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| 1.
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Furuichi, Kengo ; Yuzawa, Yukio ; Shimizu, Miho ; Hara, Akinori ; Toyama, Tadashi ; Kitamura, Hiroshi ; Suzuki, Yoshiki ; Sato, Hiroshi ; Uesugi, Noriko ; Ubara, Yoshifumi ; Hisano, Satoshi ; Ueda, Yoshihiko ; Nishi, Shinichi ; Yokoyama, Hitoshi ; Nishino, Tomoya ; Kohagura, Kentaro ; Ogawa, Daisuke ; Mise, Koki ; Shibagaki, Yugo ; Kimura, Kenjiro ; Haneda, Masakazu ; Makino, Hirofumi ; Matsuo, Seiichi ; Wada, Takashi ; 古市, 賢吾 ; 清水, 美保 ; 原, 章規 ; 遠山, 直志 ; 和田, 隆志
概要:
金沢大学医薬保健研究域医学系<br />Background. The clinical and pathologic manifestations of nephropathy due to type 2 diabetes are div
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erse, but large-scale pathologic studies with long-termobservations are limited. Methods. Kidney biopsies and clinical data of 600 patients with type 2 diabetes were collected retrospectively from 13 centres across Japan. Thirteen pathologic findings (nine glomerular lesions, two interstitial lesions and two vascular lesions) were clearly defined and scored. Results. During the observation period, there were 304 composite kidney events [dialysis, doubling of creatinine or reduction of estimated glomerular filtration rate (eGFR) by half], 31 instances of chronic kidney disease (CKD) G5D, 76 cardiovascular events and 73 deaths. The mean observation period was 72.4 months. The distribution of CKD heat map categories for the 600 patients was 103 green or yellow, 149 orange and 348 red. Even in the cases in the green and yellow category, diffuse lesions (81.6%), polar vasculosis (42.6%) and subendothelial space widening (35.1%) were commonly detected. Cox proportional hazard analysis revealed that the presence of nodular lesions [hazard ratio (HR) 21.1, 95% confidence interval (CI) 5.3-84.6], exudative lesions (HR 5.1, 95% CI 1.3-20.3) and mesangiolysis (HR 7.6, 95% CI 2.0-28.8) in cases in the green and yellow category were associated with significantly great impact on composite kidney events after adjustment for clinical risk factors. Conclusions. This nationwide study on kidney biopsy of 600 cases with type 2 diabetes revealed that pathologic findings (presence of nodular lesions, exudative lesions and mesangiolysis) were strong predictors of kidney events in low-risk patients. © The Author 2017.<br />Embargo Period 12 months
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| 2.
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Iwata, Yasunori ; Wada, Takashi ; Yokoyama, Hitoshi ; Toyama, Tadashi ; Kitajima, Shinji ; Okumura, Toshiya ; Hara, Akinori ; Yamahana, Junya ; Nakaya, Izaya ; Kobayashi, Motoo ; Kitagawa, Kiyoki ; Kokubo, Satoshi ; Yoshimoto, Keiichi ; Shimizu, Kazuaki ; Sakai, Norihiko ; Furuichi, Kengo ; Koshino, Yoshitaka ; Takaeda, Chikako ; Takeda, Shinichi ; Takasawa, Kazuya ; Ohta, Satoshi ; Takaeda, Masayoshi ; Kaneko, Shuichi
概要:
金沢大学保健管理センター<br />金沢大学大学院医学系研究科<br />金沢大学附属病院<br />Background: In hemodialysis patients, adynamic bone disease has been
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reported to be closely associated with low levels of parathyroid hormone (PTH) due to exposure to high levels of serum calcium following the administration of calcium carbonate (CaCO3) or vitamin D agents. This study was conducted to clarify the therapeutic effect of a non-calcemic phosphate binder, sevelamer hydrochloride (sevelamer), for hypoparathyroidism in hemodialysis patients with or without diabetes mellitus. Methods: Based on entry criteria, 40 Japanese chronic hemodialysis patients (22 males and 18 females with a mean age of 60.6, 14 diabetic patients and 26 non-diabetic patients) were switched from CaCO3 to sevelamer for 48 weeks. Serum calcium, phosphate, intact (i) PTH and PTH-(1-84) were analyzed. Bone remodeling activity was evaluated by determining intact osteocalcine (iOC), bone-specific alkaline phosphatase (BAP). Results: The switch from CaCO3 to sevelamer significantly decreased the serum levels of calcium, resulting in the elevation of iPTH levels from 31±18 pg/mL to 95±96 pg/mL by 48 weeks. In contrast, serum phosphate levels remained similar to those in patients with CaCO3 treatment. Concomitantly, the levels of BAP and iOC were elevated. Further, these beneficial effects on bone turnover were observed in both diabetic and non-diabetic patients. Conclusion: Sevelamer reduced the calcium concentration and thereby increased PTH levels, resulting in the improvement of markers of bone turnover. The administration of sevelamer is of therapeutic benefit for the improvement of bone remodeling activity even in hemodialysis patients with diabetes. © 2007 The Japanese Society of Internal Medicine.
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| 3.
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Iwata, Yasunori ; Wada, Takashi ; Furuichi, Kengo ; Kitagawa, Kiyoki ; Kokubo, Satoshi ; Kobayashi, Motoo ; Sakai, Norihiko ; Yoshimoto, Keiichi ; Shimizu, Miho ; Kobayashi, Kenichi ; Yokoyama, Hitoshi
概要:
金沢大学医薬保健研究域医学系<br />Objective. KL-6 is reported to be excreted from the lung alveolar and bronchial epithelial cells and
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may be a good marker for monitoring disease activity of interstitial pneumonia. This study was designed to ascertain the clinical significance of serum KL-6 levels in interstitial pneumonia associated with anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. Methods. Serum KL-6 levels were determined by an enzyme-linked immunosorbent assay. Patients. We examined 20 healthy subjects, 13 patients with perinuclear (myeloperoxidase, MPO) ANCA-related vasculitis and 12 dermatomyositis (DM)/polymyositis (PM) patients as disease controls in this study. Six out of 13 patients with ANCA-related vasculitis had interstitial pneumonia. Results. Serum levels of KL-6 in ANCA-positive patients with interstitial pneumonia were significantly elevated, while they remained as low as those of healthy subjects in ANCA- positive patients without interstitial pneumonia. Similarly, KL-6 levels in sera were higher in 12 dermatomyositis/polymyositis patients with interstitial pneumonia, while they remained low in DM/PM patients without interstitial pneumonia. Moreover, the elevated serum KL-6 level was reduced during the convalescence induced by glucocorticoid therapy and reflected the disease activity of interstitial pneumonia associated with ANCA-related vasculitis. Conclusion. These data suggest that the measurement of serum KL-6 levels may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonia of patients with ANCA-related vasculitis.
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Shindo, Takayuki ; Kurihara, Hiroki ; Kuno, Kouji ; Yokoyama, Hitoshi ; Wada, Takashi ; Kurihara, Yukiko ; Imai, Tomihiko ; Wang, Yuhui ; Ogata, Masafumi ; Nishimatsu, Hiroaki ; Moriyama, Nobuo ; Oh-hashi, Yoshio ; Morita, Hiroyuki ; Ishikawa, Takatoshi ; Nagai, Ryozo ; Yazaki, Yoshio ; Matsushima, Kouji
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金沢大学医薬保健研究域医学系<br />A disintegrin and metalloproteinase (ADAM) represents a protein family possessing both metalloprotei
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nase and disintegrin domains. ADAMTS-1, an ADAM family member cloned from cachexigenic colon adenocarcinoma, is unusual in that it contains thrombospondin type I motifs and anchors to the extracellular matrix. To elucidate the biological role of ADAMTS-1, we developed ADAMTS-1-null mice by gene targeting. Targeted disruption of the mouse ADAMTS-1 gene resulted in growth retardation with adipose tissue malformation. Impaired female fertilization accompanied by histological changes in the uterus and ovaries also resulted. Furthermore, ADAMTS-1(-/-) mice demonstrated enlarged renal calices with fibrotic changes from the ureteropelvic junction through the ureter, and abnormal adrenal medullary architecture without capillary formation. ADAMTS-1 thus appears necessary for normal growth, fertility, and organ morphology and function. Moreover, the resemblance of the renal phenotype to human ureteropelvic junction obstruction may provide a clue to the pathogenesis of this common congenital disease.
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| 5.
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Nakaya, Izaya ; Iwata, Yasunori ; Abe, Toshio ; Yokoyama, Hitoshi ; Oda, Yoshio ; Nomura, Gakuji
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金沢大学医薬保健研究域医学系<br />A 69-year-old man was admitted with a large elastic mass in the upper abdomen. Computed tomography r
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evealed a massive tumor in contact with the liver and gastrointestinal endoscopy revealed a gastric adenocarcinoma. He developed acute renal failure with massive proteinuria and died with a marked enlargement of the tumor. Autopsy revealed a tumor located in the lesser omentum. The tumor was considered to be a Gastrointestinal Stromal Tumor (GIST) because it was positive for c-kit. In addition, crescent formations and immune complexes in glomeruli were observed. We report the first case of GIST complicated by rapidly progressive glomerulonephritis and gastric carcinoma.
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Iwata, Yasunori ; Wada, Takashi ; Uchiyama, Akio ; Miwa, Atsuo ; Nakaya, Izaya ; Tohyama, Tadashi ; Yamada, Yuhji ; Kurokawa, Toshiro ; Yoshida, Takashi ; Ohta, Satoshi ; Yokoyama, Hitoshi ; Iida, Hiroyuki
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金沢大学医薬保健研究域医学系<br />We report a case with immunoglobulin A (IgA) nephropathy, showing IgA deposition which disappeared a
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fter peripheral blood stem cell transplantation (PBSCT) for acute lymphocytic leukemia (ALL). In 1996, a 28-year-old man was diagnosed with IgA nephropathy by renal biopsy. Steroid therapy improved proteinuria from 3 g/day to 1 g/day. In 2003, he received PBSCT following the initial therapy for ALL. After complete remission, urinary protein and hematuria remained at between (-) and (±). In 2004, the second renal biopsy specimen revealed no deposit of IgA or C3. These findings suggested that immune reconstruction with PBSCT following immunosuppression therapy was of benefit to IgA nephropathy. © 2006 The Japanese Society of Internal Medicine.
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| 7.
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Wada, Takashi ; Tomosugi, Naohisa I. ; Naito, Takero ; Yokoyama, Hitoshi ; Kobayashi, Kenichi ; Harada, Akihisa ; Mukaida, Naofumi ; Matsushima, Kouji
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Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interle
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ukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 ± 0.97 and 1.39 ± 0.53 mg/h, respectively) compared with those of untreated animals (0.77 ± 0.21 and 0.01 ± 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 ± 0.15 and 0.02 ± 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.
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| 8.
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Wada, Takashi ; Yokoyama, Hitoshi ; Sakai, Norihiko ; Izumiya, Yoshiaki ; Shimizu, Miho ; Furuichi, Kengo ; Segawa, Chikako ; Misaki, Tsuguho ; Kobayashi, Ken-ichi
概要:
We describe the upregulation of cytokines in a 45-year-old woman with tubulointerstitial nephritis and membranous nephro
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pathy revealed by renal biopsy. She was treated with a combination of prednisolone and cyclosporin. Histological findings showed appreciable improvement, and urinary protein excretion was decreased from 15 g/day to 1 g/day. Elevated urinary levels of chemokines, interleukin (IL)-8 and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein (MCP)-1, and serum levels of tumor necrosis factor (TNF)-α decreased during convalescence; 13 other patients with membranous nephropathy did not show elevation of these cytokines. These results suggest that the upregulation of these cytokines may participate in the pathogenesis of tubulointerstitial nephritis and that combination therapy of prednisolone and cyclosporin may be effective, possibly via inducing a decrease in these cytokines.
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Ohta, Satoshi ; Yokoyama, Hitoshi ; Ise, Takuyuki ; Takasawa, Kazuya ; Wada, Takashi ; Nakao, Sinji ; Matsuda, Tamotsu ; Kobayashi, Ken-ichi
概要:
Two cases of leukemia were treated successfully with apheresis for delayed recovery of erythropoiesis due to antibody-mediated red cell aplasia after ABO-mismatched bone marrow transplantation (BMT). A 25-year-old female (ABO
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group O) underwent BMT from her brother (group A). Immunoadsorption using Biosynsorb A performed on day 146 after BMT followed by double filtration plasma pheresis (DFPP) reduced anti-A antibody titers from 1:32 to 1:2. Anemia improved dramatically within 2 weeks. A 49-year-old female (group O) underwent BMT from her mother (group A). She was treated with DFPP on day 131 after BMT. Anti-A antibody titers dropped from 1:16 to 1:1 and anemia improved gradually.
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| 10.
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Oshima, Megumi ; Kitajima, Shinji ; Toyama, Tadashi ; Hara, Akinori ; Kitagawa, Kiyoki ; Iwata, Yasunori ; Shimizu, Miho ; Nishio, Saori ; Imura, Junko ; Yokoyama, Hitoshi ; Furuichi, Kengo ; Kaneko, Shuichi ; Wada, Takashi
概要:
We herein report a case of spontaneous pregnancy and preterm delivery in a 29-year-old patient with myeloperoxidase-anti
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neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis. Her basal serum creatinine level before pregnancy was 1.4 mg/dL and her urinary protein level was approximately 2 g/day. The proteinuria and hematuria increased during pregnancy, and the patient was admitted to our hospital and treated with prednisolone (PSL). At 27 weeks of gestation, she delivered a live infant weighing 848 g via cesarean section. No relapse of ANCA-associated glomerulonephritis occurred. © 2013 The Japanese Society of Internal Medicine.
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