Effects of light and darkness on cell-cycle progression were studied in the log-linear photoautotrophic growth mode of Euglena gracilis. We found that there are light-dependent restriction points in the post-G1 phases, quite in contrast to Chlamydomonas, where a light-dependent restriction is known to exist only in the G1 phase. Thus, in E. gracilis, there are photoinduced commitments of G1-, S- and G2-phase cells that allow them to progress to the G1, S and G2 phases in darkness, and there are dark-induced G1-, S- and G2-phase arrests. In darkness, only committed cells were able to progress to the committed phases (G1, S or G2), whereas uncommitted cells were unable to undergo a cell-cycle transition. Whether or not cells were induced to commit by irradiation, they were eventually arrested somewhere in the G1, S or G2 (but not M) phase within 14 h of being transferred to darkness. We also describe the dependence of photoinduced commitment on light intensity and discuss the results as they relate to cell-cycle progression in continuous light.
Objective: To clarify the efficacy and safety of abatacept for secondary Sjögren’s syndrome (SS) associated with rheumatoid arthritis (RA). Methods: The primary endpoint of this open-labeled, prospective, observational multicenter study for secondary SS with RA was the remission rate of Simplified Disease Activity Index (SDAI) at 52 weeks after initiation of abatacept. The secondary endpoints included Saxon’s test and Schirmer’s test. Adverse events and adherence rate during the study period were also analyzed. Results: Thirty-six patients (all females) were enrolled in this study. The mean SDAI decreased significantly from 20.6 ± 11.2 (±SD) at baseline to 10.0 ± 10.5 at 52 weeks (p < 0.05). Patients with SDAI remission increased from 0 (0 week) to 12 patients (33.3%) at 52 weeks. Saliva volume assessed by Saxon’s test increased significantly from 2136 ± 1809 (0 week) to 2397 ± 1878 (24 weeks) mg/2 min (n = 34, p < 0.05). Saliva volume increased significantly from 2945 ± 2090 (0 week) to 3419 ± 2121 (24 weeks) mg/2 min in 11 patients with Greenspan grade 1 or 2 of labial salivary gland biopsy (p < 0.05), but no change was noted in 18 patients with Greenspan grade 3 or 4. Tear volume by Schirmer’s test increased significantly from 4.2 ± 4.8 (0 week) to 6.4 ± 7.8 (24 weeks) mm/5 min (n = 30, p < 0.05). The adherence rate to abatacept was 80.6% (29/36) over the 52-week period. Twelve adverse events occurred in 10 of the 36 patients, and 7 of these events were infections. Conclusion: Abatacept seems to be effective for both RA and SS related manifestations.
ABSTRACT Objectives The aim is to clarify the differences in magnetic resonance imaging (MRI) findings between rheumatoid arthritis (RA) patients treated with certolizumab pegol (CZP) and infliximab (IFX). Methods The study included RA patients who received CZP or IFX and were examined with low-field MRI (compacTscan; compact magnetic resonance imaging) at the beginning and again within 6 months of treatment initiation. Comparisons were made regarding background, clinical course, and differences in MRI findings following initiation of tumour necrosis factor inhibitors between the CZP and IFX treatment groups. MRI findings were evaluated by scoring erosion, bone marrow oedema (BME), and synovitis. Results Ten cases in CZP and 18 cases in IFX group were compared. The biologic disease-modifying antirheumatic drug–naïve rate in the IFX group was significantly higher than that in the CZP group. After 6 months, disease activities were significantly decreased from baseline in both groups. Erosion score did not change significantly in both groups after 6 months. BME score was significantly decreased in the CZP group after 6 months, whereas in the IFX group, there was no significant change. Synovitis score was significantly decreased in both groups after 6 months. Conclusions The findings of our study suggest that, in patients with RA, CZP might improve BME more effectively than IFX.
Objective Biological disease-modifying anti-rheumatic drugs (bDMARDs) represent an important advance in alleviating rheumatoid arthritis (RA), but their effect on rheumatic airway disease (AD) and interstitial lung disease (ILD) is still unclear. This study was performed to evaluate the association of the use of different bDMARDs with new-onset or worsening of RA-AD/ILD. Methods We performed a retrospective cohort study of RA patients who received bDMARDs and assessed their AD/ILD before and after drug initiation in our hospital over the past 10 years. We evaluated the serial changes in computed tomography (CT), classified patients according to AD/ILD progression, and analyzed associations between clinical characteristics and outcomes. Results We enrolled 49 patients. Thirty patients received tumor necrosis factor inhibitors (TNFis), 12 received abatacept (ABT), and the remaining 7 received tocilizumab (TCZ). Seventeen patients had ILD, 10 had AD, and 6 had both AD and ILD before the initiation of bDMARDs. New emergence or exacerbation of AD/ILD was observed in 18 patients after drug initiation, while the remaining 31 remained stable or improved. Multiple logistic regression analyses revealed that pre-existing AD was an independent risk factor against the emergence or exacerbation of RA-AD/ILD, and ABT use was a protective factor against it. Conclusion Our study showed that pre-existing RA-AD is associated with future worsening of RA-AD/ILD, and ABT over other bDMARDs was associated with a better prognosis. Future studies to confirm our results are needed.
To compare MRI findings in rheumatoid arthritis (RA) patients treated with biologic disease-modifying anti-rheumatic drugs (DMARDs).The study subjects were 43 RA patients treated with biologic DMARDs (13 with infliximab, 15 with tocilizumab, and 15 with abatacept). They were evaluated using Simplified Disease Activity Index (SDAI) and low-field extremity MRI at baseline, and at 24 weeks and 52 weeks of treatment.Synovitis scores were significantly lower by 24 weeks in all groups, compared with baseline (P < 0.05). Significant improvement in bone marrow edema (BME) scores were noted from baseline to 24 weeks in infliximab and abatacept groups (P < 0.05), but from 24 weeks to 52 weeks in tocilizumab group (P < 0.01). No significant change was found in erosion score. The synovitis score at baseline correlated significantly with SDAI at 24 weeks (P < 0.05), and the score at 24 weeks correlated significantly with SDAI at 52 weeks (P < 0.05).The results suggest that the inflammatory improvement by infliximab and abatacept may express earlier than those by tocilizumab, despite similar improvement in SDAI. MRI-detected synovitis could be a useful predictor of SDAI at 24 weeks of treatment. The MRI remains the best tool to detect and assess the effects of biologic DMARDs in RA.
Journal Article Usefulness of MR imaging of the parotid glands in patients with secondary Sjögren's syndrome associated with rheumatoid arthritis Get access Masahiro Yokosawa, Masahiro Yokosawa Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Hiroto Tsuboi, Hiroto Tsuboi Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Katsuhiro Nasu, Katsuhiro Nasu Department of Radiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Chihiro Hagiya, Chihiro Hagiya Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Shinya Hagiwara, Shinya Hagiwara Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Tomoya Hirota, Tomoya Hirota Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Hiroshi Ebe, Hiroshi Ebe Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Hiroyuki Takahashi, Hiroyuki Takahashi Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Hiromitsu Asashima, Hiromitsu Asashima Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Yuya Kondo, Yuya Kondo Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar ... Show more Hiroshi Ogishima, Hiroshi Ogishima Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Takeshi Suzuki, Takeshi Suzuki Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Manabu Minami, Manabu Minami Department of Radiology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Hiroki Bukawa, Hiroki Bukawa Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Isao Matsumoto, Isao Matsumoto Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Search for other works by this author on: Oxford Academic Google Scholar Takayuki Sumida Takayuki Sumida Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan Correspondence to: Prof. Takayuki Sumida, Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba-city, Ibaraki 305-8575, Japan. Tel/Fax: + 81-29-853-7388. E-mail: tsumida@md.tsukuba.ac.jp Search for other works by this author on: Oxford Academic Google Scholar Modern Rheumatology, Volume 25, Issue 3, 4 May 2015, Pages 415–420, https://doi.org/10.3109/14397595.2014.958892 Published: 04 May 2015 Article history Received: 10 July 2014 Accepted: 22 August 2014 Published: 04 May 2015
We present the case of a 17-year-old woman with IgA vasculitis (IgAV) who presented with relapsing gastrointestinal (GI) symptoms that were refractory to glucocorticoid and combination therapy with cyclosporine A, azathioprine or mycophenolate mofetil (MMF). The patient responded well to remission induction with intravenous cyclophosphamide (IVCY) and was successfully maintained with MMF. Remission induction with IVCY followed by maintenance therapy with MMF was effective in a patient with multidrug-resistant IgAV with GI lesions.
To clarify the efficacy and safety of intravenous abatacept for glandular and extraglandular involvements in Sjögren's syndrome (SS) associated with rheumatoid arthritis (RA).We performed an open-label, prospective, 1-year, observational multicenter study (ROSE and ROSE II trials). The primary endpoint was the remission rate as measured by SDAI at 52 weeks. The secondary endpoints included the changes in the Saxon's test, Schirmer's test, ESSDAI and ESSPRI. Adverse events and adherence rates were also analyzed.68 patients (36 in ROSE and 32 in ROSE II, all women) were enrolled. SDAI decreased significantly from 23.6 ± 13.2 at baseline to 9.9 ± 9.5 at 52 weeks. Patients with SDAI remission increased from 0 (0 weeks) to 19 patients (27.9%) at 52 weeks. Saliva volume increased significantly at 24 weeks. Tear volume increased significantly at 52 weeks. Both ESSDAI and ESSPRI were significantly decreased at 12 weeks, and these responses were maintained up to 52 weeks. The rate of adherence to abatacept over the 52-week period was 83.8%. Twenty-two adverse events occurred in 15 patients.Abatacept ameliorated both glandular and extraglandular involvements, as well as the systemic disease activities and patient-reported outcomes based on composite measures, in SS associated with RA.
Thrombotic microangiopathy (TMA) is a rare but life-threatening complication of systemic lupus erythematosus (SLE) and is associated with adverse pregnancy outcomes. We herein report a 30-year-old pregnant woman with SLE complicated by TMA. Because her condition was unresponsive to initial corticosteroid and fresh-frozen plasma infusion treatment, we attempted plasma exchange (PE). Although thrombocytopenia and microangiopathic hemolytic anemia gradually improved, fetal death was confirmed at 23 weeks of gestation. This case suggests that PE is an effective therapeutic option but might be insufficient to maintain pregnancy in patients with SLE complicated by TMA.
