[Study of lymphatic flow of the mammary gland by application of activated carbon emulsion (CH44)].
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Biomedical subjects
Publications and source records attributed to H Tokuda.
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Ursolic acid (UA) and oleanolic acid (OA), which had been isolated from Glechoma hederacea as inhibitors of Epstein-Barr virus (EBV) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), were tested against inhibitory effect on tumor promotion by TPA in vivo. They inhibited effectively the tumor promotion in mouse skin and the activities were comparable to that of a known inhibitor of tumor promotion, retinoic acid (RA). Interestingly, UA was more effective on a single application before initial TPA-treatment than on a continuous application before each TPA-treatment, while OA and RA were ineffective in the same treatment. These data suggest that the role of UA for inhibitory action on tumor promotion differs slightly from those of RA and OA.
From an anti-inflammatory Chinese medicinal plant, Glechoma hederaceae L., two triterpene carboxylic acids, ursolic acid (UA) and oleanolic acid (OA) have been isolated as inhibitors of 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus (EBV) activation in Raji cells. Both acids significantly inhibited the activation at a 1000-fold molar ratio to TPA, and also teleocidin B-4. The dose responses of the acids were very similar to those of the antitumor promoters, retinoic acid (RA) and glycyrrhetinic acid (GA). However, a characteristic property that UA and OA possess, far higher cell viability to the Raji cells than RA to the Raji cells, has been pointed out. Furthermore, enhancement of the inhibitory activity was found in 3-keto derivatives of UA and OA, while either loss of oxygen functionality at C-3 position of UA or oxidation at C-3 of GA led to reduction of the activity. Binding assay suggested that the inhibitory activity should be exhibited by some event caused after binding of TPA to the receptor in the cells.
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Cefotiam (CTM) is a new cephalosporin with a broad spectrum of activity against both Gram-positive and Gram-negative microorganisms. Cephalosporins are widely used for prophylaxis of infections in patients undergoing thoracotomy. Augmentation by serrapeptase on tissue permeation of CTM was examined in 35 thoracotomy patients with lung cancer. The subjects were divided into two groups according to the method of the administration of CTM. Group I consisted of 17 subjects, each of whom received a single dose of 2 g of CTM alone by an instillation for 30 minutes. Group II consisted of 18 subjects, each of whom received a combination of CTM and serrapeptase; serrapeptase was given 2 tablets (10 mg) each time for three times/day until the day before surgery, and then CTM was administered by the same procedure. The following results were obtained: Individual difference was observed for the permeation of CTM into tissues. Pathologic differences also affected the permeation. Nevertheless, the CTM levels in pulmonary tissues reached about a half of those in the blood in both the single dose group and the combination group, hence sufficient concentrations exceeding MIC80 for main microorganisms that caused infections in the lung were obtained. The concentrations of CTM in inflammatory tissues have showed lower levels than those of normal tissues in both CTM single dose and the combination groups. Decrease of blood flow volume may have contributed to the reduction in levels of CTM in the inflammatory tissues. The ratio of the concentration of the drug in pulmonary tissues to that in the blood was 29.1 +/- 2.5% in the single dose group, and 44.2 +/- 6.0% in the combination group, the latter showing quite a significant increase (P less than 0.05). Combined administrations of CTM and serrapeptase deserves more trials in the case when surgical treatments of the lung are performed. An antiinflammatory effect of serrapeptase in the respiratory system is expected, and in addition, the combined use of CTM and serrapeptase should stimulate permeation of the antibiotic into tissues.
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New derivatives of (-)-indolactam V (Fig. 1), which have the basic ring-structure of teleocidins without the monoterpenoid moiety, were prepared and their Epstein-Barr virus early antigen (EBV-EA)-inducing activity was tested. (-)-14-O-Alkyl indolactam Vs (2 and 3) showed little induction of EBV-EA, while (-)-14-dehydroxyindolactam V (4) and (-)-14-chloroindolactam V (5) proved to be potent EBV-EA inducers, though their activities (EC50) were about 10 times weaker than that of (-)-indolactam V (1). These results indicate that the hydroxyl group at C-14 is not indispensable for EBV-EA induction and can be replaced. The activities (EC50) of (-)-1-N-methyl, (-)-1-N-ethyl, and (-)-1-N-butyl indolactam V (10, 11, and 12) were about 5 times weaker than that of (-)-indolactam V (1), while (-)-1-N-hexyl and (-)-1-N-octyl indolactam V (13 and 14) were even less active, suggesting that the free imino group of the indole ring in (-)-indolactam V (1) plays an important role in the activity, and that the activity cannot be enhanced by alkylation at the N-1 position of (-)-indolactam V (1).
Epstein-Barr virus (EBV) activating potency of 12 species of plants belonging to the Euphorbiaceae family, that are commonly grown in Cameroon, one of the endemic areas of Burkitt's lymphoma (BL), was investigated. The EBV-inducing activity was found in most of the plants tested and in the soil around the plants whose root extracts were active. These findings support the notion that such EBV-activating principles are one of the environmental co-factors causing BL.
Inverted membrane vesicles prepared from Vibrio alginolyticus generated a membrane potential (positive inside) and accumulated Na+ by the oxidation of NADH. Generation of the membrane potential required Na+ and was inhibited by 2-heptyl-4-hydroxyquinoline N-oxide, a specific inhibitor of the Na+-dependent NADH oxidase. Collapse of the membrane potential by valinomycin stimulated the uptake of Na+. In contrast, accumulation of H+ was not detected under all the conditions tested. These results suggest that only Na+ is translocated by the Na+-dependent NADH oxidase of V. alginolyticus.
28 anticancer agents have been surveyed for Epstein-Barr virus (EBV) activating potency. Two vinca alkaloids with antitubulin activity, vinblastine (VLB) and vincristine (VCR), enhanced the expression of EBV early antigens (EA) in a latently infected human lymphoblastoid cell line (Raji), when used in combination with n-butyrate. Other antitubulin agents, colchicine, colcemid, and podophyllotoxin, had the same effect, although their effects were less than that of the potent tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA).
Effects of electroacupuncture (EA) on pain threshold and beta-endorphin (beta-End) contents in plasma, pituitary (Pit), hypothalamus (Hyp) and cerebrospinal fluid (CSF) were studied in nontreated, dexamethasone (Dex) treated and adrenalectomized (Adrex) male SD rats by the use of specific determination of rat beta-End (combination of HPLC and RIA). EA increased pain threshold and plasma beta-End with no effect on beta-End contents in Pit, Hyp and CSF. Dex did not affect control pain threshold, but tended to reduce EA-induced increase in pain threshold (EA-analgesia, EAA) and EA-induced increase in plasma beta-End. Adrex increased plasma beta-End without change in control pain threshold. Adrex tended to reduce EAA, but a tendency of further increase in plasma beta-End was observed after addition of EA. Adrex increased Pit beta-End, but no further change in Pit beta-End was observed after addition of EA. A positive correlation between plasma beta-End and plasma ACTH was observed in nontreated, Dex treated and Adrex rats. No correlation between plasma beta-End and potency of EAA was observed in nontreated, Dex treated and Adrex rats. The hind-paw pressure test without EA increased plasma beta-End to the same degree as that produced by EA, and it produced no analgesia. These results suggest that Pit beta-End may not be mainly involved in the development of EAA.
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The respiratory chain of the marine bacterium Vibrio alginolyticus pumps out Na+ at the NADH:quinone oxidoreductase segment. The respiratory Na+ pump plays an important role in the bioenergetics of this bacterium by generating a sodium-motive force as a direct result of respiration in alkaline Na(+)-rich environments.
Endoscopy and superselective angiography has been performed in 68 preoperative patients with the depressed type gastric cancer. The results are summarized as follows. Differentiation of the cancers into the early and the advanced was correct in 91%, and classification of the cancers into 3 groups (1 ; m, 2 ; sm, 3 ; advanced) was correct in 72% by endoscopy. Differentiation of the cancers into the early and the advanced was correct in 90%, and classification of the cancers into 4 groups (1 ; m X sm, 2 ; pm, 3 ; ss X se, 4 ; sei) was correct in 81% by the angiography. The rate of misdiagnosis, taking the early simulating advanced gastric cancer as the early, was 20% by the endoscopy, as compared to 8% by the angiography. Classification of the early simulating advanced gastric cancers into 3 groups (1 ; pm, 2 ; ss X se, 3 ; sei) was correct in 68% by the angiography. Excavated type cancer was likely to be overestimated as to the depth of invasion by the angiography. Poorly differentiated type, scirrhous type, and infiltrative growth with an ill defined border were found difficult to be correctly evaluated by both endoscopy and angiography. Preoperative angiography was useful for appropriate surgical therapy of the gastric cancer.
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The Na+-motive NADH oxidase activity from Vibrio alginolyticus was extracted with octylglucoside and reconstituted into liposomes by dilution. On the addition of NADH, the reconstituted proteoliposomes generated delta psi (inside positive) and delta pH (inside alkaline) in the presence of a proton conductor CCCP, and accumulated Na+ in the presence of valinomycin. These results indicate that the NADH oxidase activity, reconstituted in opposite orientation, leads to the generation of an electrochemical potential of Na+ by the influx of Na+.
The marine bacterium, Vibrio alginolyticus, regulates the cytoplasmic pH at about 7.8 over the pH range 6.0-9.0. By the addition of diethanolamine (a membrane-permeable amine) at pH 9.0, the internal pH was alkalized and simultaneously the cellular K+ was released. Following the K+ exit, the internal pH was acidified until 7.8, where the K+ exit leveled off. The K+ exit was mediated by a K+/H+ antiporter that is driven by the outwardly directed K+ gradient and ceases to function at the internal pH of 7.8 and below. The Na+-loaded cells assayed in the absence of KCl generated inside acidic delta pH at alkaline pH due to the function of an Na+/H+ antiporter, but the internal pH was not maintained at a constant value. At acidic pH range, the addition of KCl to the external medium was necessary for the alkalization of cell interior. These results suggested that in cooperation with the K+ uptake system and H+ pumps, the K+/H+ antiporter functions as a regulator of cytoplasmic pH to maintain a constant value of 7.8 over the pH range 6.0-9.0.