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Biomedical subjects

I Azuma

Publications and source records attributed to I Azuma.

At least 235 records · Page 13Linked to original sources
PubMed1984

[Central nervous system irradiation for children with leukemia].

Between 1972 and 1981, 247 patients with acute lymphoblastic leukemia were treated with prophylactic CNS irradiation. Cranial irradiation (2400 rad) plus intrathecal methotrexate was the prophylactic CNS therapy of choice. At 5 years, the overall, relapse-free and CNS relapse-free survival rates were 51%, 47% and 79%, respectively. Our findings suggest that more attention should be paid to the inferior border of the radiation field, since the anterior and middle cranial fossae were sometimes not included and the second spine was almost always excluded.

Adolescent↗
PubMed1984

[Antitumor activity of bacterial fractions and related synthetic compounds].

We have purified the cell-wall skeletons (CWS) of Mycobacterium bovis BCG, Nocardia rubra, Propionibacterium acnes and Listeria monocytogenes as the adjuvant-active principles of these bacterial cells. These cell-wall skeleton preparations were shown to have antitumor activities in experimental tumor systems. Especially BCG-CWS and N. rubra-CWS were applied for the treatment of human cancer. The synthetic immunoadjuvants such as cord factor, mycoloyl and quinonyl derivatives of N-acetylmuramyldipeptides were prepared and their immunological properties were investigated. The effectiveness of synthetic adjuvants on the stimulation of nonspecific host resistance against bacterial and viral infections was also discussed.

Adjuvants, Immunologic↗
PubMed1984

[Prophylactic central nervous system irradiation for childhood acute lymphoblastic leukemia].

Documentation on 324 children with leukemia who underwent cranial irradiation between 1972 and 1981 was collected from 15 participating hospitals in the Kansai Cancer therapy Group. Among 182 children with acute lymphoblastic leukemia, records on 90 children treated with prophylactic cranial irradiation (2,400 rads) plus intrathecal methotrexate in 12 hospitals were available for analysis. There was no significant difference in survival between the two prognostic groups based on age and initial WBC count at diagnosis, i.e., overall, relapse-free and CNS relapse-free 5-year survivals in the good and intermediate prognostic groups were 57% vs. 51%, 55%, vs. 49%, and 83% vs. 95%, respectively.

Adolescent↗
PubMed1984

Comparison of antimetastatic effect against Lewis lung carcinoma after intratumoral and intravenous injections of cell-wall skeleton of Propionibacterium acnes C7 in C57BL/6 mice.

Antimetastatic activity of cell-wall skeleton of Propionibacterium acnes C7 (P. acnes-CWS) in C57BL/6 mice varied depending on the injection route. The kinetics of antimetastatic effect against Lewis lung carcinoma (3LL) revealed that the sooner intratumoral (it) injection of P. acnes-CWS was carried out, the better the result. However, intravenous (iv) injection of P. acnes-CWS produced the best result if P. acnes-CWS was injected at about the time when metastases began to develop in the lungs. Pretreatment with intrafootpad (ifp) injection of P. acnes-CWS inhibited primary tumor growth and subsequent pulmonary metastases especially when given 7 days before tumor inoculation into the same footpad, but tended to enhance artificial pulmonary metastases when given 7 days before iv injection of tumor cells. In contrast, pretreatment with iv injection of P. acnes-CWS enhanced spontaneous pulmonary metastases especially when given 7 days before ifp inoculation of tumor cells, but inhibited artificial pulmonary metastases when given one day or 7 days before iv injection of tumor cells. These results suggest the difficulty of treatment of tumor metastases with immunological adjuvants. In T-cell-deprived mice, it injection of P. acnes-CWS showed no antimetastatic effect against 3LL, but iv injection was still effective. This indicates that T-cells are required for the antimetastatic effect of it injection of P. acnes-CWS, but iv injection of P. acnes-CWS is able to inhibit pulmonary metastases in T-cell-deprived mice.

Animals↗
PubMed1983

Synthesis and biological activities of N-acetyl-1-thiomuramoyl-L-alanyl-D-isoglutamine and some of its lipophilic derivatives.

N-Acetyl-1-thiomuramoyl-L-alanyl-D-isoglutamine and some lipophilic analogs were synthesized from benzyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-3-O-[D-1-(methoxycarbonyl)ethyl ]- alpha-D-glucopyranoside (1). O-Debenzoylation of 2, derived from 1 by oxidation, gave 2-acetamido-2-deoxy-4,6-O-isopropylidene-3-O-[D-1-(methoxycarbonyl)ethyl ]-D-glucopyranose (3). Condensation of the alkoxy-tris(dimethylamino)phosphonium chloride (4), formed from 3 by the action of carbon tetrachloride and tris(dimethylamino)phosphine, with potassium thioacetate afforded 2-acetamido-1-S-acetyl-2-deoxy-4,6-O-isopropylidene-3-O-[ D-1-(methoxycarbonyl)ethyl]-1-thio-beta-D-glucopyranose (8). Coupling of the acid 9, obtained from 8 by hydrolysis and subsequent S-acetylation, with the methyl ester of L-alanyl-D-isoglutamine gave N-[2-O-(2-acetamido-1-S-acetyl-2,3-dideoxy-4,6-O- isopropylidene-1-thio-beta-D-glucopyranose-3-yl)-D-lactoyl]-L-alan yl-D- isoglutamine methyl ester (10), which was converted, via O-deisopropylidenation, S-deacetylation, and de-esterification, into the N-acetyl-1-thiomuramoyl dipeptide. Condensation of 11 (derived from 10 by S-deacetylation) and of 12 (obtained from 10 by S-deacetylation and de-esterification) with various acyl chlorides yielded the corresponding 1-S-acyl-N-acetylmuramoyl-L-alanyl-D-isoglutamine derivatives, which were converted into the desired, lipophilic 1-thiomuramoyl dipeptides by cleavage of the isopropylidene group. Condensation of 11 with the alkyl bromides yielded the 1-S-alkyl derivatives, which were also converted, via O-deisopropylidenation and de-esterification, into the corresponding 1-S-alkylmuramoyl dipeptides. The biological activities were examined in guinea-pigs and mice.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Chemical modification of the C-6 substituent in the carbohydrate moiety of N-acetylmuramoyl-L-alanyl-D-isoglutamine (MDP), and the immunoadjuvant activity.

N-Acetyl-6-O-mesyl-, -6-O-methyl-, and -4,6-di-O-methyl-muramoyl-L-alanyl-D-isoglutamine and N-acetyl-6-chloro-, -6-bromo-, and -6-azido-6-deoxymuramoyl-L-alanyl-D-isoglutamine were synthesized from benzyl 2-acetamido-2-deoxy-3-O-[D-1-(methoxycarbonyl) ethyl]-alpha-D-glucopyranoside and its 6-O-mesyl derivative. The immunoadjuvant activity of the products was examined, in order to clarify the structural requirements for the activity of the carbohydrate moiety in N-acetylmuramoyl-L-alanyl-D-isoglutamine.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Immunostimulation in cancer patients.

It is interesting to treat cancer patients by the potentiation of their depressed immune status. There are many immunopotentiators which showed potent antitumor activity in experimental tumor systems in vivo and in vitro, however, which were not always effective in well-designed controlled clinical trials. At the present time, we should say that cancer immunotherapy is not the first modality for cancer treatment and we should be careful not to miss more effective modalities for the treatment of cancer patients by the overestimation of cancer immunotherapy. Further extensive studies will be required to establish new modalities such as the development of more effective immunostimulation which is cytotoxic to tumor cells and the exploration of combined immunostimulation by using more than two immunotherapies, or immunotherapy combined with other cancer therapeutic modalities.

Adjuvants, Immunologic↗
PubMed1983

Muramyl dipeptides: prospect for cancer treatments and immunostimulation.

The immunopharmacological activities of bacterial cell walls and muramyl peptides were collected in table form with a comprehensive literature. The past and present studies emphasizing the host-defense enhancing activities of muramyl peptides for antitumor immunotherapy were surveyed along three possible approaches: 1) the nonspecific enhancement of natural defense ability of host against tumor cells themselves; 2) the enhancement of nonspecific resistance of host to microbial infections which are frequently encountered and difficult to treat in the advanced stage of tumor patients; and 3) the stimulation of immunity against tumor-specific or tumor-associated immunogens. Finally, the prospects of successful antitumor immunotherapy with muramyl peptides and their derivatives was discussed.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Preventive effect of a quinonyl derivative of N-acetylmuramyl dipeptide, QMDP-66, against adriamycin-induced ECG abnormalities in rats.

The effects on adriamycin cardiotoxicity of an immunoadjuvant, 2-[2-acetamido-2-deoxy-6-0-[10-(2,3-dimethoxy-5-methyl-1, 4-benzo-quinon-6-yl) decanoyl]-D-glucopyranos-3-0-yl]-D-propionyl-L-valyl D-isoglutamine methyl ester (QMDP-66), and a reference compound, ubiquinone-10, were studied in Wistar Kyoto (WKY) rats. Adriamycin, 1 mg/kg/day intra-peritoneally (i.p.) for 23 days, elicited cardiotoxicity, as judged by widening of the QRS complexes in ECGs. Electron microscopic examination of myocytes from the treated rats revealed many cytoplasmic vacuoles possibly originating from deranged endoplasmic reticula or mitochondria. In addition, the treatment significantly inhibited body weight gain, and decreased ventricular weight. QMDP-66 alone, 1 mg/kg/day i.p. for 23 days, had no effect on the parameters described above. When QMDP-66 (1 mg/kg/day, i.p.) or ubiquinone-10 (3 mg/kg/day, i.p.) was administered together with adriamycin, the widening of the QRS complexes was significantly depressed, and cytoplasmic vacuoles in myocytes were rarely observed. The QMDP-66 or ubiquinone-10 treatment, however, did not alleviate the decrease in body weight gain or ventricular weight due to adriamycin. Heart rate was not significantly changed by any of the treatments. These findings suggest that QMDP-66 is an effective antidote against adriamycin cardiotoxicity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Structural and immunochemical studies of teichoic acid of Listeria monocytogenes.

An immunologically active teichoic acid component was isolated from the cell wall of Listeria monocytogenes strain EGD. The teichoic acid component, accounting for about 20% of the weight of cell wall, contained N-acetylglucosamine, rhamnose, ribitol, and phosphorus in a molar ratio of 0.95 : 1.0 : 0.97 : 0.98. The molecular weight of the teichoic acid chain was about 120,000 as analyzed by gel filtration. The probable structure was deduced from the results of methylation analysis, Smith degradation, and proton magnetic resonance spectrometry of the teichoic acid, together with the characterization of fragments obtained by treatment with hydrofluoric acid, as follows: (formula; see text) Inhibition testing with monosaccharide and fragments obtained from HF treatment of Listeria teichoic acid in the quantitative precipitin reaction suggested that the rhamnose residue is a major antigenic determinant.

Carbohydrates↗
PubMed1983

Effect of quinonyl-N-acetyl muramyl dipeptide on immune responses in tumor-bearing mice.

The efficacy of 6-O-QS-10-N-acetyl muramyl-L-valyl-D-isoglutamine methyl ester (quinonyl-MDP-66) for restoring impaired immune status was examined in mice bearing Lewis lung carcinoma. Quinonyl-MDP-66 suspended in phosphate-buffered saline was shown to restore the depressed allogeneic cell-mediated cytotoxicity of spleen cells from mice with Lewis lung carcinoma when the chemical was injected twice intraperitoneally, intravenously, or intratumorally. However, primary tumor size and the numbers of lung metastases were not affected when quinonyl-MDP-66 was administered under the present experimental conditions. Intraperitoneal injection of quinonyl-MDP-66 in mice with Lewis lung carcinoma enhanced host resistance to Listeria monocytogenes infection.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Stimulation of nonspecific resistance to infection induced by muramyl dipeptide analogs substituted in the gamma-carboxyl group and evaluation of N alpha-muramyl dipeptide-N epsilon-stearoyllysine.

Stimulation of resistance to infection induced by the analogs of muramyl dipeptide (MDP) having substituted functions in the gamma-carboxyl group of D-isoglutamyl residue was examined in experimental Escherichia coli infections in mice. An MDP analog which is an efficient strengthener of resistance to infection, N alpha-MDP-N epsilon-stearoyllysine [MDP-Lys(L18)], was selected through the comparative assessment of a number of compounds in three categories: (i) gamma-alkylamides, (ii) gamma-esters, and (iii) N alpha-MDP-N epsilon-acyllysine derivatives. Furthermore, the antiinfectious activity of MDP-Lys(L18) was evaluated bacteriologically in comparison with that of MDP. The effect of MDP-Lys(L18) on the susceptibility of mice to infections with various species of microorganisms was studied. Protective activity was greatest against E. coli and staphylococcal infections, considerable against Pseudomonas and Candida infections, and least against Klebsiella infection. The effects of bacterial inoculum size and MDP treatment timing, dose, and route of administration on protective activity were studied. The efficacy of MDP-Lys(L18) in protection tests was demonstrated for all administration routes, even the oral. Its high potency was confirmed by the smaller influence of inoculum size and particularly small value of the minimum dosage required for inducing protective activity. A decrease in bacterial survival was observed in the blood and organs of mice treated with the analog and infected with E. coli. The following two useful effects were obtained: the synergistic effect of glycopeptide and chemotherapeutic agents and the stimulation of resistance to infection in animals immunocompromised by cyclophosphamide treatment.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Stimulation of chemiluminescence by synthetic muramyl dipeptide and analogs.

The effect on respiratory burst of murine splenic cells after in vitro exposure to synthetic muramyl dipeptide (MDP) and 6-O-acyl and quinonyl derivatives was studied at an early phase of interaction by luminol-dependent chemiluminescence (CL) in response to stimulation by zymosan. The MDP molecule enhanced CL, but the degree of CL response varied with the kinds of fatty acids introduced in the chemical structure of synthetic glycopeptide analogs. A 6-O-acyl derivative possessing an alpha-branched fatty acid chain, B30-MDP, stimulated maximum levels of CL activity. High CL responses were obtained with L8-MDP having a short chain of linear fatty acids and with QS-10-MDP-66 containing a ubiquinone compound. CL was also stimulated by MDP and its analogs in the spleen cells of nude mice lacking mature T lymphocytes, but the extent of stimulation was decreased compared with that of normal spleen cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Activation of macrophages by quinonyl-N-acetylmuramyl dipeptide.

The effect of 6-O-QS-10-N-acetylmuramyl-L-valyl-D-isoglutamine methyl ester (quinonyl-MDP-66) on various functions of macrophages was examined. Mouse peritoneal macrophages, when treated either in vitro or in vivo with quinonyl-MDP-66 suspended in phosphate-buffered saline, showed a capacity for cytolysis and cytostasis against tumor targets and released H2O2 in the presence of phorbol myristate acetate. The macrophages induced by quinonyl-MDP-66 also had both antibody-dependent cell-mediated cytotoxicity and phagocytic activity against erythroid targets. The fact that synthetic quinonyl-MDP-66 stimulates the macrophages to become more cytotoxic than do other MDP analogs suggests that the lipophilic residue (QS-10) in quinonyl-MDP-66 may be important for the development of this activity.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Macrophage activation with ubiquinones and their related compounds in mice.

The effect of ubiquinones (Q-2, -7 and -10) and their related compounds (QSA-1, -4, -6, -10 and -18) on macrophage functions was investigated. All compounds tested in this study, except QSA-4 and -6, augmented macrophage-mediated functions such as cytolysis, cytostasis and H2O2 release. Furthermore, QSA-10 and QSA-10(H2) were also shown to increase antibody-dependent cell-mediated cytotoxicity. However, QSA-10(Phenol), which lacks a quinone ring, was not observed these activities. It was suggested that quinone ring might be important for the expression of macrophage activation.

Animals↗