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Biomedical subjects

M Okada

Publications and source records attributed to M Okada.

At least 1,675 records · Page 93Linked to original sources
PubMed1982

Mutagenicity of alpha-acetoxy derivatives of N-methyl-N-benzylnitrosamine and N,N-dibenzylnitrosamine in V79 cells: a comparison between methylating and benzylating mutagens.

The mutagenicity and cytotoxicity of N-methyl-N-(alpha-acetoxybenzyl) nitrosamine, N-benzyl-N-(acetoxymethyl) nitrosamine, N-benzyl-N-(alpha-acetoxybenzyl)-nitrosamine and related compounds were examined in V79 Chinese hamster cells. These three alpha-acetoxy nitrosamines were all mutagenic, the first one (a compound ultimately yielding a methylating species) being far more strongly mutagenic than the other two (compounds ultimately giving benzylating species). The alkylating or aralkylating activity of these compounds was determined by assessing their reactivity toward 4-(rho-nitrobenzyl) pyridine. The chemical reactivity-mutagenicity correlation among these alpha-acetoxy nitrosamines and related compounds is discussed in relation to the carcinogenicity of their mother compounds.

Animals↗
PubMed1982

Mutagenicity of N-alkyl-N-(alpha-hydroperoxyalkyl) nitrosamines in V79 Chinese hamster cells in relation to alkylating activity.

Mutagenicity and cytotoxicity of a series of N-alkyl-N-(alpha-hydroperoxyalkyl)-nitrosamines (alkyl = methyl, ethyl, propyl, butyl and tert-butyl) were tested in V79 Chinese hamster cells to examine the effects of alkyl chain length and the mode of substitution at the alpha-carbon bearing the hydroperoxy group on the biological activities. Among a series of hydroperoxymethyl compounds whose carbon bearing the hydroperoxy group is primary, the N-methyl compound was the most mutagenic and cytotoxic, and the biological activities of the compounds decreased in the following order: methyl much greater than ethyl greater than propyl greater than or equal to butyl greater than tert-butyl, the last one being nonmutagenic at the concentration tested. In a series of alpha-hydroperoxyalkyl compounds whose alpha-carbon bearing the hydroperoxy group is secondary, the N-methyl compound was also found to be the most mutagenic and cytotoxic, and the biological activities of the compounds decreased in the following order: methyl greater than ethyl much greater than propyl greater than butyl. A comparison of the biological activities of the corresponding compounds having the hydroperoxy group at primary or secondary alpha-carbon showed that the latter compounds were far more active than the former. A plot of the alkylating activity of the compounds toward 4-(rho-nitrobenzyl) pyridine after deoxygenation with NaHSO3 versus their mutagenic potency in V79 cells was linear, indicating that the chemical reactivity of the compounds plays an important role in inducing mutation in V79 cells.

Alkylation↗
PubMed1981

Synthesis and antiviral activity of 5-[(cyanomethylene)oxy]-2'-deoxyuridine.

To study the influence of substitution of CN for C identical to CH in the anti-herpes virus nucleoside 5-(propynyloxy)-2'-deoxyuridine (1), 5-[(cyanomethylene)oxy]-2'-deoxyuridine (2) was prepared. When the potassium salt of 5-hydroxy-2'-deoxyuridine was reacted with iodoacetonitrile in dry DMF, the bisalkylated product 3-(cyanomethyl)-5-[(cyanomethylene)oxy]-2'-deoxyuridine (3) was the major product with a lesser amount of 3-(cyanomethyl)-5-hydroxy-2'-deoxyuridine (5) and only a trace amount of the desired product (2). In contrast, when 5-hydroxy-2'-deoxyuridine was alkylated in water in the presence of 1 equiv of KOH, compound 2 was the major product. In cultures of primary rabbit kidney (PRK) cells, compound 2 showed an anti-herpes virus activity that was comparable to that of 1 and ara-A. Compound 2 did not inhibit incorporation of [Me-3H]dThd or [1',2'-3H]dUrd into DNA of PRK cells; however, its anti-herpes virus activity was completely prevented upon the addition of either dThd or dUrd.

Animals↗
PubMed1981

Characteristics of 106 spontaneous mammary tumours appearing in Sprague-Dawley female rats.

Pathological studies were undertaken on 106 mammary tumours (89 benign, 17 malignant) appearing spontaneously in 95 normal female Sprague-Dawley rats which were killed at Day 756. The benign tumours comprised those with a predominant acinar hyperplasia and those with adenomatous or fibroadenomatous pattern. No significant differences were found histochemically between the acinar cells of the benign tumours and of the lactating gland, except that the amount of fibrous interstitial connective tissue was larger in the former. 3H- or 35S-glycosaminoglycan synthesis by the benign tumours was found to be much higher. The prolactin value in the plasma of the benign-tumour-bearing rats was about 27 times that of 6-month-old virgin rats, and similar to that of rats on the 7th day post partum. Carcinomatous proliferation of tubuloacinar cells could be seen in 5 of the 89 benign tumours. The incidence of benign tumours increases with the age of the rats.

Animals↗
PubMed1981

Establishment and characterization of human T hybrid cells secreting immunoregulatory molecules.

Hybridization of human T cells with an azaguanine-resistant human T cell line gave rise to T hybrid cell lines secreting several immunoregulatory molecules. Analyses of karyotypes, HLA phenotypes, and other surface phenotypes, such as T-cell-specific antigens or receptors for sheep erythrocytes and the patterns of mitogen responsiveness confirmed that the hypoxanthine/aminopterin/thymidine-resistant cell lines were human T-T hybridomas. One of the established hybrid clones (24-A) secreted human interleukin-2 (IL-2). The culture supernatants induced the proliferation of concanavalin A-stimulated murine T cells and supported the proliferation of an IL 2-dependent human cytotoxic T-cell line. In a clone (38-B) that did not show any IL-2 activity in culture supernatants, the addition of macrophages induced IL-2 production in the presence of phytohemagglutinin, suggesting that interleukin-1 induced IL-2 production in T hybrid cells. Hybrid cells secreting killer helper factor were also established. The culture supernatants from this clone, 55-A, helped the induction of cytotoxic T cells against UV-treated human B-blastoid cells but did not show any IL-2 activity.

Cells, Cultured↗
PubMed1981

The differentiation of cytotoxic T cells in vitro. IV. Interleukin-2 production in primary mixed lymphocyte cultures involves cooperation between Qa-1+ and Qa-1- "helper" T cells.

Studies with C57BL/6-TIaa mice have established that both Qa-1+ and Qa-1- helper T cells are required for the optimal production of Interleukin 2(IL-2) activity in primary MLC. This was established both by depletion of Qa-1 bearing cells by treatment of responder cells with anti-Qa-1 serum in the presence of complement and by positive selection (using FACS II analysis) of those cells displaying Qa-1. Furthermore, microfluoremetry revealed that the great majority of C57BL/6-TIaa and of A/J splenic T cells bore Qa-1 alloantigen but that only those with the highest antigen density were susceptible to complement-mediated lysis.

Animals↗
PubMed1981

The role of interleukin-2 (IL-2) in the differentiatin of cytotoxic T cells: the effect of monoclonal anti-IL-2 antibody and absorption with IL-2 dependent T cell lines.

A variety of approaches, including the use of a monoclonal antibody, have indicated that the lymphokine Interleukin 2 is a necessary and sufficient mediator for initiating cytotoxic T cell differentiation in vitro. Mitogen (Con A, PHA) stimulation of spleen cells and K/D or I region stimulation in primary MLC all led to IL-2 production, as measured by the growth of an IL-2 dependent T cell clone, and to the production of a "helper" factor necessary for cytotoxic T lymphocyte (CTL) differentiation against metabolically inactivated stimulator spleen cells. Several lines of evidence suggested that the IL-2 activity and CTL "helper" activity were due to a single molecular entity. These included the observations that: i) There was a linear relationship (R = 0.99) between IL-2 activity and relative CTL "helper" activity regardless of the preparation used (purified IL-2; MLC, or mitogen-induced supernatants). ii) Absorption of MLC supernatants with T cell "blasts" or with IL-2 dependent T cell lines concomitantly removed both IL-2 and CTL "helper" activities. iii) IL-2 activity purified by isoelectric focusing, or by polyacrylamide gel electrophoresis, displayed CTL "helper" activity. iv) Both CTL "helper" and IL-2 activities were neutralized by a monoclonal antibody directed against IL-2.

Absorption↗