Tadashi Suzuki

Malignant transformation of renal angiomyolipoma

In the present paper, two cases of malignant transformation of renal angiomyolipoma without tuberous sclerosis are reported. Pathological examination revealed that, in both cases, in addition to the areas affected by typical angiomyolipoma, there were areas that contained elevated numbers of perivascular epithelioid cells with prominent nuclear pleomorphism. Immunohistochemical examination revealed that both cases were negative for keratin and epithelial membrane antigen, but were positive for the melanogenesis‐related marker HMB‐45. Metastatic diseases appeared 40u2003months after radical nephrectomy in the first case and 18 months in the second case.

Are BCG Effects against Urinary Bladder Carcinoma Cell Line T24 Correlated with Apoptosis in vitro

Because we hypothesized that cell death when bacillus Calmette-Guérin (BCG) was instillated was correlated with apoptosis, cultured urinary bladder carcinoma cells were treated with BCG and examined whether they showed cell death due to apoptosis. Although the proliferative activity of T24 cells was suppressed, we could not recognize apoptosis clearly. Cell cycle analysis indicated an increased number of apoptotic cells, but no DNA degeneration was seen when DNA electrophoresis was applied, and few apoptotic cells were detected by an in situ apoptosis detection kit. As a result, cell death of T24 cells when BCG was applied may have other mechanisms except apoptosis.

Low-Dose Instillation Therapy with Bacille Calmette-Guérin Tokyo 172 Strain After Transurethral Resection: Historical Cohort Study

OBJECTIVESnTo evaluate the effectiveness and side effects of prophylactic low-dose bacille Calmette-Guérin (BCG) Tokyo 172 strain.nnnMETHODSnWe conducted a historical cohort study to compare the clinical usefulness of standard-dose versus low-dose BCG Tokyo 172 strain. A total of 156 patients with superficial bladder cancer (Stage Ta-T1) were historically allocated to either 40 or 80 mg of BCG after transurethral resection. Of the 156 patients, 89 had received standard-dose (80 mg) BCG from 1988 to 2000 and 67 had received low-dose (40 mg) BCG from 1996 to 2005. BCG was instilled into the bladder once a week for 6 consecutive weeks. We excluded 6 patients who did not complete the BCG treatment course. The median follow-up period was 66.9 months (range 2 to 176).nnnRESULTSnTumor recurrence developed in 21 (32.3%) of 65 patients in the 40-mg group and 29 (34.5%) of 85 patients in the 80-mg group. No significant difference was found in the incidence of tumor recurrence between the two groups (P = 0.6377). Tumor progression was found in 4 (6.2%) of 65 patients in 40-mg group and 9 (10.6%) of 85 patients in the 80-mg group. No significant difference was found in tumor progression between the two groups (P = 0.5010). The overall incidence of side effects and severity of pollakisuria were significantly lower in the 40-mg group than in the 80-mg group (P = 0.012 and P = 0.013, respectively).nnnCONCLUSIONSnThe low-dose BCG Tokyo 172 strain achieved identical recurrence-free and progression-free survival as the standard dose with reduced toxicity.

Adverse drug reactions of intravesical bacillus Calmette-Guérin instillation and risk factors of the development of adverse drug reactions in superficial cancer and carcinoma in situ of the bladder

Background: We examined the incidence and severity of adverse drug reactions following intravesical bacillus Calmette–Guérin (BCG) instillation for superficial bladder cancer including carcinoma in situ. We investigated the relationship between adverse drug reactions and patient background to clarify risk factors for the development of adverse drug reactions.

Role of peroxynitrite and recombinant human manganese superoxide dismutase in reducing ischemia-reperfusion renal tissue injury.

BACKGROUNDnIn an acute kidney transplant rejection rat model, we demonstrated that manganese superoxide dismutase (MnSOD) activity was significantly reduced and MnSOD was nitrated by peroxynitrite (ONOO(-)), resulting in tissue injury. We examined whether tissue injury was reduced after external supplementation of recombinant human MnSOD in a rat renal ischemia-reperfusion injury model.nnnMETHODSnMale Brown-Norway rats underwent dissection of the right kidney. The animals were divided into 3 groups. The controls had the left renal blood vessels clamped for 90 minutes to induce ischemia, followed by reperfusion for 16 hours. In the intraperitoneal administration group, MnSOD was administered 30 minutes before ischemia and immediately before reperfusion. In the sham group, neither ischemia nor reperfusion was performed. After reperfusion, blood was collected, the left kidney was dissected and renal function and tissue injury were evaluated.nnnRESULTSnSerum creatinine and K(+), blood urea nitrogen, and aspartate aminotransferase activity decreased significantly, whereas serum Na(+) and renal function improved in the MnSOD group compared with the control and sham groups. On hematoxylin and eosin staining, the histological score indicated that acute tubular necrosis was significantly reduced by MnSOD administration. Periodic acid-Schiff staining was absent in the nonadministration group, whereas it persisted in the MnSOD group. In the proximal renal tubules a large proportion of anti-nitrotyrosine staining was present before but absent after MnSOD administration.nnnCONCLUSIONSnMnSOD administration improved renal function and reduced tissue injury. It may also reduce tissue injury in acute kidney transplant rejection and other tissue injuries caused by similar molecular mechanisms.

A Monoclonal Antibody to Human Transitional Cell Carcinoma of the Bladder: Production and Characterization

In order to detect bladder tumor specific antigens, monoclonal antibodies (MoAbs) to human transitional cell carcinoma of the bladder (TCCB) were obtained. Hybridomas were cloned after being prepared by cell fusion between mouse myeloma cell line X63Ag 8.653 and the spleen cells of BALB/c mice hyperimmune to the bladder cancer cells (grade 2) from a patient. Subsequently 12 MoAb-producing clones were obtained for the panel screening by enzyme immunoassay (EIA) and three MoAbs (no. 10, 11 and 14) were selected for reactivity to bladder cancer cells from patients, including normal epithelia. Finally No. 10 was selected as the most appropriate MoAb for this study and determined IgM with kappa-light chains by EIA. We accurately tested MoAb No. 10s reactivity with 71 malignant tumors by immunoperoxidase staining (IIP). No. 10 reacted to most TCCB cells (36/43), but did not react to any of the other tissues, including five normal epithelia, two brain tumors and three sarcomas. It was also shown by both IIP and immunofluorescent staining (IIF) that No. 10s reactivity was limited to the cancer cell membrane. These results suggest that the antigen recognized by MoAb No. 10 is one of the tumor-associated antigens and that some heterogeneity exists in its distribution.

Therapeutic effects of long-term administration of an oral adsorbent in patients with chronic renal failure: two-year study.

Abstract Background:u2002 Kremezin is an oral adsorbent that attenuates the progression of chronic renal failure by removing uremic toxins and their precursors from the gastrointestinal tract. Previously two clinical studies based on reciprocal serum creatinine levels (1/Scr) have confirmed the efficacy of Kremezin (Kureha Chemical, Tokyo, Japan) in undialyzed patients who had been followed up for 6u2003months or 1u2003year. This is the first report to evaluate the therapeutic effects of long‐term administration (2u2003years.) of Kremezin in undialyzed patients.

A randomized comparative study of endocrine monotherapy and a combination of estramustine phosphate with the endocrine therapy in patients with untreated stage D prostate cancer.

We investigated the clinical efficacy and the prolongation of survival with combination therapy of estramustine phosphate (EMP) and endocrine therapy in untreated patients with progressive prostate cancer. We randomly divided 57 patients with untreated stage D prostate cancer into two groups, an endocrine monotherapy group and a group receiving combination treatment, consisting of endocrine therapy plus EMP. Treatment was continued until deterioration. There were no significant differences in the improvement rating for subjective/objective symptoms or in progression-free survival between the two groups. However, overall survival was significantly prolonged in the combination therapy group (log-rank test, P = 0.0394; generalized Wilcoxons test, P = 0.0145). In particular, overall survival was significantly prolonged, compared to that in the endocrine monotherapy group, in patients in the combination therapy group who were less than 74 years old, those with a performance status (PS) of 1 to 3, a pretreatment prostate-specific antigen (PSA) level of more than 20u2009ng/ml, moderately or poorly differentiated carcinoma, or a partial response (PR) based on the PSA level 12 weeks after the start of treatment. There was no significant difference in the incidence of side effects between the combination therapy and the endocrine monotherapy groups. A combination of EMP with endocrine therapy may be useful for initial treatment in younger patients (aged 73 or younger) and in patients at high risk of progressive prostate cancer.

Expression of nitric oxide and inducible nitric oxide synthase in acute renal allograft rejection in the rat

Background:u2002 Recent studies have shown that nitric oxide (NO) synthases, particularly inducible nitric oxide synthase (i‐NOS), are induced in acute rejection episodes following heart, liver, pancreas and kidney allotransplantation. Furthermore, tissue and cellular injury has been demonstrated to be mediated by peroxynitrite (ONOO‐), a metabolite of NO as well as a potent oxidant. However, a detailed relationship between NO, i‐NOS and graft injury in transplantation remains elusive.

Influence of ABCB1 C3435T polymorphism on the pharmacokinetics of lansoprazole and gastroesophageal symptoms in Japanese renal transplant recipients classified as CYP2C19 extensive

OBJECTIVEnLansoprazole and tacrolimus are substrates of ATP binding cassette (ABC) transporters such as P-glycoprotein (ABCBI/multidrug resistance 1) and cytochrome P450 (CYP). The purpose of this study was to investigate the implication of the ABCB1 C3435Tpolymorphism on the pharmacokinetics of (R)-lansoprazole, the major enantiomer, in CYP2C19 extensive metabolizers (EMs) and on gastroesophageal symptoms in renal transplant recipients receiving tacrolimus.nnnMATERIALSn24 recipients who were CYP2C19 EMs were studied.nnnMETHODSnOral administration of 30 mg lansoprazole was started 2 days before transplantation. On Day 2 before and Day 28 after transplantation, the plasma concentrations of (R)-lansoprazole and tacrolimus were measured.nnnRESULTSnPretransplantation, there were no significant differences in the pharmacokinetic parameters of (R)-lansoprazole between the 3 ABCBI C3435T genotypes. However, after renal transplantation, the peak plasma concentration (Cma ) and area under the plasma concentration-time curve (AUCO-24) of (R)-lansoprazole in patients with the ABCB1 C3435T C allele significantly increased, but not in patients with the TT genotype. These pharmacokinetic variations in (R)-lansoprazole did not influence the AUC of tacrolimus. There were no significant differences in the frequency of gastroesophageal symptoms among the three ABCB] C3435Tgenotypes.nnnCONCLUSIONSn(R)-lansoprazole concentrations significantly increased in CYP2C19 extensive metabolizers with the ABCB1 C3435T C allele, but not TT genotype, after renal transplantation. However, the clinical relevance of this observation may be minor because these pharmacogenetic changes were not associated with the occurrence of gastroesophageal complications.