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Biomedical subjects

S Okada

Publications and source records attributed to S Okada.

At least 1,171 records · Page 65Linked to original sources

Identification of parathyroid hormone messenger ribonucleic acid in an apparently nonfunctioning parathyroid carcinoma transformed from a parathyroid carcinoma with hyperparathyroidism.

mRNA coding for pre-pro-PTH, a precursor of PTH, was sought in an apparently nonfunctioning parathyroid carcinoma that had transformed from one that was previously functioning. Total poly(A+) RNA was prepared by phenol-chloroform-isoamyl alcohol extraction and oligo-dT-cellulose affinity chromatography from the tumor tissue and bovine parathyroid glands. In the rabbit reticulocyte lysate cell-free translation system, total poly(A+) RNA from the tumor as well as that from bovine parathyroid glands directed the translation of a product which was specifically precipitated by an anti-PTH serum and which migrated at the same position as pre-pro-PTH on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results indicated the presence of mRNA coding for pre-pro-PTH (PTH mRNA) in an apparently nonfunctioning parathyroid carcinoma, suggesting that PTH synthesis is not always absent in parathyroid carcinomas which are not accompanied by hyperparathyroidism.

Animals↗

Enhancement of antitumor activity of 5-fluorouracil by ribothymidine.

The antitumor activity of 5-fluorouracil (5-FU) in combination with ribothymidine was examined on some experimental murine carcinomas. The antitumor activity of 5-FU against Ehrlich ascites carcinoma was markedly enhanced by intraperitoneal coadministration of ribothymidine. The enhancement of the antitumor activity of 5-FU by ribothymidine was also observed against Ehrlich solid carcinoma both by oral and intraperitoneal administrations. Furthermore, the combination therapy of 5-FU and ribothymidine was effective even on 5-FU-resistant P388 leukemia. These results suggest that the combination of 5-FU and ribothymidine may be more effective than 5-FU monotherapy in clinical use.

Animals↗

Mechanisms of potentiation of antitumor activity of 5-fluorouracil by ribothymidine in a mouse tumor system.

In the presence of ribothymidine, the uptake of 5-fluorouracil (5-FU) was enhanced in Ehrlich ascites carcinoma cells in vitro, and was efficiently converted to FU-nucleotides. In these cells, almost all ribothymidine was found to be converted to thymine by, presumably, uridine phosphorylase. The enhanced uptake of 5-FU and its efficient conversion to FU-nucleotides were also observed in Ehrlich ascites carcinoma of ribothymidine-coadministered mice. The radioactivity of 5-FU-14C in the carcinoma cells, which was detected mainly in the acid-soluble fraction immediately after the administration and then shifted to the ribonucleic acid fraction, was approximately 2-fold higher in the ribothymidine-coadministered group than in the control group. On the other hand, ribothymidine-14C was also taken up by the carcinoma cells and an appreciable portion of its radioactivity appeared in the thymine fraction. Thymine produced from ribothymidine-14C was also detected in the extracellular ascitic fluid. The conversion of ribothymidine to thymine was assumed to be catalyzed by uridine phosphorylase, suggesting that ribose 1-phosphate was coproduced and served as a ribose donor for 5-FU. These results suggest that ribothymidine may act as a ribose donor for 5-FU to form FU-nucleotides via 5-fluorouridine in carcinoma cells, resulting in the potentiation of 5-FU activity.

Animals↗

Nephrotoxicity and renal cell carcinoma after use of iron- and aluminum-nitrilotriacetate complexes in rats.

Wistar male rats were tested for nephrotoxicity and carcinogenicity after administration of ferric nitrilotriacetate [(NTA) CAS: 139-13-9] (Fe-NTA) [No. of rats (n) = 24] and Al-NTA (n = 24). The control rats were given AlCl3 (n = 10), NTA (n = 10), and saline (n = 10). Sublethal doses of Fe-NTA [5-7 mg Fe/kg (body wt)] and Al-NTA [1.5-2.0 mg Al/kg (body wt)] were chosen and injected ip for 3 months. AlCl3 and NTA were given in equivalent doses and saline was given in equivalent volumes. All the rats given Fe-NTA or Al-NTA had a depressed weight gain, polyuria, and glucosuria from the 1st week. Histologically, acute tubular necrosis and regenerating epithelial cells were observed. Regenerative atypical epithelial cells in the renal cortex were seen at the termination of Fe-NTA or Al-NTA administration. Control rats had no remarkable changes. After 1 year, primary renal cell carcinoma and metastases to liver, lung, and peritoneum were observed only in Fe-NTA-treated rats (14 of 18 surviving rats). On the contrary, there were no tumors in Al-NTA-treated rats (none of 12 surviving rats). The results suggest that nephrotoxicity and renal cell carcinoma are two independent phenomena from Al-NTA treatment and that a long-term sublethal dose of Al-NTA is not related to renal carcinogenicity.

Acetates↗

[Transference of antibiotics into prostatic tissues: sampling method by transurethral resection for the measurement of the concentration of antibiotics in prostatic tissue].

The transeference of two antibiotics, i.e. cefmetazole (CMZ) and fosfomycin (FOM), into prostatic tissues was examined. Prostatic tissue samples were obtained from patients with benign prostatic hyperplasia while undergoing open prostatectomy or transurethral resection of the prostate (TUR-P). 2 g of CMZ or 4 g of FOM was intravenously administered within about 10 minutes starting 1 hour before the removal or resection of the prostate, and blood samples were collected at the end of the administration and during surgery. In TUR-P, resected prostatic tissues were washed with the TUR perfusate and the antibiotic in the tissue was presumed to be released into the perfusate. The following preliminary experiments were, therefore, carried out. The removed prostate was divided into three segments, i.e. urethral region, central region and capsular region, and the CMZ or FOM level in each tissue was measured. The remaining tissues were cut into small pieces for immersion in the TUR perfusate for 10-90 minutes. The tissue fragments were removed every 10 minutes to measure the tissue concentration of CMZ or FOM. The concentration of CMZ or FOM in the prostatic tissues did not vary among the three regions, however it markedly decreased with increase in the period of immersion. This suggested that the concentration of these agents into the prostatic tissues was represented by the concentration in the tissues near the urethra obtained immediately after the start of TUR-P.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗

Nephrotoxicity of ferric nitrilotriacetate. An electron-microscopic and metabolic study.

Repeated intraperitoneal injections of ferric nitrilotriacetate (Fe-NTA) induce nephrotoxic features such as proximal tubular necrosis and renal failure, an unexpected phenomenon for a ferric compound. The mechanism of Fe-NTA toxicity was investigated by electron microscopy and respiration studies of renal cortical mitochondria in rats. Four hours after a single intraperitoneal injection of Fe-NTA, 5 mg iron/kg body wt, loss of microvilli, increased number of cytoplasmic vacuoles, electron-dense cytoplasmic deposits, mitochondrial swelling, karyorrhexis, and rupture of cytoplasmic membrane were observed in proximal tubular epithelia. At 24 hours, an increased number of cells had become necrotic. Polarographic studies of mitochondria from renal cortex 4 hours after Fe-NTA treatment showed a significant decrease in State 3 respiration and DNP-uncoupled respiration, whereas little change was observed in State 4 respiration and ADP/O.

Acid Phosphatase↗

Glomerular podocyte vacuolation in focal segmental glomerulosclerosis.

An electron microscopic study of the nonsclerotic glomeruli or nonsclerosed segments of affected glomeruli was made in 34 children with nephrotic syndrome and focal segmental glomerulosclerosis (FSGS) and in 34 children with minimal-change nephrotic syndrome. Particular attention was paid to alterations of glomerular epithelium. The most striking glomerular change in FSGS was vacuolation of the epithelial cell. Glomerular epithelial vacuolation was found in 21 of the 34 patients with FSGS. Eleven of these 21 patients with vacuoles developed chronic renal failure, while only one of the 13 patients without vacuoles developed renal failure. In minimal-change nephrotic syndrome only five of the 34 patients showed mild epithelial vacuolation. These observations are consistent with glomerular epithelial vacuolation contributing to the development and progression of the glomerular lesion in FSGS.

Adolescent↗

Changes in adrenal function as a possible mechanism for elevation of serum glucose by a single large dose of fluoride.

Serum glucose was elevated immediately after ip administration of a single large dose of fluoride (NaF 35 mg/kg) to rats. Moreover, elevation of serum glucose following ip administration of 35 mg/kg of fluoride to rats was suppressed by adrenalectomy, dibenamine, or propranolol, but not by thyroid-parathyroidectomy. The elevation of serum glucose was associated with enhancement of glucose-6-phosphatase activities in liver and kidney in fluoride-treated rats.

17-Hydroxycorticosteroids↗