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Biomedical subjects

I Azuma

Publications and source records attributed to I Azuma.

At least 253 records · Page 14Linked to original sources
PubMed1982

Synthesis and immunoadjuvant activities of the repeating, disaccharide-dipeptide unit of the bacterial, cell-wall peptidoglycan and of some carbohydrate analogs.

The repeating disaccharide-dipeptide units of the bacterial, cell-wall peptidoglycan, one being O-(N-acetyl-beta-muramoyl-L-alanyl-D-isoglutamine)-(1 leads to 4)-2-acetamido-2-deoxy-D-glucose, and the other, O-(2-acetamido-2-deoxy-beta-D-glucosyl)-(1 leads to 4)-N-acetyl-muramoyl-L-alanyl-D-isoglutamine, have been synthesized. Some carbohydrate analogs, such as O-(N-acetyl-beta-muramoyl-L-alanyl-D-isoglutamine)-(1 leads to 4)-N-acetylmuramoyl-L-alanyl-D-isoglutamine, O-beta-D-glucosyl-(1 leads to 4)-N-acetylmuramoyl-L-alanyl-D-isoglutamine, and O-(6-acetamido-6-deoxy-beta-D-glucosyl)-(1 leads to 4)-N-acetylmuramoyl-L-alanyl-D-isoglutamine, were also synthesized. Their immunoadjuvant activities were examined in guinea-pigs.

Adjuvants, Immunologic↗
PubMed1982

Synthesis and biological activity of O-N-acetyl-beta-muramoyl-L-alanyl-D-isoglutamine)-(1 leads to 6)-2-acylamino-2-deoxy-D-glucoses.

Benzoylation of benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-alpha-D-glucopyranoside, benzyl 2-deoxy-2-(DL-3-hydroxytetradecanoylamino)-4,6-O-isopropylidene-alpha-D-glucopyranoside, and benzyl 2-deoxy-4,6-O-isopropylidene-2-octadecanoylamino-beta-D-glucopyranoside, with subsequent hydrolysis of the 4,6-O-isopropylidene group, gave the corresponding 3-O-benzoyl derivatives (4, 5, and 7). Hydrogenation of benzyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-[D-1-(methoxycarbonyl)ethyl]-alpha-D-glucopyranoside, followed by chlorination, gave a product that was treated with mercuric actate to yield 2-acetamido-1,4,6-tri-O-acetyl-2-deoxy-3-O-[D-1-(methoxy-carbonyl)ethyl]-beta-D -glucopyranose (11). Treatment of 11 with ferric chloride afforded the oxazoline derivative, which was condensed with 4, 5, and 7 to give the (1 goes to 6)-beta-linked disaccharide derivative 13, 15, and 17. Hydrolysis of the methyl ester group in the compounds derived from 13, 15, and 17 by 4-O-acetylation gave the corresponding free acids, which were coupled with L-alanyl-D-isoglutamine benzyl ester, to yield the dipeptide derivatives 19-21 in excellent yields. Hydrolysis of 19-21, followed by hydrogenation, gave the respective O-(N-acetyl-beta-muramoyl-L-alanyl-D-isoglutamine)-(1 goes to 6)-2-acylamino-2-deoxy-D-glucoses in good yields. The immuno-adjuvant activity of these compounds was examined in guinea-pigs.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Structures and biological activities of peptidoglycans of Listeria monocytogenes and Propionibacterium acnes.

The cell-wall skeletons of Listeria monocytogenes strain EGD and Propionibacterium acnes strain C7, which have the ability to induce macrophage activation, were analyzed, and the structures of the peptidoglycans were investigated. The analytical data indicate that both peptidoglycans have glucosamine residues with free amino groups, which are responsible for the resistance to lysozyme. Possible structures of these peptidoglycans were deduced from the composition and the results of determination of N- and C-terminal amino acids, together with the characterization of fragments obtained by enzymatic treatment and partial acid hydrolysis of both peptidoglycans. The results suggested that the peptidoglycan of L. monocytogenes contains a cross-linkage region of peptide chains with meso-diaminopimelic acid and D-alanine, which belongs to the A1 gamma type (Schleifer, K.H. & Kandler, O. (1972) Bacteriol. Rev. 36, 407-477), whereas the peptidoglycan of P. acnes contains a cross-linkage region of peptide chains with L,L-diaminopimelic acid and D-alanine, in which two glycine residues combine with amino and carboxyl groups of two L,L-diaminopimelic acid residues. The latter type should be classified as a new type. These cell-wall skeletons and peptidoglycans were shown to have immunoadjuvant activity on the induction of delayed-type hypersensitivity and suppressive activity on the growth of 3-methylcholanthrene-induced fibrosarcoma in BALB/c mice, and the peptidoglycans were shown to be an immunological-active principle of these cell-wall skeletons.

Amino Acids↗
PubMed1982

Adjuvant activity of purified peptidoglycan of Listeria monocytogenes in mice and guinea pigs.

The immunological properties of peptidoglycan (L-PG) purified from the cell wall skeleton (L-CWS) of Listeria monocytogenes strain EGD were investigated and compared with the properties of L-CWS. L-PG consisted of alanine, glutamic acid, alpha, epsilon-diaminopimelic acid, muramic acid, and glucosamine. L-PG showed potent adjuvant activities for circulating antibody formation and development of delayed-type hypersensitivity to bacterial alpha-amylase in vivo and for the primary immune response to sheep erythrocytes in vitro, as well as L-CWS. Both L-PG and L-CWS enhanced the generation of cell-mediated cytotoxicity in allogeneic mice and activated thioglycolate-elicited peritoneal macrophages and macrophage cell line RAW 264 to kill tumor target cells in vitro. We also found that L-PG acted on normal spleen cells as a mitogen. Both L-PG and L-CWS had tumor (Meth A)-suppressive and -regressive activities in syngeneic mice. Our results suggest that the L-PG moiety retains the adjuvant and antitumor activities of L-CWS.

Adjuvants, Immunologic↗
PubMed1982

Induction of resistance to tuberculosis in mice with defined components of Mycobacteria and with some unrelated materials.

Factors contributing to protection against experimental tuberculosis have been studied with refined and well-characterized fractions from mycobacteria and with certain unrelated antigens. Mice were vaccinated intravenously with various combinations of materials presented on minute oil droplets in saline emulsion and were later challenged by aerosol. The minimal composition of an effective vaccine was P3 (a trehalose mycolate similar to cord factor) plus an antigen, which could be tuberculo-protein, or a low-molecular-weight tuberculin-active peptide, or unrelated antigen such as bovine serum albumin or bacterial endotoxin. Development of a hypersensitivity granuloma in the lungs appeared to be essential to protection in this laboratory model.

Animals↗
PubMed1982

Induction of resistance to tuberculosis in mice with defined components of mycobacteria and with some unrelated materials.

Factors contributing to protection against experimental tuberculosis have been studied with refined and well characterized fractions from mycobacteria and with certain unrelated antigens. Mice were vaccinated intravenously with various combinations of materials presented on minute oil droplets in saline emulsions and were later challenged by aerosol. The minimal composition of an effective vaccine was P3 (a trehalose mycolate similar to cord factor) plus an antigen, which could be tuberculoprotein, or a low-molecular-weight tuberculin-active peptide, or unrelated antigen such as bovine serum albumin or bacterial endotoxin. Development of a hypersensitivity granuloma in the lungs appeared to be essential to protection in this laboratory model.

Animals↗
PubMed1982

Further study on relationship of anti-tuberculous protection to lung granulomata produced by intravenous injections of synthetic 6-0-mycoloyl-N-acetyl-muramyl-L-alanyl-D-isoglutamine with or without specific antigens.

The synthetic adjuvant, 6-0-mycoloyl-n-acetylmuramyl-L-alanyl-D-isoglutamine (mycol-MDP), is know to have a similar activity to the adjuvant moiety which resides in BCG cell walls (CW). Mycol-MDP plus a specific antigen, PPD, produced lung granulomata followed by anti-tuberculous protection in BCG CW high responder C57BL/6 (B6) mice, but not in low responder C3H/HeMs) (C3H) mice when a granuloma assay and an aerosol challenge with Mycobacterium bovis, Ravenel were carried out 4 weeks after the injection. However, when the granuloma assay and mycobacterial infection were performed 1 week after the injection, both B6 and C3H mice showed slight but definite lung granuloma formation accompanied by detectable protection. This suggested that the early development of granuloma was elicited by direct activation of macrophages with mycol-MDP. This possibility was confirmed since T-cell-deprived (B) mice produced lung granulomata 1 week after injection with mycol-MDP alone. However, contrary to our expectation, these B mice did not show anti-tuberculous protection. The role of T cells for anti-tuberculous immunity is discussed in relation to the adjuvant activity of mycol-MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

New model of a synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine- induced arthritis: clinical and histologic studies in athymic nude and euthymic rats.

A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), induced severe polyarthritis in euthymic rnu/+ rats. The rnu/+ rats were the most susceptible to MDP-induced arthritis among various rat strains tested, whereas congenitally athymic nude rats (rnu/rnu), males or females, did not develop the disease. This disease was clinically and histologically indistinguishable from classic adjuvant-induced arthritis in terms of clinical course, clinical signs, and histologic features such as (1) an initial acute exudative reaction observed primarily in stroma of the synovial membrane, periarticular tissue, about the tendons, tendon sheath, along the periosteum, between muscle bundles and in the subcutaneous tissue; (2) hypertrophy of the synovial villi, hyperplasia of the synovial lining cells; (3) the very active periosteal new bone formation; and (4) granulation tissue growth either in the articular tissues or in liver, lymph nodes, and capsule of the spleen. Thus, it is postulated that MDP-induced arthritis is basically the same disease as classic adjuvant-induced arthritis. The thymus may play an important role in promoting the development of the disease, possibly through some immune mechanisms to undetermined antigen(s). We believe that nonimmune mechanisms may also be involved in some part of acute and chronic inflammatory reactions to MDP molecules. This new model of MDP-induced arthritis will be a very useful tool to elucidate the underlying mechanisms of adjuvant-induced arthritis.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Synthesis of carbohydrate analogs (positional, configurational, and optical) of n-acetylmuramoyl-L-alanyl-D-isoglutamine, and their immunoadjuvant activities.

2-Acetamido-2-deoxy-4- and -6-O-(D-2-propanoyl-L-alanyl-D-isoglutamine)-D-glucopyranose, 2-acetamido-2-deoxy-3-O-(D-2-propanoyl-L-alanyl-D-isoglutamine)-D-allopyranose, -D-gulopyranose, -D-galactopyranose, -D-mannopyranose, and -L-idopyranose, and 3-O-(D-2-propanoyl-L-alanyl-D-isoglutamine)-D- and -L-glucopyranose were synthesized, in order to clarify the structural requirements for the immunoadjuvant activity of the carbohydrate moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine. Immunoadjuvant activity of the N-acetylmuramoyl-dipeptide analogs was examined in guinea-pigs.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Stimulation of nonspecific host resistance to infection induced by muramyldipeptides.

The effect of muramyldipeptide (MDP), N-acetylmuramyl-L-alanyl-D-isoglutamine [MDP(Ala)], and its analogs on bacterial infection was studied using the experimental model of sepsis infection in mice. Injection of MDP(Ala) gave mice definitive protection against E. coli infection, but only partial protection against P. aeruginosa or K. pneumoniae infection. Several factors influencing the protective activity of MDP(Ala) on E. coli infection were studied, and it was demonstrated that the activity was induced by various routes of administration of MDP(Ala), including the oral route, and was markedly influenced by the bacterial inoculum size. It was also shown that the effective dose of MDP(Ala) was 100 micrograms per mouse for intraperitoneal, intravenous or subcutaneous injections and 1,000 microgram per mouse when administered orally. Furthermore, the optimal interval between MDP-treatment and infection was 24 hr when the treatment was carried out before infection. Clearance of bacterial cells in blood was observed after E. coli infection in mice treated with MDP(Ala). The efficacy of MDP(Ala) and two analogs, N-acetylmuramyl-L-valyl-D-isoglutamine [MDP(Val)] and N-acetylmuramyl-L-seryl-D-isoglutamine [MDP (Ser)], was evaluated for the E. coli infection; MDP(Val) was proven to be slightly less active than MDP(Ala), and MDP(Ser) to be the least effective, although MDP(Val) or MDP(Ser) was reported to have higher adjuvanticity than MDP (Ala) for the development of delayed-type hypersensitivity.

Acetylmuramyl-Alanyl-Isoglutamine↗