研究者総覧

長嶋 孝夫 (ナガシマ タカオ)

  • 内科学講座(アレルギー膠原病学部門) 准教授
Last Updated :2021/12/04

研究者情報

ホームページURL

J-Global ID

研究キーワード

  • MRL-lpr   全身性エリテマトーデス   lpr   スタチン   フルバスタチン   アポトーシス   lprマウス   Fluvastatin   

研究分野

  • ライフサイエンス / 感染症内科学
  • ライフサイエンス / 膠原病、アレルギー内科学

経歴

  • 2004年  自治医科大学助手

研究活動情報

論文

  • Jun Nakamura, Takao Nagashima, Katsuya Nagatani, Taku Yoshio, Masahiro Iwamoto, Seiji Minota
    INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES 19 5 470 - 475 2016年05月 [査読有り][通常論文]
     
    Objective: To examine the incidence of hepatitis B virus (HBV) reactivation in patients with rheumatoid arthritis (RA) receiving biological disease-modifying antirheumatic drugs (DMARDs). Methods: We retrospectively reviewed RA patients treated with biological DMARDs at our institution from July 2010 to December 2012. Patients with antibodies for hepatitis B core antigen and/or hepatitis B surface antigen were regarded as having prior HBV infection. Clinical data on these patients, including HBV-DNA levels, were retrieved from the medical records. Results: During the study period, 251 patients were administered various biological DMARDs. Six patients with a history of HBV vaccination and one patient with positive HBV surface antigen were excluded from the study. Fifty-seven of the remaining 244 patients (23.4%) had prior HBV infection. These patients were followed for a median of 18 months (range: 2-27 months) and HBV-DNA was examined a median of seven times (range: 227). HBV-DNA was detected in three patients (5.3%), comprising two receiving tocilizumab and one receiving etanercept. However, HBV-DNA levels were below the quantitation limit (<2.1 log copies mL(-1)) in all three patients. HBV-DNA became negative again within several months in all three patients, while biological DMARDs were continued and liver function tests remained normal throughout. Conclusion: HBV-DNA reactivation occurred in 5.3% of RA patients with prior HBV infection during treatment with biological DMARDs, but there were no associated clinical manifestations. Accordingly, it seems that biological DMARDs can be used safely in patients with RA.
  • Takao Nagashima, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 34 7 1025 - 1026 2014年07月 [査読有り][通常論文]
  • Takamasa Murosaki, Takao Nagashima, Kyoko Honne, Yoko Aoki, Seiji Minota
    INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES 17 4 476 - 478 2014年05月 [査読有り][通常論文]
  • Takao Nagashima, Kazuko Matsumoto, Takamasa Murosaki, Mari Okada, Masahiro Iwamoto, Shinji Makino, Seiji Minota
    Rheumatology International 33 7 1915 - 1916 2013年07月 [査読有り][通常論文]
  • Kyoko Honne, Takao Nagashima, Sachiko Onishi, Katsuya Nagatani, Masahiro Iwamoto, Seiji Minota
    Journal of Clinical Rheumatology 19 2 104 - 105 2013年03月 [査読有り][通常論文]
  • Akihito Maruyama, Takao Nagashima, Yasuyuki Kamata, Katsuya Nagatani, Takamasa Murosaki, Taku Yoshio, Seiji Minota
    Rheumatology International 33 1 267 - 268 2013年01月 [査読有り][通常論文]
  • Akihito Maruyama, Takao Nagashima, Kohei Ikenoya, Yoko Aoki, Yasushi Matsuyama, Masahiro Iwamoto, Seiji Minota
    INTERNAL MEDICINE 52 16 1833 - 1837 2013年 [査読有り][通常論文]
     
    We herein report the findings of 2 cases of normotensive scleroderma renal crisis (SRC) that developed soon after the commencement of a glucocorticoid therapy. We also review 8 cases of normotensive SRC reported in Japan, including our cases. The common characteristics of these 8 cases are as follows: the recent onset of systemic sclerosis, the presence of diffuse skin sclerosis, the presence of myositis and/or serositis, a high titer of antinuclear antibody and positivity for anti-Scl-70 antibody. In 7 of the 8 patients, thrombotic microangiopathy developed within one month of starting the glucocorticoid treatment. We should be careful with the use of glucocorticoids in systemic sclerosis patients exhibiting these features in order to avoid cases of normotensive SRC.
  • Jun Nakamura, Takao Nagashima, Yoichiro Akiyama, Seiji Minota
    Internal Medicine 52 24 2837  2013年 [査読有り][通常論文]
  • Nagashima T, Okazaki H, Kamata Y, Minota S
    Modern rheumatology / the Japan Rheumatism Association 22 4 638 - 639 4 2012年08月 [査読有り][通常論文]
  • Takao Nagashima, Akihito Maruyama, Yasuyuki Kamata, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 32 7 2231 - 2232 2012年07月 [査読有り][通常論文]
  • Takao Nagashima, Akihito Maruyama, Shino Takatori, Meri Saito, Jun-ichi Osuga, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 32 6 1851 - 1852 2012年06月 [査読有り][通常論文]
  • Matsuyama Y, Okazaki H, Hoshino M, Onishi S, Kamata Y, Nagatani K, Nagashima T, Iwamoto M, Yoshio T, Ohto-Ozaki H, Tamemoto H, Komine M, Sekiya H, Tominaga S, Minota S
    Rheumatology international 32 5 1397 - 1401 5 2012年05月 [査読有り][通常論文]
     
    Although TNF inhibitors have dramatically improved the outcome of patients with rheumatoid arthritis, 30-40% of patients do not respond well to them and treatment needs to be changed. In an effort to discriminate good and poor responders, we focused on the change in serum and synovial fluid levels of interleukin (IL-) 33 before and after treatment with TNF inhibitors. They were also measured in synovial fluids from 17 TNF inhibitor-na < ve patients, and fibroblast-like synoviocytes (FLS) in-culture from 6 patients and correlated with various pro-inflammatory cytokines. Serum levels of IL-33 at 6 months after treatment decreased significantly in responders, while they did not change in non-responders. Synovial fluid levels of IL-33 in 6 patients under treatment with TNF inhibitors stayed high in 3 who were refractory and slightly elevated in 2 moderate responders, while they were undetectable in one patient under remission. Among inflammatory cytokines measured in 17 synovial fluids from TNF inhibitor-na < ve patients, levels of IL-33 showed a significant positive correlation only to those of IL-1 beta. IL-1 beta increased IL-33 expression markedly in FLS in vitro, compared to TNF-alpha. IL-1 beta might be inducing RA inflammation through producing pro-inflammatory IL-33 in TNF inhibitor-hypo-responders. Sustained elevation of serum and/or synovial levels of IL-33 may account for a poor response to TNF inhibitors, although how TNF inhibitors affect the level of IL-33 remains to be elucidated.
  • Masahiro Iwamoto, Takeshi Kamimura, Takao Nagashima, Yasuyuki Kamata, Yoko Aoki, Sachiko Onishi, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 32 3 801 - 804 2012年03月 [査読有り][通常論文]
     
    Prospective observational study was performed to elucidate the incidence and characteristics of healthcare-associated infections in a university hospital for rheumatology care. In this study, a total of 1,226 patients were prospectively enrolled between March 2004 and February 2006 and between April 2008 and December 2008. Healthcare-associated infection was defined as an infection developing after the third day of admission to the rheumatology ward. We detected the following 54 healthcare-associated infections in 49 patients: respiratory tract infection, 14 cases; Clostridium difficile infection, 2 cases; urinary tract infection, 4 cases; bloodstream infection, 9 cases; skin infection, 2 cases; reactivation of latent cytomegalovirus infection, 6 cases; herpes zoster infection, 5 cases; Candida infection, 7 cases; others, 4 cases. The incidence rate of respiratory tract infection was the highest. Methicillin-resistant Staphylococcus aureus was the causative bacterium in 21% of respiratory tract infections cases. Bloodstream infection due to the insertion of a catheter and opportunistic infection by a latent virus were also occurred commonly. Respiratory tract infection, bloodstream infection and opportunistic infection by a latent virus were the most common causes of healthcare-associated infection in rheumatology. It is important to pay more attention to healthcare-associated infection.
  • Kazuko Matsumoto, Takao Nagashima, Masahiro Iwamoto, Seiji Minota
    INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES 15 1 e2 - e3 2012年02月 [査読有り][通常論文]
  • Nagashima T, Iwamoto M, Matsumoto K, Minota S
    Internal medicine (Tokyo, Japan) 51 449; author reply 451  4 2012年 [査読有り][通常論文]
  • Takamasa Murosaki, Takao Nagashima, Kazuko Matsumoto, Seiji Minota
    INTERNAL MEDICINE 51 11 1451 - 1451 2012年 [査読有り][通常論文]
  • Takamasa Murosaki, Takao Nagashima, Yoko Aoki, Yukiko Imai, Masahiro Iwamoto, Seiji Minota
    INTERNAL MEDICINE 51 22 3181 - 3183 2012年 [査読有り][通常論文]
     
    A 59-year-old woman with a 10-year history of rheumatoid arthritis (RA) presented with chronic ulcers on both feet while undergoing treatment with etanercept. Rheumatoid vasculitis (RV) was diagnosed, and the patient was treated with immunosuppressant drugs and skin grafting. Although anti-tumor necrosis factor (TNF) agents are known to induce vasculitis, vasculitis can also be caused by active RA. Accordingly, the cause of vasculitis in RA patients receiving anti-TNF therapy must be evaluated carefully.
  • Takao Nagashima, Masahiro Iwamoto, Seiji Minota
    CLINICAL RHEUMATOLOGY 30 6 875 - 876 2011年06月 [査読有り][通常論文]
  • Takao Nagashima, Masahiro Iwamoto, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 31 5 705 - 706 2011年05月 [査読有り][通常論文]
  • Nagashima T, Minota S
    The Journal of rheumatology 38 574; author reply 575  3 2011年03月 [査読有り][通常論文]
  • Matsuyama Y, Nagashima T, Honne K, Kamata Y, Iwamoto M, Okazaki H, Sato K, Ozawa K, Minota S
    Internal medicine (Tokyo, Japan) 50 6 639 - 642 6 2011年 [査読有り][通常論文]
     
    A 63-year-old woman receiving tumor necrosis factor (TNF) inhibitors for rheumatoid arthritis (RA) was found to have smoldering IgA-kappa type multiple myeloma (MM). Retrospective examination of stored serum samples revealed a steady increase of serum IgA levels after the start of TNF inhibitor therapy. The patient's articular symptoms showed marked exacerbation when TNF inhibitors were discontinued because of fear of worsening the MM. Tocilizumab improved RA symptoms dramatically and stabilized serum IgA levels for 13 months after a transient steep rise. This case suggests that tocilizumab can be used safely in patients with inflammatory disorders with coexisting MM.
  • Onishi S, Yoshio T, Nagashima T, Minota S
    Modern rheumatology / the Japan Rheumatism Association 20 5 528 - 530 5 2010年10月 [査読有り][通常論文]
  • Kyoko Honne, Akihito Maruyama, Sachiko Onishi, Takao Nagashima, Seiji Minota
    JOURNAL OF RHEUMATOLOGY 37 10 2194 - 2196 2010年10月 [査読有り][通常論文]
  • Takao Nagashima, Toshimi Imai, Kazuko Matsumoto, Sachiko Onishi, Shino Takatori, Masahiro Iwamoto, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 30 11 1549 - 1550 2010年09月 [査読有り][通常論文]
  • Takao Nagashima, Seiji Minota
    CLINICAL RHEUMATOLOGY 29 7 819 - 820 2010年07月 [査読有り][通常論文]
  • Takao Nagashima, Seiji Minota
    JOURNAL OF RHEUMATOLOGY 37 5 1066 - 1066 2010年05月 [査読有り][通常論文]
  • Takao Nagashima, Seiji Minota
    CLINICAL RHEUMATOLOGY 29 4 449 - 450 2010年04月 [査読有り][通常論文]
  • Yasushi Matsuyama, Hitoaki Okazaki, Hiroyuki Tamemoto, Hirotaka Kimura, Yasuyuki Kamata, Katsuya Nagatani, Takao Nagashima, Morisada Hayakawa, Masahiro Iwamoto, Taku Yoshio, Shin-Ichi Tominaga, Seiji Minota
    JOURNAL OF RHEUMATOLOGY 37 1 18 - 25 2010年01月 [査読有り][通常論文]
     
    Objective. To determine levels of interleukin 33 (IL-33) in serum and synovial fluid (SF) and their clinical associations in patients with rheumatoid arthritis (RA). To evaluate the ability of activated peripheral blood mononuclear cells (PBMC) and fibroblast-like synoviocytes (FLS) from RA patients to release IL-33. Methods. Sera were obtained from 59 patients with RA, 10 patients with infectious diseases, and 42 healthy volunteers. SF samples were obtained from 15 patients with RA and 13 with osteoarthritis. IL-33 levels were measured using a sandwich ELISA after removal of rheumatoid factor with protein A-Sepharose beads. FLS were stimulated with IL-1 beta and tumor necrosis factor, and treated with or without chemical damage. PBMC were stimulated with anti-CD3/CD28 antibodies. The levels of IL-33 were measured in the culture supernatants and cell lysates by ELISA or immunoblotting. Results. Serum IL-33 levels were significantly higher in RA patients, especially in the high disease activity group compared to the moderate or low activity group. IL-33 levels in SF were elevated in all 15 RA patients measured. IL-33 levels were higher in SF samples than in sera in 7 RA patients measured simultaneously. The 30-kDa IL-33 precursor was detected in the culture supernatants of damaged FLS but was not detected in those of activated PBMC and non-damaged FLS. Conclusion. IL-33 levels were elevated in sera and SF samples from patients with RA, and correlated with disease activity. IL-33 was produced mainly in inflamed joints; IL-33/ST2L signaling might play an important role in joint inflammation of human RA. (First Release Nov 15 2009; J Rheumatol 2010;37;18-25; doi:10.3899/jrheum.090492)
  • Yoko Aoki, Masahiro Iwamoto, Yasuyuki Kamata, Takao Nagashima, Taku Yoshio, Hitoaki Okazaki, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 29 11 1327 - 1330 2009年09月 [査読有り][通常論文]
     
    The objective of this study is to investigate the clinical markers of life-threatening Pneumocystis pneumonia (PCP) in patients with collagen vascular diseases (CVD). The patients who contracted Pneumocystis jeroveccii were retrospectively selected from our medical charts and conditions related to the patients' death were reviewed. The findings indicated that lower levels of serum albumin and cholinesterase, increased alveolar-arterial oxygen gradient, intratracheal intubation, and necessity to treat in the intensive care unit were significantly related to deaths associated with PCP in CVD. A special attention should be paid to decreased serum albumin and cholinesterase as ominous predictors in PCP occurred in patients with CVD.
  • Takao Nagashima, Hidetomo Sato, Seiji Minota
    JOURNAL OF RHEUMATOLOGY 36 9 2133 - 2134 2009年09月 [査読有り][通常論文]
  • Takao Nagashima, Sachiko Onishi, Yasuyuki Kamata, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 29 10 1261 - 1262 2009年08月 [査読有り][通常論文]
  • Nagashima T, Hoshino M, Shimoji S, Morino N, Kamimura T, Okazaki H, Minota S
    Rheumatology international 29 7 817 - 820 7 2009年05月 [査読有り][通常論文]
     
    Protein-losing gastroenteropathy (PLGE) is a rare manifestation of primary Sjogren's syndrome (SS). We report a case of a 41-year-old Japanese man, who is the first male patient, with PLGE associated with primary SS. Although serum anti-SSA and SSB antibodies were detected, he had no subjective sicca symptoms. He had multiple annular erythema: a characteristic skin manifestation of Asian SS patients. A diagnosis of PLGE was made from results of Tc-99m-labelled albumin scintigraphy and a faecal alpha-1-antitrypsin clearance test. Intravenous administration of high-dose glucocorticoid was not effective, but pulse methylprednisolone therapy alleviated disease manifestations. As all cases of PLGE associated with primary SS have been reported from East Asia, this complication could be essentially limited to Asian patients.
  • Ken Futaki, Mayumi Komine, Satomi Hosoda, Miho Hirashima, Hideto Yokokura, Tomoko Yamada, Satoru Murata, Yasushi Matsuyama, Takao Nagashima, Hiroyuki Nara, Seiji Minota, Mamitaro Ohtsuki
    EUROPEAN JOURNAL OF DERMATOLOGY 19 3 266 - 267 2009年05月 [査読有り][通常論文]
  • Kazuko Matsumoto, Takao Nagashima, Shino Takatori, Yuta Kawahara, Masaki Yagi, Masahiro Iwamoto, Hitoaki Okazaki, Seiji Minota
    CLINICAL RHEUMATOLOGY 28 4 485 - 487 2009年04月 [査読有り][通常論文]
     
    We report a 29-year-old Japanese woman with disseminated intravascular coagulation (DIC) and adult onset Still's disease (AOSD). Her disease was refractory to high-dose glucocorticoids, two courses of steroid pulse therapy, and addition of cyclosporine (3.5 mg/kg/day). The serum interleukin-6 level was markedly elevated. Therefore, we administered an anti-interleukin-6 receptor antibody (tocilizumab, 8 mg/kg fortnightly), which dramatically improved her symptoms and the levels of acute-phase proteins. In addition, rapid tapering of the glucocorticoid dose was possible. Four months later, she was maintained on tocilizumab infusion once a month with low-dose steroid therapy. Cyclosporine is one of the first-line immunosuppressants for AOSD, especially when associated with DIC, hepatic failure, or hemophagocytic syndrome. In patients with cyclosporine-resistant AOSD, tocilizumab may be another useful option.
  • Takao Nagashima, Yoko Aoki, Sachiko Onishi, Masahiro Iwamoto, Hitoaki Okazaki, Seiji Minota
    CLINICAL RHEUMATOLOGY 27 11 1451 - 1453 2008年11月 [査読有り][通常論文]
     
    We report two Japanese women with severe hepatic dysfunction and adult onset Still's disease. A 51-year-old woman had been diagnosed with adult onset Still's disease 3 years earlier. She relapsed while on maintenance therapy with prednisolone and methotrexate. After induction of remission with methylprednisolone pulse therapy, indomethacin, and methotrexate, severe hepatic failure occurred. This patient lacked the typical symptoms of adult onset Still's disease. The second patient was a 32-year-old woman with typical adult onset Still's disease. Remission was induced by high-dose prednisolone and methylprednisolone pulse therapy plus cyclosporine. After she stopped cyclosporine, severe liver dysfunction occurred. In both patients, liver dysfunction occurred during high-dose steroid therapy, and oral cyclosporine (3 mg/kg per day) dramatically improved their liver function. When steroid-resistant severe hepatic failure occurs in patients with adult onset Still's disease, cyclosporine may be the immunosuppressant of choice.
  • Takao Nagashima, Kazuko Matsumoto, Reiko Yamamoto, Masahiro Iwamoto, Seiji Minota
    RHEUMATOLOGY INTERNATIONAL 28 10 1065 - 1066 2008年08月 [査読有り][通常論文]
  • Takao Nagashima, Hikaru Okubo-Fornbacher, Yoko Aoki, Yasuyuki Kamata, Hirotaka Kimura, Takeshi Kamimura, Hiroyuki Nara, Masahiro Iwamoto, Taku Yoshio, Hitoaki Okazaki, Seiji Minota
    JOURNAL OF RHEUMATOLOGY 35 5 936 - 938 2008年05月 [査読有り][通常論文]
  • Takao Nagashima, Masahiro Iwamoto, Seiji Minota
    Modern Rheumatology 16 5 330 - 331 2006年10月 [査読有り][通常論文]
  • Yoko Aoki, Takao Nagashima, Takeshi Kamimura, Masahiro Iwamoto, Seiji Minota
    JOURNAL OF RHEUMATOLOGY 33 8 1705 - 1706 2006年08月 [査読有り][通常論文]
  • Nagashima T, Kamimura T, Nara H, Iwamoto M, Okazaki H, Minota S
    Circulation 114 e10 - 1 1 2006年07月 [査読有り][通常論文]
  • T Nagashima, H Okazaki, K Yudoh, H Matsuno, S Minota
    ARTHRITIS AND RHEUMATISM 54 2 579 - 586 2006年02月 [査読有り][通常論文]
     
    Objective. To determine whether statins induce apoptosis in rheumatoid arthritis (RA) synoviocytes. Methods. The effects of lipophilic and hydrophilic statins (fluvastatin and pravastatin, respectively) on the apoptosis of cultured RA synoviocytes were examined in vitro. Apoptosis was analyzed by flow cytometry after staining with JC-1. (to measure the mitochondrial transmembrane potential), active caspase 3, annexin V, and propidium iodide. Add-back experiments were conducted to determine which downstream products of the mevalonate pathway could suppress apoptosis. Modulation of various signaling pathways induced by statins, including protein prenylation, was also investigated. Results. Fluvastatin, but not pravastatin, induced apoptosis in RA synoviocytes in a concentration-dependent (1-1.0 mu M) and time-dependent (48-96 hours) manner. Another lipophilic statin, pitavastatin, displayed almost the same effects as fluvastatin. In sharp contrast lipophilic statins did not significantly increase apoptosis in synoviocytes from patients with ostcoarthropathy. Apoptosis induced by fluvastatin was mitochondrial- and caspase 3-dependent and was abrogated by mevalonate and geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate. In addition, the geranylgeranyl transferase inhibitor GGTI-298 mim-icked the effect of fluvastatin on RA synoviocytes. Treatment of RA synoviocytes with the RhoA kinase inhibitor Y-27632 caused apoptosis. Fluvastatin decreased the amount of RhoA protein in the membrane fraction, but increased the amount in the cytosolic fraction. Conclusion. Fluvastatin induced apoptosis in RA synoviocytes through a mitochondrial- and caspase 3-dependent pathway and by the blockage of mevalonate pathways, particularly through the inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathways. These findings suggest that lipophilic statins have potential as novel therapeutic agents for RA.
  • T Nagashima, J Masuyama, H Okubo, S Minota
    JOURNAL OF RHEUMATOLOGY 32 6 1168 - 1169 2005年06月 [査読有り][通常論文]
  • Okazaki H, Nagashima T, Minota S
    Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology 27 357 - 360 6 2004年12月 [査読有り][通常論文]
  • Daisuke Hirata, Takao Nagashima, Shin Saito, Hitoaki Okazaki, Shogo Kano, Seiji Minota
    Modern Rheumatology 12 2 186 - 189 2002年 [査読有り][通常論文]
     
    We report a case of hypocalcemic myopathy confounded by polymyositis due to an elevated level of serum creatine kinase (CK). A 30-year-old man was referred to our hospital for the treatment of provisionally diagnosed polymyositis. His presentation with tetany, hyporeflexia, and general fatigue, in addition to muscle weakness on admission, prompted us to scrutinize a blood sample in search of secondary myopathy. Blood chemistry revealed an elevated level of serum CK, marked hypocalcemia, hyperphosphatemia, and a low serum level of intact parathyroid hormone. The Ellsworth Howard test confirmed the diagnosis of hypoparathyroidism. Supplementation with calcium and 1α-hydroxyvitamin D3 improved his muscle weakness rapidly, and his serum CK level returned to the normal range. Hypoparathyroidism should be included in differential diagnoses of elevated serum CK.
  • Nagashima T, Hirata D, Yamamoto H, Okazaki H, Minota S
    American journal of kidney diseases : the official journal of the National Kidney Foundation 37 E38  5 2001年05月 [査読有り][通常論文]

MISC

  • 中村 潤, 秋山 陽一郎, 上田 佳孝, 永谷 勝也, 長嶋 孝夫, 岩本 雅弘, 簑田 清次 アレルギー 62 (3) 2013年04月 [査読無し][通常論文]
  • 丸山 暁人, 長嶋 孝夫, 石澤 彩子, 室崎 貴勝, 本根 杏子, 釜田 康行, 永谷 勝也, 吉尾 卓, 岡崎 仁昭, 岩本 雅弘, 簑田 清次 日本臨床免疫学会会誌 36 (5) 409a -409a 2013年 [査読無し][通常論文]
     
    【目的】当科におけるSLE患者のループス腸炎合併例の臨床的検討を行った.【方法】2001年1月~2012年12月までに入院したSLE患者431例中,ループス腸炎と診断した16例(3.7%)(再発含め延べ22例)を対象とした.ループス腸炎の診断は,画像で腸管壁の肥厚を認め,副腎皮質ステロイドによる治療を要した症例とした.【結果】ループス腸炎発症時の年齢(35歳,18~66歳)(中央値,範囲),SLE発症からループス腸炎発症までの期間(5年,0~19年),臨床症状は腹痛が19/22例,下痢が17/22例,悪心・嘔吐が16/22例であった.白血球減少 0/22例;血小板減少 1/22例;貧血 2/22例;低補体血症 15/22例;抗ds-DNA抗体上昇 15/22例,抗SS-A抗体陽性 11/16例,抗RNP抗体陽性 5/16例,CRP(0.81 mg/dl,0.01~17.5 mg/dl),SLEDAI(8.5,0~23)であった.腸管浮腫の部位は小腸+大腸が最も多く17/22例.腹水 18/22例,水腎症 7/22例を認めた.治療は15/22例にステロイドパルス療法が併用され,免疫抑制薬の併用は3例であった.再発は5/16例に認めた.【結論】当科におけるループス腸炎の特徴は,抗SS-A抗体陽性例が多く,血球異常はほとんど認めず,治療経過は良好であった.
  • 室崎 貴勝, 永谷 勝也, 小川 美織, 青木 葉子, 長嶋 孝夫, 岩本 雅弘, 簑田 清次 アレルギー 61 (3) 2012年04月 [査読無し][通常論文]
  • 室崎 貴勝, 永谷 勝也, 長嶋 孝夫, 簑田 清次 アレルギー 60 (3) 2011年04月 [査読無し][通常論文]
  • 長嶋 孝夫, 小池 裕美子, 本根 杏子, 釜田 康行, 大槻 マミ太郎, 簑田 清次 アレルギー 59 (3) 2010年04月 [査読無し][通常論文]
  • 松山 泰, 長嶋 孝夫, 増田 智一, 岩本 雅弘, 吉尾 卓, 岡崎 仁昭, 大槻 マミ太郎, 簑田 清次 自治医科大学紀要 32 63 -69 2010年03月 [査読無し][通常論文]
     
    症例は55歳男性。15年前より関節症性乾癬に対して治療を受けておりコントロール良好であった。2007年2月に自己判断にて治療薬を中止したところ,皮膚および関節症状が再燃し,著しい疼痛により離床不能となり臀部に褥創を形成するに至った。シクロスポリンA,経口プレドニゾロンによる治療を行ったが効果不充分であり副作用を認めた。血清β-D-glucanの上昇を認め,本邦の生物学的製剤の使用ガイドラインに基づけばインフリキシマブの適応外となるが,臨床所見や他の検査によって活動性の真菌感染症は否定的であったことから同意取得後にインフリキシマブを開始した。結果,皮膚および関節症状は著明に改善し,真菌感染症を発症することなく血清β-D-glucanは正常化した。現在,インフリキシマブを継続して通常の生活を送ることができている。ガイドラインは一つの指針に過ぎず,重要なことは患者の全体像を臨床的に判断することである。
  • 松山 泰, 岡崎 仁昭, 長嶋 孝夫, 岩本 雅弘, 吉尾 卓, 簑田 清次 アレルギー 57 (9) 2008年10月 [査読無し][通常論文]
  • 松山 泰, 岡崎 仁昭, 木村 洋貴, 長嶋 孝夫, 簑田 清次 アレルギー 57 (3) 2008年04月 [査読無し][通常論文]
  • 高鳥 志乃, 長嶋 孝夫, 上村 健, 岩本 雅弘, 吉尾 卓, 岡崎 仁昭, 簑田 清次 アレルギー 57 (3) 2008年04月 [査読無し][通常論文]
  • 青木 葉子, 岩本 雅弘, 木村 洋貴, 長嶋 孝夫, 吉尾 卓, 岡崎 仁昭, 簔田 清次 自治医科大学紀要 30 29 -36 2007年12月 [査読無し][通常論文]
     
    Objective Prednisolone has traditionally been tapered below 30 mg daily before patients are discharged from hospitals in Japan because of concerns regarding the development of infectious complications. We undertook this study to compare the incidence of infectious complications in patients taking more than 30 mg of prednisolone daily with those taking less than 30 mg. Patients and Methods The medical records of fifty-seven patients with systemic lupus erythematosus (SLE) were reviewed retrospectively, and divided into three groups based on the dose of glucocorticoids at the time of discharge: group A (n=13), newly-diagnosed SLE patients taking more than 30 mg of prednisolone daily; group B (n=22), newlydiagnosed SLE patients taking less than 30 mg; and group C (n=22), patients with an established diagnosis taking more than 30 mg daily for the treatment of an exacerbation of symptoms. The development of infectious complications within two months after discharge was identified from a review of the medical records to determine the effect of glucocorticoid dose at the time of discharge on the subsequent development of infectious complications. Results Two patients in group A and three in group C developed infectious complications within two months following discharge, while no patients in group B contracted an infection. These included herpes zoster in group A (n=2) and herpes zoster, urinary tract infection and Pneumocystis jirovecii pneumonia in group C (n=3, one each). However, the incidence of infectious complications comparing groups A and B, and groups A and C was not statistically significantly different( p>0.05). There was no correlation between the incidence of infection and the total dose of glucocorticoids given during admission.Conclusion Although this study was retrospective and involved only a small number of patients with SLE, there is no increased risk of developing infectious complications in pa-tients receiving more than 30 mg of prednisolone daily at the time of hospital discharge, compared to those taking less than 30 mg. Based on these results, prolonging hospitalization only to reduce the dose of prednisolone to less than 30 mg daily lacks justifiable grounds, even if it has been a tacit consensus in Japan.
  • 大西 佐知子, 奈良 浩之, 水品 佳子, 長嶋 孝夫, 星野 東明, 上村 健, 吉尾 卓, 岡崎 仁昭, 簑田 清次 アレルギー 56 (3) 2007年04月 [査読無し][通常論文]
  • 釜田 康行, 岩本 雅弘, 青木 葉子, 長嶋 孝夫, 奈良 浩之, 上村 健, 吉尾 卓, 岡崎 仁昭, 簑田 清次 自治医科大学紀要 29 163 -167 2006年12月 [査読無し][通常論文]
     
    2005年1月から6月までにアレルギーリウマチ科に入院した100症例を対象とし,入院時と入院1週間後に血中Dダイマー値を測定した。Dダイマーレベルが高値またはその変化が大きかった症例と,下肢深部静脈血栓症(DVT)を疑わせる症状を有する症例について下肢静脈超音波検査を行い,DVTの有無を検査した。その結果,100例中5例にDVTを認めた。うち3例は入院前からDVTを発症しており,2例は入院中に新たにDVTを発症した。DVTがみつかった5症例は全例臨床症状を伴っていたが,臨床症状を伴っていてもDダイマーレベルが上昇していない症例は,下肢静脈超音波検査にてDVTは見られなかった。Dダイマーレベルの変化と臨床症状が見られた症例に対して下肢静脈超音波検査を行うことにより,効率的にDVTを診断できるものと考えられた。
  • 大西 佐知子, 長嶋 孝夫, 奈良 浩之, 上村 健, 釜田 康行, 岩本 雅弘, 吉尾 卓, 岡崎 仁昭, 簑田 清次 アレルギー 55 (8) 2006年09月 [査読無し][通常論文]
  • 長嶋 孝夫, 上村 健, 奈良 浩之, 岩本 雅弘, 岡崎 仁昭, 簑田 清次 アレルギー 54 (3) 2005年04月 [査読無し][通常論文]
  • 岡崎 仁昭, 長嶋 孝夫, 簑田 清次 日本臨床免疫学会会誌 = Japanese journal of clinical immunology 27 (6) 357 -360 2004年 [査読無し][通常論文]
     
    スタチン系薬物は高脂血症治療薬として現在,国内外で広く使用されている.   近年のスタチン系薬物を使用した大規模臨床試験によると,虚血性心疾患の初発と再発とを予防することが示されている.この動脈硬化性病変への効果は,必ずしもコレステロール低下作用だけに基づくものではないことが最近の研究成果から明らかとなってきた.すなわちスタチンは血清コレステロール低下作用以外にも多面的効果(pleiotropic effect)を有し,例えば,抗酸化作用,血管内皮細胞の分化増殖の促進とその機能障害の改善,血栓形成改善作用,抗炎症作用など直接的に冠動脈イベントなどの動脈硬化を抑制することが示されている.さらに,最近になってスタチンの多面的効果の一つとして,免疫抑制(調整)作用を示す報告が相次いでなされ,注目を浴びている.本稿ではスタチンの免疫系への作用について文献的考察を含めて概説し,最後に我々の研究結果の一部を紹介する.
  • 佐藤 英智, 平田 大介, 奈良 浩之, 長嶋 孝夫, 岡崎 仁昭, 岩本 雅弘, 吉尾 卓, 益山 純一, 上村 健, 狩野 庄吾, 蓑田 清次 アレルギー 49 (9) 2000年10月 [査読無し][通常論文]
  • 島野 靖正, 大野 修一, 本間 寿美子, 船山 いずみ, 柳場 悟, 宮田 幸雄, 丹波 嘉一郎, 間藤 尚子, 長嶋 孝夫, 平田 大介, 蓑田 清次, 浅野 泰 日本アフェレシス学会雑誌 19 (1) 64 -65 2000年02月 [査読無し][通常論文]
  • 金子 尚子, 三森 明夫, 馬場 聡, 奈良 浩之, 城田 祐子, 長嶋 孝夫, 平田 大介, 吉尾 卓, 岡崎 仁昭, 狩野 庄吾, 簑田 清次 リウマチ 40 (3) 633 -638 2000年 [査読無し][通常論文]
     
    A fifteen-year-old boy was admitted to our hospital because of lower abdominal pain, watery diarrhea and mucobloody stool. Two years before admission, he was diagnosed to have Still's disease presenting with polyarthritis, sore throat, remittent fever and typical skin rash. He had been treated with non- steroidal anti-inflammatory agents, oral prednisolone and low- dose methotrexate. Although he was almost free of symptoms during the next two years, serum C-reactive protein (CRP) levels continued to be elevated moderately. He began to complain of lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody diarrhea in June. Laboratory data on admission showed an elevated level of serum CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum revealed the deposition of amyloid protein of AA type, which confirmed the diagnosis of secondary amyloidosis. The dose of prednisolone was increased and dimethyl sulfoxide per os or rectum was instituted, which improved his gastrointestinal symptoms to some extent. However, fever, arthritis and diarrhea recurred along with tapered prednisolone dosage. In addition to gastro-intestinal symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to reflect general deposition of amyloid in his body. He is now on immunosuppressive agent and high-dose prednisolone. Several studies report the higher frequency of γ- allele of SAA 1 gene in the cases of rheumatoid arthritis with AA-amyloidosis than in those without. In the patient presented here, molecular biological analysis revealed that his SAA 1 gene was composed of β-and γ-allele. The presence of γ-allele in his SAA 1 gene might be one of the factors that predisposed him for generalized deposition of amyloid protein in such a short period of time.


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