Effect of phenobarbital administration on hepatocytes constituting the hyperplastic nodules induced in rat liver by 3'-methyl-4-dimethylaminoazobenzene.
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Biomedical subjects
Publications and source records attributed to T Kaku.
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In the course of a chemical study on pure ginsenosides, a ginsenoside-Rg2 was isolated as colorless needles, from the lateral root of Panax ginseng C. A. Meyer. For the characterization of Rg2, a chikusetsusaponin-I (ginsenoide-Rg2) was isolated as colorless needles from rhizome of Panax japonicus C. A. Meyer. The optical rotation value of both saponins were opposite to the published data. On the large scale isolation of ginsenosides, trace amount of ginsenoside-Rg2 was isolated as crystals. Three compounds, A, B and C, were isolated from the reaction mixture on hydrolysis of ginsenoside-Rb1, Rb2 and Rc with 50% aqacetic acid. A was 20R-prosapogenin and it was identical with Rg3. On the other hand, B was found to be 20S-prosapogenin. And C was estimated to be prosagenin dehydrated at C20-OH and named as delta 20-prosapogenin. It was found that an equilibration is present among A, B and C at the earlier stage on acid hydrolysis.
A carboxylesterase (carboxylic-ester hydrolase, EC 3.1.1.1) was induced in the liver of rats after repeated administration of phenobarbital. This enzyme migrated most rapidly towards the anode among Triton X-100-solubilized liver esterases by electrophoresis on the cellulose acetate membrane and it was tentatively designated as L-I. L-I increased in the microsomal fraction and was mainly concentrated in the fraction of smooth endoplasmic reticulum that proliferated after phenobarbital treatment. L-I- was separated from other liver esterases and purified about 800-fold. The purified L-I was homogeneous as judged by polyacrylamide gel electrophoresis and exhibited a molecular weight of about 55 000 as determined by gel filtration. L-I split the 1-naphthyl ester of butyric acid faster than esters of acetic, propionic or valeric acids; it therefore seemed to be a butyrylesterase.
A microsomal butyrylesterase (L-I) was purified from the livers of male W rats treated with phenobarbital, and an antiserum against this purified L-I was raised in a rabbit. By the Ouchteriony double-diffusion test, a precipitin line was observed between the anti-L-I antiserum and each Triton X-100 extract of livers during development, regeneration after partial hepatectomy, and carcinogenesis and of hyperplastic nodules and hepatomas, all of which revealed L-I in their esterase isoenzyme patterns. These precipitin lines exhibited esterase activity. The fusion of the lines of these tissue extracts and that of the purified L-I indicated the presence of an antigen site common to their esterases. The extracts of adult and fetal livers and also of hepatomas resembling fetal liver in the esterase isoenzyme pattern did not produce a precipitin line with anti-L-I antiserum.
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Two surgical cases of retinal dysplasia are reported. The one is unlateral (left-sided) with microphthalmus and the other bilateral. Chromosome test in the latter case showed no abnormality. In both cases the left eye was enucleated under the clinical diagnosis of retinoblastoma. There was a mass of loose connective tissue behind the lens which was covered by a completely detached retina. Histological examination revealed the presence of branching tubes of primitive retinal structure and large rosettes. The use of the term retinal dysplasia in distinction from Reese's syndrome is mentioned and some morphological characteristics of primitive retinal structure are described.
For the purpose of clarification of pharmacological actions of ginseng saponins we tried the isolation of ginseng saponins on a larger scale and succeeded in the isolation of eight saponins in a pure state and in sufficient amounts for the pharmacological assay. These eight saponins agreed all completely with the authentic samples of Shibata-Shoji and co-workers in molecular formula of saponins and sapogenins, sugars and TLC. The physical properties of saponins were shown. As other components of ginseng, there were isolated small amounts of panaxadiol, panaxatriol, daucosterol from the first running of column chromatography and mannitol, sucrose and glucose from the ethanol insoluble aqueous extract.
The pharmacological properties of seven pure saponins isolated from Panax ginseng C. A. Meyer were studied. 1. The ginseng saponins showed weak toxicities in mice. Especially, Rg1, Rf and Rb 1, which contained glucose as a sugar component, were weaker in their toxicities than the rest, which contained arabinose and/or rhamnose. It was also noted that the saponins containing protopanaxadiol as sapogenin were more toxic than those containing protopanaxatriol. 2. All the saponins diminished ACh-induced contraction of the isolated ileum of the guinea pig. On the other hand high concentrations of Rb 2 caused contraction of the ileum by itself. 3. All of the saponins induced a decrease in heart rate and showed biphasic actions on the blood pressure in rats, while they little affected respiration. They caused blood pressure fall preceded by slight rise. Among them, Rg 1 showed the most prominent action and it produced a blood pressure rise with doses of 30 to 100 mg/kg. The pressor as well as depressor action was not influenced by the pretreatment with any of atropine, diphenhydramine, phentolamine and propranolol. 4. Rg 1 and Re showed vasodilator action in dogs, the potencies of which were 1/20 and 1/50 of that of papaverine, respectively. Rc and Rb 2 showed very weak vasodilator actions but Rb 1 did not. 5. Among the 7 saponins, Rd, Re and Rb 2 showed more potent hemolytic actions than those of the rest and the potencies were proportional to their toxicities. 6. Whereas single administration of Rf, Re and Rd significantly suppressed the conditioned avoidance response, repeated administration of them caused facilitation of the response. On the other hand, Rb 2 always showed very weak suppressant action. 7. Rg 1, Rf, Re and Rd significantly suppressed the fighting of mice induced by foot shock, while Rb 1, Rb 2 and Re little affected the fighting. 8. All the saponins showed antifatigue action. They markedly increased the movement after compulsory gait and the action was consistent and independent of their action on the movement before compulsory gait. 9. The saponins showed moderate depressant actions on the EEG and the behavior in cats. They were qualitatively similar in their actions, although Rg 1, Re and Rb 2 were more potent than the rest. They also suppressed EEG arousal response induced by electrical stimulation of the mid brain in cats.
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