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Biomedical subjects

S Toyoshima

Publications and source records attributed to S Toyoshima.

At least 163 records · Page 9Linked to original sources
PubMed1981

In vivo distribution of 14C-labeled N4-behenoyl-1-beta-D-arabinofuranosylcytosine in mice.

In order to clarify the pharmacological characteristics of N4-behenoyl-1-beta-d-arabinofuranosylcytosine (BHAC) and 1-beta-D-arabinofuranosylcytosine (AraC) with regard to their distribution in vivo, 14C-labeled BHAC and 13C-labeled AraC were injected intravenously into mice. Their in vivo distribution was determined by whole-body macroautoradiography and by an oxidation method. The disappearance rates of BHAC[cytosine-2-14C] and BHAC[behenoyl-l-14C] from the blood were slower than that of AraC[cytosine-2-14C], and the elimination rates of BHAC[cytosine-2-14C] and BHAC[behenoyl-14C] into the urine and feces were also slower than that of AraC[cytosine-2-14C]. The total amounts of BHAC[cytosine-2-14C] and BHAC[behenoyl-1-14C] eliminated within 48 hr after the injection were small. AraC[cytosine-2-14C] was equally distributed in each organ, while large amounts of BHAC[cytosine-2-14C] were found in and the placentae. The BHAC[behenoyl-1-14C]level in the thymus was lower than that of BHAC[cytosine-2-14C]. A very low level of radioactivity was found in most of the organs 6 hr after the injection of Arac[cytosine-2-14C], but BHAC[cytosine-2-14C] was observed even 24 hr after the injection. Radioactivity was still found in the liver, spleen, kidneys and adrenal glands of mice injected with BHAC[behenoyl-1-14C] even after 72 hr. In pregnant mice, AraC]cytosine-2-14C] was transmitted to the fetuses, but only a very small amount of 14C-BHAC was transmitted to the fetuses.

Animals↗
PubMed1980

Phospholipid methylation: a biochemical signal modulating lymphocyte mitogenesis.

Phospholipid methylation in murine T lymphocytes but not B cells was stimulated by mitogenic lectins such as concanavalin A and phytohemagglutinin, and the methylation was then returned to the control level by the concomitant activation of phospholipase A2. A parallelism between dose-response curves of concanavalin A for phospholipid methylation and thymidine incorporation was found. Inhibition of either synthesis or degradation of methylated phospholipids resulted in a decrease in the thymidine incorporation. Although prostaglandins such as the E and F series were the main products of arachidonic acid released by phospholipase A2 activation, inhibition of synthesis of these compounds by indomethacin did not reduce the thymidine incorporation significantly. These results suggest that the mitogenesis of murine T lymphocytes is triggered by the activation of both phospholipid methyltransferase(s) and phospholipase A2.

Animals↗
PubMed1980

Influence of chemical modification of N alpha-cocoyl-L-arginine ethyl ester on its hepatitis B surface antigen-inactivating effect.

We have reported previously that N alpha-cocoyl-L-arginine ethyl ester (CAE) strongly inactivates hepatitis B surface antigen (HBsAg; Sugimoto and Toyoshima, Antimicrob. Agents Chemother. 16:329--332, 1979). Replacement of the L-arginine moiety of CAE by L-lysine did not decrease the HBsAg-inactivating effect of CAE, whereas replacement by some neutral amino acids and L-ornithine decreased it. Esterification of the carboxyl group of N alpha-acyl-L-arginine enhanced its inactivating effect. When the ethyl ester of CAE was converted to an amide group, the effect was appreciably decreased. Modification of the carboxyl group was essential for the inactivation. The effectiveness of N alpha-acyl-L-arginine ethyl ester depends upon the length of the acyl group, with the optimum length for the inactivation of HBsAg being C12 to C14. In addition to CAE, N alpha-lauroyl-L-lysine ethyl ester and N alpha-cocoyl-L-arginine amide were found to be strong inactivators of HBsAg. Significant inactivating effects on HBsAg were not observed in many anionic detergents containing an amino acid. These results suggest that for strongly inactivating HBsAg, a compound should contain a special amino acid, such as L-arginine, and a long acyl group and exhibit a cationic property.

Amino Acids↗
PubMed1979

Antiviral effect of N-phenylacetoaminomethylene-DL-p-nitrophenylalanine (A-101) on murine leukemia viruses.

N-Phenylacetoaminomethylene-DL-p-nitrophenylalanine (A-101), when administered ip to male DDY mice infected with Friend leukemia virus, significantly inhibited virus-induced splenomegaly, reduced viable virus titers in spleen and plasma, and significantly prolonged survival time. A-101 also inhibited multiplication of the Friend and Moloney viruses in tissue culture systems.

Animals↗
PubMed1979

N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt, as an inactivator of hepatitis B surface antigen.

N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt (CAE), exhibited a strong inactivating effect on hepatitis B surface antigen. Concentrations of CAE required for 50 and 100% inactivation of the antigen were 0.01 to 0.025% and 0.025 to 0.05% respectively. CAE completely inactivated hepatitis B surface antigen at the lowest concentration compared with various compounds including about 500 amino acid derivatives, sodium hypochlorite, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and some detergents. Furthermore, CAE inactivated vaccinia virus, herpes simplex virus, and influenza virus, whereas poliovirus was not inactivated at all. The results suggest that the inactivating effects of CAE are related to interaction with lipid-containing viral envelopes.

Antiviral Agents↗
PubMed1979

[The difference of drug sensitivity of tumor cells on N-ethyloxycarbonylaminomethyl-L-isoleucine (A-145 (author's transl)].

N-Ethyloxycarbonylaminomehyl-L-isoleucine (A-145), a novel antitumor amino acid derivative, is an anti-tumor agent effect in cases of Ehrlich ascites rather than against Sarcoma-180. The chemotherapeutic index of A-145 was 14.9 for Ehrlich ascites carcinoma and 4.2 for ascites Sarcoma-180. Experimental studies on ddy mice regarding the difference in susceptibility of these two tumor cell lines to A-145 gave the following results. In in vivo experiments, the uptake of 14C-A-145 by Ehrlich ascites carcinoma was greater than by Sarcoma-180, i. e. the uptake ratio of Ehrlich ascites carcinoma/Sarcoma-180 was 1.52 at 30 min and 2.7 at 24 hr after injection. In in vivo experiments, there was no remarkable difference between Ehrlich ascites carcinoma and Sarcoma 180 in the subcellular distribution of 14C-A-145, and the majority of the radioactivity taken up was distributed in nuclei and cytosol fractions. In in vitro experiments, the uptake of 14C-A-145 by both cell lines was found to be temperature sensitive, glucose dependent, and decreased on addition of KCN, 2, 4-dinitrophenol or iodoacetic acid. In in vitro experiments, competitive inhibition by L-isoleucine on 14C-A-145 uptake into tumor cells was observed in both cell lines, however, in vitro experiments, the inhibitory effect of A-145 on cell growth in cultured Sarcoma-180 was not reversed by L-isoleucine.

Amino Acids↗
PubMed1978

Isolation and partial characterization of the major sialoglycoprotein of human T-lymphoblastoid cells of a MOLT-4B cell line.

A sialoglycoprotein with an approx. mol.wt. of 95000 was isolated from human lymphoblastoid cells of a MOLT-4B cell line, which was of human T-lymphocyte origin, by ion-exchange chromatography, affinity chromatography on a column of wheat-germ agglutinin-Sepharose and preparative slab-gel electrophoresis. The localization of this glycoprotein on the cell surface was indicated by surface labelling by the periodate/NaB3H4 and lactoperoxidase-catalysed iodination methods. Carbohydrate analyses of this glycoprotein revealed that its total carbohydrate content is 28% (w/w), and it contains fucose, galactose, mannose, N-acetylglucosamine, N-acetylgalactosamine and sialic acid in molar proportions 1.0:4.0:3.7:3.5:1.2:2.5, suggesting that it has two types of sugar chain, i.e. sugar chains like those of serum glycoproteins and sugar chains of the type found in mucins. Actually, alkaline borohydride treatment of this glycoprotein yielded tri- and tetra-saccharide, the latter containing 1 molecule of fucose in addition to each molecule of galactose, N-acetylgalactosamine and sialic acid. This glycoprotein bound to Ricinus communis agglutinin and concanavalin A as well as to wheat-germ agglutinin.

Borohydrides↗
PubMed1978

Antitumor activity of a new amino acid derivative, N6,N9-bis-(butyloxycarbonylaminomethyl)-L-citrulline.

Approximately 800 amino acid derivatives have been synthesized and screened in order to evaluate their antitumor activity against various transplantable rat ascites hepatomas. Among them, N6,N9-bis(butyloxycarbonylaminomethyl)-L-citrulline (A-924) was found to be highly effective against various rat ascites hepatomas. A-924, when given orally, exhibited prolongation of survival of rats implanted intravenously with ascites hepatoma cells such as AH-44, AH-66, AH-130, AH-66F, or AH-41C.

Administration, Oral↗