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Biomedical subjects

M Seto

Publications and source records attributed to M Seto.

At least 253 records · Page 14Linked to original sources

Serological analysis of early mouse embryo with rat monoclonal antibodies produced against mouse teratocarcinoma cells.

Rat-mouse hybridoma antibodies were produced against mouse teratocarcinoma F9 or PCC4 aza1 cells, and four clones were established. Both the F11 (IgM) and F20 (IgG2c) antibodies showed a similar specificity, reacting only with nullipotential teratocarcinoma cells. They were also found to agglutinate sheep red blood cells. Solid-phase enzyme-linked immunofluorescence assay showed that, among the neutral glycolipids studied, they only reacted with the Forssman antigen. P2 antibody (IgG2b) reacted with the undifferentiated-type and embryonal endodermtype teratocarcinoma cells. During the preimplantation stage, this antibody did not stain mouse embryos, but it reacted very weakly with the inner cell mass of blastocysts cultured in vitro. In the 5th-day embryo, the embryonic ectoderm as well as the visceral and parietal endoderm were positive, but the extraembryonic ectoderm was not. Mesoderm of the 7.5th-day embryo also reacted with this antibody. However, P2 antigen was not observed in the 16th-day embryo or in adult tissues. F2 antibody (IgG2a), which was reactive with all of the cultured cell lines tested, showed an immunoreaction with mouse embryos throughout the preimplantation stage. However, in the 7.5th-day embryo, the presence of F2 was limited to the cells forming the parietal endoderm. This antigen was present in some epithelial tissues of the 16th-day embryo and adult mouse. Of these antigens, P2 and F2 are probably novel differentiation antigens of the early mouse embryo. Together with the Forssman antigen, these will be important markers for analyzing cell-surface antigens of mouse teratocarcinoma cells as well as embryos.

Animals↗

Effect of bacterial density and substrate concentration on yield coefficients.

Measurements were made of the yield coefficient during the aerobic metabolism of glucose by a heterogeneous bacterial mixture. Expressed in terms of carbon, the coefficient was approximately 0.48. The value did not vary with initial bacterial densities ranging from 0.4 pg to 40 micrograms of cell carbon per ml and with glucose concentrations ranging from 43 pg to 100 micrograms of carbon per ml. Under all these circumstances, about 44% of the glucose carbon was converted to CO2, and 7.4% was excreted as organic products. The significance of uncharacterized organic substrates contaminating the medium to the coefficients calculated for low glucose concentrations is discussed.

Bacteria↗

Clearance and metabolism of glandular kallikrein in the rat.

This study was undertaken to characterize the clearance of circulating rat glandular kallikrein and to determine the contribution of various organs and the urinary excretion to the removal of glandular kallikrein from the bloodstream. We injected either active 125I-kallikrein or kallikrein inactivated with phenylmethylsulfonyl fluoride (125I-PMSF-kallikrein) intravenously into intact or nephrectomized rats and then studied the disappearance rate of trichloroacetic acid (TCA)-precipitable radioactivity from the circulation. Inactivation by PMSF markedly reduced the binding of kallikrein to plasma protease inhibitors. The removal rate of the acid-precipitable radioactivity fit a biexponential curve for both active and inactive kallikrein. In the intact rats approximately 50% of the radioactivity was removed from the circulation 30 min after the injection of active 125I-kallikrein. Removal of the kidneys did not significantly affect the clearance of active kallikrein. On the other hand, inactive 125I-PMSF-kallikrein was removed from blood faster than active 125I-kallikrein in normal animals. Approximately 50% of the radioactivity was removed from the circulation 8 min after the injection, and the half-life of inactive 125I-PMSF-kallikrein was markedly prolonged by bilateral nephrectomy. Active 125I-kallikrein was taken up by tissues, particularly the liver and the kidney. In urine, less than 2% of the radioactivity was excreted in 60 min as TCA-precipitable material. We concluded that glandular kallikrein is cleared rapidly from the circulation of the rat, probably in the form of a complex with a plasma protease inhibitor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Two mouse monoclonal antibodies detecting two different epitopes of an activated lymphocyte antigen on adult T-cell leukemia cells.

Mouse monoclonal antibodies were produced against MT-2 cell line derived from adult T-cell leukemia or human T-cell leukemia virus-rich fraction therefrom. Two IgG1 antibodies, Ta60a and Ta60b, were found to be reactive not only with cell lines derived from adult T-cell leukemia or cutaneous T-cell lymphomas, but also with activated peripheral blood lymphocytes, suggesting the similarity of Ta60 antigen group to Tac antigen which is present on interleukin 2 receptor. Thus, the relationship among these antigens was studied. Two Ta60 antibodies and Tac antibody immunoprecipitated the molecule with almost identical electrophoretic mobility, approximately a Mr 60,000 antigen from [3H]glucosamine-labeled activated peripheral blood lymphocytes or MT-2, MT-1, or ATN-1 cells from adult T-cell leukemia and a Mr 53,000 antigen from HUT-102 cells derived from cutaneous T-cell lymphomas. Further, Tac antibody was found to immunoprecipitate Ta60b molecule on 125I-labeled MT-2 cells by sequential immunoprecipitation, indicating that these two epitopes are on the same molecule. Antibody binding inhibition assays with either 3H-labeled Ta60a or Ta60b antibody demonstrated that Ta60a and Tac are the same epitope, but different from Ta60b. Thus, at least two epitopes were demonstrated to be present on interleukin 2 receptor molecule. However, Ta60b antibody showed almost no blocking effects on proliferation of an interleukin-2-dependent cell line, whereas Ta60a antibody did. Various hematopoietic tumor cells were typed with these two antibodies, but the results with Ta60b antibody were described, because they showed a similar specificity. Ta60b antibody reacted with all adult T-cell leukemia cases, but did not react with T-cell acute lymphoblastic leukemia, lymphoblastic lymphoma, or mature T-cell lymphoma. Interestingly, 3 of 12 acute myeloblastic leukemia and 2 of 5 chronic myelocytic leukemia in blastic crisis showed positive reactions. One-third of B-cell chronic lymphocytic leukemia and B-cell lymphoma as well as a few B-cell lines were also weakly reactive with this antibody. A part of the results with direct tests was confirmed by the absorption tests. The results obtained demonstrated the presence of Ta60b on a certain fraction of malignant hematopoietic cells of other than T-cell origin.

Antibodies, Monoclonal↗

[Fundamental and clinical study on cefpiramide in obstetrics and gynecology. Obstetrics and Gynecology Study Group for Cefpiramide].

Fundamental and clinical studies on a new cephalosporin antibiotic, cefpiramide (CPM), was carried out under a joint study program, in order to evaluate the usefulness of the drug in treating infection of the female genital organs. The results obtained were as follows: CPM was readily transported to female genital organ tissues, and the concentrations of the drug exceeded 35 micrograms/g in various organ tissues in about 1 hour, following intravenous injection of 1 g. A level of more than 2 micrograms/g was maintained even 14 hours after the injection. The transport of CPM to various tissues was also studied following intravenous drip infusion of 1 g for 1 hour. The concentrations in tissues were slightly low but similar to those following intravenous injection. The peak concentration of the drug in the dead space exudate was 3.1-20.4 micrograms/ml, following intravenous injection and intravenous drip infusion of 1 g. The MIC80 of CPM were 3.13-12.5 micrograms/ml against S. aureus, Klebsiella sp., P. mirabilis and P. aeruginosa. Clinical effects of CPM were analyzed in 158 patients, including 56 cases with intrauterine infection, 37 cases with intrapelvic infection, 22 cases with external genital infection, 31 cases with adnexitis, 6 cases with postoperative wound infection and 6 cases with other infections. Excellent response was seen in 28 cases (17.7%), good response in 120 (75.9%) poor response in 10 (6.3%). The rate of response was calculated as 93.7%. Safety of the drug was analyzed in 258 patients, and side effects occurred in 4 (1.6%). Of these 4 patients, rash was in 1 patient, heat sensation in 1 patient, nausea in 1 patient and rash accompanying edema in 1 patient. Abnormal values in clinical laboratory findings were seen in 7 patients. Elevations of transaminase were seen in 5 patients and decrease of platelet was seen in a patient, and then elevations of transaminase with decrease of platelet was seen in a patient, and no other changes of particular note appeared.

Adult↗

Five antigens on human T cells detected by mouse monoclonal antibodies.

Five antigen systems were defined by the monoclonal antibodies (MoAb) produced against mature T cells. The antigens recognized were grouped into two categories based on the antigen distribution on T cells. (a) Tp 120 [mol. wt 120 kilodaltons (120kD)] and Tp40 (40kD), these are on most peripheral T cells, but not on any other cell lineages, i.e. pan-T antigen. (b) Ts32 (32kD), Ts145 (145kD) and TsA (not determined), these antigens are present only on certain populations of peripheral T cells, i.e., T subset antigen. Among these five, Ts145 and TsA are probably novel T cell antigens. Cell surface phenotypes of leukaemias and lymphomas were typed with these MoAb. Ia like antigen negative, null cell type acute lymphocytic leukaemia (Ia- null ALL) are Tp40+, suggesting that this type of ALL belongs to a T cell lineage. T cell ALL (T-ALL) and lymphoblastic lymphoma (LL) were both Tp40+, Ts32+, TsA+ and a half of the cases were Tp120+, but the expression of Tp40 was stronger on LL cells. Mature T cell (T2) lymphoma and adult T cell leukaemia (ATL) were Tp120+, TsA+, while Tp40 was weakly expressed on only one third of the cases. These MoAb were found to be useful to estimate the origin of various T cell malignancies.

Animals↗

Two monoclonal antibodies detecting allotypic determinants of HLA-A.

Three mouse hybridomas producing cytotoxic antibodies against HLA were established. By standard microcytotoxicity test against panels of normal controls, the antigen defined by MA-9 antibody (IgM) showed a good correlation with HLA-A9 alloantigen detected by conventional typing alloantisera (r = 1.0). Family studies also showed that MA-9 determinant segregated with HLA-A9. MA-10 antibody (IgM) reacted with all HLA-A10 positive lymphocyte donors and cross-reacted with two thirds of HLA-AW33 positive donors. Ml-1 antibody (IgG2a) reacted with all the panel cells tested and immunoprecipitated a molecule of 43,000 daltons from Nonidet P-40 lysates of 3H-glucosamine-labelled cells. The results showed that MA-9 and MA-10 antibodies can be used as routine tissue typing reagents.

Adult↗

Synthesis and antibacterial activity of asparagine derivatives of aminobenzylpenicillin.

In order to improve the antibacterial activity of aminobenzylpenicillin, penicillin derivatives having an asparagine moiety in the 6-acyl side chain (11a approximately g, 12a, b, f, g) were synthesized. The structure-activity relationship of new penicillins, N4-alkyl-asparaginylaminobenzylpenicillins, was investigated. N4-Methyl-D-asparaginylamoxicillin (11a), TA-058, was found to possess a broad spectrum of antibacterial activity against Gram-positive and Gram-negative bacteria. In acute toxicity, TA-058 showed good tolerance in mice (LD50 greater than 10 g/kg, i.v.).

Amoxicillin↗

[Preparation and anti-tumor activity of monoclonal antibody against ascitic mammary tumor MM46 cells].

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 a 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 microgram/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 compared that of 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 microgram of anti-MM46 conjugate on days 1, 3, and 5, all mice survived tumor free, although those treated with 1 microgram of anti-MM46 IgG died before day 20 with a life span similar to those of mice treated with nonimmune conjugate or phosphate-buffered saline (control). Anti-MM46 conjugate also showed antitumor effects when injected i.v. to C3H/He mice bearing s.c. inoculated MM46 (inoculum, 2 X 10(6] on Day 1 at a dose of 5 to 50 micrograms. Thus, the in vivo efficacy of anti-MM46 conjugate over anti-MM46 IgG alone was demonstrated by therapeutic experiments as well as by tumor-neutralizing assays.

Animals↗