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K Kuribayashi

Publications and source records attributed to K Kuribayashi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Suppression of intracellular Cu-Zn SOD results in enhanced motility and metastasis of Meth A sarcoma cells.

We have previously described an inverse relationship between Cu-Zn superoxide dismutase (SOD) activity and invasiveness of a clone of human tongue cancer cells. In these cells, suppression of Cu-Zn SOD activity by transfection with anti-sense cDNA enhanced motility in vitro. The present studies were undertaken to determine whether the inverse relationship between intracellular Cu-Zn SOD activity and motility is a general property of other tumor cells and whether this enzyme indeed defines in vivo metastatic potential. Murine Meth A sarcoma-derived ML-01 cells, which have low metastatic activity, were transfected with anti-sense Cu-Zn SOD cDNA. Two clones with very different SOD activities--ML-AS2, with the most suppressed, and ML-AS5, with the least suppressed activity-were analyzed for their motility and metastatic capability. Compared to the mocktransfectant ML-neo, the metastatic potential and motility of the ML-AS2 and ML-AS5 were increased 4.5- and 2.1-fold, respectively. Superoxide treatment enhanced the motility of the AS clones but not that of the ML-neo cells. Our results clearly show that there is an inverse relationship between the intracellular level of Cu-Zn SOD, cell motility and in vivo metastatic potential.

Animals↗
PubMed1997

Involvement of T-cell subsets and natural killer (NK) cells in the growth suppression of murine fibrosarcoma cells transfected with interleukin-12 (IL-12) genes.

A 3-methylcholanthrene-induced fibrosarcoma cell line of BALB/c origin, CMS5j, was co-transfected with cDNA for the p40 and p35 subunits of interleukin-12 (IL-12). Injection of transfected cells producing 5 x 10(3) U IL-12/10(6) cells/ml/day in nude mice with an established fibrosarcoma at a contralateral site efficiently eliminated tumor growth in the early phase (injection on day 0 or 4) but not later (day 8). This effect could be abrogated by simultaneous i.v. injection of antibodies against NK1.1 or ASGM1 (asialoGM1 = ganglio-N-tetraosyl-ceramide), which indicates that natural killer (NK) cells play a major role in tumor eradication or suppression when stimulated by IL-12. In wild-type mice, application of IL-12-secreting CMS5j cells abrogated growth of tumors established 8 days before but not earlier. Based on our experiments with antibody blocking in vivo, all CD4+, CD8+ and ASGM1+ cells are involved in tumor rejection. However, in our system, CD4+ cells or CD8+ cells alone, but not ASGM1+ cells alone, also could lead to tumor rejection. IL-12-engineered fibrosarcoma cells may constitute an efficient and safe system for immunotherapy of cancer.

Animals↗
PubMed1997

Mutated mitogen-activated protein kinase: a tumor rejection antigen of mouse sarcoma.

The molecular basis of the polymorphic tumor rejection antigens of chemically induced sarcomas of inbred mice remains a mystery, despite the discovery of these antigens over 40 years ago and their critical importance to the foundation of tumor immunology. In an analysis of a panel of BALB/c 3-methylcholanthrene-induced tumors, we identified one tumor, CMS5, that elicited a strong cytotoxic T cell response with exquisite specificity for CMS5. A stable cloned line of T cells with this specificity (C18) was used to screen a CMS5 cDNA expression library. The gene encoding the C18-defined antigen was identified as a mutated form of a mouse mitogen-activated protein kinase, ERK2, and a peptide incorporating the resulting amino acid substitution (lysine to glutamine) was efficiently recognized by C18. Vaccination with this peptide elicited specific resistance to CMS5 challenge. Extensive efforts to isolate antigen-loss variants of CMS5 were unsuccessful, suggesting that the mutated mitogen-activated protein kinase is essential for maintenance of the malignant phenotype.

Amino Acid Sequence↗
PubMed1997

Intra-mesenteric artery steroid administration relieved severe refractory gastro-intestinal graft-vs.-host disease in an allogeneic bone marrow transplantation patient.

We report a case of severe gastro-intestinal (G-I) graft-vs.-host disease (GVHD) successfully treated with intra-mesenteric artery steroid administration. A 29-year-old man with severe aplastic anemia (SAA) was submitted to HLA-identical unrelated allogeneic bone marrow transplantation (BMT) and was found to be suffering from grade IV G-I GVHD. Although cyclosporine, steroid pulse therapy, and FK506 proved ineffective, 30 mg of water-soluble prednisolone as administered into each the superior and inferior mesenteric artery with remarkable effects. This treatment was repeated two times, and the symptoms of G-I GVHD disappeared completely.

Adult↗
PubMed1997

The effectiveness of active specific immunotherapy using interferon-gamma-gene-transduced tumor cells in a murine tumor model.

Active specific immunotherapy was examined in BALB/c mice using sonicated tumor extract(SE) from plasmacytoma MOPC104E or interferon-gamma-(IFN-gamma)-gene-transduced MOPC104E (Mu gamma), employing interleukin-1 (IL-1) as an adjuvant. Subcutaneous (s.c.) MOPC104E tumor growth was significantly suppressed in mice given a single preimmunization of IL-1 plus Mu gamma-SE, 9 days prior to inoculation, whereas the tumor growth in mice similarly pretreated with IL-1 alone or IL-1 plus MOPC104E-SE(MOPC-SE) was not affected; the mean tumor diameters on day 21 being 6.8 mm, 15.3 mm, and 13.2 mm, respectively. Two-dose preimmunization with Mu gamma-SE alone or IL-1 alone given 10 and 7 days prior to s.c. inoculation also resulted in profound suppression of tumor growth compared to the control. As postsurgical immunization, MOPC104E cells were injected into the foot pads of mice, followed by amputation of the tumor-bearing foot 20 days later, then treatment with IL-1 plus MOPC-SE or IL-1 plus Mu gamma-SE on days 4, 7, and 10 after the amputation. The mean survival of the mice treated with IL-1 plus Mu gamma-SE was significantly prolonged compared to that of the mice treated with IL-1 plus MOPC-SE, at 90.3 days vs 40.9 days, respectively (P < 0.05 by the Cox-Mantel test). These results suggest that SE prepared from IFN-gamma-gene-transduced MOPC104E is more effective for active specific immunotherapy than SE prepared from MOPC104E.

Animals↗
PubMed1997

Susceptibility of nude mice carrying the Fv-4 gene to Friend murine leukemia virus infection.

Fv-4 is a mouse gene that dominantly confers resistance to infection with Friend murine leukemia virus (F-MuLV) (S. Suzuki, Jpn. J. Exp. Med. 45:473-478, 1975). Despite complete resistance to ecotropic MuLV infection in mice carrying the Fv-4 gene, it is known that cells carrying the resistance gene in tissue culture do not always show resistance as extensive as that in vivo (H. Yoshikura and T. Odaka, JNCI 61:461-463, 1978). To investigate the immunological effect on resistance in vivo, we introduced the Fv-4 gene into BALB/c nude mice (Fv-4-/- nude[nu/nu]) by mating them with Fv-4 congenic BALB/c mice (Fv-4r/r nude+/+) and examined the susceptibility of the F2 progeny to F-MuLV. All BALB/c nude mice without the Fv-4 gene (Fv-4-/- nude[nu/nu]) were permissive to F-MuLV and developed erythroleukemia within 2 weeks after virus inoculation. The BALB/c nude mice with the Fv-4 gene (Fv-4r/r nude[nu/nu]) did not develop leukemia, and no or little virus was detected in the spleen 7 weeks after virus inoculation. The resistance to F-MuLV was dominant in (Fv-4 congenic BALB/c x BALB/c nude) F1 mice with the Fv-4r/- nude(nu/+) genotype as strictly as in (Fv-4 congenic BALB/c x BALB/c) F1 mice with the Fv-4r/- nude+/+ genotype. However, almost all BALB/c nude mice with the Fv-4r/- nude(nu/nu) genotype developed the disease within 7 weeks, and the virus was detected in all of their spleens even in the mice without leukemia. These results show that the resistance caused by the Fv-4 gene is recessive in nude mice and dominant in BALB/c mice. Some immunological effects, perhaps cell-mediated immunity, may play important roles in the resistance to F-MuLV infection in vivo in addition to the dosage effect of the Fv-4 product.

Animals↗
PubMed1997

Secretion patterns of Th1- and Th2-type cytokines in immune deviation caused by dendritic cells.

The expression of cytokine mRNAs in mice during immune deviation was examined. A subcutaneous injection of antigen-pulsed dendritic cells (DCs) induced strong delayed-type hypersensitivity (DTH) but not humoral immunity, but an intravenous injection of DCs increased the titer of specific antibodies while inducing weak DTH. There was more interleukin-4 and interleukin-5 mRNA in mice given DCs subcutaneously than in those given DCs intravenously. Therefore, synthesis of cytokines from type 2 helper T (Th2) cells was greater when there was DTH but little or no antibody production. This pattern of cytokine synthesis was in accordance with the pattern of isotypes of the specific antibodies produced. In the mice given DCs intravenously, there was more mRNA of Th1 cytokines, and the production of IgG2a, IgG2b, and IgG3 antibodies increased, but that of IgG1 antibody did not. In immune deviation induced by antigen-pulsed DCs, cross-regulation of Th1 and Th2 cells may be more complicated.

Animals↗
PubMed1996

Comparative study of regional cerebral blood flow values measured by Xe CT and Xe SPECT.

The regional cerebral blood flow (rBCF) values measured by stable xenon-enhanced computed tomography (Xe XT) and by radioactive xenon-133 single photon emission computed tomography (Xe SPECT) were compared in 16 patients with cerebral infarct. On the non-lesion side Xe SPECT recorded 10.7% higher rCBF values than Xe CT in the anterior cerebral artery territory, while Xe CT recorded 9.6% higher values than Xe SPECT in the middle cerebral artery territory. These differences were not statistically significant. Although the rCBF values were almost the same, no correlation was found between the two methods in the posterior cerebral artery territory and the basal ganglia. Only hemispheric CBF on the non-lesion side showed the same value and a good correlation between the Xe CT and the Xe SPECT. There was a good correlation in the hemispheric CBF values on the lesion side, too. The difference of rCBF between the non-lesion side and the lesion side was expressed smaller in the Xe SPECT than in the Xe CT. This is in agreement with the previous reports that Xe SPECT overestimates the flow in the low flow areas. The higher rCBF values in the anterior cerebral artery territory measured by the Xe SPECT was ascribed to the artifact from the radioactivities in the inhalation mask and the air passages as reported previously. In conclusion, there is no good correlation between the rCBF values measured by the Xe CT and by the Xe SPECT. Only hemispheric CBF shows a good correlation between the two methods.

Adult↗
PubMed1996

Possible origin of murine AIDS (MAIDS) virus: conversion of an endogenous retroviral p12gag sequence to a MAIDS-inducing sequence by frameshift mutations.

The murine AIDS (MAIDS) virus has a unique sequence in its p12gag region, which is responsible for MAIDS development. A transcript hybridizing with this sequence is expressed in normal C57BL/6 mice. The transcript, designated Edv, has been previously cloned and sequenced (Y. Kubo, Y. Nakagawa, K. Kakimi, H. Matsui, K. Higo, L. Wang, H. Kobayashi, T. Hirama, and A. Ishimoto, J. Gen. Virol. 75:881-888, 1994). Compared with the nucleotide sequence of the helper LP-BM5 ecotropic virus, the pathogenic replication-defective MAIDS virus has a 16-bp deletion and a 1-bp insertion in the 5' and 3' regions of the p12gag sequence, respectively, and the Edv transcript contains only a 3-bp deletion. Therefore, the amino acid sequence of the defective MAIDS virus p12gag region is not homologous to that of the helper virus and the Edv transcript because of the frameshift. To determine whether the amino acid sequence resulting from the frameshift is critical for MAIDS development, we constructed chimeric viruses that contained the p12gag regions of the helper virus and the Edv transcript, respectively, with and without the same frame as the defective MAIDS virus by the artificial frameshift mutations. The mutant viruses with the frameshift mutations induced MAIDS in inoculated mice, but the viruses without the mutations did not. These results suggested that the MAIDS virus was generated by frameshift mutations in the p12gag region of Edv or a related sequence.

Animals↗
PubMed1996

[Case of adult T-cell leukemia without antibodies for HTLV-I but with for pX gene region].

A 76-year-old woman had lymphocytosis with lymphocytes having convoluted or lobulated nuclei. These abnormal lymphocytes (leukemic cells) were positive for CD4, and some expressed IL-2R (CD25) and CD3 molecules, respectively. These morphologic and phenotypic features were compatible with adult T-cell leukemia, but serum antibodies to human T-cell lymphotropic virus type I (HTLV-I) were not detected by the particle aggregation method and an enzyme-linked immunosorbent assay. The polymerase chain reaction showed that the LTR, gag, pol, and env regions of HTLV-I proviral DNA had not been incorporated into the leukemic cells. Only the pX region was detected in these leukemic cells.

Aged↗
PubMed1995

Immunization with a single T helper cell epitope abrogates Friend virus-induced early erythroid proliferation and prevents late leukemia development.

Synthetic peptide vaccines containing a single Th cell epitope identified in the gp70 envelope glycoprotein of Friend murine leukemia helper virus induced potent protective immunity against Friend virus infection. H-2a/b mice immunized by a single s.c. injection of the CFA emulsion containing a peptide that represented the N-terminal gp70 epitope recovered slowly from initial development of splenomegaly, and most did not develop late leukemia, whereas most of the control mice given an injection of CFA alone showed sustained leukemic splenomegaly after the challenge with Friend virus. The mice of the same genetic background immunized with the C-terminal Th cell epitope by a single injection of a separate synthetic peptide eliminated virus-producing cells from the spleen within 12 days after inoculation of Friend virus complex, and did not develop early splenomegaly or polycythemia. H-2a/a mice were not protected by immunization with either one of the two synthetic peptides. Earlier production and more rapid class switching of virus-neutralizing Abs were observed in H-2a/b mice immunized with the peptide vaccines after the challenge with Friend virus, compared with the responses of the control mice. Detailed kinetic and immunohistopathologic analyses suggested that Th cells might be directly involved in the growth inhibition and elimination of virus-infected erythroid precursor cells.

Amino Acid Sequence↗
PubMed1995

Hepatitis C virus core region: helper T cell epitopes recognized by BALB/c and C57BL/6 mice.

In this study, we characterized the B cell and T cell responses to the hydrophilic portion of hepatitis C virus (HCV) core protein in two strains of mice and identified the respective antigen determinants. BALB/c (H-2d) and C57BL/6 (B6:H-2b) mice were immunized by a subcutaneous injection of recombinant HCV core protein together with Freund's complete adjuvant. The level of antibody production, as determined by ELISA, was consistently higher in BALB/c than in B6 mice. However, antibodies in sera from each strain bound to the N-terminal region of the core protein within amino acids 1 to 28 (MSTNPKPQRKIKRNTNRRPQDVKFPGGG), according to an experiment using non-overlapping peptides that covered the hydrophilic portion of HCV core protein. The T cell responses were also higher in BALB/c than in B6 mice with respect to the proliferative responses of the draining lymph node cells in vitro. By limiting dilution cultures of the draining lymph node cells in vitro repetitively stimulated with recombinant core protein, T cell clones were established from both strains of mice and characterized. The surface markers of these clones were Thy-1.2+, CD3+, TCR alpha beta+, CD4+ and CD8+. The proliferative responses were inhibited in the presence of anti-CD4 or anti-MHC class II monoclonal antibodies. The T cell lines in BALB/c mice recognized an epitope in HCV core at amino acids 72 to 91 (EGRAWAQPGYPWPLYGNEGL). The T cell lines in B6 mice recognized an epitope at amino acids 55 to 74 (RPQPRGRRQPIPKARQPEGR). Thus, mice with different MHC haplotypes recognized different non-overlapping T cell antigenic determinants of HCV core proteins.

Amino Acid Sequence↗
PubMed1995

Effect of parent genetic background on latency and antigenicity of UV-induced tumors originating in F1 hybrids.

Wide variations in susceptibility to skin tumor development by chronic ultraviolet light (UV) exposure and antigenicity of induced tumors which is estimated by tumor rejection in syngeneic recipients have been recognized among various murine strains. To examine the effect of parent genetic background on latency and antigenicity of UV-induced tumors originating in F1 hybrids, we induced skin tumors in three mouse strains: BALB/c, C57BL/6, (B6), and C3H/HeMs (C3H/He), and their F1 hybrids: (BALB/c x C3H/He)F1 (CC3F1), (BALB/c x B6)F1 (CB6F1) and (C3H/HexB6)F1 (C3B6F1) by exposing mice to UV radiation (0.44 mW/cm2 for 1 h) three times a week, and analyzed whether the UV-induced tumors originating in F1 hybrids possess the similar property in latency or antigenicity as seen in the UV-induced tumors derived from the parent strains. The latency of tumor induction by chronic UV exposure in C3H/He, BALB/c and their F1 hybrid CC3F1 was relatively short whereas that of B6 was relatively long, and that of F1 hybrids with B6 (CB6F1 and C3B6F1) was intermediate. On the other hand, the low antigenicity as progressive growth behavior of UV-induced tumors in syngeneic recipients was observed not only in tumors derived from C3H/He but also in those from F1 hybrids with C3H/He (C3B6F1 and CC3F1) whereas most tumors derived from B6, BALB/c and their F1 hybrid CB6F1 were highly antigenic as to be rejected in syngeneic recipients. These findings suggest that the parent genetic quality regulating the susceptibility to tumor induction by chronic UV exposure is co-dominantly inherited into F1 hybrids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A single retroviral gag precursor signal peptide recognized by FBL-3 tumor-specific cytotoxic T lymphocytes.

Several dominant T-cell receptors of cytotoxic T-lymphocyte (CTL) clones specific for FBL-3 tumor antigen were clonally amplified in mixed lymphocyte tumor cell cultures derived from an individual immune mouse. Every CTL clone analyzed had a common specificity for a single epitope in the precursor to cell membrane-associated nonstructural gag-encoded protein, Pr75gag, which can be minimally identified by nine amino acid residues, SIVLCCLCL. This epitope is located within the hydrophobic signal sequence motif that mediates translocation of the protein into the endoplasmic reticulum. These novel observations suggest that expression of Pr75gag in FBL-3 tumor cells led to the amplification of CTLs which recognize the signal sequence of the nonstructural gag-encoded glycoprotein precursor.

Amino Acid Sequence↗
PubMed1995

[Abnormality of CD4 molecule--OKT4 epitope deficiency].

The individuals with OKT4 epitope deficiency are identified as incomplete (heterozygote carriers) and complete (homozygotes) by the difference in the number of OKT4 epitopes on the surface of lymphocytes. The incidence of homozygotes in the Japanese population was found to be 0.47% by examination of 1,478 random samples, and on the basis of this value, the incidence of heterozygotes was estimated to be 12.8% by the Hardy-Weinberg's formula. This deficiency was transmitted as an autosomal codominant trait. DNA from the lymphocytes with complete OKT4 epitope deficiency from the members of three families was sequenced, and a single nucleotide base substitution (CGG-->TGG) was found. This mutation was confirmed to be responsible for OKT4 epitope deficiency by using the mouse L cells transfected with mutant CD4 cDNA. The mutation results in arginine being replaced by tryptophan. Analysis showed different hydrophobicity at positions 239 and 240 from the control, probably giving rise to a conformational change in CD4 accounting for lack of reactivity with the OKT4 monoclonal antibody. The lymphocytes with OKT4 epitope deficiency did not show any abnormality in their susceptibility to HIV infection, the internalization of CD4 molecules by TPA-treatment, the capability of producing IL-2 in vitro, and the expression of IL-2 receptors (alpha/beta-chain) by PHA-stimulation.

CD4 Antigens↗
PubMed1994

Immunological characterization of tumor-rejection antigens on ultraviolet-light-induced tumors originating in the CB6F1 mouse.

Six ultraviolet-light(UV)-induced tumors of (BALB/c x C57BL/6)F1 (H-2d/b) mouse origin were analyzed for the effector T cell subsets involved in tumor rejection, the MHC class I to which cytolytic T lymphocytes (CTL) are restricted, and the effect of UV radiation on tumor rejection, to characterize their tumor-rejection antigens (TRA) recognized by CTL. All tumors were rejected in syngeneic normal mice but grew progressively in nude mice. CD8+ T cells mediated the antitumor responses for all tumors and CD4+ T cells could also do so for one tumor 6.1B. Each tumor induced potent CTL that recognized the specific TRA in preferential association with MHC class I haplotypes not from H-2b but from H-2d; that is, Kd, Dd or Ld. Profiles of TRA expression on two tumors were obtained by the analyses of their antigen-loss variants. Female 1A codominantly expressed at least four distinct TRA associated with Kd, all of which induced CTL. On the other hand, UV male 1 had at least two distinct TRA, one of which, associated with Kd, exclusively induced CTL. However, in the absence of the dominant TRA, another TRA associated with Ld on R95C, a variant of UV male, 1, induced CTL. Unlike other tumors, R95C grew progressively in short-term-UV-irradiated syngeneic mice. Nude mice reconstituted with a combination of CD4+ T cells from short-term-UV-irradiated mice and CD8+ T cells from normal mice did not reject R95C. An increase in the former T cell population led the reconstituted mice to reject the tumor. These findings suggest some functional defects of CD4+ T cells rather than the generation of suppressor cells in short-term-UV-irradiated mice. The UV-induced tumors used in the present study provide a unique system for analyzing the preferential sorting of TRA as well as for elucidation of the TRA itself.

Animals↗
PubMed1994

The role of CD4+ and CD8+ cells in normal F1 hybrid host in the resistance to lethal graft-versus-host disease induction by transfer of parent spleen cells.

Transfer of a certain number of C57BL/6 (B6) spleen cells into (BALB/cxB6)F1 (CB6F1) nu/nu mice, which are deficient in T cells, causes lethal graft-versus-host disease (GVHD) in the recipients. However, when normal CB6F1 mice are used as recipients, lethal GVHD does not occur. Using this lethal GVHD system, we investigated which roles CD4+ and CD8+ T cells play in the resistance to lethal GVHD induction by parent cell transfer in the normal F1 hybrid host. Lethal GVHD induction by B6 spleen cells in CB6F1 nu/nu mice was blocked by prior reconstitution of the recipients with normal syngeneic spleen cells. In addition, all nu/nu mice reconstituted with syngeneic CD8+ spleen cells developed lethal GVHD, whereas none of the nu/nu mice reconstituted with CD4+ cells did. Both spleen weight and number of spleen cells in the former prominently decreased in contrast to the slight increase (peak at 15 weeks) seen in the latter after transfer of donor spleen cells. H-2Dd- Thy1.2+ cells, which are considered to derive from donor B6 T cells, existed in the spleen from the CD4+ spleen cell-reconstituted GVHD mice, peaking at 5 weeks then gradually decreasing after transfer of donor cells. However, they disappeared in the normal spleen cell-reconstituted GVHD mice 5 weeks later. These findings suggest that CD4+ cells in the normal F1 hybrid host play a critical role in the resistance to lethal GVHD induction by parent spleen cell transfer, although CD8+ cells are required for the prompt elimination of donor cells.

Animals↗