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Biomedical subjects

M Seto

Publications and source records attributed to M Seto.

At least 271 records · Page 15Linked to original sources
PubMed1983

In vivo antitumor effects of monoclonal antibodies with different immunoglobulin classes.

Monoclonal antibodies were produced against MM46, an MM antigen-positive, ascitic mouse mammary tumor of C3H/He mice, and 14 clones were found to produce antibodies reactive with MM46, but not with an MM antigen-negative MM48 tumor. Among these 14 antibodies, 10 reacted also with lymph node cells of C3H.B6-Ly-6b, Ly-6.2 congenic mice. The antigen defined by the 10 antibodies was provisionally designated MM1, and the one defined by the other 4 was designated MM2. Further analysis of MM1 by antibody binding inhibition assay with 3H-labeled MM1-gamma 2b-1 antibody revealed that 8 of the 10 antibodies as well as monoclonal anti-Ly-6.2 showed significant inhibition. This result indicated that there were more than two antigenic determinants on MM1 antigen. The immunoglobulin class of eight antibodies detecting the same antigenic determinant on MM1 was examined and was found to cover major classes of mouse immunoglobulin (mu, gamma 1, gamma 2a, gamma 2b, gamma 3, and alpha). Therefore, the in vivo effect against MM46 tumor cells by these antibodies was studied by a serological tumor neutralization assay. Tumor cells (4 X 10(5)) were treated with antibodies and then injected s.c. into syngeneic C3H/He mice. Ten days later, the tumor was weighed. gamma 2a antibody showed significant suppression of tumor growth, and both gamma 2b and gamma 1 antibodies also revealed suppression. However, mu, gamma 3, and alpha antibodies did not show any significant effect on the tumor growth. To elucidate the mechanisms of tumor suppression by antibodies, the role of macrophages was studied by the antibody-dependent macrophage-mediated cytotoxicity test. In accordance with the in vivo tumor effects, gamma 2a antibody showed 40 to 60% cytotoxicity up to the concentration of 1 microgram/ml, and both gamma 2b and gamma 1 antibodies were also cytotoxic, although less so than gamma 2a. Neither mu nor alpha antibody showed any significant cytotoxicity. gamma 3 antibody showed very weak cytotoxicity against MM46 tumor cells. Thus, a good correlation was observed between the in vivo antitumor effects and in vitro antibody-dependent macrophage-mediated cytotoxicity activity with regard to each class of immunoglobulin, which suggested that macrophages may play an important role in the in vivo antitumor effect of the antibodies used.

Animals↗
PubMed1983

[Clinical evaluation of latamoxef in the perinatal period].

Latamoxef (LMOX), a new oxacephem antibiotic with high activity against Gram-negative bacteria has been investigated for use in No. of 58 mothers in perinatal period, and obtained following results. Concentration of LMOX in maternal serum was 43.4 micrograms/ml at the 1 hour after intravenous administration of 1 g. In umbilical cord serum and amniotic fluid, LMOX showed good translation after intravenous administration of 1 g into the mother, but no adverse effect appeared in the neonate. LMOX is highly useful antibiotic in perinatal infections, and the safe dose of LMOX to the mother in perinatal period is 1--2 g per day considerably.

Amniotic Fluid↗
PubMed1983

[In vitro and in vivo antitumor activity of monoclonal anti-MM46 antibody-ricin A chain conjugate].

In an approach to antitumor agents with improved tumor specificity, the ricin toxic subunit A chain was covalently coupled with a monoclonal IgG2b antibody directed against MM antigen, a tumor-specific antigen on syngeneic mouse mammary tumor MM46 cells (anti-MM46 IgG), using N-succinimidyl-3-(2-pyridyldithio) propionate as cross-linking agent. The conjugate thus prepared (anti-MM46 conjugate) showed potent dose-dependent cytotoxicity against MM antigen-positive MM46 cells in vitro and inhibited the cell growth at concentrations above 1 micrograms/ml. The immunological specificity was verified by the observation that anti-MM46 conjugate did not show cytotoxicity against MM antigen-negative MM48 cells. In Winn-type tumor-neutralizing assay in which C3H/He mice were inoculated i.p. or s. c. with MM46 cells preincubated with a test material, anti-MM46 conjugate showed greater activity than did anti-MM46 IgG. When a group of five C3H/He mice inoculated i.p. with 5 X 10(4) MM46 cells were treated with an i.p. injection of 1 micrograms of anti-MM46 conjugate on days 1, 3, and 5, all five mice survived tumor free, although those treated with 1 micrograms of anti-MM46 IgG died before day 20 with a life span similar to those of mice treated with non-immune conjugate or phosphate-buffered saline (the control). Anti-MM46 conjugate also showed antitumor effects when injected i.v. to C3H/He mice bearing s. c. inoculated MM46 (inoculum, 4 X 10(6)) on day 1 at doses of 5 to 50 micrograms. Thus, the results demonstrated that in vivo efficacy of anti-MM46 conjugate over anti-MM46 IgG alone by therapeutic experiments as well as by tumor-neutralizing assay and suggested the potential use of monoclonal antibody-cytotoxic agent conjugates in cancer therapy.

Animals↗
PubMed1982

Production of monoclonal antibodies against MM antigen: the serologic identification of MM antigen with Ly-6.2 alloantigen.

Monoclonal antibodies against MM46, an ascitic mouse mammary tumor of C3H/H2, were produced by fusing mouse myeloma cell line NS-1 with spleen cells from a (BALB/c X C3H/HeN)F1 mice hyperimmunized with MM46, an MM antigen-positive tumor. Eight antibodies showed cytotoxicity against MM46, but not against MM48, an MM antigen-negative ascitic mammary tumor, and one hybridoma produced an agglutinating antibody. One of the cytotoxic monoclonal antibodies, 3-3-C, was selected, and the strain distribution and the tissue distribution of MM antigen were studied. The results demonstrated that MM antigen had a strain distribution identical to Ly-6.2 antigen, and a similar tissue distribution. Therefore, the characterization of MM antigen and Ly-6.2 antigen was investigated. Ly-6.2 antibody was shown to be cytotoxic for MM46, but not for MM48, in accordance with 3-3-C. Genetic segregation analysis of MM and Ly-6.2 antigens in 33 backcross mice demonstrated complete concordance between these two antigens. In addition, MM antigen phenotype of an Ly-6.2 congenic strain, C3H.B6-Ly-6b, was studied, and it was found to be positive in contrast to C3H/HeN. Furthermore, cross-absorption studies revealed that both MM46 cells and C3H.B6-Ly-6b lymph node cells could absorb cytotoxic activities of 3-3-C and monoclonal anti-Ly-6.2 antibody. The results so far obtained suggested strongly that these two loci controlling expression of MM and Ly-6.2 antigens were identical or very closely linked.

Absorption↗
PubMed1982

Establishment of hybridoma clones which produce anti-chick embryo DNA polymerase alpha monoclonal antibodies.

Four hybridoma clones which produce monoclonal antibodies against chick embryo DNA polymerase alpha have been established. Antibodies produced by the four clones all belonged to the gamma 1-type IgG and precipitated enzyme activity in the presence of Staphylococcus aureus cells. An affinity column prepared with one of the monoclonal antibodies (clone 6-1E) and protein A-Sepharose retained DNA polymerase alpha activity as well as the 135,000 approximately 150,000 and 50,000 approximately 60,000 dalton polypeptides of this enzyme. Thus, the antibody is specific to DNA polymerase alpha.

Animals↗