Kazunobu Sugimura

Osaka City University, Ōsaka, Ōsaka, Japan

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Publications (105)278.87 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocyte growth factor (HGF) facilitates the regeneration of injured kidney in acute renal failure (ARF). HGF is produced as a single-chain precursor by cells of mesenchymal origin and is converted to a biologically active, heterodimeric molecule by proteol ytic processing. We studied HGF mRNA and protein levels in systemic organs of glycerol-induced ARF rats, a model of crush syndrome. HGF protein concentration of tissue homogenate was measured by ELISA. Both mRNA and protein levels were increased in liver and spleen at 24 hours after the glycerol injection whereas HGF protein level was decreased in the injured kidney. Expression of HGF receptor/c-met mRNA was elevated only in the kidney. These results suggest that HGF supplied in an endocrine manner may play an important role in the regenerating process following ARF. Next, we measured serum HGF concentration by ELISA in 8 ARF patients caused by crush syndrome and the molecular size of serum HGF was determined byimmun oblotting. Although serum HGF levels elevated in all patients, the HGF levels did not associate with their prognoses. While a single-chain molecule was predominantly observed in sera from chronic renal failure patients and healthy subjects, the majority of serum HGF was a heterodimeric form in 7 ARF patients. In one patient who developed disseminated intravascular coagulation syndrome and had a poor prognosis, a single-chain molecule was predominant although the serum HGF concentration was equivalent. These data suggest that the activity of proteolytic processing may be also an important factor for the expression of the biological function of HGF.
    Renal Failure 07/2009; 23(3-4):597-603. DOI:10.1081/JDI-100104741 · 0.94 Impact Factor
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    ABSTRACT: It is recognized that matrix metalloproteinase-3 (MMP-3) is abundantly expressed in active rheumatoid synovium, and that serum level of MMP-3 is a useful marker for diagnosis of rheumatoid arthritis and for evaluation of prognosis in joint destruction. Little is known about serum MMP-3 levels in haemodialysis (HD) patients, and thus, the association between serum MMP-3 and dialysis-related amyloidosis (DRA) has yet to be elucidated. Serum levels of MMP-3 were measured by enzyme immunoassay in 150 HD patients, 90 without DRA and 60 with DRA, before HD. Simple regression analysis was performed to investigate the relationship between serum level of MMP-3 and clinical parameters, including age, HD duration, C-reactive protein and beta2 microglobulin (BMG). Serum levels of MMP-3 were significantly higher in HD patients with DRA than in HD patients without DRA (258.2 +/- 118.1 vs 201.5 +/- 98.4 pg/mL, P = 0.0017), and both levels were significantly higher than those of healthy subjects (45.6 +/- 13.4 pg/mL, P < 0.0001). Serum MMP-3 levels significantly correlated with serum levels of BMG (r = 0.197, P = 0.0164) and HD duration (r = 0.168, P = 0.0427). Moreover, serum MMP-3 levels significantly correlated with serum BMG levels in HD patients without DRA (r = 0.341, P = 0.0012), but not in HD patients with DRA. Our results suggest that matrix metalloproteinase activity increases in HD patients, which may be associated with BMG and DRA.
    Nephrology 04/2008; 13(2):104-8. DOI:10.1111/j.1440-1797.2007.00845.x · 2.08 Impact Factor
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    ABSTRACT: The prevalence of metabolic syndrome (MS) after renal transplantation has yet to be elucidated. In the present study, we investigated the prevalence of MS in Japanese renal transplant recipients. A cross-sectional study was conducted to determine the prevalence of MS in 101 renal transplant recipients at Osaka City University Hospital. The prevalence of MS was determined using the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria (modified and original) and the International Diabetes Federation (IDF) criteria. Using the modified (Japanese) NCEP criteria, a total of 24 out of 101 patients (23.8%) had MS including 21 out of 64 male patients (32.8%) and three out of 37 female patients (8.1%). Using the modified (Asian) NCEP criteria, MS was diagnosed in 23 patients (22.8%); 19 male (29.7%) and four female (10.8%). Using the original NCEP criteria, MS was diagnosed in 15 patients (14.9%); 12 male (18.8%) and three female (8.1%). Using the IDF criteria, MS was diagnosed in 16 patients (15.8%); 15 male (23.4%) and one female (2.7%). The prevalence of MS differed according to the NCEP criteria used, which had different cut-off points for waist circumference (14.9-23.8%). By the IDF criteria, which cites central obesity as an essential component, the prevalence of MS was slightly lower. Furthermore, in our study, MS was more prevalent in male renal transplant recipients.
    Nephrology 09/2007; 12(4):413-7. DOI:10.1111/j.1440-1797.2007.00791.x · 2.08 Impact Factor
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    ABSTRACT: Although intravesical instillation of bacillus Calmette-Guerin (BCG) is a clinically well-recognized therapy for bladder carcinoma in situ and recurrence prophylaxis, these mechanisms have not been fully understood. We studied the effects of BCG infection (Connaught strain) on target cancer cells and host immune systems in murine bladder cancer. The bladder cancer cell line, MB49, was used in C57/BL6 mice in vivo and in vitro. In vitro cytotoxicities against the cancer cell line were measured by 24-h 51Cr release assay. For effector cells, spleen mononuclear cells were obtained from mice injected intraperitoneally with BCG or BCG-infected irradiated MB49 cells. Although BCG infection of cancer cells did not affect the proliferation speed in vitro, the mice injected subcutaneously with BCG-infected MB49 cells survived significantly longer than those given untreated cancer cells. The mice surviving without tumor growth after injection of BCG-infected cancer cells could not reject a second injection of intact MB49 cells. In vitro cytotoxicity was enhanced by BCG infection of target cancer cells, but not by immunizing the mice with BCG from which effector cells were obtained. Moreover, cytotoxicity disappeared by depleting natural killer (NK) cells from effector cells. Although in vitro cytotoxicity was increased by immunizing the mice with BCG-infected irradiated MB49 cells, survival did not improve in these mice. These results suggest that a major part of BCG's anti-tumor effects can be attributed to the elimination of BCG-infected cancer cells by NK cells.
    Oncology Reports 07/2007; 17(6):1469-74. DOI:10.3892/or.17.6.1469 · 2.30 Impact Factor
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    Ishun Go · Yoshiaki Takemoto · Kenji Tsuchida · Kazunobu Sugimura · Tatsuya Nakatani ·
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    ABSTRACT: Renal anemia is a very serious problem in hemodialysis patients. In this regard, the investigation was focused on whether ultrapure dialysate could improve renal anemia and the mechanism of renal anemia. Ultrapure dialysate was used over a 2 years period for 61 patients on maintenance hemodialysis. During this period, the changes in renal anemia and red blood cell life span were investigated. The changes in the latter were evaluated using the creatine concentration in red blood cell. The hemoglobin concentration, RBC count, and hematocrit concentration before the use of the ultrapure dialysate were 9.1 +/- 0.2 g/dL, 309.9 +/- L7.2 x 10(4)/microL, and 28.8 +/- 0.6%, respectively. These values significantly increased to 10.2 +/- 0.1 g/dL, 349.7 +/- 5.6 x 10(4)/microL, and 32.6 +/- 0.3%, respectively, after 2 years of ultrapure dialysate use. The increase in reticulocyte count indicated enhanced erythropoiesis by ultrapure dialysate. The red blood cell life span evaluated by creatine concentration in red blood cell was also prolonged after the use of ultrapure dialysate. Ultrapure dialysate is considered to improve the renal anemia of dialysis patients by promoting erythropoiesis and prolonging red blood cell life span.
    Osaka city medical journal 07/2007; 53(1):17-23.
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    ABSTRACT: Bisphosphonates have been reported to be effective in reducing bone pain and skeletal-related events associated with bone metastases in hormone-refractory prostate cancer (HRPC). However, whether bone resorption is reduced primarily by these particular drugs is difficult to evaluate because patients with HRPC are usually treated with secondary or tertiary hormonal manipulations including second-line antiandrogens, high-dose diethylstilbestrol, or low-dose dexamethasone therapies, some of which may also be effective. Thus, we assessed changes in the level of the carboxyterminal telopeptide of type-I collagen (ICTP), a bone resorption marker, before and after pamidronate administration in HRPC patients with increasing prostate-specific antigen (PSA) levels. Twenty-one HRPC patients with bone metastases and increasing PSA levels were intravenously treated with pamidronate at a dose of 30 mg either every 2 or every 4 weeks. Pamidronate administration was started immediately after confirmation of three consecutive increases in the PSA level. In 14 patients (67%), the ICTP levels decreased after the administration of pamidronate, despite increasing PSA levels. In 7 of these cases, the ICTP levels were lower than those recorded for 6 months or longer before the start of pamidronate administration. The characteristics of the responders were compared with those of the non-responders. In 67% of the HRPC patients with increasing PSA levels, pamidronate reduced the accelerated turnover of bone metabolism caused by metastases of prostate cancer.
    Urologia Internationalis 02/2007; 78(4):345-50. DOI:10.1159/000100840 · 1.43 Impact Factor
  • Article: MP12.12
    T. Sonoda · K. Sugimura · K. Matsumura · S. Ikemoto · T. Nakatani ·

    Urology 11/2006; 68:132-132. DOI:10.1016/j.urology.2006.08.417 · 2.19 Impact Factor
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    ABSTRACT: Renal ischemia-reperfusion (I/R) injury during renal transplantation is a significant cause of renal dysfunction. The pathological role of free radicals in this process is a major concern. We investigated the effect of a free radical scavenger, edaravone (MCI-186), in renal I/R injury. Male Lewis rats (270 to 320 g) were used for the model. The right kidney was harvested and left renal artery and vein were clamped as laparotomy. The kidney was reperfused after 90 minutes of ischemia. Edaravone (10 mg/kg) was delivered intravenously before ischemia and after reperfusion to prevent the neutrophil activation. In the nontreatment I/R group, no rat survived beyond 4 days. However, in the edaravone I/R treatment group, one among five rats survived more than 7 days. These results suggested that treatment with edaravone ameliorated renal I/R injury, and that the agent has the potential to ameliorate preservation injury in renal transplantation.
    Transplantation Proceedings 10/2006; 38(7):2199-200. DOI:10.1016/j.transproceed.2006.06.077 · 0.98 Impact Factor
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    ABSTRACT: Approximately 70% of patients with advanced prostate cancer have bone metastases, which are associated with considerable skeletal morbidity, accompanied by severe bone pain that requires narcotics or palliative radiation therapy, pathological fractures, spinal cord compression and hypercalcemia of malignancy (HCM), which consequentiy lower the patient's quality of life. Bisphosphonates, potent inhibitors of osteoclast activity and survival, therefore inhibiting osteoclast-mediated bone absorption, transiently palliative bone pain and decrease analgesic usage in patients who have hormone-refractory prostate cancer (HRPC) with bone metastases. Recently, a randomized controlled trial showed that a third-generation bisphosphonate, zoledronic acid reduced bone pain and skeletal-related events (SREs). In this manuscript, we reviwed the efficacy of bisphosphonates in HRPC with bone metastases from several clinical studies and discuss treatment of advanced prostate cancer with bisphosphonates.
    Hinyokika kiyo. Acta urologica Japonica 07/2006; 52(6):491-4.
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    ABSTRACT: We report the first case of primary extragonadal seminoma arising in the perineum. A 34-year-old-man presented with a 2-cm painless mass in the perineum. He underwent surgical resection, and histology showed poorly differentiated adenocarcinoma. Three months later, local recurrence occurred. Whole evaluation including ultrasound and MRI of the testes were normal, so he underwent surgical wide excision, and pathology showed the tumor was pure seminoma. He received two courses of bleomycin, etoposide and cisplatin (BEP) therapy, and there has been no evidence of recurrence for 1 month.
    Urologia Internationalis 02/2006; 76(4):364-7. DOI:10.1159/000092065 · 1.43 Impact Factor
  • T Kurisu · T Tanaka · J Ishii · K Matsumura · K Sugimura · T Nakatani · H Kawashima ·
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    ABSTRACT: Steroid receptor RNA activator (SRA) was first isolated as a steroid receptor co-activator that functioned as an RNA transcript. Later, we demonstrated that SRA needs to be translated in order to co-activate androgen receptor (AR). Here, we showed that three isoforms of human SRA enhanced AR activities. Small interfering RNA against SRA suppressed AR activities in PC-3 cells transfected with pSG5AR and in LNCaP cells that have an endogenous mutated-AR. Western blot showed that SRA protein was expressed at a higher level in PC-3 than in LNCaP cells, suggesting that SRA may be related to hormone-independent growth of prostate cancer.
    Prostate Cancer and Prostatic Diseases 02/2006; 9(2):173-8. DOI:10.1038/sj.pcan.4500867 · 3.43 Impact Factor
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    ABSTRACT: Cardiovascular disease is the leading cause of death in hemodialysis (HD) patients. We have previously reported a higher incidence of silent cerebral infarction (SCI) in HD patients compared with the control group using MRI studies. In the present study, we examined whether or not SCI could predict vascular events in HD patients. Cranial magnetic resonance imaging (MRI) was performed on 119 HD patients without symptomatic cerebrovascular disease. SCI was detected by MRI, and the patients were prospectively followed up. The end points of the study were the incidence of major events related to vascular events (cerebral events, cardiac events, and sudden deaths). We investigated the prognostic role of SCI in cerebral, cardiac, and vascular events by using the Kaplan-Meier method and Cox proportional hazards analysis. The prevalence of SCI was 49.6% in HD patients. During a follow-up period of maximum 60 months, vascular events, which included 13 cerebral events, 5 cardiac events, and 3 sudden deaths, occurred in 21 patients. The presence of SCI was predictive for a higher cerebral and vascular morbidity compared to the absence of SCI [18.6% (N= 11) vs. 3.3% (N= 2), P= 0.0169, and 30.5% (N= 18) vs. 5.0% (N= 3), P= 0.0006, respectively]. By multivariate Cox proportional hazards analysis, SCI remained a powerful independent predictor of cerebral and vascular events (hazard ratio for cerebral events 7.33, 95% CI 1.27-42.25: for vascular events 4.48, 95% CI 1.09-18.41). The findings of the present study indicate that the presence of SCI is a new risk factor for vascular events in HD patients.
    Kidney International 07/2005; 67(6):2434-9. DOI:10.1111/j.1523-1755.2005.00351.x · 8.56 Impact Factor
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    ABSTRACT: Peritoneal fibrosis is a major complication of long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. Transforming growth factor-beta (TGF-beta) has been reported to play an important role in the fibrosis of various tissues by stimulating connective tissue growth factor (CTGF) expression. In order to elucidate the mechanism of CAPD-related peritoneal fibrosis, we studied the influence of high glucose concentrations and inflammatory cytokines on mRNA expressions of TGF-beta and CTGF in cultured human peritoneal mesothelial cells (HPMC). HPMC were isolated from normal omentum and cultured with 0.5 or 1.0% glucose or mannitol for 7 days. TGF-beta1 and CTGF mRNA were quantified by one step real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). TGF-beta1 and CTGF mRNA expression levels were significantly increased (p<0.05) by glucose in a dose-dependent manner, but not by mannitol. The expression levels were correlated between TGF-beta1 and CTGF. Effects of inflammatory cytokines were also examined by adding tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or interleukin-6 (IL-6) to the medium at 0.1 ng/ml for 2 days. TGF-beta1 expression tended to be increased by TNF-alpha and IL-6. On the other hand, CTGF expression was significantly decreased (p<0.01) by IL-1 but not changed by TNF-alpha or IL-6. These results suggest that high glucose concentration may play a central role in peritoneal fibrosis. Responses of TGF-beta1 and CTGF to inflammatory cytokines were not necessarily identical, suggesting that CTGF may be a better therapeutic target for peritoneal fibrosis than TGF-beta1.
    International Journal of Molecular Medicine 06/2005; 15(6):907-11. DOI:10.3892/ijmm.15.6.907 · 2.09 Impact Factor

  • European Urology Supplements 03/2005; 4(3):156-156. DOI:10.1016/S1569-9056(05)80618-9 · 3.37 Impact Factor
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    ABSTRACT: Prostatic neuroendocrine (NE) carcinoma is a rare disease with a poor prognosis because of its rapid progression and the androgen-independent characteristic, for which no successful therapy is available presently. We report a case of NE differentiated prostate cancer, which was diagnosed as adenocarcinoma initially and progressed with NE differentiation during the combined androgen blockade therapy.
    Hinyokika kiyo. Acta urologica Japonica 02/2005; 51(1):33-5.
  • Shinichi Ikemoto · Kazunobu Sugimura · Naomasa Yoshida · Tatsuya Nakatani ·
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    ABSTRACT: Chondrosarcoma is a very rare tumor of the urinary bladder, with only 4 cases reported to date. In this study, we report on a case of a 73-year-old male who presented bladder mass and right hydroureteronephrosis. Radical cystectomy, right nephrectomy and left ureterocutaneoustomy were performed, and histological study disclosed chondrosarcoma of the urinary bladder. As reported in other cases, the tumor was highly aggressive with a short clinical course, and the patient died of carcinomatous pleuritis at one month after surgery. Subsequently, we successfully established a human chondrosarcoma cell line (OCUU-6) from the pleural effusion of the patient.
    Human Cell 10/2004; 17(3):93-6. DOI:10.1111/j.1749-0774.2004.tb00025.x · 1.41 Impact Factor
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    ABSTRACT: Although there have been several studies suggesting the involvement of growth factor receptor tyrosine kinases in ligand-independent activation of the androgen receptor (AR) and progression of prostate cancer, limited studies have been reported actually showing the enhancement of phosphorylation of the AR in vivo in response to growth factors or activation of their receptors in prostate cancer cells. In this study, we have demonstrated that overexpression of HER2/Neu enhanced in vivo phosphorylation of the AR and MAP kinase in DU-145 cells, and that the HER2/Neu inhibitor TAK165 reduced the HER2/Neu-enhanced phosphorylated AR and MAP kinase, indicating that the MAP kinase pathway seems to be involved in the phosphorylation of the AR by HER2/Neu. Both HER2/Neu inhibitor TAK165 and EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) successfully reduced the HER2/Neu-induced transactivation activity of the AR in PC-3 and DU-145 cells, suggesting that these inhibitors are possible therapeutic drugs for patients with hormone-refractory prostate cancer. The transactivation activity of the AF-1+DBD of the AR was enhanced by HER2/Neu overexpression while that of the AF-2+DBD was not, demonstrating that the enhancement of the AR activity by HER2/Neu was mainly mediated through the AF-1 of the AR.
    Oncology Reports 07/2004; 11(6):1273-9. DOI:10.3892/or.11.6.1273 · 2.30 Impact Factor
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    ABSTRACT: Some types of dialysis membrane are known to adsorb endotoxin (ET). It is suggested that the biocompatibility of dialysis membrane is enhanced by adsorption and inhibition of ET. This study attempts to clarify the membrane-mediated biological reaction of the ET that is adsorbed to a dialysis membrane. After a dialysis circuit was prepared, contaminated dialysate was introduced on the dialysate side of a polyether polymer alloy (PEPA) membrane that adsorbs ET while saline solution or blood were introduced on the blood side, and the difference in ET adsorption between the two set-ups was measured. Further, the side filled with blood was left standing for 2 h, after which the changes in the amount of interleukin 1 receptor antagonist (IL-1Ra) produced from the whole blood were also assayed. Significantly more ET was adsorbed to the dialysis membrane when blood rather than saline was on the other side. In addition, the IL-1Ra production from the dialysis membrane that adsorbed ET was significantly higher. The ET adsorbed to the dialysis membrane may influence a living body even if it does not pass through the membrane. Accordingly, it is difficult to assume that the adsorption of ET to the membrane enhances its biocompatibility.
    Artificial Organs 03/2004; 28(2):231-4. DOI:10.1111/j.1525-1594.2003.47157.x · 2.05 Impact Factor
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    Shinichi Ikemoto · Kazunobu Sugimura · Katuyuki Kuratukuri · Tatuya Nakatani ·
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    ABSTRACT: Arachidonic acid (AA) metabolites derived from both the lipoxygenase (LOX) and cyclooxygenase (COX) pathways transduce a variety of signals related to cell growth. Selective blockade of the different metabolic pathways of AA (using a general LOX inhibitor NDGA, a 5-LOX inhibitor AA861, a 12-LOX inhibitor baicalein and a general COX inhibitor ibuprofen) revealed that murine bladder cancer cell line (MBT-2) cell proliferation was inhibited by the LOX inhibitors concentration-dependently, but not by the COX inhibitor. Among the LOX inhibitors, baicalein showed the strongest inhibition and induced apoptosis of MBT-2. Proliferation of MBT-2 was also significantly inhibited by 12-LOX antisense oligonucleotides. In an in vivo experiment, the antitumor effects of baicalein administration on C3H/HeN mice implanted with MBT-2 were recognized. These results suggested that LOX inhibition may be significant in the treatment of bladder cancer.
    Anticancer research 03/2004; 24(2B):733-6. · 1.83 Impact Factor
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    ABSTRACT: We performed four living related kidney transplantations from donors with double inferior vena cava (D-IVC), in which the left kidney was selected in two cases and the right in two cases. By dissecting the right internal iliac vein and isolating the right external iliac vein, the surgical procedure of the recipient side was so devised as to avoid any complications. In one patient, the surgical procedure of the donor side was modified to extend the donor left renal vein by anastomosis of part of the donor IVC to the renal vein. In the other case, no special treatment was necessary due to the patient's slender physique. In all four cases, transplants were successfully performed. The following conclusions can be made from these results: If the donor has D-IVC, it is essential to carefully conduct pre-operative examinations including angiography and venography to investigate other possible anomalies and blood flow of the renal vein. In addition, the graft must be carefully selected so that it is not disadvantageous to the donor. If there is no disadvantage to the donor as to which kidney is selected, the kidney with the longer renal vein should be transplanted.
    Urologia Internationalis 02/2004; 72(4):358-60. DOI:10.1159/000077695 · 1.43 Impact Factor