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T Oohara

Publications and source records attributed to T Oohara.

At least 55 records · Page 3Linked to original sources

Altered expression of extracellular matrix molecules and their receptors in chronic pancreatitis and pancreatic adenocarcinoma in comparison with normal pancreas.

The aim of this study was to elucidate the expression and distribution patterns of both integrins and extracellular matrix (ECM) molecules in chronic pancreatitis (CP) and pancreatic adenocarcinoma (PC) compared with normal pancreas (NP). Expression of nine alpha-subunits (alpha 2-alpha 6, alpha V, alpha L, alpha M, and alpha X), four beta-subunits (beta 1, beta 3-beta 5), and four ECM molecules (type IV collagen, laminin, fibronectin, and vitronectin) was investigated immunohistochemically. In CP, all integrins except alpha V showed nearly the same staining patterns compared with NP. Some acinar cells in CP expressed alpha V. Whereas alpha 2, alpha 3, and alpha 6 expression was stronger and diffuse, no alpha 5 expression was seen in PC. Basement membrane (BM) showed continuous staining in CP, whereas it showed discontinuous/absent staining in PC with antitype IV collagen, laminin, and vitronectin antibodies. Some carcinoma cells showed reverse correlation between alpha 2, alpha 3, and alpha 6 expression and type IV collagen and laminin expression. Fibronectin showed diffuse stromal expression in CP and PC. Some acinar cells or duct cells in CP carcinoma cells in PC showed intracellular VN expression. These results suggest that these integrins and ECM molecules are involved in inflammatory and malignant processes in pancreas.

Adenocarcinoma↗

Frequent mutations of the p53 gene and infrequent H- and K-ras mutations in urinary bladder carcinomas of NON/Shi mice treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

To elucidate whether common genetic events in human urinary bladder carcinogenesis also occur in rodent models, we investigated the presence of p53, H- and K-ras mutations in 18 urinary bladder carcinomas induced by various concentrations of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male NON/Shi mice. Histopathologically, all were invasive, 11 being squamous cell carcinomas (SCCs) and the remaining seven being transitional cell carcinomas (TCCs). Using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) analysis followed by DNA sequencing, p53, H- and K-ras mutations were observed in 14 (78%; exons 5-7), two (11%; one each on exons 1 and 2) and one (5.6%; exon 1) animals respectively. The frequencies of mutations in p53 exons 5, 6 and 7 were 7 (39%), 4 (22%), and 9 (50%) respectively, and no mutation was found in exon 8. All mutations involved one base-pair substitution with or without amino acid changes and the types of base-pair substitution were random. No evident association was observed between mutation sites and the histological phenotypes. In conclusion, p53 mutations are frequent in BBN-induced mouse invasive urinary bladder tumors, at similar levels to those observed for human high-grade invasive carcinomas, and this plus their distribution suggests their possible participation in this model of urinary bladder carcinogenesis.

Amino Acid Sequence↗

[Correlation between tissue blood flow and tissue concentration of 5-FU and its metabolite in hepatic metastasis model for rats].

Correlation between 5-FU (20mg/kg) administrated via the peripheral vein and tissue concentration of its metabolite was studied in hepatic metastasis model prepared for rats. The measurement of tissue samples collected 30 min. after the 5-FU administration suggested a possible negative correlation between the F-dUMP concentration and the blood flow in the normal hepatic tissue of the control group and the tumor tissue in the metastasis group. In administering 5-FU, a time-dependent anticancer drug, to the tumor rich in the tissue blood flow, washing-off effect of the drug by blood outflow cannot be neglected. Some device of prolonging the exposure time of anti-cancer agent to the tumor tissue will be necessary.

Animals↗

Thymosin fraction 5 does not influence urinary tract carcinogenesis by phenacetin and N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice.

The effect of thymosin fraction 5 (TF5) on the promotion and progression phases of urinary tract carcinogenesis induced by consecutive administration of phenacetin and N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in NON/Shi mice was investigated. The study was carried out twice with a minor modification to the protocol in the second experiment. Fifty-seven male NON/Shi mice in experiment 1 and 100 mice in experiment 2 were each divided into four groups. Phenacetin was administered for 8 weeks in experiment 1 and 12 weeks in experiment 2, and subsequently BBN was given for 6 weeks in both cases, for total observation periods of 30 and 34 weeks, respectively. Sixty micrograms of TF5 per mouse was inoculated subcutaneously twice a week during (group 2) or after (group 3) BBN exposure, or both periods (group 4). Group 1 served as a control group without TF5 treatment. Histopathological examination revealed no effects on either induction of urinary tract carcinomas or distant metastasis from renal pelvic carcinomas in either experiment.

Animals↗

Lymph node involvement correlation with survival in advanced gastric carcinoma: univariate and multivariate analyses.

The aim of this study was to elucidate what factors affect the survival of patients with advanced gastric carcinoma. The relationship between the survival of 282 patients over a period of 15 years and 12 prognostic factors was investigated. In univariate analysis, lymph node involvement, depth of invasion, gross form, type of operation, maximum tumor diameter, and lymphatic invasion were found to correlate significantly with survival. Lymph node involvement, gross form, type of operation, and depth of invasion were selected by the Cox proportional hazard model with variable selection methods and found significant. Lymph node involvement was shown to correlate most significantly with survival by both univariate and multivariate analyses. Kaplan-Meier survival curves could indicate that the survival rates of the selected factors were worsening in proportion to the relative risk ratios. These results suggest that further contrivance of therapies should be considered for patients in high risk categories.

Adult↗

Effect of phenacetin pretreatment on renal pelvic carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine in NON/Shi mice of both sexes.

Influences of phenacetin (PH) pretreatment on renal pelvic carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined in NON/Shi mice of both sexes. Histopathological examination revealed that PH pretreatment enhanced not only the induction of urinary tract carcinoma but also distant metastasis of renal pelvic carcinoma by BBN in male mice. The high incidence of urinary tract carcinoma by PH pretreatment might be due to hydronephrosis and epithelial proliferative lesions enhanced by PH, since a single treatment of PH induced hydronephrosis in all mice and simple hyperplasia in 70-80% of mice used.

Animals↗

Results of subtotal gastrectomy with complete dissection of the N2 lymph nodes preserving the spleen and pancreas in surgery for gastric cancer.

In radical resection for gastric cancer, dissection of the N2 lymph nodes is recommended, and total gastrectomy with splenectomy and distal pancreatectomy is sometimes necessary, even if the cancer is located in the middle part of the stomach. However, splenectomy affects the immunological status, and distal pancreatectomy induces diabetes mellitus. In 22 patients with macroscopic Stage II gastric cancer located in the middle part of the corpus, we performed a complete N2 lymph node dissection without splenectomy or pancreatectomy and preserving the short and splenic vessels. Of the 22 cases, 6 had early gastric cancer and 16 advanced cancer. Twenty cases underwent subtotal gastrectomy and 2 cases total gastrectomy. The average number of lymph nodes dissected was 39 (13-82), and 8 patients (36%) showed positive lymph node metastasis (N1(+) 2 cases, N2(+) 6 cases). Postoperative complications were observed in 4 patients (18%), one of whom died of an intraabdominal abscess; the others are alive with no recurrence. This operation is safe and rational, and is recommended mainly in patients with mid-stage gastric cancer located in the middle part of the corpus.

Adult↗

Severe gastric mucosal changes following vagotomy with duodenogastric reflux.

We conducted an experimental study of the morphological changes in gastric mucosa following vagotomy, in particular of the chronic effects of duodenogastric reflux. Male Wistar rats were divided into four groups: sham operation, duodenogastric reflux (DGR), truncal vagotomy with duodenogastric reflux (TV + DGR), and truncal vagotomy with bypass (TV + bypass). The last operation was performed to observe the effects of vagotomy without reflux. The duodenogastric reflux procedure was established by cutting the duodenum just distal to the orifice of bile and pancreatic ducts following gastrojejunostomy. After 12 and 30 weeks, animals were killed for morphological studies of gastric mucosa. The TV + DGR group showed formation of multiple elevated lesions macroscopically, and microscopically showed marked atrophy of gastric glands and proliferation of cystically dilated adenomatous lesions, which were regarded as precancerous or paracancerous lesions. The DGR group showed chronic gastric ulcer and hyperplasia of the gastric glands. However, the TV + bypass group showed no remarkable changes in the gastric mucosa. These results indicate that chronic effects of duodenogastric reflux following vagotomy induce severe inflammatory changes as well as structural alteration of the gastric mucosa. Therefore, a regular follow-up observation is necessary after vagotomy when combined with a drainage procedure because the latter could promote duodenogastric reflux and produces pathological changes to the stomach.

Animals↗

[A case of chronic fibrosing mediastinitis].

This case report describes a 32-year-old male patient with superior vena cava syndrome due to chronic fibrosing mediastinitis involving superior vena cava, bilateral brachiocephalic, subclavian, and internal jugular veins. Although the ringed ePTFE graft was placed between left internal jugular vein and right atrium twice, it occluded each time. Pathological examination of the removed specimen showed invasion of the fibrous tissue into the lumen of the graft at the anastomotic site and severe fibroelastosis in the intima of the jugular vein. The third reconstruction of the venous system with the ringed ePTFE substitute was done in the same manner. Postoperative venography demonstrated the patent graft and the interruption at the midportion of the left internal jugular vein. The patient remains free from the symptoms one year and nine months after the last operation.

Adult↗

Recombinant interleukin-1 alpha inhibits the growth of rat mesangial cells in culture.

We have investigated the effect of interleukin-1 (IL-1) on the growth of mesangial cells isolated from rat kidney. Recombinant IL-1 alpha inhibited 3H-thymidine uptake by mesangial cells in a dose-dependent manner in the presence of either 0.5% or 5% fetal bovine serum (FBS). In the presence of high concentration of FBS (10%), the effect of IL-1 was not prominent. The inhibitory effect of IL-1 on the growth of mesangial cells was also confirmed by a change in cell numbers and measurements of protein synthesis with 3H-leucine. IL-1-induced inhibition of mesangial cell growth was not affected by indomethacin. IL-1 showed no effects on intracellular Ca2+ levels in mesangial cells. These observations indicate that IL-1 inhibits the growth of mesangial cells, and thus may play a protective role for mesangial cells from abnormal proliferation in some pathophysiological states.

Angiotensin II↗

Interleukin 6 stimulates growth of vascular smooth muscle cells in a PDGF-dependent manner.

We have investigated the effect of interleukin 6 (IL-6) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortas. Murine recombinant IL-6 significantly increased the number of VSMC and stimulated tritiated thymidine incorporation into VSMC in a dose-dependent manner. The IL-6-induced thymidine incorporation into VSMC was totally inhibited by the Ca2+ channel blocker verapamil; however, IL-6 showed no effects on the intracellular Ca2+ level ([Ca2+]i) in VSMC. Antibody against platelet-derived growth factor (PDGF) also totally inhibited the IL-6-induced thymidine uptake. PDGF caused a significant increase in the [Ca2+]i, which was totally inhibited by verapamil. IL-6 mRNA was not detected in unstimulated "quiescent" VSMC, but its expression was stimulated by exposure of VSMC to 10% fetal bovine serum. Immunohistochemical study using anti-PDGF antibody showed that IL-6 stimulated PDGF production in VSMC. These results support the premise that IL-6 is released by VSMC in an autocrine manner and promotes the growth of VSMC via induction of endogenous PDGF production.

Animals↗

[Classification of DNA histogram perturbed with 5-FU and its clinical application].

Analysis of cell kinetics may be beneficial for evaluation of the therapeutic effect of anticancer agents. Therefore, using flow cytometry, the authors could classify perturbations of DNA histogram of cultured colon cancer cells treated with 5-FU into 4 types. Perturbation of DNA histogram of cancer cells treated with 5-FU of different concentrations was closely associated with the degree of cell damage indicated by the growth curve. Then, tumor samples before and after injection of 5-FU were collected from 9 preoperative patients with colon cancer and classified into the above 4 types. The results show that 2 cases were classified into type I (S/G1 ratio: 1.5 greater than, G1.G2M comparison: G1 greater than G2M) and another two into type IV (CV ratio: 1.5 less than or equal to, S/G1 ratio: 1.5 less than or equal to, G1.G2M comparison: G1 greater than G2M). However, 5 cases could not be classified (not evaluated) because of the absence of stemline and the presence of heterogeneity in tumor samples. The authors consider that the classification of perturbation of DNA histogram is a useful method to evaluate the degree of cell damage with 5-FU, if tumor samples are appropriately selected and analysis is made with careful attention.

Aneuploidy↗

Depressed adenoma in the large intestine. Endoscopic features.

To clarify the presence of depressed adenomas in the human large intestine, a prospective study was performed from January 1986 to December 1987. During these two years, 997 colonoscopies were conducted in patients, excluding cases of familial adenomatosis coli. Of 32 small, depressed lesions biopsied, seven were depressed adenomas, demonstrating that depressed adenomas do exist in the colon and rectum, and can be detected endoscopically. Resembling a sucker, they are easily detected through inflation and deflation.

Adenoma↗

Mitogenic action of interleukin-1 alpha on vascular smooth muscle cells mediated by PDGF.

We have investigated the effect of interleukin-1 (IL-1) on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. Murine recombinant IL-1 alpha increased tritiated leucine incorporation into VSMC. IL-1 also stimulated tritiated thymidine uptake by VSMC in a dose-dependent manner. On the other hand, Ca2(+)-channel blocker, verapamil, inhibited the IL-1-induced thymidine uptake by VSMC with an IC50 of 10(-8) M. Antibody specific for platelet-derived growth factor (PDGF) also totally inhibited the IL-1-induced thymidine uptake. IL-1 showed no effects on the intracellular Ca2+ level in VSMC. Above results support the premise that IL-1 promotes the growth of VSMC via induction of endogenous PDGF production and might thus participate in the abnormal proliferation of VSMC that occurs early in atherogenesis.

Animals↗

Effects of oxygen supply on protein metabolism in surgically injured rats. Oxygen as a nutrient.

The effect of various inspired oxygen concentrations on protein metabolism after surgery was investigated in rats. Surgical injury was produced by transecting the stomach. Rats were divided into three groups, i.e., a hyperoxic group, a hypoxic group, and a normoxic control group, which were supplied with 40%, 10%, and 21% oxygen, respectively, for 7 days after operation. All rats were fed intravenously (257 kcal/kg/day, kcal/N: 185.5) and whole-body protein turnover was measured using the constant infusion of 15N glycine technique developed by Picou and Taylor-Roberts. For six days after operation, the cumulative nitrogen balance was negative for the hypoxic rats, while hyperoxic rats showed a positive balance that was significantly higher than in control rats (p less than 0.01). Protein synthesis and breakdown rates increased markedly and the rate of synthesis exceeded that of breakdown in the hyperoxic group, but in the hypoxic group synthesis remained unchanged while breakdown increased moderately. These results indicate that oxygen, as a nutrient, is effective for improving postoperative protein metabolism.

Animals↗