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Biomedical subjects

I Azuma

Publications and source records attributed to I Azuma.

At least 91 records · Page 5Linked to original sources

Immunological activities of multiprenylacetyl derivatives of muramyldipeptides.

The immunological properties of six kinds of multiprenylacetic acids and six kinds of multiprenylacetyl muramyldipeptide (MDP) derivatives were examined by using experimental models in mice and guinea-pigs. All the multiprenylacetyl MDP derivatives, particularly TMD-232, showed potent adjuvant activity on the circulating antibody formation against bacterial alpha-amylase in mice, and induction of delayed-type hypersensitivity to monoazobenzenearsonate N-acetyl-L-tyrosine in guinea-pigs. All multiprenylacetic acid preparations tested in this study, however, showed no adjuvant activity in these immune systems. Both TMD-17 and TMD-232 entrapped into multilamellar vesicles showed potent host stimulation activity against Sendai virus infection in mice.

Acetylmuramyl-Alanyl-Isoglutamine

Induction of tumoricidal macrophages and production of cytokines by synthetic muramyl dipeptide analogues.

The ability of various synthetic muramyl dipeptide (MDP) derivatives to induce the production of interleukin-1 (IL-1) and colony stimulating factor (CSF) in vitro and in vivo and to induce cytotoxic macrophages was studied. 6-O-L18-MDP(Me) and MDP-Lys(L18), which were potent inducers of IL-1 and CSF production and of cytotoxic macrophages, had protective activity against Sendai virus infection in mice. In contrast, 1-O-L18-(6-O-P)-MDP(Me) and 2-N-L18-MDP exhibited weak or no ability to induce IL-1 and CSF production and no induction of tumoricidal macrophages, and did not protect against infection of Sendai virus. MDP derivatives, except 2-N-L18-MDP, efficiently rendered macrophages cytotoxic against target cells in the presence of murine recombinant interferon-gamma in vitro. The derivatives that induced cytokines and cytotoxic macrophages appeared to produce anti-viral activity.

Acetylmuramyl-Alanyl-Isoglutamine

Prostaglandin D2 reduces intraocular pressure.

When PGD2 was topically applied to the rabbit eye a reduction of intraocular pressure (IOP) was observed within 30 min. The IOP reduction lasted throughout the observation period of 7 hours. No increase of IOP was observed during the period. The effect of PGD2 was dose-dependent (0.4 microgram to 250 micrograms), and the minimum effective dose was estimated to be 2.0 micrograms. The application of PGD2 did not affect the pupil diameter. No sign of inflammatory response was observed by PGD2 application, that is, no hyperaemia, no flare, no irritation, and no increase of protein content in the aqueous humour. These results suggest that PGD2 or its analogues may be useful for treating glaucoma.

Animals

Effects of prostaglandin D2 and its analogues on intraocular pressure in rabbits.

Studies were carried out of the effects of topically applied prostaglandin (PG) D2 and its metabolites and analogues on the intraocular pressure (IOP) in rabbits, and the results were compared with those of studies using PGE2 and F2 alpha. The application of PGD2 (0.4-250 micrograms) reduced the IOP, in a dose-dependent manner without causing a hypertensive phase. The hypotensive effect was observed within 30 minutes after the application and lasted for over 7 hours. Higher doses of PGE2 (10, 50 micrograms) or PGF2 alpha (50 micrograms) caused initial IOP elevation followed by a prolonged hypotensive phase. Lower doses of PGF2 alpha (2, 10 micrograms) caused a prolonged (over 7 hours) reduction in the IOP following a latency of over 2 hours. The IOP reduction by 2 micrograms of PGE2 lasted for 5 hours. No miotic response followed the use of these PG's. Conjunctival and iridal hyperemia, aqueous flare, irritation (defined by lid-closing), and aqueous protein content were examined at equi-hypotensive doses of the three PG's (50 micrograms for PGD2, 2 micrograms for PGE2, and 10 micrograms for PGF2 alpha). PGE2 was the strongest in causing these side effects, followed by PGF2 alpha. PGD2 did not cause any of these responses except for some development of conjunctival hyperemia. All of the 4 PGD2 metabolites were ineffective in reducing IOP. Among 6 PGD2 analogues, BW245C, PGD3, and PGD2 methyl ester more effectively reduced IOP than did PGD2. PGD1 and 16,16-dimethyl PGD2 were not effective.

Administration, Topical

Antimetastatic effect of Lactobacillus casei YIT9018 (LC 9018) on a highly metastatic variant of B16 melanoma in C57BL/6J mice.

The effect of Lactobacillus casei YIT9018 (LC 9018) on a highly metastatic variant of B16 melanoma, B16-BL6, was determined in C57BL/6 mice. Intralesional (i.l.) injection of LC 9018 inhibited tumor growth and prolonged the survival after s.c. inoculation of B16-BL6 into C57BL/6 mice. Injection of LC 9018 i.v. protected the mice against pulmonary metastasis after i.v. inoculation of B16-BL6. Injection of LC 9018 i.l. before surgical excision of the primary tumor inhibited axillary lymph node metastasis and i.v. injection of LC 9018 after surgical excision of the primary tumor inhibited both axillary lymph node and lung metastases. On the other hand, the combination of i.l. and i.v. injections of LC 9018 markedly inhibited both lymph node and lung metastases. Natural killer cell activity of axillary lymph node cells was augmented by the injection of LC 9018 into a front footpad, while the cytolytic activity of axillary lymph node cells was significantly enhanced. However, the cytolytic activity was diminished by depleting whole lymph node cells of the plastic adherent cells. Furthermore, alveolar macrophage-mediated cytotoxic activity was augmented by the i.v. injection of LC 9018.

Animals

Effect of multiporous microspheres derived from chitin and partially deacetylated chitin on the activation of mouse peritoneal macrophages.

Multiporous microspheres were prepared from 80% deacetylated chitin (DAC-80) and chitin, and their effects on the activation of murine peritoneal macrophages in vivo and on the production of monokines such as colony-stimulating factor (CSF) and interleukin 1 (IL-1) were examined. Multiporous DAC-80 microspheres of mean diameter 2.5 microns [MS-DAC-80(2.5)] enhanced the cytolytic activity of peritoneal macrophages and the production of CSF in vitro by macrophages, spleen cells and bone marrow cells, and in vivo. MS-DAC-80(2.5) also stimulated the production of IL-1 by both resident and thioglycolate-induced peritoneal macrophages. Multiporous chitin microspheres [MS-chitin(2.5)] showed no effect on the activation of peritoneal macrophages in vivo and on the production of IL-1 in vitro, but slightly enhanced the production of CSF in serum in vivo.

Acetylation

Stimulation of non-specific host resistance against Sendai virus and Escherichia coli infections by chitin derivatives in mice.

The efficacy of chitin derivatives on non-specific host resistance to Sendai virus and Escherichia coli infections was studied in mice. Seventy percent deacetylated chitin (DAC-70) and N-trimethylated DAC-70 [DAC-70(Me)3] showed protective activity against Sendai virus infection; however, carboxymethyl-chitin (CM-chitin) did not. DAC-70 also showed protective activity against E. coli infection.

Administration, Intranasal

Suppression of Sendai virus growth by treatment with N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine in mice.

Mice that received N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine [MDP-Lys (L18)] were resistant to Sendai virus infection. In these protected mice, a significant growth inhibition of the virus was confirmed repeatedly at 10(0.2) to 10(0.4) of haemadsorbing units at an early non-specific phase but not at a late virus-eliminating phase of the infection. Virus growth was enhanced by treatment with silica but not by treatment with anti-asialo GM1 serum in MDP-Lys (L18)-treated mice. Peritoneal adherent cells activated by MDP-Lys(L18) showed an enhanced uptake and ability to inactivate Sendai virus in vitro. Excess interferon production in MDP-Lys (L18)-treated mice was seen on day 1 but not on days 2 to 7 of the infection. The possible role of macrophages and interferon in providing non-specific protection against Sendai virus in the MDP-Lys (L18)-treated mice is discussed.

Acetylmuramyl-Alanyl-Isoglutamine

Structural studies of cell wall polysaccharides from Bifidobacterium breve YIT 4010 and related Bifidobacterium species.

The chemical compositions of the cell walls obtained from 8 strains in 5 species of Bifidobacterium were analyzed. These cell walls were shown to be composed of peptidoglycan and polysaccharide moieties. Some variations with respect to contents of neutral sugars and content of phosphorus were observed with some cell wall preparations from the same species. The neutral polysaccharides in cell walls of 4 strains of Bifidobacterium (B. bifidum YIT 4007, B. breve YIT 4010, B. infantis YIT 4025, and B. longum ATCC 15707) were purified and their chemical structures were analyzed. One of these polysaccharides, obtained from B. breve YIT 4010, was analyzed in detail by GLC, 1H- and 13C-NMR spectroscopic analyses, methylation, Smith degradation and acetolysis, and the results suggested the following structure for the repeating unit of the polysaccharide: (Formula: see text).

Amino Acids

Structural requirements of muramylpeptides for induction of necrosis at sites primed with Mycobacterium tuberculosis in guinea pigs.

Intracutaneous injection of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) in guinea pigs caused an extensive necrotic reaction in footpads prepared by injection of heat-killed Mycobacterium tuberculosis in water-in-mineral-oil emulsion. We examined a variety of analogs and derivatives of muramylpeptides for their ability to provoke this reaction. A maximum and a minimum structure responsible for the necrotic reaction were found to be N-acetylglycosaminyl-beta(1-4)-N-acetylmuramyl-tripeptide (GlcNAc-MurNAc-L-Ala-D-isoGln-meso-A2pm) and MDP, respectively. An unexpected finding was that GlcNAc-MurNAc-tetrapeptides having L-amino acids at their C termini, unlike comparable compounds having C-terminal D-amino acids, exhibited definite necrosis-inducing activity, probably due to their tendency to undergo in vivo degradation to GlcNAc-MurNAc-tripeptide. Introduction of some acyl groups, especially the stearoyl group, to the 6-O position of the muramic acid or the peptide moiety of muramylpeptides increased the necrosis-inducing activity of the parent molecules. However, this was not observed with 1-thio-muramic acid analogs of MDP. Modification of the alpha- or gamma-carboxyl groups of the glutamic acid residues of muramylpeptides tended to decrease their necrosis-inducing ability. Analogs and derivatives of muramylpeptides which are capable of inducing necrosis at a primed site, with few exceptions, exhibited powerful adjuvanticity against ovalbumin in guinea pigs. However, the reverse was not necessarily true.

Acetylmuramyl-Alanyl-Isoglutamine

Therapeutic effect of cell-wall skeleton of Propionibacterium acnes in combination with a monoclonal antibody (C6-1.2) on the lung metastases of Lewis lung carcinoma.

The purpose of this study was to determine whether the combination of C6-1.2 monoclonal antibody (MoAb) (established in our laboratory), which is specifically reactive with Lewis lung carcinoma (3LL), and cell-wall skeleton of Propionibacterium acnes C7 (P. acnes-CWS) would significantly decrease established spontaneous metastases of 3LL. C6-1.2 MoAb combined with intratumoral (or intralesional) injection of P. acnes-CWS, when administered at an early stage of the experiment, showed a significant reduction of lung metastases in 3LL-bearing mice. The treatment modality of C6-1.2 MoAb alone did not decrease the lung tumor colonies. On the other hand, the combined treatment of intravenous injection of P. acnes-CWS and C6-1.2 MoAb did not significantly reduce the lung metastases of 3LL tumors in 3LL-bearing mice compared with the treatment of P. acnes-CWS alone. In contrast, when the primary tumor was surgically removed, the most remarkable reduction of lung metastases was observed by the combination of intravenous administration of both C6-1.2 MoAb and P. acnes-CWS. We concluded that the antimetastatic activity of C6-1.2 MoAb and P. acnes-CWS varies depending on the injection route, and also that surgical excision of the primary tumor can lead to remarkable reduction of 3LL lung metastases.

Animals

Radiation therapy for nasopharyngeal carcinoma. Retrospective review of 105 patients based on a survey of Kansai Cancer Therapist Group.

One hundred five patients with nasopharyngeal carcinoma were treated with radiation therapy combined with or without chemotherapy at 16 of the participating institutes in Kansai Cancer Therapist Group, Japan, from January 1978 to December 1980. The study comprised 77 males and 28 females; their ages ranged from 15 to 80 years (mean, 53 years). Five-year survival rates according to stage were as follows: Stage I, 100%; Stage II, 67%; Stage III, 44%; and Stage IV, 34%. As far as Stage IV disease was concerned, the radiation therapy only group showed significantly poorer prognosis than the combined radiation and chemotherapy group (P less than 0.05). Concerning the N stage and treatment method, the radiation therapy only group showed a higher metastatic rate than the chemotherapy combined group (35% versus 14%, P less than 0.05).

Adolescent

Bioactive chitin derivatives. Activation of mouse-peritoneal macrophages by O-(carboxymethyl)chitins.

The effect of O-(carboxymethyl)chitins (CM-chitins) on the activation of mouse-peritoneal macrophages in vivo and their mitogenic activity on mouse spleen-cells were investigated. The induction of cytotoxic macrophages is enhanced by an increase of negative charge at O-6 and decreased by further modification at O-3 of the GlcNAc residue. CM-Chitins had a minor effect on mitogenic activity that was independent of the site of modification; partially N-deacetylated chitins had little activity. Although there was remarkable enhancement of accessibility to lysozyme upon modification at O-6 of the GlcNAc residue, the accessibility was decreased by further substitution at O-3.

Animals

Stimulation of cytokine production in mice using deacetylated chitin.

The effect of 70% deacetylated chitin (DAC-70) on the production of cytokines in mice was examined. DAC-70 stimulated the production of colony-stimulating factor and interferon at 6 to 12 h and 24 h after intraperitoneal injection, respectively. Interleukin 1 and colony-stimulating activity were induced in the supernatants of thioglycolate-induced macrophages stimulated with DAC-70 in vitro. However, DAC-70 did not stimulate the production by spleen cells of interleukin 2, interferon, colony-stimulating or macrophage-activating factor or of interferon by macrophages in vitro. DAC-70 showed no effect on the production of tumour necrosis factor in vivo.

Adjuvants, Immunologic