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K Tani

Publications and source records attributed to K Tani.

At least 19 recordsLinked to original sources
PubMed2003

Effective transduction and stable transgene expression in human blood cells by a third-generation lentiviral vector.

Difficulty in gene transduction of human blood cells, including hematopoietic stem cells, has hampered the development of gene therapy applications for hematological disorders, encouraging the development and use of new gene delivery systems. In this study, we used a third-generation self-inactivating (SIN) lentiviral vector system based on human immunodeficiency virus type 1 (HIV-1) to improve transduction efficiency and prevent vector-related toxicity. The transduction efficiency of the HIV-1-based vector was compared directly with the Moloney murine leukemia virus (MLV) SIN vector in human leukemia cell lines. Initial transduction efficiencies were almost 100% for the HIV and less than 50% for the MLV vectors. Similar results were observed in 11 types of primary cells obtained from leukemia or myeloma patients. Transgene expression persisted for 8 weeks in cells transduced with the HIV vector, but declined with the MLV vector. In addition, resting peripheral blood lymphocytes and CD34(+) hematopoietic cells were transduced successfully with the HIV vector, but not with the MLV vector. Finally, we confirmed vector gene integration in almost all colony-forming cells transduced with the HIV vector, but not with the MLV vector. In conclusion, this lentiviral vector is an excellent gene transduction system for human blood cells because of its high gene transduction and host chromosome integration efficiency.

Cells, Cultured↗
PubMed2003

Development of multicolour digital image analysis system to enumerate actively respiring bacteria in natural river water.

AIMS: To develop a rapid and simple method for the assessment of metabolic activity of bacteria in natural environment. METHODS AND RESULTS: A rapid and simple multicolour digital image analysis system for enumerating viable bacteria based on active fluorescent staining has been developed. This system can accurately differentiate actively respiring bacteria and non-respiring bacteria by distinctive colour information in the digital image captured by an epifluorescence microscope equipped with low magnification objective lens. An algorithm to distinguish bacteria from considerable detritus, which produced bright fluorescence in different colours, by colour segmentation has also been developed. This system was applied to river water samples, and the total and respiratory active bacterial counts by digital image analysis were highly related to those by epifluorescence microscopy (r2 = 0.96 and 0.93, respectively). CONCLUSION: This system allowed the rapid and simple differentiation of bacteria from detritus and concurrent assessment of their metabolic activity, with results being available within 1 h. SIGNIFICANCE AND IMPACT OF THE STUDY: The low magnification image analysis allows more rapid and simple quantification of bacteria and could considerably decrease image data amount and acquisition time. This system could be easily applied to the rapid analysis of microbes in various environments.

Algorithms↗
PubMed2002

Acute disseminated encephalomyelitis (ADEM) after allogeneic bone marrow transplantation for acute myeloid leukemia.

Acute disseminated encephalomyelitis (ADEM) is a rare inflammatory demyelinating disease of the central nervous system. We describe here a patient who developed ADEM after allogeneic bone marrow transplantation (BMT). A 48-year-old woman with acute myeloid leukemia (M2) underwent allogeneic BMT from her HLA-identical sister. Cyclosporin for prophylaxis of acute graft-versus-host disease (GVHD) was discontinued from day 15 because of its toxicity. She was relatively well after the resolution of cytomegalovirus reactivation and chronic GVHD. Nine months after BMT, she suddenly developed diplopia, dysarthria, and gait disturbance. Computed tomography of the brain at that time revealed no abnormal findings. Leukemia recurrence was not revealed. The neurological symptoms were very mild without further deterioration. Her clinical course was carefully watched without therapy. Two weeks after onset, fluid attenuated inversion recovery magnetic resonance imaging (MRI) revealed multifocal abnormal high-signal intensity mainly in the white matter of the cerebrum as well as in the cerebellum and brainstem. Cerebrospinal fluid examination showed no abnormal findings. No laboratory findings suggested the presence of infectious agents. The typical MRI findings and an acute monophasic clinical course of this patient led to a diagnosis of ADEM. Twelve weeks after onset, the symptoms had almost resolved. Follow-up MRI showed a substantial improvement of the previous lesions without any new lesions. The symptoms had completely resolved 5 months after onset. This is a rare case of ADEM developing after allogeneic BMT.

Acute Disease↗
PubMed2002

Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis.

The brain-specific angiogenesis inhibitor 1 gene has been isolated in an attempt to find fragments with p53 "functional" binding sites. As reported herein and by others, brain-specific angiogenesis inhibitor 1 expression is present in some normal tissues, but is reduced or lost in tumour tissues. Such data and its particular structure prompted the hypothesis that brain-specific angiogenesis inhibitor 1 may act as a mediator in the local angiogenesis balance. We herein demonstrate that brain-specific angiogenesis inhibitor 1 over-expression suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice. The inhibitory effect of brain-specific angiogenesis inhibitor 1 was documented using our intravital microscopy system, strongly implicating brain-specific angiogenesis inhibitor 1 as a mediator in the control of tumour angiogenesis. In contrast, in vitro tumour cell proliferation was not inhibited by brain-specific angiogenesis inhibitor 1 transfection, whereas some level of cytotoxicity was assessed for endothelial cells. Immunohistochemical analysis of tumour samples confirmed a reduction in the microvessel density index in brain-specific angiogenesis inhibitor 1-overexpressing tumours. At messenger level, moderate changes could be detected, involving the down-regulation of vascular endothelial growth factor and collagenase-1 expression. Furthermore, brain-specific angiogenesis inhibitor 1 expression that was lost in a selection of human cancer cell lines could be restored by wild-type p53 adenoviral transfection. Brain-specific angiogenesis inhibitor 1 should be considered for gene therapy and development of efficient drugs based on endogenous antiangiogenic molecules.

Adenocarcinoma↗
PubMed2002

Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim.

We performed stem cell rescue and allogeneic skin transplantation on a lethally neutron-irradiated nuclear accident victim. HLA-DRB1 mismatched unrelated umbilical cord blood cells (2.08 x 10(7)/kg recipient body weight) were transplanted to an 8-10 Gy equivalent neutron-irradiated patient because of a lack of a suitable bone marrow or peripheral blood donor. Pre-transplant conditioning consisted of anti-thymocyte gamma-globulin alone, and GVHD prophylaxis was a combination of cyclosporine (CYA) and methylprednisolone (mPSL). Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoietin (TPO) were concurrently administered after transplantation. The absolute neutrophil count reached 0.5 x 10(9)/l on day 15, the reticulocyte count rose above 1% on day 23, and the platelet count was over 50 x 10(9)/l on day 27, respectively. Cytogenetic studies of blood and marrow showed donor/recipient mixed chimerism. Rapid autologous hematopoietic recovery was recognized after withdrawal of CYA and mPSL. Repeated pathological examinations of the skin revealed no evidence of acute GVHD. Eighty-two days after the irradiation, skin transplantation was performed to treat radiation burns. Almost 90% of the transplanted skin engrafted. Immunological examination after autologous hematopoietic recovery revealed an almost normal T cell count. However, immune functions were severely impaired. The patient died from infectious complication 210 days after the accident.

Adult↗
PubMed2002

Differential graft-versus-leukaemia effect by CD28 and CD40 co-stimulatory blockade after graft-versus-host disease prophylaxis.

Co-stimulatory blockade may be a promising strategy for tolerance induction in transplantation. In allogeneic bone marrow transplantation (BMT) for leukaemia treatment, however, preservation of the graft-versus-leukaemia (GVL) effect is another critical requirement for clinical application. In this study, we have compared the effect on GVL of using CD28 and CD40 co-stimulatory blockades as graft-versus-host disease (GVHD) prophylaxis in a murine allogeneic BMT model with simultaneous transfer of BCL1 leukaemia. Despite the relative improvement of GVHD as assessed by survival and body weight in both treatment regimes, treatment with anti-CD154 moAb clearly diminished the GVL effect, whereas treatment with anti-CD80 and CD86 MoAbs maintained this effect. Although T cell-mediated effector function at 14 days post-BMT assessed by IFNgamma expression and cytotoxicity against host alloantigen was comparable between both co-stimulatory blockades, IL-12 mRNA expression was preferentially reduced by CD40 blockade. Our results suggest the differential involvement of the CD28 and CD40 co-stimulatory pathways in the development of GVHD and GVL effects. CD28 blockade may be a favourable strategy for tolerance induction in leukaemia patients undergoing BMT.

Animals↗
PubMed2002

The skin fungus-induced Th1- and Th2-related cytokine, chemokine and prostaglandin E2 production in peripheral blood mononuclear cells from patients with atopic dermatitis and psoriasis vulgaris.

BACKGROUND: It is suggested that skin fungi may be involved in the development of atopic dermatitis (AD) and psoriasis vulgaris (PV). OBJECTIVE: We studied skin fungus-induced Th1- or Th2-related cytokine, chemokine and prostaglandin E2 (PGE2) secretion in peripheral blood mononuclear cells (PBMC) from patients with AD and PV and normal subjects. METHODS: PBMC were cultured with the extracts of Malassezia furfur (MF), Candida albicans (CA) and Trichophyton rubrum (TR). The cytokine, chemokine and PGE2 amounts in the supernatants were measured by enzyme-linked immunosorbent assays. RESULTS: MF induced IL-4 and macrophage-derived chemokine (MDC) secretion in AD patients, while induced IFN-gamma and interferon-inducible protein of 10 kDa (IP-10) secretion in PV patients, however, did not induce either secretion in normal subjects. CA induced IL-4, MDC, IFN-gamma and IP-10 secretion in AD and PV patients and normal subjects. In AD patients, the magnitude of IL-4 and MDC responses to CA was higher than that to MF. Compared with PV patients and normal subjects, the magnitude of IL-4 and MDC responses to CA was higher while that of IFN-gamma and IP-10 responses to CA was lower in AD patients. TR induced moderate IL-4 and MDC secretion only in AD patients. The three fungi induced higher levels of PGE2 secretion in AD patients than in PV patients and normal subjects. Cyclooxygenase-2 inhibitor NS-398 suppressed PGE2 responses to MF, CA and TR, and partially suppressed IL-4 and MDC responses to MF, CA and TR, while enhanced IFN-gamma and IP-10 responses to CA in AD patients, and these effects of NS-398 were reversed by cyclic AMP analogue. CONCLUSION: AD patients manifest Th2-skewed responses to MF, CA and TR, which may be partially attributable to the enhanced PGE2 responses to these fungi. PV patients manifest Th1-skewed responses to MF.

Adult↗
PubMed2002

Expression of T helper 1 and T helper 2 cytokine mRNAs in freshly isolated peripheral blood mononuclear cells from dogs with atopic dermatitis.

Using reverse transcription-polymerase chain reaction (RT-PCR) and semi-quantitative PCR techniques, mRNA expression for canine interferon (IFN)-gamma, interleukin (IL)-4, IL-5 and IL-10 in freshly isolated peripheral blood mononuclear cells (PBMCs) was examined in dogs with or without atopic dermatitis (AD). The expression of IFN-gamma mRNA in dogs with AD was lower than that in dogs without AD (healthy control). The expression of IL-5 mRNA was higher in dogs with AD than in control dogs, but there were no significant differences in IL-4 mRNA and IL-10 mRNA expression between the groups. The number of circulating eosinophils was higher in dogs with AD than in control dogs, although eosinophilia was found in only one dog with AD. These results suggest that there is a tendency for the PBMCs of atopic dogs to express a type 2 cytokine pattern that is similar to the pattern observed in human AD patients.

Animals↗
PubMed2001

Highly diastereoselective dihydride formation by activation of methanol with IrCl((S)-binap)(PPh3).

Reaction of [IrCl((S)-binap)(PPh3)] ((S)-3) with methanol gave one of the diastereomers of the cis,mer-dihydride, cis,mer-OC-6-44-A-[IrCl(H2)((S)-binap)(PPh3)] ((S)-4a) stereoselectively, the structure of which was determined crystallographically, whereas the reaction of (S)-3 with H2 produced a 1:1 mixture of the diastereomers of the cis,mer-dihydride, (S)-4a and cis,mer-OC-6-44-C-[IrCl(H2)((S)-binap)(PPh3)] ((S)-4b).

Journal Article↗
PubMed2001

Design and synthesis of a highly selective EP2-receptor agonist.

EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.

Alprostadil↗
PubMed2001

Novel centrifugal method for simple and highly efficient adenovirus-mediated green fluorescence protein gene transduction into human monocyte-derived dendritic cells.

Dendritic cells (DC) are professional antigen-presenting cells in the immune system. Gene transduction of DC with tumor-associated antigen (TAA) or other genes that enhance the immune reaction has been considered theoretically useful for DC-based immunotherapy. However, gene transduction of DC generated from human peripheral blood monocytes has been difficult due to its low efficiency, even when adenoviral vector was used at high multiplicity of infection (MOI). In the present study, we examined the effect of centrifugal force to enhance efficiency of adenovirus-mediated gene transduction into human monocyte-derived DC at various rotor speeds at various temperatures for various times. We judged the transduction efficiency using enhanced green fluorescence protein (EGFP)-expressing adenoviral vector, and the best condition for centrifugal transduction was determined as 2000 x g at 37 degrees C for 2 h at an MOI of 10 or greater. At an MOI of 50 without centrifugation, the gene transduction efficiency was about 66% and mean fluorescence intensity (MFI) of EGFP expression was about 150 (at 37 degrees C for 2 h). With centrifugal transduction (2000 x g at an MOI of 50 at 37 degrees C for 2 h), 86% or more DC were gene-modified, and especially, MFI of EGFP expression was highly enhanced (MFI: about 3100 or greater). Centrifugally gene-transduced DC were not damaged and were thoroughly functional as measured by mixed lymphocyte reaction (MLR). The centrifugal method was also applicable to human monocytes and K562 cells. The centrifugal transduction method with adenoviral vector might be helpful for the generation of gene-modified DC.

Adenoviridae↗
PubMed2001

The neutrophil granule protein cathepsin G activates murine T lymphocytes and upregulates antigen-specific IG production in mice.

Cathepsin G is a neutrophil granule derived antimicrobial chymotrypsin-like enzyme. Our previous study showed that cathepsin G induces chemotactic migration of human phagocytic leukocytes and increases random migration of T lymphocytes. In this study, we investigated the capacity of cathepsin G to activate T lymphocytes and to modulate antigen-specific humoral responses in mice. We found that cathepsin G is mitogenic for and induces production of IFN-gamma by murine T cells in vitro. Injection of cathepsin G in BALB/c mice immunized with keyhole limpet hemocyanin (KLH) adsorbed to aluminum hydroxide resulted in a significantly increased production of KLH-specific IgG1 and IgG2a antibodies. There was a dose-dependent increase in KLH-specific proliferation of lymphocytes from draining lymph nodes from mice treated with KLH and cathepsin G when compared with those treated with KLH alone. Subsequent analysis of IFN-gamma and IL-4 release following in vitro re-stimulation of draining lymph node lymphocytes obtained from KLH-immunized mice suggested that cathepsin G augments KLH-specific Ig antibody production via activation of T cells, presumably involving both Th1 and Th2 pathways. Thus, neutrophil granule cathepsin G, in addition to its capacity to kill microbes and to enhance leukocyte motility, activates T lymphocytes and modulates humoral immunity.

Adjuvants, Immunologic↗
PubMed2001

Unusually short distances between the carbonyl oxygen and the tin atom in RCOSMR'3 (M = Ge, Sn, Pb): the importance of intramolecular n(O) --> sigma*(MS) orbital interactions.

[structure: see text]. We found that the C=O.Sn distance in RCOSSnR'3 was shorter than the C=O.Ge distance in RCOSGeR'3 and theoretically confirmed that the orbital interactions between the nonbonding orbitals on the carbonyl oxygen (n(O)) and the sigma*(SnS) orbitals were important in regard to the shortness.

Journal Article↗
PubMed2001

EXAFS study of Sb-Te alloy films.

The local structures of three phases; stable compound Sb2Te3, metastable crystalline c-SbTe and amorphous a-SbTe films having the atomic ratio Sb/Te=3: in Sb-Te system have been studied by EXAFS. The c-SbTe has a partly similar local structure to crystalline Sb2Te3. The a-SbTe film has a local structure of NaCl-type, which is topologically analogous to the crystalline form. The amorphous phase has shorter bond distances 2.86A (around Sb-site) and 2.83A (around Te-site) than the corresponding distances 2.89A and 2.87A in the crystalline phase. This unbalanced bond distances between the Sb-site and Te-site implies that site-disordering occurs. Shortening of bond distances in the amorphous phase is due to the relaxation of locally distorted crystalline structure.

Journal Article↗
PubMed2001

Sb K-edge absorption fine structure of Sb2Te3.

In order to study the local structure of some antimony compounds, Sb K-edge XAFS spectra were measured for Sb2Te3 and InSb. The measurements were performed in the transmission mode at BL-01 of SPring-8. Though crystal structure of antimony telluride Sb2Te3 is known by X-ray diffraction analysis, the EXAFS analyses give controversial result on the Sb-Te distance and the coordination number of Sb2Te3. Comparing the observed XANES spectra for Sb2Te3 with FEFF8 calculation, we can explain the controversial results which are also supported by the observed X-ray powder diffraction.

Journal Article↗
PubMed2001

Multiple scattering approach to K-edge XANES of Sb-Te systems.

The Sb-Te systems are important for optical memories. The local structures of these Sb-Te systems are crucial to understand the properties. Here we study three different Sb-Te systems, Sb2Te3, c- and a-SbTe (c; crystalline, a; amorphous) by use of XANES analyses. The present calculations for Sb2Te3 system show quite good agreement with the observed spectra. In contrast to Sb2Te3 system, both c- and a-SbTe systems, in which a ratio of Sb to Te is 3, are metastable; both of the structures have not been known yet. We thus investigate these local structures by use of the multiple scattering approach, and propose a possible model for each of c- and a-SbTe.

Journal Article↗