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Biomedical subjects

Y Isobe

Publications and source records attributed to Y Isobe.

209 records · Page 12Linked to original sources
PubMedDate not supplied

Rat epididymal sperm motion changes induced by ethylene glycol monoethyl ether, sulfasalazine, and 2,5-hexandione.

Epididymal sperm was examined using the Hamilton-Thorne Sperm analyzer (HTM-IVOS, version 10.6) in male rats treated with known male reproductive toxicants that act by different mechanisms to detect effects on sperm motion. Three agents known to produce changes in sperm motion at high exposure levels were administered at lower levels. Ethylene glycol monoethyl ether (EGEE), sulfasalazine (SASP), and 2,5-hexandione (2,5-HD) were administered by oral gavage to adult male Sprague-Dawley rats at 250 or 500 mg/kg/day, at 300 or 600 mg/kg/day, or at 100 or 250 mg/kg/day, respectively. The males were treated with EGEE, SASP, and 2,5-HD for 35, 28, and 28 days, respectively. The males treated with EGEE and SASP were mated with untreated females to assess male fertility. All males were examined for body weight, testicular and epididymal weight, epididymal sperm count, and sperm motion. The sperm motion parameters included percentage of motile sperm, percentage of progressively motile sperm (progressive motility), curvilinear velocity (VCL), average path velocity (VAP), straight line velocity (VSL), amplitude of lateral head displacement (ALH), beat cross frequency (BCF), linearity (LIN), and straightness (STR). For the male rats treated with SASP, no treatment-related effects on percentages of motile sperm or sperm count were observed despite impaired male fertility. However, abnormal motion of epididymal sperm from the SASP treated males was detected by a significant reduction in mean progressive motility, VAP, and ALH, and an increase in BCF and STR. For the males treated with 2,5-HD for 4 weeks, most parameters generated by the HTM-IVOS indicated decreased sperm motion despite no remarkable changes in testicular weight, epididymal weight, or sperm count. In the EGEE-treated males at 250 mg/kg/day for 5 weeks, abnormal motion of epididymal sperm was detected by decreased progressive motility and increased BCF, although there were no treatment-related effects on testicular weight or male fertility. Progressive motility was decreased in all treated groups and the difference from the control value was of the greatest magnitude among the sperm motion parameters generated by the HTM-IVOS. Velocity parameters (VAP, VSL, VCL) responded sensitively to abnormal sperm motion in the SASP and 2,5-HD studies. In spite of decreased sperm motion, BCF values were significantly increased in all treated groups except the 7-week EGEE high-dose group, where there were no motile sperm to evaluate. ALH was significantly decreased in the treated groups in which remarkable effects on sperm motion were noted. There were no significant changes in ALH at the low-dose of EGEE at which only mild effects on sperm motion were observed. STR was increased for epididymal sperm from the males treated with SASP when compared with the controls. For the males treated with EGEE and 2,5-HD, however, STR was decreased when compared with the controls. There were no significant differences in LIN in any of the groups treated with SASP, in which remarkably reduced sperm motion was detected by the other parameters. In conclusion, among the parameters generated by the HTM-IVOS, progressive motility was significantly decreased in all treated groups and the most valuable for detecting slight changes in sperm motion induced by these three different target toxicants. Further investigation with a larger set of compounds is needed to evaluate which IVOS parameters are the most sensitive in detecting motion changes.

Animals↗
PubMedDate not supplied

Reconstruction of GABAergic transmission and behavior by striatal cell grafts in rats with ischemic infarcts in the middle cerebral artery.

Fetal striatal cell suspensions were grafted stereotaxically into the infarcted striatum of rats, and reconstruction of striatopallidal GABA transmission and behavior were investigated. Occlusion of the middle cerebral artery (MCA) for one hour induced ischemic infarcts mainly in the lateral striatum, as detected by magnetic resonance imaging (MRI) and histology. Ischemic rats had deficits in the performance of a passive avoidance task, both acquisition and retention, but no changes in general circadian actograms. In these animals pallidal GABA, detected by microdialysis, decreased to about half of control levels. There were suggestions of an improvement in passive avoidance performance in the grafted animals. Pallidal GABA concentrations recovered almost to control levels, and were increased by infusions of the GABA uptake blocker nipecotic acid. These data indicate that neural transplantation is a promising approach to improve the deficits in chemical transmission and behavior following ischemic infarcts in rat striatum.

Animals↗
PubMedDate not supplied

Overexpression of p53 protein and proliferative activity in colorectal adenoma.

Overexpression of p53 was studied immunohistochemically in colorectal tumors. We found p53-positive cells in 17 (58.6%) of 29 specimens of cancer in adenoma. Expression of p53 protein was detected in the nuclei of the tumor cells. We also found p53-positive cells in 7 (7.1%) of 99 specimens of adenoma. p53 immunoreactivity for severe dysplasia was higher than that for mild or moderate dysplasia. p53 expression in adenomas was restricted to a few glands, and the proliferating-cell nuclear antigen (PCNA)-positive rate for the p53-positive glands was significantly higher than that for p53-negative glands. The results suggested that the p53-positive glands might have high growth fractions, and that immunohistochemical detection of p53 expression in tubular adenomas might contribute to identifying the potential for malignant transformation.

Adenoma↗
PubMedDate not supplied

Effect of OK-432 on cytotoxic activity in cancer patients without tumor burden.

The present study was designed to determine the optimal therapeutic protocol for OK-432, a streptococcal preparation, and to clarify the kinetics of various immunological parameters following intracutaneous administration of OK-432 in 39 disease-free postoperative patients with early cancer. These patients were randomly divided into 4 groups according to the dose (1KE or 5KE) and the frequency of administration (one or 3 times every other day) of OK-432. NK activity 3-4 days after the first injection increased significantly in patients whose pretreatment baseline activity was below the lower level of normal values (60 LU) in all study groups (P < 0.05). The elevation of post-therapeutic NK activity lasted for 2 weeks in the group of patients given repeated injections. The serum content of cytotoxic activity against L-M cells increased significantly after the injection of OK-432 at doses of more than 5 KE doses (p < 0.05). These findings suggest that repeated injections of OK-432 over a period of a week have important immunotherapeutic results.

Adult↗
PubMedDate not supplied

Radiotherapy-centered multimodal treatment of unresectable pancreatic carcinoma.

Multimodal treatment procedures, including intraoperative and external beam radiotherapy, chemotherapy and hyperthermotherapy, used for treatment of unresectable pancreatic carcinoma for the past two years have been described. Among the ten progressive cases where multimodal treatment was applied, marked reduction in tumor mass was observed in three cases. The cases receiving such treatment reported prolonged survival, the median survival period being 250 days as compared with 85.4 days in the non-multimodal group. The conclusion is that optimal palliative effects can be achieved by sustained application of both intraoperative and postoperative radiotherapy, hyperthermia and other techniques of multimodal therapy in cases of unresectable pancreatic carcinoma.

Adult↗
PubMedDate not supplied

Gastric protective effects of gastric secretagogues on 0.6N HCl-induced gastric lesions in rats.

The effects of gastric secretagogues on 0.6N HCl-induced gastric lesions and gastric mucosal prostaglandin E2 (PGE2) contents were investigated in rats. Secretagogues such as histamine (Hist) and amogastrin (Gast) significantly inhibited the formation of gastric lesions induced by 0.6N HCl. The time course of the gastric protective effect of these secretagogues paralleled the increase of gastric acid secretion. This increase was due to the increase in acidity, not to the volume of the gastric juice. The gastric protective effects of Hist and Gast were inhibited by pretreatment with cimetidine, timoprazole and indomethacin. Hist and Gast caused an increase of PGE2 contents in gastric mucosa. These increases were inhibited by the administration of cimetidine and timoprazole. Carbachol (CCh), however, did not have any gastric protective effect; nor did it have any effect on PGE2 contents. CCh caused an increase of acid secretion due to the increase of the volume of gastric juice, but not to an increase in acidity. These results suggest that the gastric protective effect of Hist and Gast, induced by the increase of acidity in gastric juice, is due to the endogenous PGE2 synthesized by the stimulation of acid in the gastric mucosa.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMedDate not supplied

Effects of OK-432 on in vitro secondary responses of the non-adherent cells to IL-2 and OK-432 in cancer patients without tumor burden.

We examined the effect of OK-432 intracutaneous injection on the in vitro responses of non-adherent cells to IL-2 and OK-432, along with changes in lymphocyte subpopulations, in early cancer patients who underwent surgery. We found that 1) repeated injections of OK-432 resulted in an enhancement of LAK activity, the peak of which was seen between 7 and 10 days after the first administration, 2) this augmentation of LAK activity was not associated with changes in lymphocyte subpopulations CD8+ CD11- and CD8+ CD11+ phenotypes, and 3) the cytotoxic activity of lymphocytes stimulated in vitro with OK-432 did not show a definite change in specific pattern after in vitro OK-432 treatment. These findings indicate that repeated injections of OK-432 over a period of a week effectively enhanced LAK activity.

Adult↗
PubMedDate not supplied

5-Hydroxytryptamine3 receptor and regulation of gastric emptying in rats.

We investigated the role of the 5-hydroxytryptamine3 (5-HT3) receptor in the regulation of gastric emptying in rats using various 5-HT3 receptor antagonists, including GK128, a novel and selective 5-HT3 receptor antagonist. GK128 dose-dependently accelerated gastric emptying in rats. The accelerating effect of GK128 on gastric emptying was more potent than that of the other 5-HT3 receptor antagonists used in this study. However, the rank order of potency of the selective 5-HT3 receptor antagonists, except for the benzamide derivatives, on the accelerating effect of gastric emptying, was not consistent with that of their 5-HT3 receptor-binding affinity in the rat cortex. GK128 improved the gastric emptying delayed by m-chlorophenylbiguanide, a 5-HT3 receptor agonist, and by cisplatin, which is known to cause damage to the small intestine and to release 5-HT from enterochromaffin cells. Furthermore, 5,7-dihydroxytryptamine, an indoleamine neurotoxin known to destroy 5-HT-containing neurons, significantly accelerated gastric emptying, and no further acceleration was observed after administration of GK128. These results may suggest that 5-HT3 receptor antagonists induce, at least in part, the acceleration of gastric emptying in rats via a peripheral mechanism, and that endogenous serotonin has an inhibitory regulatory effect on gastric emptying in rats. Furthermore, the difference in rank order between the accelerating effect of gastric emptying and the 5-HT3 receptor antagonistic potencies in the cortex suggests that the 5-HT3-like receptor, modulating gastric emptying, is not identical to the classically defined 5-HT3 receptor.

Animals↗