研究者詳細 - 竹内　勤

論文 - 竹内　勤

分割表示 514 件中 381 - 400 件目／全件表示 >>

Messenger ribonucleic acid expression profile in peripheral blood cells from RA patients following treatment with an anti-TNF-α monoclonal antibody, infliximab

Sekiguchi N., Kawauchi S., Furuya T., Inaba N., Matsuda K., Ando S., Ogasawara M., Aburatani H., Kameda H., Amano K., Abe T., Ito S., Takeuchi T.

Rheumatology 47 （ 6 ） 780 - 788 2008年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1462-0324

Objectives. We monitored the mRNA expression profiles of peripheral blood cells during treatment with a TNF-α inhibitor, infliximab, in patients with RA. Using a DNA microarray analysis, we demonstrated a unique set of genes, with distinct baseline and post-treatment changes in expression between responders and non-responders to infliximab treatment. Methods. Using a customized low-density cDNA microarray with 747 genes and a reliable data collection system, we monitored the mRNA expression profiles of whole blood cells from 18 RA patients before and after the infusion of infliximab for up to 22 weeks. The clinical response to treatment with infliximab was determined using the ACR response criteria, the disease activity score of 28 joints (DAS28), and individual clinical parameters. The patients were classified as responders or non-responders based on their ACR50% response at 22 weeks. Results. Approximately 15% of the total genes were found to exhibit a >1.5-fold change, compared with their reference values, at one or more time points during the 22 weeks of infliximab therapy. The expression of inflammatory genes, such as IFN-related genes, was strongly correlated with the serum level of CRP and the DAS28. The increased expression of inflammatory genes in responders was normalized within 2 weeks and then remained at a normal level during the treatment period. In contrast, in the non-responders, the elevated expression at baseline, although it was significantly decreased at 2 weeks, returned to the baseline level after 14 weeks. In addition to inflammatory genes, we identified several groups of genes with distinct differences in expression between the responders and non-responders. Conclusions. Our results suggest that a customized low-density microarray is useful for monitoring mRNA expression profiles in peripheral blood cells, enabling us to identify a unique set of genes with differentially regulated expressions in responders and non-responders to a TNF inhibitor among patients with RA. © The Author 2008. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Access to Document (DOI)

Severe degenerative change of multiple organs mediated by chronic active Epstein-Barr virus infection with infected T-cell expansion

Tokuhira Michihide, Iizuka Atsushi, Watanabe Reiko, Sekiguchi Naoya, Sato Norihide, Chien Chen Kang, Sekiguchi Yasunobu, Nemoto Tomoe, Hanzawa Kyoko, Tamaru Jun Ichi, Itoyama Shinji, Suzuki Hiroshi, Takeuchi Tsutomu, Mori Shigehisa, Kizaki Masahiro

International Journal of Hematology 87 （ 5 ） 520 - 526 2008年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0925-5710

We here report the case of a young Japanese woman diagnosed with chronic active Epstein-Barr virus (EBV) infection. Intensive therapy with the CHOP regimen was partially able to control virus expansion, but various central nervous system symptoms appeared and gradually progressed. EBV-encoded RNA, detected using in situ hybridization, disclosed the presence of EBV in liver and bone marrow tissue, and real-time PCR revealed the presence of EBV in the cerebrospinal fluid (CSF) and serum. CD3+CD4+CD8-CD56- T-cell expansion in the peripheral blood (PB) and CSF was also observed. Atrophic brain changes were progressive, and the patient died of central nervous system disturbance and pulmonary hemorrhage a year after diagnosis. Autopsy revealed that EBV-infected T lymphocytes with a phenotype similar to those seen in PB and CSF had infiltrated multiple organs: the lymph nodes, bone marrow, endocardium, pericardium, myocardium, spleen, liver, and spinal cord. There have been few previous reports of severe degenerative changes in the myocardium, liver, and spinal cord in patients with EBV infection. Although EBV occasionally infiltrates the central nervous system and brain, atrophic changes mediated by EBV are rare. The autopsy results of this case suggest the possibility of EBV-mediated, severe degenerative changes in multiple organs. © 2008 The Japanese Society of Hematology.

Access to Document (DOI)

Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan

Tanaka Yoshiya, Takeuchi Tsutomu, Inoue Eisuke, Saito Kazuyoshi, Sekiguchi Naoya, Sato Eri, Nawata Masao, Kameda Hideto, Iwata Shigeru, Amano Kouichi, Yamanaka Hisashi

Modern Rheumatology 18 （ 2 ） 146 - 152 2008年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

Biologics targeting TNF have brought about a paradigm shift in the treatment of rheumatoid arthritis (RA) and infliximab, anti-TNF-α chimeric monoclonal antibody, was marketed in 2003 in Japan. We previously reported on the RECONFIRM study, a retrospective clinical study on the efficacy of infliximab therapy in a RA management group in Japan, where we evaluated the clinical response after 22 weeks of the therapy in 258 patients. The study reported here was aimed at reconfirming the clinical efficacy of the infliximab therapy and demographic factors related to the efficacy over a 54-week study period in 410 RA patients in the same study group. Infliximab was infused according to the domestically approved method, and the clinical response was evaluated following 54 weeks of infliximab therapy using the European League Against Rheumatism (EULAR) response criteria. Disease activity was assessed by DAS28-CRP (Disease Activity Score including a 28-joint count/C-reactive protein). Infliximab was discontinued in 24.4% of the 410 patients at 54 weeks and 9.3% and 8.1% discontinued the therapy due to adverse events and inefficiency, respectively. Average DAS28-CRP decreased from 5.5 at week 0 to 3.1 at week 54 after the therapy. Patients in remission and those showing low-, moderate-, and high-disease activity changed from 0.0, 1.0, 9.0 and 90.0%, respectively, at the start of the study to 27.6, 11.7, 34.4 and 26.3%, respectively, at week 54. Younger age, RF-negativity and low scores of DAS28-CRP showed significant correlations with remission at week 54. EULAR response criteria - good, moderate, and no response to infliximab - were 37.0, 41.7 and 21.2%, respectively. In conclusion, we reconfirmed the clinical efficacy of infliximab and demographic factors related to the efficacy over a 54-week study period in 410 Japanese patients with RA using DAS28-CRP and EULAR response criteria. © Japan College of Rheumatology 2008.

Access to Document (DOI)

Molecular effects to human regulatory T cells by treatment with T cell activation inhibitor and TNF blockade

竹内勤

FASEB Journal 22 S626 - S627 2008年04月

研究論文（国際会議プロシーディングス）, 共著, 査読有り, ISSN 0892-6638

Conservative sequences in 3′UTR of TCRζ mRNA regulate TCRζ in SLE T cells

Tsuzaka Kensei, Itami Yuka, Kumazawa Chika, Suzuki Miyuki, Setoyama Yumiko, Yoshimoto Keiko, Suzuki Katsuya, Abe Tohru, Takeuchi Tsutomu

Biochemical and Biophysical Research Communications 367 （ 2 ） 311 - 317 2008年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0006-291X

We have demonstrated that T-cell receptor ζ (ζ) mRNA with a 562-bp deleted alternatively spliced 3′-untranslated region (3′UTR) observed in T cells of patients with systemic lupus erythematosus (SLE) can lead to a reduction in ζ and TCR/CD3 (J. Immunol., 2003 & 2005). To determine the region in ζ mRNA 3′UTR for the regulation of ζ, ζ mRNA with 3′UTR truncations ligated into pDON-AI was used to infect murine T-cell hybridoma MA5.8 cells, which do not contain ζ. As a Western blot analysis demonstrated the importance of the regions from +871 to +950, containing conservative sequence 1 (CS1), and +1070 to +1136, containing CS2, for the production of ζ, we constructed MA5.8 mutants carrying ζ mRNA 3′UTR with deletions of these regions (ΔCS1 and ΔCS2 mutants). Western blot and FACS analyses showed significant reduction in the cell surface ζ and TCR/CD3 in both these mutants, and IL-2 production was decreased, compared with MA5.8 cells transfected with wild-type ζ mRNA. Furthermore, real-time PCR demonstrated the instability of ζ mRNA with 3′UTR deletions in these MA5.8 mutants. In conclusion, CS1 and CS2 may be responsible for the regulation of ζ and TCR/CD3 through the stability of ζ mRNA in SLE T cells. © 2007 Elsevier Inc. All rights reserved.

Access to Document (DOI)

Postmarketing surveillance of the safety profile of infliximab in 5000 Japanese patients with rheumatoid arthritis

Takeuchi Tsutomu, Tatsuki Y., Nogami Y., Ishiguro N., Tanaka Y., Yamanaka H., Kamatani N., Harigai M., Ryu J., Inoue K., Kondo H., Inokuma S., Ochi T., Koike T.

Annals of the Rheumatic Diseases 67 （ 2 ） 189 - 194 2008年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0003-4967

Objectives: A large-scale postmarketing surveillance (PMS) study was carried out to determine the safety profile of infliximab in Japanese patients with rheumatoid arthritis (RA). Methods: The PMS study was performed for all patients with RA who were treated with infliximab. They were consecutively registered in the PMS study at the initiation of infliximab treatment and were prospectively monitored with all adverse events noted for a period of 6 months. All case reports, which include safety-related events, were collected monthly. Results: Adverse drug reactions (ADRs) were assessed for 6 months in 5000 patients who were consecutively enrolled in the PMS study. The incidence rates of total and serious ADRs were 28.0% and 6.2%, respectively. "Infections" or "respiratory disorders" were most commonly observed among serious ADRs. Bacterial pneumonia developed in 2.2%, tuberculosis in 0.3%, suspected Pneumocystis jiroveci pneumonia (PCP) in 0.4% and interstitial pneumonitis in 0.5%. Bacterial pneumonia (for which individuals of male gender, of older age and those with advanced rheumatoid arthritis and comorbid respiratory disease were most at risk) began to develop immediately after the start of treatment, while tuberculosis, PCP and interstitial pneumonitis developed about 1 month later. Serious infusion reactions were observed in 0.5% and were more likely to occur in patients who had participated in previous clinical trials of infliximab. Conclusion: This postmarketing surveillance study of patients treated with infliximab showed that infliximab in combination with low-dose MTX was well tolerated in Japanese patients with active RA.

Access to Document (DOI)

Interaction of KLRG1 with E-cadherin

Rosshart Stephan, Hofmann Maike, Schweier Oliver, Pfaff Anne Kathrin, Yoshimoto Keiko, Takeuchi Tsutomu, Molnar Eszter, Schamel Wolfgang W., Pircher Hanspeter

European Journal of Immunology 38 （ 12 ） 3354 - 3364 2008年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0014-2980

The killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor expressed by memory T cells and NK cells in man and mice. It is frequently used as a cell differentiation marker and members of the cadherin family are ligands for KLRG1. The present study provides new insights into the interaction of mouse KLRG1 with E-cadherin. Firstly, we demonstrate that co-engagement of KLRG1 and CD3/TCR in a spatially linked manner was required for inhibition arguing against the notion that KLRG1-ligation per se transmits inhibitory signals. Secondly, experiments with T cells carrying Y₇F-mutant KLRG1 molecules with a replacement of the tyrosine residue to phenylalanine in the single ITIM indicated that the inhibitory activity of KLRG1 is counteracted to some degree by increased interaction of KLRG1⁺ T cells with E-cadherin expressing target cells. Thirdly, we demonstrate that deletion of the first or the second external domain of E-cadherin abolished reactivity in KLRG1-reporter cell assays. Finally, we made the intriguing observation that KLRG1 formed multimeric protein complexes in T cells in addition to the previously described mono- and dimeric molecules. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

Access to Document (DOI)

Retrospective clinical study on the notable efficacy and related factors of infliximab therapy in a rheumatoid arthritis management group in Japan

Takeuchi Tsutomu, Yamanaka Hisashi, Inoue Eisuke, Nagasawa Hayato, Nawata Masao, Ikari Katsunori, Saito Kazuyoshi, Sekiguchi Naoya, Sato Eri, Kameda Hideto, Iwata Shigeru, Mochizuki Takeshi, Amano Kouichi, Tanaka Yoshiya

Modern Rheumatology 18 （ 5 ） 447 - 454 2008年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

The anti-TNF-α chimeric monoclonal antibody infliximab is the first biologic to be approved for rheumatoid arthritis (RA) in Japan, and post-marketing surveillance of all of the Japanese cases treated with infliximab has been conducted to explore the safety of infliximab therapy. In addition, a retrospective clinical study on the notable efficacy and related factors of infliximab therapy in an RA management group in Japan (RECONFIRM and RECONFIRM-2) has demonstrated clinical responses. However, information on the effect of infliximab on joint destruction in Japanese RA patients remains insufficient. In this study, we retrospectively analyzed X-ray data from 67 patients in whom both hand and foot X-rays at baseline and at 54 weeks had been available among the 410 cases in the RECONFIRM-2 study. By scoring the X-rays according to the modified van der Heijde (vdH)-Sharp method, we found that the total vdH-Sharp score in the RA patients before infliximab therapy was 104.40 ± 87.34 and the yearly progression was 21.33, indicating relatively rapid progression. After infliximab therapy for 54 weeks, the total vdH-Sharp score at 54 weeks was 104.37 ± 86.87 and the estimated yearly progression was -0.03, indicating the almost complete inhibition of progression. The RECONFIRM-2J study confirmed the significant ability of infliximab to halt joint destruction in Japanese RA patients, and showed that joint destruction was significantly associated with disease activity and the dose of MTX in the patients with moderate and advanced disease durations, respectively, before infliximab therapy. © Japan College of Rheumatology 2008.

Access to Document (DOI)

Proposals for leflunomide use to avoid lung injury in patients with rheumatoid arthritis

Inokuma Shigeko, Sato Takeo, Sagawa Akira, Matsuda Takemasa, Takemura Tamiko, Ohtsuka Takeshi, Saeki Yukihiko, Takeuchi Tsutomu, Sawada Tetsuji

Modern Rheumatology 18 （ 5 ） 442 - 446 2008年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

Among the 5,043 consecutive patients registered in the postmarketing surveillance for leflunomide, 61 were reported to have lung injury and 24 died from it. The adjusted multivariate logistic regression analysis of the risk factors showed that preexisting interstitial lung disease posed the greatest risk, as well as loading dose, smoking history, and low body weight of 40 kg or less with odds ratios of 8.17, 3.97, 3.12, and 2.91, respectively. In 12 patients, lung injury developed even 2 months after leflunomide withdrawal. When patients with (n = 9) and without (n = 13) fatal outcome were compared, eight out of the former, and six out of the latter had preexisting interstitial lung disease; the former showed severe hypoxemia, high serum C-reactive protein level, hypoalbuminemia, and continuous lymphocytopenia, and required mechanical ventilation. On the basis of these results and literature review, the committee proposes that leflunomide should only be recommended as a second-line drug, should not be administered to patients with preexisting interstitial lung disease, should also not be administered to patients with smoking history or those with low body weight, and should be administered without loading dose. Careful monitoring is necessary, and when lung injury develops, leflunomide elimination using colestyramine is mandatory. © Japan College of Rheumatology 2008.

Access to Document (DOI)

Clinical and radiological features of Pneumocystis pneumonia in patients with rheumatoid arthritis, in comparison with methotrexate pneumonitis and Pneumocystis pneumonia in acquired immunodeficiency syndrome: A multicenter study

竹内勤

Internal Medicine 47 （ 10 ） 915 - 923 2008年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0918-2918

Access to Document (DOI)

Update on the Japanese guidelines for the use of infliximab and etanercept in rheumatoid arthritis

Koike Ryuji, Takeuchi Tsutomu, Eguchi Katsumi, Miyasaka Nobuyuki

Modern Rheumatology 17 （ 6 ） 451 - 458 2007年12月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

Application of biological agents targeting tumor necrosis factor-α (TNF-α) caused a paradigm shift in the treatment of rheumatoid arthritis (RA). The introduction of infliximab in 2003 and etanercept in 2005 in Japan had a significant impact on both Japanese rheumatologists and RA patients, although serious adverse effects such as bacterial pneumonia, tuberculosis and Pneumocystis jiroveci pneumonia are significant concerns. Based on the data from post-marketing surveillance in Japan and accumulating evidence worldwide, the Internal Medicine Rheumatology Study Group of the Ministry of Health, Labor and Welfare (MHLW), Japan, has updated the guidelines for the use of anti-TNF-α agents for RA, which were subsequently approved by the Board of Japan College of Rheumatology (JCR). In the present revised guidelines, we combined the guidelines for use of each of infliximab and etanercept together with some modifications and precautions, paying special attention to serious adverse reactions. Although it is still controversial whether the use of TNF-α blocking agents per se increases the risk of infection or not, bacterial pneumonia, regardless of the pathogens, is the most frequent complications in RA. The risk factors associated with pneumonia identified in the post-marketing surveillance of infliximab in Japan are presented in this guideline. The diagnostic algorithm is also designed for early diagnosis and treatment of pulmonary lesions seen during the treatment of biological agents. Preventive measures and precautions against tuberculosis, another frequent and significant complication in Japan, are also described. Furthermore, risk factors for developing Pneumocystis pneumonia, which uniquely occurs at 30- to 50-fold frequency under TNF-α blockade therapy in Japan, are described here and its preventive measures are discussed. It is stressed that secondary-care rheumatologists should be better familiarized with the proper use of TNF-α blocking agents and be alert to any adverse events for a better management of RA patients. © Japan College of Rheumatology 2007.

Access to Document (DOI)

Clinical significance of elevated serum levels of matrix metalloproteinase-3 and C-reactive protein in patients with rheumatoid arthritis

Nagasawa Hayato, Kameda Hideto, Amano Koichi, Takeuchi Tsutomu

APLAR Journal of Rheumatology 10 （ 4 ） 295 - 299 2007年12月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0219-0494

Aim: Serum levels of C-reactive protein (CRP) and matrix metalloproteinase-3 (MMP-3) are used as indicators of the activity of rheumatoid arthritis (RA). The aim of this study was to characterize the clinical features of patients showing exclusive elevation of either serum CRP or MMP-3, and the differences in the time-course of changes between the serum levels of MMP-3 and CRP after initiation of therapy. Methods: A total of 129 RA patients were classified into four groups according to the serum levels of CRP and MMP-3 at the time of enrolment: Negative for both CRP and MMP-3 levels; positive for both; positive for CRP alone (CRP-positive group); and positive for MMP-3 alone (MMP-3-positive group). The analysis included evaluation of the serum CRP and MMP-3 levels, and the Lansbury Articular Index at enrolment and at final observation. Results: In the CRP-positive group (19%), 21% of the patients remained CRP-positive at the final observation; 42% became double-negative, and 31% became double-positive. In contrast, in the MMP-3-positive group (9%), about two-thirds of the patients remained MMP-3-positive at the final observation. The disease duration in the MMP-3-positive group was significantly longer, and the ratio of the number of large swollen joints to the total number of swollen joints was higher as compared with that in the other groups. Furthermore, elevated serum CRP responded faster to disease-modifying antirheumatic drug therapy than elevated serum MMP-3. Conclusions: Serum CRP is a better predictor of the response to treatment than serum MMP-3, which is associated to a greater extent with large joint involvement. © 2007 Asia Pacific League of Associations for Rheumatology.

Access to Document (DOI)

Down-regulation of Fas-ligand mRNA in Sjögren's syndrome patients with enlarged exocrine glands

Tsuzaka Kensei, Matsumoto Yukihiro, Sasaki Yasumasa, Abe Tohru, Tsubota Kazuo, Takeuchi Tsutomu

Autoimmunity 40 （ 7 ） 497 - 502 2007年11月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0891-6934

We have reported that Sjögren's syndrome (SS) patients with enlarged exocrine glands (EEG) formerly referred to as Mikulicz's disease were defective with Fas-ligand (FasL) expression in PBL and lacrimal glands (LGs). To investigate the mechanisms of reduced FasL expression in SS patients with EEG, FasL mRNA expression level was determined using real-time PCR. The FasL gene promoter region (from -1197 to -3) was also amplified using PCR and specific primers. Expression of the FasL mRNA in the LGs and PBLs of three SS patients with EEG was significantly decreased. Direct sequencing revealed a heterozygous point mutation (-259T/C) in the FasL gene promoter region in one SS patient with EEG. A luminescent β-galactosidase (β-gal) reporter assay using a pβgal Enhancer Vector demonstrated that β-gal activity from the vector including the mutant (-259C) FasL (pβgal/mFasL) gene promoter region (735±42) was similar (p = 0.13) to that from a pβgal Enhancer Vector without the gene promoter region (603±66). On the other hand, the β-gal activity was significantly lower (p<0.0001) than that from a vector including the wild-type (-259T) FasL (pbeta;gal/wFasL) (3226±148). In conclusion, the down-regulation of FasL in SS patients with EEG may be due to transcriptional regulation, and the point mutation at -259T/C in the FasL gene promoter region may lead to the down-regulation of FasL mRNA expression and the lymphoproliferative process observed in SS patients with EEG.

Access to Document (DOI)

Study of active controlled monotherapy used for rheumatoid arthritis, an IL-6 inhibitor (SAMURAI)

Nishimoto Norihiro, Hashimoto Jun, Miyasaka Nobuyuki, Yamamoto Kazuhiko, Kawai Shinichi, Takeuchi Tsutomu, Murata Norikazu, Van Heijde Desiree Der, Kishimoto Tadamitsu

Annals of the Rheumatic Diseases 66 （ 9 ） 1162 - 1167 2007年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0003-4967

Objective: To evaluate the ability of tocilizumab (a humanised anti-IL-6 receptor antibody) monotherapy to inhibit progression of structural joint damage in patients with RA. Methods: In a multi-centre, x ray reader-blinded, randomised, controlled trial, 306 patients with active RA of <5 years' duration were allocated to receive either tocilizumab monotherapy at 8 mg/kg intravenously every 4 weeks or conventional disease-modifying antirheumatic drugs (DMARDs) for 52 weeks. Radiographs of hands and forefeet were scored by the van der Heijde modified Sharp method. Results: Patients had a mean disease duration of 2.3 years and a disease activity score in 28 joints of 6.5 at baseline. Mean total modified Sharp score (TSS) was 29.4, which was very high despite the relatively short disease duration. At week 52, the tocilizumab group showed statistically significantly less radiographic change in TSS (mean 2.3; 95% CI 1.5 to 3.2) than the DMARD group (mean 6.1; 95% CI 4.2 to 8.0; p<0.01). Tocilizumab monotherapy also improved signs and symptoms. The overall incidences of AEs were 89% and 82% (serious AEs: 18% and 13%; serious infections: 7.6% and 4.1%) in the tocilizumab and DMARD groups, respectively. Conclusion: Tocilizumab monotherapy was generally well tolerated and provided radiographic benefit in patients with RA.

Access to Document (DOI)

The importance of biochemical markers of bone and cartilage turnover as the predictors of radiographic progression in patients with early rheumatoid arthritis

竹内勤

Journal of Bone and Mineral Resaerch 22 S472 - S472 2007年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0884-0431

Lymphomatoid granulomatosis and diffuse alveolar damage associated with methotrexate therapy in a patient with rheumatoid arthritis

竹内勤

Clinical Rheumatology 26 （ 9 ） 1585 - 1589 2007年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0770-3198

Access to Document (DOI)

A multicenter phase I/II trial of rituximab for refractory systemic lupus erythematosus

Tanaka Yoshiya, Yamamoto Kazuhiko, Takeuchi Tsutomu, Nishimoto Norihiro, Miyasaka Nobuyuki, Sumida Takayuki, Shima Yoshihito, Takada Kazuki, Matsumoto Isao, Saito Kazuyoshi, Koike Takao

Modern Rheumatology 17 （ 3 ） 191 - 197 2007年06月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

Although corticosteroids and immunosuppressants are widely used for the treatments of systemic lupus erythematosus (SLE), safer and more effective therapies are prerequisite. We and others have reported that anti-CD20 antibody rituximab targeting B cells are effective for refractory SLE and, therefore, safety and clinical efficacy of rituximab in SLE was evaluated by a multicenter phase I/II clinical trial. An open-label, multicenter study of 15 patients with active and refractory SLE (total British Isles Lupus Assessment Group [BILAG] score 8 to 17) was conducted. Rituximab was administered to 5 SLE patients as 4 infusions of 500 mg/body every week and to 10 SLE patients as 2 infusions of 1000 mg/body every other week. Assessment of safety, infusion reactions and adverse effects was used as the primary outcome for clinical tolerability and was evaluated by 28 weeks. Rituximab was well tolerated, with most experiencing no significant adverse effects. B cells rapidly reduced in all patients and remained low until 6 months post-treatment. Four patients developed human antichimeric antibodies without affecting efficacy of rituximab. Changes in routine safety laboratory tests clearly related to rituximab were not observed. Nine among 14 evaluable patients achieved the major or partial clinical response of BILAG score and prednisolone dose significantly decreased at the 28 weeks. Rituximab therapy appears to be safe for the treatment of active SLE patients and holds significant therapeutic promise, at least for the majority of patients experiencing profound B-cell depletion. © Japan College of Rheumatology 2007.

Access to Document (DOI)

Prospective study of low-dose cyclosporine A in patients with refractory lupus nephritis

Ogawa Hiroe, Kameda Hideto, Nagasawa Hayato, Sekiguchi Naoya, Takei Hirofumi, Tsuzaka Kensei, Amano Koichi, Takeuchi Tsutomu

Modern Rheumatology 17 （ 2 ） 92 - 97 2007年04月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

We evaluated the efficacy and safety of low-dose cyclosporine A (CsA) in patients with refractory lupus nephritis. Nine patients with systemic lupus erythematosus who had lupus nephritis resistant to previous treatment with glucocorticoids and immunosuppressants other than CsA were enrolled in a prospective, open-label study. All patients initially received 2.5 mg/kg per day of CsA; the dosage was adjusted to reach a blood trough level of 80-150ng/ml. The urinary protein concentration decreased significantly 2 weeks after the initiation of treatment. After 30 weeks of CsA treatment, the mean urinary protein concentration was more than 50% lower than the baseline value, and urinary casts had decreased significantly. There were no significant changes in the levels of serum creatinine, serum anti-double-stranded DNA antibodies, or CH50 during any part of the study. The dose of glucocorticoids was significantly tapered by approximately 50%, without any disease flare. Hypertension developed in one patient, but was controlled with antihypertensive agents. Our results suggest that low-dose CsA therapy is an effective and less toxic alternative to conventional cyclophosphamide therapy for the management of refractory lupus nephritis. © Japan College of Rheumatology 2007.

Access to Document (DOI)

Lymphoproliferative disorders in rheumatoid arthritis

Hoshida Yoshihiko, Xu Jing Xian, Fujita Shigeki, Nakamichi Itsuko, Ikeda Jun Ichiro, Tomita Yasuhiko, Nakatsuka Shin Ichi, Tamaru Jun Ichi, Iizuka Atsushi, Takeuchi Tsutomu, Aozasa Katsuyuki

Journal of Rheumatology 34 （ 2 ） 322 - 331 2007年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0315-162X

Objective. Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA. Methods. We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD. Results. Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%). Conclusion. The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD. and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD.

De novo CD5+ diffuse large B cell lymphoma with basophilia in the peripheral blood

Tokuhira Michihide, Watanabe Reiko, Iizuka Atsushi, Sekiguchi Yasunobu, Nemoto Tomoe, Hanzawa Kyoto, Takamatsu Ichiro, Maruyama Taro, Tamaru Jun Ichi, Itoyama Shinji, Suzuki Hiroshi, Takeuchi Tsutomu, Mori Shigehisa

American Journal of Hematology 82 （ 2 ） 162 - 167 2007年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0361-8609

Basophils play an important role in allergic inflammation and are pathologically related to hematological disturbances, such as iron deficiency anemia and myeloproliferative disorders; however, they are only rarely encountered in lymphoid malignancies. Here, we report the case of a 33-year-old man with a bulky mass of the small intestine, multiple paraaortic lymphoadenopathy, pleural effusion, and ascites, who was diagnosed as a case of de novo CD5+ diffuse large B cell lymphoma (DLBCL). This patient showed a marked elevation of the basophil count in the peripheral blood, which appeared to run in parallel with the tumor burden. High dose chemotherapy followed by autologous peripheral blood cell transplantation yielded complete remission, and the patient has remained disease free for 5 years. To the best of our knowledge, this is the first report of a case of de novo CD5+ DLBCL showing marked elevation of the PB basophil count. © 2006 Wiley-Liss, Inc.

Access to Document (DOI)

　前のページ - 次のページ　

竹内 勤

論文 - 竹内 勤

竹内　勤

論文 - 竹内　勤