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Masataka Umeda,
Keita Fujikawa,
Tomoki Origuchi, Toshiaki Tsukada,
Akira Kondo,
Shinya Tomari,
Yuichi Inoue,
Hisashi Soda,
Hideki Nakamura,
Shoko Matsui,
Atsushi Kawakami
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ABSTRACT: We report a 72-year-old man with respiratory involvement of immunoglobulin G4 (IgG4)-related disease, who developed dry cough and shortness of breath on effort. The chest computed tomography scan image showed massive and diffuse ground-glass opacity, interlobular thickening, and bronchial wall thickening. The infiltration of IgG4-positive plasma cells in the transbronchial lung biopsy and high serum IgG4 concentrations were found. The patient was treated with 0.6 mg/kg oral prednisolone and showed rapid improvement. This is a case of IgG4-related disease in which the only complication was respiratory involvement.
Modern Rheumatology 02/2012; · 1.58 Impact Factor
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Tomoki Origuchi,
Kazuhiko Arima,
Shin-Ya Kawashiri,
Mami Tamai,
Satoshi Yamasaki,
Hideki Nakamura, Toshiaki Tsukada,
Toshiyuki Aramaki,
Masako Furuyama,
Taiichiro Miyashita,
Yojiro Kawabe,
Nozomi Iwanaga,
Kaoru Terada,
Yukitaka Ueki,
Takaaki Fukuda,
Katsumi Eguchi,
Atsushi Kawakami
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ABSTRACT: Recently, it was reported that remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome could be complicated with solid tumors. In a retrospective, multicenter study between October, 2003 and September, 2010, we investigated the characteristics of patients with paraneoplastic RS3PE syndrome who fulfilled following criteria: (1) bilateral pitting edema of hands or feet or both, (2) sudden onset of polyarthritis, and (3) age >50 years, (4) seronegativity for rheumatoid factor (RF). A total of 33 cases fulfilled the above criteria. Eight patients (seven men and one woman) developed cancer within 2 years of RS3PE syndrome onset. There was no significant difference between the neoplastic and nonneoplastic groups in the proportions of patients with fever, symmetrical polyarthritis, pitting edema, and good response to corticosteroids. Serum matrix metalloproteinase 3 (MMP-3) level (median 437.3 ng/ml) in the paraneoplastic RS3PE patients was significantly higher than that in patients without neoplasia (median 114.7 ng/ml) (p < 0.05). We found that high serum MMP-3 is characteristic of patients with paraneoplastic RS3PE syndrome.
Modern Rheumatology 11/2011; 22(4):584-8. · 1.58 Impact Factor
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Junko Kita,
Mami Tamai,
Kazuhiko Arima,
Yoshikazu Nakashima,
Takahisa Suzuki,
Shin-ya Kawashiri,
Akitomo Okada,
Tomohiro Koga,
Satoshi Yamasaki,
Hideki Nakamura,
Tomoki Origuchi,
Toshiyuki Aramaki,
Munetoshi Nakashima,
Keita Fujikawa, Toshiaki Tsukada,
Hiroaki Ida,
Kiyoshi Aoyagi,
Masataka Uetani,
Katsumi Eguchi,
Atsushi Kawakami
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ABSTRACT: We aimed to investigate whether delayed treatment with tumor necrosis factor (TNF) inhibitors in incomplete responders to synthetic disease-modifying anti-rheumatic drugs (DMARDs) was effective among patients with very early rheumatoid arthritis (RA) with poor prognosis factors. We examined 22 patients with very early RA who were positive for anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. The mean disease duration at entry was 14.1 weeks. A treat-to-target strategy, aiming at simplified disease activity index (SDAI) remission, was initiated with synthetic DMARDs. SDAI remission was not achieved in 9 of the 22 patients with synthetic DMARDs alone, and TNF inhibitors were added in these patients. SDAI values in these 9 patients were further examined for the following 6 months. The TNF inhibitors (infliximab 8, etanercept 1) were added at a mean interval of 34.1 weeks after the initiation of synthetic DMARDs. SDAI remission was achieved in 4 of the 9 patients (44.4%) at 3 months and in 8 of the 9 patients (88.9%) at 6 months after the introduction of the TNF inhibitors. Radiographic damage had not progressed in these patients. Delayed treatment with TNF inhibitors is effective and tolerable for patients with very early RA with poor prognosis factors.
Modern Rheumatology 09/2011; 22(2):195-201. · 1.58 Impact Factor
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Shintaro Hara,
Tomoko Henmi,
Atsushi Kawakami,
Keita Fujikawa,
Hiroshi Mukae,
Yuji Ishimatsu,
Noriho Sakamoto,
Tomoyuki Kakugawa,
Kenzou Kaji,
Manabu Fujimoto, [......], Toshiaki Tsukada,
Katsuya Satoh,
Masakatsu Motomura,
Mami Tamai,
Hideki Nakamura,
Hiroaki Ida,
Tomayoshi Hayashi,
Tomoki Origuchi,
Katsumi Eguchi,
Shigeru Kohno
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ABSTRACT: We report the first 3 cases of inflammatory myopathy with abundant macrophages (IMAM) to be found in an Asian country. Diagnosis of IMAM was based on the infiltration of CD68+ macrophages into biopsied specimens, particularly the fascia. Proximal skeletal muscle symptoms and signs, elevation of creatine kinase, and myogenic changes in electromyography were found in all of the cases, and magnetic resonance imaging clearly revealed thickening of the fascia. Since dermatomyositis (DM)-specific skin alterations were not found, none of the patients in this study fulfilled Bohan and Peter's criteria for DM; however, anti-PL-7 antibody was detected in case number 1. In addition, CD20+ B-cell infiltration into the fascia was also detected in all of the cases, indicating further transition to DM. Severe illness, namely macrophage activation syndrome and acute respiratory distress syndrome, occurred in case 1 but was resolved with intensive combination therapy. The other 2 cases also required glucocorticoids to achieve remission.
Rheumatology International 12/2010; · 1.88 Impact Factor
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Kunihiro Ichinose,
Tomoki Origuchi,
Shin-ya Kawashiri,
Naoki Iwamoto,
Keita Fujikawa,
Toshiyuki Aramaki,
Makoto Kamachi,
Kazuhiko Arima,
Mami Tamai,
Hideki Nakamura,
Hiroaki Ida,
Atsushi Kawakami, Toshiaki Tsukada,
Yukitaka Ueki,
Katsumi Eguchi
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ABSTRACT: Mizoribine (MZR) is an immunosuppressant that inhibits nucleic acid metabolism and is a relatively safe disease-modifying anti-rheumatic drug (DMARD). We evaluated the efficacy and safety of one single dose per day for patients with rheumatoid arthritis (RA).
In this study 32 patients with RA received MZR therapy. We evaluated the average dose of MZR and prednisolone, response to treatment and peak plasma level of MZR.
The average dose of MZR was 146.1±31.2 (range: 50-200) mg/day. The average dose of prednisolone was 4.63±3.59 (range: 0-14) mg/day. The average plasma level of MZR, measured after 3 hours, was 2.20±0.49 µg/mL in the responder group and 1.59±0.82 µg/mL in the non-responder group (p=0.020). The treatment with MZR for 24 weeks was completed by 71.9% of patients and the proportion of patients who achieved a good and moderate response rate according to the European League Against Rheumatism (EULAR) criteria was 56.3% at 24 weeks. The plasma level of MZR which was greater than or equal to 2.12 µg/mL was significantly correlated with the clinical response (p<0.01). Only one of thirty-two cases discontinued the treatment, because of skin eruption.
This study included patients that could not be treated with other DMARDs and/or biologic agents because of age, interstitial pneumonia and other complications. We show that MZR may be a useful and relatively safe therapy for patients in this group.
Internal Medicine 01/2010; 49(20):2211-8. · 0.94 Impact Factor
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Naoki Iwamoto,
Atsushi Kawakami,
Keita Fujikawa,
Toshiyuki Aramaki,
Shin-Ya Kawashiri,
Mami Tamai,
Kazuhiko Arima,
Kunihiro Ichinose,
Makoto Kamachi,
Satoshi Yamasaki, [......], Toshiaki Tsukada,
Kiyoshi Migita,
Fumiko Shoumura,
Yojiro Kawabe,
Kazutaka Shibatomi,
Masanobu Mine,
Hiroaki Ida,
Tomoki Origuchi,
Kiyoshi Aoyagi,
Katsumi Eguchi
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ABSTRACT: We tried to determine which baseline variables are responsible for remission induction at 6 months in unselected rheumatoid arthritis (RA) patients of Japanese population treated with etanercept. One hundred forty-one patients with RA who were administered etanercept were registered. Thirty-four patients were started on etanercept monotherapy, 60 patients on cotherapy with methotrexate (MTX) (MTX cotherapy), and 47 patients on cotherapy with other non-MTX nonbiologic disease-modifying antirheumatic drugs (DMARDs) (non-MTX cotherapy). None of the patients were treated with both MTX and non-MTX nonbiologic DMARDs at entry. Outcome was set as achievement of disease activity score 28 (DAS28)-ESR remission at 6 months. We examined association of gender, DAS at baseline, MTX cotherapy at baseline, non-MTX cotherapy at baseline, and prednisolone use at baseline with achievement of remission at 6 months by logistic regression analysis. All subjects were classified as having high (N = 109) or moderate disease activity (N = 32) at entry. One hundred twenty out of 141 patients (85.1%) continued treatment with etanercept at 6 months. Continuation rate was statistically higher in MTX cotherapy (93.3%) compared with etanercept monotherapy (73.5%), and tended to be higher than with non-MTX cotherapy (85.1%). Logistic regression analysis identified that MTX cotherapy at entry and moderate disease activity at entry were independent variables for remission induction at 6 months. Accordingly, DAS28-ESR at 6 months was significantly lower with MTX cotherapy as compared with etanercept monotherapy or non-MTX cotherapy. To a lesser extent, DAS28-ESR with non-MTX cotherapy at 6 months was lower than with etanercept monotherapy. In this study of unselected patients, use of MTX and moderate disease activity at entry were associated with higher likelihood of response to etanercept. Non-MTX nonbiologic DMARDs may be an alternative in RA patients administrated etanercept who are intolerant to MTX.
Modern Rheumatology 08/2009; 19(5):488-92. · 1.58 Impact Factor
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ABSTRACT: In MDCK cells, hepatocyte growth factor/scatter factor (HGF/SF) induces epithelial cell dissociation, scattering, migration, growth and formation of branched tubular structures. By contrast, these cells neither scatter nor form tubular structures in response to the epidermal growth factor (EGF) family of growth factors. Heparin-binding EGF-like growth factor (HB-EGF) is a member of the EGF family of growth factors and is synthesized as a membrane-associated precursor molecule (proHB-EGF). ProHB-EGF is proteolytically cleaved to release a soluble ligand (sHB-EGF) that activates the EGF receptor. Although recent studies suggest possible physiological functions, the role of proHB-EGF remains largely undefined. Using MDCK cells stably expressing proHB-EGF, a noncleavable deletion mutant of proHB-EGF or soluble HB-EGF, we show that epithelial cell functions differ depending on the form of HB-EGF being expressed. Expression of noncleavable membrane-anchored HB-EGF promoted cell-matrix and cell-cell interactions and decreased cell migration, HGF/SF-induced cell scattering and formation of tubular structures. By contrast, expression of soluble HB-EGF induced increased cell migration, decreased cell-matrix and cell-cell interactions and promoted the development of long unbranched tubular structures in response to HGF/SF. These findings suggest that HB-EGF can not only modulate HGF/SF-induced cellular responses in MDCK cells but also that membrane-bound HB-EGF and soluble HB-EGF give rise to distinctly different effects on cell-cell and cell-extracellular matrix interactions.
Journal of Cell Science 04/2004; 117(Pt 8):1365-79. · 6.11 Impact Factor
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昇 高村,
勝美 江口,
清志 右田,
敏昭 塚田,
明成 溝上,
智樹 折口,
重信 長瀧,
雅浩 泉,
卓 中村,
Noboru Takamura,
Katsumi Eguchi,
Kiyoshi Migita, Toshiaki Tsukada,
Akinari Mizokami,
Tomoki Origuchi,
Shigenobu Nagataki,
Masahiro Izumi,
Takashi Nakamura
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ABSTRACT: 肺門部リンパ節腫脹,間質性肺炎,間質性腎炎を合併したSjogren症候群の男性症例を経験した.症例は60歳男性で, 57歳時人間ドックで高γグロブリン血症を指摘された.主訴は全身倦怠感と発熱で当科に入院した.胸部X線とCT検査で肺門部リンパ節腫脹と間質性肺炎の所見が得られた.入院9カ月前より両眼ぶどう膜炎あり,サルコイドーシスが疑われたが, ACE, リンパ節生検と肺生検から否定された.高γグロブリン血症と抗核抗体陽性からSjogren症候群が疑われたが,眼・口腔乾燥症状はなかった. Schirmerテストとrose bengalテスト陽性から乾燥性角結膜炎があり,小唾液腺生検では単核球の著しい浸潤が認められた. 耳下腺MRI所見では, T1およびT2強調画像で多数の点状の高信号域のため不均一となっており,耳下腺組織の破壊が高度で脂肪変性をきたしていると診断した. 腎生検所見では間質・尿細管の病変が著明でいわゆるtubulo-interstitial nephritisを示した. 本症例は男性で潜在型Sjogren症候群であり,耳下腺MRI所見が本症の診断に有用であった.本検査は侵襲が少なく, Sjogren症候群の診断法の1つとして繁用されることが期待される Here we report a case of primary Sjogren's syndrome with hilar lymphadenopathy, interstitial pneumonitis and interstitial tubulo-nephritis. A 60-year old man was admitted to our hospital in May 1993 because of general fatigue and fever.He was noted to have hypergammaglobulinemia and had positive antibodies to nuclear antigens since 1990 in the absence of clinical manifestations. Since 9 months before admission, he presented with general fatigue, low grade fever and uveitis.On admission, chest X-ray and CT scan showed bilateral hilar lymphadenopathy and interstitial pneumonitis. The negative results for both serum angiotensin converting enzyme and histological findings of the cervical lymph node and the lung excluded the diagnosis of sarcoidosis. Serological examination exhibited marked elevation of polyclonal IgG leveland anti-nuclear antibody, but neither anti-SS-A(Ro) nor anti-SS-B(La) antibody was detected. He did not have symptoms of xerophthalmia and xerostomia. Keratoconjunctivitis sicca was diagnosed by positive Schirmer's and rose bengal tests. His labial glandbiopsy demonstrated severe mononuclear cell infiltration around the ducts. MRI findings ofthe parotid glands revealed heterogenous and dotted high signal intensity similar to those in fat tissues in the T1-and T2-weighted images. These findings depicted that bilateral parotid gland was extensively destructed and was replaced by lipid tissue. Renal biopsy showed interstitial tubulo-nephritis. On the basis of the above findings, he was diagnosed to have primary Sjogren's syndrome and uveitis. Therefore, MR image of the parotid gland is considered to be a noninvasive and useful method for diagnosis of Sjogren's syndrome
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ABSTRACT: Oxidative stress is a potent inducer of apoptosis and activates protein tyrosine kinases and cytokine receptors, such as the epidermal growth factor receptor (EGFR). Previous studies suggest that cytokine receptors are potential effectors for anti-apoptotic signals, but it has not previously been determined whether cytokine receptors regulate down-stream protein kinases. To investigate the role of EGFR on oxidative stress-induced apoptosis and its downstream protein kinases, we blocked EGFR activation with Tyrphostin AG1478, a highly selective EGFR inhibitor. We determined that Tyrphostin AG1478 accelerated hydrogen peroxide-induced apoptosis in A431 cells, with activation of caspases 3 and 9, and decreased mitochondrial membrane potential. Hydrogen peroxide induced-activation of EGFR, Akt/PKB, MAPK, and Bad (both Ser-112 and Ser-136 residues) were inhibited by Tyrphostin AG1478. These results suggest that early upstream signaling events, such as EGFR activation, exert anti-apoptotic effects by regulating MAPK, Akt/PKB, and phosphorylation of Bad
