratory Society


Transduction of KAI1/CD82 cDNA promotes hematogenous spread of human lung-cancer cells in natural killer cell-depleted SCID mice

KAI1, which is identical to CD82, was initially identified as a metastasis-suppressor gene for human prostate cancer, and its expression is reported to be a favorable prognostic factor for operable human lung cancer. In this study, we examined the functional role of KAI1/CD82 in the late phase of metastatic spread of human lung-cancer cells. For this, KAI1/CD82 cDNA was introduced into KAI1/CD82 low-expressing human lung-cancer cell lines, SBC-3 and PC-14, and then the metastatic potential of the transformants was analyzed by i.v. inoculation of KAI1/CD82-transduced cells, SBC-3/KAI1 and PC-14/KAI1, into NK cell-depleted SCID mice. Contrary to our expectations, KAI1/CD82 gene transfer promoted multiorgan metastasis of i.v.-inoculated human lung-cancer cells, while s.c. tumor growth was unaffected. Cancer cells from metastatic tumors of NK cell-depleted SCID mice injected i.v. with SBC-3/KAI1 expressed appreciable cell-surface KAI1/CD82, and cells not expressing KAI1/CD82 (revertants) were not detected in the tumors. Our findings indicate that under conditions where the host's natural cytotoxicity is suppressed, KAI1/CD82 may enhance the formation of tumors by circulating lung-cancer cells at metastatic sites.


Novel centrifugal method for simple and highly efficient adenovirus-mediated green fluorescence protein gene transduction into human monocyte-derived dendritic cells

Dendritic cells (DC) are professional antigen-presenting cells in the immune system. Gene transduction of DC with tumor-associated antigen (TAA) or other genes that enhance the immune reaction has been considered theoretically useful for DC-based immunotherapy. However, gene transduction of DC generated from human peripheral blood monocytes has been difficult due to its low efficiency, even when adenoviral vector was used at high multiplicity of infection (MOI). In the present study, we examined the effect of centrifugal force to enhance efficiency of adenovirus-mediated gene transduction into human monocyte-derived DC at various rotor speeds at various temperatures for various times. We judged the transduction efficiency using enhanced green fluorescence protein (EGFP)-expressing adenoviral vector, and the best condition for centrifugal transduction was determined as 2000 x g at 37 degrees C for 2 h at an MOI of 10 or greater. At an MOI of 50 without centrifugation, the gene transduction efficiency was about 66% and mean fluorescence intensity (MFI) of EGFP expression was about 150 (at 37 degrees C for 2 h). With centrifugal transduction (2000 x g at an MOI of 50 at 37 degrees C for 2 h), 86% or more DC were gene-modified, and especially, MFI of EGFP expression was highly enhanced (MFI: about 3100 or greater). Centrifugally gene-transduced DC were not damaged and were thoroughly functional as measured by mixed lymphocyte reaction (MLR). The centrifugal method was also applicable to human monocytes and K562 cells. The centrifugal transduction method with adenoviral vector might be helpful for the generation of gene-modified DC.


Enhanced efficiency by centrifugal manipulation of adenovirus-mediated interleukin 12 gene transduction into human monocyte-derived dendritic cells.

Transduction of dendritic cells (DCs) with genes encoding tumor-associated antigen or with other genes that enhance immune reaction has been theorized to be potentially useful for enhancing the efficiency of DC-based immunotherapy. However, gene transduction of DCs generated from human peripheral blood monocytes has been of limited use because of the low efficiency. Here, we report that the efficiency of in vitro adenovirus-mediated gene transduction into human monocyte-derived DCs can be dramatically enhanced by centrifugation. The best conditions for centrifugal gene transduction were determined to be as follows: 2000 x g at 37 degrees C for 2 hr at a multiplicity of infection (MOI) of 10 or greater. By this centrifugal method, approximately 88 and 70% of DCs were gene transducible at an MOI of 50 and 10, respectively. Functional analysis showed that DCs transduced with human interleukin 12 (IL-12)-expressing adenoviral vector under the optimal conditions of centrifugation stably produced IL-12 protein at high levels (8.1 ng/10(6) cells/48 hr). IL-12 gene-modified DCs (DC/IL-12) displayed a more mature phenotype than nontransduced DCs, as judged by decreased expression of CD1a and increased expression of CD83, B7.1 (CD80), B7.2 (CD86), and MHC class I and II molecules. DC/IL-12 showed a high phagocytic ability similar to nontransduced DCs and were significantly superior to control DCs in the stimulation of autologous and allogeneic T lymphocyte responses. The centrifugal transduction method with adenoviral vector might be useful for efficient generation of gene-modified DCs because it is very simple, highly efficient, reproducible, and not cytopathic. IL-12 gene-modified human DCs may be therapeutically useful as a good adjuvant in DC-based immunotherapy.


Symposium on molecular pathogenesis of respiratory diseases and its clinical implication. 4. Molecular pathogenesis of lung cancer and its molecular targeted therapy


嚢胞状変化を呈した肺サルコイドーシスの1例

嚢胞状変化を呈した肺サルコイドーシスの1例


Down-regulation by a new anti-inflammatory compound, FR167653, of differentiation and maturation of human monocytes and bone marrow CD34(+) cells to dendritic cells

International Journal of Immunopharmacology


Effect of clarythromycin on the distant metastases of human lung cancer cells in SCID mice

Recently, the use of macrolides is suggested to be therapeutically effective in prolonging the survival of patients with inoperable non-small cell lung cancer. The purpose of this study was to examine therapeutic effects of a macrolide, clarythromycin (CAM) on the metastastic developments of two different human non-small cell lung cancers (squamous cell lung carcinoma RERF-LC-AI, and adenocarcinoma PC-14) in severe combined immunodeficient (SCID) mice depleted or undepleted of natural killer (NK) cells, respectively. CAM, injected subcutaneously at doses of 5 and 10 mg/kg body weight/day from day 7 to 41 after i.v. inoculation of human lung cancer cells, was not effective in inhibiting their distant organ metastases in SCID mice. CAM at concentrations of less than 10 micrograms/ml did not have a direct influence on the proliferation of these tumor cells in vitro. Although CAM alone was not effective in augmenting NK activity, it augmented the IL-2-induced killer (LAK) activity against Daudi cells in vitro. These results suggest that CAM alone may not be enough to control the spread of non-small cell lung cancer in the patient with T cell dysfunction.

The Journal of Medical Investigation : JMI


Model of malignant pleural effusion of human lung adenocarcinoma in SCID mice

Malignant pleural effusion (PE) is a frequent problem in lung cancer. In this study, we established a model of malignant PE of human adenocarcinoma cells, PC-14, in SCID mice. Intravenously injected PC-14 cells formed colonies in the lungs as early as week 4 after tumor inoculation, and produced bloody PE in all recipient SCID mice by week 8. Pretreatment of SCID mice with anti-mouse IL-2 receptor beta chain antibody (TM-beta 1) to deplete natural killer (NK) cells markedly promoted the production of bloody PE and metastases to multiple organs, such as the lungs, liver, kidneys, and lymph nodes 4 weeks after tumor inoculation. Histological studies indicated that PC-14 cells formed colonies in the lungs, and then invaded the pleura and spread to the pleural cavity. To establish cell lines with a high potential to produce PE, we harvested PE, expanded the tumor cells in vitro, and injected them into SCID mice again. By four in vivo selection cycles in this way we obtained PC-14-PM4 cells, which produce lung metastases and PE earlier than PC-14 cells. The survival of SCID mice inoculated with PC-14-PM4 cells was significantly shorter than that of mice inoculated with PC-14 cells. The expressions of adhesion molecules, such as CD44, CD49d, ICAM-1, and MHC class I, on PC-14-PM4 cells tended to increase compared with PC-14 cells. These changes of adhesion molecules seem to be one of possible mechanisms involved in higher metastatic potential of PC-14-PM4 cells. PE models with PC-14 and PC-14-PM4 cells should be useful for biological and preclinical studies on malignant PE produced by human lung cancer.


Transduction of the macrophage colony-stimulating factor gene into human multidrug resistant cancer cells: enhanced therapeutic efficacy of monoclonal anti-P-glycoprotein antibody in nude mice

To develop a therapeutic modality for overcoming multidrug-resistant (MDR) cancer with anti-MDR1 antibody, we examined the effect of macrophage colony-stimulating factor (M-CSF) gene transfection into MDR AD10 cells on therapy of MDR cancer with anti-MDR1 antibody (MRK17) in nude mice. MDR human ovarian cancer (AD10) cells were transduced with the human M-CSF gene inserted into an expression vector to establish gene-modified cells capable of producing low (ML-AD10), intermediate (MM-AD10) nd high (MH-AD10) amounts of M-CSF. Systemic administration of MRK17 resulted in significant dose-dependent inhibition of subcutaneous growth of ML-AD10 tumors. In contrast, systemic administration of recombinant M-CSF in combination with MRK17 did not augment the therapeutic efficacy of MRK17 alone, but rather promoted the growth of the parent AD10 cells. To test the efficacy of in vivo M-CSF gene therapy combined with antibody, we mixed the parent AD10 cells with MH-AD10 cells producing a large amount of M-CSF, and inoculated the mixed cells subcutaneously. Treatment with MRK17 inhibited growth of the mixed cells more than that of the parent cells alone. Thus, combined therapy with anti-MDR1 mAb and M-CSF gene modification of MDR cancer cells may provide a new immunotherapeutic modality for overcoming MDR in humans.


Serum levels of interleukin 6 in patients with lung cancer

Journal of Japan Association of Breast Cancer Screening


Loss of heterozygosity on chromosome arm 17p in small cell lung carcinomas, but not in neurofibromas, in a patient with von Recklinghausen neurofibromatosis.

The formation of SCLC may result from several genetic alterations, including inactivation of tumor-suppressor gene on chromosome 17p, most likely P53, although it still is unknown whether or not a mutation of the NF1 gene on 17q was involved in the development of SCLC in this patient.


The Significance of CA-50, SLX and ST-439 in Lung Cancer.

肺癌におけるCA‐50，SLX， ST‐439の検討

The Japanese Journal of Thoracic Diseases