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Toshikado Sugimoto

Publications and source records attributed to Toshikado Sugimoto.

7 recordsLinked to original sources

Concentration gradient of oxalate from cortex to papilla in rat kidney.

BACKGROUND: The kidney eliminates the major fraction of plasma oxalate. It is well known that oxalate is freely filtered by glomeruli and secreted by the proximal tubules. However, the renal handling of oxalate in distal nephrons, which is considered as playing an important role in stone formation, remains obscure. METHODS: At 15-180 min after intravenous injection of 14C-oxalate to rats, the intrarenal localization of radioactivity was quantitatively measured by the radioluminographic method using a bioimaging analyzer. Tissue radioactivity was compared with plasma, and urinary radioactivities were measured by a liquid scintillation counter. The control study was conducted with 14C-inulin. RESULTS: The radioactivity of 14C-oxalate in the papilla was 10 times greater than in the cortex and eight times greater than in the medulla 180 min after injection when almost no radioactivity was present in the urine. In contrast, the radioactivity of 14C-inulin was nine times less in the papilla than in the cortex at the same time. CONCLUSION: Oxalate remains in the renal papilla for an extended period. This accumulation of oxalate may be attributed to calcium oxalate crystal fixation along the deep nephron which is considered to be the first step of stone formation.

Animals↗

The preventive effect of sodium pentosan polysulfate against renal stone formation in hyperoxaluric rats.

Sodium pentosan polysulfate (SPP), a semi-synthetic glycosaminoglycan, was administered to rats with hyperoxaluria, induced by a vitamin B6 deficient diet, as a model of calcium oxalate stone formation. We studied the preventive effects of SPP on stone formation as well as its inhibitory effects on stone growth by autoradiography and radioluminography after intravenous injection of (14)C-oxalate. The rats were divided into non-treated and SPP-treated groups. The non-treated rats were divided into three groups: one group was fed a regular diet, while the other two groups were fed a vitamin B6 deficient diet for 2 and 4 weeks, respectively. The SPP-treated rats were divided into two groups: one group was intravenously injected with SPP from the start of the vitamin B6 deficient diet for a total of 4 weeks and the other group was injected with the same amount of SPP after 2 weeks of the diet for 2 weeks. (14)C-oxalate renal macroautoradiograms were prepared, and calcium oxalate deposits in the renal tissues were compared between the non-treated and SPP-treated groups. The preventive effects on calcium oxalate stone formation were clearly observed in the group injected with SPP for 4 weeks. Even in the other SPP-treated group, in which the administration of SPP was started at 2 weeks after the start of the diet when calcium oxalate stone formation was already observed, the size of the calcium oxalate deposits observed after 4 weeks was smaller than that in the non-treated group fed a vitamin B6 deficient diet for 4 weeks. In conclusion, our results show that SPP has not only preventive effects on calcium oxalate stone formation but also growth inhibitory effects on stones in hyperoxaluric rats.

Animals↗

NADPH-cytochrome P-450 reductase in the plasma membrane modulates the activation of hypoxia-inducible factor 1.

Hypoxia induces a group of physiologically important genes that include erythropoietin (EPO) and vascular endothelial growth factor (VEGF). Hypoxia-inducible factor 1 (HIF-1) was identified as a hypoxia-activated transcription factor; however, the molecular mechanisms that underlie hypoxia signal transduction in mammalian cells remain undefined. In this study, we found that a flavoprotein, NADPH-P450 reductase (NPR), could regulate the induction of EPO mRNA under hypoxic conditions. Hypoxic EPO mRNA induction in Hep3B cells was inhibited by diphenyleneiodonium chloride, which is an inhibitor of NADPH-dependent enzymes. NPR antisense cDNA was transfected into Hep3B cells, and NPR-deficient hepatocyte cells (NPR(-) cells) were established. NPR(-) cells lacked EPO induction under hypoxia, and HIF-1alpha in NPR(-) cells did not respond to either transcriptional activation or translocation to the nucleus based on electrophoretic mobility shift assays and reporter gene assay including hypoxia response element. In contrast, NPR overexpression in Hep3B cells enhanced the DNA binding activity of HIF-1alpha by luciferase reporter gene assay. A study with HeLa S3 cells produced the same results. Furthermore, anti-NPR IgG inhibited EPO induction. EPO induction inhibited by diphenyleneiodonium chloride was recovered by bovine serum albumin-NADPH (a covalent binding complex of bovine serum albumin and NADPH) as well as NADPH. These results suggested that NPR located at the plasma membrane regulates EPO expression in hypoxia, including HIF-1 activation and translocation. We further studied the expression of NPR and VEGF mRNAs in human tumor tissues and found that the NPR mRNA levels were correlated with the VEGF mRNA levels, suggesting that NPR might be an important factor in the hypoxic induction of genes such as VEGF in vivo.

Cell Membrane↗

Metastatic urinary bladder tumor from extragonadal germ cell tumor: a case report.

A 37-year old male patient complained of lower back pain. Investigations revealed a retroperitoneal tumor and left-sided cervical lymphadenopathy without abnormal findings in both testicles. The diagnosis of extragonadal germ cell tumor was made based on a lymph node biopsy. Following chemotherapy and retroperitoneal lymphoadenectomy, at outpatient follow-up, beta-HCG elevated again. He complained of gross hematuria, cystoscopy showed a bladder tumor, and abdominal MRI scan showed a right ureteral tumor. Total cystectomy and right nephroureterectomy were performed, which revealed that the bladder and ureteral tumors were metastatic germ cell tumors. Six months later, the patient developed hepatic and mesenteric lymph node metastases that failed to respond to treatment, and died. Germ cell tumors metastasizing to the urinary tract are extremely uncommon, and this is the first report of bladder metastases, other than through direct invasion, from an extratesticular germ cell tumor.

Adult↗