Yamakawa K

Mitogen-activated protein kinase pathway is involved in α6 integrin gene expression in androgen-independent prostate cancer cells: role of proximal Sp1 consensus sequence

Metastatic diseases of prostate cancer reveal high expression of alpha6 integrin and the activation of mitogen-activated protein kinases (MAP kinase). Therefore, the present study was conducted to examine whether MAP kinase pathway is involved in the alpha6 integrin gene expression in androgen-independent prostate cancer cell lines. alpha6 integrin mRNA expression, the alpha6 integrin promoter-induced luciferase activities and MAP kinase enzyme activities in androgen-independent LNCaP and PC-3 cell lines were higher than those in androgen-dependent LNCaP. Deletion and mutation analysis showed that Sp1 consensus sequence at -48 to -43 bp from the transcription start site was necessary for basal promoter activity. Binding of Sp1 to its consensus sequence in three cell lines was confirmed by electrophoretic mobility shift assays. Sp1 binding to its consensus sequence, as well as promoter activity and mRNA expression, were found to be inhibited by an inhibitor of MAP kinase kinase 1 and 2, U0126, in the androgen-independent cell lines. Our results indicate that the proximal Sp1 is necessary for basal promoter activity of the alpha6 integrin, suggesting that signal transduction from MAP kinases to activation of Sp1 might be involved in alpha6 integrin gene expression in androgen-independent prostate cancer cell lines.

The formation of oxalate from glycolate in rat and human liver

In this study, we attempted to elucidate the metabolic pathway and enzymes actually involved in oxalate formation from glycolate in rat and human liver. In rat liver, the formation of oxalate from glycolate appeared to take place predominantly via glyoxylate. The oxalate formation from glycolate observed with crude enzyme preparations was almost entirely accounted for by the sequential actions of glycolate oxidase and xanthine oxidase (XOD) or lactate dehydrogenase (LDH). Under the conditions used, no significant activity was attributable to glycolate dehydrogenase, an enzyme reported to catalyze the direct oxidation of glycolate to oxalate. Among the three enzymes known to catalyze the oxidation of glyoxylate to oxalate, glycolate oxidase and XOD showed much lower activities (a higher Km and lower Vmax) toward glyoxylate than those with the respective primary substrates. As to LDH, none of the LDH subunit-deficient patients examined showed profoundly lowered urinary oxalate excretion. Based on the results obtained, the presumed efficacies in vivo of individual enzymes, as catalysts of glyoxylate oxidation, and the in vivo conditions assumed to allow their catalysis of oxalate production are discussed.

DIABETES INSIPIDUS DUE TO PITUITARY METASTASIS FROM BLADDER CANCER

We report a 41-year-old man with bladder cancer who developed polyuria following successful treatment of hypercalcemia and who was found to have a transitional cell carcinoma within the pituitary gland at autopsy. He also had widespread bone metastases. Although primary urogenital cancers rarely metastasize to the pituitary, the patients clinical course led us to suspect metastatic disease from the bladder cancer. Metastasis to the pituitary gland is more common than generally thought and should be considered in patients with advanced cancer who develop polyuria and polydipsia.

Prediction of residual total renal function before nephron-sparing surgery using99mTc-DMSA renal scintigraphy

BackgroundAlthough radical nephrectomy is the standard treatment for renal cell carcinoma, nephron-sparing surgery is the preferred treatment in patients with a single functioning kidney. It is important before surgery to evaluate the level of residual renal function likely after the operation. In this study, we investigated the prediction of residual renal function, using technetium Tc 99m dimercaptosuccinic acid (99mTc-DMSA) renal scintigraphy, before nephron-sparing surgery for renal tumors.MethodsPreoperative and postoperative evaluation of renal function was done in 11 patients with renal cell carcinoma or renal angiomyolipoma, using99mTc-DMSA scintigraphy. Nine patients had renal cell carcinoma and 2 had renal angiomyolipoma. Partial nephrectomy was performed in 4 patients and surgical enucleation in 7 patients. Both the predicted total DMSA renal uptake rate prior to surgery and the actual postoperative total99mTc-DMSA renal uptake rate were obtained. Endogenous creatinine clearance and serum creatinine levels were also obtained.ResultsThere was a good relationship between the predicted and postoperative total99mTc-DMSA renal uptake rates. The ratio of the postoperative total DMSA renal uptake rate to the predicted total99mTc-DMSA renal uptake rate was 85% after partial nephrectomy, and 101% after surgical enucleation. There was also a significant correlation between the postoperative total99mTc-DMSA renal uptake rate and creatinine clearance, and postoperative total99mTc-DMSA renal uptake rate levels above 11.4% coincided with serum creatinine levels below 2.0 mg/dL.ConclusionPreoperative assessment with99mTc-DMSA renal scintigraphy is clinically useful for predicting residual renal function after nephron-sparing surgery.

Sodium Chloride–Dependent Oxalate Absorption in the Human Gut

We investigated the effect of sodium chloride intake on oxalate and calcium metabolism in the human body. In healthy subjects with a simultaneous intake of sodium oxalate (4 μmoles/kg body weight) and sodium chloride (1.2 mmoles/kg body weight), the change in oxalate–creatinine ratio was 2.04 ± 0.74, and 3.25 ± 1.29 (means ± SD), respectively, after 2 and 4 hours of oxalate intake (n= 8). The magnitude of the change in the ratio was significantly greater in the case with simultaneous intake of sodium chloride and sodium oxalate in comparison to the case with an intake of sodium oxalate alone (P < 0.05 and P < 0.01 after 2 and 4 hours of intake of oxalate, respectively). In subjects with an intake of sodium chloride alone, the change in calcium–creatinine ratio was 49.07 ± 29.96 and 0.363 ± 0.309 (means ± SD), respectively, after 2 and 4 hours of sodium chloride intake (n= 3). The results suggest that high sodium intake can be one of the risk factors for urolithiasis.

OXALATE:BICARBONATE EXCHANGE ON THE BRUSH BORDER MEMBRANE OF RAT PROXIMAL TUBULES

Recently, Na-oxalate co-transport across the brush border membrane of the rabbit renal proximal tubule1 and oxalate(sulfate): bicarbonate exchange across the basolateral membrane of the rabbit renal proximal tubule2 have been demonstrated. Although we reported oxalate: OH exchange across the brush border membrane of the rat renal proximal tubule3, the physiological role of the oxalate: OH exchanger remains unclear. A high-animal-protein diet increases the urinary excretions of calcium, oxalate and uric acid and simultaneously produces acidosis4. Therefore, the purpose of this study was to examine the presence of oxalate: bicarbonate exchange across the brush border membrane of the rat proximal tubules.

Erythrocyte Oxalate Self-Exchange Rates in Japan

Hyperoxaluria is one of the risk factors in idiopathic calcium oxalate nephrolithiasis, but detail of oxalate metabolism is still unclear. Baggio et al1 reported that the abnormal oxalate influx rate of erythrocytes suggests a defect in cellular transport of oxalate resulting in higher intestinal absorption and urinary excretion of oxalate. In order to clarify the effect of an abnormality in oxalate transport in erythrocytes in calcium oxalate nephrolithiasis, we determined erythrocyte oxalate self-exchange rates in 30 patients with recurrent calcium oxalate nephrolithiasis and 20 healthy controls.

Sodium-Chloride-Dependent Oxalate Absorption in the Human Intestine

High urinary oxalate excretion is one of the important determinants of stone formation in idiopathic calcium oxalate (CaOx) stone formers. High oxalate excretion is often observed in CaOx stone formers. In such patients, foods containing high oxalate levels (such as rhubarb, spinach, chocolate) should be restricted.

Oxalate Synthesizing Enzymes in Rat Liver

Glyoxylate is believed to be the immediate precursor of oxalate, and three enzymes, lactate dehydrogenase (LDH), xanthine oxidase (XOD), and glycolate oxidase (GOD) have been known to catalyze the oxidation of glyoxylate to oxalate. In 1979, Fry and Richardson (1) purified an enzyme from human liver which oxidizes glycolate to oxalate without forming glyoxylate as a free intermediate. They named the enzyme “glycolate dehydrogenase (GDH)”. However, which of the four enzymes is mainly responsible for the production of oxalate still remains to be elucidated.