Efficacy of Semiannual Single Fixed Low-Dose Rituximab Therapy in Steroid-Dependent Minimal Change Nephrotic Syndrome: A Case Series

The frequency of using rituximab to treat refractory nephrotic syndrome has recently been increasing, and the conventional dose of rituximab used to treat it, 375 mg/m2 body surface area once weekly for 4 weeks, has been modelled on the chemotherapy regimen for B-cell non-Hodgkin’s lymphoma. The dose and intervals of rituximab in refractory nephrotic syndrome remain controversial. Clear lymphoma cell hyperplasia is seen in lymphoma patients, but not in nephrotic syndrome patients. Since we thought that it might be possible to reduce the dose of rituximab if only used for the purpose of depleting CD20-positive B cells in nephrotic patients’ peripheral blood, we tried semiannually with a single fixed rituximab dose of 100 mg/body, and a complete remission was attained in 3 cases without treatment with prednisolone or cyclosporine. Our report strongly suggests considering appropriate dose and interval of rituximab therapy in the treatment of steroid-dependent nephrotic syndrome

E3 Ubiquitin Ligase Synoviolin Is Involved in Liver Fibrogenesis

Chronic hepatic damage leads to liver fibrosis, which is characterized by the accumulation of collagen-rich extracellular matrix. However, the mechanism by which E3 ubiquitin ligase is involved in collagen synthesis in liver fibrosis is incompletely understood. This study aimed to explore the involvement of the E3 ubiquitin ligase synoviolin (Syno) in liver fibrosis.The expression and localization of synoviolin in the liver were analyzed in CCl(4)-induced hepatic injury models and human cirrhosis tissues. The degree of liver fibrosis and the number of activated hepatic stellate cells (HSCs) was compared between wild type (wt) and Syno(+/-) mice in the chronic hepatic injury model. We compared the ratio of apoptosis in activated HSCs between wt and Syno(+/-) mice. We also analyzed the effect of synoviolin on collagen synthesis in the cell line from HSCs (LX-2) using siRNA-synoviolin and a mutant synoviolin in which E3 ligase activity was abolished. Furthermore, we compared collagen synthesis between wt and Syno(-/-) mice embryonic fibroblasts (MEF) using quantitative RT-PCR, western blotting, and collagen assay; then, we immunohistochemically analyzed the localization of collagen in Syno(-/-) MEF cells.In the hepatic injury model as well as in cirrhosis, synoviolin was upregulated in the activated HSCs, while Syno(+/-) mice developed significantly less liver fibrosis than in wt mice. The number of activated HSCs was decreased in Syno(+/-) mice, and some of these cells showed apoptosis. Furthermore, collagen expression in LX-2 cells was upregulated by synoviolin overexpression, while synoviolin knockdown led to reduced collagen expression. Moreover, in Syno(-/-) MEF cells, the amounts of intracellular and secreted mature collagen were significantly decreased, and procollagen was abnormally accumulated in the endoplasmic reticulum.Our findings demonstrate the importance of the E3 ubiquitin ligase synoviolin in liver fibrosis

Rupture and Rhythm: A Phenomenology of National Experiences

This article investigates how people make sense of ruptures in the flow of everyday life as they enter new experiential domains. Shifts in being-in-time create breaks in the natural attitude that offer the opportunity to register national—or, for example, religious, gender, or class—experiences. People interpret ruptures in perception and proprioception by drawing connections with domains in which similar or contrasting kinds of disruption are evident. Normalizing the transition, rhythm—as both cadence and overall flow—helps people adjust to new circumstances, align action, and smooth subsequent ruptures. Based on extensive qualitative fieldwork, I examine the specific case of how novice and experienced tea ceremony practitioners in Japan move into, interpret, and normalize action within tea spaces

Dynamic change of histone H2AX phosphorylation independent of ATM and DNA-PK in mouse skin in situ.

Histone H2AX undergoes phosphorylation on Ser 139 (gamma-H2AX) rapidly in response to DNA double-strand breaks induced by exogenous stimuli, such as ionizing radiation. However, the endogenous phosphorylation pattern and modifier of H2AX remain unclear. Here we show that H2AX is regulated physically at the level of phosphorylation at Ser139 during a hair cycle in the mouse skin. In anagen hair follicles, gamma-H2AX-positive cells were observed in the outer root sheath (ORS) and hair bulb in a cycling inferior region but not in a permanent superficial region. In telogen hair follicles, gamma-H2AX-positive cells were only detected around the germ cell cap. In contrast, following X-irradiation, gamma-H2AX was observed in various cell types including the ORS cells in the permanent superficial region. Furthermore, gamma-H2AX-positive cells were detected in the skin of mice lacking either ATM or DNA-PK, suggesting that these kinases are not essential for phosphorylation in vivo

Histone H2AX Phosphorylation Independent of ATM after X-irradiation in Mouse Liver and Kidney in situ

Histone H2AX undergoes phosphorylation at Ser-139 (gamma-H2AX) rapidly in response to DNA double-strand breaks (DSBs) induced by ionizing radiation. The post-translational modification of H2AX plays a central role in responses to radiation, including the repair of DSBs. Although ataxia telangiectasia mutated (ATM) kinase phosphorylates Ser-139 of H2AX in vitro, the post-translational modification pattern and the modifier of H2AX in organs in vivo are not yet well understood. In this study, we detected phosphorylation of H2AX at Ser-139 in cells of the mouse ear, liver, and kidney after X-irradiation. Moreover, the phosphorylation of H2AX was regulated depending on not only the cell type, but also the organ type and the localization of a cell type in an organ. Following X-irradiation, H2AX was phosphorylated in the liver and kidney of ATM gene knockout mice, suggesting that ATM kinase is not essential for phosphorylation of H2AX in these organs after X-irradiation in vivo

IgA腎症患者に対する低用量ステロイド剤の有効性に関する検討

IgA腎症患者に対するステロイド剤の有効投与量の決定に関しては不明な点が多い.今回われわれは,腎生検時の血清クレアチニン値が0.62mg/dlから1.58mg/dlの範囲のIgA腎症患者20例を対象に,低用量ステロイド剤の有効性について検討した.腎生検で軽度の炎症性変化を示した症例に, 1日20～30mgのステロイド剤の投与を行った.ステロイド治療前後の血清クレアチニン値の変化によって2つの群に分類した.グループ1は血清クレアチニン値が低下または変化がなかった群,グループ2は血清クレアチニン値が上昇した群である.検討した20例すべてにおいて,ステロイド治療による血清クレアチニン値の有意な変化は認められなかった.しかし,ステロイド治療12ヵ月後に蛋白尿は有意に減少した(1.0±0.8g/day vs. 0.5±1.1g/day, p=0.0202).また,ステロイド治療12ヵ月後に血尿は有意に減少した. (30.0±32.7RBC/HPF vs. 6.1±6.7RBC/HPF, p=0.0032). ステロイド治療中の収縮期および拡張期血圧の有意な変化はなかった.腎生検所見を比較すると,グループ2に比しグループ1で動脈硬化の程度は軽度であった(0.4±0.5 vs. 0.8±0.4,p=0.001).今回の結果から,腎生検で軽度の炎症性変化を示し,軽度の血管病変を有するIgA腎症患者では,低用量ステロイド剤治療により,蛋白尿が有意に減少し腎機能障害の進展が阻止される可能性が示唆された.The effectiveness of low-dose steroid therapy has not been determined in patients with IgA nephropathy. Twenty IgA nephropathy patients whose serum creatinine levels ranged from 0.62mg/dl to 1.58mg/dl at the time of renal biopsy were studied. The patients, with mild inflammatory activities such as cellular and/or fibro-cellular crescents, mesangial interposition with mononuclear cell infiltration, and interstitial inflammatory cell infiltration, were treated with prednisolone (20-30mg/day). The patients were then divided into two groups according to changes in the serum creatinine levels after steroid therapy: group I, improved renal function or no significant changes in renal function; group II, deterioration of renal function. In all of the patients studied, serum creatinine levels did not significantly change during steroid therapy (p=0.4493). However, proteinuria significantly reduced after 12 months of steroid therapy (1.0±0.8g/day vs. 0.5±1.1g/day, p=0.0202). In addition, hematuria significantly reduced after 12 months of steroid therapy (30.0±32.7 RBC/HPF vs. 6.1±6.7 RBC/HPF, p=0.0032). Blood pressure did not significantly change during steroid therapy. When serum creatinine levels were compared over the time course, the grade of arteriosclerosis was lower in group I than in group II (0.4±0.5 vs. 0.8±0.4, p=0.001). In conclusion, our data suggested that low-dose steroid therapy for IgA nephropathy patients with mild inflammatory activities could reduce the amount of urinary protein excretion and prevent deterioration of renal function, provided the histological findings in the renal biopsies showed mild arteriosclerosis

IgA腎症患者に対する低用量ステロイド剤の有効性に関する検討

IgA腎症患者に対するステロイド剤の有効投与量の決定に関しては不明な点が多い.今回われわれは,腎生検時の血清クレアチニン値が0.62mg/dlから1.58mg/dlの範囲のIgA腎症患者20例を対象に,低用量ステロイド剤の有効性について検討した.腎生検で軽度の炎症性変化を示した症例に, 1日20～30mgのステロイド剤の投与を行った.ステロイド治療前後の血清クレアチニン値の変化によって2つの群に分類した.グループ1は血清クレアチニン値が低下または変化がなかった群,グループ2は血清クレアチニン値が上昇した群である.検討した20例すべてにおいて,ステロイド治療による血清クレアチニン値の有意な変化は認められなかった.しかし,ステロイド治療12ヵ月後に蛋白尿は有意に減少した(1.0±0.8g/day vs. 0.5±1.1g/day, p=0.0202).また,ステロイド治療12ヵ月後に血尿は有意に減少した. (30.0±32.7RBC/HPF vs. 6.1±6.7RBC/HPF, p=0.0032). ステロイド治療中の収縮期および拡張期血圧の有意な変化はなかった.腎生検所見を比較すると,グループ2に比しグループ1で動脈硬化の程度は軽度であった(0.4±0.5 vs. 0.8±0.4,p=0.001).今回の結果から,腎生検で軽度の炎症性変化を示し,軽度の血管病変を有するIgA腎症患者では,低用量ステロイド剤治療により,蛋白尿が有意に減少し腎機能障害の進展が阻止される可能性が示唆された.The effectiveness of low-dose steroid therapy has not been determined in patients with IgA nephropathy. Twenty IgA nephropathy patients whose serum creatinine levels ranged from 0.62mg/dl to 1.58mg/dl at the time of renal biopsy were studied. The patients, with mild inflammatory activities such as cellular and/or fibro-cellular crescents, mesangial interposition with mononuclear cell infiltration, and interstitial inflammatory cell infiltration, were treated with prednisolone (20-30mg/day). The patients were then divided into two groups according to changes in the serum creatinine levels after steroid therapy: group I, improved renal function or no significant changes in renal function; group II, deterioration of renal function. In all of the patients studied, serum creatinine levels did not significantly change during steroid therapy (p=0.4493). However, proteinuria significantly reduced after 12 months of steroid therapy (1.0±0.8g/day vs. 0.5±1.1g/day, p=0.0202). In addition, hematuria significantly reduced after 12 months of steroid therapy (30.0±32.7 RBC/HPF vs. 6.1±6.7 RBC/HPF, p=0.0032). Blood pressure did not significantly change during steroid therapy. When serum creatinine levels were compared over the time course, the grade of arteriosclerosis was lower in group I than in group II (0.4±0.5 vs. 0.8±0.4, p=0.001). In conclusion, our data suggested that low-dose steroid therapy for IgA nephropathy patients with mild inflammatory activities could reduce the amount of urinary protein excretion and prevent deterioration of renal function, provided the histological findings in the renal biopsies showed mild arteriosclerosis