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Biomedical subjects

H Tokuda

Publications and source records attributed to H Tokuda.

At least 307 records · Page 17Linked to original sources

Screening of edible plants against possible anti-tumor promoting activity.

One hundred twenty-one species of edible plants (133 test-parts) were screened against possible anti-tumor promoting activity by an in vitro short-term assay system of inhibition of Epstein-Barr virus (EBV) activation induced by a phorbol-ester promoter, 12-O-hexadecanoylphorbol-13-acetate (HPA). The methanol-extracts (ME) of 14 species of the edible plants strongly inhibited the activation, 7 moderately and 12 weakly inhibited it. On partition of the randomly selected inactive ME (26 species) with ethyl acetate and water, 13 and 2 species were active, more or less, in the ethyl acetate and water soluble part, respectively. Thus, this result suggested that anti-tumor promoters occur in a wide variety of edible plants. The anti-tumor promoting activity in the crude extracts may be enhanced or reduced with co-occurring factors acting additively, synergistically or antagonistically.

Antineoplastic Agents, Phytogenic↗

Roles of the respiratory Na+ pump in bioenergetics of Vibrio alginolyticus.

Bioenergetic characteristics of Na+ pump-defective mutants of a marine bacterium Vibrio alginolyticus were compared with those of the wild type and revertant. Generation of membrane potential and motility at pH 8.5 in the mutants were completely inhibited by a proton conductor, carbonylcyanide m-chlorophenylhydrazone, whereas those in the wild type or revertant were resistant to the inhibitor. Motility and amino acid transport were driven by the electrochemical potential of Na+ not only in the wild type or revertant but also in the mutants. In the absence of the proton conductor, motility and amino acid transport of the mutants did not significantly differ from those of the wild type or revertant even at pH 8.5, where the Na+ pump has maximum activity. Therefore, the electrochemical potential of Na+ in the mutants seemed to be maintained at a normal level by a respiration-dependent H+ pump and Na+/H+ antiporter. On the other hand, growth of the mutants became defective as the medium pH increased, especially on minimal medium. These results indicate that the Na+ pump is an important energy-generating mechanism when nutrients are limited at alkaline pH.

Aminoisobutyric Acids↗

["Super-extensive lymph node dissection" for advanced gastric cancer].

Our "super-extensive lymph node dissection" (SELD) for gastric cancer is designed to remove the nodes as thoroughly as possible from the n4-area, i.e., para-aortic area from diaphragmatic crus to IMA, and para-superior mesenteric trunk. One hundred and sixty three cases of gastric cancer, treated with SELD is reviewed. 1) ps (+) cases had n4 metastasis in 25.8%, incidence being compatible to n1 or n2 cases. 2) Prognosis was relatively good in the cases whose cancer positive rate of the dissected n4 lymph nodes was found below 25%. 3) Recurrence was noted in the remaining lymph nodes in the cases, whose rate of lymph node metastasis had been high in preceding surgery. This fact seems to warrant SELD for advanced gastric cancer. 4) SELD however, was accompanied by the longer duration of surgery with more blood loss and by higher incidence of complications, than conventional R2, R3 dissection.

Humans↗

Tumor-promoting activity of extracts of human semen in SENCAR mice.

Application of ether extracts of pooled human semen that induce Epstein-Barr virus (EBV) activation promoted skin tumor production in female SENCAR mice previously treated with 100 micrograms of 7, 12-dimethylbenz(a)anthracene (DMBA). Twice-weekly applications of 60 micrograms ether extract samples produced papillomas in SENCAR mice. Several samples of human semen were tested to determine the relationship between tumor-promoting activity and EBV activation in human semen. Pooled human semen that induced more than 10% EBV activation effectively promoted tumor production, but samples that induced less than 0.1% EBV activation were ineffective.

9,10-Dimethyl-1,2-benzanthracene↗

Conjugation-dependent recovery of the Na+ pump in a mutant of Vibrio alginolyticus lacking three subunits of the Na+ pump.

The Na+ pump-deficient mutant, Nap1, of Vibrio alginolyticus was found to lack three subunits of Na+-dependent NADH:quinone oxidoreductase complex. Although a spontaneous Na+ pump positive revertant did not appear from Nap1, transconjugants that recovered both the Na+ pump activity and the subunits were isolated from Nap1 conjugated with the wild type. Moreover, the wild type was found to contain two different sizes of plasmids. These results suggest the possibility that the Na+ pump is encoded by a plasmid.

Biological Transport, Active↗

Immunohistochemical demonstration of estrogen, progesterone, CEA and ferritin in breast cancer and their clinical value for the prediction of early postoperative recurrence.

The aim of this paper is to determine whether the incidence of estrogen-, progesterone-, CEA-, and ferritin- positive staining of primary tumors, by using the PAP method, is related to the prognosis of breast cancer status. A significantly higher incidence (71 per cent) of CEA-positive tumors was observed in patients who had a recurrence of breast cancer within 2 years after radical operation. Patients, whose tumors were positive in estrogen or negative in CEA, showed a relatively good prognosis, even after a recurrence of the disease. Distant metastases were seen in most of the patients positive in CEA (78 per cent). Before the recurrence of breast cancer, those patients positive in progesterone had a good prognosis. After the recurrence, however, there was no relationship between the prognosis of recurrent disease and the progesterone-staining of primary tumors. Our data suggest that the immunohistological staining of estrogen, progesterone and CEA might offer the effective prognostic indices in breast cancer patients.

Breast Neoplasms↗

The metabolism of indole alkaloid tumor promoter, (-)-indolactam V, which has the fundamental structure of teleocidins, by rat liver microsomes.

Metabolic activation and/or deactivation of indole alkaloid tumor promoter, (-)-indolactam V (ILV), was examined using rat liver microsomes. Reaction of ILV with the microsomes supplemented with NADPH and MgCl2 gave three major metabolites, which were identified as (-)-N13-desmethylindolactam V and two diastereomers of (-)-2-oxyindolactam V at C-3. The tumor-promoting activities of these metabolites were evaluated by induction of Epstein-Barr virus early antigen and inhibition of specific binding of [3H]-12-O-tetradecanoylphorbol-13-acetate to a mouse epidermal particulate fraction, and proved to be conspicuously lower than that of ILV. These results demonstrate that the metabolism of ILV results in detoxification, and that it itself is the tumor-promoting entity. Studies on the enzymes concerned with this metabolism suggested the involvement of cytochrome P-450-containing mixed-function oxidases. Similar deactivation seems to be possible by skin, where the mixed-function oxidases are known to exist.

Animals↗

Effects of extracellular potassium on acid release and motility initiation in Toxoplasma gondii.

The internal pH (pHi) of Toxoplasma gondii was estimated by measuring the accumulation of the weak base 9-aminoacridine in buffers with various ionic compositions. The pHi of the metabolizing parasite increased when the extracellular K+ was elevated in alkaline medium or when the external pH (pHe) was substantially increased in medium employing high external K+ (90 mM). The parasite in mouse peritoneal fluid, or in potassium sulfate buffer (pH 8.2), where the pHi was demonstrated to be increased to 7.9, became motile when acidic buffer was substituted for the original suspension medium. This acid-induced independent movement subsided within 5 min but was repeatedly induced if the pHe was serially lowered to 6.0. Basic buffers, on the other hand, abolished motility when applied to the moving parasites. Nigericin, which is known to collapse pH gradients across the membrane, also abolished motility.

Animals↗

Primary testicular carcinoid tumor in a 19-year-old boy.

This report describes a primary carcinoid tumor of the testis arising in a 19-year-old boy. Symptoms suggestive of a carcinoid syndrome were not noted in this case. The pathological specimen did not contain teratomatous components. Histochemically, the argyrophil reaction was positive. The immunohistochemical finding of immunoreactive cells for 5-hydroxytryptamine (serotonin) was also positive. To our knowledge, this is the youngest case to be reported.

Adult↗

Structure-activity studies of the indole alkaloid tumor promoter teleocidins.

New teleocidin derivatives with various substituents at positions 2, 5 and 7 of the indole ring were prepared from (-)-indolactam V, which is the fundamental structure of teleocidins and has a tumor-promoting activity, to examine the contribution of the alkyl substituents of teleocidins to the activity. Their possible tumor-promoting activities in vivo were evaluated by Epstein-Barr virus early antigen-inducing activity and inhibition of specific binding of [3H]TPA to a mouse epidermal particulate fraction. These two biological activities correlated well for each derivative. Large substituents at positions 2 and 5 remarkably lowered the activities, indicating that the structural requirements for the activities of these domains are especially strict. To investigate in detail the contribution of position 2 of (-)-indolactam V to the activities, new microbial metabolites, (-)-2-oxy-indolactam V, and blastmycetin B and C, were also tested. These compounds proved to be inactive, suggesting that the double bond at position 2 plays an important role for the activities. Substituents at position 7 generally enhanced the activities and even blastmycetin A, which is a dimer of (-)-indolactam V, showed high activities. The effects of the substituents on binding ability to the 12-O-tetradecanoylphorbol-13-acetate receptor were analyzed quantitatively using physicochemical substituent parameters and regression analysis. The results exhibited the fact that hydrophobicity of the substituents plays a critical role for receptor binding, and supported the hypothesis that the monoterpenoid moiety of teleocidins is involved in the non-specific hydrophobic interaction with phospholipids in cell membrane.

Animals↗

[Studies on para-aortic metastatic lymph nodes in gastric cancer after endoscopic injection of activated carbon particles].

When activated carbon particles are injected into the tissues, they are absorbed into the lymphatic capillary and reach to the regional lymph nodes. Utilising this property of the activated carbon, we injected small sized carbon particles (CH-44) around the gastric cancer using endoscope to examine para-aortic lymph node metastasis. Sixty eight patients with gastric cancer existing serosal invasion were subjected to extended radical gastrectomy dissecting para-aortic lymph nodes as well as regional lymph nodes. Twenty patients (29.4%) had para-aortic lymph node metastasis. Cumulative 5-year survival rate of these patients after surgery was 20.0 per cent. High incidence of metastasis in para-aortic lymph nodes was found in the lymph nodes larger than 4mm in diameter, but 15.9 per cent of lymph nodes less than 2mm in diameter had metastasis. Large lymph nodes occupied almost wholly by cancer cells were stained scarcely by activated carbon particles, but lymph nodes with moderate or slight metastasis were stained black well and this method was very useful for lymph node dissection, even for micro-lymph nodes which seemed to escape from naked eye at surgery.

Aorta↗

Determination of dye intermediates in oxidative hair dyes by fused-silica capillary gas chromatography.

A fused-silica capillary gas chromatographic method is described for the determination of dye intermediates in oxidative hair dyes. An appropriate amount of hair dye sample is dissolved in 10 ml of methanol containing 0.25 g of ammonium thioglycolate and an appropriate amount of 2-amino-4-methylphenol as an internal standard. This solution is directly injected into a gas chromatograph. A fused-silica capillary column with cross-linked methyl silicone OV-1 or SE-54 as a liquid phase yields excellent resolution of dye intermediates. Some factors affecting the quantitation of dye intermediates are discussed. The proposed method gave good recoveries and reproducibilities, and permits simultaneous determination of various types of dye intermediates without any pretreatment. The use of a nitrogen-phosphorus detector allows the selective detection of nitrogen-containing dye intermediates. This simple and versatile method is applicable for the determination of dye intermediates in commercial hair dyes.

Ammonia↗

N-ethylmaleimide desensitizes pH-dependence of K+/H+ antiporter in a marine bacterium, Vibrio alginolyticus.

The K+/H+ antiporter of a marine bacterium, Vibrio alginolyticus, is strongly dependent upon the cytoplasmic pH and functions only at an internal pH above 7.7. In alkaline buffer with an outwardly directed chemical gradient of K+ (delta pK), the internal pH was maintained at about 7.7. Addition of N-ethylmaleimide (NEM) released cellular K+ and acidified the cytosol below pH 7.7. The NEM effect was reversed by the addition of 2-mercaptoethanol: K+ efflux ceased, and the internal pH returned to about 7.7. In acidic buffer, the internal pH was also regulated at about 7.6 even in the absence of delta pK. Following addition of NEM, the internal pH decreased below 7.6, dissipating delta pH. These results suggest that NEM desensitizes the pH-dependence of the K+/H+ antiporter, allowing the antiporter to function at an internal pH below 7.7.

Carrier Proteins↗

Generation of Na+ electrochemical potential by the Na+-motive NADH oxidase and Na+/H+ antiport system of a moderately halophilic Vibrio costicola.

Cells of Vibrio costicola at pH 8.5 generate both membrane potential (inside negative) and delta pH (inside acidic) in the presence of a proton conductor, carbonyl cyanide m-chlorophenylhydrazone (CCCP). The generation of CCCP-resistant membrane potential was inhibited by 2-heptyl-4-hydroxyquinoline-N-oxide that is known to inhibit the Na+-motive NADH oxidase of Vibrio alginolyticus. NADH oxidase, but not lactate oxidase, of inverted membrane vesicles prepared from V. costicola required Na+ for a maximum activity and was inhibited by 2-heptyl-4-hydroxyquinoline-N-oxide. By the oxidation of NADH, inverted membrane vesicles generated concentration gradients of Na+ across the membrane, whose magnitude was always larger than that of delta pH by about 50 mV. In contrast, magnitudes of delta pH and Na+ concentration gradients generated by the oxidation of lactate were similar. Na+ translocation in the presence of lactate was inhibited by CCCP but little affected by valinomycin. On the other hand, Na+ translocation in the presence of NADH was resistant to CCCP and stimulated by valinomycin. Amiloride, an inhibitor for a eucaryotic Na+/H+ antiport system, inhibited the lactate-dependent Na+ translocation but had little effect on the NADH-dependent Na+ translocation. These results indicate that a primary event of lactate oxidation is the translocation of H+, which then causes the generation of Na+ concentration gradients via the secondary Na+/H+ antiport system. We conclude that the NADH oxidase of V. costicola translocates Na+ as an immediate result of respiration, leading to the generation of Na+ electrochemical potential.

Amiloride↗