Harutaka Yamada

Publications of Harutaka Yamada

• Extracellular-superoxide dismutase expression in COS7 cells exposed to cadmium chloride.

  Authors: Aya Obara, Tetsuro Kamiya, Misato Izumi, Hirokazu Hara, Harutaka Yamada, Tetsuo Adachi

  Biological & pharmaceutical bulletin. 01/2011; 34(9):1443-7.

  Cadmium (Cd), an industrial and environmental pollutant, preferentially accumulates in the kidney, a major target for Cd-related toxicity. It has been reported that Cd exposure produces reactiveCadmium (Cd), an industrial and environmental pollutant, preferentially accumulates in the kidney, a major target for Cd-related toxicity. It has been reported that Cd exposure produces reactive oxygen species (ROS) and induces cytotoxicity. Extracellular-superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects the cells from damaging effects of ROS; however, the effect of Cd on the expression of EC-SOD in COS7 cells remains unclear. In this study, exposure to cadmium chloride (CdCl₂) enhanced intracellular ROS generation and induced COS7 cell death. Moreover, exposure to Cd decreased the expression of EC-SOD at mRNA and protein levels, but not of other SOD isozymes, copper-and zinc-containing SOD and manganese-containing SOD. The reduction of EC-SOD and cell viability was partially attenuated by pretreatment with an antioxidant, N-acetylcysteine. Further, we determined the involvement of p38-mitogen-activated protein kinase (p38-MAPK) in the reduction of EC-SOD. From these observations, p38-MAPK signaling cascades activated by ROS play a pivotal role in the reduction of EC-SOD, and it is concluded that the reduction of EC-SOD leads to a decrease in the resistance to oxidative stress of Cd-exposed COS7 cells.

• Effects of combination therapy with angiotensin II type I receptor blockers and calcium channel blockers on renal function in hypertensive patients/a retrospective, "real-world" comparative study.

  Authors: Harutaka Yamada, Norihiro Suga, Kunihiro Maeda, Yukihiro Kimura, Naoto Miura, Arao Futenma, Hirokazu Imai

  Arzneimittel-Forschung. 01/2010; 60(2):64-70.

  Combination therapies with angiotensin II type I receptor blockers (ARBs) and calcium channel blockers (CCBs) are frequently administered to hypertensive patients, because these regimens haveCombination therapies with angiotensin II type I receptor blockers (ARBs) and calcium channel blockers (CCBs) are frequently administered to hypertensive patients, because these regimens have renoprotective and antihypertensive effects. However, few studies have focused on the renoprotective effects of individual CCBs when combined with ARBs for hypertension. Two hundred eighty-six outpatients prescribed three different CCBs (benidipine [CAS 91599-74-5], amlodipine [CAS 111470-99-6] and controlled release nifedipine (nifedipine CR) [CAS 21829-25-4]) for hypertension in combination with ARBs during a 4-year period were registered in a retrospective comparative study. The factors that influenced the appearance of renal events defined as doubling of serum creatinine were investigated. The renal event rate was significantly lower in the benidipine than in the amlodipine (p < 0.05) and nifedipine CR (p < 0.01) groups. Multivariate analysis revealed hazard ratios for renal events to be significantly higher with chronic kidney disease (CKD) and lower with benidipine. Moreover, among patients with CKD, the benidipine group showed a significantly lower renal event rate than the amlodipine (p < 0.05) and nifedipine groups (p < 0.05). In hypertensive patients treated with ARB and CCB, benidipine exhibits a better renoprotective effect than other drugs of this class (amlodipine and nifedipine CR).

• An IgA1-lambda-type monoclonal immunoglobulin deposition disease associated with membranous features in a patient with chronic hepatitis C viral infection and rectal cancer.

  Authors: Naoto Miura, Yuko Uemura, Natsuko Suzuki, Norihiro Suga, Kunihiro Maeda, Satoshi Yamaguchi, Wataru Kitagawa, Harutaka Yamada, Kazuhiro Nishikawa, Hirokazu Imai

  Clinical and experimental nephrology. 10/2009;

  A 61-year-old man infected with hepatitis C virus developed urinary protein. Two-dimensional electrophoresis and immunoblotting of sera revealed no monoclonal proteins. Light microscopy andA 61-year-old man infected with hepatitis C virus developed urinary protein. Two-dimensional electrophoresis and immunoblotting of sera revealed no monoclonal proteins. Light microscopy and immunofluorescence of a kidney biopsy specimen demonstrated bubbling appearance and formation of spikes, associated with predominantly IgA1-lambda deposition, but not IgG, along glomerular capillary walls. Electron microscopy showed electron-dense deposits without any fibrillary structure located in the glomerular basement membrane. Seven months after the kidney biopsy, the patient had a surgical operation for rectal cancer. One year later, the urinary protein was still present. The present case is the first report of an IgA1-lambda-type monoclonal immunoglobulin deposition disease associated with membranous features.

• Cobalt chloride decreases EC-SOD expression through intracellular ROS generation and p38-MAPK pathways in COS7 cells.

  Authors: Tetsuro Kamiya, Hirokazu Hara, Harutaka Yamada, Hirokazu Imai, Naoki Inagaki, Tetsuo Adachi

  Free radical research. 12/2008;

  It is known that cells suffer a chronic hypoxic condition during the development of proximal tubulointerstitial disease. However, it is accepted that extracellular-superoxide dismutase (EC-SOD)It is known that cells suffer a chronic hypoxic condition during the development of proximal tubulointerstitial disease. However, it is accepted that extracellular-superoxide dismutase (EC-SOD) protects the cells from oxidative stress. The purpose of this study was to elucidate the regulation of EC-SOD expression in cells under hypoxia. The results show that the expressions of EC-SOD mRNA and protein in cobalt chloride (CoCl(2))-treated COS7 cells decreased in a dose- and time-dependent manner, whereas the expressions of other SOD isoforms (Cu/Zn-SOD and Mn-SOD) were not changed. The down-regulation of EC-SOD mRNA was suppressed by pre-treatment with the antioxidant trolox and the p38 mitogen-activated protein kinase (p38-MAPK) inhibitor SB203580. It is concluded that the expression of EC-SOD is decreased through ROS and p38-MAPK signalling cascades and that the down-regulation of EC-SOD leads to a decrease in the resistance to oxidative stress of COS7 cells under hypoxia induced by CoCl(2).

• Membranous nephropathy (bubbling appearance and spike formation) without immunoglobulin deposition in a patient with systemic lupus erythematosus.

  Authors: Naoto Miura, Yuki Mori, Masabumi Yoshino, Norihiro Suga, Wataru Kitagawa, Harutaka Yamada, Kazuhiro Nishikawa, Hirokazu Imai

  Clinical and experimental nephrology. 11/2008;

  A 53-year-old Japanese man with systemic lupus erythematosus developed proteinuria and hematuria after a urinary stone episode. A light microscopic study of a kidney biopsy specimen demonstrated aA 53-year-old Japanese man with systemic lupus erythematosus developed proteinuria and hematuria after a urinary stone episode. A light microscopic study of a kidney biopsy specimen demonstrated a bubbling appearance and spike formation of the basement membrane. Immunofluorescent studies revealed that there were no significant depositions of immunoglobulins, such as IgG (-), IgA (-), IgM (+/-), kappa light chain (+/-), lambda light chain (+/-), or C3 (-) in the glomerular capillary wall, though C1q was present as one-plus positive staining in mesangial areas. Electron microscopic studies showed that the thickness of the basement membrane varied from thin to thick without electron dense deposits, and that the cellular components of the podocyte were irregularly present in the basement membrane. Urinary protein decreased after the usage of prednisolone and mizoribine; however, proteinuria aggravated after an episode of urinary stone during the same treatment.

• Massive proteinuria and acute renal failure after oral bisphosphonate (alendronate) administration in a patient with focal segmental glomerulosclerosis.

  Authors: Naoto Miura, Natsuko Mizuno, Ryuhei Aoyama, Wataru Kitagawa, Harutaka Yamada, Kazuhiro Nishikawa, Hirokazu Imai

  Clinical and experimental nephrology. 09/2008;

  A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6A 61-year-old Japanese man with nephrotic syndrome due to focal segmental glomerulosclerosis was initially responding well to steroid therapy. The amount of daily urinary protein decreased from 15.6 to 2.8 g. Within 14 days of the oral bisphosphonate (alendronate sodium) administration, the amount of daily urinary protein increased rapidly up to 12.8 g with acute renal failure. After discontinuing the oral alendronate, the patient underwent six cycles of hemodialysis and four cycles of LDL apheresis. Urinary volume and serum creatinine levels recovered to the normal range, with urinary protein disappearing completely within 40 days. This report demonstrates that not only intravenous, but also oral bisphosphonates can aggravate proteinuria and acute renal failure.

• Membranous nephropathy and pulmonary alveolar proteinosis.

  Authors: Harutaka Yamada, Naoto Miura, Wataru Kitagawa, Yukari Kashima, Seiko Matsui, Norio Ozeki, Kazuhiro Nishikawa, Hirokazu Imai

  Internal medicine (Tokyo, Japan). 02/2007; 46(17):1441-6.

  A 47-year-old woman with a severe cough and high-grade fever demonstrated proteinuria of 3.2 g/day. Chest radiograph and CT scan revealed scattered small nodules and ground-glass opacities withA 47-year-old woman with a severe cough and high-grade fever demonstrated proteinuria of 3.2 g/day. Chest radiograph and CT scan revealed scattered small nodules and ground-glass opacities with interlobular septal thickening in both lungs. The serum levels of surfactant A, surfactant D, and KL-6 were increased to 190 ng/ml (normal: 0-43.8), 360 ng/ml (normal: 0-110), and 4850 U/ml (normal: 0-500), respectively. Video-assisted thoracoscopic lung biopsy revealed eosinophilic amorphous material within alveoli and thickened alveolar septa, which is compatible with pulmonary alveolar proteinosis. Kidney biopsy exhibited membranous nephropathy (Stage I-II) accompanied by granular IgG deposition along the glomerular basement membrane. Although the patient refused treatment with granulocyte macrophage colony stimulating factor (GM-CSF) for pulmonary alveolar proteinosis, her proteinuria and the pulmonary lesion gradually diminished and disappeared after one year.

• Acute renal failure due to IgM-lambda glomerular thrombi and MPGN-like lesions in a patient with angioimmunoblastic T-Cell lymphoma.

  Authors: Naoto Miura, Keisuke Suzuki, Masabumi Yoshino, Wataru Kitagawa, Harutaka Yamada, Hiroshi Ohtani, Kensuke Joh, Hirokazu Imai

  American journal of kidney diseases : the official journal of the National Kidney Foundation. 08/2006; 48(1):e3-9.

  A 70-year-old man with angioimmunoblastic T-cell lymphoma developed acute renal failure. Laboratory data showed decreased levels of serum C3, C4, and CH50, elevated immunoglobulin M (IgM) levels, andA 70-year-old man with angioimmunoblastic T-cell lymphoma developed acute renal failure. Laboratory data showed decreased levels of serum C3, C4, and CH50, elevated immunoglobulin M (IgM) levels, and the presence of cryoglobulinemia (IgM-lambda). Renal biopsy showed membranoproliferative glomerulonephritis-like lesions with azan-red-stained thrombi in the glomerular capillary lumen. Immunofluorescence showed that IgM-lambda stained strongly in the glomerular capillary lumen, equal to the azan-red-stained thrombi, whereas C3 and C4 staining was negative. Electron microscopy showed electron-dense deposits in the subendothelial space and glomerular thrombi lacking fine fibrillar structure. These findings suggest that cryoglobulin, which consists of monoclonal IgM-lambda, induced glomerular thrombi and acute renal failure in a patient with angioimmunoblastic T-cell lymphoma.

• The increase of antiglomerular basement membrane antibody following pauci-immune-type crescentic glomerulonephritis.

  Authors: Wataru Kitagawa, Naoto Miura, Harutaka Yamada, Kazuhiro Nishikawa, Arao Futenma, Hirokazu Imai

  Clinical and experimental nephrology. 03/2005; 9(1):69-73.

  A 50-year-old woman was admitted because of high fever and fatigue. Proteinuria, hematuria, and elevated BUN (47.8 mg/dl) and creatinine (3.4 mg/dl) suggested rapidly progressive glomerulonephritis.A 50-year-old woman was admitted because of high fever and fatigue. Proteinuria, hematuria, and elevated BUN (47.8 mg/dl) and creatinine (3.4 mg/dl) suggested rapidly progressive glomerulonephritis. The serological study revealed all negative results for rheumatoid factor, antinuclear antibody, serum cryoglobulins, MPO-ANCA, PR3-ANCA, and anti-streptolysin O. Antiglomerular basement membrane (GBM) antibody, as assessed by ELISA, was 11 EU (normal, <10). Kidney biopsy on the eighth hospital day demonstrated pauci-immune-type crescentic glomerulonephritis without ANCA. Methylprednisolone pulse therapy (500 mg/day, 3 days) and 45 mg/day prednisolone orally were started. At 3 weeks after kidney biopsy, the anti-GBM antibody value increased from 11 EU/ml to 116 EU/ml, and MPO and PR3-ANCA were still negative. HLA type was DR8 and DR 15(2), with a genotype of HLA-DRB1*08021 and HLA-DRB1*15011. The present case suggests that HLA-DR15 plays an important role on antibody production against alpha 3(IV) NC1 autoantigen after severe nephritis or tissue damage.

• [Extracellular-superoxide dismutase production in mesangial cell growing in extracellular matrix]

  Authors: Harutaka Yamada, Tetsuo Adachi, Yasukazu Yamada, Sachiko Misao, Keisuke Suzuki, Hitoshi Watanabe, Wataru Kitagawa, Naoto Miura, Cyouryu You, Masahito Sakuma, Kazuhiro Nishikawa, Arao Futenma, Hirokazu Imai

  Nippon Jinzo Gakkai shi. 02/2005; 47(1):32-7.

  To study the protective function against oxygen radicals in the mesangial area, we assessed extracellular superoxide dismutase (EC-SOD) production in mesangial cells (MCs) in vitro. These cells haveTo study the protective function against oxygen radicals in the mesangial area, we assessed extracellular superoxide dismutase (EC-SOD) production in mesangial cells (MCs) in vitro. These cells have a major protective function against oxygen radicals in the extracellular space. In two different kinds of culture conditions: "growth medium" with fetal cow serum, and "differentiation medium" with reduced growth factor, and four extracellular matrixes; type I collagen, type IV collagen, laminin and fibronectin, were added to the MC culture. With the difference in the culture media, differentiation medium induced EC-SOD hyper-production associated with the both of the slowing down of cell proliferation and the suppression of IL-6 and IL-8 production. With difference in the extracellular matrix, the presence of type VI collagen and laminin promoted higher production of EC-SOD than fibronectin and type I collagen. Type IV collagen and laminin associated with the physiological condition of the glomeruli promoted EC-SOD production compared with the presence of type I collagen and fibronectin dominantly located in pathological condition. Suppression of EC-SOD production in growth medium along with MC proliferation and chemokine hyper-production compared with production in differentiation medium might mimic reduction of the protective capacity against oxygen radical toxity during mesangial proliferation in the glomerular nephritis. MC proliferation with type I collagen and fibronectin might enhance oxygen radical toxity in the glomeruli, and accelerate glomerular sclerosis through the suppression of EC-SOD production.

• Establishment of anti-rat-Cu,Zn-superoxide dismutase monoclonal antibodies applied to a highly sensitive immunoassay and immunohistochemistry system.

  Authors: Harutaka Yamada, Yasukazu Yamada, Sachiko Misao, Wataru Kitagawa, Takafumi Nomura, Takanari Aoki, Naoto Miura, Masato Sakuma, Kazuhiro Nishikawa, Arao Futenma, Hirokazu Imai

  Hybridoma and hybridomics. 09/2004; 23(4):232-6.

  The superoxide anion has been implicated in a wide range of diseases. The major protector against superoxide anion in the cell cytosol is Cu,Zn-superoxide dismutase (Cu,Zn-SOD). In this study, antiThe superoxide anion has been implicated in a wide range of diseases. The major protector against superoxide anion in the cell cytosol is Cu,Zn-superoxide dismutase (Cu,Zn-SOD). In this study, anti rat Cu,Zn-SOD was established in murine monoclonal antibodies for the first time. These antibodies were applied to both a highly sensitive EIA system in serum and immunohistochemical methods for detection in gastric mucosa tissues. The proposed EIA method had a high sensitivity within the assay range, 10-300 pg/mL, good percentage, 96.9 +/- 5.60%, and good reproducibility; within-day assay CV = 8.6-10.2%, between-day assay CV = 6.5-11.7%. Inmmunohistochemically, Cu,Zn-SOD localized in the esophagus epithelial cells, gastric oxyntic cells, surface of the gastric lumen side in the small intestine and colonic epithelial cells. The establishment of anti-rat CuZn-SOD monoclonal antibody allows both specific analysis of immunoquantitation in rat Cu,Zn-SOD and highly specific detection of Cu,Zn-SOD location by immunohistochemical methods.

• [Differential diagnosis of kidney diseases: an approach in the diagnosis of kidney diseases]

  Authors: Hirokazu Imai, Harutaka Yamada

  Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine. 06/2004; 93(5):858-65.

• Extracellular superoxide dismutase and glomerular mesangial cells: its production and regulation.

  Authors: Harutaka Yamada, Tetsuo Adachi, Atsushi Fukatsu, Sachiko Misao, Yasukazu Yamada, Takanari Aoki, Naoto Miura, Masato Sakuma, Kazuhiro Nishikawa, Arao Futenma, Shinichi Kakumu

  FEBS letters. 06/2002; 519(1-3):77-81.

  Extracellular superoxide dismutase (EC-SOD) is synthesized in mesenchymally derived cells and prevents the oxygen radical-induced injury. We studied whether kidney mesangial cells (MCs) produceExtracellular superoxide dismutase (EC-SOD) is synthesized in mesenchymally derived cells and prevents the oxygen radical-induced injury. We studied whether kidney mesangial cells (MCs) produce EC-SOD and how its production is associated with chemokine secretion. Under unstimulated condition, MCs produced EC-SOD, and its production was correlated positively with cyclic adenosine monophosphate (cAMP), but negatively with interleukin (IL)-6 or IL-8 production. By prednisolone or phorbol myristate acetate treatment, EC-SOD levels were correlated negatively with levels of IL-6 and IL-8. The presence of adenylate cyclase inhibitor 2',3'-dideoxyadenosine lost the prednisolone effect. The stimulation of EC-SOD production might be one of the important effects of prednisolone via cAMP pathway in MCs.

• Quantitative and qualitative changes of extracellular-superoxide dismutase in patients with various diseases

  Authors: Tetsuo Adachi, Makoto Nakamura, Harutaka Yamada, Arao Futenma, Katsumi Kato, Kazuyuki Hirano

  Clinica Chimica Acta.

  Extracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein that is the major SOD isozyme in extracellular fluids. It has previously been shown that EC-SOD levels in sera from healthyExtracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein that is the major SOD isozyme in extracellular fluids. It has previously been shown that EC-SOD levels in sera from healthy persons are clearly divided into two discontinuous groups: a lower group (named Group I, below 120 ng/ml) and a higher group (Group II, above 400 ng/ml). The family studies have shown that the high EC-SOD level in healthy persons is genetically transmitted. We report here on the EC-SOD levels in the sera of patients with various diseases. The EC-SOD levels were distinctly higher in patients with renal diseases and moderately higher in liver diseases and diabetes than those in normal healthy persons. In cerebrovascular diseases, heart diseases and acute digestive diseases, significant differences of EC-SOD were not observed. In patients with renal diseases, the increase of EC-SOD was accompanied by the lack of renal function. Serum EC-SOD in Group I healthy persons is known to be heterogeneous with regard to heparin affinity and can be separated into three fractions: A without affinity, B with weak affinity and C with relatively strong heparin affinity, whereas the EC-SOD in Group II is mainly one fraction of C-type. Also in the case of hemodialysis patients, serum EC-SOD in Group I or Group I' (~120–400 ng/ml) was divided into three fractions. EC-SOD in Group II showed two different profiles on heparin-Sepharose column chromatographies: one consisted mainly of EC-SOD C and the other consisted of EC-SOD A and C. It is probable that the high serum EC-SOD level in hemodialysis patients was due to two possible factors: the genetic transmitted factor and unknown pathophysiological factor(s).