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Biomedical subjects

Moritaka Suga

Publications and source records attributed to Moritaka Suga.

At least 37 records · Page 2Linked to original sources
PubMed2003

Induction of arginase I and II in bleomycin-induced fibrosis of mouse lung.

Arginase, which hydrolyzes arginine to urea and ornithine, is a precursor for the synthesis of polyamines and proline, which is abundant in collagen. The supply of proline can be a crucial factor in the process of lung fibrosis. We investigated the induction of arginine metabolic enzymes in bleomycin-induced mouse lung fibrosis. Histological studies and quantification of lung hydroxyproline showed that lung fibrosis develops in up to 14 days after bleomycin treatment. Under these conditions, collagen I mRNA was induced gradually in up to 15 days, and the content of hydroxyproline reached a maximum at 10 days. Arginase I mRNA was undetectable before bleomycin treatment but was induced 5-10 days after this treatment. Arginase I protein was induced at 7 days and remained little changed for up to 10 days and decreased at 14 days. On the other hand, arginase II mRNA that was detectable before treatment was increased gradually for up to 10 days and decreased at 14 days. Arginase II protein began to increase at day 5, increased for up to 10 days, and was decreased at day 14. mRNAs for cationic amino acid transporter-2 and ornithine decarboxylase were induced in a manner similar to that seen with collagen I mRNA. Immunohistochemical analysis showed that arginase I is induced in macrophages, whereas arginase II is induced in various cell types, including macrophages and myofibroblasts, and roughly colocalizes with the collagen-specific chaperone heat shock protein 47. Our findings suggest that arginine metabolic enzymes play an important role in the development of lung fibrosis, at least in mice.

Animals↗
PubMed2003

Diffuse alveolar damage after ZD1839 therapy in a patient with non-small cell lung cancer.

ZD1839 is an orally active inhibitor selective for the epidermal growth factor receptor tyrosine kinase and has shown promise in the treatment of non-small cell lung cancer (NSCLC). We now present a case of diffuse alveolar damage (DAD) that developed in a 67-year-old man treated with ZD1839. On day 8 of ZD1839 administration, the patient complained of dyspnea and a new-ground glass opacity was apparent on a chest X-ray and computed tomography scan. Despite high-dose steroid therapy, the patient died 13 days after the first administration of ZD1839. Postmortem analysis of lung tissue revealed a pattern of DAD. No evidence of infection or of other specific etiologies was apparent. This case is the first reported of respiratory failure after ZD1839 treatment in a patient with NSCLC. Physicians should therefore be aware of the potential pulmonary toxicity of ZD1839.

Administration, Oral↗
PubMed2003

Clinical and CT characteristics of Chinese medicine-induced acute respiratory distress syndrome.

OBJECTIVE: The aim of the present study was to explore the clinical and radiographic characteristics of Chinese medicine-induced acute respiratory distress syndrome (ARDS), focusing on high resolution CT (HRCT) findings. METHODOLOGY: Five patients diagnosed with Chinese medicine-induced ARDS were enrolled in the study. Details regarding clinical history, previous medical history, and laboratory data were collected and reviewed. The extent of involvement of each HRCT abnormality was assessed for each of three zones of each lung and was estimated to the nearest 10% of parenchymal involvement. RESULTS: The causative Chinese medicines were as follows: Sho-saiko-to (two cases), Sai-rei-to (two cases) and Otsu-ji-to (one case). Scutellariae radix was the common ingredient in these drugs. The mean duration of medication use before the onset of ARDS was 22 days (range 7-49 days). High levels of C-reactive protein and lactate dehydrogenase (LDH), and mild liver dysfunction were common laboratory findings. The major HRCT findings were as follows: ground-glass opacity 50.2% (range 37-68%); airspace consolidation 16.0% (7-27%); spared area 26.6% (7-45%). In addition, the abnormalities tended to predominate in the peribronchovascular regions. Furthermore, architectural distortion was seen in all five cases, interlobular septal thickening occurred in four, irregular interface in four, and interlobar effusion in two. Corticosteroid therapy was very effective, and partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FIO2) improved in proportion to the decrease in LDH level. CONCLUSIONS: Patients with Chinese medicine-induced acute lung injury exhibited ARDS. However, their prognosis was satisfactory, which suggests that a hypersensitivity reaction or a permeability oedema with minimal epithelial injury may be involved in the pathophysiology.

Adrenal Cortex Hormones↗
PubMed2003

Expression of constitutively activated EGFRvIII in non-small cell lung cancer.

The epidermal growth factor receptor (EGFR) variant type III (variously called EGFRvIII, de2-7 EGFR or deltaEGFR) has an in-frame deletion of the extracellular domain and is found in numerous types of human tumors. Since EGFRvIII has been reported to be tumor-specific and has oncogenic potential, it is being investigated as a potential therapeutic target. Because the cell-specific expression of EGFRvIII in lung has not been well documented, we examined the expression of EGFRvIII in 76 non-small cell lung cancers (NSCLCs) and 10 non-neoplastic lung tissues by immunohistochemistry using a new monoclonal antibody specific for this variant receptor. We found a higher incidence (30 of 76, 39%) of enhanced EGFRvIII expression in NSCLC than previously described. Interestingly, the presence of EGFRvIII was also observed in several normal tissue components of lung (e.g., normal bronchial epithelium). Given the high prevalence of EGFRvIII in NSCLC, a newly developed phospho-specific (activated) EGFR antibody was employed for immunohistochemical analysis that permitted visualization of activated EGFR and/or EGFRvIII in tumors. This study presents evidence, for the first time, that EGFRvIII expressed in human tumors is phosphorylated and hence activated. Our results suggest that the sustained activation of EGFRvIII is implicated in the pathogenesis of NSCLC and thus EGFRvIII is a potential therapeutic target in this challenging disease.

3T3 Cells↗
PubMed2003

Successful treatment of primary pulmonary angiosarcoma.

Angiosarcoma in the lung is an uncommon disorder and is usually attributable to metastasis from a primary site. Primary pulmonary angiosarcoma is extremely rare, and the prognosis of affected individuals is dismal, with most patients dying within months of presentation. Indeed, there have been no reported instances of successful treatment of this condition. We now report the case of a patient with primary pulmonary angiosarcoma who responded to a combination of radiotherapy and immunotherapy with recombinant interleukin-2. The patient remains well without signs of recurrence 1 year after initial presentation. This combination therapy may be a promising strategy to prolong the survival of patients with primary pulmonary angiosarcoma.

Adult↗
PubMed2003

Multicentric Castleman's disease manifesting in the lung: clinical, radiographic, and pathologic findings and successful treatment with corticosteroid and cyclophosphamide.

Multicentric Castleman's disease (MCD) is an uncommon and often incurable lymphoproliferative disorder. There has been some recent evidence that rare cases of MCD manifest diffuse lung involvement, but the features in these cases are not well characterized. We report just such a biopsy-proven case of MCD with typical laboratory abnormalities including serum interleukin-6 elevation and characteristic high-resolution CT findings. Immunopathologically, the features of the lung tissue resembled those of lymphocytic interstitial pneumonia with predominant infiltration of B cells and plasma cells. In addition, the abnormal appearance of B cells in bronchoalveolar lavage fluid was of diagnostic value. Although MCD is often refractory to treatment including corticosteroid, chemo- and immuno-therapy, we show successful treatment with corticosteroid and cyclophosphamide and 4 years of complete remission.

Biopsy, Needle↗
PubMed2003

Absence of gallium uptake in unicentric and multicentric Castleman's disease.

Castleman's disease is a rare and poorly understood condition involving lymph nodes at various sites, predominantly in the mediastinum. Individuals with this disease often present with lymphadenopathy and general symptoms suggestive of lymphomatous disease, and they are at risk of developing malignant lymphoma. It is thus important to distinguish Castleman's disease from other lymphoproliferative disorders. 67Ga scintigraphy is a non-invasive and practical diagnostic tool for the investigation of patients with lymphoproliferative disorders. However, the value of this technique for the diagnosis of Castleman's disease is not clear. Here, we describe five consecutive patients with various types of Castleman's disease and show that none of these individuals exhibited 67Ga uptake. Our results suggest the potential value of 67Ga scintigraphy in both the diagnosis and management of Castleman's disease.

Adult↗
PubMed2003

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2001)].

From October 2001 to September 2002, we collected the specimen from 370 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of the isolated bacteria to various antibacterial agents and antibiotics and patients' characteristics. Of 458 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 456 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 69, Streptococcus pneumoniae 72, Haemophilus influenzae 85, Pseudomonas aeruginosa (non-mucoid) 44, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 32, Moraxella subgenus Branhamella catarrhalis 32, and others. Of 69 S. aureus strains, those with 4 micrograms/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 43.5%. Vancomycin and arbekacin showed the most potent activities against MRSA as observed in 2000. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 59.7% and both rates of PISP and PRSP were the highest after 1992. Carbapenems had strong activities against S. pneumoniae. Especially, panipenem and imipenem inhibited the growth of all 72 strains at 0.125 and 0.5 microgram/mL, respectively. Generally, all drugs had strong activities against H. influenzae with MIC90s of 16 micrograms/mL or less. The drug that had the strongest activity against H. influenzae was levofloxacin, which inhibited the growth of 80 of the 85 strains at 0.063 microgram/mL. Against P. aeruginosa mucoid strain, meropenem had a strong activity with MIC90 of 0.5 microgram/mL while, against non-mucoid strain, tobramycin had a strong activity with MIC90 of 2 micrograms/mL. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and minocycline, and the MIC90s were 4 micrograms/mL or less. Particularly, cefmenoxime, cefpirome, and imipenem had the strongest activity (MIC90: 0.125 microgram/mL), and cefozopran had a strong activity, inhibiting the growth of all strains at 0.25 microgram/mL. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC90s of all drugs were 4 micrograms/mL or less. The drug that had the strongest activity was minocycline and levofloxacin inhibiting all 32 strains at 0.063 microgram/mL. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (40.5%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 39.2% and 37.3% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (19.3%) and S. pneumoniae (19.9%). In contrast, H. influenzae (22.0%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (20.8%) and H. influenzae (21.5%). S. pneumoniae and H. influenzae decreased after the initiation of drug administration while S. aureus increased. The isolation frequency of P. aeruginosa was higher after than before the initiation of drug administration. The bacteria were frequently isolated from the patients who had already treated with cephems were S. aureus and P. aeruginosa. From the patients who had already treated with macrolides, S. pneumoniae was the most frequently isolated while S. aureus was the most frequently isolated from the patients pre-treated with quinolones.

Adult↗
PubMed2003

[A case of loxoprofen sodium-induced bronchiolitis obliterans organizing pneumonia (BOOP)].

A 78-year-old man was referred to our department because of an abnormal shadow on the chest radiograph and liver dysfunction after lung resection for lung cancer. Following the operation, loxoprofen sodium was administered to control his chest pain. A chest radiograph on admission showed airspace consolidation in the right lower lung field. In addition, leukocytosis and elevation of CRP were observed. Although piperacillin sodium was given to him, airspace consolidation on a chest radiograph was increased. A bronchoalveolar lavage fluid study showed that total cell counts and proportion of lymphocytes were increased, and the CD4/CD8 ratio was 1.77. A transbronchial lung biopsy specimen revealed organizing pneumonia with Masson bodies. Furthermore, a lymphocyte stimulation test for loxoprofen sodium was positive. From the clinical course, laboratory data and pathologic findings, we considered this case to be loxoprofen sodium-induced BOOP. Withdrawal of loxoprofen sodium and treatment with corticosteroid resulted in marked improvement of the clinical findings. Although a rare occurrence, it is important to recognize that BOOP can be caused by loxoprofen sodium.

Aged↗
PubMed2002

Redistribution of ERK/MAP kinase to uropod-like structures in interleukin-3-induced cell shape changes.

Interleukin-3 (IL-3) is one of the cytokines of significance for the regulation of hematopoiesis and inflammation. Recently, we established IL-3-dependent Ba/F3 pro-B cells ectopically expressing RON tyrosine kinase, a receptor for macrophage-stimulating protein (MSP), and showed that MSP stimulation specifically promoted cell morphological changes through tyrosine phosphorylation of the IL-3 common beta-chain receptor subunit (betac) by activated RON kinase without activation of JAK2 tyrosine kinase. Here we investigate the IL-3 signaling pathway leading to morphological changes through tyrosine phosphorylation of betac. Treatment of RON-expressing cells with PD98059 or U0126, inhibitors of mitogen-activated protein kinase kinase activity, blocked both IL-3- and MSP-induced morphological changes. Upon stimulation with IL-3 or MSP, extracellular-regulated kinase (ERK) and F-actin were redistributed in uropod-like structures. ERK and F-actin were colocalized within uropod-like structures, and a majority of F-actin were localized around the peripheries of accumulated ERK. Tyrosine phosphorylation of ERK was detected after stimulation with IL-3 or MSP, whereas treatment with U0126 specifically inhibited IL-3- or MSP-induced ERK phosphorylation but not tyrosine phosphorylation of betac. These results suggest that the activation and localization of ERK to uropod-like structures play a role in IL-3-induced morphological changes.

Animals↗
PubMed2002

Acute interstitial pneumonia: comparison of high-resolution computed tomography findings between survivors and nonsurvivors.

This study compared high-resolution computed tomography (CT) findings between 10 survivors and 21 nonsurvivors of acute interstitial pneumonia and evaluated whether the CT findings were predictive of patients' response to treatment. The survivor and nonsurvivor groups with pathologically or clinically diagnosed acute interstitial pneumonia were similar in age, sex, disease duration, and lung injury score. Retrospective, subjective evaluations of the CT scans were conducted by two independent observers without knowledge of patient outcomes. CT findings were graded on a one to six scale corresponding to consecutive pathologic phases as follows: areas of (1) normal attenuation, (2) ground-glass attenuation, (3) consolidation, (4) ground-glass attenuation associated with traction bronchiolectasis or bronchiectasis, (5) consolidation associated with traction bronchiolectasis or bronchiectasis, and (6) honeycombing. An overall score was obtained by quantifying the extent of each abnormality in three lung zones in each lung. The extent of ground-glass attenuation or consolidation associated with traction bronchiolectasis or bronchiectasis was less in survivors than nonsurvivors (p = 0.004 and p = 0.009, respectively). Architectural distortion was less frequent, and ground-glass attenuation or consolidation without traction bronchiolectasis or bronchiectasis was more extensive in survivors than in nonsurvivors (p = 0.007, p = 0.002, and p = 0.029, respectively). Overall CT scores of survivors were significantly lower than those of nonsurvivors (p = 0.0003). A CT score of less than 245 had an 80% positive and a 90% negative predictive value for survival. There was good interobserver agreement in the assessment of the CT findings (Kappa 0.75). The results indicate that CT assessment is potentially helpful in predicting patient prognosis in acute interstitial pneumonia regardless of the degree of physiologic abnormality.

Acute Disease↗
PubMed2002

Quantitative analysis of mycobacterial and propionibacterial DNA in lymph nodes of Japanese and European patients with sarcoidosis.

The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.

Actinomycetales Infections↗
PubMed2002

Nonspecific interstitial pneumonia: correlation between thin-section CT findings and pathologic subgroups in 55 patients.

PURPOSE: To characterize thin-section computed tomographic (CT) findings of pathologic subgroups of nonspecific interstitial pneumonia (NIP) in a sizeable number of patients. MATERIALS AND METHODS: The study included 55 cases of pathologically proven NIP. The 55 cases were categorized histologically into four grades: grade 1, interstitial inflammation without fibrosis (n = 6); grade 2, interstitial inflammation predominating over fibrosis (n = 16); grade 3, fibrosis predominating over inflammation (n = 5); and grade 4, fibrosis only (n = 28). Two independent observers evaluated the presence, extent, and distribution of various CT findings. Thin-section CT findings and histologic grades were compared by using the Spearman rank correlation coefficient. Observer agreement was assessed. RESULTS: Areas with ground-glass attenuation and architectural distortion were present in all 55 patients. Traction bronchiectasis and intralobular reticular opacities were seen in 52 and 48 patients, respectively. The extent of traction bronchiectasis (r = 0.68; P <.001) and intralobular reticular opacities (r = 0.35; P <.05) correlated with the histologic grade. Honeycombing was seen in 12 (43%) of 28 patients with grade 4 NIP and in three (11%) of the remaining 27 patients (chi(2) test, P <.001). There was good agreement between the observers for the presence (kappa = 0.7-1.0) and extent (Spearman rank correlation; r = 0.87-0.98; P <.001) of various abnormalities. CONCLUSION: The extent of traction bronchiectasis and intralobular reticulation at thin-section CT correlates with increased fibrosis in NIP. Honeycombing is seen almost exclusively in patients with fibrotic NIP.

Adult↗
PubMed2002

Two cases of Sjögren's syndrome with multiple bullae.

Here, we report two rare female cases of Sjögren's syndrome with multiple bullae, involving a 66- and a 51-year-old. Neither had any obvious pulmonary complaint. Chest radiographs and high-resolution CT (HRCT) scans showed interstitial linear and nodular opacities and multiple bullae. In the first case spirometry indicated an obstructive change judged by FEV1.0 and V50/V25. In both cases, histologic examination of the lung revealed thickening of alveolar septa and interstitial mononuclear cell infiltration. In the first case the bullae decreased in size with corticosteroid treatment. Airway narrowing due to peribronchiolar mononuclear cell infiltration causes a check-valve mechanism, which may lead to bullae formation. Although a rare occurrence, it is important to recognize that cystic or bullous lung disease can accompany Sjögren's syndrome.

Aged↗
PubMed2002

Systemic lupus erythematosus complicated by cytomegalovirus-induced hemophagocytic syndrome and colitis.

Here, we report a case of systemic lupus erythematosus (SLE) complicated by cytomegalovirus (CMV)-induced hemophagocytic syndrome (HPS) and colitis. A 44-year-old woman with SLE was treated with corticosteroid and cyclophosphamide for lupus nephritis. Although her lupus nephritis improved, fever, progressive pancytopenia and intestinal bleeding were observed. A bone marrow aspiration showed an increase in mature histiocytes with hemophagocytosis. In addition, a colonoscopy showed hemorrhagic colitis with ulcer and the biopsy specimen from the colon revealed typical CMV cells with CMV inclusions confirmed by immunohistochemistry. Furthermore, a large number of CMV antigen-positive leukocytes was detected, suggesting an active CMV infection. CMV infection is serious in compromised hosts. Therefore clinicians should be aware of the clinical settings in which this infection can arise and the target organs potentially affected in order to initiate the appropriate intervention.

Adult↗