研究者詳細 - 竹内　勤

論文 - 竹内　勤

分割表示 514 件中 361 - 380 件目／全件表示 >>

Efficacy and safety of cyclosporine A in patients with refractory systemic lupus erythematosus in a daily clinical practice

Ogawa H., Kameda H., Amano K., Takeuchi T.

Lupus 19 （ 2 ） 162 - 169 2010年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0961-2033

We investigated the efficacy and safety of cyclosporine A (CsA; targeted serum trough level: 80-150 ng/ml) in a daily clinical practice for treating patients with systemic lupus erythematosus (SLE), who had been, or were expected to be, refractory to glucocorticoids (GCs) and other immunosuppressants. Fifty-nine patients with SLE receiving CsA were observed for at least 6 months (21.5 months on average). A significant reduction of proteinuria was noted 2 weeks after initiation of treatment in patients with nephritis, resulting in a clinical response in five of eight patients in the GC dose-up group and 11 of 18 patients in the stable GC dose group, respectively. Notably, the mean score for disease activity on the SLE Disease Activity Index decreased significantly from 8.6 ± 5.3 to 4.4 ± 2.5 after CsA treatment in patients in the stable GC dose group (n = 40). Moreover, the mean flare rate decreased by approximately 60% with CsA. Side effects of CsA appeared in 32.2% of patients and all of them subsided through dose reduction or discontinuation (n=8) of CsA. Consequently, the cumulative 2-year survival rate of CsA was 75%. The results suggest that CsA should be considered for patients with SLE refractory to GCs. Lupus (2010) 19, 162-169.

Access to Document (DOI)

CLINICAL AND IMMUNOLOGICAL CHARACTERISTICS OF JAPANESE PATIENTS WITH CONNECTIVE TISSUE DISEASE AND PULMONARY ARTERIAL HYPERTENSION

竹内勤

Clinical and Experimental Rheumatology 28 （ 2 ） S125 - S126 2010年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0392-856X

Reduced expression of TCR zeta is involved in the abnormal production of cytokines by peripheral T cells of patients with systemic lupus erythematosus

Yoshimoto Keiko, Setoyama Yumiko, Tsuzaka Kensei, Abe Tohru, Takeuchi Tsutomu

Journal of Biomedicine and Biotechnology 2010 6 2010年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1110-7243

Accumulating evidence suggests that dysfunction of T cells underlies the pathogenesis of systemic lupus erythematosus (SLE). We revealed that SLE T cells produced an abnormally excessive amount of IFN- in vitro upon stimulation through TCR, and the expression level of TCR zeta was significantly reduced. The production of IFN- by SLE T cells was negatively correlated with the expression level of TCR zeta. This correlation was abolished when the cells were stimulated with TPA and ionomycin, which bypass TCR and introduce signals directly into the cells, but the production of IFN- by SLE T cells remained abnormally elevated. Taken together, these data suggest that regulatory mechanisms not only for the expression of TCR zeta but also for the production of IFN- were impaired in SLE T cells. These impairments may be responsible for the aberrant responses of SLE T cells and partly involved in the development of SLE. © 2010 Keiko Yoshimoto et al.

Access to Document (DOI)

Normalisation of physical function by infliximab in patients with RA

Nagasawa Hayato, Kameda Hideto, Sekiguchi Naoya, Amano Koichi, Takeuchi Tsutomu

Clinical and Experimental Rheumatology 28 （ 3 ） 365 - 372 2010年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0392-856X

Objectives: We conducted a two-year prospective study to identify possible factors associated with normalisation of physical function by infliximab treatment in 125 patients with rheumatoid arthritis (RA). Methods RA patients who had been scheduled to receive infliximab at 3 mg/kg were registered and prospectively examined for disease activity, joint damage, and physical function for 102 weeks using the Disease Activity Score of 28 Joints (DAS-28) using C-reactive protein, van der Heijde-modified Sharp score (vdH-Sharp score) of hand and foot x-ray, and Health Assessment Questionnaire Disability Index (HAQ-DI). Normal physical function and clinical remission were defined as a HAQ-DI of 0.5 or less, and DAS28 (CRP) <2.6, respectively. Results: Forty-two of 125 patients (42%) achieved normal physical function at 102 weeks. The percentage of normal physical function at 102 weeks was significantly higher in the patients achieving clinical remission at 102 weeks (60%) than in those without (16%). In the patients with clinical remission at 102 weeks, less structural damage at baseline was correlated with a higher rate of normal physical function, suggesting the critical importance of joint destruction prior to infliximab therapy, in addition to clinical response. Logistic regression analysis further identified HAQ-DI, serum MMP-3 level, vdH-Sharp score, and methotrexate (MTX) dose as baseline factors contributing to normal physical function with 2-year infliximab treatment. Conclusion: Treatment with anti-TNF biologics in combination with MTX may achieve the normalisation of physical function in patients with established RA. Critical factors contributing to the normalisation of function were tight control of disease activity and less joint damage. © Copyright Clinical and Experimental Rheumatology 2010.

Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study)

Nishimoto N., Miyasaka N., Yamamoto K., Kawai S., Takeuchi T., Azuma J.

Annals of the Rheumatic Diseases 68 （ 10 ） 1580 - 1584 2009年10月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0003-4967

Objectives: To evaluate the safety and efficacy of 5-year, long-term tocilizumab monotherapy for patients with rheumatoid arthritis. Methods: In an open-label, long-term extension trial following an initial 3-month randomised phase II trial, 143 of the 163 patients who participated in the initial blinded study received tocilizumab monotherapy (8 mg/kg) every 4 weeks. Concomitant therapy with non-steroidal anti-inflammatory drugs and/or oral prednisolone (10 mg daily maximum) was permitted. All patients were evaluated with American College of Rheumatology (ACR) improvement criteria, disease activity score (DAS) in 28 joints, and the European League Against Rheumatism response, as well as for safety issues. Results: 143 patients were enrolled in the open-label, long-term extension trial and 94 (66%) patients had completed 5 years as of March 2007. 32 patients (22%) withdrew from the study due to adverse events and one patient (0.7%) due to unsatisfactory response. 14 patients withdrew because of the patient's request or other reasons. The serious adverse event rate was 27.5 events per 100 patient-years, with 5.7 serious infections per 100 patient-years, based on a total tocilizumab exposure of 612 patient-years. Of the 88 patients receiving corticosteroids at baseline, 78 (88.6%) were able to decrease their corticosteroid dose and 28 (31.8%) discontinued corticosteroids. At 5 years, 79/94 (84.0%), 65/94 (69.1%) and 41/94 (43.6%) of the patients achieved ACR20, ACR50, and ACR70 improvement criteria, respectively. Remission defined as DAS28 less than 2.6 was achieved in 52/94 (55.3%) of the patients. Conclusion: In this 5-year extension study, tocilizumab demonstrated sustained long-term efficacy and a generally good safety profile.

Access to Document (DOI)

Factors associated with fatal outcome of leflunomide-induced lung injury in Japanese patients with rheumatoid arthritis.

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

Rheumatology (Oxford, England) 48 （ 10 ） 1265 - 1268 2009年10月

研究論文（学術雑誌）, 共著, 査読有り

OBJECTIVE: To elucidate the factors associated with poor prognosis of LEF-induced lung injury in patients with RA. METHODS: The background and clinical and laboratory features of LEF-induced lung injury were examined and compared between patients who died of and who recovered from it. RESULTS: Among 22 patients who developed LEF-induced lung injury, 9 died of and 13 recovered from it. The patients who died tended to have pre-existing interstitial pneumonia (8/9 vs 6/13, P = 0.07). The loading and maintenance doses, serum concentration of the LEF metabolite A771726 and administration period did not differ between the groups. Patients who died had more frequently hypoxaemia of <60 Torr and mechanical ventilation, and had a high serum CRP level (19.3 +/- 9.4 vs 10.1 +/- 8.1 mg/dl, P = 0.03) and a low albumin level (2.7 +/- 0.6 vs 3.3 +/- 0.5 g/dl, P = 0.03) at the lung injury onset. The peripheral blood lymphocyte count decreased in both groups at the lung injury onset, and it remained low until fatal outcome, in contrast to a re-increase upon recovery (406 +/- 394 vs 1203 +/- 399/microl, P = 0.006). The main histopathological finding in two autopsied patients was diffuse alveolar damage, in contrast to the alveolitis observed in a biopsied patient who recovered. CONCLUSIONS: Pre-existing interstitial pneumonia, extremely high serum CRP and low albumin levels, severe hypoxaemia and mechanical ventilation indicated poor prognosis. Peripheral blood lymphocytopenia developed in association with lung injury, and a sustained low lymphocyte count indicated a fatal outcome.

Leflunomide-induced interstitial lung disease

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

Rheumatology 48 （ 9 ） 1069 - 1072 2009年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1462-0324

Objective: The possible link between LEF and interstitial lung disease (ILD) has evoked increasing concern. The aim of the present study was to elucidate the prevalence and risk factors for newly developed and/or exacerbated ILD, based on post-marketing surveillance data, in which all RA patients receiving LEF were pre-registered and monitored for 24 weeks in Japan. Methods: We analysed data from a cohort of 5054 RA patients who were prescribed LEF since its launch in September 2003 in Japan. Multivariable logistic analysis was performed to identify the risk factors for newly developed and/or exacerbation of ILD. Results: Sixty-one (1.2%) of 5054 RA patients who received LEF were reported to have development and/or exacerbation of ILD as an adverse drug reaction to LEF, judged by the attending physicians. Multivariable logistic regression analysis identified pre-existing ILD [odds ratio (OR) 8.17; 95% CI 4.63, 14.4], cigarette smoking (3.12; 95% CI 1.73, 5.60), a low body weight (<40 kg vs >50 kg) (2.91; 95% CI 1.15, 7.37) and the use of a loading dose (3.97; 95% CI 1.22, 12.9) as independent risk factors for LEF-induced ILD. Conclusions: Pre-existing ILD was the most important risk factor for LEF-induced ILD. We suggest that LEF should not be prescribed for RA patients complicated with ILD. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.

Access to Document (DOI)

Prediction of efficacy of anti-TNF biologic agent, infliximab, for rheumatoid arthritis patients using a comprehensive transcriptome analysis of white blood cells

竹内勤

Biochemical and Biophysical Research Communications 387 （ 2 ） 261 - 265 2009年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0006-291X

Access to Document (DOI)

Postmarketing surveillance of the safety and effectiveness of etanercept in Japan

Koike Takao, Harigai Masayoshi, Inokuma Shigeko, Inoue Kazuhiko, Ishiguro Naoki, Ryu Junnosuke, Takeuchi Tsutomu, Tanaka Yoshiya, Yamanaka Hisashi, Fujii Koichi, Freundlich Bruce, Suzukawa Michio

Journal of Rheumatology 36 （ 5 ） 898 - 906 2009年05月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0315-162X

Objective. Postmarketing surveillance (PMS) was conducted evaluating safety and effectiveness of etanercept (ETN; Enbrel®) in Japan, following all patients with rheumatoid arthritis (RA) during the conditional approval period of ETN. Methods. Registration of patients from 1,334 medical sites was conducted between March 2005 and April 2007. Patients were followed for 24 weeks; data regarding patients' background, safety, and effectiveness was recorded centrally. Adverse events (AE) and adverse drug reactions (ADR) were coded using the Medical Dictionary for Regulatory Activities. Effectiveness was measured using the Disease Activity Score 28 (DAS28). Results. Of 14,369 patients registered, data collection and evaluation for 7,091 patients by March 2006 is reported. At least 1 AE was observed for 2,173 patients (30.6%); 60% of AE occurred within 8 weeks of starting ETN. Most frequent AE were injection site reaction (n = 377, 5.3%) and rash (n = 228, 3.2%). Serious AE occurred in 403 patients (5.7%); most frequent were pneumonia (n = 59, 0.8%) and interstitial lung disease (n = 42, 0.6%). Pneumonia was the most common specifically important ADR (n = 102, 1.4%). Mean baseline DAS28 was 6.0, which reduced to 4.4 within 4 weeks, and to 3.9 within 24 weeks. The proportion of patients having good or moderate EULAR response measured by DAS28 was 84.1% at Week 24. Effectiveness rates were more favorable in patients concomitantly using methotrexate. Good or moderate EULAR response rate among patients switched from infliximab was 84.9%. Conclusion. This extensive observational trial, including all patients with RA in Japan taking ETN, found ETN to be both effective and well tolerated by Japanese patients with RA. Trial registration: clinicaltrials.gov identifier NCT00503503. The Journal of Rheumatology Copyright © 2009. All rights reserved.

Access to Document (DOI)

Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab

Komano Yukiko, Harigai Masayoshi, Koike Ryuji, Sugiyama Haruhito, Ogawa J. U N, Saito Kazuyoshi, Sekiguchi Naoya, Inoo Masayuki, Onishi Ikuko, Ohashi Hiroyuki, Amamoto Fujio, Miyata Masayuki, Ohtsubo Hideo, Hiramatsu Kazuko, Iwamoto Masahiro, Minota Seiji, Matsuoka Naoki, Kageyama Goichi, Imaizumi Kazuyoshi, Tokuda Hitoshi, Okochi Yasumi, Kudo Koichiro, Tanaka Yoshiya, Takeuchi Tsutomu, Miyasaka Nobuyuki

Arthritis Care and Research 61 （ 3 ） 305 - 312 2009年03月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 2151-4658

Objective. To establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan. Methods. Data from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case-control study to compare patients with and without PCP were performed. Results. The median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground-glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived. Conclusion. PCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy. © 2009, American College of Rheumatology.

Access to Document (DOI)

Single center prospective study of tacrolimus efficacy and safety in treatment of rheumatoid arthritis

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

Rheumatology International 29 （ 4 ） 431 - 436 2009年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0172-8172

The aim of this study was to prospectively evaluate the efficacy and safety of tacrolimus for treating rheumatoid arthritis (RA) patients in clinical practice. Fifty-five active RA patients who had been resistant or intolerant to other disease-modifying antirheumatic drugs were enrolled in this open-label trial. Patients were administered tacrolimus at a dosage of 1, 2 or 3 mg once daily, and followed up for 24 weeks. They were divided into three groups according to their dosage. Efficacy and safety were evaluated utilizing clinical and laboratory findings. Eighty percent of the patients had moderate or high disease activity; 55% were elderly and 53% had complications; 65% of the patients were started on tacrolimus as a monotherapy. Moderate or good response rates were achieved as follows: 38.2% (4 weeks); 41.8% (12 weeks); and 45.6% (24 weeks). Adverse events were observed in seven cases (12.7%). Only one case required hospitalization due to severe hyperglycemia caused by a high tacrolimus concentration (24.2 ng/ml); we suspected a drug interaction in this subject. Mean concentrations were dose-dependent in the 1, 2, and 3 mg/day groups (2.96, 4.29, and 8.32 ng/ml, respectively). Four cases of high concentration (over 10 ng/ml), without any signs or symptoms, were observed in the 3 mg/day group; in these cases, doses were decreased and no severe adverse events occurred. Tacrolimus was found to be both effective and safe in treating active RA patients with complicated backgrounds in clinical practice. Blood concentration measurements and dose adjustments should be performed to prevent severe adverse events in a 3 mg/day group. © 2009 Springer-Verlag.

Access to Document (DOI)

Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with an inadequate response to methotrexate (SATORI)

竹内勤

Modern Rheumatology 19 （ 1 ） 12 - 19 2009年02月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

Access to Document (DOI)

A combination of biochemical markers of cartilage and bone turnover, radiographic damage and body mass index to predict the progression of joint destruction in patients with rheumatoid arthritis treated with disease-modifying anti-rheumatic drugs

Hashimoto Jun, Garnero Patrick, van der Heijde Désirée, Miyasaka Nobuyuki, Yamamoto Kazuhiko, Kawai Shinichi, Takeuchi Tsutomu, Yoshikawa Hideki, Nishimoto Norihiro

Modern Rheumatology 19 （ 3 ） 273 - 282 2009年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

The aim of this study was to evaluate the predictive value of biological, radiological and clinical parameters for the progression of radiographic joint damage in rheumatoid arthritis (RA) patients treated with conventional disease-modifying anti-rheumatic drugs (DMARDs). We analyzed the 145 patients with active RA for less than 5 years who were participating in the prospective 1-year randomized controlled trial of tocilizumab (SAMURAI trial) as a control arm treated with conventional DMARDs. Progression of joint damage was assessed by sequential radiographs read by two independent blinded X-ray readers and scored for bone erosion and joint space narrowing (JSN) using the van der Heijde-modified Sharp method. Multivariate analysis revealed that increased urinary levels of C-terminal crosslinked telopeptide of type II collagen (U-CTX-II), an increased urinary total pyridinoline/total deoxypyridinoline (U-PYD/DPD) ratio and low body mass index (BMI) at baseline were independently associated with a higher risk for progression of bone erosion. In addition to these three variables, the JSN score at baseline was also significantly associated with an increased risk of progression of the JSN score and total Sharp score. High baseline U-CTX-II levels, U-PYD/DPD ratio and JSN score and a low BMI are independent predictive markers for the radiographically evident joint damage in patients with RA treated with conventional DMARDs. © Japan College of Rheumatology 2009.

Access to Document (DOI)

Improvement of the HAQ score by infliximab treatment in patients with RA

Nagasawa Hayato, Kameda Hideto, Sekiguchi Naoya, Amano Kouichi, Takeuchi Tsutomu

Modern Rheumatology 19 （ 2 ） 166 - 172 2009年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

We conducted a two-year prospective study to clarify the efficacy of infliximab at improving the health assessment questionnaire (HAQ) score and associated factors in 67 patients with advanced rheumatoid arthritis (RA). All patients were scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2, 6 and every eight weeks thereafter through to week 102, and were fully examined at the time of each infusion. Parameters of disease activity such as the serum level of C-reactive protein (CRP), the serum level of matrix metalloproteinase-3 (MMP-3) and the 28-joint disease activity score (DAS28) were obtained, and the functional capabilities of the patients were assessed using the HAQ score. The serum CRP, the MMP-3, the DAS28(CRP) level, and the mean HAQ score decreased rapidly at two weeks after the start of infliximab treatment (CRP from 3.7 to 0.9 mg/dl, MMP-3 from 362.3 to 192.8 ng/ml, DAS28(CRP) from 5.6 to 3.7, and HAQ score from 1.5 to 0.9). Compared with the baseline values, the mean progression of the modified van der Heijde (vdH) - Sharp score after one year was 4.4 ± 5.8 (median: 3.0), and that after two years was 3.1 ± 6.9 (median: 1.0). A 93% reduction in the rate of joint destruction, as measured using the vdH-Sharp score, was estimated after infliximab therapy. Patients with less joint damage (shorter disease duration or lower vdH-Sharp score) regained more of their daily activities. The present study demonstrated the importance of activity control before the progression of irreversible factors, such as joint destruction, for maintaining the functional capacities of RA patients. © Japan College of Rheumatology 2008.

Access to Document (DOI)

Notable difference between the development of vertebral fracture and osteonecrosis of the femoral head in patients treated with high-dose glucocorticoids for systemic rheumatic diseases

Kameda Hideto, Amano Koichi, Nagasawa Hayato, Ogawa Hiroe, Sekiguchi Naoya, Takei Hirofumi, Suzuki Katsuya, Takeuchi Tsutomu

Internal Medicine 48 （ 22 ） 1931 - 1938 2009年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0918-2918

Objective: Vertebral fracture (VF) and osteonecrosis of the femoral head (OFH) are serious concerns in patients with rheumatic diseases treated with high-dose glucocorticoids (GCs). We comparatively examined the risk factors of VF and OFH in patients who had recently received high-dose GC therapy. Patients and Methods: Patients with rheumatic diseases receiving GCs (≥0.5 mg/kg/day for prednisolone equivalent) within the past 2 months were enrolled in this study, and treated with 200 mg/day of etidronate cyclically. The bone mineral density (BMD) of the lumbar spine (L2-4) was examined by QDR2000. OFH was evaluated by magnetic resonance imaging (MRI). [ClinicalTrials.gov identifier: NCT00679978]. Results: Forty-four patients completed the 2-year study including annual X-rays and the BMD analysis. MRI evaluation at entry and 2 years was performed in 41 patients. The BMD values with anteroposterior (AP) and lateral views decreased by 6.4% and 9.7%, respectively, in the first year, but were stable in the second year. Eleven patients developed VF and 9 patients developed OFH. The risk factors for VF included previous VF and a low BMD value (T score<-1.5) of AP view at baseline with an odds ratio (OR) of 14.9 (95% CI 2.9-76.4), while the risk factor for OFH was a recent maximum GC dosage (>1.2 mg/kg/day versus≤; OR=7.7, 95%CI 1.3-45.5) and a decrease in BMD value of lateral view (>15% versus≤ OR=6.7, 95% CI 1.2-36.1) in the first year. Conclusion: The development of VF relies on the predisposing factors, while that of OFH depends on the response to high-dose GC therapy. © 2009 The Japanese Society of Internal Medicine.

Access to Document (DOI)

Impact of trough serum level on radiographic and clinical response to infliximab plus methotrexate in patients with rheumatoid arthritis

Takeuchi Tsutomu, Miyasaka Nobuyuki, Inoue Kazuhiko, Abe Tohru, Koike Takao

Modern Rheumatology 19 （ 5 ） 478 - 487 2009年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1439-7595

This study is a prospective, randomized, double-blind study to compare the efficacy and safety of 10 mg/kg infliximab with those of 3 mg/kg infliximab treatment in methotrexate-refractory rheumatoid arthritis patients. After the patients received 3 mg/kg infliximab infusion at weeks 0, 2, and 6, they were randomly assigned to be administered 3, 6 or 10 mg/kg infliximab every 8 weeks from week 14 to 46. Mean American College of Rheumatology improvement (ACR-N) at week 54, the primary endpoint, was 51.3% and 58.3% for the 3 mg/kg and 10 mg/kg groups, respectively, with a statistically significant difference. Treatment with 10 mg/kg was found to be remarkably beneficial in patients who had not responded to three infusions with 3 mg/kg at week 10. The median changes in the modified Sharp score were 0.0 in the two groups. There were no significant differences in the incidences of adverse events between the groups. In patients who achieved better clinical response or greater inhibition of progression of joint damage, trough serum infliximab level was significantly higher than in patients who did not. The magnitudes of both efficacies were correlated with the trough serum infliximab level (ClinicalTrials.gov number: NCT00691028). © Japan College of Rheumatology 2009.

Access to Document (DOI)

Severe acute thrombotic exacerbation in two cases with anti-phospholipid syndrome after retreatment with rituximab in phase I/II clinical trial for refractory systemic lupus erythematosus

Suzuki K., Nagasawa H., Kameda H., Amano K., Kondo T., Itoyama S., Tanaka Y., Takeuchi T.

Rheumatology 48 （ 2 ） 198 - 199 2009年

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1462-0324

Access to Document (DOI)

Effect of interleukin-2 on synthesis of B cell activating factor belonging to the tumor necrosis factor family (BAFF) in human peripheral blood mononuclear cells

竹内勤

Cytokine 44 （ 1 ） 44 - 48 2008年10月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1043-4666

Access to Document (DOI)

Tacrolimus has pleiotropic morelecular effects on human regulatory T cells

竹内勤

Arthritis and Rheumatism 58 （ 9 ） S839 - S839 2008年09月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0004-3591

Altered distribution of aquaporin 5 and its C-terminal binding protein in the lacrimal glands of a mouse model for Sjögren's syndrome

Ohashi Yoshiki, Tsuzaka Kensei, Takeuchi Tsutomu, Sasaki Yasumasa, Tsubota Kazuo

Current Eye Research 33 （ 8 ） 621 - 629 2008年08月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 0271-3683

Purpose: To investigate the distribution and expression of aquaporin 5 (AQP5) and its C-terminal binding protein in the apical membrane of the lacrimal glands (LGs) in a mouse model for Sjogren's syndrome (SS). Methods: The LGs of NOD mice (mouse model for SS) and ICR mice (normal control) were homogenized and delivered into the affinity columns bound to synthetic AQP5 C-terminal peptide. The eluates were analyzed by electrophoresis and liquid chromatography mass spectrometry/mass spectrometry (LC-MS/MS) techniques.Results: AQP5 from the NOD mice exhibited the capacity to bind a 21-kDa protein that was lacking in the ICR mice. Instead, ICR mouse expressed a 17-kDa AQP5 binding protein that was absent in LGs of SS. LC-MS/MS analysis revealed these respective proteins to be major urinary protein 4 (MUP4) and prolactin-inducible protein (PIP). The treatment of ICR mice with antisense PIP oligonucleotides decreased immunostaining of AQP5 in the apical membrane. Conclusions: These observations suggest that the binding of PIP to the C-terminal portion of AQP5 may cause AQP5 to be transported to the apical membrane of LGs. Correction of the aberrant binding of PIP to the AQP5 C-terminus could normalize AQP5 trafficking to the apical membrane, leading to a treatment for patients with SS. Copyright © Informa Healthcare USA, 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