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Biomedical subjects

S Okuda

Publications and source records attributed to S Okuda.

At least 271 records · Page 15Linked to original sources

Deduction of duodenal ulcer recurrence by healing with cimetidine plus sulpiride.

The effect of combined treatment with sulpiride plus cimetidine was compared against that of cimetidine alone on the healing of duodenal ulcer and on the subsequent relapse rate. In a double blind study, 35 patients with duodenal ulcer diagnosed by endoscopy were randomly assigned to receive cimetidine 800 mg daily and 38 patients to receive cimetidine 800 mg plus sulpiride 200 mg daily. Sixty patients whose ulcers were healed at three months continued to be observed after stopping treatment and underwent endoscopy to detect recurrences when symptomatic or at three and at six months if asymptomatic. Recurrence was observed in 18 (72%) of 25 patients whose ulcers had healed on cimetidine alone, but in only 11 (38%) of 29 patients whose ulcers healed on cimetidine plus sulpiride.

Adult↗

Relationships between the cryptic and temperate viruses of alfalfa, beet and white clover.

Small isometric virus particles containing double-stranded RNA have been independently reported in Europe and Japan from apparently healthy alfalfa (Medicago sativa), beet (Beta vulgaris), and white clover (Trifolium repens). They have been called cryptic viruses in Europe and temperate viruses in Japan. Serological comparison using immunoelectron microscopy, and polyacrylamide gel electrophoresis of the RNAs indicate that alfalfa cryptic and temperate viruses are the same, beet cryptic virus is probably a mixture of two different viruses, one of which is similar to or the same as beet temperate virus, and white clover temperate virus is a mixture of at least three different viruses, two of them indistinguishable from white clover cryptic viruses 1 and 2, respectively, and the third very likely the same as white clover cryptic virus 3.

Electrophoresis, Polyacrylamide Gel↗

Value of serum alpha-fetoprotein and ferritin in the diagnosis of hepatocellular carcinoma.

Alpha-fetoprotein (AFP) and ferritin in the serum were determined by radioimmunoassay and enzyme immunoassay, respectively, in 224 healthy subjects, 55 patients with benign hepatic disease and 44 patients with hepatocellular carcinoma (HCC). The AFP levels in the serum were significantly higher in patients with HCC than in healthy subjects and in patients with benign hepatic disease, but this level was not a satisfactory indicator of small HCC since it was elevated in only 75.0% of the patients with a tumor of less than 3.0 cm in its greatest diameter. Although serum ferritin was elevated in only 56.8% of the patients with HCC, the combination of these two tests raised the diagnostic rate of HCC from 65.9% by serum AFP measurement alone to 88.6% with no appreciable decrease in the specificity for HCC. In particular, it raised the diagnostic rates of lesions of less than 3.0 cm in the greatest diameter from 75.0% by measuring AFP alone to 100%. Thus the combination of AFP and ferritin measurement in the serum is useful for the early detection of HCC.

Adult↗

Studies on macrocyclic lactone antibiotics. VIII. Absolute structures of rhizoxin and a related compound.

The absolute structure of rhizoxin, a potent antifungal and antitumor antibiotic, was determined by interrelation with compound 2 whose structure was established by X-ray analysis. Since a 18OH group was introduced at C-3 on a hydrolytic cleavage of C-2, C-3 epoxy group with alkaline H2(18)O, the original epoxy oxygen should be retained at C-2. The stereo-chemistry at C-2 and C-3 positions in rhizoxin was, therefore, determined as 2R,3S.

Chemical Phenomena↗

Rhizoxin, a macrocyclic lactone antibiotic, as a new antitumor agent against human and murine tumor cells and their vincristine-resistant sublines.

Rhizoxin, isolated from a plant pathogenic fungus which causes rice seedling blight, inhibits the mitosis of the tumor cells in a manner similar to that of Vinca alkaloids as revealed by morphological study and flow cytometry analysis. This new 16-membered macrocyclic lactone showed similar chemotherapeutic effects to those of vincristine against L1210 and P388 leukemia-bearing mice. The drug is also effective against B16 melanoma inoculated i.p. or s.c. Rhizoxin, in contrast to the ansamacrolide, maytansine, was effective against human and murine tumor cells resistant to vincristine and Adriamycin in vitro and in vivo. A maximum 60% increase in life span was obtained in mice inoculated with P388 leukemia resistant to vincristine. Rhizoxin showed greater cytotoxicity in cultured tumor cells than did vincristine. Rhizoxin seems to bear consideration for further development as a new chemotherapeutic agent.

Animals↗

Effect of blood pressure on the progress of renal deterioration in rats with renal mass reduction.

The effect of hypertension on the progress of renal deterioration with renal mass reduction was investigated in spontaneously hypertensive rats. Nephrectomies of five sixths, two thirds, and one third were performed. The antihypertensives guanethidine and hydralazine were given to half of the rats. Increase in urinary protein excretion and decreases in serum total protein and albumin were greater in rats with a larger nephrectomy. With the same extent of nephrectomy, these changes were severe in the group of rats with untreated hypertension, as compared with findings in rats given the antihypertensive drugs (AHD). Similar changes were obtained in BUN and creatinine levels. Only the animals with a five-sixths nephrectomy and hypertension became uremic. Glomerulosclerosis in five-sixths nephrectomized rats with hypertension was present in 71% of the glomeruli, whereas it was reduced to 34% in rats treated with AHD. The diameter of normal-appearing glomeruli increased significantly in rats with a large nephrectomy, but did not differ between the groups given or not given AHD. Medical thickening of the arterial walls, which increased with the reduction of renal mass, was significantly greater in five-sixths nephrectomized rats with hypertension than in those treated with AHD. These results indicate that a hyperdynamic state of the glomeruli, that is, a prominent urinary protein excretion and compensatory glomerular hypertrophy, may play a causative role in the progress of glomerulosclerosis in rats with extreme renal mass reduction. The hypertensive state may aggravate these renal dysfunctions.

Animals↗

[Pharmacokinetic studies of a new oral cephem T-2588. Pharmacokinetics in gastrectomized volunteers and the renal excretory system in healthy volunteers].

According to the result of the pharmacokinetic examination of T-2588 (esterified prodrug of T-2525) administered to adult male volunteers who have undergone gastrectomy, it appears that the absorption of T-2588 is delayed in the hypoacidity or the anacidity and also the excretion ratio of T-2525A (an inactive metabolite of T-2525) showed a tendency to become higher in these subjects. Again, according to the result of the pharmacokinetic examination of T-2588 when it was administered together with probenecid to normal healthy volunteers, it appears that the T-2525 is excreted from the kidneys not only into the glomerular filtration but also partly through renal tubules.

Adult↗

Values of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic material in the diagnosis of malignant pancreatic tumor.

The diagnostic accuracy of the measurement of CA 19-9 in the serum, pure pancreatic juice, and aspirated pancreatic fluid in the diagnosis of pancreatic tumors was assessed in 32 patients with malignant pancreatic tumors and 19 patients with pancreatitis. Pure pancreatic juice was collected from the pancreatic duct by endoscopic cannulation with a duodenofiberscope after intravenous administration of secretin. Pancreatic material was obtained by percutaneous fine-needle aspiration biopsy under ultrasonic guidance. Abnormally high CA 19-9 levels in the serum were significantly more frequent in patients with malignant pancreatic tumors than in those with pancreatitis: they were elevated in 71.9% of the patients with pancreatic tumors. High CA 19-9 levels were found primarily in patients with a tumor of the head of the pancreas, in those with a tumor greater than 3 cm in its greatest diameter, and in those with an unresectable cancer. Only 57.1% of seven patients with a tumor of less than 3 cm in its greatest diameter showed an increase in CA 19-9 level. The CA 19-9 levels in pure pancreatic juice were significantly higher in patients with pancreatic tumors than in patients with pancreatitis without pancreatic stone. However, it was not useful for differentiating pancreatic tumors from pancreatitis with pancreatolithiasis. The CA 19-9 level in pancreatic materials obtained by aspiration biopsy was significantly higher in patients with malignant pancreatic tumors than in those with pancreatitis. Eight patients (80%) with pancreatic tumors had values above 1000 U/ml, whereas all five patients with pancreatitis had values of less than 30 U/ml. Although CA 19-9 levels in pancreatic materials was useful only when cytologic examination did not provide any evidence of malignancy, the combination of the CA 19-9 assay and the cytologic study of specimens obtained by percutaneous fine-needle aspiration biopsy of the pancreas increased the diagnostic rate to 100%.

Adult↗

Endoscopic diagnosis of minute gastric cancer of less than 5 mm in diameter.

The accuracy of diagnosis by endoscopic visual and histocytologic examination of minute gastric cancers of less than 5 mm in longest diameter was investigated. Between 1959 and 1981, 55 minute cancers were found in 54 patients at The Center for Adult Diseases, Osaka in Japan: 15 foci were solitary and 40 were associated with other larger gastric cancer. Histologic and/or cytologic confirmation of carcinoma was obtained before operation in 73.3% of cases with a solitary lesion, but in only 7.5% of cases with multiple lesions, for an overall positive result of 25.5%. The diagnostic rate was higher for elevated type and depressed type with converging folds than for flat type and depressed type without converging folds. No cancers of less than 3 mm in longest diameter were correctly diagnosed before operation. Because endoscopic visual diagnosis itself is not sufficiently reliable in determining the nature of the minute lesions, the final diagnosis should be confirmed by endoscopic direct biopsy. However, the first biopsy should be done as carefully as possible, because bleeding in the target area may prevent multiple direct biopsy specimens from being taken. Results also indicate that lesions which could not be diagnosed before operation could not be endoscopically inspected. Therefore, endoscopic detection and subsequent accurate biopsy of suspicious lesions is very important for diagnosis of minute gastric cancer.

Adenoma↗

Biosynthetic studies on saframycin A, a quinone antitumor antibiotic produced by Streptomyces lavendulae.

The biosynthesis of saframycin A, a heterocyclic quinone antitumor antibiotic isolated from Streptomyces lavendulae 314, was studied by feeding experiments with 14C and 13C precursors. Highly increased production of saframycin A and prolongation of the maximum production period of saframycin A were attained by constant pH control of the culture and by addition of chloramphenicol to the culture. The biosynthetic origin of the quinone skeleton common to the saframycin group was confirmed to be two tyrosine molecules which condense to generate the basic ring system of saframycin A. Feeding experiments with [1-13C]tyrosine showed specific labeling of C-11 and C-21 carbons of saframycin A, and the enrichment of the carbons was 40-fold over natural abundance. Two O- and two C-methyl and one N-methyl carbons arose directly from methionine, and alanine and glycine were the precursors for the pyruvoyl amide side chain of saframycin A.

Amino Acids↗

Chromoendoscopic observations on extension and development of fundal gastritis and intestinal metaplasia.

The development and extension of fundal gastritis and intestinal metaplasia were investigated by the endoscopic Congo red-methylene blue test in 44 healthy subjects, 106 patients with gastric ulcer, and 26 patients with gastric polyp. Follow-up chromoendoscopic examinations were made an average of 3.4 yr (range 1-10 yr) after the initial endoscopic assessment. Fundal gastritis and intestinal metaplasia developed or became more extensive with time in only 3 (6.8%) and 2 (4.5%) healthy subjects, respectively. In patients with gastric ulcer and in those with gastric polyp, fundal gastritis and intestinal metaplasia developed or extended significantly more frequently and more rapidly than in healthy subjects. Fundal gastritis and intestinal metaplasia developed or became more extensive, respectively, in 26 (24.5%) and 23 (21.7%) patients with gastric ulcer and in 10 (38.5%) and 10 (38.5%) patients with gastric polyp. Fundal gastritis and intestinal metaplasia extended with time mainly in an upward direction.

Adult↗

Histocytologic diagnosis of pancreatic cancer by percutaneous aspiration biopsy under ultrasonic guidance.

Percutaneous aspiration biopsy of the pancreas using a heparinized 22-gauge fine needle was performed under ultrasonic guidance in five patients with benign pancreatic diseases and in 18 patients with pancreatic cancer. Using a heparinized needle and syringe, it was possible to make good smears containing abundant tumor cells and to obtain small tissue specimens. Using egg albumin as binding material, a new cell-block technic was developed to conveniently obtain histologic specimens. In this way, a correct diagnosis was made cytologically in all 23 patients suspected of having a pancreatic malignancy. Histologic specimens were obtained in 22 (95.6%) our of 23 patients. A correct diagnosis was established histologically in all patients from whom histologic materials were obtained. This procedure thus has proved a very reliable method for diagnosing pancreatic cancer.

Adenocarcinoma↗

Rapidly progressive renal deterioration in partially nephrectomized rats with experimental membranous nephropathy.

The effects of nephron loss on the clinical and histological picture of experimental membranous nephropathy were examined for 18 weeks in five-sixths nephrectomized rats with Heymann nephritis (HN-5/6N group). Heymann nephritis-induced rats without nephrectomy (HN group), normal rats with 5/6 nephrectomy (5/6N group) and normal rats without nephrectomy (control group) were also examined for comparison. A rapidly progressive increase in urinary protein, BUN and serum creatinine was observed after renal ablation in the HN-5/6N group. Light microscopic study revealed global or segmental sclerosis in most of the glomeruli, crescent formation in some of the glomeruli and marked tubulointerstitial changes. Electron microscopic study demonstrated vacuolation and necrosis of podocytes, detachment of podocytes from the glomerular basement membrane (GBM) and fibrin exudation into Bowman's space. Proteinuria was also marked but renal function was not impaired in the HN group. In the 5/6N group, proteinuria was mild and elevation in BUN and serum creatinine was apparent but not progressive. There were no differences in the depositions of IgG, C3 and electron-dense materials on GBM between the HN-5/6N group and the HN group. In conclusion, renal mass reduction associated with high flow and pressure to the remnant glomeruli could lead to extensive glomerular sclerosis and to a deterioration in renal function, in the case of pre-existing nephritic lesions.

Animals↗