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T Kataoka

Publications and source records attributed to T Kataoka.

At least 235 records · Page 13Linked to original sources
PubMed1985

In yeast, RAS proteins are controlling elements of adenylate cyclase.

S. cerevisiae strains containing RAS2val19, a RAS2 gene with a missense mutation analogous to one that activates the transforming potential of mammalian ras genes, have growth and biochemical properties strikingly similar to yeast strains carrying IAC or bcy1. Yeast strains carrying the IAC mutation have elevated levels of adenylate cyclase activity. bcy1 is a mutation that suppresses the lethality in adenylate cyclase deficient yeast. Yeast strains deficient in RAS function exhibit properties similar to adenylate cyclase deficient yeast. bcy1 suppresses lethality in ras1- ras2- yeast. Compared to wild-type yeast strains, intracellular cyclic AMP levels are significantly elevated in RAS2val19 strains, significantly depressed in ras2- strains, and virtually undetectable in ras1- ras2- bcy1 strains. Membranes from ras1- ras2- bcy1 yeast lack the GTP-stimulated adenylate cyclase activity present in membranes from wild-type cells, and membranes from RAS2val19 yeast strains have elevated levels of an apparently GTP-independent adenylate cyclase activity. Mixing membranes from ras1- ras2- yeast with membranes from adenylate cyclase deficient yeast reconstitutes a GTP-dependent adenylate cyclase.

Adenylyl Cyclases↗
PubMed1985

Preferential rearrangement of the immunoglobulin kappa chain joining region J kappa 1 and J kappa 2 segments in mouse spleen DNA.

The V kappa-KpnI family, which constitutes approximately equal to 36% of mouse kappa chain variable region gene (V kappa) segments, conserves the Kpn I site (G-G-T-A-C-C) at the position corresponding to residues 35-37. Using this cleavage site, we were able to assess the relative recombination frequency of the kappa chain joining region gene (J kappa) segments in mouse spleen DNA. The J kappa 1 and J kappa 2 segments were used 2- to 5-fold more frequently than were the J kappa 4 and J kappa 5 segments. The J kappa 3 segment was shown to be incapable of recombining with the V kappa segment. The relative recombination frequency of the J kappa segments did not change significantly by lipopolysaccharide stimulation of normal mouse spleens. The relative frequency of the J kappa usage was unaltered in immune disorders such as in nude (nu/nu), MRL (lpr/lpr), and BXSB mice. Seven V kappa-KpnI-J kappa 1 clones were isolated, and their nucleotide sequences were determined. Two of them were derived from the identical germ-line V kappa segment but differed in the nucleotide sequence of the V-J junction. The maximal number of V kappa germ-line segments was estimated to be less than 300 by statistical calculation.

Animals↗
PubMed1985

224Ra correction for determination of 226Ra in environmental materials.

The most commonly available 226Ra determination was too time-consuming to be suited to 226Ra monitoring for the accidental release. The formula for determination of 226Ra was derived by 224Ra correction for WHO's equation. A rapid determination of 226Ra in environmental materials was made possible by using this formula. The 226Ra values of the soil and natural water at Ningyoh-Tohge obtained by the present method were in good agreement with those by the conventional WHO method. It was demonstrated that 226Ra of more than about 37 mBq (1 pCi) in the sample could be determined within 4 days by this method.

Japan↗
PubMed1985

Treatment regimen and host T-cell-dependent therapeutic effect of interferon in mouse solid tumors.

A highly purified hybrid human interferon (IFN)-alpha A/D, was used to define optimum treatment regimens for Meth A fibrosarcoma intradermally inoculated in syngeneic BALB/c mice. Treatments from the sixth day post-tumor inoculation were most effective, and 10 consecutive injections of IFN completely suppressed the tumor growth for a prolonged time without recurrence after the last injection of IFN. Intraperitoneal and intravenous injections were similarly effective. The therapeutic effect of IFN was abrogated by the injection of rabbit alpha-mouse thymocyte globulin but not normal rabbit globulin. The therapeutic effect of IFN was much poorer in BALB/c nu/nu mice, which are athymic and defective in T-cell immunity, than in BALB/c +/+ mice. Mice in which Meth A growth was completely suppressed by IFN were refractory to Meth A, but not Meth 1 tumor, another antigenically distinct fibrosarcoma, whereas mice in which Meth 1 growth was suppressed completely by IFN were refractory to Meth 1 but not Meth A tumor. These three findings suggest that the therapeutic effect of IFN depended on host T-cell immunity and that tumors were eventually eliminated by tumor-selective antitumor immunity provoked during IFN therapy. Under the present experimental conditions, the direct anticellular activity of IFN was presumed to contribute very little to the therapy for solid tumors, since the therapeutic effect of IFN on three different solid tumors was not correlated with their in vitro sensitivity to this substance: Colon 26, which was as sensitive to IFN as Meth A in the in vitro antiproliferation, responded most poorly to IFN therapy, while Meth A and Meth 1 responded similarly well to IFN therapy, although there was more than a 2500 times difference in their in vitro IFN sensitivity.

Animals↗
PubMed1985

In vivo inhibition of concanavalin A-induced suppressor T cells by 5-fluorouracil.

Spleen cells of mice inoculated intravenously (iv) with concanavalin A (Con A) suppressed the in vitro normal spleen cell blastogenesis. The suppressor cells, as determined by measuring the inhibition of in vitro T cell blastogenesis by Con A, were resistant to X-irradiation. They lacked surface Ig and were abrogated by treatment with alpha Thy 1.2 antibody and complement, but not with complement alone, indicating that these suppressor cells are not B cells but T cells. Inoculation of 5-fluorouracil (5-FU) inhibited the induction and/or activity of these suppressor cells, whereas that of cyclophosphamide (CY), adriamycin, vincristine, or 3-[(4-amino-2-methyl-5-pyrimidinyl)-methyl]-1-(2-chloroethyl)-1-nitro sou rea (ACNU) did not at any interval tested. Since two other antimetabolic agents, 6-mercaptopurine and 2'-deoxyguanosine, were also effective in inhibiting these suppressor T cells, it was supposed that Con A-induced suppressor T cells are metabolically more active than the other T subpopulations. The findings that CY and ACNU decreased the number of T cells as much as or more than 5-FU did, but that they did not inhibit these suppressor T cells, suggests that 5-FU more or less selectively inhibited this suppressor T-cell subpopulation.

Animals↗
PubMed1985

Suppressor macrophages in tumor-bearing mice and their selective inhibition by 6-mercaptopurine.

Using the in vitro polyclonal blastogenesis test, we identified peritoneal suppressor cells from L1210 leukemia-bearing mice as Ia-negative macrophages. These cells manifested adherence to plastic tubes and sensitivity to silica but not to X-irradiation and treatment with alpha Thy 1.2 or alpha Ia 7 antibody plus complement. The suppressor activity of peritoneal macrophages was detected as early as 3 days after L1210 inoculation; however, the number of suppressor macrophages did not increase until Day 7. 6-Mercaptopurine (6-MP) inhibited their suppressor activity, whereas three other antineoplastic agents, including cyclophosphamide, did not. 6-MP-dependent suppressor inhibition was induced irrespective of whether treatment was combined with tumor vaccine. In vitro, the sensitivity of suppressor macrophages to 6-MP was not enhanced. This and the finding that 6-MP induced an increase rather than a decrease in the number of peritoneal macrophages indicated that, in vivo, 6-MP selectively inhibited suppressor macrophages. The inverse correlation of their suppressor activity and the therapeutic response in tumor-bearing mice administered with tumor vaccine and antineoplastic agents suggests that peritoneal suppressor macrophages were involved in modulating the efficacy of active immunotherapy. This was further substantiated by the finding that the strongly immunosuppressive macrophages of L1210-bearing and cyclophosphamide-treated mice inhibited the antitumor response of L1210 vaccine-primed mice.

Animals↗
PubMed1985

Antitumor activity of the DNA fraction from Mycobacterium bovis BCG. II. Effects on various syngeneic mouse tumors.

MY-1, a fraction extracted from BCG and composed of 70.0% DNA and 28.0% RNA, was examined for its antitumor activity against 9 different syngeneic mouse tumors. Tumor regression was induced in almost all of the mice bearing any of five kinds of solid tumors by repeated intralesional injections of 100 micrograms MY-1. When cells of some tumors were inoculated intradermally together with MY-1, tumor growth was suppressed, lung metastases were inhibited, and the survival times of mice bearing 1 of 3 leukemic tumors were prolonged. Repeated sc injections with MY-1 in sites remote from tumor cell inoculation or repeated iv injections were more or less effective against three kinds of solid tumors. Mice inoculated with Lewis lung carcinoma cells in a hind footpad and whose legs were amputated 9 days later were given iv or sc injections of MY-1 every other day (8 times in total), resulting in substantial prolongation of survival. No direct cytotoxicity of MY-1 for these tumors could be shown in three kinds of experiments, which indicates that the antitumor mechanism of MY-1 is host mediated. MY-1 was equally effective in mice with or without presensitization with BCG, whereas BCG was much more effective in BCG-sensitized mice. This finding suggests that a delayed-type hypersensitivity reaction elicited by BCG protein is not required for the antitumor activity of MY-1.

Animals↗
PubMed1985

[A case of acute promyelocytic leukemia complicated with severe esophageal stenosis caused by aclacinomycin A].

Aclacinomycin A (ACM) is different from other anthracycline antibiotics in its antitumor activity and clinical effect. We report a case of acute promyelocytic leukemia complicated with severe esophageal ulcer by BH-AC . AMP therapy. The patient was 24 years old. In 1983, he achieved complete remission with BH-AC . DMP therapy but we confirmed relapse in April, 1984. ACM caused nausea, vomiting, diarrhea, alimentary tract bleeding and sore throat, together with a complication of esophageal stenosis. In about half of 10 cases receiving BH-AC . AMP therapy in our hospital, we noticed severe bleeding in the urinary treat, genital organs and alimentary tract. Care should therefore be taken with regard to mucosal injury when ACM therapy is used.

Aclarubicin↗
PubMed1985

Production of antitumor T-cells in tumor-bearing mice treated with tumor vaccine and 6-mercaptopurine.

Treatment with both L1210 murine leukemia cell vaccine (L1210 vaccine) and 6-mercaptopurine (6-MP) induced antitumor effector cells in the spleen and peritoneal cavity of L1210-bearing mice. The in vivo neutralization test showed that the spleen cells and peritoneal cells of mice treated with both agents, but not with either agent alone, prolonged the life span of animals simultaneously inoculated i.p. with live L1210 cells. These results indicate that these antitumor cells were associated with the augmented therapeutic response in L1210-bearing mice treated with both agents. The neutralizing activity of peritoneal cells was located to a fraction not adhering to plastic flasks and abolished by the treatment of anti-Thy 1.2 antibody and complement, indicating that they were T-cells. The in vitro antiproliferation test confirmed these observations. The spleen cells and peritoneal T-cells of these mice suppressed L1210 proliferation. Their activity was tumor specific since they suppressed the in vitro proliferation of L1210 but not P388 and L5178Y cells. The in vivo association of antitumor T-cells with the augmented therapeutic effect was substantiated by the finding that rabbit anti-mouse thymocyte globulin abolished the induced therapeutic effect.

Animals↗
PubMed1984

Isolation and characterization of endonuclease J: a sequence-specific endonuclease cleaving immunoglobulin genes.

An endonuclease activity which cleaves close to the recombination sites of the immunoglobulin JK segments was found in extracts of chicken bursa of Fabricius and characterized after partial purification. The enzyme preparation also cleaved a VK segment at its 3' end. A similar activity was found in mouse liver, mouse myelomas and Hela cells. The enzyme designated as endonuclease J introduces double-stranded cleavages preferentially at sequences containing G clusters of pBR322 as well as the JK segments. However, not all the G clusters were cleaved by endonuclease J, suggesting that the enzyme recognizes additional sequences. Deletion of the conserved nonamer (GGTTTTTGT) located immediately 5' to the JK4 segment drastically reduced the cleavage activity of its immediate downstream G cluster. Although biological function of endonuclease J is not clear at this stage, the possibilities of its involvement in the immunoglobulin gene recombination and general recombination were discussed.

Animals↗
PubMed1984

Effect of levamisole on cytotoxic T-cell-mediated immune resistance to L1210 murine leukemia in hyperimmune mice.

The effect of levamisole (LMS) on T-cell-mediated antitumor immunity was examined in adult and aged mice hyperimmune to L1210 leukemia. The immune resistance of aged mice was depressed compared with that of adult mice, which almost completely rejected 5 X 10(7) L1210 cells inoculated IP. A significant level of tumor-specific cytotoxicity was detected in the spleen cells of adult hyperimmune mice by the 51Cr-release assay after in vitro sensitization with mitomycin C-treated L1210 cells. This was mediated by cytotoxic T cells, since in vivo administration of antithymocyte serum or in vitro treatment of the spleen cells with anti-Thy 1.2 antibody and complement abrogated the cytotoxicity completely. In aged mice, however, cytotoxic T-cell activity was lower although the animals were immune to L1210. Administration of LMS (0.38 mg/kg) restored the depressed cytotoxicity of aged mice to the level seen in adult mice. Furthermore, in adult hyperimmune mice LMS augmented T-cell-mediated cytotoxic activity and restored the reduced cytotoxicity caused by in vivo administration of antithymocyte serum. These results indicate that LMS was effective in augmenting T-cell-mediated tumor immunity in immunologically competent or deficient hosts.

Aging↗
PubMed1984

Genes in S. cerevisiae encoding proteins with domains homologous to the mammalian ras proteins.

The ras genes, which were first identified by their presence in RNA tumor viruses and which belong to a highly conserved gene family in vertebrates, have two close homologs in yeast, detectable by Southern blotting. We have cloned both genes (RAS1 and RAS2) from plasmid libraries and determined the complete nucleotide sequence of their coding regions. They encode proteins with nearly 90% homology to the first 80 positions of the mammalian ras proteins, and nearly 50% homology to the next 80 amino acids. Yeast RAS1 and RAS2 proteins are more homologous to each other, with about 90% homology for the first 180 positions. After this, at nearly the same position that the mammalian ras proteins begin to diverge from each other, the two yeast ras proteins diverge radically. The yeast ras proteins, like the proteins encoded by the mammalian genes, terminate with the sequence cysAAX, where A is an aliphatic amino acid. Thus the yeast ras proteins have the same overall structure and interrelationship as the family of mammalian ras proteins. The domains of divergence may correspond to functional domains of the ras proteins. Monoclonal antibody directed against mammalian ras proteins immunoprecipitates protein in yeast cells containing high copy numbers of the yeast RAS2 gene.

Amino Acid Sequence↗
PubMed1984

Genetic analysis of yeast RAS1 and RAS2 genes.

We present a genetic analysis of RAS1 and RAS2 of S. cerevisiae, two genes that are highly homologous to mammalian ras genes. By constructing in vitro ras genes disrupted by selectable genes and introducing these by gene replacement into the respective ras loci, we have determined that neither RAS1 nor RAS2 are by themselves essential genes. However, ras1 - ras2 - spores of doubly heterozygous diploids are incapable of resuming vegetative growth. We have determined that RAS1 is located on chromosome XV, 7 cM from ade2 and 63 cM from his3; and RAS2 is located on chromosome XIV, 2 cM from met4 . We have also constructed by site-directed mutagenesis a missense mutant, RAS2val19 , which encodes valine in place of glycine at the nineteenth amino acid position, the same sort of missense mutation that is found in some transforming alleles of mammalian ras genes. Diploid yeast cells that contain this mutation are incapable of sporulating efficiently, even when they contain wild-type alleles.

Animals↗
PubMed1984

A product of yeast RAS2 gene is a guanine nucleotide binding protein.

Yeast Saccharomyces cerevisiae contains two genes, RAS1 and RAS2, which show remarkable homology to mammalian ras genes. To characterize these gene products, we have expressed the RAS2 gene in yeast using an inducible GAL10 promoter. After labeling with [35S]methionine and immunoprecipitating with a monoclonal antibody Y13-259, which reacts with p21 encoded by mammalian ras genes, a major band having an apparent molecular weight of 41,000 is detected. This band has also been identified in cell-free translation products of polyadenylated RNA extracted from yeast cells grown in the presence of galactose. Crude extracts of cells expressing the RAS2 gene exhibit guanine nucleotide binding activity. This is detected by incubation with [3H]GDP followed by immunoprecipitation with the antibody Y13-259. The binding of labeled GDP is inhibited by a 20-fold excess of GDP, GTP, and, to a lesser extent, by UTP, a characteristic similar to that possessed by the mammalian ras proteins. However, the activity of the yeast protein differs from that of the mammalian proteins in its strong dependence on temperature. The guanine nucleotide binding activity provides an assay to purify the yeast protein.

Cloning, Molecular↗