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Biomedical subjects

M Harada

Publications and source records attributed to M Harada.

At least 1,243 records · Page 69Linked to original sources

Immunohistochemical localization of dipeptidyl aminopeptidase IV in rat kidney, liver, and salivary glands.

Specific antibodies directed against dipeptidyl aminopeptidase (DAP) IV prepared from rat and pig kidneys were produced in rabbits. Using a peroxidase-labeled or fluorescein isothiocyanate-labeled antibody method, localization of DAP IV was investigated in various tissues of the rat (kidney, liver and salivary glands). DAP IV was mainly localized in the brush border of the proximal tubules (kidney), in the cell membrane around bile canaliculi of hepatic cells (liver), and in the cell membrane of serous acinar cells (parotid and submaxillary glands). These results substantiate that DAP IV is a membrane-bound peptidase.

Animals↗

Peripheral and central effects of atropine and chlorpromazine on gastric motility and ulceration in stressed rats.

In rats exposed to restraint and water immersion stress, inhibitory effects of atropine (ATR) and chlorpromazine (CPZ) on stress-induced gastric ulceration and motility were studied to clarify which of central and peripheral origins was responsible for these effects. The drug dose ratio of peripheral (intravenous, i.v.) route versus central (intracerebroventricular, i.c.v.) route required to produce an approx. 50% inhibition of gastric ulceration or motility was estimated. Gastric ulceration was prevented by pretreatment with each drug via either route, and there was no great difference in the dose ratio of each drug (i.v.:i.c.v. = 4:1) for the inhibition. The stress-enhanced gastric motility was immediately depressed by each drug via either route. This inhibitory effect of CPZ was short-lasting as compared with that of ATR, and the complete blockade was observed after administration of i.v. ATR or i.c.v. CPZ at higher doses. The ATR dose ratio for this inhibition was less than 10, while the CPZ dose ratio was from 10 to 25. The treatment with CPZ, but not with ATR, caused a definite change in EEG patterns, along with a decrease in body temperature or heart rate. The effect of pretreatment with ATR or CPZ on gastric motility during stress was also investigated. Only the administration of ATR, via either route, appreciably inhibited the gastric motility. Thus, it was suggested that: (1) the inhibitory effect of ATR on gastric motility may be of peripheral rather than central origin, while that of CPZ predominantly of central origin; (2) the anti-ulcerogenic effect of ATR and CPZ may be predominantly of peripheral origin, and the mechanisms involved in ATR may be associated with inhibition of gastric motility, which is different from those in CPZ.

Animals↗

Contribution of alkaloid fraction to pressor and hyperglycemic effect of crude Ephedra extract in dogs.

In anesthetized dogs, pressor and hyperglycemic effects of Ephedra aqueous extract as well as its alkaloid fraction and adsorption of alkaloid from the digestive tract were studied in order to investigate how closely effects of the alkaloid fraction relate to those of the Ephedra extract itself. Blood pressure, heart rate, and blood glucose concentration were increased by intraduodenal administration of the extract and the alkaloid fraction on the bases of the same alkaloid content (20 mg/Kg). In respect to the pressor and hyperglycemic effects, changes in time course of the effects produced by these two drug preparations were similar and in either of the two physiological parameters the maximal value given by the extract was about a half that given by the alkaloid fraction. A maximal level of blood pressure and blood glucose concentration was reached 10-15 min after the administration of the two drug preparations, while the amount of alkaloid absorbed in the portal vein until this time was about 2-3 times as much under administration of the alkaloid fraction as under administration of the extract. Absorption of alkaloid in the extract occurred slowly and lasted longer compared with that of the alkaloid fraction itself. On the contrary, the alkaloid-free extract administered intraduodenally showed no virtual effects on blood pressure and blood glucose concentration except producing tachycardia. It seems that the effect of Ephedra extract on blood pressure and blood glucose concentration was mostly qualitatively and quantitatively represented by that of alkaloid contained and that effect of the extract mainly depended on that of alkaloid absorbed early after its application.

Alkaloids↗

Effect of vasoactive drugs on gastric blood flow measured by a cross thermocouple method in rats.

To make a continuous recording of gastric blood flow (GBF) in rats, application of a cross thermocouple method was investigated together with related pharmacological studies. When secretagogues (tetragastrin, histamine and methacholine) were given intravenously in a dose sufficient to stimulate acid secretion, the increases in GBF observed were much the same as those seen when the aminopyrine clearance technique was used. When epinephrine and norepinephrine were administered via a close intraarterial route in the stomach, there was an initial decrease followed by an increase in the GBF. This biphasic response was antagonized by phentolamine, but not by propranolol, thereby suggesting that those agonists predominantly stimulate alpha-adrenoceptors. On the contrary, isoprenaline produced an increase in GBF which was attenuated by propranolol. Acetylcholine produced an increase in GBF, which was blocked by atropine. Histamine increased the GBF, and such was inhibited by diphenhydramine, but not by cimetidine, suggesting a stimulation of H-1 receptors by histamine. Serotonin, in a lower dose, and tetragastrin also elicited an increase in GBF. However, with a higher dose of serotonin, there was an increase followed by an apparent decrease in GBF. From these results, it was concluded that the cross thermocouple method is practical for a continuous recording the rat GBF in response to vasoactive drugs.

Acetylcholine↗

A model of malignant urinary bladder tumor in rabbits.

We attempted to produce a malignant urinary bladder tumor in rabbits by transplanting tumor cells. Each of 51 male mixed-bred rabbits received 0.3 ml V2 carcinoma cell suspension. The transplantation was done after laparotomy via injection into the bladder wall. Within 2 weeks malignant tumors were observed in the bladder. Without any manipulation to the mucosa, all of the tumors were led to exulceration into the bladder lumen. The incidence of malignant tumor reached 96 per cent. Metastases in these animals were seen in the lungs and para-aortic lymph nodes. This malignant tumor model seems especially suitable for the study of new methods of transurethral treatment of bladder cancer.

Animals↗