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Biomedical subjects

I Azuma

Publications and source records attributed to I Azuma.

At least 109 records · Page 6Linked to original sources

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

Adjuvant and antitumour activities of synthetic lipid A analogues.

The biological activities of synthetic glycolipids, which were chemically synthesized and based on the structure of lipid A of the lipopolysaccharide (LPS) from Escherichia coli, were examined with special reference to their adjuvant activity on the induction of delayed-type hypersensitivity, activity on the induction of tumour necrotic factor (TNF) and tumour regressive activity on line 10 hepatoma in strain 2 guinea pigs. Among them, a compound structurally corresponding to free E. coli lipid A (compound 506) as well as LPS exhibited potent adjuvant activity in the induction of delayed-type hypersensitivity in guinea pigs and TNF inducing activity in the sera of mice which were presensitized with Propionibacterium acnes. Compound 506 showed potent lethal toxicity in the intravenous administration of BALB/c mice presensitized with P. acnes. The regressive activity on line 10 hepatoma was observed by the multiple intralesional injection of squalane-treated compounds 504 and 505 in strain 2 guinea pigs.

Adjuvants, Immunologic

Structural studies on teichoic acids in cell walls of several serotypes of Listeria monocytogenes.

Structural studies were carried out on the teichoic acids in cell walls of Listeria monocytogenes serotypes 3a, 4b, 4f, 6, and 7. The structure of the dephosphorylated repeating units, obtained by treatment with 46% hydrogen fluoride or alkaline hydrolysis, was examined by methylation analysis, acetolysis, and 1H-NMR spectroscopy. The results of Smith degradation of the teichoic acids and 13C-NMR spectroscopy led to the following most likely structures of the repeating units of the teichoic acids:----1-[N-acetylglucosaminyl(alpha 1----4)]ribitol-5-phosphate----for serotype 3a,----4-[galactosyl(alpha 1----6)][glucosyl(beta 1----3)]N -acetylglucosaminyl(beta 1----2)ribitol-5-phosphate----for serotype 4b,----4-[galactosyl(alpha 1----6)][N -acetylglucosaminyl(alpha 1----3)]N-acetylglucosaminyl(beta 1----2)ribitol -5-phosphate----for serotype 4f,----4-N-acetylglucosaminyl(beta 1----4)ribitol -5-phosphate----for serotype 6, and----1-ribitol-5-phosphate----for serotype 7. About 40% of the repeating units of the teichoic acid from serotype 4f were not substituted at C-3 of beta-N-acetylglucosaminyl residues.

Carbohydrate Conformation

Monoclonal antibodies distinguish between the head portions of two myosin isozymes from chicken breast muscle.

Monoclonal antibodies against chicken breast myosin and its subfragment-1(S-1) were produced. One antibody, 2G41, reacted with S-1 containing a light chain 3 (LC3), but not with another S-1 containing a light chain 1 (LC1) or a mixture of the light chains. A structural difference can be assumed to exist between the head portions of the two myosin isozymes. Antigenicity of S-1 toward 2G41 could not be detected after tryptic digestion into three fragments of 50K, 27K, and 20K daltons. Another monoclonal antibody, M68, was obtained from mice immunized with myosin. M68 preferably recognized the heavy chain from S-1 containing LC3 rather than that from that containing LC1 or S-1. M68 reacted with the 27K fragment among the three.

Animals

Structural studies on lipoteichoic acids from four Listeria strains.

The lipoteichoic acids were isolated from phenol extracts of four Listeria strains representing serotypes 4a, 4b, 6a, and 6 to compare the differences in structure of amphiphilic polysaccharides from various serotypes of Listeria spp. The lipoteichoic acids from the four strains examined had the same structure in both hydrophilic chains and lipid portions. On the basis of the results of nuclear magnetic resonance spectroscopy and Smith degradation, the hydrophilic chains were shown to be 1,3-linked poly(glycerol phosphate) in which some of the glycerol residues had alpha-galactosyl substituents. The lipid portions were released by treatment with 46% hydrogen fluoride or 98% acetic acid. They were determined to be 3(1)-(2'-O-alpha-D-galactopyranosyl-alpha-D-glucopyranosyl)-1(3), 2-diacylglycerol and 3(1)-[6'-phosphatidyl-2'-O-(alpha-D-galactopyranosyl)-alpha- D-glucopyranosyl]-1(3),2-diacylglycerol. The degrees of glycosyl substitution and proportions of the two lipids varied to some extent among these four strains.

Acetates

Suppressive effect of indazole adenine dinucleotides on proliferation of normal and malignant cells.

The suppressive effects of newly synthesized NAD-analogs, indazole adenine dinucleotides (IAD), on the cellular proliferation of normal and L5178Y cells were investigated in connection with their inhibitory activity on inosine 5'-monophosphate dehydrogenase (IMPD). All the dinucleotides, except compounds VIII and IX, were observed to show a certain extent of suppression at a concentration of 100 micrograms/ml. In particular, some compounds (II, VII, X and XI) among them showed a strong suppression (70-90%) in the leukemic cell system. The suppression seemed to be roughly correlative with the degree of IMPD inhibition of the dinucleotide.

Adenine Nucleotides

Antitumor activity on line 10 hepatoma in strain 2 guinea pigs and pharmaceutical properties of quinonyl-MDP preparations.

The pharmaceutical properties of quinonyl-MDP-66 were discussed with special reference to the stability of oil-in-water emulsion, distribution capacity into regional lymph nodes and tumor regressive activity. The oil-in-water emulsion of quinonyl-MDP-66, which was prepared by treatment of quinonyl-MDP-66 with squalane (25 x) and emulsified with aqueous solution of 5% HCO-60 and 5.6% d-mannitol, was kept in lyophylized state and used after reconstitution by the addition of water before use. The reconstituted suspension of quinonyl-MDP-66 in oil-in-water emulsion was stable for more than 24 hrs. The oil-in-water emulsion of quinonyl-MDP-66 as prepared above was effective for the distribution of quinonyl-MDP-66 into regional lymph node in rats and for the regression of line 10 hepatoma in strain 2 guinea pigs by intralesional injection.

Acetylmuramyl-Alanyl-Isoglutamine