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K Takeda

Publications and source records attributed to K Takeda.

At least 127 records · Page 7Linked to original sources
PubMed2001

Fission yeast living mitosis visualized by GFP-tagged gene products.

The fission yeast Schizosaccharomyces pombe has been used as a model organism to study cell cycle control and dynamic chromosome behavior during anaphase segregation as genetic and cytological approaches are easily amenable. To understand the role of gene products involved in these cellular events, it is important to determine intracellular localization of each gene product during the cell cycle. In this article, visualization in living cells of several gene products involved in cell cycle control and sister chromatid separation is described. The genes tagged with jellyfish green fluorescent protein (GFP) include sad1(+) (encoding a spindle pole body (SPB) protein), atb2(+) (alpha-tubulin), mis6(+) (a kinetochore protein), eat1(+) (a novel actin-like protein localized in the nucleus) and cdc13(+) (a mitotic cyclin). In addition, LacI which is bound to a DNA segment containing LacO repeat sequences integrated near the centromere (cen1) is visualized. These are useful to monitor cell cycle events in living cells.

Cell Cycle↗
PubMed2001

Treatment of chronic aortic dissection by transluminal endovascular stent-graft placement: preliminary results.

PURPOSE: To investigate efficacy of stent-graft repair for the treatment of patients with chronic aortic dissection. MATERIALS AND METHODS: Fifteen patients with chronic aortic dissection were treated with endovascular stent-grafts. Entry tears were located in the descending thoracic aorta in all patients. The mean maximum diameter of the descending thoracic aorta was 47 mm +/- 8. The mean diameter of the true lumen at the same level was 20 mm +/- 5. The mean interval between diagnosis and stent-graft procedure was 32 months +/- 91. Stent-grafts were fabricated from expanded polytetrafluoroethylene and Z-stents. RESULTS: Stent-grafts were placed successfully in all patients. Two stent-grafts were required in one patient. Entry closure and thrombosis of the false lumen of the descending thoracic aorta were also achieved in all patients. No procedure-related complications were observed except for postimplantation syndrome, including fever and leukocytosis. The diameter of the true lumen was significantly increased (mean, 31 mm +/- 6) at the level of the descending thoracic aorta (P <.01) and the diameter of the aorta was significantly decreased (mean, 44 mm +/- 8) at the same level (P <.01). There were no deaths and no instances of aortic rupture during the subsequent average follow-up period of 24 months. Secondary stent-graft procedures were required to treat the abdominal component of dissection during follow-up in one patient. CONCLUSIONS: Stent-graft repair of chronic aortic dissection is a safe and effective method and may be an alternative to surgical graft replacement in selected patients. However, further evaluation is mandatory before this method is widely employed.

Adult↗
PubMed2001

Malignant portal venous obstructions treated by stent placement: significant factors affecting patency.

PURPOSE: To identify factors affecting stent occlusion after stent placement in the portal vein in patients with malignant portal vein invasion. MATERIALS AND METHODS: Forty patients were studied. Twenty-three patients had hepatocellular carcinoma, nine patients had pancreatic cancer, and eight patients had bile duct cancer. Stents were placed in the portal venous system across stenotic (n = 28) or obstructive (n = 12) lesions after percutaneous transhepatic portography. Bare stents were used in 33 patients and covered stents were used in seven patients. Twenty-two variables were analyzed with use of univariate and multivariate analyses to identify significant factors affecting stent occlusion. RESULTS: Stents remained patent during a mean follow-up period of 11.9 months (range, 2-61 mo) in 60% of the patients. Stent occlusion was found in 40% of the patients, with a mean period until occlusion of 3.7 months (range, 0.2-16 mo). In the univariate analysis, the following five factors were significantly associated with a higher probability of stent occlusion: (i) splanchnic vein involvement, (ii) Child-Pugh class C, (iii) obstruction of the portal venous system, (iv) pancreatic cancer, and (v) lack of anticancer treatment after stent placement. In the multivariate analysis, the first three factors were found to have independent value for stent occlusion. CONCLUSIONS: Splanchnic vein involvement, severe hepatic dysfunction, and obstruction of the portal venous system are the most important factors affecting stent occlusion in patients with malignant portal vein invasion.

Adult↗
PubMed2001

Involvement of tumor necrosis factor-related apoptosis-inducing ligand in surveillance of tumor metastasis by liver natural killer cells.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in various tumor cells in vitro, but its physiological role in tumor surveillance remains unknown. Here, we report that TRAIL is constitutively expressed on murine natural killer (NK) cells in the liver and plays a substantial role in suppressing tumor metastasis. Freshly isolated NK cells, but not natural killer T cells or ordinary T cells, from the liver expressed cell surface TRAIL, which was responsible for spontaneous cytotoxicity against TRAIL-sensitive tumor cells in vitro along with perforin and Fas ligand (FasL). Administration of neutralizing monoclonal antibody against TRAIL significantly increased experimental liver metastases of several TRAIL-sensitive tumor cell lines. Such an anti-metastatic effect of TRAIL was not observed in NK cell-depleted mice or interferon-gamma-deficient mice, the latter of which lacked TRAIL on liver NK cells. These findings provide the first evidence for the physiological function of TRAIL as a tumor suppressor.

Animals↗
PubMed2001

Toll-like receptors: critical proteins linking innate and acquired immunity.

Recognition of pathogens is mediated by a set of germline-encoded receptors that are referred to as pattern-recognition receptors (PRRs). These receptors recognize conserved molecular patterns (pathogen-associated molecular patterns), which are shared by large groups of microorganisms. Toll-like receptors (TLRs) function as the PRRs in mammals and play an essential role in the recognition of microbial components. The TLRs may also recognize endogenous ligands induced during the inflammatory response. Similar cytoplasmic domains allow TLRs to use the same signaling molecules used by the interleukin 1 receptors (IL-1Rs): these include MyD88, IL-1R--associated protein kinase and tumor necrosis factor receptor--activated factor 6. However, evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.

Animals↗
PubMed2001

Toll-like receptors control activation of adaptive immune responses.

Mechanisms that control the activation of antigen-specific immune responses in vivo are poorly understood. It has been suggested that the initiation of adaptive immune responses is controlled by innate immune recognition. Mammalian Toll-like receptors play an essential role in innate immunity by recognizing conserved pathogen-associated molecular patterns and initiating the activation of NF-kappaB and other signaling pathways through the adapter protein, MyD88. Here we show that MyD88-deficient mice have a profound defect in the activation of antigen-specific T helper type 1 (TH1) but not TH2 immune responses. These results suggest that distinct pathways of the innate immune system control activation of the two effector arms of adaptive immunity.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Microphthalmia-associated transcription factor (MITF): multiplicity in structure, function, and regulation.

Microphthalmia-associated transcription factor (MITF) regulates the differentiation and development of melanocytes and retinal pigment epithelium and is also responsible for pigment cell-specific transcription of the melanogenesis enzyme genes. Heterozygous mutations in the MITF gene cause auditory-pigmentary syndromes. MITF consists of at least five isoforms, MITF-A, MITF-B, MITF-C, MITF-H, and MITF-M, differing at their N-termini and expression patterns. Here we show a remarkable similarity between the N-terminal domain of MITF-A and cytoplasmic retinoic acid-binding proteins. To date, four isoform-specific first exons have been identified in the MITF gene: exons 1A, 1H, 1B, and 1M in the 5' to 3' direction, each of which encodes the unique N-terminus of a given isoform. The 5'-flanking regions of these isoform-specific exons are termed A, H, B, and M promoters, respectively. Among these promoters, the M promoter has received particular attention, because it is functional only in melanocyte-lineage cells and is upregulated by Wnt signaling via the functional LEF-1-binding site. Moreover, the M promoter is upregulated by other transcription factors, PAX3, SOX10, and CREB. The activity and degradation of MITF-M are regulated by extracellular signals via protein phosphorylation, such as c-Kit signaling. Together, multiple signals appear to converge on the M promoter as well as on MITF proteins, leading to the proper regulation of MITF-M in melanocytes and other MITF isoforms in many cell types.

Amino Acid Sequence↗
PubMed2001

T-cell-immunity-based inhibitory effects of orally administered herbal medicine juzen-taiho-to on the growth of primarily developed melanocytic tumors in RET-transgenic mice.

We examined the effect of oral administration of juzen-taiho-to, one of the most popular herbal medicines in Japan, on primary melanocytic tumor growth in RET-transgenic mice. There was virtually no difference between the lengths of tumor-free stages in the juzen-taiho-to-treated mice and the untreated littermate control mice. The rate of tumor growth in the juzen-taiho-to-treated mice, however, was greatly suppressed during the entire period after the initial tumor development. Correspondingly, the life span of juzen-taiho-to-treated transgenic mice was longer (over 6 mo in mean value) than that of control mice. We partially elucidated the mechanism of the antitumor effect of juzen-taiho-to. The addition of juzen-taiho-to at any of a wide range (50-1600 microg per ml) of concentrations to in vitro cultures of Mel-Ret cells, a malignant melanoma cell line derived from a RET-transgenic mouse, caused neither cell death nor cell cycle arrest directly. The addition of 50-400 microg per ml of juzen-taiho-to to cultures of murine spleen cells, however, promoted their DNA synthesis. More importantly, peritoneal exudate cells from the juzen-taiho-to-treated transgenic mice, in which the ratio and number of T cells were increased, displayed an antitumor immunity against Mel-Ret cells in vitro. Interestingly, the peritoneal-exudate-cell-associated antitumor immunity was further augmented by the addition of 200-400 microg per ml of juzen-taiho-to in vitro. This immunity, which was primarily conveyed by Thy-1+ T cells, was antigen (RET/melanoma) specific and cytotoxic. Amongst various chemical ingredients of juzen-taiho-to examined in this study, glycirrhizin displayed an action, partially replacing that of juzen-taiho-to, in promoting anti-Mel-Ret immunity when supplementarily added in vitro. These results suggest that juzen-taiho-to suppresses once-developed primary melanocytic tumors through potentiation of T-cell-mediated antitumor cytotoxic immunity in vivo.

Administration, Oral↗
PubMed2001

Roles of Toll-like receptors in innate immune responses.

Innate immunity recognizes invading micro-organisms and triggers a host defence response. However, the molecular mechanism for innate immune recognition was unclear. Recently, a family of Toll-like receptors (TLRs) was identified, and crucial roles for these receptors in the recognition of microbial components have been elucidated. The TLR family consists of 10 members and will be expanding. Each TLR distinguishes between specific patterns of microbial components to provoke innate immune responses. The activation of innate immunity then leads to the development of antigen-specific adaptive immunity. Thus, TLRs control both innate and adaptive immune responses.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7.

BACKGROUND: BMP2 is known to play a wide variety of roles, including some in the development of the nervous system. This cytokine has been reported to induce neurite outgrowth in rat pheochromocytoma PC12 cells via the activation of a p38 MAP kinase, although its regulatory mechanism remains largely to be elucidated. RESULTS: BMP2-induced neurite outgrowth in PC12 cells was inhibited by the introduction of a kinase-negative form of a MAP kinase kinase kinase, TAK1, an upstream regulatory kinase for p38 kinase. Following BMP2 stimulation, the expression of Smad6 and Smad7, inhibitory Smad species that are known to inhibit the BMP2-restricted Smad species, Smad1, Smad5 and Smad8, was up-regulated. Unexpectedly, over-expression of either Smad6 or Smad7 in PC12 cells repressed the BMP2-induced neurite outgrowth and severely impeded the p38 kinase pathway. Both of these inhibitory Smads were found to interact physically with TAK1-binding protein, a molecule required for TAK1 activation. CONCLUSIONS: This study demonstrates that BMP2-induced neurite outgrowth in PC12 cells involves activation of the TAK1-p38 kinase pathway which is inhibited by Smad6 and Smad7.

Animals↗
PubMed2001

Physical locations of 5S and 18S-25S rDNA in Asian and American diploid Hordeum species with the I genome.

The physical locations of 5S and 18S-25S rDNA sequences in 15 diploid Hordeum species with the I genome were examined by double-target in situ hybridization with pTa71 (18S-25S rDNA) and pTa794 (5S rDNA) clones as probes. All the three Asian species had a species-specific rDNA pattern. In 12 American species studied, eight different rDNA types were found. The type reported previously in H. chilense (the 'chilense' type) was observed in eight American species. The chilense type had double 5S rDNA sites - two sites on one chromosome arm separated by a short distance - and two pairs of major 18S-25S rDNA sites on two pairs of satellite chromosomes. The other seven types found in American species were similar to the chilense type and could be derived from the chilense type through deletion, reduction or addition of a rDNA site. Intraspecific polymorphisms were observed in three American species. The overall similarity in rDNA patterns among American species indicates the close relationships between North and South American species and their derivation from a single ancestral source. The differences in the distribution patterns of 5S and 18S-25S rDNA between Asian and American species suggest differentiation between the I genomes of Asian and American species. The 5S and 18S-25S rDNA sites are useful chromosome markers for delimiting Asian species, but have limited value as a taxonomic character in American species. On the basis of rDNA patterns, karyotype evolution and phylogeny of the I-genome diploid species are discussed.

Americas↗
PubMed2001

Increase of cord blood cytokine-producing T cells in intrauterine infection.

BACKGROUND: Although infection is a frequent and important cause of morbidity and mortality in the neonatal period, evaluation of the immune system in cases of intrauterine infection is not easy. The subsets of T helper (Th) 1, which produce mainly interferon gamma (IFN-gamma), and Th2, which produce interleukin (IL) -4, have been implicated in the regulation of many immune responses. In this study, we investigated Th1 and Th2 subsets in the cord blood (CB) to evaluate the role of CB T cells in the intrauterine infections. METHODS: We used an intracellular cytokine-staining technique with determination by flow cytometry to study IFN-gamma-producing T cells and IL-4-producing T cells in the CB of six neonates with perinatal intrauterine infection and 17 uninfected neonates. RESULTS: The CB from neonates with intrauterine infections had more IFN-gamma-producing CD3+T cells than that from uninfected neonates. The percentage of CB IFN-gamma-producing CD3+T cells in the infected neonates correlated with the duration of membrane rupture before the onset of labor, but not with the level of C-reactive protein. The infected neonate born after the longest duration of membrane rupture showed an increased percentage of IL-4-producing CD3+T cells. CONCLUSIONS: Our results suggest that the increase of CB IFN-gamma and IL-4- producing T cells is part of the immune system directed against perinatal intrauterine infections.

Female↗
PubMed2001

Pro-apoptotic effect of presenilin 2 (PS2) overexpression is associated with down-regulation of Bcl-2 in cultured neurons.

Presenilin 2 (PS2) is a polytopic membrane protein that is mutated in some cases of familial Alzheimer's disease (AD). The normal functions of PS2 and its pathogenic role in AD remain unclear. We investigated the biological role of this protein in neurons, using adenovirus-mediated transduction of the PS2 gene into rat primary cortical neurons. Immunocytochemical analyses demonstrated increased PS2 immunoreactivity in most neurons infected with recombinant adenoviruses expressing PS2. Neurons infected with wild-type or mutant (N141I) PS2-expressing adenoviruses showed a significant increase in basal cell death, compared with those infected with control beta-galactosidase-expressing adenovirus. Moreover, PS2 overexpression markedly increased neuronal susceptibility to staurosporine-induced apoptosis. Mutant PS2 was more effective in enhancing apoptosis than its wild-type counterpart. Staurosporine-induced death was significantly inhibited by a specific caspase 3 inhibitor. Western analyses revealed that Bcl-2 protein expression was specifically down-regulated in neurons overexpressing PS2, which temporally corresponded to the accumulation of C- and N-terminal fragments of PS2. Additionally, expression of mutant, but not wild-type PS2, increased the production of beta-amyloid protein (Abeta) 42. These data collectively suggest that the pro-apoptotic effect of PS2 is mediated by down-regulation of Bcl-2. PS2 mutations may increase the susceptibility of neurons to apoptotic stimuli by perturbing the regulation of cell death.

Adenoviridae↗
PubMed2001

Macrophage-derived IL-18-mediated intestinal inflammation in the murine model of Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is associated with an increased number of infiltrating macrophages, which release a variety of proinflammatory cytokines. Interleukin (IL)-18 has been implicated in the modulation of mucosal CD4(+) T cells towards Th1 responses, which are implicated in the pathogenesis of CD. Here we assess the role of macrophages and of IL-18 in the murine model of intestinal inflammation that mimics the immunologic characteristics of human CD. METHODS: Colitis was induced in C57BL/6 mice immunized with 2,4,6-trinitrobenzene sulfonic acid (TNBS) followed by rectal administration of TNBS in ethanol. Mice were treated with either an antibody directed against macrophages conjugated to the ribosome-inactivating protein saporin (anti-Mac-1-saporin) or with a neutralizing antibody against IL-18. In addition, we assessed whether an identical TNBS immunization/challenge protocol could induce colitis in IL-18(-/-) mice. RESULTS: The colonic mucosa of TNBS-treated mice was marked by infiltration of Mac-1-positive macrophages and up-regulation of IL-18. The administration of the anti-Mac-1-saporin antibody or the neutralizing anti-IL-18 antibody resulted in a dramatic attenuation of mucosal inflammation in this model. In addition, TNBS was unable to induce significant colitis in the IL-18(-/-) mice. CONCLUSIONS: Our data underscore the pivotal role of macrophages, and the macrophage-derived IL-18, in the establishment of TNBS-induced colitis in mice. Our results highlight the potential use of therapy directed against IL-18 in the treatment of patients with CD.

Animals↗
PubMed2001

Human parvovirus B19 in cord blood of premature infants.

We investigated whether intrauterine parvovirus B19 infection is associated with premature birth by evaluating parvovirus B19 antibodies and DNA in umbilical cord blood from 76 premature infants. We performed enzyme-linked immunoadsorbent (ELISA) and polymerase chain reaction (PCR) assays to detect B19-specific IgM antibodies and parvovirus DNA. No parvovirus DNA was detected in cord blood sera, and no sample was positive for anti-parvovirus B19 IgM antibodies. Parvovirus appears unlikely to lead to premature birth.

Antibodies, Viral↗
PubMed2001

Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men.

BACKGROUND AND OBJECTIVES: Fluvoxamine, a selective serotonin reuptake inhibitor, is known to inhibit several hepatic cytochrome P450 (CYP) isozymes, in particular CYP1A2. Mexiletine is mainly catalyzed by CYP2D6 and partially catalyzed by CYP1A2. Our objective was to study the potential pharmacokinetic interaction between fluvoxamine and mexiletine. METHODS: A randomized crossover design with two phases was used. A 7-day washout period separated the two treatment conditions. In the one phase, 6 healthy Japanese men received an oral dose of 200 mg of mexiletine alone (study 1); in the other phase, the men received fluvoxamine (50 mg twice a day) for 7 days, and on the eighth day they received oral mexiletine (200 mg) and fluvoxamine concomitantly (study 2). The concentrations of mexiletine were measured with HPLC. RESULTS: The area under the concentration-time curve and serum peak concentration of mexiletine in study 2 were significantly increased compared with those in study 1 (10.4 +/- 4.85 versus 6.70 +/- 3.21 microg x h/mL, P =.006 and 0.623 +/- 0.133 versus 0.536 +/- 0.164 microg/mL, P =.008, respectively). CONCLUSION: The effect of fluvoxamine on the mexiletine disposition is comparatively large, and when mexiletine and fluvoxamine are coadministered careful monitoring of mexiletine is needed.

Administration, Oral↗
PubMed2001

Aneurysmal degeneration of the aorta after stent-graft repair of acute aortic dissection.

PURPOSE: Stent-graft repair of acute aortic dissection has only recently begun, and the true efficacy and safety of this technique have not yet been clarified. In this report, we describe a significant, previously unreported complication following stent-graft repair of acute aortic dissection. MATERIALS AND METHODS: Fourteen patients with acute aortic dissection underwent stent-graft repair. All of the entry tears were located in the descending thoracic aorta. Five patients had type A aortic dissection, and nine patients had type B aortic dissection. The entry tears were closed with stent-grafts, which were fabricated from expanded polytetrafluoroethylene and Z-stents. RESULTS: Stent-graft placement was successfully performed without any complications in all patients. Entry closure was achieved in 13 (93%) of 14 patients. The mean follow-up period was 18 months (range, 9 days to 36 months). During this period, four patients had saccular aneurysms in the proximal descending thoracic aorta. A saccular aneurysm was noted during a mean follow-up period of 63 days (range, 38-99 days). Two of these patients were treated with stent-grafts. Conventional surgical repair is planned in one patient. The other patient is being treated with conservative management. CONCLUSIONS: Stent-graft repair is a technically feasible and effective method for the treatment of acute aortic dissection in selected patients. However, careful follow-up is mandatory to check for the development of saccular aneurysms.

Aged↗