Endobronchial lesions of sarcoidosis.
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Aged↗
Biomedical subjects
Shosaku Abe
Publications and source records attributed to Shosaku Abe.
[Quantification of the inflammatory mediators and their significance].
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Asthma↗
Pulmonary collectins enhance phagocytosis of Mycobacterium avium through increased activity of mannose receptor.
Collectins, including surfactant proteins A (SP-A) and D (SP-D) and mannose binding lectin (MBL), are the important constituents of the innate immune system. Mycobacterium avium, a facultative intracellular pathogen, has developed numerous mechanisms for entering mononuclear phagocytes. In this study, we investigated the interactions of collectins with M. avium and the effects of these lectins on phagocytosis of M. avium by macrophages. SP-A, SP-D, and MBL exhibited a concentration-dependent binding to M. avium. The binding of SP-A to M. avium was Ca(2+)-dependent but that of SP-D and MBL was Ca(2+)-independent. SP-A and SP-D but not MBL enhanced the phagocytosis of FITC-labeled M. avium by rat alveolar macrophages and human monocyte-derived macrophages. Excess mannan, zymosan, and lipoarabinomannan derived from the M. avium-intracellular complex, significantly decreased the collectin-stimulated phagocytosis of M. avium. Enhanced phagocytosis was not affected by the presence of cycloheximide or chelation of Ca(2+). The mutated collectin, SP-A(E195Q, R197D) exhibited decreased binding to M. avium but stimulated phagocytosis to a level comparable to wild-type SP-A. Enhanced phagocytosis by cells persisted even after preincubation and removal of SP-A or SP-D. Rat alveolar macrophages that had been incubated with SP-A or SP-D also exhibited enhanced uptake of (125)I-mannosylated BSA. Analysis by confocal microscopy and flow cytometry revealed that the lung collectins up-regulated the cell surface expression of mannose receptor on monocyte-derived macrophages. These results provide compelling evidence that SP-A and SP-D enhance mannose receptor-mediated phagocytosis of M. avium by macrophages.
Animals↗
Pulmonary surfactant protein A augments the phagocytosis of Streptococcus pneumoniae by alveolar macrophages through a casein kinase 2-dependent increase of cell surface localization of scavenger receptor A.
Pulmonary surfactant proteins A (SP-A) and D (SP-D), members of the collectin family, play important roles in the innate immune system of the lung. Here, we show that SP-A but not SP-D augmented phagocytosis of Streptococcus pneumoniae by alveolar macrophages, independent of its binding to the bacteria. Analysis of the SP-A/SP-D chimeras, in which progressively longer carboxyl-terminal regions of SP-A were replaced with the corresponding SP-D regions, has revealed that the SP-D region Gly(346)-Phe(355) can be substituted for the SP-A region Leu(219)-Phe(228) without altering the SP-A activity of enhancing the phagocytosis and that the SP-A region Cys(204)-Cys(218) is required for the SP-A-mediated phagocytosis. Acetylated low density lipoprotein significantly reduced the SP-A-stimulated uptake of the bacteria. SP-A failed to enhance the phagocytosis of S. pneumoniae by alveolar macrophages derived from scavenger receptor A (SR-A)-deficient mice, demonstrating that SP-A augments SRA-mediated phagocytosis. Preincubation of macrophages with SP-A at 37 degrees C but not at 4 degrees C stimulated the phagocytosis. The SP-A-mediated enhanced phagocytosis was not inhibited by the presence of cycloheximide. SP-A increased cell surface localization of SR-A that was inhibitable by apigenin, a casein kinase 2 (CK2) inhibitor. SP-A-treated macrophages exhibited significantly greater binding of acetylated low density lipoprotein than nontreated cells. The SP-A-stimulated phagocytosis was also abolished by apigenin. In addition, SP-A stimulated CK2 activity. These results demonstrate that SP-A enhances the phagocytosis of S. pneumoniae by alveolar macrophages through a CK2-dependent increase of cell surface SR-A localization. This study reveals a novel mechanism of bacterial clearance by alveolar macrophages.
Acetylation↗
Expression of survivin mRNA and livin mRNA in non-small-cell lung cancer.
It has been suggested that suppression of apoptosis may contribute to the development and progression of cancer. Anti-apoptotic survivin and livin genes are highly expressed in cancer cells and transformed cells, but show little or no expression in normal differentiated tissues. However, there are no available data concerning livin expression in non-small-cell lung cancer (NSCLC). We therefore measured livin mRNA and survivin mRNA expression in 38 NSCLC cancer samples and 15 paired non-cancerous lung tissue samples using a quantitative reverse transcription-polymerase chain reaction (RT-PCR). While both mRNAs showed higher expression in cancers than non-cancerous tissues (P < 0.001), livin mRNA and survivin mRNA expression did not correlate with one another. When a cut-off value for positivity was set at the mean + S.D. for expression values in non-cancerous tissues, positivity rates for livin mRNA and survivin mRNA expression were 76.3% (29 of 38) and 36.8% (14 of 38) in lung cancers and 6.7% (1 of 15) and 0% (0 of 15), respectively, in paired non-cancerous lung tissue samples. Livin mRNA and survivin mRNA expression in tumors were up-regulated in 23 of 31 (74.2%) early-stage NSCLC patients and 11 of 31 (35.5%), respectively. Expression of both mRNAs in tumors varied independently of tumor histology. These results support the possibility that the livin gene may play a role in NSCLC development and increased expression of livin mRNA may serve as a new target for lung cancer treatment as well as survivin.
Adaptor Proteins, Signal Transducing↗
Acute lung injury as an adverse event of gefitinib.
Gefitinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, is an effective treatment for patients with non-small cell lung cancer (NSCLC). Some investigators have recently reported several patients complicated by acute lung injury after the initiation of gefitinib administration. In this report, we investigated the efficacy and adverse events during treatment with gefitinib. The subjects of this study were all of the 110 patients with NSCLC who were treated in our hospital and its eight branch hospitals. Patients received gefitinib at a dose of 250 mg once daily. The response rate was 30%. The frequently reported adverse events were skin disorders, gastrointestinal disturbances, liver dysfunction and acute lung injury. Five of the 12 patients who were considered to have suffered acute lung injury died of progressive respiratory failure. Of the nine patients who had pulmonary fibrosis before use of gefitinib, five developed acute lung injury during the treatment. Sera from three of the 12 patients were evaluated and all three showed increases of surfactant protein (SP)-A, SP-D and KL-6. We conclude that gefitinib was clinically useful. However, several patients suffered acute lung injury which could have been caused by gefitinib. A detection system including SP-A, SP-D and KL-6 as prime candidates as markers should be established as promptly as possible. Clinicians should be aware that treatment of NSCLC with gefitinib involves the risk of acute lung injury and therefore careful consideration should be given before deciding whether or not gefitinib is indicated for treatment. Further study is necessary to elucidate the mechanism of acute lung injury by gefitinib.
Adult↗
Elevated serum surfactant protein A and D in a case of acute eosinophilic pneumonia.
A 29-year-old man was admitted to our hospital because of fever elevation, dry cough, malaise, skin eruption, and dyspnea with hypoxemia. His serum levels of surfactant protein (SP) -A and SP-D were markedly high, but serum KL-6 was not. He was diagnosed as acute eosinophilic pneumonia (AEP) on the basis of CT imaging, bronchoalveolar lavage findings and the clinical course. He showed good response to steroid therapy and serum levels of SP-A and SP-D returned to almost normal levels. Our experience suggested that serum SP-A and SP-D might be helpful markers for monitoring the clinical course in AEP.
Acute Disease↗
Peripheral primitive neuroectodermal tumor of the chest wall of a 69-year-old man.
We report a case of peripheral primitive neuroectodermal tumor (pPNET), which belongs to the pPNET/Ewing's sarcoma family, arising in the chest wall of a 69-year-old man. He had high levels of serum neuron-specific enolase and pro-gastrin-releasing peptide, which are believed to be useful diagnostic blood markers for small cell lung carcinoma (SCLC). Microscopically, the tumor was composed of solid nests and sheets of monotous, primitive, small round cells with a few rosettes, making it difficult to distinguish from SCLC. Immunohistochemically, the tumor cells showed intense cell membranous immunoreactivity for MIC2 protein (CD99). EWS/FLI-1 chimeric mRNA that originated from the characteristic t(11;22)(q24;q12) chromosomal translocation was detected by RT-PCR and nucleotide sequence analysis. These results confirmed the diagnostic validity of the present tumor being a pPNET, thus raising the possibility that in the past, pPNETs which have arisen in the chest have been mistakenly diagnosed as SCLC.
Aged↗
Successful treatment of hypersensitivity pneumonitis caused by Grifola frondosa (Maitake) mushroom using a HFA-BDP extra-fine aerosol.
We successfully treated a patient with occupational hypersensitivity pneumonitis (HP) caused by Grifola frondosa (Maitake) mushroom spore with an extra-fine aerosol corticosteroid; beclomethasone dipropionate (BDP) dissolved in hydrofluoroalkane-134a (HFA). A 49-year-old woman developed respiratory symptoms 3 months after beginning work on a mushroom farm. She was diagnosed as HP based on radiological and serological findings. Oral prednisolone therapy improved her HP and she returned to the same farm. Her HP relapsed after 5 months, and daily 400 microg of HFA-BDP was administered with gradual improvement. An extra-fine particle inhaled corticosteroid might reach appropriate alveoli to be effective therapy for mild HP.
Administration, Inhalation↗
[Two younger male patients with rapidly progressing pulmonary pleomorphic carcinoma].
We report 2 cases of pulmonary pleomorphic carcinoma. The patient in case 1 was a 44-year-old man who was admitted to our hospital complaining of dry cough and dyspnea on exertion. Chest radiography and CT showed a huge tumor with left pleural effusion. Percutaneous biopsy suggested malignancy. As distant metastasis was not found and as cytological examination of pleural effusion gave a result of class II, we attempted to perform left pneumonectomy. However, we performed partial resection of the tumor because it had invaded the aorta, pulmonary artery, pericardium and pleura. The pathological diagnosis was pleomorphic carcinoma, p-T4 N2 M0. After the operation, we performed systemic chemotherapy, including cisplatin and irinotecanm with little effect (PD). The patient died of progression of the tumor. Case 2 was a 34-year-old man who was admitted to our hospital complaining of fever and general malaise. Chest radiography and CT showed a tumor in the left upper lobe. As no distant metastasis was found, we tried left upper lobectomy. However, we performed left upper segmentectomy and lymph node dissection because of invasion of the aorta and the chest wall, and because of hypersegmentation of the left upper lobe. Pathological diagnosis was pleomorphic carcinoma, p-T4 N0 M0. After the operation, the mediastinum was subjected to radiation therapy. However, a metastatic tumor was found in the pelvis after this radiation was given. We performed systemic chemotherapy with substances including cisplatin, gemcitabine and vinorelbine, but with little effect (PD). The patient died of peritonitis and pleuritis due to the recurrence and progression of the tumor. Both cases had rapidly growing neoplasms showing little sensitivity to chemotherapy or radiotherapy. Pulmonary pleomorphic carcinoma is suggested to be type of lung cancer with a poor prognosis when the tumor is not resected in the early stages.
Adenocarcinoma↗
[A case of stage I adenocarcinoma of the lung complicated with inflammatory lesions with an 8-year clinical course before surgery; CT and pathological correlations].
A nodular shadow near left hilum of lung was detected by chest radiography in November 1993 in a 79-year-old woman with hypertension and diabetes. Chest radiography in April 2001 revealed growth of the shadow. Chest CT showed a localized ground-glass opacity in the periphery of the lesion shadow. The resected specimen showed that the nodular shadow was papillary adenocarcinoma and the localized ground-glass opacity indicated the presence of inflammatory lesions. The pathological stage was stage I. Our case was a rare adenocarcinoma complicated with inflammatory changes including a granuloma that appeared 8 years later.
Adenocarcinoma, Papillary↗
T helper 1 inhibitor TAK-603 inhibits IFN-gamma and IL-12 production with no effect on IL-18: an observation in sarcoidosis patients.
BACKGROUND AND AIM: Sarcoidosis is immunologically characterized by highly enhanced Th1 responses in active stage. TAK-603 is a new quinoline derivative, which selectively suppresses Th1 cytokine production. Thus, the present study was designed to investigate whether TAK-603 ameliorates excess IFN-gamma production in active sarcoidosis. METHODS: We evaluated inhibitory effects of TAK-603 on IFN-gamma, IL-12 and IL-18 production in stimulated bronchoalveolar lavage (BAL) fluid cells and peripheral blood mononuclear cells (PBMCs) of sarcoidosis patients and healthy subjects. RESULTS: TAK-603 inhibited IFN-gamma production in stimulated BAL fluid cells and PBMCs of sarcoidosis patients and healthy subjects. TAK-603 inhibited IL-12 production in stimulated BAL fluid cells of sarcoidosis patients and healthy subjects. TAK-603 tended to inhibit IL-12 production in stimulated PBMCs of sarcoidosis patients and healthy subjects. However, TAK-603 did not affect IL-18 production in stimulated BAL fluid cells and PBMCs. TAK-603 did not affect TNF-alpha production in stimulated BAL fluid cells of sarcoidosis patients. TAK-603 inhibited IL-12 production in stimulated blood monocytes of healthy subjects, whereas IL-18 was increased by treatment with TAK-603. TAK-603 inhibited IFN-gamma production in PHA-stimulated blood T lymphocytes of healthy subjects with stimulation of IL-12 or a combination of IL-12 and IL-18. TAK-603 did not increase IL-10 or TGF-beta1 production in LPS-stimulated BAL fluid cells of sarcoidosis patients. CONCLUSIONS: TAK-603 inhibits IFN-gamma production in activated T lymphocytes and IL-12 production in activated monocytes/macrophages independently of increased production of IL-10 and TGF-beta1. TAK-603 may ameliorate excess IFN-gamma production and be a therapeutic tool for refractory sarcoidosis.
Adult↗
[A case of pyogenic spondylitis mimicking a spinal invasion of lung cancer].
A 58-year old man was admitted to our hospital complaining of right back pain, fever, abdominal fullness and epigastralgia. Chest CT revealed a mass shadow in the right S6 together with destruction of the thoracic vertebrae. These findings suggested lung cancer and its spinal invasion. A transbronchial lung biopsy specimen showed inflammatory lymphocyte infiltration. MRI T2 image of the spine showed a high intensity at the Th7/8 disc space, suggesting pyogenic spondylitis. After broad-spectrum antibiotics including PAMP/BP and CLDM were administered, both the spinal lesion and the pulmonary lesion improved gradually. The clinical course suggested that the pulmonary inflammatory lesion had spread from pyogenic spondylitis. In our case, the pyogenic spondylitis was mimicking a spinal invasion of lung cancer. In addition, MRI is thought to be useful for diagnosing spinal lesions.
Diagnosis, Differential↗
[Pulmonary surfactant proteins (SP-A, SP-D)].
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Humans↗
[A case of chronic eosinophilic pneumonia with significant elevation and variation of serum parainfluenza virus 3 antibody titer].
A 67-year old man visited our hospital because of cough and sputum. Chest radiograph revealed various consolidations of the bilateral lung fields. Eosinophilic pneumonia was diagnosed by transbronchial lung biopsy speciments. The clinical course and the treatment with corticosteroids improved chest radiographic findings quickly confirmed the diagnosis of chronic eosinophilic pneumonia. Based upon the significant elevation and variation of serum parainfluenza virus (PIV) 3 antibody titer, it was suggested that PIV 3 caused the chronic eosinophilic pneumonia.
Aged↗
Polymorphism of Clara cell 10-kD protein gene of sarcoidosis.
Clara cell 10-kD protein (CC10) exhibits potent antiinflammatory properties. G38A polymorphism was found in the CC10 gene. We investigated the genetic influence of the allele on the development of sarcoidosis using case control analysis in a Japanese population (265 sarcoidosis cases and 258 control subjects). The A allele frequency in sarcoidosis cases (45.1%) was significantly higher than healthy control subjects (34.9%, p = 0.0002). According to outcomes, we divided 223 patients with follow-up periods of 3 years or more into two subgroups (55 progressive and 168 regressive disease). The A allele frequency in patients with progressive disease was significantly higher than control subjects (odds ratio = 4.55; 95% confidence interval, 2.97-6.97; p < 0.0001), whereas that of regressive disease was not. The A/A genotypes had significantly lower bronchoalveolar lavage fluid CC10 levels than the G/G (nonsmokers, p = 0.0054, and smokers, p = 0.0045) and G/A genotypes (nonsmokers, p = 0.0022, and smokers, p = 0.0402). The reporter gene assay showed significantly lower reporter activities in the presence of interferon-gamma for the 38A construct than the 38G construct (p = 0.0177). The G38A polymorphism in the CC10 gene may influence protein expression and be associated with the development of progressive sarcoidosis.
Amino Acid Substitution↗
Increased airway vascularity in newly diagnosed asthma using a high-magnification bronchovideoscope.
Hypervascularity in the bronchial wall is part of airway remodeling, but has remained an ill-defined process in asthma pathogenesis. Previous morphologic assessment has been limited to biopsy specimens, and therefore a high-magnification bronchovideoscope (side-viewing type) was developed for less invasive examination of subepithelial vessels. We evaluated vascularity in the lower trachea, using this novel scope in 12 normal control subjects, 13 patients with chronic obstructive pulmonary disease, and 24 subjects with stable asthma; 8 were steroid naive with newly diagnosed asthma (Group A) and 16 had been treated with inhaled corticosteroids for more than 5 years (Group B). The redness of bronchial mucosa in patients with asthma observed by conventional fiberoptic bronchoscopy proved to be due to a fine vascular network. Morphometric measurements of subepithelial vessels showed that both vessel area density and vessel length density were significantly (p<0.0001) increased in subjects with asthma as compared with control subjects and patients with chronic obstructive pulmonary disease. The degree of increase in vessels did not differ between Group A and Group B. The increase in subepithelial vessels of the airway is present even in newly diagnosed asthma. This novel bronchovideoscope is useful for assessment of vessel network in the surface of the airway lumen in vivo.
Adult↗