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Biomedical subjects

H Tokuda

Publications and source records attributed to H Tokuda.

At least 343 records · Page 19Linked to original sources

Na+ is translocated at NADH:quinone oxidoreductase segment in the respiratory chain of Vibrio alginolyticus.

The coupling site of the Na+ pump to the respiratory chain of Vibrio alginolyticus was examined using membrane fractions prepared from the wild type, Na+ pump-deficient mutants, and spontaneous revertant. NADH oxidase of the wild type and revertant specifically required NA+ for maximum activity, whereas Na+ was not essential for the NADH oxidase of mutants. Similar to the Na+ pump in whole cells, the Na+-dependent NADH oxidase in membranes had a pH optimum in the alkaline region. A respiratory inhibitor, 2-heptyl-4-hydroxyquinoline-N-oxide (HQNO), inhibited the Na+-dependent NADH oxidase but had little effect on the NA+-independent activity of mutant membranes. NADH:quinone oxidoreductase was found to be the Na+-dependent HQNO-sensitive site of the NADH oxidase. In the wild type cells, HQNO was also found to cause a strong inhibition of the Na+ pump with little effect on the overall H+ extrusion by respiration. The inhibition of the Na+ pump by HQNO was overcome by oxidized, but not reduced, N,N,N',N'-tetra-methyl-p-phenylenediamine (TMPD). In the presence of oxidised TMPD, the electron flow NADH to oxygen seemed to bypass the HQNO-sensitive site and energize the Na+ pump. From these results, it was concluded that the Na+ pump is coupled to the respiratory chain at the step of NADH:quinone oxidoreductase.

Ascorbic Acid↗

Abnormalities of cone photopigments in genetic carriers of protanomaly.

Anomaloscopic color matching was performed in 57 protanomalous boys. The relative luminous efficiencies of their mothers were measured by flicker photometry to clarify the characteristics of protanomaly carriers. The sensitivity loss of protanomaly carriers in the long wave-length region had a highly significant correlation with the anomalous quotients ( AQs ) of their protanomalous sons. This correlation means that both the luminous efficiencies of the protanomaly carriers and the AQs of their sons are determined by the same "anomalous" cone pigments.

Adolescent↗

Epstein-Barr virus-activating principle in human semen.

During the screening of natural and physiological products for their Epstein-Barr virus (EBV)-activating potency, we found that a considerable number of human semen specimens obtained from infertility clinics (30 cases) possess a marked capacity to induce EBV early antigen (EA) in non-producer Raji cell system when assayed in combination with n-butyrate. The EBV EA-inducing activity of the semen samples was comparable to that of the most efficient EBV EA inducers, the plant diterpene esters such as 12-O-tetradecanoylphorbol-13-acetate (TPA). Since many, if not all, of such active agents show overlapping with the tumor promoters in their biological reactions, these findings may provide a new insight for assessing the role of semen in the etiology of certain types of human genital malignancies.

Adult↗

Effect of an anticancer agent, vinblastine, on mouse skin.

The effect of vinblastine (VLB), an anticancer agent which has recently been shown to have Epstein-Barr virus (EBV)-activating potency, on CD-1 mouse skin was investigated. A single topical application of either 15 or 100 micrograms of VLB induced epidermal hyperplasia. Twice weekly applications of these doses of VLB either for 29 weeks after a 7,12-dimethylbenz(a)anthracene (DMBA) initiation (one-stage promotion) or for 27 weeks after DMBA initiation and a limited treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA) (two-stage promotion) failed to show any significant tumor-promoting activity at 30 weeks. The problem of EBV activation and its relationship to tumor promotion should await more definitive studies.

9,10-Dimethyl-1,2-benzanthracene↗

[A specific and quantitative determination of rat beta-endorphin. Combination of HPLC and RIA].

A specific and quantitative method for the determination of rat beta-endorphin by the combination of HPLC and RIA was developed. Rabbit antiserum against camel beta-endorphin (c beta-E) was raised and used for RIA at the final concentration of 1:10000. The quantitative range estimated from the displacement curve was 0.1-2.0 ng. Cross-reactivities with Met-Enk, Leu-Enk, alpha-MSH, alpha-endorphin, ACTH and human beta-E were less than 0.1, less than 0.1, less than 0.1, less than 0.1, 2 and 100%, respectively. These peptides were separated from each other by reversed phase HPLC with UV254 nm detection, and the minimum detectable dose of c beta-E was found to be 1 microgram. beta-E-like immunoreactivity (beta-ELIR) in the HPLC effluent was determined by RIA. The HPLC-RIA chromatogram of authentic c beta-E exhibited a single peak which coincided with the peak of c beta-E detected by UV, and 80% of the injected c beta-E (1-100 ng) was detected in the c beta-E fraction. The HPLC-RIA chromatogram of rat pituitary, hypothalamus, cerebrospinal fluid and plasma revealed the presence of 1-3 peaks, one of which was observed at the position of c beta-E. The HPLC elution of rat pituitary resolved the material into two peaks of biological activity, one of which coincided with the peak of beta-ELIR at the position of c beta-E. The HPLC-RIA chromatogram of the c beta-E fraction from pituitary obtained by gel-chromatography exhibited three peaks, one of which coincided with c beta-E. These results suggest that beta-ELIR in the c beta-E fraction of the HPLC elution may reflect rat beta-E accurately.

Animals↗

Effect of sultopride on prolactin secretion in rats.

Oral administration of sultopride caused a significant and dose-related increase in serum prolactin levels in the rat. Sultopride was 4-6 times as potent as sulpiride in stimulating prolactin secretion. Both drugs produced much greater stimulations of prolactin release in female rats than in male rats, suggesting the sex difference in response to drugs. CB-154, a dopamine agonist, inhibited the sultopride-induced prolactin release. Stereoselective activity of sultopride-isomers was observed in increasing rat prolactin secretion. Sultopride had no significant effects on LH and FSH basal levels in female rats. In a successive study, basal prolactin levels in the male rat were higher at 2-3 days, but lower at 6 and 14 days. Prolactin response 1 hr after sultopride administration was observed throughout the experiments. Sultopride neutralized the dopamine-mediated inhibition of prolactin secretion from the anterior pituitary in vitro. These results suggest that sultopride, like sulpiride, stimulates prolactin secretion by blocking the dopamine receptor in the pituitary.

Amisulpride↗

[Angiographic analysis of vascular anatomy in gastric cancer].

Celiac, left gastric, common hepatic and superior mesenteric angiography was performed in 296 gastric cancer patients. Relationship between anatomical variations and the mode of lymphatic metastasis was discussed. The emergence of right gastric artery was from hepatic artery proper in 46.9%, right, middle and left hepatic in 26.4%, common hepatic and gastroduodenal in 18.6%, and others in 5.4%. The rate of metastasis to suprapyloric nodes was the highest (20.0%) among the cases, in which the right gastric artery was given off distal to the hepatic artery proper. Left gastric artery emerged from the celiac in 94.9%, splenic in 2.7%, abdominal aorta in 2.1%, and common hepatic in 0.3%. Knowledge of the origin of the arteries is essential to thorough dissection of the perivascular lymph nodes. The accessory hepatic arteries emerged from left gastric artery in 17.9% of the cases, in which the rate of lymph node metastasis along left gastric artery was higher than others. Left gastric artery should be severed at its point of emergence for thorough dissection of lymph nodes along this artery in gastric cancer. However, the fact that 20.8% of accessory left hepatic arteries were perfusing more than 2 liver segments must be into consideration.

Angiography↗

Isolation of Vibrio alginolyticus mutants defective in the respiration-coupled Na+ pump.

When the respiration-coupled Na+ pump functions, V. alginolyticus is able to grow in the presence of an extremely high concentration of proton conductor, carbonylcyanide m-chlorophenylhydrazone. The mutants which became sensitive to the proton conductor were isolated and examined in regard to the Na+ pump activity. Although the activity of a respiration-dependent H+ extrusion by the mutants is comparable to that by the wild type, the Na+ pump activity of the mutants is significantly reduced. Furthermore, NADH oxidase of membranes isolated from the mutants is altered to be independent of Na+. It is concluded that the mutants have an alteration in the respiratory chain which simultaneously results in a lack of the Na+ pump.

Biological Transport, Active↗

Therapeutic effect of a retinoid (Ro 10-9359) on rats with bladder tumours induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine upon administration alone or in combination with mitomycin C.

The therapeutic effect of an aromatic retinoic acid analogue (Ro 10-9359) and mitomycin C (MMC) on rats with bladder tumours induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. Eight-week-old female Wistar rats were given 0.05% BBN in drinking water for 8 weeks. Therapy was started at week 26 and all rats were killed at week 30. MMC at a dose of 0.3 mg/kg twice a week ip for 3 weeks significantly reduced the incidence and the mean number of tumours. With oral Ro 10-9359 at a dose of 100 mg/kg once weekly for 4 weeks, no significant effect was observed. The combination of MMC and Ro 10-9359 significantly reduced the mean number, but not the incidence, of tumours. The difference between the effect of MMC alone and that of MMC given in combination with Ro 10-9359 was not statistically significant. Thus no favorable effect of the retinoid could be demonstrated either alone or in combination with MMC.

Animals↗

Epstein-Barr virus activation by tung oil, extracts of Aleurites fordii and its diterpene ester 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate.

During the screening of plant oils for their Epstein-Barr virus (EBV)-activating potency, we found that tung oil possesses an activity comparable to croton oil. Tung oil from various sources and the extracts from its parental plant Aleurites fordii (Chinese tung oil tree), when used in combination with n-butyrate, were shown to efficiently activate EBV persisting in human lymphoblastoid Raji cells (non-producer). The major diterpene ester in the plant extract, 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate (HHPA), also exerted a similar activity. In producer P3HR-1 cells, both tung oil and HHPA increased the yield of infectious EBV by approximately five-fold. Since tung oil is used for the manufacture of oil paints, varnishes, waterproof substance, anticorrosives and other products, the implication of using such an agent with EBV-activating potency in our daily life is assessed and discussed.

Cells, Cultured↗

Growth of a marine Vibrio alginolyticus and moderately halophilic V. costicola becomes uncoupler resistant when the respiration-dependent Na+ pump functions.

The growth of Vibrio alginolyticus and V. costicola, which possess respiration-dependent Na+ pumps, was highly resistant to the proton conductor carbonyl cyanide-m-chlorophenyl hydrazone (CCCP), in alkaline growth media, even though the membrane was rendered permeable to H+. The pH dependence of CCCP-resistant growth was similar to that of the Na+ pump. In contrast, Escherichia coli ML308-225 showed neither Na+ pump activity nor CCCP-resistant growth, even when grown in alkaline, Na+-rich media. These results suggest that certain bacteria possess the Na+ pump and are thus able to grow under the conditions where H+ circulation across the membrane does not take place. Moreover, V. alginolyticus growing in the presence of CCCP maintains normal levels of internal K+, Na+, and H+. The Na+ pump, therefore, makes the growth of these organisms resistant to CCCP by maintaining the intracellular cation environments.

Biological Transport, Active↗

Distribution and characterization of environmental promoter substances as assayed by synergistic Epstein-Barr virus-activating system.

The application of a new screening procedure which utilizes the synergistic effect of short-chain fatty acids and tumor-promoting diterpene esters enabled rapid and easy detection of environmental substances with Epstein-Barr virus (EBV)-activating/tumor-promoting potency. Over 500 samples were tested and more than 30 substances with such activities were identified. Most, if not all, were plant diterpene esters derived from Euphorbiaceae and Thymelaeaceae families and a few were indole alkaloids of microbial origin. We attempted to link these laboratory findings with those of epidemiological field studies on three virus-associated diseases, Burkitt's lymphoma, nasopharyngeal carcinoma, and adult T-cell leukemia/lymphoma, which are known to have a peculiar geographical distribution. Our hypothesis was that EBV-activating/tumor-promoting substances might be present in the abundant areas where such diseases are endemic. We noticed that many active diterpene ester-containing plants are widely used as herbal medicaments in Africa and China and determined many plant species that had such activities. One example is Aleurites fordii, a plant commonly grown in Southern China for industrial purposes which yielded a potent promoter substance (12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate, HHPA). The active diterpene esters were purified and their possible mechanism was studied from the view of receptor-binding, protein kinase C activation and transmembrane signaling.

Animals↗

[Histopathological evaluation of transarterial one shot infusion of adriamycin as a preoperative adjuvant chemotherapy for the breast cancer].

Thirty patients with resectable breast cancer were treated with transarterial one shot infusion of 20 mg of adriamycin as a preoperative adjuvant chemotherapy. After breast angiography by Seldinger's method, adriamycin at a dose of 20 mg was administered through the feeding artery with one shot injection. Anticancer effect of adriamycin was evaluated microscopically after radical mastectomy. In the primary tumor, the effective histological changes were found in 9 (30%) of 30 cases. In the metastatic lymph nodes, the effective changes were found in 5 (50%) of 10 cases. Mild side effects were seen in 70% of the cases, but not serious. It was suggested that transarterial one shot infusion of 20 mg adriamycin was a histopathologically effective procedure as preoperative chemotherapy for breast cancer.

Adult↗