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Biomedical subjects

I Azuma

Publications and source records attributed to I Azuma.

At least 343 records · Page 19Linked to original sources

Adjuvant activity of mycobacterial fractions: adjuvant activity of synthetic N-acetylmuramyl-dipeptide and the related compounds.

Immunological activity of synthetic cell wall peptidoglycan subunits was examined in guinea pigs and mice. It was concluded that the minimal adjuvant-active subunit of cell wall peptidoglycan for the induction of delayed-type hypersensitivity to monoazobenzenearsonate-N-acetyl-L-tyrosine and for circulating-antibody formation to bacterial alpha-amylase and the thymus-independent antigen DNP-Ficoll was N-acetylmuramyldipeptide, MurNAc-L-Ala-D-isoGln. N-acetylmuramyldipeptide and 6-O-stearoyl-N-acetylmuramyldipeptide showed no adjuvant activity in the generation of cell-mediated cytotoxic effector cells in the spleens of C57Bl/6J mice after in vivo immunization with the allogeneic antigen mastocytoma P815-X2 cells, but N-acetylmuramyldipeptide showed adjuvant activity after in vitro sensitization of C57Bl/6J mouse spleen cells to the alloantigen mitomycin C-treated DBA/2 mouse spleen cells. It was also shown that 6-O-stearoylation of N-acetylmuramylpeptide could not potentiate the adjuvant activity of N-acetylmuramyldipeptide. Mitogenic and antitumor activities were not observed in either N-acetylmuramyldipeptide or 6-O-stearoyl-N-acetylmuramyldipeptide in mouse systems.

Adjuvants, Immunologic↗

The effect of ubiquinone-7 and its metabolites on the immune response. III. The effect on the immune response to sheep erythrocytes and DNP-Lys-Ficoll in mice.

The effects of Q acid-11, Q-7 and vitamin A palmitate on humoral immune response to two different types of antigens were examined. Particulate T-dependent antigen (SRBC) and T-independent antigen (DNP-Lys-Ficoll) were used to study the mode of action on immune system. Sodium-salt of Q acid-II (Q acid-11 Na) in the form of saline solution or water-in-oil emulsion showed suppressive effect on the direct and indirect PFC responses when administered simultaneously with SRBC. The suppressive effect of Q acid-II Na, however, was not observed when Q acid-II Na was administered two days before immunization. When Q acid-II Na was administered one day after immunization, the suppressive effect of Q acid-II Na was diminished and the level of PFC response was nearly equal to that of the control group. On the other hand, Q acid-II Na, Q-7 and vitamin A palmitate markedly enhanced the immune response to DNP-Lys-Ficoll (T-independent antigen). From the comparison of these humoral immune response, their modes of action are discussed.

Animals↗

The effect of ubiquinone-7 and its metabolites on the immune response. II. Adjuvant activity on the circulating antibody production and the effect on the liver lysosomal membrane.

The effects of the fat-soluble vitamins (retinol, alpha-tocopherol, phylloquinone and ubiquinone) and their related compounds were investigated on the immune response in vivo. E acid-I, dihydro E acid-I, ES-6, K acid-I, Q acid-II and QS-3 act as adjuvants on the production of circulating antibody to bacterial alpha-amylase in mice when they are immunized with in the water phase of water-in-oil emulsion. These compounds, however, can not act as adjuvants in enhancing helper activity of carrier-primed T-cells using an adoptive transfer system in mice. It is also shown that these compounds have no adjuvant activity on the development of delayed type hypersensitivity to ABA-N-acetyltyrosine in guinea pigs. No definite correlation between the adjuvant activity of these compounds and their labilizing activity on rat-liver lysosomal membrane was found.

Adjuvants, Immunologic↗

Effect of oil-attached BCG cell-wall skeleton on the induction of pleural fibrosarcomas in mice.

The effect of oil-attached BCG cell-wall skeleton on the induction of pleural fibrosarcomas by 3-methylcholanthrene in mice was examined. The pleural fibrosarcomas were induced by a substernal injection of 3-methylcholanthrene into the thoracic cavity of ddO mice. One week after the injection of 3-methylcholanthrene, 100 mug of oil-attached BCG cell-wall skeleton was injected subcutaneously every week for 10 weeks. In the observation period of 130 days, the incidence of pleural fibrosarcoma was 67% in the control mice and 39% in the mice treated with BCG cell-wall skeleton. The latent period of tumor induction was prolonged in the mice treated with BCG cell-wall skeleton.

Animals↗

Adjuvant and antitumor activities of Nocardia cell-wall skeletons.

The adjuvant activity of the cell-wall skeletons prepared from eight species (ten strains) of Nocardia was determined by Brunner's method using allogeneic cell-mediated cytotoxicity test. The antitumor activity of the cell-wall skeleton of N. rubra, which showed the most potent adjuvant activity, was examined using EL-4 leukemia and MH-134 hepatoma cells in syngeneic mice. Its results suggest that the cell-wall skeleton of N. rubra is more potent than BCG cell-wall skeleton as the immunotherapeutic agent for cancer immunotherapy in man. The chemical properties of the cell-wall skeleton of N. rubra were also described.

Adjuvants, Immunologic↗

Experimental immunotherapy of neoplastic pleural effusion with oil-attached BCG cell-wall skeleton in mice.

An experimental model for neoplastic pleural effusion was made using a transplantable pleural fibrosarcoma MC-106 in ddO mice, and a local immunotherapy of neoplastic pleural effusion with oil-attached BCG cell-wall skeleton was attempted. Viable cells (3 X 10(5)) of MC-106 were injected into the right pleural cavity of the mice on day 0 with a tuberculin syringe which was joined to a two-way tap attached to a capillary manometer. All of the mice in the control group, which received intrapleurally saline solution 24 hr after the injection of tumor cells, died within 24 days and the mean survival time was 16.9 +/- 3.4 (SD) days. Macroscopically massive blooded pleural effusion in both pleural cavities and multiple tumor nodules on the surface of parietal and visceral pleura were observed. On the other hand, the mice which received intrapleurally 100 mug of oil-attached BCG cell-wall skeleton 24 hr after the injection of tumor cells survived much longer. About 50% of the mice remained alive and were killed on day 95. They revealed histologically no malignant lesion of the pleura except for residual changes of inflammatory reactions.

Animals↗

Adjuvant activity of 6-O-mycoloyl-N-acetylmuramuyl-L-alanyl-D-isoglutamine.

Immunological properties of synthetic 6-O-mycoloyl-N-acetylmuramyl-L-alanyl-D-isoglutamine (6-O-mycoloyl-N-acetylmuramyldipeptide) and 6-O-mycoloyl-N-acetylmuramic acid were examined in guinea pigs and mice in comparison with those of BCG cell-wall skeleton, N-acetylmuramyl-L-alanyl-D-isoglutamine, and 6-O-stearoyl-N-acetylmuramyl-L-alanyl-D-isoglutamine. 6-O-Mycoloyl-N-acetylmuramyldipeptide showed a potent adjuvant activity for the induction of delayed type hypersensitivy to N-acetyl-L-tyrosine-3-azobenzene-4'-arsonic acid (ABA-N-acetyltyrosine). It was also found that 6-O-mycoloyl-N-acetylmuramyldipeptide treated with oil droplets or suspended in phosphate-buffered saline was as effective as oil-attached BCG cell-wall skeleton for the generation of cell-mediated cytotoxic effector cells to mastocytoma P815-X2 cells in the spleen of C57BL/6J mice in vivo. However, 6-O-mycoloyl-N-acetyl-muramyldipeptide was less active as adjuvant than BCG cell-wall skeleton and N-acetylmuramyldipeptide in enhancing the circulating antibody formation to T-independent antigen, 2,4-dinitrophenyl-lysyl (DNP-Lys)-Ficoll in vivo, and on the generation of helper function of carrier-primed T-cells, and was inactive as a mitogen on normal mouse spleen cells. On the other hand, although 6-O-mycoloyl-N-acetylmuramic acid was shown to be inactive as adjuvant on immune systems described above, it was active as a mitogen on normal mouse spleen cells.

Adjuvants, Immunologic↗

Immunotherapy of cancer: tumor suppression and regression by cell walls of Mycobacterium phlei attached to oil droplets.

Components of mycobacterial cell wall(s) (CW) attached to oil droplets were evaluated for their ability 1) to inhibit the growth of line-10 tumor transplants in the skin of syngeneic guinea pigs when inoculated together with 10(6) tumor cells (suppression experiments) and 2) to regress established 7-day-old intradermal tumors and eradicate microscopic lymph node metastases upon injection into the tumors (regression experiments). CW and cell-wall skeleton (CWS) preparations from Mycobacterium phlei, a fast-growing saprophyte of group IV of the atypical mycobacteria, suppressed tumor growth in essentially all animals when 37.5-mug doses were administered; at a dose of 300 mug, they cured 50-60% of the animals in regression tests. The addition of 300 mug of a purified trehalose mycolate, isolated from M. tuberculosis strain Aoyama B, to 300 mug M. phlei CW or CWS preparations significantly increased their tumor regressive potency to provide cure rates to about 90%. Because M. phlei can be propagated more readily, it can be used advantageously in place of BCG to prepare stable, non-living immunologic adjuvants of defined composition and consistently high potency to meet the need for standards with minimal residual malignant disease.

Animals↗

Chemical studies on the cell walls of Leptorspira biflexa strain Urawa and Treponema pallidum strain Reiter.

The preparation and chemical properties of the cell walls of Leptospira biflexa Urawa and Treponema pallidum Reiter are described. Both cell walls are composed mainly of polysaccharides and peptidoglycans. The data of chemical analysis indicate that the cell wall of L. biflexa Urawa contains rhamnose, arabinose, xylose, mannose, galactose, glucose and unidentified sugars as neutral sugars, and alanine, glutamic acid, alpha, epsilon-diaminopimelic acid, glucosamine and muramic acid as major amino acids and amino sugars. As major chemical constituents of the cell wall of T. pallidum Reiter, rhamnose, arabinose, xylose, mannose, galactose, glucose, alanine, glutamic acid, ornithine, glycine, glucosamine and muramic acid have been detected. The chemical properties of protein and polysaccharide fractions prepared from the cells of T. pallidum Reiter were also partially examined.

Amino Acids↗

Adjuvant activity of mycobacterial fractions. III. Adjuvant effect of cell wall of Mycobacterium bovis BCG on cell-mediated cytotoxicity in mice.

A quantitative assay and characterization of oil-attached cell wall of Mycobacterium bovis BCG (BCG-CWS) which stimulates cell-mediated immunity of spleen cells to alloantigens in mice were carried out by an in vitro cell-mediated cytotoxicity test using 51Cr-labeled target cells. C57BL/6J mice (H-2b) were immunized intraperitoneally with mastocytoma cells (H-2d) with or without oil-attached BCG-CWS. The cytotoxicity, comparable to that of spleen cells from mice immunized with mastocytoma cells (3 X 10(7)), could be induuced in spleens of mice immunized with a mixture of mastocytoma cells (10(4)) and oil-attached BCG-CWS. The enhancing effect persisted from 55 days or more after the alloantigenic immunization. Oil-attached BCG-CWS enhanced cell-mediated cytotoxicity of T cells in the spleen and the mesenteric lymph node, but not in the thymus. The cytotoxicity showed specificity toward the alloantigen used for immunization. In addition to BCG-CWS, the cell walls of Nocardia rubra and Corynebacterium diphtheriae PW8 and the peptidoglycolipids of Mycobacterium tuberculosis Aoyama B were found to be potent stimulants of cell-mediated cytotoxicity in mice. Oil-attached BCG-CWS did not enhance humoral response to mastocytoma cells but enhanced cell-mediated cytotoxicity when viable mastocytoma cells were used as antigen. The above result was supported by the fact that anti-hapten antibody response induced by viable trinitrophenyl (TNP)-mastocytoma cells (10(4)) plus oil-attached BCG-CWS did not increase to the maximum levels as was observed in mice immunized with a larger number of mastocytoma cells (3 X 10(7)) alone, while cell-mediated cytotoxicity induced by the same treatment increased to the maximum level obtained by immunization with mastocytoma cells (3 X 10(7)) alone.

Adjuvants, Immunologic↗