122 results on '"Yasutsugu Fukushima"'
Search Results
2. Effect of adjusting the combination of budesonide/formoterol on the alleviation of asthma symptoms
- Author
-
Ryosuke Souma, Kumiya Sugiyama, Hiroyuki Masuda, Hajime Arifuku, Kentaro Nakano, Hiroyoshi Watanabe, Tomoshige Wakayama, Shingo Tokita, Masamitsu Tatewaki, Hideyuki Satoh, Kenya Koyama, Yumeko Hayashi, Fumiya Fukushima, Hirokuni Hirata, Masafumi Arima, Kazuhiro Kurasawa, Takeshi Fukuda, and Yasutsugu Fukushima more...
- Subjects
Adjustable maintainable dose (AMD) ,Asthma ,Budesonide ,Formoterol ,Peak expiratory flow (PEF) ,Symbicort maintenance and reliever therapy (SMART) ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background The combination of budesonide + formoterol (BFC) offers the advantages of dose adjustment in a single inhaler according to asthma symptoms. We analyzed the relationship between asthma symptoms in terms of peak expiratory flow (PEF) and dose adjustment by the patient. Methods Twenty-eight patients with asthma who used BFC for alleviation of their symptoms (12 men, 16 women; 60 years old) were instructed that the inhaled BFC dose could be increased to a maximum of 8 inhalations per day according to symptom severity. Patients measured and recorded PEF every morning and evening in their asthma diary along with their symptoms and the dose of drugs taken. Results Sixteen of the 28 patients increased their dose for asthma symptoms. The time to recovery from the asthma symptoms was significantly shorter when cough was the only symptom present compared with dyspnea or wheeze (1.4 vs. 5.3 or 6.6 days, p more...
- Published
- 2018
- Full Text
- View/download PDF
Catalog
3. Survey on the proper use of an adrenaline auto-injector in 551 Japanese outdoor workers after Hymenoptera stings
- Author
-
Hirokuni Hirata, Naruo Yoshida, Masamitsu Tatewaki, Sadaaki Shiromori, Kozo Sato, Tomoshige Wakayama, Shingo Tokita, Kumiya Sugiyama, Masafumi Arima, Kazuhiro Kurasawa, Takeshi Fukuda, Daisuke Shima, and Yasutsugu Fukushima more...
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2018
- Full Text
- View/download PDF
4. Prescription of adrenaline auto-injectors to 1145 Japanese outdoor workers in 2015
- Author
-
Masamitsu Tatewaki, Hirokuni Hirata, Yoshihiko Ikeno, Ikuo Akutsu, Seiko Sekiguchi, Natsumi Suzuki, Kumiya Sugiyama, Masafumi Arima, Kazuhiro Kurasawa, Takeshi Fukuda, Daisuke Shima, and Yasutsugu Fukushima more...
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2016
- Full Text
- View/download PDF
5. Specific IgE sensitization to honey bee venom and auto-injector adrenaline prescriptions for Japanese beekeepers
- Author
-
Hirokuni Hirata, Masamitsu Tatewaki, Sadaaki Shiromori, Yoshihiko Ikeno, Ikuo Akutsu, Kumiya Sugiyama, Masafumi Arima, Kazuhiro Kurasawa, Takeshi Fukuda, Daisuke Shima, and Yasutsugu Fukushima
- Subjects
Immunologic diseases. Allergy ,RC581-607 - Published
- 2017
- Full Text
- View/download PDF
6. Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells
- Author
-
Takashi Ogasawara, Yuko Kohashi, Jun Ikari, Toshibumi Taniguchi, Nobuhide Tsuruoka, Haruko Watanabe-Takano, Lisa Fujimura, Akemi Sakamoto, Masahiko Hatano, Hirokuni Hirata, Yasutsugu Fukushima, Takeshi Fukuda, Kazuhiro Kurasawa, Koichiro Tatsumi, Takeshi Tokuhisa, and Masafumi Arima more...
- Subjects
B-cell lymphoma 6 ,naturally occurring memory phenotype T cells ,allergy ,TH2 cells ,asthma ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Transcriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production in naïve CD4+ T cell-derived memory TH2 cells. To investigate Bcl6 function in allergic responses in naturally occurring memory phenotype CD4+ T (MPT) cells and their derived TH2 (MPTH2) cells, Bcl6-manipulated mice, highly conserved intron enhancer (hcIE)-deficient mice, and reporter mice for conserved noncoding sequence 2 (CNS2) 3′ distal enhancer region were used to elucidate Bcl6 function in MPT cells. The molecular mechanisms of Bcl6-mediated TH2 cytokine gene regulation were elucidated using cellular and molecular approaches. Bcl6 function in MPT cells was determined using adoptive transfer to naïve mice, which were assessed for allergic airway inflammation. Bcl6 suppressed IL-4 production in MPT and MPTH2 cells by suppressing CNS2 enhancer activity. Bcl6 downregulated Il4 expression in MPTH2 cells, but not MPT cells, by suppressing hcIE activity. The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. more...
- Published
- 2018
- Full Text
- View/download PDF
7. Improved sensitivity to venom specific-immunoglobulin E by spiking with the allergen component in Japanese patients suspected of Hymenoptera venom allergy
- Author
-
Naruo Yoshida, Hirokuni Hirata, Mineaki Watanabe, Kumiya Sugiyama, Masafumi Arima, Yasutsugu Fukushima, and Yoshiki Ishii
- Subjects
Hymenoptera venom ,rPol d 5 ,rVes v 5 ,Specific IgE ,Spiking ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Ves v 5 and Pol d 5, which constitute antigen 5, are recognized as the major, most potent allergens of family Vespidae. Several studies have reported the diagnostic sensitivity of the novel recombinant (r)Ves v 5 and rPol d 5 allergens in routine clinical laboratory settings by analyzing a group of Vespula and Polistes venom-allergic patients. In this study, we analyzed the sensitivity to venom specific (s)IgE by spiking with rVes v 5 and rPol d 5 in Japanese patients suspected of Hymenoptera venom allergy. Methods: Subjects were 41 patients who had experienced systemic reactions to hornet and/or paper wasp stings. Levels of serum sIgE against hornet and paper wasp venom by spiking with rVes v 5 and rPold d 5, respectively, as improvement testing, compared with hornet and paper wasp venom, as conventional testing, were measured by ImmunoCAP. Results: Of the 41 patients, 33 (80.5%) were positive (≥0.35 UA/ml) for hornet and/or paper wasp venom in conventional sIgE testing. sIgE levels correlated significantly (P more...
- Published
- 2015
- Full Text
- View/download PDF
8. Epidemiologic Investigation of Hornet and Paper Wasp Stings in Forest Workers and Electrical Facility Field Workers in Japan
- Author
-
Yumeko Hayashih, Hirokuni Hirata, Mineaki Watanabe, Naruo Yoshida, Tatsuya Yokoyama, Yoshiki Murayama, Kumiya Sugiyama, Masafumi Arima, Yasutsugu Fukushima, Takeshi Fukuda, and Yoshiki Ishii
- Subjects
forestry and field workers ,hornet stings ,Hymenoptera allergy ,paper wasp stings ,venom-specific IgE ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background:: Forestry and field workers who work outdoors are at high risk for Hymenoptera stings and may develop occupation-related allergies from being stung. However, clinical and immunological surveys of Hymenoptera stings in the occupational setting have rarely been reported. We surveyed the natural history of Hymenoptera stings in Japanese forestry workers (FWs) and electrical facility field workers (EFFWs), and we assessed the utility of measuring specific (s)IgE Ab to Hymenptera venom. Methods:: Questionnaires on hornet and paper wasp stings were completed by 999 FWs, 354 EFFWs, and 365 office workers as controls between July and November 2009. Sera from these participants were tested for sIgE Ab levels to Hymenptera venom with a CAP system using a fluoroenzyme immunoassay. Results:: Of the participants who had experienced Hymenoptera stings, 914 (91.5%) were FWs, 293 (82.8%) were EFFWs, and 295 (80.8%) were controls. Of the participants who had experienced systemic reactions, 210 (21.0%) were FWs, 51 (14.4%) were EFFWs, and 39 (10.7%) were controls. sIgE Ab in response to hornet and wasp venom was positive (≥ class 2) in 42.4% and 41.4% of FWs, 30.1% and 31.4% of EFFWs, and 15.1% and 18.1% of controls, respectively. The likelihood of being sIgE-positive to wasp and hornet venom was significantly higher in FWs and EFFWs than in controls (P < 0.05). Conclusions:: 21% of FWs and 14% of EFFWs had experienced systemic reactions to Hymenoptera stings with a higher frequency compared with office workers in the same area. 40% of FWs and 30% of EFFWs had sera that were sIgE positive to Hymenoptera venom. more...
- Published
- 2014
- Full Text
- View/download PDF
9. A Patient with Bronchial Asthma in Whom Eosinophilic Bronchitis and Bronchiolitis Developed during Treatment
- Author
-
Yasutsugu Fukushima, Kuniyoshi Kamiya, Masamitsu Tatewaki, Fumiya Fukushima, Hirokuni Hirata, Yoshiki Ishii, and Takeshi Fukuda
- Subjects
bronchial asthma ,bronchiolitis ,eosinophilic bronchiolitis ,eosinophilic lung disease ,Immunologic diseases. Allergy ,RC581-607 - Abstract
A 56-year-old woman was referred to our hospital because of dyspnea, wheezing, and a productive cough. Eight years before presentation, bronchial asthma was diagnosed and the patient received inhaled corticosteroids plus antiasthmatic agents (a long-acting inhaled p2-agonist, leukotriene modifiers, and theophylline). Chest radiography showed small diffuse nodular shadows, and a computed tomographic scan showed thickening of the bronchi and bronchioles, with diffuse centrilobular nodules in both lung fields. A blood test and microscopic examination of the bronchoalveolar fluid revealed marked eosinophilia. Transbronchial lung biopsy and transbronchial biopsy showed eosinophilic bronchitis and bronchiolitis. After treatment with oral prednisolone (40 mg daily) and inhaled corticosteroids, the symptoms, blood eosinophilia, and radiographic findings improved. Recently, several similar cases of eosinophilic bronchiolitis have been reported. Studies of further cases and elucidation of the pathophysiology of eosinophilic bronchiolitis are necessary to establish a concept for this disease and to determine whether it should be classified as a subtype of bronchial asthma or as a distinct entity. more...
- Published
- 2010
- Full Text
- View/download PDF
10. A Case of Persistent SARS-CoV-2 PCR Positive after Chemotherapy for B-cell Lymphoma
- Author
-
Hisanori, Hirokawa, Hirokuni, Hirata, Ryo, Kitajima, Masahira, Irokawa, Tomoyuki, Ishiguro, Tomoki, Hasegawa, Junya, Sato, Atsutaka, Ozaki, Masafumi, Arima, Shinji, Teramoto, Kosuke, Haruki, Takamitsu, Okamura, Hideto, Tamura, Koshi, Hashimoto, and Yasutsugu, Fukushima more...
- Subjects
B-cell lymphoma ,SARS-CoV-2 ,pneumonia ,chemotherapy ,antibody cocktail ,immunocompromised host - Abstract
The patient was a 68-year-old woman who was hospitalized for SARS-CoV-2 pneumonia while receiving chemotherapy for B-cell lymphoma. She experienced repeated episodes of pneumonia that temporarily went into remission with steroid and remdesivir and but then relapsed or worsened. However, no particular subjective symptoms or deterioration on imaging was observed by an antibody cocktail treatment after Day 119. SARS-CoV-2 IgM and IgG antibody levels were below the limit of detection on Day 180 but she tested positive for SARS-CoV-2 by PCR on Day 151. In the case of this patient who had persistent SARS-CoV-2 infection due to being immunocompromised, treatment temporarily stalled the worsening of symptoms. However, new treatments for such patients should be established soon. more...
- Published
- 2022
11. Effect of inhaled corticosteroids on bone mineral density in patients with asthma
- Author
-
Kenya Koyama, Hirokuni Hirata, Shingo Tokita, Masafumi Arima, Yasutsugu Fukushima, Hajime Arifuku, Naotatsu Otsuji, Kazuhiro Kurasawa, Hiroyoshi Watanabe, Kumiya Sugiyama, Tomoshige Wakayama, and Kentaro Nakano more...
- Subjects
Bone mineral ,medicine.medical_specialty ,Bone density ,Cumulative dose ,business.industry ,Immunology ,Osteoporosis ,Urology ,General Medicine ,medicine.disease ,Bone remodeling ,medicine.anatomical_structure ,Immunology and Allergy ,Medicine ,Cortical bone ,business ,Cancellous bone ,Asthma - Abstract
Background Inhaled corticosteroids (ICS) are a safe treatment for asthma. However, at higher doses, ICS use has been reported to inhibit adrenocortical function. Objective This study aimed to evaluate the effect of ICS on bone mineral density (BMD) in adult patients with asthma. Methods Ultrasonic bone densitometry was performed in 40 patients (14 men, 26 women, mean age 61.2 years, mean duration of asthma 6.19 years) who were receiving ICS for asthma, and the whole bone density, thickness of cortical bone, and density of cancellous bone of the radius was measured. The age-matched mean was set as 100%. Lifetime cumulative dose of ICS was calculated using all past prescriptions. Results No significant correlations were observed between lifetime cumulative ICS dose and whole bone density (r² = 0.011), cortical bone thickness (r² = 0.022), and cancellous bone density (r² = 0.004). No significant differences were observed between lower and higher lifetime cumulative ICS dose among these BMD parameters (104% vs 97%, 103% vs 99%, and 106% vs 91%, respectively). No significant correlations or differences in lifetime cumulative ICS dose were observed by asthma severity, asthma duration, and pulmonary function. Also, serum markers of bone metabolism showed no significant correlations or differences with lifetime cumulative ICS dose. Conclusions In the entire study population, long-term ICS use was safe and was not associated with an increased risk of osteoporosis. more...
- Published
- 2023
- Full Text
- View/download PDF
12. Treatment with Both Nintedanib and Steroid in Bleomycin-induced Pulmonary Fibrosis Model Mice didn’t Inhibit Lung Fibrosis
- Author
-
Sadaaki, Shiromori, Hirokuni, Hirata, Kozo, Sato, Kazuhiro, Tada, Masafumi, Arima, and Yasutsugu, Fukushima
- Subjects
steroid ,nintedanib ,bleomycin-induced pulmonary fibrosis ,respiratory system ,respiratory tract diseases - Abstract
Background:In the clinical setting, the optimal timing of administration of nintedanib in the active or inactive phase of idiopathic pulmonary fibrosis (IPF) has not been clarified. Also, no consideration has been made of synergistic actions with steroids.Objectives:We used bleomycin-induced pulmonary fibrosis model mice to analyze the effects of the timing of nintedanib administration and synergistic actions in combination with steroids.Method:In the bleomycin-induced pulmonary fibrosis mouse model, nintedanib was given before or after bleomycin administration and the effects on pulmonary fibrosis and fibroblast growth factors in bronchoalveolar lavage (BAL) fluid were analyzed. Then, treatment with both steroid and nintedanib was administered in the same model and the effects of combined use on lung fibrosis were analyzed. Severity of lung fibrosis was analyzed using the Ashcroft score. Fibroblast growth factors in BAL fluid were measured using Magnetic Luminex® assay and enzyme-linked immunosorbent assay.Results:Pretreatment with nintedanib before administration of bleomycin, but not after administration of bleomycin, reduced the Ashcroft score (2.4±1.4 vs 4.9±1.3, P<0.01) and decreased TGF-b 1 in BAL fluid (95.7±48.4 pg/mL vs 147.1±11.7 pg/mL, P<0.05). Conversely, pretreatment with both steroid and nintedanib did not decrease the Ashcroft score compared with pretreatment of saline as a control( Score:3.8±1.3 vs 4.6±1.1). There was also no synergistic effect of both steroid and nintedanib on pulmonary fibrosis.Conclusions:Nintedanib may be useful when administered early in patients with IPF. Further more, clinical administration of combined nintedanib and steroid requires caution in view of the effects on pulmonary fibrosis and side effects. more...
- Published
- 2021
13. Effect of inhaled corticosteroids on bone mineral density in patients with asthma.
- Author
-
Hiroyoshi Watanabe, Kumiya Sugiyama, Naotatsu Otsuji, Kentaro Nakano, Hajime Arifuku, Tomoshige Wakayama, Shingo Tokita, Kenya Koyama, Hirokuni Hirata, Masafumi Arima, Kazuhiro Kurasawa, and Yasutsugu Fukushima more...
- Published
- 2023
- Full Text
- View/download PDF
14. An Exploratory Randomized Phase II Trial Comparing CDDP Plus S-1 With Bevacizumab and CDDP Plus Pemetrexed With Bevacizumab Against Patients With Advanced Non-squamous Non-small Cell Lung Cancer
- Author
-
Noriaki Sunaga, Reiko Sakurai, Yasutsugu Fukushima, Ryousuke Souma, Norimitsu Kasahara, Takeshi Hisada, Mie Kotake, Ichiro Naruse, Yosuke Miura, Tamotsu Ishizuka, Yasuhiko Koga, Koichi Minato, Shinsuke Kitahara, Kyoichi Kaira, Yusuke Tsukagoshi, and Hisao Imai more...
- Subjects
Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Pemetrexed ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Lung cancer ,Aged ,Neoplasm Staging ,Tegafur ,Cisplatin ,Chemotherapy ,business.industry ,Thymidylate Synthase ,General Medicine ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Drug Combinations ,Oxonic Acid ,Regimen ,Tolerability ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Background/aim It remains unclear which chemotherapeutic regimens are better for the addition of bevacizumab. We conducted an exploratory randomized phase II trial comparing first-line S-1 plus cisplatin with bevacizumab and pemetrexed plus cisplatin with bevacizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC). Patients and methods Chemotherapy-naive patients received S-1 (80 mg/m2) from day 1 to day 14 plus cisplatin (80 mg/m2) on day 1 with bevacizumab (15 mg/kg) on day 1, followed by maintenance with bevacizumab plus S-1 (SCB) on day 1 every 3 weeks and pemetrexed (500 mg/m2) on day 1 plus cisplatin (75 mg/m2) on day 1 with bevacizumab (15 mg/kg) on day 1 followed by maintenance bevacizumab plus pemetrexed (PCB) on day 1 every 3 weeks. The expression of thymidylate synthase (TS) was analyzed using immunohistochemistry. Results Forty-eight patients were enrolled in this study, and eligible patients were randomly assigned at 1:1 ratio to receive SCB (n=24) or PCB (n=24). The median number of chemotherapy and maintenance therapy for SCB and PCB was 4 (range, 1-6 cycles) and 4 (range, 2-6 cycles), and 5 (range, 0-39 cycles) and 5 (range, 0-28 cycles), respectively. The overall response rate (ORR) for PCB and SCB were 54.2% and 83.3%, respectively (p=0.06). The median progression-free survival (PFS) and overall survival (OS) for PCB and SCB were 406 and 351 days, (p=0.96), and 678 and 1190 days, respectively (p=0.23). The mild adverse events were observed in both regimens. TS expression was more predictive of the chemotherapeutic response in SCB compared to PCB, but not for PFS. Conclusion The combination regimen of SCB was identified as having a similar activity and tolerability to that of PCB in patients with advanced non-squamous NSCLC. more...
- Published
- 2019
- Full Text
- View/download PDF
15. The role of anti-elastin antibodies in a mouse model of asthma
- Author
-
Hajime Arifuku, Yasutsugu Fukushima, Naotatsu Otsuji, Shingo Tokita, Hirokuni Hirata, Masafumi Arima, Kumiya Sugiyama, Kenya Koyama, Kei Sugitate, Takayoshi Owada, and Tomoshige Wakayama
- Subjects
COPD ,Lung ,integumentary system ,medicine.diagnostic_test ,biology ,Inhalation ,business.industry ,Immunology ,macromolecular substances ,General Medicine ,respiratory system ,Eosinophil ,medicine.disease ,respiratory tract diseases ,Allergic inflammation ,Ovalbumin ,Bronchoalveolar lavage ,medicine.anatomical_structure ,cardiovascular system ,medicine ,biology.protein ,Immunology and Allergy ,business ,Sensitization - Abstract
Background The role of anti-elastin antibody (Ab) in the lung is unclear, although they may be involved in chronic obstructive pulmonary disease (COPD). Recently, increased anti-elastin Ab levels were reported in asthma. Objective To elucidate the role of anti-elastin Ab in asthma, we created a murine asthma model. Anti-elastin Ab in the airway was neutralized by intratracheal administration of elastin peptide, and the inhibitory effects of anti-elastin Ab on airway remodeling were evaluated. Methods BALB/c mice were immunized with ovalbumin (OVA) on days 0 and 14. After immunization, the mice received booster OVA via inhalation twice per week for 9 weeks, and bronchoalveolar lavage fluid (BALF) and lung tissues were evaluated. Results In lung tissues, airway remodeling occurred after 9 weeks of OVA sensitization. Peak levels of anti-elastin Ab and eosinophils in BALF were detected after 3 weeks of OVA sensitization. Anti-elastin Ab and eosinophil levels in BALF were significantly reduced after 3 weeks by the neutralization of anti-elastin Ab. Peak transforming growth factor-β1 levels in BALF were detected at 3 weeks after OVA sensitization and were significantly reduced by the neutralization of anti-elastin Ab. Airway remodeling in lung tissues was also significantly inhibited by the neutralization of anti-elastin Ab. Conclusions In our murine asthma model, anti-elastin Ab was recruited to the airway by OVA-induced allergic inflammation. Airway remodeling was inhibited by the neutralization of anti-elastin Ab. Anti-elastin Ab may contribute to the progression of airway remodeling. more...
- Published
- 2021
- Full Text
- View/download PDF
16. Elevation of anti-elastin antibody in patients with asthma
- Author
-
Kenya Koyama, Yoshihiko Ueda, Shingo Tokita, Masafumi Arima, Hirokuni Hirata, Yasutsugu Fukushima, Naotatsu Otsuji, Kei Sugitate, Hajime Arifuku, Takayoshi Owada, Tomoshige Wakayama, and Kumiya Sugiyama more...
- Subjects
medicine.medical_specialty ,COPD ,biology ,business.industry ,Immunology ,General Medicine ,medicine.disease ,Gastroenterology ,respiratory tract diseases ,Allergic inflammation ,Internal medicine ,medicine ,biology.protein ,Immunology and Allergy ,Biomarker (medicine) ,Sputum ,Antibody ,medicine.symptom ,Airway ,business ,Elastin ,Asthma - Abstract
BACKGROUND It is often difficult to differentiate between asthma and chronic obstructive pulmonary disease (COPD), and useful biomarkers are needed for accurate diagnosis. OBJECTIVE We evaluated anti-elastin antibody to identify useful biomarkers for differentiating between a diagnosis of asthma and COPD. METHODS Patients with asthma (male to female ratio = 10/13; mean age, 67.3 years), COPD (16/0; 74.8 years) and controls (8/4; 72.3 years) were enrolled. Samples from sputum and serum were collected and levels of anti-elastin Ab were measured. RESULTS The levels of anti-elastin Ab in sputum were significantly higher in asthma (11.4 ± 7.16 μg/mL) than in COPD (5.82 ± 5.16 μg/mL; P < 0.01), and serum levels in asthma (67.4 ± 29.7 μg/mL) were also significantly higher than in COPD or controls (45.0 ± 12.8 μg/mL; P < 0.05, 38.6 ± 10.4 μg/mL; P < 0.01, respectively). Anti-elastin Ab in sputum showed a positive correlation with smoking in asthma (r2 = 0.218, P < 0.05). However, no significant differences were observed in the levels of anti-elastin Ab and eosinophils, asthma phenotypes, inhaled corticosteroids, or severity in patients with asthma. Elastin was strongly expressed under the airway basement membrane in asthma compared with COPD or the healthy control. CONCLUSIONS Anti-elastin Ab in sputum could be a useful biomarker for COPD and asthma in ever-smokers. In asthma, anti-elastin Ab was recruited to the airways by both airway allergic inflammation and smoking, and it may contribute to the progression of airway remodeling via autoimmune inflammation, but not emphysema, in COPD. more...
- Published
- 2021
- Full Text
- View/download PDF
17. Effect of tocilizumab on interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA)
- Author
-
Kenya Koyama, Hiroyoshi Watanabe, Kumiya Sugiyama, Tomoshige Wakayama, Yasutsugu Fukushima, Naotatsu Otsuji, Hirokuni Hirata, Kentaro Nakano, and Hajime Arifuku
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,behavioral disciplines and activities ,Gastroenterology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Tocilizumab ,Internal medicine ,medicine ,In patient ,030212 general & internal medicine ,business.industry ,Pulmonary Complication ,Interstitial lung disease ,Mean age ,respiratory system ,medicine.disease ,respiratory tract diseases ,body regions ,030228 respiratory system ,chemistry ,Rheumatoid arthritis ,Biomarker (medicine) ,Methotrexate ,business ,medicine.drug - Abstract
Background: ILD is the most common pulmonary complication in patients with RA. Certain drugs, such as methotrexate, have been associated with the progression of ILD. Therefore, drugs used for treating RA with ILD should be administered carefully. Aims: This study aimed to evaluate the safety of tocilizumab on ILD in patients with RA. Methods: Subjects were 34 patients (17 men, 17 women, mean age 69.4 years) with both RA and ILD. The effect of tocilizumab was evaluated before, 2 months after, and 6 months after administration. Results: Mean levels of matrix metalloproteinase-3 (MMP-3), which is a biomarker of RA disease activity, were 380 ± 370, 214 ± 216, and 208 ± 245 ng/mL, respectively. Significant differences were observed between before and after administration of tocilizumab (before vs 2 months: p Conclusions: The disease activity of RA was significantly improved by administration of tocilizumab, and ILD did not progress. In patients with both RA and ILD, tocilizumab could be administrated safely without progression of ILD. more...
- Published
- 2020
- Full Text
- View/download PDF
18. Th2 cell differentiation from naive<scp>CD</scp>4+T cells is enhanced by autocrine<scp>CC</scp>chemokines in atopic diseases
- Author
-
Yasutsugu Fukushima, Kazuhiro Kurasawa, Masafumi Arima, Takeshi Fukuda, Tatsuo Yukawa, Ayae Tanaka, Tomoyuki Miyao, and Hirokuni Hirata
- Subjects
0301 basic medicine ,Chemokine ,Thymic stromal lymphopoietin ,biology ,business.industry ,Cellular differentiation ,Immunology ,CCR4 ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,030228 respiratory system ,biology.protein ,Immunology and Allergy ,CCL17 ,Medicine ,business ,CC chemokine receptors ,Autocrine signalling ,CCL22 - Abstract
Background Chemokines are involved not only in regulating leucocyte recruitment, but also in other activities. However, functions other than cell recruitment remain poorly understood. We have already shown that the production of CC chemokine ligand (CCL)17 and CCL22 by antigen-stimulated naive CD4+ T cells was higher in asthmatic patients than in healthy controls. However, the role of these chemokines in stimulated naive CD4+ T cells remains unclear. Objective To clarify the biological function of CCL17 and CCL22 on naive CD4+ T, we examined effects of these two chemokines on naive CD4+ T cells expressing CC chemokine receptor (CCR)4 (a receptor for CCL17 and CCL22) during differentiation of Th2 cells in asthmatic patients as allergic subjects. Methods Naive CD4+ T cells were prepared from healthy controls and patients with asthma. We analysed effect of CCL17 and CCL22, and blocking their receptor on differentiation of Th2 cells. Results Production of CCL17 and CCL22 by activated naive CD4+ T cells under Th2 condition was much more in asthmatic patients than in healthy controls. Proliferation and survival of the Th2 differentiating cells and restimulation-induced IL-4 production were much greater in asthmatic patients than in healthy controls. These cell biological phenomena were inhibited by blockade of CCR4. The biological effects of exogenous CCL17 and CCL22 were apparently observed in both healthy controls and asthmatic patients. The effectiveness of these chemokines on naive CD4+ T cells from healthy controls was stronger than those from asthmatic patients. We found that thymic stromal lymphopoietin (TSLP), a Th2 promoting chemokine, is involved in the activation of CD4+ naive T cells via production of CCL17 and CCL22. Conclusions and clinical relevance These data suggest that CCL17 and CCL22 produced by TSLP-primed naive CD4+ T cells in asthma might contribute to an increase in Th2 cells via autocrine loops. more...
- Published
- 2018
- Full Text
- View/download PDF
19. Risk factors for disseminated intravascular coagulation in patients with lung cancer
- Author
-
Hideyuki Satoh, Yasutsugu Fukushima, Naruo Yoshida, Hiroyoshi Watanabe, Kei Sugitate, Sadaaki Shiromori, Kentaro Nakano, Kumiya Sugiyama, Ryosuke Souma, Hirokuni Hirata, Tomoshige Wakayama, Shingo Tokita, Hajime Arifuku, Kenya Koyama, and Masamitsu Tatewaki more...
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Disseminated intravascular coagulation ,medicine.medical_specialty ,business.industry ,Respiratory disease ,Cancer ,General Medicine ,medicine.disease ,Fibrinogen ,Thrombomodulin ,Gastroenterology ,Small-cell carcinoma ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,business ,Lung cancer ,Prospective cohort study ,medicine.drug - Abstract
BACKGROUND The mortality rate from disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in non-lung cancer patients. Moreover, the prevalence of DIC varies among the pathologic types of lung cancer. This study analyzed the relationship between coagulation factors and the pathologic types of lung cancer. METHODS Twenty-six patients with progressive, inoperable stage IIB or higher lung cancer (20 men, 6 women; mean age 71 years; 11 Adeno, 10 squamous cell carcinoma, and 5 small cell carcinoma) and five healthy volunteers without respiratory disease (3 men, 2 women; mean age 72 years) were enrolled in the study. Blood samples were collected at lung cancer diagnosis, before treatment. RESULTS White blood cell count, platelet count, serum C-reactive protein, fibrin/fibrinogen degradation products, fibrinogen, thrombin-antithrombin complex, and D-dimer levels differed significantly between lung cancer patients and the control group, but not among the pathologic types of lung cancer. Thrombomodulin levels were significantly higher in patients with Adeno and squamous cell carcinoma than in those with small cell carcinoma (P < 0.05 and P < 0.01, respectively). Antithrombin levels were significantly lower in patients with squamous cell carcinoma than in those with Adeno (P < 0.05). CONCLUSION Coagulation disorders may develop secondary to chronic inflammation in patients with progressive lung cancer. DIC in lung cancer may be attributed to changes in anticoagulation factors, such as thrombomodulin and antithrombin, but not in other coagulation factors. more...
- Published
- 2018
- Full Text
- View/download PDF
20. Molecular biological analysis in a patient with multiple lung adenocarcinomas
- Author
-
Ryosuke Souma, Hideyuki Satoh, Hirokuni Hirata, Hiroki Imada, Yasutsugu Fukushima, Takeshi Fukuda, Kazuhiro Kurasawa, Shunsuke Suka, Masafumi Arima, Masamitsu Tatewaki, Tomoshige Wakayama, Kozo Sato, Motohiko Tamura, Kumiya Sugiyama, and Yuji Matsumura more...
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Lung ,business.industry ,Nodule (medicine) ,General Medicine ,Gene mutation ,medicine.disease ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Oncology ,Egfr mutation ,030220 oncology & carcinogenesis ,Adenocarcinoma of the lung ,medicine ,Adenocarcinoma ,Histopathology ,In patient ,medicine.symptom ,business - Abstract
The utility of molecular biological analysis in lung adenocarcinoma has been demonstrated. Herein we report a rare case presenting as multiple lung adenocarcinomas with four different EGFR gene mutations detected in three lung tumors. After opacification was detected by routine chest X-ray, the patient, a 64-year-old woman, underwent chest computed tomography which revealed a right lung segment S4 ground-glass nodule (GGN). Follow-up computed tomography revealed a 42 mm GGN nodule with a 26 mm nodule (S6) and a 20 mm GGN (S10). Histopathology of resected specimens from the right middle and lower lobes revealed all three nodules were adenocarcinomas. Four EGFR mutations were detected; no three tumors had the same mutations. Molecular biological analysis is a promising tool for the diagnosis of primary tumors in patients with multiple lung carcinomas of the same histotype, enabling appropriate treatment. more...
- Published
- 2018
- Full Text
- View/download PDF
21. Effect of Thrombomodulin Alfa on Disseminated Intravascular Coagulation in Patients with Lung Cancer
- Author
-
Hideyuki Satoh, Shingo Tokita, Kenya Koyama, Hiroyoshi Watanabe, Masamitsu Tatewaki, Kumiya Sugiyama, Ryosuke Souma, Tomoshige Wakayama, Hirokuni Hirata, Kentaro Nakano, Hiroyuki Masuda, Yasutsugu Fukushima, Naruo Yoshida, Takayoshi Fujimatsu, and Hajime Arifuku more...
- Subjects
Male ,medicine.medical_specialty ,Lung Neoplasms ,Thrombomodulin ,030204 cardiovascular system & hematology ,Significant negative correlation ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Platelet ,In patient ,Lung cancer ,Aged ,Disseminated intravascular coagulation ,business.industry ,Mortality rate ,Significant difference ,General Medicine ,Disseminated Intravascular Coagulation ,Middle Aged ,medicine.disease ,Blood Coagulation Factors ,lung cancer ,Thrombomodulin Alfa ,030220 oncology & carcinogenesis ,Original Article ,Female ,business ,thrombomodulin alfa ,circulatory and respiratory physiology - Abstract
Objective The mortality rate due to disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in those without. We examined the effect of treatment with thrombomodulin alfa (TM-α) for DIC in lung cancer patients. Methods Subjects were 57 patients with DIC (43 men, 14 women; mean age, 71.7 years), comprising 31 with lung cancer and 26 without. DIC patients with or without lung cancer did not differ significantly in their background characteristics. Results No significant difference was noted in the mortality rate between patients with lung cancer (61.3%) and those without (57.7%). However, the dose of TM-α was higher for survivors with lung cancer than for non-survivors (473.1 U/kg/day vs. 380.6 U/kg/day; p more...
- Published
- 2017
- Full Text
- View/download PDF
22. Survey on the proper use of an adrenaline auto-injector in 551 Japanese outdoor workers after Hymenoptera stings
- Author
-
Masafumi Arima, Kumiya Sugiyama, Tomoshige Wakayama, Hirokuni Hirata, Yasutsugu Fukushima, Daisuke Shima, Kazuhiro Kurasawa, Shingo Tokita, Naruo Yoshida, Kozo Sato, Sadaaki Shiromori, Takeshi Fukuda, and Masamitsu Tatewaki more...
- Subjects
lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,Epinephrine ,Outdoor workers ,Insect bites and stings ,03 medical and health sciences ,0302 clinical medicine ,Japan ,medicine ,Animals ,Humans ,Immunology and Allergy ,Anaphylaxis ,Ecology ,business.industry ,Insect Bites and Stings ,General Medicine ,medicine.disease ,Health Surveys ,Hymenoptera ,Auto-Injector ,030104 developmental biology ,030228 respiratory system ,Pre-Exposure Prophylaxis ,Medical emergency ,lcsh:RC581-607 ,business - Published
- 2018
- Full Text
- View/download PDF
23. Emergency Treatment of Anaphylaxis in Japanese Beekeepers
- Author
-
Hideyuki Satoh, Hirokuni Hirata, Yasutsugu Fukushima, Kazuhiro Kurasawa, Masafumi Arima, Kozo Sato, Kumiya Sugiyama, Ryosuke Souma, Sadaaki Shiromori, Takeshi Fukuda, and Masamitsu Tatewaki
- Subjects
Adult ,Male ,medicine.medical_specialty ,Epinephrine ,Emergency treatment ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Japan ,Health care ,medicine ,Animals ,Humans ,0501 psychology and cognitive sciences ,Bites and Stings ,Medical prescription ,Anaphylaxis ,Emergency Treatment ,050107 human factors ,business.industry ,05 social sciences ,Public Health, Environmental and Occupational Health ,Bees ,medicine.disease ,030210 environmental & occupational health ,Systemic reaction ,Family medicine ,Anaphylactic shock ,Female ,business ,Beekeeping - Abstract
Objectives: Honeybee stings often lead to anaphylactic shock. We surveyed Japanese beekeepers to examine whether adrenaline auto-injectors are properly used after honeybee stings.Methods: We contacted representatives of the Japanese Beekeeping Association in all 47 prefectures for assistance distributing allergist-developed questionnaires. Representatives in 33 prefectures distributed questionnaires to their members and we received valid responses from 826 beekeepers.Results: Adrenaline auto-injectors had been prescribed to only 46 of the 826 participants (5.6%) to prevent systemic reaction (SR) to honeybee stings. Of the 33 beekeepers who experienced a honeybee sting after adrenaline auto-injector prescription, 16 (48.5%) developed SRs; 9 of these 16 (56.3%) were treated with an adrenaline auto-injector.Conclusions: Japanese beekeeping organizations should consider encouraging medical institutions to prescribe adrenaline auto-injectors. Furthermore, physicians and other health care workers should better educate beekeepers and others who have been prescribed an adrenaline auto-injector in order to improve compliance and raise awareness of the risk posed by SRs. more...
- Published
- 2019
24. The role of eosinophils in necrosis mainly in single-system Langerhans cell histiocytosis
- Author
-
Yoshinori Kawabata, Takashi Ogura, Masashi Kawamoto, Yoshihiko Shimizu, Kazuyoshi Kurashima, Yasutsugu Fukushima, Nobukazu Tomichi, and Mishie Ann Tanino
- Subjects
Pathology ,medicine.medical_specialty ,Necrosis ,Langerhans cell histiocytosis ,business.industry ,medicine ,Cyst ,medicine.symptom ,medicine.disease ,business ,Infiltration (medical) - Abstract
Background: Single-system Langerhans cell histiocytosis (LCH) shows massive infiltration of eosinophils and occasional necrosis and cyst/cavity formation, but the cause of the necrosis remains unclear.The role more...
- Published
- 2021
- Full Text
- View/download PDF
25. Prescription of adrenaline auto-injectors to 1145 Japanese outdoor workers in 2015
- Author
-
Natsumi Suzuki, Ikuo Akutsu, Masafumi Arima, Yoshihiko Ikeno, Masamitsu Tatewaki, Yasutsugu Fukushima, Hirokuni Hirata, Daisuke Shima, Kazuhiro Kurasawa, Seiko Sekiguchi, Takeshi Fukuda, and Kumiya Sugiyama more...
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Epinephrine ,business.industry ,MEDLINE ,Outdoor workers ,General Medicine ,medicine.disease ,Drug Prescriptions ,Injections ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Japan ,030228 respiratory system ,Humans ,Medicine ,Immunology and Allergy ,Medical emergency ,Medical prescription ,business ,lcsh:RC581-607 ,Anaphylaxis - Published
- 2016
26. Exogenous S100A4 Protein Attenuates Bleomycin-induced Pulmonary Fibrosis in Mice by Reducing the Levels of Fibroblast Growth Factors
- Author
-
Mineaki, Watanabe, Hirokuni, Hirata, Masamitsu, Tatewaki, Kenya, Kohyama, Kumiya, Sugiyama, Yasutsugu, Fukushima, Yoshiki, Ishii, Takeshi, Fukuda, and Masafumi, Arima
- Subjects
Fibroblast Growth Factors ,Pulmonary Fibrosis ,S100A4 ,respiratory system ,respiratory tract diseases ,Bleomycin-treated Mice - Abstract
Background and objective:The calcium-binding protein S100A4 belongs to the S100 family and is involved in fibrotic and inflammatory processes, in which tissue remodeling, cell motility, and epithelialmesenchymal transition play major roles. Cytoplasmic S100A4 is a marker of lung fibroblasts in pulmonary fibrosis;however, the effects of exogenous S100A4 on fibrotic and inflammatory processes in pulmonary fibrosis are unclear. This study examined the effects of exogenous S100A4 protein in mice with bleomycin-induced pulmonary fibrosis.Methods:Bleomycin was administered to mice by intratracheal instillation on day 1. Intratracheal S100A4 protein was administered 4 times after bleomycin treatment. Bronchoalveolar lavage fluid was obtained and lung histological examinations were performed on day 14 after bleomycin administration. Lung tissue was homogenized on the same day to assess the mRNA expression of cytokines, fibroblast growth factors, and S100A4.Results:Unexpectedly, we observed that the administration of exogenous S100A4 protein apparently reduced lung fibrosis in bleomycin-treated mice. In addition, the levels of lymphocyte accumulation and insulin-like growth factor-1 mRNA were significantly reduced in bleomycin-treated lung by S100A4 administration.Conclusions:Exogenous S100A4 protein attenuates bleomycin-induced pulmonary fibrosis in mice by reducing lymphocyte function and the levels of fibroblast growth factors. more...
- Published
- 2016
27. Specific IgE sensitization to honey bee venom and auto-injector adrenaline prescriptions for Japanese beekeepers
- Author
-
Ikuo Akutsu, Hirokuni Hirata, Masafumi Arima, Sadaaki Shiromori, Takeshi Fukuda, Masamitsu Tatewaki, Yasutsugu Fukushima, Daisuke Shima, Kazuhiro Kurasawa, Kumiya Sugiyama, and Yoshihiko Ikeno
- Subjects
Male ,0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Epinephrine ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Occupational Exposure ,Animals ,Humans ,Immunology and Allergy ,Medicine ,Ige sensitization ,Traditional medicine ,business.industry ,Insect Bites and Stings ,General Medicine ,Bees ,Immunoglobulin E ,Auto-Injector ,Honey bee venom ,Bee Venoms ,030104 developmental biology ,030228 respiratory system ,Female ,business ,lcsh:RC581-607 ,Beekeeping - Published
- 2017
28. Emergency treatment of anaphylaxis in Japanese beekeepers
- Author
-
Yasutsugu Fukushima and Kozo Sato
- Subjects
medicine.medical_specialty ,business.industry ,Immunology ,Emergency medicine ,medicine ,Immunology and Allergy ,Emergency treatment ,medicine.disease ,business ,Anaphylaxis - Published
- 2020
- Full Text
- View/download PDF
29. Sensitization to Api m 1, Api m 2, and Api m 4 in Japanese beekeepers who had experienced systemic reactions to honeybee stings
- Author
-
Sadaaki Shiromori, Takeshi Fukuda, Takeshi Ogasawara, Hirokuni Hirata, Yasutsugu Fukushima, Daisuke Shima, Kazuhiro Kurasawa, Masafumi Arima, Hideyuki Satoh, Tatsuo Funakoshi, Masamitsu Tatewaki, Kozo Sato, Kumiya Sugiyama, and Ryosuke Souma more...
- Subjects
Adult ,Male ,medicine.medical_specialty ,Hyaluronoglucosaminidase ,Phospholipases A ,Asian People ,medicine ,Hypersensitivity ,Immunology and Allergy ,Animals ,Humans ,Sensitization ,Aged ,business.industry ,Insect Bites and Stings ,General Medicine ,Allergens ,Bees ,Immunoglobulin E ,Middle Aged ,Dermatology ,Systemic reaction ,Bee Venoms ,medicine.anatomical_structure ,Insect Proteins ,Female ,business ,Beekeeping - Published
- 2018
30. Th2 cell differentiation from naive CD4
- Author
-
Hirokuni, Hirata, Tatsuo, Yukawa, Ayae, Tanaka, Tomoyuki, Miyao, Takeshi, Fukuda, Yasutsugu, Fukushima, Kazuhiro, Kurasawa, and Masafumi, Arima
- Subjects
Adult ,CD4-Positive T-Lymphocytes ,Hypersensitivity, Immediate ,Male ,Apoptosis ,Cell Differentiation ,Immunoglobulin E ,Lymphocyte Activation ,Asthma ,Immunophenotyping ,Autocrine Communication ,Th2 Cells ,T-Lymphocyte Subsets ,Case-Control Studies ,Chemokines, CC ,Humans ,Female ,Lymphocyte Count ,Biomarkers - Abstract
Chemokines are involved not only in regulating leucocyte recruitment, but also in other activities. However, functions other than cell recruitment remain poorly understood. We have already shown that the production of CC chemokine ligand (CCL)17 and CCL22 by antigen-stimulated naïve CD4To clarify the biological function of CCL17 and CCL22 on naïve CD4Naïve CD4Production of CCL17 and CCL22 by activated naive CD4These data suggest that CCL17 and CCL22 produced by TSLP-primed naïve CD4 more...
- Published
- 2018
31. Allergic TH2 Response Governed by B-Cell Lymphoma 6 Function in Naturally Occurring Memory Phenotype CD4+ T Cells
- Author
-
Akemi Sakamoto, Takashi Ogasawara, Haruko Watanabe-Takano, Lisa Fujimura, Yasutsugu Fukushima, Hirokuni Hirata, Yuko Kohashi, Nobuhide Tsuruoka, Kazuhiro Kurasawa, Jun Ikari, Toshibumi Taniguchi, Takeshi Fukuda, Masafumi Arima, Masahiko Hatano, Koichiro Tatsumi, and Takeshi Tokuhisa more...
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Adoptive cell transfer ,Immunology ,03 medical and health sciences ,Immune system ,immune system diseases ,hemic and lymphatic diseases ,B-cell lymphoma 6 ,medicine ,naturally occurring memory phenotype T cells ,Immunology and Allergy ,B-cell lymphoma ,Enhancer ,Interleukin 4 ,Regulation of gene expression ,Chemistry ,asthma ,medicine.disease ,BCL6 ,allergy ,Phenotype ,Cell biology ,030104 developmental biology ,TH2 cells ,lcsh:RC581-607 - Abstract
Transcriptional repressor B-cell lymphoma 6 (Bcl6) appears to regulate TH2 immune responses in allergies, but its precise role is unclear. We previously reported that Bcl6 suppressed IL-4 production in naive CD4+ T cell-derived memory TH2 cells. To investigate Bcl6 function in allergic responses in naturally occurring memory phenotype CD4+ T (MPT) cells and their derived TH2 (MPTH2) cells, Bcl6-manipulated mice, highly conserved intron enhancer (hcIE)-deficient mice, and reporter mice for conserved noncoding sequence 2 (CNS2) 3' distal enhancer region were used to elucidate Bcl6 function in MPT cells. The molecular mechanisms of Bcl6-mediated TH2 cytokine gene regulation were elucidated using cellular and molecular approaches. Bcl6 function in MPT cells was determined using adoptive transfer to naive mice, which were assessed for allergic airway inflammation. Bcl6 suppressed IL-4 production in MPT and MPTH2 cells by suppressing CNS2 enhancer activity. Bcl6 downregulated Il4 expression in MPTH2 cells, but not MPT cells, by suppressing hcIE activity. The inhibitory functions of Bcl6 in MPT and MPTH2 cells attenuated allergic responses. Bcl6 is a critical regulator of IL-4 production by MPT and MPTH2 cells in TH2 immune responses related to the pathogenesis of allergies. more...
- Published
- 2018
- Full Text
- View/download PDF
32. [HYMENOPTERA VENOM AND ANAPHYLAXIS HYMENOPTERA VENOM ALLERGY]
- Author
-
Hirokuni, Hirata and Yasutsugu, Fukushima
- Subjects
Bee Venoms ,Desensitization, Immunologic ,Hypersensitivity ,Animals ,Humans ,Bees ,Immunoglobulin E ,Anaphylaxis ,Skin Tests - Published
- 2018
33. Effect of adjusting the combination of budesonide/formoterol on the alleviation of asthma symptoms
- Author
-
Hideyuki Satoh, Masafumi Arima, Takeshi Fukuda, Hiroyuki Masuda, Ryosuke Souma, Hajime Arifuku, Kenya Koyama, Kentaro Nakano, Shingo Tokita, Kumiya Sugiyama, Masamitsu Tatewaki, Hiroyoshi Watanabe, Yasutsugu Fukushima, Kazuhiro Kurasawa, Hirokuni Hirata, Yumeko Hayashi, Tomoshige Wakayama, and Fumiya Fukushima more...
- Subjects
Budesonide ,medicine.medical_specialty ,Allergy ,Evening ,Biochemistry ,Symbicort maintenance and reliever therapy (SMART) ,immune system diseases ,Wheeze ,Internal medicine ,medicine ,Formoterol ,Asthma ,lcsh:RC705-779 ,Adjustable maintainable dose (AMD) ,business.industry ,Inhaler ,Research ,Organic Chemistry ,Peak expiratory flow (PEF) ,lcsh:Diseases of the respiratory system ,medicine.disease ,respiratory tract diseases ,Budesonide/formoterol ,medicine.symptom ,business ,medicine.drug - Abstract
Background The combination of budesonide + formoterol (BFC) offers the advantages of dose adjustment in a single inhaler according to asthma symptoms. We analyzed the relationship between asthma symptoms in terms of peak expiratory flow (PEF) and dose adjustment by the patient. Methods Twenty-eight patients with asthma who used BFC for alleviation of their symptoms (12 men, 16 women; 60 years old) were instructed that the inhaled BFC dose could be increased to a maximum of 8 inhalations per day according to symptom severity. Patients measured and recorded PEF every morning and evening in their asthma diary along with their symptoms and the dose of drugs taken. Results Sixteen of the 28 patients increased their dose for asthma symptoms. The time to recovery from the asthma symptoms was significantly shorter when cough was the only symptom present compared with dyspnea or wheeze (1.4 vs. 5.3 or 6.6 days, p more...
- Published
- 2018
34. Analysis of the Characteristics of Patients Presenting with Exacerbation of Asthma to Emergency Care Units
- Author
-
Hideyuki, Satoh, Kumiya, Sugiyama, Ryosuke, Souma, Shingo, Tokita, Tomoshige, Wakayama, Naruo, Yoshida, Kentaro, Nakano, Takeshi, Fukuda, and Yasutsugu, Fukushima
- Subjects
Fatal Asthma ,Exacerbation Of Asthma ,Emergency Room ,Asthma ,Pulse Oximetry - Abstract
Background:Fatal asthma remains a serious problem, and patient self-management of asthma is important to prevent exacerbation. To reduce the asthma mortality rate, we analyzed the characteristics of patients who visited an emergency care unit with exacerbation of asthma.Methods:Subjects were 317 patients(135 men, 182 women;mean age, 47.0 years)who visited the emergency room at Dokkyo Medical University Hospital or Dokkyo Medical University Koshigaya Hospital for exacerbation of asthma between April 2010 and March 2011. When categorized by severity, 41.3% ofpatients were step 1, 8.2% were step 2, 18.9% were step 3, 30.9% were step 4, and 0.6% were unknown. When categorized by primary care physician, 60.3% of patients had a primary care physician at Dokkyo Medical University, 13.6% had one at another hospital, and 26.2% had no primary care physician. When categorized by recovery from exacerbation, control was achieved within 1 day in 63.1% of cases, after more than 1 day in 30.6% of cases, and required admission in 6.3% of cases.Results:The rate of admissions was highest for cases with step 1 severity(step 1, 55.0%;step 2, 20.0%;step 3, 0.0%;and step 4, 25.0%). The rate of admissions did not differ significantly by age(age 15-39 years, 40.0%;40-65 years, 25.0%;>65 years, 35.0%). Initial value of oxyhemoglobin saturation(SpO_2) measured by pulse oximetry was significantly lower in the admission group(SpO_2 92.4%)than in the nonadmissiongroup(SpO_2 95.2%, p more...
- Published
- 2015
35. Mechanism of Airway Remodeling Induced by Repeated Inhalation of Methacholine in a Mouse Model of Asthma
- Author
-
Ryosuke, Souma, Kumiya, Sugiyama, Naoto, Fueki, Kentaro, Nakano, Hideyuki, Satoh, Hironori, Sagara, and Yasutsugu, Fukushima
- Subjects
Eosinophils ,Methacholine ,Airway Remodeling ,Animal Model ,respiratory system ,hormones, hormone substitutes, and hormone antagonists ,Asthma - Abstract
Background:Increased severity of asthma is contributed by airway tissue remodeling, which may be associated with chronic allergic inflammation. A recent study revealed the potential capacity of repeated bronchoconstriction, e.g. induced by a muscarine agonist, methacholine(Mch)challenge, to involve in airway remodeling, even though allergic inflammation is not implicated. We have evaluated the influence of repeated bronchoconstriction induced by Mch inhalation on airway remodeling in a murine model of asthma and have examined its machanisms. Methods:Mice were immunized with ovalbumin(OVA), and consequently, challenged by either daily OVA inhalation(the OVA group;a model of asthma with allergic inflammation)or daily Mch inhalation(the Mch group;a model of asthma without allergic inflammation). Lung tissues were obtained and were evaluated histologically after 5, 10, and 15 consecutive inhalation challenges of both OVA and Mch.Results:Eosinophilia in the airway observed only on the OVA group. Subepithelial collagen-band thickness increased also in the OVA group(p more...
- Published
- 2015
36. Development of chronic allergic responses by dampening Bcl6-mediated suppressor activity in memory T helper 2 cells
- Author
-
Kenji Matsumoto, Toshibumi Taniguchi, Yasutsugu Fukushima, Hirokuni Hirata, Kazuhiro Kurasawa, Lisa Fujimura, Masafumi Arima, Jun Ikari, Haruko Watanabe-Takano, Hirohisa Saito, Masahiko Hatano, Akemi Sakamoto, Susumu Nakae, Takeshi Tokuhisa, Nobuhide Tsuruoka, Hisae Satake, Koichiro Tatsumi, Takashi Ogasawara, Takeshi Fukuda, and Kumiya Sugiyama more...
- Subjects
Lipopolysaccharides ,0301 basic medicine ,Ovalbumin ,medicine.medical_treatment ,Mice, Transgenic ,Biology ,Histones ,03 medical and health sciences ,Th2 Cells ,Immune system ,immune system diseases ,hemic and lymphatic diseases ,Interleukin 25 ,medicine ,Animals ,IL-2 receptor ,Interleukin 4 ,Mice, Inbred BALB C ,Multidisciplinary ,Suppressor of cytokine signaling 1 ,GATA3 ,Immunoglobulin E ,BCL6 ,Asthma ,030104 developmental biology ,Cytokine ,PNAS Plus ,Immunology ,Proto-Oncogene Proteins c-bcl-6 ,Cytokines - Abstract
Mice deficient in the transcriptional repressor B-cell CLL/lymphoma 6 (Bcl6) exhibit similar T helper 2 (TH2) immune responses as patients with allergic diseases. However, the molecular mechanisms underlying Bcl6-directed regulation of TH2 cytokine genes remain unclear. We identified multiple Bcl6/STAT binding sites (BSs) in TH2 cytokine gene loci. We found that Bcl6 is modestly associated with the BSs, and it had no significant effect on cytokine production in newly differentiated TH2 cells. Contrarily, in memory TH2 (mTH2) cells derived from adaptively transferred TH2 effectors, Bcl6 outcompeted STAT5 for binding to TH2 cytokine gene loci, particularly Interleukin4 (Il4) loci, and attenuated GATA binding protein 3 (GATA3) binding to highly conserved intron enhancer regions in mTH2 cells. Bcl6 suppressed cytokine production epigenetically in mTH2 cells to negatively tune histone acetylation at TH2 cytokine gene loci, including Il4 loci. In addition, IL-33, a pro-TH2 cytokine, diminished Bcl6's association with loci to which GATA3 recruitment was inversely augmented, resulting in altered IL-4, but not IL-5 and IL-13, production in mTH2 cells but no altered production in newly differentiated TH2 cells. Use of a murine asthma model that generates high levels of pro-TH2 cytokines, such as IL-33, suggested that the suppressive function of Bcl6 in mTH2 cells is abolished in severe asthma. These findings indicate a role of the interaction between TH2-promoting factors and Bcl6 in promoting appropriate IL-4 production in mTH2 cells and suggest that chronic allergic diseases involve the TH2-promoting factor-mediated functional breakdown of Bcl6, resulting in allergy exacerbation. more...
- Published
- 2017
- Full Text
- View/download PDF
37. Epidemiologic Investigation of Hornet and Paper Wasp Stings in Forest Workers and Electrical Facility Field Workers in Japan
- Author
-
Yoshiki Ishii, Takeshi Fukuda, Yasutsugu Fukushima, Tatsuya Yokoyama, Masafumi Arima, Yoshiki Murayama, Kumiya Sugiyama, Hirokuni Hirata, Mineaki Watanabe, Yumeko Hayashih, and Naruo Yoshida
- Subjects
lcsh:Immunologic diseases. Allergy ,paper wasp stings ,forestry and field workers ,Poison control ,Wasp Venoms ,Insect bites and stings ,Office workers ,Toxicology ,Japan ,Surveys and Questionnaires ,Humans ,Immunology and Allergy ,Medicine ,Workplace ,Paper wasp ,medicine.diagnostic_test ,business.industry ,Radioallergosorbent test ,venom-specific IgE ,Insect Bites and Stings ,Forestry ,General Medicine ,Immunoglobulin E ,medicine.disease ,Health Surveys ,Hymenoptera venom ,Bee Venoms ,Systemic reaction ,hornet stings ,Hymenoptera allergy ,Hornet venom ,business ,lcsh:RC581-607 ,Power Plants ,Demography - Abstract
Background: Forestry and field workers who work outdoors are at high risk for Hymenoptera stings and may develop occupation-related allergies from being stung. However, clinical and immunological surveys of Hymenoptera stings in the occupational setting have rarely been reported. We surveyed the natural history of Hymenoptera stings in Japanese forestry workers (FWs) and electrical facility field workers (EFFWs), and we assessed the utility of measuring specific (s)IgE Ab to Hymenptera venom. Methods: Questionnaires on hornet and paper wasp stings were completed by 999 FWs, 354 EFFWs, and 365 office workers as controls between July and November 2009. Sera from these participants were tested for sIgE Ab levels to Hymenptera venom with a CAP system using a fluoroenzyme immunoassay. Results: Of the participants who had experienced Hymenoptera stings, 914 (91.5%) were FWs, 293 (82.8%) were EFFWs, and 295 (80.8%) were controls. Of the participants who had experienced systemic reactions, 210 (21.0%) were FWs, 51 (14.4%) were EFFWs, and 39 (10.7%) were controls. sIgE Ab in response to hornet and wasp venom was positive (≥ class 2) in 42.4% and 41.4% of FWs, 30.1% and 31.4% of EFFWs, and 15.1% and 18.1% of controls, respectively. The likelihood of being sIgE-positive to wasp and hornet venom was significantly higher in FWs and EFFWs than in controls (P Conclusions: 21% of FWs and 14% of EFFWs had experienced systemic reactions to Hymenoptera stings with a higher frequency compared with office workers in the same area. 40% of FWs and 30% of EFFWs had sera that were sIgE positive to Hymenoptera venom. more...
- Published
- 2014
38. Sensitization to Api m 1, Api m 2, and Api m 4 in Japanese beekeepers who had experienced systemic reactions to honeybee stings
- Author
-
Sadaaki Shiromori, Hirokuni Hirata, Kozo Sato, Yasutsugu Fukushima, and Kumiya Sugiyama
- Subjects
Systemic reaction ,medicine.anatomical_structure ,business.industry ,Immunology ,Immunology and Allergy ,Medicine ,business ,Sensitization - Published
- 2019
- Full Text
- View/download PDF
39. Leukotriene C4aggravates bleomycin-induced pulmonary fibrosis in mice
- Author
-
Yasutsugu Fukushima, Takeshi Fukuda, Masafumi Arima, Kumiya Sugiyama, Hirokuni Hirata, and Takeshi Tokuhisa
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.diagnostic_test ,Leukotriene C4 ,business.industry ,Transgene ,Interleukin ,respiratory system ,Bleomycin ,medicine.disease ,Pranlukast ,chemistry.chemical_compound ,Bronchoalveolar lavage ,Endocrinology ,chemistry ,Internal medicine ,Pulmonary fibrosis ,Medicine ,business ,medicine.drug ,Transforming growth factor - Abstract
Background and objective Synthesis of cysteinyl leukotrienes (cys-LT) is thought to cause inflammatory disorders such as bronchial asthma and allergic rhinitis. Recent reports have suggested that leukotriene C4 (LTC4) is an important regulator of pulmonary fibrosis. This study examined the effect of LTC4 in LTC4 synthase-overexpressed transgenic mice with bleomycin-induced pulmonary fibrosis. The function of lung-derived fibroblasts from transgenic mice was also investigated. Methods Bleomycin was administrated to transgenic mice and wild-type (WT) mice by intratracheal instillation. Concentrations of interleukin (IL)-4 and -13, interferon-γ, and transforming growth factor (TGF)-β1 in bronchoalveolar lavage fluid were measured 1, 3, 7 and 14 days after the administration of bleomycin. Lung tissue was examined histopathologically on day 14. In addition, lung-derived fibroblasts from transgenic and WT mice were cultured for 7 days. Expression of TGF-β1 mRNA was measured by real-time polymerase chain reaction. Results Both the pathological scores for pulmonary fibrosis (3.8 ± 0.4 vs 2.0 ± 0.1, P more...
- Published
- 2013
- Full Text
- View/download PDF
40. Clinical Significance of Propionibacterium acnes in the Formation of Noncaseating Epithelioid-Cell Granulomas of the Mediastinal Lymph Nodes and Lung in Patients with Lung Cancer:Differential Diagnosis Between Sarcoid Reactions and Sarcoidosis
- Author
-
Yasutsugu, Fukushima, Mineaki, Watanabe, Naruo, Yoshida, Naoya, Ikeda, Shogo, Onishi, Yushi, Nomura, Hirokuni, Hirata, Kumiya, Sugiyama, and Takeshi, Fukuda
- Subjects
lung cancer ,sarcoid reactions ,hemic and lymphatic diseases ,Propionibacterium acnes ,sarcoidosis - Abstract
Objectives:Sarcoidosis is a systemic noncaseating epithelioid-cell granulomatous disease of unknown origin.Granulomas occurring around malignant tumors and regional lymph nodes can be caused by sarcoid reactions.The mechanisms underlying sarcoidosis and sarcoid reactions remain unclear. Whether increaseduptake of fluorodeoxyglucose( FDG) in lymph nodes on positron emission tomography( PET) is caused bytumor metastasis, the concurrent presence of sarcoidosis, or sarcoid reactions must be determined to ensureproper disease staging and selection of treatment policy. We studied patients who underwent surgery forlung cancer and had no histopathological evidence of lymph-node metastasis in whom concurrent sarcoidosisor sarcoid reactions were diagnosed.Methods:In six patients who underwent surgery for primary lung cancer, granulomatous lesions werehistopathologically studied in dissected lymph nodes and lung. Tissue sections were stained with monoclonalantibodies against Propionibacterium acnes( PAB antibodies).Results:The six patients had noncaseating epithelioid-cell granulomas in mediastinal lymph nodes andlung. Clinically, concurrent sarcoidosis was suspected, but the results of staining the tissue specimens withPAB antibodies( in granulomas, alveolar macrophages, Hamazaki-Wesenberg bodies, and lymphatic sinuses)suggested sarcoid reactions in 5 patients. In one patient in whom granulomas stained positive with PAB antibodies,concurrent sarcoidosis was diagnosed.Conclusions:In patients with lung cancer who have no distinct systemic evidence of sarcoidosis, thepresence of noncaseating epithelioid-cell granulomas in the lung hilum or mediastinum is usually caused bysarcoid reactions. more...
- Published
- 2013
41. Clinical Characteristics of Acute Exacerbations of Idiopathic Pulmonary Fibrosis and Involvement of Viral, Mycoplasma pneumoniae, and Chlamydophila pneumoniae Infections
- Author
-
Makiko, Anzai, Yasutsugu, Fukushima, Kazuki, Obara, Kazuhiko, Matsuno, Yasuko, Kikkawa, Hirokuni, Hirata, Kumiya, Sugiyama, and Takeshi, Fukuda
- Subjects
viral infection ,respiratory system ,Chlamydophila pneumoniae ,idiopathic pulmonary fibrosis ,acute exacerbation ,respiratory tract diseases ,Mycoplasma pneumoniae - Abstract
Background and Objective:To clarify the clinical characteristics of acute exacerbation of idiopathic pulmonaryfibrosis (IPF) and the involvement of infections with pathogenic microorganisms and viruses inacute exacerbation.Methods:During the 12 years from 2000 through 2011, we studied 50 patients who were admitted andreceived treatment for acute exacerbation of IPF in our department. Demographic characteristics, imagingfindings, laboratory findings, changes in antibody titers against bacteria, Mycoplasma pneumoniae, Chlamydophilapneumoniae, and known viruses, and outcomes were studied.Results:Among the 50 patients with acute exacerbation of IPF( 41 men and 9 women) 29 patients died(mortality rate, 58.0%). Computed tomography showed subpleural peripheral ground-glass opacities( GGO)in 5 patients, multiple patchy GGO in 19, and diffuse GGO in 26. Only the PaO2/FiO2 ratio was significantlylower in the non-survivors compared with survivors. Three patients had high titers of IgM antibodiesagainst C. pneumoniae, but acute infection was ruled out by the changes in IgA and IgG antibodies in pairedserum samples. Antibody titers against known viruses significantly increased in 2 patients( respiratory syncytialvirus in 1 and adenovirus 11 in 1). In acute-phase serum samples, 7 patients had increased antibodytiters against parainfluenza virus 3, resulted in no significant change in paired serum samples.Conclusions:Our results suggest that known pathogens do not play a role in acute exacerbation of IPF.The outcomes of IPF remain poor, and the elucidation of the causes and pathological features of acute exacerbationof IPF, including the identification of unknown pathogens, is awaited. more...
- Published
- 2013
42. IL-33 and RANTES( Regulated on Activation, Normal T Cell Expressed and Secreted) in BAL Fluid in Asthma Patients Without Cigarette Smoking
- Author
-
Masamitsu, Tatewaki, Hirokuni, Hirata, Fumiya, Fukushima, Yasutsugu, Fukushima, Kumiya, Sugiyama, and Takeshi, Fukuda
- Subjects
RANTES ,smoker ,BAL fluid ,IL-33 ,atopy ,asthma ,respiratory tract diseases - Abstract
Background:Inflammatory cytokines and chemokines have been reported to play important roles in thepathogenesis of bronchial asthma. However, no criteria for the classification of `smoker' and `atopic' in bronchialasthma have been defined. In this study, we compared the levels of several cytokines found in thebronchoalveolar lavage( BAL) fluid of patients classified as having bronchial asthma.Methods:Cell subpopulations in BAL fluid were counted. BAL fluid levels of interleukin( IL)-4, -5, -13,-17, and -33 and RANTES (regulated on activation, normal T cell expressed and secreted were measuredusing a bead suspension array in 36 asthma patients (13 males, 23 females;mean age, 39.5±92.8 years)who were non-smokers, 18 asthma patients( 11 males, 7 females;mean age, 30.7±2.7 years) who were exor current smokers( Brinkman index( BI):1−399), and 10 asthma patients( 9 males, 1 female;mean age,50.2±5.5 years) who were current heavy smokers( BI:≥ 400). Relationships were assessed by Spearman'srank correlation analysis.Results:The number of lymphocytes in BAL cell subpopulations of non-smokers( 25±7×103/ml) weresignificantly (p more...
- Published
- 2013
43. Involvement of Bird-related IgG Antibodies in Interstitial Pneumonia
- Author
-
Kazuki, Mashio, Yasutsugu, Fukushima, Fumito, Oomi, Takafumi, Umetsu, Naruo, Yoshida, Naoya, Ikeda, Hirokuni, Hirata, Kumiya, Sugiyama, and Takeshi, Fukuda
- Subjects
chronic interstitial pneumonia ,bird-related hypersensitivity pneumonitis ,idiopathic pulmonary fibrosis ,chronic hypersensitivity pneumonitis - Abstract
Background and Objective:Chronic interstitial pneumonia (IP) might include chronic hypersensitivity pneumonitis (HP) and chronic bird-related hypersensitivity pneumonitis (BRHP). A specific antigen is difficult to identify in these diseases, and such evidence would provide important clues suggesting a diagnosis of HP. In this study, we used an ImmunoCAP analysis system to measure specific IgG antibodies against pigeons and budgerigars in the sera of patients with IP and investigated the involvement of bird-related IgG antibodies in IP.Methods:The study group comprised 22 patients with idiopathic pulmonary fibrosis (IPF), 8 with chronic IP, 7 with subacute HP, 7 with chronic HP, and 10 with control diseases. All cases were diagnosed from 2000 through 2011 at the Institute of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University. Clinical features, results of laboratory examinations, and levels of serum IgG antibodies against pigeons and budgerigars were compared.Results:There were no significant differences among the disease groups in C-reactive protein, leukocyte count, lactate dehydrogenase, and the results of blood gas analysis. KL-6 and surfactant protein D were significantly higher in subacute HP and chronic HP. The levels of anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies in each disease group were respectively as follows:IPF, 11.02±5.97 mg/l, 5.03±3.97 mg/l;chronic IP, 10.04±8.55 mg/l, 3.30±1.47 mg/l;subacute HP, 14.39±9.13 mg/l, 7.96±6.47 mg/l;chronic HP, 24.97±16.19 mg/l, 11.50±13.80 mg/l;and control diseases, 8.66±3.15 mg/l, 3.77±1.05 mg/l. The mean levels of anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies were significantly higher in chronic HP. There was a positive correlation between anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies (R2 = 0.715, p more...
- Published
- 2013
44. Involvement of antigen-driven mechanisms in interstitial pneumonia with polymyositis
- Author
-
Tomoe Furihata, Takaji Matsutani, Hirokuni Hirata, Fumiya Fukushima, Reika Maezawa, Kumiya Sugiyama, Masato Okada, Akira Takeda, Yasutsugu Fukushima, Takeshi Fukuda, and Masaaki Miyoshi
- Subjects
Rheumatology ,Antigen ,business.industry ,Immunology ,medicine ,Pharmacology (medical) ,Interstitial pneumonia ,medicine.disease ,business ,Polymyositis - Published
- 2013
- Full Text
- View/download PDF
45. A Case of Inflammatory Lung Disease and Retroperitoneal Fibrosis Attributed to Systemic IgG4-related Disease
- Author
-
Masamitsu, Tatewaki, Hirokuni, Hirata, Fumiya, Fukushima, Kuniyoshi, Kamiya, Yumeko, Hayashi, Ryo, Arai, Makiko, Anzai, Reika, Maezawa, Kumiya, Sugiyama, Yasutsugu, Fukushima, Kazuhiro, Kurasawa, Kouichi, Honma, Yoshiki, Ishii, Takeshi, Fukuda, Masamitsu, Tatewaki, Hirokuni, Hirata, Fumiya, Fukushima, Kuniyoshi, Kamiya, Yumeko, Hayashi, Ryo, Arai, Makiko, Anzai, Reika, Maezawa, Kumiya, Sugiyama, Yasutsugu, Fukushima, Kazuhiro, Kurasawa, Kouichi, Honma, Yoshiki, Ishii, and Takeshi, Fukuda more...
- Abstract
type:Case Report, Recently, immunoglobulin (Ig) G4-related diseases such as autoimmune pancreatitis (AIP), sclerosingsialadenitis, retroperitoneal fibrosis, and sclerosing cholangitis have been reported. IgG4-related diseases arecharacterized by high serum IgG4 concentrations, sclerosing inflammation with numerous IgG4-positiveplasma cells, and steroid sensitivity, irrespective of their organ of origin. We describe a case of inflammatorylung disease and retroperitoneal fibrosis, suggested to involve IgG4. The patient was a 76-year-old man. Acomputed tomographic scan of the chest showed nodular air-space consolidation in the left upper lobe. Theserum IgG4 concentration was abnormally elevated, but there was no evidence of AIP. Bilateral hydronephrosisassociated with thickened soft tissue around the abdominal aorta had been diagnosed previously. Hehad undergone surgery, and retroperitoneal fibrosis was diagnosed histologically (hematoxylin and eosinstain). Histological examination of bronchoscopic specimens taken from the left S3 region showed mononuclear-cell infiltration of the fibrotic bronchial wall, including many IgG4-positive plasma cells. Specimens ofthe region affected by retroperitoneal fibrosis were retrospectively reanalyzed, and the cells were positivefor IgG4 on immunostaining, similar to the lung tissue. The patient responded to treatment with corticosteroids.In conclusion, the present case shared many clinical and clinicopathological similarities with systemicIgG4-related autoimmune disease. To our knowledge, however, this is the first reported case of inflammatorylung disease with retroperitoneal fibrosis in a patient with systemic IgG4-related autoimmune disease., identifier:6, identifier:KJ00006372599 more...
- Published
- 2017
46. Involvement of Bird-related IgG Antibodies in Interstitial Pneumonia
- Author
-
Kazuki, Mashio, Yasutsugu, Fukushima, Fumito, Oomi, Takafumi, Umetsu, Naruo, Yoshida, Naoya, Ikeda, Hirokuni, Hirata, Kumiya, Sugiyama, Takeshi, Fukuda, Kazuki, Mashio, Yasutsugu, Fukushima, Fumito, Oomi, Takafumi, Umetsu, Naruo, Yoshida, Naoya, Ikeda, Hirokuni, Hirata, Kumiya, Sugiyama, and Takeshi, Fukuda more...
- Abstract
type:ENG, Background and Objective:Chronic interstitial pneumonia (IP) might include chronic hypersensitivity pneumonitis (HP) and chronic bird-related hypersensitivity pneumonitis (BRHP). A specific antigen is difficult to identify in these diseases, and such evidence would provide important clues suggesting a diagnosis of HP. In this study, we used an ImmunoCAP analysis system to measure specific IgG antibodies against pigeons and budgerigars in the sera of patients with IP and investigated the involvement of bird-related IgG antibodies in IP.Methods:The study group comprised 22 patients with idiopathic pulmonary fibrosis (IPF), 8 with chronic IP, 7 with subacute HP, 7 with chronic HP, and 10 with control diseases. All cases were diagnosed from 2000 through 2011 at the Institute of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University. Clinical features, results of laboratory examinations, and levels of serum IgG antibodies against pigeons and budgerigars were compared.Results:There were no significant differences among the disease groups in C-reactive protein, leukocyte count, lactate dehydrogenase, and the results of blood gas analysis. KL-6 and surfactant protein D were significantly higher in subacute HP and chronic HP. The levels of anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies in each disease group were respectively as follows:IPF, 11.02±5.97 mg/l, 5.03±3.97 mg/l;chronic IP, 10.04±8.55 mg/l, 3.30±1.47 mg/l;subacute HP, 14.39±9.13 mg/l, 7.96±6.47 mg/l;chronic HP, 24.97±16.19 mg/l, 11.50±13.80 mg/l;and control diseases, 8.66±3.15 mg/l, 3.77±1.05 mg/l. The mean levels of anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies were significantly higher in chronic HP. There was a positive correlation between anti-pigeon IgG antibodies and anti-budgerigar IgG antibodies (R2 = 0.715, p<0.001). Conclusions:In patients with clinically diagnosed chronic HP, high levels of anti-pige, identifier:6, identifier:KJ00008416759 more...
- Published
- 2017
47. IL-33 and RANTES( Regulated on Activation, Normal T Cell Expressed and Secreted) in BAL Fluid in Asthma Patients Without Cigarette Smoking
- Author
-
Masamitsu, Tatewaki, Hirokuni, Hirata, Fumiya, Fukushima, Yasutsugu, Fukushima, Kumiya, Sugiyama, Takeshi, Fukuda, Masamitsu, Tatewaki, Hirokuni, Hirata, Fumiya, Fukushima, Yasutsugu, Fukushima, Kumiya, Sugiyama, and Takeshi, Fukuda more...
- Abstract
type:Original, Background:Inflammatory cytokines and chemokines have been reported to play important roles in thepathogenesis of bronchial asthma. However, no criteria for the classification of `smoker' and `atopic' in bronchialasthma have been defined. In this study, we compared the levels of several cytokines found in thebronchoalveolar lavage( BAL) fluid of patients classified as having bronchial asthma.Methods:Cell subpopulations in BAL fluid were counted. BAL fluid levels of interleukin( IL)-4, -5, -13,-17, and -33 and RANTES (regulated on activation, normal T cell expressed and secreted were measuredusing a bead suspension array in 36 asthma patients (13 males, 23 females;mean age, 39.5±92.8 years)who were non-smokers, 18 asthma patients( 11 males, 7 females;mean age, 30.7±2.7 years) who were exor current smokers( Brinkman index( BI):1−399), and 10 asthma patients( 9 males, 1 female;mean age,50.2±5.5 years) who were current heavy smokers( BI:≥ 400). Relationships were assessed by Spearman'srank correlation analysis.Results:The number of lymphocytes in BAL cell subpopulations of non-smokers( 25±7×103/ml) weresignificantly (p<0.05) higher than those of heavy smokers (12±3×103 /ml). The number of neutrophilswas significantly( p<0.05) higher in heavy smokers( 18±9×103/ml) than in non-smokers( 4±2×103/ml).Levels of IL-33 and RANTES were significantly (P<0.05) higher in non-smokers (26.1±7.3 pg/ml and42.8±10.3 pg/ml, respectively) than in heavy smokers (13.7±4.5 pg/ml and 27.4±5.4 pg/ml, respectively).In addition, the levels of IL-33 and RANTES in non-smokers were significantly( P<0.05) higher in atopicasthma patients (33.0±9.8 pg/ml and 47.8±14.0 pg/ml, respectively) than in non-atopic asthma patients(9.1±3.8 pg/ml and 29.5±7.8 pg/ml, respectively). A good correlation was noted between RANTES andlymphocytes (R=0.365, P<0.05) or IL-33 (R=0.561, P<0.05) in atopic asthma patients who were nonsmokers.Conclusions:Differences in the cell types of BAL fluid, as well as in th, identifier:5, identifier:KJ00008416399 more...
- Published
- 2017
48. Analysis of the Characteristics of Patients Presenting with Exacerbation of Asthma to Emergency Care Units
- Author
-
Hideyuki, Satoh, Kumiya, Sugiyama, Ryosuke, Souma, Shingo, Tokita, Tomoshige, Wakayama, Naruo, Yoshida, Kentaro, Nakano, Takeshi, Fukuda, Yasutsugu, Fukushima, Hideyuki, Satoh, Kumiya, Sugiyama, Ryosuke, Souma, Shingo, Tokita, Tomoshige, Wakayama, Naruo, Yoshida, Kentaro, Nakano, Takeshi, Fukuda, and Yasutsugu, Fukushima more...
- Abstract
type:Original, Background:Fatal asthma remains a serious problem, and patient self-management of asthma is important to prevent exacerbation. To reduce the asthma mortality rate, we analyzed the characteristics of patients who visited an emergency care unit with exacerbation of asthma.Methods:Subjects were 317 patients(135 men, 182 women;mean age, 47.0 years)who visited the emergency room at Dokkyo Medical University Hospital or Dokkyo Medical University Koshigaya Hospital for exacerbation of asthma between April 2010 and March 2011. When categorized by severity, 41.3% ofpatients were step 1, 8.2% were step 2, 18.9% were step 3, 30.9% were step 4, and 0.6% were unknown. When categorized by primary care physician, 60.3% of patients had a primary care physician at Dokkyo Medical University, 13.6% had one at another hospital, and 26.2% had no primary care physician. When categorized by recovery from exacerbation, control was achieved within 1 day in 63.1% of cases, after more than 1 day in 30.6% of cases, and required admission in 6.3% of cases.Results:The rate of admissions was highest for cases with step 1 severity(step 1, 55.0%;step 2, 20.0%;step 3, 0.0%;and step 4, 25.0%). The rate of admissions did not differ significantly by age(age 15-39 years, 40.0%;40-65 years, 25.0%;>65 years, 35.0%). Initial value of oxyhemoglobin saturation(SpO_2) measured by pulse oximetry was significantly lower in the admission group(SpO_2 92.4%)than in the nonadmissiongroup(SpO_2 95.2%, p<0.01).Conclusion:Patients with step 1 severity who visit an emergency unit with exacerbation of asthma may need regular treatment for asthma. When initial SpO_2 is less than 92%, we should consider hospitalization for treatment of asthma., identifier:3, identifier:KJ00009786640 more...
- Published
- 2017
49. Exogenous S100A4 Protein Attenuates Bleomycin-induced Pulmonary Fibrosis in Mice by Reducing the Levels of Fibroblast Growth Factors
- Author
-
Mineaki, Watanabe, Hirokuni, Hirata, Masamitsu, Tatewaki, Kenya, Kohyama, Kumiya, Sugiyama, Yasutsugu, Fukushima, Yoshiki, Ishii, Takeshi, Fukuda, Masafumi, Arima, Mineaki, Watanabe, Hirokuni, Hirata, Masamitsu, Tatewaki, Kenya, Kohyama, Kumiya, Sugiyama, Yasutsugu, Fukushima, Yoshiki, Ishii, Takeshi, Fukuda, and Masafumi, Arima more...
- Abstract
type:Original, Background and objective:The calcium-binding protein S100A4 belongs to the S100 family and is involved in fibrotic and inflammatory processes, in which tissue remodeling, cell motility, and epithelialmesenchymal transition play major roles. Cytoplasmic S100A4 is a marker of lung fibroblasts in pulmonary fibrosis;however, the effects of exogenous S100A4 on fibrotic and inflammatory processes in pulmonary fibrosis are unclear. This study examined the effects of exogenous S100A4 protein in mice with bleomycin-induced pulmonary fibrosis.Methods:Bleomycin was administered to mice by intratracheal instillation on day 1. Intratracheal S100A4 protein was administered 4 times after bleomycin treatment. Bronchoalveolar lavage fluid was obtained and lung histological examinations were performed on day 14 after bleomycin administration. Lung tissue was homogenized on the same day to assess the mRNA expression of cytokines, fibroblast growth factors, and S100A4.Results:Unexpectedly, we observed that the administration of exogenous S100A4 protein apparently reduced lung fibrosis in bleomycin-treated mice. In addition, the levels of lymphocyte accumulation and insulin-like growth factor-1 mRNA were significantly reduced in bleomycin-treated lung by S100A4 administration.Conclusions:Exogenous S100A4 protein attenuates bleomycin-induced pulmonary fibrosis in mice by reducing lymphocyte function and the levels of fibroblast growth factors., identifier:2, identifier:KJ00010247939 more...
- Published
- 2017
50. A Case of Pulmonary Benign Metastasizing Leiomyoma Occurring after Uterine Myomectomy
- Author
-
Yasutsugu, Fukushima, Hiroyuki, Hirata, Reika, Maezawa, Naruo, Yoshida, Yumeko, Hayashi, Ryo, Arai, Fumiya, Fukushima, Kumiya, Sugiyama, Kazuhiro, Kurasawa, Yoshiki, Ishii, Takeshi, Fukuda, Yasutsugu, Fukushima, Hiroyuki, Hirata, Reika, Maezawa, Naruo, Yoshida, Yumeko, Hayashi, Ryo, Arai, Fumiya, Fukushima, Kumiya, Sugiyama, Kazuhiro, Kurasawa, Yoshiki, Ishii, and Takeshi, Fukuda more...
- Abstract
type:Case Report, Benign metastasizing leiomyoma (BML) is a very rare disease, and although it was reported as early as1939 to result from metastasis of benign uterine myoma to the lungs and lymph nodes, its pathology remainsobscure. Here, we describe a case of pulmonary BML occurring after uterine myomectomy in a42-year-old woman. She presented with a 2-week history of dry cough on exertion. Chest radiography andcomputed tomography( CT) revealed bilateral multiple nodular lesions. The patient had a history of uterinemyoma and previously underwent myomectomy. For definitive diagnosis, lung biopsy was performed byvideo associated thoracoscopic surgery. Histopathologic examination of biopsy specimens revealed pulmonaryBML occurring after uterine myomectomy. For treatment of the pulmonary BML, gonadotropin-releasinghormone was initially administered, and 1 month later the patient underwent complete hysterectomyand bilateral salpingo-oophorectomy. Chest CT 6 months after surgery showed that the size and number oflung multiple nodular lesions did not increase compared with those before surgery. In future studies, we aimto investigate a larger number of pulmonary BML cases, as well as establish specific treatments and investigatethe prognosis of the disease.Abbreviations:BML:benign metastasizing leiomyomaSS:Sjögren's syndromeCT:computed tomographyH&E:hematoxylin and eosinVATS:video associated thoracoscopic surgeryCA:carbohydrate antigenIg:immunoguloblina SMA:a smooth muscle actin, identifier:12, identifier:KJ00006378199 more...
- Published
- 2017
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.