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Biomedical subjects

S Okuda

Publications and source records attributed to S Okuda.

At least 235 records · Page 13Linked to original sources

Early carcinoma of the stomach after gastric surgery: comparison with early carcinoma in the non-operated stomach.

The relationships between the gross and histological types of early gastric carcinoma and non tumorous gastric mucosa were investigated in 12 cases of carcinoma of the stomach after operation and 46 cases of cardiac carcinoma within 5 cm of the squamocolumnar junction. Histological studies were made by examining specimens obtained by gastrectomy. Grossly elevated and histologically differentiated carcinomas were statistically more frequent after gastric surgery, than before. Comparison between cases of elevated and differentiated adenocarcinoma that had undergone gastric surgery with those that had not showed that atrophic gastritis and intestinal metaplasia in the surrounding mucosa of the tumor were significantly slighter after gastric operation than in unoperated cases. Results suggested that early carcinomas developing after gastric surgery are different from those in the upper portion of the unoperated stomach.

Cardia↗

[Indications for and limitations of HpD photodynamic therapy for esophageal cancer and gastric cancer].

HpD photodynamic therapy (PDT) was performed on 4 patients with superficial esophageal cancer, 20 patients with 22 early gastric cancer lesions and one patient with advanced gastric cancer. About 50 h before irradiation, 3 mg/kg of HpD or 1.3-2.5 mg/kg of Photofrin II was injected intravenously. The entire lesion including a 5-mm border of normal surrounding mucosa, was irradiated with an argon dye laser at 630nm wavelength with an output of 100-400mW at the tip of the fiber. Complete response (CR) to HpD-PDT was obtained in 2 of 2 mucosal esophageal cancers, and one of 2 submucosal lesions, totalling 3 of 4, and in 13 of 13 mucosal gastric cancers and 7 of 9 submucosal lesions totalling 20 of 22. The depths of cancer involvement were determined endoscopically. In Borrmann 1 lesion with muscularis externa involvement, in spite of two trials with HpD-PDT, only partial response (PR) was obtained. Tumor laser dose had to be more than 90 J/cm2, and in several cases combined hot biopsy with electrodiathermy and/or repeated HpD-PDT was needed to obtain CR. HpD-PDT is indicated for superficial esophageal cancer and depressed and/or assembled protuberant-type of early gastric cancer with poor risk.

Aged↗

Rhizoxin binding to tubulin at the maytansine-binding site.

The binding of rhizoxin, a potent inhibitor of mitosis and in vitro microtubule assembly, to porcine brain tubulin was studied. Tubulin possesses one binding site for rhizoxin per molecule with a dissociation constant (Kd) of 1.7.10(-7) M. Ansamitocin P-3, a homologue of maytansine, was a competitive inhibitor of rhizoxin binding, with an inhibition constant of 1.3.10(-7) M. Vinblastine also inhibited rhizoxin binding, but was not fully competitive, and the inhibition constant was 2.9.10(-6) M. In contrast, both rhizoxin and ansamitocin P-3 were potent inhibitors of vinblastine binding. Rhizoxin inhibited tau-promoted tubulin assembly, but it, differing from vinblastine, did not induce tubulin aggregation into spirals, even at a concentration as high as 2.10(-5) M. In addition, rhizoxin strongly inhibited vinblastine-induced tau-dependent tubulin aggregation. Rhizoxin binding to tubulin was completely independent from colchicine binding. These effects resemble those of maytansine. The results suggested that rhizoxin binds to the maytansine-binding site and that the binding sites of rhizoxin and vinblastine are not the same.

Animals↗

Enhancement by vasoactive intestinal peptide of experimental carcinogenesis induced by azoxymethane in rat colon.

The effects of vasoactive intestinal peptide (VIP) on the incidence and histology of colonic tumors induced by azoxymethane (AOM) were investigated in Wistar rats. Rats were given 20 micrograms/kg body weight of VIP every other day for 12 weeks and from experimental week 3, were given 10 weekly injections of 7.4 mg/kg body weight of AOM. The administration of VIP before and during AOM treatment resulted in a significant increase in the incidence of colonic tumors in week 40. Furthermore, it caused a significant increase in the labeling index of the colonic mucosa during AOM treatment. These findings indicate that VIP enhanced the development of colonic tumors. This effect may have been related to its effect in increasing proliferation of cells in the colonic mucosa during administration of the carcinogen.

Animals↗

Glycylproline dipeptidyl aminopeptidase and gamma-glutamyl transpeptidase in human hepatic cancer and embryonal tissues.

Changes of glycylproline dipeptidyl aminopeptidase (GPDA) and gamma-glutamyl transpeptidase (gamma-GTP) activities and their subcellular distributions were compared in human hepatic cancer and embryonal tissues. The activity of GPDA in cancer tissues was significantly higher than that found in healthy liver, though there were no significant differences between fetal and adult livers. The placenta, however, had the highest GPDA activity. The activity of gamma-GTP, on the other hand, was increased significantly not only in cancer tissues but also in live tissues adjacent to the tumor, and it was higher in the fetal liver but much lower in the placenta. Subcellular distribution of GPDA was also different from that of gamma-GTP in cancer tissues, especially after postmortem changes. These results suggest the possibility that GPDA has carcinoembryonic characters similar to gamma-GTP, but the mechanisms, whereby serum activities of these two enzymes were increased in hepatocellular carcinoma patients, are different from each other.

Adult↗

Influence of age on deterioration of the remnant kidney in uninephrectomized rats.

To investigate the influence of age on the remnant kidney, unilateral nephrectomy was performed in rats at 1 day (group N-0), 2 weeks (group N-2), 4 weeks (group N-4) or 8 weeks (group N-8) of age. Serial changes in urinary protein during 48 weeks after the uninephrectomy and blood chemistries and renal histology at week 48 were compared between the groups. The increase in proteinuria was significantly greater in groups N-0, N-2 and N-4 than in group N-8 from week 32 to week 48 after the uninephrectomy. There was no significant difference in urinary protein between groups N-0, N-2 and N-4. Hypoproteinaemia and hypoalbuminaemia were also more severe in groups N-0, N-2 and N-4 than in group N-8 at week 48. A compensatory renal growth in groups N-0 and N-4 was significantly greater than that in group N-8 at week 48 after the uninephrectomy. Focal and segmental glomerular sclerosis, a characteristic finding in the uninephrectomy groups, was significantly more marked in groups N-0, N-2 and N-4 than in group N-8 at week 48. We conclude that uninephrectomy at young ages leads to increased incidence of glomerular sclerosis in rats compared with uninephrectomy in the adult.

Aging↗

Effect of different levels of protein intake on renal deterioration and nutritional state in experimental renal disease.

We examined the effects of various levels of dietary protein on the course of adriamycin-induced nephropathy in rats fed with high (30%), intermediately low (10%) or strictly low (5%) protein diets for 24 weeks. In the rats fed on the 30% protein diets, there were massive proteinuria, progressive increases in serum creatinine and focal glomerular sclerosis associated with severe tubulo-interstitial changes. With the 5% dietary protein, proteinuria was decreased, the levels of serum creatinine were preserved within normal ranges and renal histological changes diminished. Weight loss and hypoproteinaemia were more marked. With intermediate protein restriction (10% protein), renal function and plasma protein were preserved but body weight did not increase normally. Aggregated human immunoglobulin G, which had been intravenously injected at weeks 12 and 24, accumulated in the glomeruli more densely in rats fed on the 30% protein diet than in those fed on the 10% or 5% protein diets. We tentatively conclude that functional and histological deterioration of focal glomerular sclerosis can be prevented by appropriate restriction of dietary protein; however, severe protein restriction does aggravate nutritional states.

Animals↗

Small-cell carcinoma of the esophagus: a case treated by chemotherapy.

A patient with small-cell carcinoma of the esophagus treated with cyclophosphamide and vincristine is described. Within 2 months after the beginning of therapy, two coexisting tumors had disappeared and the main primary lesion and metastases in the liver and lymph nodes were markedly reduced in size. The patient relapsed 5 months after the start of therapy and died with widespread metastases. Autopsy revealed that the patient was in partial remission.

Aged↗

Histological features and recurrence of completely and incompletely healed gastric ulcers classified by the methylene blue dye method.

Histological features and recurrence of gastric ulcers classified as completely or incompletely healed by the methylene blue dye method were investigated. On chromo-endoscopic examination, complete healing was defined as a scarred area completely covered with granular patterns, while incomplete healing was defined as a scarred area surrounded only marginally by granular patterns. The methylene blue dye method was significantly more accurate than routine endoscopy for determining the histological completeness of healing. Recurrences were significantly more frequent in incompletely healed ulcers classified by the dye method than in completely healed ulcers. Heavy smoking, male sex, and location of ulcers were closely related to recurrence. Therapy should be continued until the healed ulcers are wholly covered by granular patterns, and physicians should encourage their patients to stop smoking.

Diagnostic Errors↗

Relationship of erosive gastritis to the acid secreting area and intestinal metaplasia, and the healing effect of pirenzepine.

The extent of acid secreting areas and the distribution of intestinal metaplasia in patients with erosive gastritis, and the healing effects of pirenzepine were examined. Studies were done with the endoscopic Congo red-methylene blue test developed in our hospital. Compared with control patients with no gastroduodenal disease, erosive gastritis was associated significantly more frequently with large acid secreting areas, but little or no intestinal metaplasia was detected in the stomach. A double blind trial was carried out, using 100 mg pirenzepine tablets or placebo for three months in 43 patients with erosive gastritis. Endoscopically, complete healing was significantly more frequent in the pirenzepine treated groups three months after the start of the treatment, as compared with the placebo treated group (p less than 0.05).

Adult↗

Cerebral hemorrhage in patients on maintenance hemodialysis. CT analysis of 25 cases.

Site of hematoma and clinical outcome in cerebral hemorrhage were analyzed in 25 maintenance hemodialysis (HD) patients and compared with those in 27 non-HD patients. Ganglionic-thalamic hemorrhage was found in 56% of HD and 74% of non-HD patients, lobar hemorrhage in 36% and 11%, respectively. Size of hematoma, expressed as a ratio (%) of hematoma area to entire brain on CT slice, was 6.5 +/- 4.2% (mean +/- SD) in HD, being significantly larger than that of 4.7 +/- 3.5% in non-HD patients (p less than 0.05). Mortality rate was 60% in HD patients, nearly twice as much as the 33% in non-HD patients. The hematomas were significantly larger in the death cases (8.4 +/- 3.7%) than the survivors on HD (3.6 +/- 3.1%, p less than 0.005). Likewise, the fatal cases in the non-HD group had bigger hematomas (6.9 +/- 4.3%) than the non-fatal ones (3.6 +/- 2.4%, p less than 0.05). Intraventricular hemorrhage (IVH) was found in 40% of HD and 44% of non-HD patients. Hematomas were significantly larger in HD patients with IVH (9.3 +/- 3.3%) than in those without IVH (4.6 +/- 3.7, p less than 0.005). Ninety percent of the HD patients with IVH but only 42% of non-HD patients died of hemorrhage. Hypertension was equally seen in HD (76%) and non-HD patients (74%). It is concluded that in HD patients cerebral hemorrhage is more severe in terms of hematoma size, association of IVH and clinical outcome. Chronic systemic heparinization might be responsible to the severity in HD patients.

Adult↗

Effects of acute reduction in blood pressure on the renal function of rats with diseased kidneys.

We studied the effect of an acute reduction in blood pressure, induced by diltiazem, on the renal hemodynamics of spontaneously hypertensive rats (SHR) with focal glomerular sclerosis, as induced by adriamycin (ADR). Renal plasma flow (RPF) and glomerular filtration rate (GRF) were determined before (first period) and during (second period) intravenous infusion of diltiazem in SHR 4-6 weeks after ADR treatment (group 1), 14-20 weeks after treatment (group 2), and in controls without treatment (group 3). Rats in group 1 had a normal renal function (RPF and GFR) in the first period, which was not significantly different from control rats (group 3). Rats in group 2 showed a reduced renal function, reflected by the lower levels of RPF and GFR, compared with groups 1 and 3. Mean blood pressure decreased equally in the 3 groups by about 50 mm Hg after the infusion of diltiazem. During the second period, 13.4 or 12.4% increase in RPF and a 29.0 or 23.2% elevation of GFR were evident in groups 1 or 3, respectively. In contrast, a 32.0% reduction of RPF was observed in group 2, accompanied by a 25.7% decline of GFR. A reduction in renal function (percent change of RPF or GFR) significantly correlated with the severity of renal dysfunction (RPF or GFR in the first period) in group 2. Thus, the renal function of rats with diseased kidneys is sensitive to an acute reduction in blood pressure by diltiazem, and the sensitivity depends on the degree of renal deterioration.

Animals↗

Isolation, structural elucidation and biological properties of neoenactins B1, B2, M1 and M2, neoenactin congeners.

The structures of three neoenactin congeners, designated as neoenactins B1, B2 and M2 were elucidated by 1H and 13C NMR and mass spectroscopic studies. Another minor component, neoenactin M1, isolated from the crude mixture, was identified as lipoxamycin. All three new compounds were structurally related to neoenactin A. While B1 was proved to be a positional isomer of B2, M2 was found to be a dihydro derivative of A. All the compounds were active against yeasts and fungi and potentiated the activities of polyene antifungal antibiotics such as trichomycins A and B and amphotericin B.

Antifungal Agents↗

Studies on macrocyclic lactone antibiotics. XI. Anti-mitotic and anti-tubulin activity of new antitumor antibiotics, rhizoxin and its homologues.

The mode of action of rhizoxin (1a), a new antitumor macrolide, was investigated. Rhizoxin inhibited fusion of the male and the female pronuclei in fertilized sea urchin eggs and inhibited cilia formation in the deciliated sea urchin embryos. In vitro, polymerization of tubulin isolated from porcine brains was completely inhibited at a 1 X 10(-5) M concentration of rhizoxin, and tubulin which had been polymerized by incubation at 37 degrees C for 30 minutes was depolymerized by addition of 1 X 10(-5) M of the drug. Activity of rhizoxin against tubulin polymerization was compared with those of other anti-tubulin drugs such as colchicine, vinblastine and ansamitocin P-3. The homologues of rhizoxin, 1b-3b, also inhibited polymerization of the purified microtuble protein at almost the same extent as rhizoxin.

Animals↗