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Biomedical subjects

Takao Ohta

Publications and source records attributed to Takao Ohta.

At least 19 recordsLinked to original sources
PubMed2006

Growth dynamics of domains in ternary fluid vesicles.

We have studied the growth dynamics of domains on ternary fluid vesicles composed of saturated (dipalmitoylphosphatidylcholine), unsaturated (dioleoylphosphatidylcholine) phosphatidylcholine lipids, and cholesterol using a fluorescence microscopy. The domain coarsening processes are classified into two types: normal coarsening and trapped coarsening. For the normal coarsening, the domains having flat circular shape grow in a diffusion-and-coalescence manner and phenomenologically the mean size grows as a power law of approximately t(2/3). The observed growth law is not described by a two-dimensional diffusion-and-coalescence growth mechanism following the Saffman and Delbrück theory, which may originate from the two-body hydrodynamic interactions between domains. For trapped coarsening, on the other hand, the domain coarsening is suppressed at a certain domain size because the repulsive interdomain interactions obstruct the coalescence of domains. The two-color imaging of the trapped domains reveals that the repulsive interactions are induced by the budding of domains. The model free energy consisting of the bending energy of domains, the bending energy of matrix, the line energy of domain boundary, and the translation energy of domains can describe the observed trapped coarsening. The trapping of domains is caused by the coupling between the phase separation and the membrane elasticity under the incompressibility constraint.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2006

Relationship between lipid abnormalities and insulin resistance in Japanese school children.

OBJECTIVE: Dyslipidemia and insulin resistance (IR) are risk factors for coronary heart disease (CHD) in adults. To help prevent the development of CHD, it may be useful to understand the relationship between lipid abnormalities and IR during childhood. METHODS AND RESULTS: IR was assessed by the homeostasis model approximation index. We studied 1175 Japanese school children (642 boys and 533 girls), aged between 7 and 12 years. Obesity was defined by the body mass index standard deviation score (BMISD) (obese: BMISD > or = 2.0). BMISD was most significantly associated with IR in nonobese children (P=0.000). Associations of IR with lipid-related parameters were affected by BMISD. After being corrected by BMISD, in nonobese children, log triglycerides (TG), apoB and low-density lipoprotein (LDL) size in boys and log TG, LDL size, and high-density lipoprotein (HDL) cholesterol in girls were still significantly associated with IR (P=0.000 to 0.017). In obese children, all parameters except for LDL cholesterol in boys and LDL size in girls were significantly associated with IR (P=0.000 to 0.030). Multiple regression analysis showed that log TG and LDL size in nonobese children, log TG in obese boys and LDL size in obese girls were independently associated with IR. Children with IIb and IV hyperlipidemia had significantly higher IR than those with normolipidemia and IIa, even after correcting for BMISD and age. CONCLUSIONS: Our results suggest that in addition to controlling body weight, it may be important for school children to characterize lipid phenotypes to prevent progression to CHD and/or type 2 diabetes and to identify subjects who are at high risk for these disorders.

Body Weight↗
PubMed2006

Opitz trigonocephaly C syndrome in a boy with a de novo balanced reciprocal translocation t(3;18)(q13.13;q12.1).

Opitz trigonocephaly C syndrome (OTCS) is a multiple congenital anomaly syndrome characterized by trigonocephaly, mental retardation, a typical facial appearance, redundant skin, joint and limb abnormalities, and visceral anomalies. We describe a patient with the manifestations of OTCS who also had a de novo balanced reciprocal translocation t(3;18)(q13.13q12.1). His phenotype is a mild form with mild developmental delay and no severe visceral anomalies. Our findings suggest the possible existence of a new locus responsible for OTCS either on 3q13.13 or 18q12.1.

Abnormalities, Multiple↗
PubMed2006

Serum C-reactive protein and its relation to cardiovascular risk factors and adipocytokines in Japanese children.

BACKGROUND: C-Reactive protein (CRP) is an independent risk factor for atherosclerotic coronary heart diseases (ACHD) in adults. To help prevent ACHD, it may be useful to understand risk factors during childhood. OBJECTIVE: The objective of this study was to investigate serum CRP and its relation to other risk factors for ACHD and adipocytokines (adiponectin, IL-6, and TNF-alpha) in Japanese children. METHODS: CRP, conventional risk factors for ACHD, and adipocytokines were determined in 568 children (340 boys and 228 girls, aged 7-10 yr). Serum concentrations of adipocytokines were measured by sandwich ELISA. RESULTS: Children with high CRP concentrations (highest tertile) had higher body mass index (BMI) sd scores, insulin, insulin resistance, uric acid, and adipocytokines and had more atherogenic lipoprotein profiles than other children. However, after being corrected by BMI sd, only high-density lipoprotein cholesterol, apolipoprotein A-I, IL-6, and TNF-alpha for boys and high-density lipoprotein cholesterol, apolipoprotein B, uric acid, IL-6, and TNF-alpha for girls were significantly correlated with CRP. IL-6 was the strongest predictive variable for CRP and accounted for 26.2 and 27.7% of the variability in serum concentrations of CRP in boys and girls, respectively. Serum concentrations of IL-6 were partly dependent on BMI sd and TNF-alpha in both boys and girls. CONCLUSION: Although serum concentrations of CRP are partly regulated by adipocytokines and conventional risk factors for ACHD, high CRP levels were associated with atherogenic profiles of cardiovascular risk factors in children. Our findings suggest that it may be important to control body weight to prevent an increase in serum CRP in children.

Adiponectin↗
PubMed2006

Transactivation of the ICAM-1 gene by CD30 in Hodgkin's lymphoma.

The ICAM-1/LFA-1 complex mediates cell-cell interaction. ICAM-1 is overexpressed in Hodgkin/Reed-Sternberg (H/RS) cells, and serum levels of its soluble form are higher in Hodgkin's lymphoma (HL) patients than in controls. There are no data, however, regarding the regulation of expression of ICAM-1 in H/RS cells. CD30 was identified in H/RS cells of HL and has attracted much interest as a molecular marker of HL. To analyze ICAM-1 expression in H/RS cells, we examined the expression of ICAM-1, LFA-1, CD30 and CD30L in HL-derived cell lines. All cell lines expressed ICAM-1 and CD30, but not LFA-1 or CD30L. CD30 induced ICAM-1 expression. Analysis of the ICAM-1 promoter showed the importance of NF-kappaB binding site for CD30-induced ICAM-1 gene expression. Coexpression of IkappaB, IKK, NIK and TRAF dominant-negative constructs with CD30 inhibited CD30-induced activation of ICAM-1 promoter, suggesting that CD30 induces ICAM-1 via NF-kappaB signalling. The ICAM-1 promoter was activated by the C-terminal region of CD30, which activated NF-kappaB signalling. A decoy CD30 lacking the cytoplasmic region inhibited ICAM-1 promoter activity in HL cell lines. Thus, in H/RS cells, ligand-independent activation of CD30 signalling activates NF-kappaB and this leads to constitutive ICAM-1 expression, suggesting a link between 2 well known phenotypic characteristics of HL, CD30 and ICAM-1 overexpression.

Antigens, CD↗
PubMed2006

Curcumin (diferuloylmethane) inhibits constitutive active NF-kappaB, leading to suppression of cell growth of human T-cell leukemia virus type I-infected T-cell lines and primary adult T-cell leukemia cells.

Adult T-cell leukemia (ATL) is a fatal malignancy of T lymphocytes caused by infection with human T-cell leukemia virus type I (HTLV-I) and remains incurable. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, can be potentially effective by promoting cell apoptosis. Here we examined whether curcumin is effective in the treatment of ATL. Curcumin prevented cell growth of HTLV-I-infected T-cell lines and primary ATL cells but not of normal peripheral blood mononuclear cells. Curcumin induced cell cycle arrest by reducing the expression of cyclin D1, Cdk1 and Cdc25C and apoptosis by reducing the expression of XIAP and survivin. Most of these genes are known to be regulated by NF-kappaB, which plays a critical role in oncogenesis by HTLV-I. Curcumin suppressed constitutive active NF-kappaB of HTLV-I-infected T-cell lines and primary ATL cells by inhibiting phosphorylation of IkappaBalpha. Curcumin also inhibited Tax-induced NF-kappaB transcriptional activity. However, curcumin-induced suppression of cell growth did not correlate with Tax expression level. Curcumin inhibited the growth of HTLV-I-infected T-cell tumors implanted subcutaneously in SCID mice. Our results indicate that curcumin has tumor-suppressive activity against ATL.

Adult↗
PubMed2005

Interconnected Turing patterns in three dimensions.

We study numerically the Turing pattern in three dimensions in a FitzHugh-Nagumo-type reaction-diffusion system. We have found that interconnected periodic domain structures such as a gyroid, Fddd, and perforated lamellar structures appear in three dimensions, which never exist in lower dimensions. The stability analysis of these structures is also performed by means of a mode expansion.

Journal Article↗
PubMed2005

Dynamics of traveling waves under spatiotemporal forcing.

We study dynamics of traveling waves under spatiotemporal forcing in nonequilibrium systems. Based on the model equations where phase separation and chemical reactions take place simultaneously so that traveling waves are formed in a self-organized manner, we apply a space-time dependent external force. Entrainment and modulation of traveling waves are investigated numerically in one dimension. We develop a theoretical analysis to understand the dynamics obtained.

Journal Article↗
PubMed2005

Curcumin suppresses constitutive activation of AP-1 by downregulation of JunD protein in HTLV-1-infected T-cell lines.

Activation of the activator protein 1 (AP-1) plays a critical role in oncogenesis by human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent of adult T-cell leukemia (ATL), and is required for maintenance of the malignant phenotype. Curcumin (diferuloylmethane), the major pigment of the spice turmeric, has anti-tumor activity; however, the effect of curcumin against ATL has not been elucidated. In this study, we examined the effects of curcumin on AP-1 activity in HTLV-1-infected T-cell lines. Curcumin suppressed the constitutive AP-1 DNA-binding and transcriptional activity in HTLV-1-infected T-cell line. Curcumin also inhibited HTLV-1 Tax-induced AP-1 transcriptional activity. JunD was detectable as a major component of the AP-1-DNA complex in HTLV-1-infected T-cell lines using the supershift assay. The expression of JunD was suppressed by curcumin treatment. Curcumin inhibited the growth of HTLV-1-infected T-cell lines by inducing cell cycle arrest followed by apoptosis. Our results suggest that suppression of the constitutively active AP-1 by curcumin is due to, at least in-part, reducing the expression of JunD by curcumin. Inhibition of AP-1 activity by curcumin may be one of the mechanisms responsible for the anti-ATL effect of curcumin. We propose that curcumin is a potentially promising compound for the treatment of ATL.

Apoptosis↗
PubMed2005

Human T cell leukemia virus type I-infected patients with Hashimoto's thyroiditis and Graves' disease.

CONTEXT: Autoimmune thyroid diseases have been reported to be associated with human T cell leukemia virus type I (HTLV-I) infection. HTLV-I proviral load is related to the development of HTLV-I-associated myelopathy/tropical spastic paraparesis and has also been shown to be elevated in the peripheral blood of HTLV-I-infected patients with uveitis, arthritis, and connective tissue disease. OBJECTIVE: The objective of the study was to evaluate the proviral load in HTLV-I-infected patients with Hashimoto's thyroiditis (HT) or Graves' disease (GD) and ascertain the ability of HTLV-I to infect thyroid cells. PATIENTS AND METHODS: A quantitative real-time PCR assay was developed to measure the proviral load of HTLV-I in peripheral blood mononuclear cells from 26 HTLV-I-infected patients with HT, eight HTLV-I-infected patients with GD, or 38 asymptomatic HTLV-I carriers. Rat FRTL-5 thyroid cells were cocultured with HTLV-I-infected T cell line MT-2 or uninfected T cell line CCRF-CEM. After coculture with T cell lines, changes in Tax and cytokine mRNA expression were studied by RT-PCR. RESULTS: HTLV-I proviral load was significantly higher in the peripheral blood of patients with HT and GD than asymptomatic HTLV-I carriers. In the peripheral blood from HTLV-I-infected patients with HT, HTLV-I proviral load did not correlate with the thyroid peroxidase antibody or thyroglobulin antibody titer. After coculture with MT-2 cells, FRTL-5 cells expressed HTLV-I-specific Tax mRNA. These cocultured FRTL-5 cells with MT-2 cells expressed IL-6 mRNA and proliferated more actively than those cocultured with CCRF-CEM cells. CONCLUSION: Our findings suggest the role of the retrovirus in the development of autoimmune thyroid diseases in HTLV-I-infected patients.

Adult↗
PubMed2005

Relation between insulin resistance and fast-migrating LDL subfraction as characterized by capillary isotachophoresis.

The proportion of the electronegative low density lipoprotein [LDL(-)] subfraction, which is atherogenic, is increased in type 2 diabetes but is not reduced by glycemic control. Therefore, we evaluated the ability of a new technique, capillary isotachophoresis (cITP), to quantify charge-based LDL subfractions and examined the relation between insulin resistance and the cITP fast-migrating (f) LDL levels. Seventy-five 10-year-old boys were included. The two cITP LDL subfractions, fLDL and major LDL subfractions, were proportional to the LDL protein content within the range of 0.1-0.8 mg/ml LDL protein. Levels of cITP fLDL were positively correlated with triglyceride (TG) levels and negatively correlated with LDL size. Insulin resistance as assessed by the homeostasis model assessment (HOMA-IR) was positively correlated (P < 0.01) with cITP fLDL levels (r = 0.41). The relation between HOMA-IR and cITP fLDL levels depended on TG levels but was independent of body mass index and LDL size. cITP lipoprotein analysis is an accurate and sensitive method for quantifying charge-based LDL subfractions in human plasma, and insulin resistance is related to cITP fLDL independent of LDL size.

Aged↗
PubMed2005

Transcriptional activation of survivin through the NF-kappaB pathway by human T-cell leukemia virus type I tax.

Survivin, a unique member of the inhibitor of apoptosis protein family, is overexpressed in many cancers and considered to play an important role in oncogenesis. We previously reported the survivin expression profile in ATL, a CD4-positive T-cell malignancy caused by HTLV-I. HTLV-I Tax is thought to play an important role in immortalization of T cells. We have shown also that the expression of Tax protected the mouse T-cell line CTLL-2 against apoptosis induced by deprivation of IL-2 and converted its growth from being IL-2 dependent to being IL-2 independent through the NF-kappaB pathway. In our study, we demonstrate that constitutive expression of survivin was associated with resistance to apoptosis after IL-2 deprivation in Tax-expressing CTLL-2 cells. Transient transfection assays showed that survivin promoter was transactivated by Tax, via the activation of NF-kappaB. Pharmacological NF-kappaB inhibition resulted in suppression of survivin expression and caused apoptosis of Tax-expressing CTLL-2 cells. Our findings suggest that activated NF-kappaB signaling contributes directly to malignant progression of ATL by preventing apoptosis, acting through the prosurvival protein survivin.

Animals↗
PubMed2005

Sanfilippo type B syndrome: five patients with an R565P homozygous mutation in the alpha-N-acetylglucosaminidase gene from the Okinawa islands in Japan.

Sanfilippo type B syndrome (mucopolysaccharidosis type IIIB; MPS IIIB) is an autosomal recessive lysosomal storage disorder that is caused by defective alpha- N-acetylglucosaminidase (NAGLU). We performed NAGLU gene analysis in five patients with MPS IIIB whose respective parents from the Okinawa islands in Japan were not apparently consanguineous. We found a missense mutation (R565P) in all five patients (all homozygotes). We screened this mutation in 200 healthy subjects and found one heterozygote (none of the subjects were related to the patients). These results suggest that there may be a founder effect that results in the accumulation of R565P mutation in this area.

Acetylglucosaminidase↗
PubMed2005

Transactivation of the CCL5/RANTES gene by Epstein-Barr virus latent membrane protein 1.

Chemokines and chemokine receptors mediate lymphocyte migration and tissue localization. To analyze CCL5 (RANTES) expression by EBV-infected cells, we examined the expression of CCL5 in BL cell lines. Among 4 BL cell lines, those infected with EBV selectively expressed the CCL5 gene and secreted CCL5. Four cell lines also expressed CCR5, a receptor for CCL5. EBV-encoded LMP-1, a pleiotropic protein that effects gene expression, cell transformation, growth and death, induces expression of CCL5 mRNA and secretion of CCL5 in the EBV-negative BL cell line BJAB and the embryonic kidney cell line 293T. HDACI-stimulated endogenous LMP-1 also induced CCL5 expression in an EBV-positive BL cell line. Analysis of the CCL5 promoter revealed that it is activated by both LMP-1 C-terminal activation domains, CTAR-1 and CTAR-2, which can activate NF-kappaB signaling. Coexpression of IkappaBalpha, IkappaBbeta, IKKalpha, IKKbeta, NIK and TRAF2 dominant-negative constructs, with LMP-1 inhibited the activation of the CCL5 promoter by LMP-1, suggesting that LMP-1 induces CCL5 via NF-kappaB signaling. The NF-kappaB binding sites, R(A/B), located at positions -71 to -43 relative to the putative transcription start site in the CCL5 promoter, were essential for the activation of CCL5 gene expression by LMP-1. These results indicate that the activation of the NF-kappaB pathway by LMP-1 is required for the activation of CCL5 expression.

Binding Sites↗
PubMed2005

Dengue virus-induced apoptosis in hepatic cells is partly mediated by Apo2 ligand/tumour necrosis factor-related apoptosis-inducing ligand.

Although hepatic injury is reported in cases with dengue haemorrhagic fever and dengue shock syndrome, its mechanism remains poorly understood. Several findings suggest that dengue virus (DEN) induces apoptosis of hepatocytes in vivo. In this work, DEN type 2 (DEN-2) strain NGC was shown to induce apoptosis in the hepatic cell line HepG2, and infection of HepG2 cells was found to induce Apo2 ligand (Apo2L, also known as tumour necrosis factor-related apoptosis-inducing ligand or TRAIL) expression. Furthermore, Apo2L/TRAIL induced apoptosis in HepG2 cells, which expressed the Apo2L/TRAIL receptor DR5/TRAIL-R2 on their surface. Analysis of the Apo2L/TRAIL promoter revealed that this gene was activated by DEN-2 infection, whose responsive element was overlapping NF-kappaB- and Sp1-binding sites located at nt -75 to -65. The proteasome inhibitor N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal (LLnL) inhibited Apo2L/TRAIL mRNA expression, and LLnL and anti-Apo2L/TRAIL antibody inhibited DEN-2-induced apoptosis. It was proposed that DEN infection promotes apoptosis partly through the induction of Apo2L/TRAIL expression.

Apoptosis↗
PubMed2005

Resistance to Apo2 ligand (Apo2L)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis and constitutive expression of Apo2L/TRAIL in human T-cell leukemia virus type 1-infected T-cell lines.

Adult T-cell leukemia (ATL), a CD4+-T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1), is difficult to cure, and novel treatments are urgently needed. Apo2 ligand (Apo2L; also tumor necrosis factor-related apoptosis-inducing ligand [TRAIL]) has been implicated in antitumor therapy. We found that HTLV-1-infected T-cell lines and primary ATL cells were more resistant to Apo2L-induced apoptosis than uninfected cells. Interestingly, HTLV-1-infected T-cell lines and primary ATL cells constitutively expressed Apo2L mRNA. Inducible expression of the viral oncoprotein Tax in a T-cell line up-regulated Apo2L mRNA. Analysis of the Apo2L promoter revealed that this gene is activated by Tax via the activation of NF-kappaB. The sensitivity to Apo2L was not correlated with expression levels of Apo2L receptors, intracellular regulators of apoptosis (FLICE-inhibitory protein and active Akt). NF-kappaB plays a crucial role in the pathogenesis and survival of ATL cells. The resistance to Apo2L-induced apoptosis was reversed by N-acetyl-L-leucinyl-L-leucinyl-lLnorleucinal (LLnL), an NF-kappaB inhibitor. LLnL significantly induced the Apo2L receptors DR4 and DR5. Our results suggest that the constitutive activation of NF-kappaB is essential for Apo2L gene induction and protection against Apo2L-induced apoptosis and that suppression of NF-kappaB may be a useful adjunct in clinical use of Apo2L against ATL.

Apoptosis↗
PubMed2005

Fucoidan extracted from Cladosiphon okamuranus Tokida induces apoptosis of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells.

Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) and remains incurable. The highest endemic area of HTLV-1 carriers in Japan is located in Okinawa, and novel treatments are urgently needed in this area. We extracted fucoidan, a sulfated polysaccharide, from the brown seaweed Cladosiphon okamuranus Tokida cultivated in Okinawa, Japan and examined its tumor-suppression activity against ATL. Fucoidan significantly inhibited the growth of peripheral blood mononuclear cells of ATL patients and HTLV-1-infected T-cell lines but not that of normal peripheral blood mononuclear cells. Fucoidan induced apoptosis of HTLV-1-infected T-cell lines mediated through downregulation of cellular inhibitor of apoptosis protein-2 and survivin and G1 phase accumulation through the downregulation of cyclin D2, c-myc, and hyperphosphorylated form of the retinoblastoma tumor suppressor protein. Further analysis showed that fucoidan inactivated NF-kappaB and activator protein-1 and inhibited NF-kappaB-inducible chemokine, C-C chemokine ligand 5 (regulated on activation, normal T expressed and secreted) production, and homotypic cell-cell adhesion of HTLV-1-infected T-cell lines. In vivo use of fucoidan resulted in partial inhibition of growth of tumors of an HTLV-1-infected T-cell line transplanted subcutaneously in severe combined immune deficient mice. Our results indicate that fucoidan is a potentially useful therapeutic agent for patients with ATL.

Animals↗