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Biomedical subjects

T Shiba

Publications and source records attributed to T Shiba.

At least 289 records · Page 16Linked to original sources

Synergistic effect of polyriboinosinic acid:polyribocytidylic acid and either bacterial peptidoglycans or synthetic N-acetylmuramyl peptides on production of adjuvant-induced arthritis in rats.

Lewis rats developed polyarthritis after a single injection of a water-in-oil emulsion containing various peptidoglycans (PGs) derived from Lactobacillus plantarum. A copolymer of polyriboinosinic acid and polyribocytidylic acid markedly potentiated the arthritogenicity of these PGs. The synthetic adjuvants N-acetylmuramyl-L-alanyl-D-isoglutamine (MurNAc-L-Ala-D-isoGln) and MurNAc-L-Ala-D-Gln were non-arthritogenic, but they did produce severe arthritis when mixed in a water-in-oil emulsion with a copolymer of polyriboinosinic acid and polyribocytidylic acid. Substitution of either L-isoGln or D-isoAsn for the D-isoGln in the MurNAc-L-Ala-D-isoGln markedly reduced its capacity to induce the disease. Taken together with the results of skin testing against various PGs and MurNAc-L-Ala-D-isoGln in the diseased rats, the present results suggest that (i) a minimal essential structure required for development of polyarthritis is related to a larger molecule than either MurNAc-L-Ala-D-isoGln or a monomer of PG, probably to a dimer of PG, and (ii) an antigenic determinant(s) for the delayed-type skin hypersensitivity to PGs exists on a common structure shared among these PGs, possibly somewhere on a monomer of PG not on N-acetylmuramyl peptides.

Acetylmuramyl-Alanyl-Isoglutamine↗

Immunization of experimental monkeys against Plasmodium falciparum: use of synthetic adjuvants.

The replacement of Freund's adjuvant by a possible safe adjuvant for effective immunization of owl monkeys (Aotus trivirgatus griseimembra) against a human malaria parasite, Plasmodium falciparum, has been investigated. Experiments involved the use of two synthetic adjuvants: MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine) and stearoyl-MDP (6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-isoglutamine). In both cases, P. falciparum merozoites obtained through short-term in vitro cultivation were used as antigen. MPD was used as adjuvant in 5 owl monkeys; 2 control monkeys died and of the 3 experimental monkeys only 1 survived. In contrast, in another experiment where stearoyl-MDP was used as adjuvant, there was 100% protection of 4 immunized monkeys against a challenge with the homologous strain of P. falciparum. The results of the second experiment are encouraging for the development of an effective and safe vaccine for human malaria.

Acetylmuramyl-Alanyl-Isoglutamine↗

Vaccination of experimental monkeys against Plasmodium falciparum: a possible safe adjuvant.

Owl monkeys (Aotus trivirgatus griseimembra) were effectively immunized against a human malaria parasite, Plasmodium falciparum. Two injections of antigen, primarily mature segmenters with fully developed merozoites, mixed with adjuvant (6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-isoglutamine and liposomes) were administered intramuscularly at a 4-week interval. Approximately 2 weeks after the second vaccination, the monkeys were challenged with the homologous strain of P. falciparum. All immunized monkeys survived the challenge. The substitution of Freund's complete adjuvant is an encouraging step toward the development of an effective and safe vaccine for human malaria.

Acetylmuramyl-Alanyl-Isoglutamine↗

Adjuvant activity of synthetic 6-O-"mycoloyl"-N-acetylmuramyl-L-alanyl-D-isoglutamine and related compounds.

Adjuvant and antitumor activities of synthetic 6-O-"mycoloyl"-N-acetylmuramyl-L-alanyl-D-isoglutamine were examined. All the synthetic 6-O-corynomycoloyl-, 6-O-mocardomycoloyl-, and 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine were active as adjuvants for cell-mediated immune responses. However, 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine was less active as an adjuvant on circulating antibody formation. It was shown that pyrogenic activity of N-acetylmuramyldipeptide was reduced by 6-O-acylation with mycolic acid, but not with nocardomycolic or corynomycolic acid. Tumor-suppression activity was observed by the synthetic 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine by using transplantable tumor in syngenic mice.

Acetylmuramyl-Alanyl-Isoglutamine↗