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Biomedical subjects

T Ujiie

Publications and source records attributed to T Ujiie.

At least 55 records · Page 3Linked to original sources
PubMed1988

Diverse effects of ADP-ribosyl transferase inhibitors on G2 progression and lethality in Chinese hamster ovary cells damaged by DNA-interfering agents.

DNA-damaging agents used in this study could be divided into two groups, according to their ability to retard G2 traverse. One group included monofunctional alkylating agents, such as N-methyl-N-nitrosourea, dimethyl sulfate, and Streptozotocin. Cells treated with them, which at the tested doses only slightly affected cell cycle progression from the G2 phase to mitosis, were retarded in going through mitosis by subsequent treatment with adenosine diphosphate-ribosyl transferase (ADPRT) inhibitors, such as benzamide, 3-aminobenzamide, nicotinamide, and theophylline, but not by caffeine. Effects of caffeine on G2 progression could be distinguished from those of the other ADPRT inhibitors, and even from the effects of another methylxanthine, theophylline. In addition, the lethality of the monofunctional alkylating agents was markedly enhanced by all of the ADPRT inhibitors, including caffeine. The other group consisted of a variety of agents, including intercalators (Adriamycin and Actinomycin D), a radiomimetic agent, Bleomycin, and a bifunctional alkylating antibiotic, Mitomycin C. They prevented cells from going through mitosis to different degrees. The G2-prolonged cells were variously responsive to ability of the ADPRT inhibitors to release G2-arrest and to enhance cell death.

Animals↗
PubMed1988

Adoptive immunotherapy in tumor-bearing mice with OK-432-induced killer cells.

Murine spleen cells cultured for 3 or more days in medium with streptococcal preparation OK-432 became cytotoxic in vitro against several allogeneic and syngeneic tumor cells. These cytotoxic cells were designated OK-432-induced killer (OIK) cells. This study examined the in vivo antitumor efficacy of OIK cells in adoptive immuno- and immunochemo-therapy in mice bearing syngeneic tumors, such as EL-4 lymphoma, Meth-A fibrosarcoma, and MOPC-31C plasmacytoma. OIK cells neutralized these tumor cells, as shown by Winn-type tests, and the cell transfer prolonged the survival of mice inoculated intraperitoneally (ip) with EL-4 or Meth-A cells. Concomitant administration of OK-432 plus recombinant interleukin 2 (rIL-2) significantly improved the therapeutic efficacy of the transferred OIK cells. In mice inoculated with 1 x 10(4) EL-4 cells, chemoimmunotherapy consisting of ip administration of 200 mg/kg cyclophosphamide on day 3 followed by treatment with OIK cell (1 x 10(7)) transfer and with OK-432 (50 KE/kg) plus rIL-2 (50 units/mouse) 6 hr later and on day 6, prolonged the survival. Therefore, the immunotherapy with OIK-cell transfer followed by administration of OK-432 and rIL-2 may be clinically useful as an adjunct of cytoreductive chemotherapy for cancer.

Animals↗
PubMed1987

[The relationship between affective responses in preseparation episodes and patterns of attachment behaviors in the strange situation].

Fifty-six first born Japanese 12-month-old infants were observed in the Strange Situation and the relationship between affective responses in the preseparation episodes and patterns of attachment behaviors in the following episodes was examined. In the preseparation episodes, 18 infants were rated as displaying distress (HS) and 38 infants did not display distress (LS). HS infants were acutely distressed in the separation episodes, and did not easily recover from distress even after regaining close physical contact with mother in the reunion episodes. In contrast, LS infants did not show distress in the first separation and reunion episodes. Although they were distressed in the second separation, they recovered more easily than HS infants in the second reunion episode. Resistant behaviors in the second reunion were observed more frequently and were stronger in HS infants than LS infants. Eighty-three percent of B4 and C were HS infants and 84% of B were LS infants. These results indicated that the affective responses in the preseparation episodes could predict the patterns of attachment behaviors in the following episodes.

Affect↗
PubMed1987

Chemoimmunotherapy of L1210 leukemia with adriamycin, cyclophosphamide, and OK-432, and their effects on the generation of antitumor immunity.

The synergistic effects of combined chemotherapy with adriamycin (ADR) and cyclophosphamide (CY) on L1210 tumors in mice were potentiated by use of a streptococcal preparation, OK-432, in a time- and dose-dependent way. Some mice were cured by treatment with the three agents, and resisted a later challenge by L1210 but not P388 leukemia cells. This immunity was blocked by administration of antimacrophage agents or CY. The effects of OK-432 were also studied with mice sensitized by L1210 cells attenuated with mitomycin C. OK-432 potentiated syngeneic and semi-syngeneic transplantation resistance in vivo and augmented primary and secondary cytotoxicity mediated by spleen cells in vitro. In vivo administration of ADR and CY together enhanced in vivo tumor transplantation resistance and in vitro cytotoxicity was blocked, but this inhibition was reversed by injection of OK-432. The results suggested that OK-432 acted by increasing the activity of cytotoxic spleen cells against L1210 cells, which are fast-growing and poorly immunogenic, and that this cytotoxicity killed tumor cells that survived the chemotherapy.

Animals↗
PubMed1987

Effect of an antitumor chelator, 2-(2-hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic acid (HQ-II) on DNA synthesis, clonogenicity, and cell cycle progression of HeLa cells.

A newly synthesized antitumor chelator, 2-(2-hydroxy-5-n-hexylphenyl)-8-quinolinol-4-carboxylic acid (HQ-II), was further investigated for the mechanism of action, employing a HeLa cell line. As the result, HQ-II prevented proliferation of HeLa cells in culture and the inhibition was ascribable to the interference of HQ-II with extra and/or intracellular iron component vital for cell growth. HQ-II selectively inhibited DNA biosynthesis and the inhibition resumed by washing out of the agent or by adding ferric or ferrous salts. The cell cycle progression was blocked at G1/S boundary phase by an exposure of 0.07 mM HQ-II. Cells washed out of the agent could synchronously traverse through S phase to mitosis with an index of synchrony of 0.48. However, HQ-II at much higher concentrations resulted in prolongation of S, G2, and G1 phases, in keeping with the result of cell kill kinetic analysis, which indicated that HQ-II was a S phase-specific but self-limiting agent. A ratio of B/A, where A is the concentration causing 50% inhibition of HeLa cell growth and B is that of the DNA biosynthesis, was found to be an effective criterion for screening antitumor agent among metal binding agents, chelators.

Animals↗
PubMed1987

Generation of activated killer-like cells by OK-432-mediated production of interleukin 1, interleukin 2, and interferon-gamma in vitro.

Human peripheral blood mononuclear (PBM) cells incubated for 3 or more days in medium containing streptococcal preparation OK-432 developed toxicity to natural killer-resistant tumor cell lines. The generation of cytotoxic cells by OK-432 was potentiated by exogenous lymphokines such as interleukin 2 (IL-2) and interferon-gamma (IFN-gamma), the former being much more effective than the latter, and was blocked by antibodies to these cytokines such as interleukin 1 (IL-1), IL-2, and IFN-gamma. Although monocyte-depleted PBM cells were barely responsive to OK-432, they gave rise to activated killer (AK) cells after being incubated in medium with both IL-2 and IFN-gamma. Their generation was augmented by exogenous IL-1 but not by OK-432. These data indicate that AK-like cells are generated from human PBM cells through mediation of IL-1, IL-2, and IFN-gamma produced by OK-432 in vitro.

Biological Products↗
PubMed1987

OK-432-mediated augmentation of antitumor immunity and generation of cytotoxic T lymphocytes.

Sensitization with mitomycin C-treated L1210 or EL-4 tumor cells followed by intraperitoneal injection of a streptococcal preparation OK-432 rendered histocompatible or syngeneic mice immune to the corresponding tumor cells. The antitumor immunity, which was more potent than that induced by attenuated tumor cells alone, was manifested by transplantation resistance to challenge tumor cells, and by cytotoxic activity of spleen cells from the primed mice. The former activity was closely related to the latter, which was found to be mainly due to tumor-specific cytotoxic T lymphocytes. The in vivo immunoaugmentation by OK-432 was susceptible to macrophage toxins such as trypan blue and carragheenins, and was partly dependent on the activity of noncytotoxic Ia-positive peritoneal macrophages. OK-432-mediated enhancement of Ia-positive macrophage functions was confirmed by concanavalin A-blastogenesis and T cell-dependent antibody formation. Allo-reactive cytotoxicity induced in allogeneic or semiallogeneic mice, which had been primed with clonogenic or attenuated tumor cells, was also augmented by concomitant administration of OK-432. These results suggest that OK-432 augments induction of antitumor immunity and alloreactive cytotoxicity, associated with stimulation of noncytotoxic Ia-positive accessory macrophage activity.

Animals↗
PubMed1987

Enhanced generation of OK-432-induced killer cells by interleukin 2.

Spleen cells of untreated mice became nonspecifically cytotoxic after cultivation in the presence of a streptococcal preparation, OK-432, for 3 or more days. The cytotoxic cells, named OK-432-induced killer (OIK) cells, injured a variety of target cells including syngeneic EL-4 cells resistant to natural killer (NK) cells, but not NK-susceptible YAC-1 cells. C57BL/6 splenic cells cultured for 5 days in the presence of both OK-432 and interleukin 2 (IL-2) were highly cytotoxic to both EL-4 and YAC-1 cells, and had Thy-1+, Lyt-1,2-, and asialogGM1+ phenotypes, which were identical with those of OIK cells. A test for competitive inhibition with cold target cells and fractionation by centrifugation onto discontinuous density gradients of Percoll showed that cytotoxic cells generated by OK-432 plus IL-2 comprised at least two populations; the cells in the first population were cytotoxic to EL-4 cells but not to YAC-1 cells, and were smaller in size than those in the second population, which were cytotoxic to YAC-1 cells and had NK morphology. Therefore, generation of OIK cells was augmented by IL-2.

Animals↗
PubMed1987

[Clinical experience with cefbuperazone in complicated urinary tract infection].

Cefbuperazone (CBPZ) was administered to inpatients with complicated urinary tract infections (UTI) at our department. Clinical efficacy and safety were evaluated in 22 chronic cases by the criteria for evaluation of clinical of antimicrobial agents on urinary tract infection. Overall clinical efficacy was excellent in 8 cases, moderate in 9 cases and poor in 5 cases with an effectiveness rate of 77%. Twenty-four of the 34 strains isolated from the patients were eradicated and eradication rate was 71%. Neither subjective nor objective adverse reactions were observed. Abnormal changes in laboratory tests were found in 9 patients, but were probably not related to CBPZ administration. Judging from these results, CBPZ is considered to be an effective and safe antibacterial for the treatment of complicated UTI.

Adult↗
PubMed1987

Augmentation by OK-432 of generation of culture-induced killer cells.

A streptococcal preparation, OK-432, injected intraperitoneally, potentiated rejection of L1210 leukemic cells in semiallogeneic BALB/c mice. This increased rejection was further enhanced by a transfer of peritoneal exudate T (PET) cells, but not of spleen cells. Spleen cells incubated in vitro for 3 or more days were as effective as PET cells in stimulating tumor rejection, and were cytotoxic in vitro as tested by a 4-hr 51Cr-release assay. This cytotoxicity was closely related to the OK-432-mediated augmentation of L1210 rejection in vivo. In vitro treatment with OK-432 of spleen cells from intact mice generated nonspecific cytotoxic cells. The cells were nonadherent to plastic, radioresistant, and of Thy-1+, Lyt-1,2-, and asialoGM1+ phenotypes, and were tentatively named OK-432-induced killer (OIK) cells. They were cytotoxic to tumor cells resistant to natural killer (NK) cells, and different from NK cells or lymphokine-activated killer cells. For their generation, macromolecular synthesis and participation of plastic-adherent cells (probably macrophages) were needed. The in vivo growth of L1210 leukemic cells could not be inhibited by simultaneous administration of PET cells primed in vivo with OK-432, of spleen cells primed in vivo with OK-432 and then cultured, or of spleen cells primed in vitro with OK-432 and then cultured (OIK cells). However, a prophylactic adoptive transfer of these cells was effective in immunocompetent mice as well as in athymic nu/nu mice, but not in mice irradiated with 400 rad. The in vivo activity was attributable mainly to Lyt-1+, -2- cells radioresistant and adherent to nylon wool, which were probably amplifier/helper T cells.

Animals↗