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K Okumura

Publications and source records attributed to K Okumura.

At least 19 recordsLinked to original sources
PubMed2007

Correlation in a Gaussian chain with the ends fixed.

We consider an ideal chain whose ends are fixed without fluctuation at different points, possibly by optical tweezers. We derive a two-point probability distribution of a corresponding random walk and explicitly calculate the scattering function. We find that the contour plot of the resulting function shows a kind of normal butterfly pattern, contaminated by wavy texture. These results are compared with some representative previous models.

Biophysics↗
PubMed2006

Resistance of infant leukemia with MLL rearrangement to tumor necrosis factor-related apoptosis-inducing ligand: a possible mechanism for poor sensitivity to antitumor immunity.

Malignant cells generally acquire some immune escape mechanisms for clonal expansion. Immune escape mechanisms also contribute to the failure of graft-versus-leukemia (GVL) effect after allogeneic hematopoietic stem cell transplantation (allo-SCT). Infant leukemias with mixed-lineage leukemia (MLL) rearrangement have a remarkably short latency, and GVL effect after allo-SCT has not been clearly evidenced in these leukemias. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)- and FasL-mediated cytotoxic pathways play important roles in cytotoxic T-lymphocyte- and natural killer cell-mediated antitumor immunity and optimal GVL activity. We investigated the in vitro sensitivity of MLL-rearranged acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML) cells to TRAIL- and FasL-mediated cytotoxicity. Most of cell lines and primary leukemia cells were highly resistant to TRAIL primarily owing to low cell-surface expression of death receptors in ALL and simultaneous expression of decoy receptors in AML. Nearly half of cell lines and majority of primary leukemia cells showed low sensitivity to FasL. These results suggest that resistance to death-inducing ligands, particularly to TRAIL, could be one of the mechanisms for a rapid clonal expansion and a poor sensitivity to the GVL effect in infant leukemias with MLL rearrangement.

Drug Resistance, Neoplasm↗
PubMed2006

Measurement of atmospheric neutrino flux consistent with tau neutrino appearance.

A search for the appearance of tau neutrinos from nu(mu) <--> nu(tau) oscillations in the atmospheric neutrinos has been performed using 1489.2 days of atmospheric neutrino data from the Super-Kamiokande-I experiment. A best fit tau neutrino appearance signal of 138+/-48(stat)-32(+15)(syst) events is obtained with an expectation of 78+/-26(syst). The hypothesis of no tau neutrino appearance is disfavored by 2.4 sigma.

Journal Article↗
PubMed2006

Reactive oxygen species mediate crosstalk between NF-kappaB and JNK.

The activation of NF-kappaB inhibits apoptosis via a mechanism involving upregulation of various antiapoptotic genes, such as cellular FLICE-inhibitory protein (c-FLIP), Bcl-xL, A1/Bfl-1, and X chromosome-liked inhibitor of apoptosis (XIAP). In contrast, the activation of c-Jun N-terminal kinase (JNK) promotes apoptosis in a manner that is dependent on the cell type and the context of the stimulus. Recent studies have indicated that one of the antiapoptotic functions of NF-kappaB is to downregulate JNK activation. Further studies have also revealed that NF-kappaB inhibits JNK activation by suppressing accumulation of reactive oxygen species (ROS). In this review, we will focus on the signaling crosstalk between the NF-kappaB and JNK cascades via ROS.

Animals↗
PubMed2006

Interleukin-12 is involved in the enhancement of human natural killer cell activity by Lactobacillus casei Shirota.

We conducted a placebo-controlled, cross-over trial to examine the effect of Lactobacillus casei Shirota (LcS) on natural killer (NK) cell activity in humans. NK cell activity exhibited a declining trend during the period of placebo ingestion, but NK cell activity increased after intake for 3 weeks of fermented milk containing 4 x 10(10) live LcS. When human peripheral blood mononuclear cells were cultured in the presence of heat-killed LcS, NK cell activity was enhanced. The ability of LcS to enhance NK cell activity and induce interleukin (IL)-12 production was correlated, and the addition of anti-IL-12 monoclonal antibody reduced the enhancement of NK cell activity triggered by LcS. In addition, separation of NK cells from LcS-stimulated monocytes with membrane filter reduced NK cell activity to the intermediate level and almost deprived monocytes of the ability to produce IL-12. These results demonstrate that LcS can enhance NK cell activity in vivo and in vitro in humans, and IL-12 may be responsible for enhancement of NK cell activity triggered by LcS.

Aged↗
PubMed2006

A case of coagulation factor V deficiency caused by compound heterozygous mutations in the factor V gene.

We investigated the molecular basis of a severe factor V (FV) deficiency in a Japanese female, and identified two distinct mutations in the FV gene, a novel cytosine insertion (1943insC) and a previously reported point mutation (A5279G). We expected the patient to be a compound heterozygote for those mutations, as a 1943insC, but not an A5279G, was found in the mother and a sibling. The 1943insC will cause a frame-shift after 590Gln, resulting in amino acid substitutions with two abnormal residues followed by a stop codon in the FV A2 domain (FS592X). The A5279G will cause an amino acid alteration in the FV A3 domain (Y1702C), which has been observed in several ethnic groups. We found that both mutant mRNAs were detected by reverse transcriptase polymerase chain reaction (RT-PCR) in the patient's platelets, whereas no FV antigen and activity were detected in plasma. On the one hand, the RT-PCR signal from the FS592X-FV mutant mRNA was markedly reduced, suggesting that the RNA surveillance system would eliminate most of the abnormal FS592X-FV transcripts with a premature termination. On the other hand, expression analyses revealed that only small amounts of Y1702C-FV with a low specific activity were secreted, and that the FS592X-FV was not detected in cultured media. These data indicated that both mutant FV molecules would be impaired, at least in part, during the post-transcriptional process of protein synthesis and/or in secretion. Taken together, it seems to suggest that each gene mutation could be separately responsible for severe FV deficiency, while this phenotype is due to the in-trans combination of the two defects.

Adult↗
PubMed2006

Imprinting disruption of the CDKN1C/KCNQ1OT1 domain: the molecular mechanisms causing Beckwith-Wiedemann syndrome and cancer.

Human chromosomal region 11p15.5, which is homologous to mouse chromosome region 7F5, is a well-known imprinted region. The CDKN1C/KCNQ1OT1 imprinted domain, which is one of two imprinted domains at 11p15.5, includes nine imprinted genes regulated by an imprinting center (IC). The CDKN1C/KCNQ1OT1 IC is a differentially methylated region of KCNQ1OT1(KCNQ1OT-DMR) with DNA methylation on the maternal allele and no methylation on the paternal allele. CDKN1C (alias p57KIP2), an imprinted gene with maternal expression, encoding a cyclin-dependent kinase inhibitor, is a critical gene within the CDKN1C/KCNQ1OT1 domain. In Beckwith-Wiedemann syndrome (BWS), approximately 50% of patients show loss of DNA methylation accompanied by loss of histone H3 Lys9 dimethylation on maternal KCNQ1OT-DMR, namely an imprinting disruption, leading to diminished expression of CDKN1C. In cancer, at least three molecular mechanisms--imprinting disruption, aberrant DNA methylations at the CDKN1C promoter, and loss of heterozygosity (LOH) of the maternal allele--are seen and all three result in diminished expression of CDKN1C. Imprinting disruption of the CDKN1C/KCNQ1OT1 domain is involved in the development of both BWS and cancer and it changes the maternal epigenotype to the paternal type, leading to diminished CDKN1C expression. In this review, we describe recent advances in epigenetic control of the CDKN1C/KCNQ1OT1 imprinted domain in both humans and mice.

Animals↗
PubMed2005

Effects of cilostazol on lipid and fatty acid metabolism.

Cilostazol is a selective inhibitor of phosphodiesterase III with anti-platelet-aggregatory and vasodilating properties. Randomised, double-blind, placebo-controlled trials in 2702 patients with intermittent claudication demonstrated that cilostazol significantly increased walking distances compared with placebo. Furthermore, the agent has beneficial effects on the serum lipid profile and fatty acid composition in plasma. Consequently, cilostazol may be useful to prevent atherosclerosis from progressing by ameliorating lipid and fatty acid metabolism.

Aged↗
PubMed2005

Various costimulatory pathways are essential for induction of regulatory cells by intratracheal delivery of alloantigen.

BACKGROUND: We previously reported that intratracheal delivery of alloantigen induced regulatory cells in a mouse heart transplantation model. We investigated the roles of costimulatory pathways in the induction of regulatory cells by intratracheal delivery of alloantigen. METHODS: CBA (H-2k) mice were pretreated with intratracheal delivery of splenocytes (1 x 10(7)) from C57BL/10 (H-2b) mice and administration of monoclonal antibodies (mAb) specific for programmed death (PD)-1 and its ligands, programmed death-ligand (PD-L)1 and PD-L2, CD70, CD134 ligand (CD134L), CD153, CD137L, or receptor activator of nuclear factor-kappaB (NF-kappaB) (RANK). Seven days later, naive CBA mice underwent adoptive transfer of splenocytes (5 x 10(7)) from the pretreated CBA mice and transplantation of C57BL/10 heart. RESULTS: Adoptive transfer of splenocytes from CBA mice that had been pretreated with intratracheal delivery of C57BL/10 splenocytes significantly prolonged the survival of C57BL/10 allograft (median survival time [MST], 68 days) as compared with adoptive transfer from untreated CBA mice (MST, 12 days). Concomitant administration of control immunoglobulin (Ig)G, anti-PD-L2 mAb, or anti-CD137L along with intratracheal delivery did not significantly affect the prolongation (MST, 72, 68, and 65 days, respectively). In contrast, anti-PD-1, anti-PD-L1, anti-CD70, anti-CD134L, anti-CD153, or anti-RANK mAb abrogated the prolongation induced by adoptive transfer from the pretreated mice with intratracheal delivery (MST, 18, 17, 16, 14, 10, and 18 days, respectively). CONCLUSION: The PD-1/PD-L1, CD27/CD70, CD134/CD134L, CD30/CD153, and tumor necrosis factor (TNF)-related activation-induced cytokine (TRANCE)/RANK interactions are independently required for generation of regulatory cells by intratracheal delivery of alloantigen.

Adoptive Transfer↗
PubMed2005

CDK5 regulates cell-cell and cell-matrix adhesion in human keratinocytes.

BACKGROUND: CDK5 is a member of proline-directed serine/threonine kinases. Although its cDNA was originally cloned as a homologue to those for the other members of the cyclin-dependent kinase (CDK) family, CDK5 has been shown to function differently from other CDKs. CDK5 is activated by non-cyclin partners, p35 and p39, and important during brain development by influencing adhesion, migration and differentiation of neurones. OBJECTIVES: We sought to investigate the expression and functions of CDK5 in human keratinocytes. METHODS: Expression of CDK5/p35, interaction of CDK5/p35 with adhesion molecules, and its roles in cell-cell and cell-matrix adhesion were studied by reverse transcriptase-polymerase chain reaction, immunoblotting and aggregation/adhesion assays in primary cultured normal human keratinocytes from infant foreskins and a human keratinocyte HaCaT cell line. Localization of CDK5 and p35 in normal human epidermis and psoriatic epidermis was studied by immunohistochemistry. RESULTS: Both CDK5 and p35 were expressed in primary cultured keratinocytes, HaCaT cells and normal human epidermis. Roscovitine, an inhibitor of CDK5, enhanced Ca2+-dependent (cadherin-dependent) aggregation of HaCaT cells whereas it inhibited adhesion of HaCaT cells to fibronectin associated with reduced active states of beta1 integrin. Interestingly, psoriatic skin showed reduced CDK5 and p35 expression in the lower half of the epidermis, which might be associated with decreased amount of activated beta1 integrin in the epidermis of psoriatic skin. CONCLUSIONS: CDK5/p35 may be involved in cell-cell and cell-matrix adhesion in human keratinocytes by differently regulating cadherins and integrins. Furthermore, reduced expression of CDK5/p35 in the epidermis might be involved in the pathogenesis of psoriasis.

Calcium↗
PubMed2005

Clinicostatistical study of carotid calcification on panoramic radiographs.

OBJECTIVE: The purpose was to evaluate carotid calcifications on panoramic radiographs, and relate to risk factors for vascular diseases. METHOD: Between 1997 and 2001, 2568 radiographs were retrospectively collected from new patients at Mie University Hospital whose ages ranged from 50 to 70 years. The mean age of the subjects was 62.2 years (men 61.9 years, women 62.3 years). Medical and social data were collected from case notes, and body weight, height, and age of menopause confirmed by telephone interviews. RESULT: About 106 carotid calcifications were found on the panoramic radiographs of 26 males and 80 females. The ratio of males to females was 1:3.07. The subjects with carotid calcifications had medical histories that included hypertension (27.6%), obesity (21.1%), hyperlipidemia (14.5%), and cardiovascular diseases (13.2%), all with recognized risk factors for atheromas. Of 76 patients who responded to follow up interviews, two (2.63%) died from cardiovascular stroke during an average follow up of 2.43 years. CONCLUSIONS: The results show carotid calcifications detected on panoramic radiographs can be used to help predict vascular strokes in patients. In cases where calcified carotid artery atheromas are detected, the dentist or oral and maxillofacial surgeon should refer the patient to a specialized physician.

Aged↗
PubMed2004

Evidence for an oscillatory signature in atmospheric neutrino oscillations.

Muon neutrino disappearance probability as a function of neutrino flight length L over neutrino energy E was studied. A dip in the L/E distribution was observed in the data, as predicted from the sinusoidal flavor transition probability of neutrino oscillation. The observed L/E distribution constrained nu(micro)<-->nu(tau) neutrino oscillation parameters; 1.9x10(-3) 0.90 at 90% confidence level.

Journal Article↗
PubMed2004

Blockade of 4-1BB (CD137)/4-1BB ligand interactions increases allograft survival.

We investigated the role of 4-1BB, a T cell co-stimulatory molecule, in alloimmune responses. In vivo mixed lymphocyte reactions showed that 4-1BB was preferentially expressed on actively dividing CD4(+) and CD8(+) T cells. Furthermore, following alloantigen challenge, the draining lymph nodes contained subpopulations of 4-1BB-expressing CD4(+) and CD8(+) T cells. 4-1BB-deficient C57BL/6 mice showed a delayed rejection of cardiac transplants mismatched for the major histocompatibility complex. Longer transplant survival was induced by blockade of 4-1BB/4-1BB ligand (4-1BBL) interactions using an anti-4-1BBL monoclonal antibody. Histological analysis showed that prolonged transplant survival in the 4-1BB-deficient and anti-4-1BBL-treated mice correlated with reduced lymphocytic infiltration and vasculitis in the donor heart tissue. Taken together, our data suggest that blockade of 4-1BB/4-1BBL interactions inhibited the expansion of alloreactive T cells and reduced CTL activity against host alloantigen, which in turn resulted in the prolongation of allograft survival. Blockade of the 4-1BB co-stimulatory pathway may be useful for preventing allograft rejection.

4-1BB Ligand↗
PubMed2004

Effects of near-infrared irradiation to stellate ganglion in glossodynia.

OBJECTIVE: This study was designed to assess the effect of stellate ganglion near-infrared irradiation (SGR) on glossodynia and the mechanism of action. STUDY DESIGN: Thirty-seven patients with glossodynia received SGR once weekly for 4 weeks. The response to treatment was evaluated on the basis of the change in pain intensity, assessed with a visual analogue scale (VAS) before and after 4 weeks of treatment. The temperature and blood flow of the tongue were also measured before and after first SGR. As control, eight healthy subjects were studied. RESULTS: Tongue pain as assessed by the VAS decreased in 28 of the 37 patients (75.7%). Mean pain intensity decreased significantly from 5.1 +/- 2.2 to 1.9 +/- 2.1 (P < 0.05). Tongue blood flow at rest in the patients with glossodynia [7.2 +/- 1.6 ml min(-1) (100 g)(-1)] was significantly lower than that in the healthy subjects [7.8 +/- 0.23 ml min(-1) (100 g)(-1)]. Five minutes after SGR, the temperature of the tongue rose 1.5 +/- 0.21 degrees C, and blood flow increased to 8.5 +/- 1.2 ml min(-1) (100 g)(-1). Tongue blood flow (at rest) after 4 weeks of SGR had increased to 7.7 +/- 1.1 ml min(-1) (100 g)(-1). CONCLUSION: SGR is an effective treatment for glossodynia. The mechanism by which SGR improves symptoms associated with glossodynia is thought to be as follows: SGR inhibits abnormally increased sympathetic activity associated with glossodynia. This is followed by normalization of decreased tongue blood flow, thereby alleviating pain.

Aged↗
PubMed2004

Reproducibility of nifedipine absorption from GITS tablets: comparison of single-dose pharmacokinetics using 10, 20, 40 and 60 mg nifedipine.

OBJECTIVE: To examine the reproducibility of nifedipine absorption from gastrointestinal therapeutic system (GITS) tablets by comparing the single-dose pharmacokinetic profiles of 4 different dosages administered orally. METHODS: Twelve healthy male volunteers, aged between 22 and 29 years were enrolled in the open, 4-way, dose escalation study with single oral doses of 10, 20, 40 and 60 mg (two 30 mg) nifedipine GITS tablets. Each administration was separated by a 1-week washout period. Coefficients of variation (CV) of dose-corrected area under the concentration-time curve (AUC) and peak plasma drug concentrations (Cmax) were calculated from the pharmacokinetic profiles. RESULTS: Mean AUC and mean Cmax were dose-proportional from 10 to 60 mg. Although the CV of 4 mean dose-corrected AUC and Cmax were 5.5% and 17.5%, respectively, CV of dose-corrected AUC and Cmax in each subject varied from 5.1 to 37.4% (mean 11.0%) and from 14.1% to 46.4% (mean 25.8%), respectively. CONCLUSIONS: Whereas mean plasma nifedipine concentration remained markedly stable over a 16- to 24-hour interval and mean dose-corrected AUC showed good reproducibility with nifedipine GITS, the CV of dose-corrected AUC of the nifedipine GITS tablets in each subject showed large variability.

Administration, Oral↗
PubMed2003

Therapeutic effect of anti-OX40L and anti-TNF-alpha MAbs in a murine model of chronic colitis.

Interaction of OX40 (CD134) on T cells with its ligand (OX40L) on antigen-presenting cells has been implicated in pathogenic T cell activation. This study was performed to explore the involvement of OX40/OX40L in the development of T cell-mediated chronic colitis. We evaluated both the preventive and therapeutic effects of neutralizing anti-OX40L MAb on the development of chronic colitis in SCID mice induced by adoptive transfer of CD4(+)CD45RB(high) T cells as an animal model of Crohn's disease. We also assessed the combination of anti-OX40L and anti-TNF-alpha MAbs to improve the therapeutic effect. Administration of anti-OX40L MAb markedly ameliorated the clinical and histopathological disease in preventive and therapeutic protocols. In vivo treatment with anti-OX40L MAb decreased CD4(+) T cell infiltration in the colon and suppressed IFN-gamma, IL-2, and TNF-alpha production by lamina propria CD4(+) T cells. The combination with anti-TNF-alpha MAb further improved the therapeutic effect by abolishing IFN-gamma, IL-2, and TNF-alpha production by lamina propria CD4(+) T cells. Our present results suggested a pivotal role of OX40/OX40L in the pathogenesis of T cell-mediated chronic colitis. The OX40L blockade, especially in combination with the TNF-alpha blockade, may be a promising strategy for therapeutic intervention of Crohn's disease.

Animals↗
PubMed2003

Monocyte chemoattractant protein (MCP)-1 production via functionally reconstituted Fcalpha receptor (CD89) on glomerular mesangial cells.

BACKGROUND: Fc alpha receptor (FcalphaR; CD89) is the receptor for Fc portion of IgA in various cells, and displays various immunological responses on binding. It is important to analyze the mesangial functions via FcalphaR in the pathogenesis of IgA nephropathy. However, it is still controversial whether FcalphaR is expressed on mesangial cells. To assess biological functions of FcalphaR on the mesangial cells, we established mesangial transfectants that expressed FcalphaR with or without FcRgamma chain that is a common signaling molecule of FcRs. The production of monocyte chemoattractant protein-1 (MCP-1) by mesangial cells is known to contribute to cellular infiltration into glomeruli and subsequent glomerular injuries. METHODS: Murine mesangial cell lines (SV40 MES 13) were transfected with cDNA of the human FcalphaR. Furthermore, we co-transfected some of the FcalphaR transfectants with cDNA of human FcRgamma chain. The tyrosine phosphorylation of the intra-mesangial proteins after FcalphaR cross-linking was examined by immunoprecipitation. MCP-1 production from each transfectant stimulated with heat aggregated IgA was determined by sandwich ELISA. RESULTS: Two kinds of mesangial transfectants stably expressed human FcalphaR with or without FcRgamma chain (FcalphaR(+), FcalphaR(+)/gamma(+)). Phosphorylation of FcRgamma chain and syk kinase was detected in FcalphaR(+) and FcalphaR(+)/gamma(+) cells, but not in untransfected cells. Aggregated IgA induced significantly higher MCP-1 production in FcalphaR(+)/gamma(+) than those in FcalphaR(+) or untransfected control. CONCLUSIONS: Present study demonstrated that FcalphaR and FcRgamma chain could be reconstituted in mesangial cells and mediated MCP-1 production by aggregated IgA in a dose-dependent manner. Current data would argue that FcalphaR can be activated in mesangial cells through their own machinery, although underlying mechanisms for FcalphaR induction in mesangial cells remain unclear.

Animals↗