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Biomedical subjects

Y Kawakami

Publications and source records attributed to Y Kawakami.

At least 19 recordsLinked to original sources
PubMed2006

Thyroid hormone receptor beta is widely expressed in the brain and pituitary of the Japanese eel, Anguilla japonica.

In a previous study, we cloned the thyroid hormone receptor betaB (TRbetaB) from a teleostean fish, the Japanese conger eel (Conger myriaster). The gene encoding this receptor is expressed in the brain and pituitary. In this study, we cloned TRbetaB from the brain of the Japanese eel (Anguilla japonica) to extend our studies into thyroid hormone function in fish. RT-PCR analysis demonstrated that the TRbetaB transcripts were abundant in both the brain and pituitary. The TRbetaB cDNA encoded a 379 amino acid protein with much higher homology to the conger eel TRbetaB than to other fish TRs, supporting the existence of a TRbetaB isoform, at least in anguilliforms. In a transiently transfected Japanese eel cell line, Hepa-E1, TRbetaB and its splice variants in the ligand-binding domain (TRbetaBL) showed thyroid hormone (TH)-dependent activation of transcription from the TH-responsive promoter. In situ hybridization studies revealed the presence of TRbetaB transcripts in the pars distalis of the pituitary.

Amino Acid Sequence↗
PubMed2006

Effects of exercise on adiponectin and adiponectin receptor levels in rats.

Adiponectin reportedly reduces insulin-resistance. Exercise has also been shown to lessen insulin-resistance, though it is not known whether exercise increases levels of adiponectin and/or its receptors or whether its effects are dependent on exercise intensity and/or frequency. Catecholamine levels have been shown to increase during exercise and to fluctuate based on exercise intensity and duration. In light of this information, we examined the effects of exercise on catecholamine, adiponectin, and adiponectin receptor levels in rats. Our data showed that blood adiponectin levels increased by 150% in animals that exercised at a rate of 30 m/min for 60 min 2 days per week, but not 5 days, per week; no such increase was observed in rats that exercised at a rate of 25 m/min for 30 min. The effects of exercise on adiponectin receptor mRNA were variable, with adiponectin receptor 1 (AdipoR1) levels in muscle increasing up to 4 times while adiponectin receptor 2 (AdipoR2) levels in liver fell to below half in response to exercise at a rate of 25 m/min for 30 min 5 days per week. We also observed that urinary epinephrine levels and plasma lipids were elevated by exercise at a rate of 25 m/min for 30 min 2 days per week. Exercise frequency at a rate of 25 m/min for 30 min correlated with AdipoR1 and AdipoR2 mRNA expression in the muscle and liver, respectively (r=0.640, p<0.05 and r=-0.808, p<0.0005, respectively). Urinary epinephrine levels correlated with AdipoR2 mRNA expression in liver tissues (r=-0.664, p<0.05) in rats that exercised at a rate of 25 m/min for 30 min. Thus, exercise may regulate adiponectin receptor mRNA expression in tissues, which might cause increases in glucose uptake and fatty acid oxidation in the muscle. The effect of exercise on adiponectin levels depends on the specific conditions of the exercise.

Adiponectin↗
PubMed2006

Fatigue behavior of resin composites in aqueous environments.

OBJECTIVES: Interaction between mechanical and chemical fatigue of resin composites was investigated. METHODS: Fatigue fracture resistance of composites after (1) water immersion and under (2) dry and (3) aqueous conditions was analyzed using a fatigue crack propagation test. The characteristics of fatigue crack propagation were expressed as the correlation between the fatigue crack growth rate (da/dN) and stress intensity factor range (DeltaK) and by the fatigue crack growth threshold (DeltaKth). Following the fatigue test, a fractographic examination was performed by scanning electron microscopy. RESULTS: Contrary to common perception, fatigue crack propagation was retarded under aqueous conditions but accelerated after water immersion. In addition, fatigue cracks detoured around inorganic macro-fillers, but penetrated organic fillers. SIGNIFICANCE: It was concluded that the inverse effects of water on fatigue resistance of composites are dependent on the experimental conditions. Moreover, inorganic macro-fillers were shown to be functional in retarding fatigue cracks in composites.

Composite Resins↗
PubMed2006

Frequent immune response to a melanocyte specific protein KU-MEL-1 in patients with Vogt-Koyanagi-Harada disease.

AIM: To isolate autoantigens possibly involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. METHODS: Autoantigens recognised by immunoglobulin G antibodies (IgG Ab) in sera from VKH patients were isolated by screening the lambda phage cDNA libraries made from melanocytes and a highly pigmented melanoma cell line with the patients' sera. Presence of IgG specific for the autoantigens in sera from patients with various panuveitis and healthy individuals was evaluated. Relation between the specific IgG and various clinicopathological features was examined. RESULTS: KU-MEL-1 was found to be one of the 81 isolated positive clones representing 35 distinct genes, which is a previously isolated melanoma antigen preferentially expressed in melanocytes. The IgG Ab specific for KU-MEL-1 was detected in sera from patients with VKH in significantly higher amounts than in sera from patients with Behçet's disease, sarcoidosis, and from healthy individuals. Positive serum KU-MEL-1 Ab was significantly associated with HLA-DRB1*0405 and male VKH patients. CONCLUSION: KU-MEL-1 was identified as a new autoantigen for VKH. The highly frequent induction of IgG Ab for KU-MEL-1 in HLA-DRB1*0405 positive VKH patients may suggest the possible involvement of KU-MEL-1 specific CD4(+) T cells in the pathogenesis of VKH, suggesting the possible use in the development of diagnostic and therapeutic treatments for VKH patients.

Adult↗
PubMed2006

Prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation: associations with impaired platelet production and increased platelet turnover.

To evaluate the mechanisms underlying prolonged thrombocytopenia after allogeneic hematopoietic stem cell transplantation (SCT), an index for plasma glycocalicin normalized for the individual platelet count (GCI), plasma thrombopoietin (TPO), and circulating B cells producing anti-GPIIb-IIIa antibodies were measured in 50 SCT recipients with or without prolonged thrombocytopenia, 42 patients with idiopathic thrombocytopenic purpura, nine patients with aplastic anemia, and 22 healthy individuals. All three indices were significantly higher in the SCT recipients with thrombocytopenia than in those without (P < 0.01 for all comparisons), and were significantly correlated with the platelet count in SCT recipients. Stepwise multiple regression analysis of the samples from the SCT recipients revealed that GCI and TPO independently pointed to specific mechanisms of thrombocytopenia. The GCI and TPO status in SCT recipients with thrombocytopenia had a pattern similar to that seen in aplastic anemia, suggesting a major role for impaired thrombopoiesis. An antiplatelet antibody response was frequently detected in SCT recipients, but the development of thrombocytopenia is likely to depend on additional factors, such as reticuloendothelial function. In summary, post transplant prolonged thrombocytopenia is associated with complex mechanisms, including impaired thrombopoiesis and increased platelet turnover.

Adult↗
PubMed2006

Promoter polymorphism in the macrophage migration inhibitory factor gene is associated with obesity.

OBJECTIVE: To explore the association of promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene with obesity. SUBJECTS: In total, 213 nondiabetic Japanese subjects. They were divided into three groups according to World Health Organization definitions: lean (body mass index (BMI) <25 kg/m2), overweight (25 < or = BMI < 30 kg/m2) and obese (BMI> or = 30 kg/m2). METHODS: We examined two polymorphic loci in the MIF gene in the subjects: a single-nucleotide polymorphism at position -173 (G/C) and a CATT-tetranucleotide repeat polymorphism at position -794, which both can affect promoter activity in different cells. RESULTS: We detected four alleles: 5-, 6-, 7- and 8-CATT at position -794. Genotypes without the 5-CATT allele (X/X, X refers to 6-, 7- or 8-CATT alleles) were more common in obese subjects than in lean or overweight groups (P = 0.013). The X-CATT allele was more frequent in obese subjects than in lean or overweight subjects (P = 0.030). In contrast, -173G/C was not associated with obesity. Among the haplotypes of the two promoter polymorphisms, G/5-CATT ((-173G/C)/(-794[CATT](5-8))) was associated with a decreased risk of obesity (P = 0.025) and G/6-CATT with an increased risk of overweight (P=0.028). CONCLUSION: Promoter polymorphism in the MIF gene is linked with obesity.

Adult↗
PubMed2005

Autoantibody to CD40 ligand in systemic lupus erythematosus: association with thrombocytopenia but not thromboembolism.

OBJECTIVES: To examine the prevalence, clinical associations and pathogenic roles of autoantibodies to CD40 ligand (CD40L) in patients with systemic lupus erythematosus (SLE). METHODS: Plasma anti-CD40L antibodies from 125 patients with SLE, 24 with primary antiphospholipid syndrome (APS) and 90 with idiopathic thrombocytopenic purpura (ITP) and from 62 healthy individuals were measured with an enzyme-linked immunosorbent assay (ELISA). HeLa cells transfected with human CD40L cDNA (HeLa/CD40L) were used to confirm the presence of anti-CD40L autoantibodies. The effect of anti-CD40L antibodies on the CD40L-CD40 interaction was evaluated by observing CD40L-induced IkappaB activation in CD40-expressing fibroblasts. RESULTS: Anti-CD40L autoantibody was detected in seven (6%) SLE, three (13%) primary APS and 11 (12%) ITP patients, but in no healthy controls. Antibody binding in an ELISA was competitively inhibited by membrane components of HeLa/CD40L. Anti-CD40L antibody-positive IgG specifically bound the surface of living HeLa/CD40L, as shown by flow cytometry. The frequency of thrombocytopenia was significantly higher in SLE patients with the anti-CD40L antibody than in those without (100 vs 14%; P<0.00001), whereas there was no association between the anti-CD40L antibody and thrombosis. Binding of the anti-CD40L antibodies in patients' plasma to CD40L was competitively inhibited by a series of mouse anti-CD40L monoclonal antibodies. Anti-CD40L antibody-positive IgG failed to inhibit CD40L-induced IkappaB activation. CONCLUSIONS: Anti-CD40L autoantibody is associated with thrombocytopenia but not thromboembolism. Our findings are potentially useful in understanding the complex roles of CD40L in the pathophysiology of thrombosis and haemostasis as well as the thromboembolic complications that occur during treatment with anti-CD40L humanized antibody.

Adult↗
PubMed2005

Gene therapy for human small-cell lung carcinoma by inactivation of Skp-2 with virally mediated RNA interference.

Increase of Skp-2, which is involved in the degradation of cell cycle regulators including p27Kip1, p21 and c-myc, is one of the important mechanisms for dysregulation of cell cycles in various cancers. We applied RNA interference (RNAi) for Skp-2 by using HIV-lentiviral or adenoviral vectors for a human small-cell lung carcinoma cell line with increased Skp-2 to evaluate RNAi strategy for cancer gene therapy. HIV-lentivirus-mediated RNAi for Skp-2 resulted in efficient inhibition of the in vitro cell growth of cancer cells with increased Skp-2 through the increase of p27Kip1 and p21, but no significant effect on the growth of cells without high Skp-2 expression. Furthermore, intratumoral administration of adenovirus siRNA vector for Skp-2 efficiently inhibited growth of established subcutaneous tumor on NOD/SCID mice. These results indicate that the Skp-2 RNAi may be a useful strategy for gene therapy of cancers with high Skp-2 expression.

Adenoviridae↗
PubMed2005

A human adenoviral vector with a chimeric fiber from canine adenovirus type 1 results in novel expanded tropism for cancer gene therapy.

The development of novel therapeutic strategies is imperative for the treatment of advanced cancers like ovarian cancer and glioma, which are resistant to most traditional treatment modalities. In this regard, adenoviral (Ad) cancer gene therapy is a promising approach. However, the gene delivery efficiency of human serotype 5 recombinant adenoviruses (Ad5) in cancer gene therapy clinical trials to date has been limited, mainly due to the paucity of the primary Ad5 receptor, the coxsackie and adenovirus receptor (CAR), on human cancer cells. To circumvent CAR deficiency, Ad5 vectors have been retargeted by creating chimeric fibers possessing the knob domains of alternate human Ad serotypes. Recently, more radical modifications based on 'xenotype' knob switching with non-human adenovirus have been exploited. Herein, we present the characterization of a novel vector derived from a recombinant Ad5 vector containing the canine adenovirus serotype 1 (CAV-1) knob (Ad5Luc1-CK1), the tropism of which has not been previously described. We compared the function of this vector with our other chimeric viruses displaying the CAV-2 knob (Ad5Luc1-CK2) and Ad3 knob (Ad5/3Luc1). Our data demonstrate that the CAV-1 knob can alter Ad5 tropism through the use of a CAR-independent entry pathway distinct from that of both Ad5Luc1-CK2 and Ad5/3-Luc1. In fact, the gene transfer efficiency of this novel vector in ovarian cancer cell lines, and more importantly in patient ovarian cancer primary tissue slice samples, was superior relative to all other vectors applied in this study. Thus, CAV-1 knob xenotype gene transfer represents a viable means to achieve enhanced transduction of low-CAR tumors.

Adenoviruses, Canine↗
PubMed2005

Stimulation of catecholamine biosynthesis via the PKC pathway by prolactin-releasing peptide in PC12 rat pheochromocytoma cells.

We have previously shown that prolactin-releasing peptide (PrRP) stimulates catecholamine release from PC12 cells (rat pheochromocytoma cell line). However, it is not known whether PrRP also affects catecholamine biosynthesis. Thus, we examined the effect of PrRP on catecholamine biosynthesis in PC12 cells. PrRP31 (>10 nM) and PrRP20 (>100 nM) significantly increased the activity and expression level of tyrosine hydroxylase (TH), a rate-limiting enzyme, in catecholamine biosynthesis. However, the PrRP20-stimulated TH activity was markedly weaker than that of PrRP31. PrRP31 (>1 nM) and PrRP20 (>10 nM) significantly induced an increase in the level of PKC activity. Both Ro 32-0432 (a protein kinase C inhibitor) and H89 (a protein kinase A inhibitor) effectively suppressed the PrRP31 (100 nM)-induced TH mRNA level. Next, we examined the effect of PrRP on mitogen-activated protein kinases (MAPKs). PrRP31 (1 microM) significantly induced an increase in the activity of extracellular signal-related kinases (ERKs) and the stress-activated protein kinase/c-jun N terminal kinase (SAPK/JNK). In contrast to ERKs and JNK, PrRP31 did not affect P38 MAPK activity. Consistent with these findings, pretreatment of cells with the MEK-1-inhibitor, PD-98059 (50 microM), significantly inhibited the PrRP31 (100 nM)-induced increase in TH mRNA. These results indicate that PrRP stimulates catecholamine synthesis through both the PKC and PKA pathways in PC12 cells.

Animals↗
PubMed2004

Lack of circulating autoantibodies to bone morphogenetic protein receptor-II or activin receptor-like kinase 1 in mixed connective tissue disease patients with pulmonary arterial hypertension.

OBJECTIVES: To examine whether autoantibodies against bone morphogenetic protein receptor-II (BMPR-II) or activin receptor-like kinase 1 (ALK-1) are associated with pulmonary arterial hypertension (PAH) in patients with mixed connective tissue disease (MCTD). METHODS: We studied sera from 37 MCTD patients with or without PAH, six patients with idiopathic PAH, and 30 healthy controls. Circulating anti-BMPR-II and anti-ALK-1 antibodies were detected using immunoprecipitation of recombinant antigens generated by in vitro transcription/translation and indirect immunofluorescence of cultured cells that were induced to express these antigens by gene transfer. Anti-BMPR-II antibodies were further examined by immunoprecipitation and immunoblotting using a recombinant fragment of the extracellular domain of BMPR-II. RESULTS: Serum anti-BMPR-II and anti-ALK-1 autoantibodies were not detected in MCTD patients irrespective of the presence or absence of PAH, or in patients with idiopathic PAH. CONCLUSIONS: Our finding does not support the hypothesis that autoantibody-mediated dysregulation of signals through BMPR-II or ALK-1 contributes to the development of PAH in patients with connective tissue diseases.

Activin Receptors, Type I↗
PubMed2004

Response durations encode nociceptive stimulus intensity in the rat medial prefrontal cortex.

We examined whether the medial prefrontal cortex (mPFC) encodes nociceptive stimulus intensity by applying mechanical pressure stimulation, for 2 s at 50, 100, or 300 g constant force (gf) to the tails of urethane-anesthetized rats. In a total of 1208 neurons sampled, 242 (20.0%) were responsive to mechanical stimuli. One hundred thirteen of the 242 (46.7%) were mechanical high threshold neurons (nociceptive specific neurons, NS; threshold >or=100 gf), and 35 (14.5%) exhibited a graded increase in excitator responses to a stepwise increase in stimulus intensity (wide dynamic range-like neurons, WDR-L). These 148 response discharges persisted during stimulation followed by post-stimulus discharges. The nociceptive response duration of NS neurons, but not discharge frequency, was reduced dose-dependently by intraventricular injection of morphine (0.3, and 30 microg/3 microl). Different doses of morphine may set the stimulus intensity at relatively different brain activity levels. Thus, the NS neurons used the response duration as a sensory transduction code. In WDR-L neurons, the response duration, but not always the firing frequency, was linearly related to stimulus intensity. The WDR-L neurons in the mPFC encoded stimulus intensity with response duration, although the coding method is not likely to be the same as that of sensory discriminating WDR cells in the primary somatosensory cortex. Both types of mPFC neurons encode nociceptive (absolute or relative) stimulus intensity and transform the information into the temporal duration of the next stage of pain-related modulation in animal behavior.

Action Potentials↗
PubMed2004

Alanine aminotransferase elevation not associated with fatty liver is frequently seen in obese Japanese women.

OBJECTIVE: To determine the prevalence of fatty liver and alanine aminotransferase (ALT) elevation in obese Japanese women and to clarify the factors contributing to fatty change and ALT elevation in the cohort. DESIGN: Cross-sectional and population-based study. SUBJECTS: From 4366 women who received their annual health check-up, 4211 women were selected for analysis. All 4211 women were negative for hepatitis virus markers. MEASUREMENTS: Peripheral blood cell counts, liver biochemical tests, fasting glucose, cholesterol and triglyceride levels, uric acids, glycosylate hemoglobin A1c, and ultrasound examination. RESULTS: Ultrasonographic evidence of fatty liver and ALT elevation was seen in 391 (9.3%) and 238 (5.7%), respectively, of the 4211 women. Frequencies of both fatty liver and ALT elevation increased with increase in the degree of obesity. The frequency of ALT elevation was higher in women with fatty liver than in women without fatty liver among the nonobese or mildly obese group. However, the frequency of ALT elevation was not significantly different between women with fatty liver and women without fatty liver among the severely obese group. Multivariate analysis showed that obesity, hemoglobin (> or = 14 g/dl), triglyceride (> or = 150 mg/dl), diabetes mellitus, and fatty liver were significant predictors of ALT elevation. However, only two variables, hemoglobin (> or = 14 g/dl) and presence of diabetes, were significant in the severely obese group. CONCLUSIONS: ALT elevation not associated with fatty liver was frequently seen in obese women, suggesting that obesity is directly associated with the elevated ALT level in Japanese obese women. In addition, hemoglobin (> or = 14 g/dl) was a strong predictor of ALT elevation in the severely obese group.

Adult↗
PubMed2003

Observation of B0 -->D0K0 and B0 -->D0K*0 decays.

We report on a search for B(0)-->D(*0)K(*0) decays based on 85 x 10(6) BB events collected with the Belle detector at KEKB. The B(0)-->D0K(0) and B(0)-->D0K(*0) decays have been observed for the first time with the branching fractions B(B(0)-->D0K(0))=(5.0(+1.3)(-1.2)+/-0.6)x10(-5) and B(B(0)-->D0K(*0))=(4.8(+1.1)(-1.0)+/-0.5)x10(-5). No significant signal has been found for the B(0)-->D(*0)K*0) and B(0)-->D(*0)K(*0) decay modes, and upper limits at 90% C.L. are presented.

Journal Article↗
PubMed2003

Studies of the decay B+/- -->D(CP)K+/-.

We report studies of the Cabibbo-suppressed decay B+/--->D(CP)K+/-, where D(CP) denotes CP eigenstates of the D0-D0; system. The analysis is based on a 29.1 fb(-1) sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-) storage ring. We measure ratios of branching fractions, relative to Cabibbo-favored B+/--->D(CP)pi(+/-), of B(B--->D1K-)/B(B--->D1pi(-))=0.125+/-0.036+/-0.010 and B(B--->D2K-)/B(B--->D2pi(-))=0.119+/-0.028+/-0.006; the index 1 (2) denotes the CP=+1 (-1) eigenstate. We also extract the partial rate asymmetries for B+/--->D(CP)K+/-, finding A(1)=0.29+/-0.26+/-0.05 and A(2)=-0.22+/-0.24+/-0.04.

Journal Article↗
PubMed2003

Measurement of branching fractions for B-->eta(c)K(*) decays.

We report measurements of branching fractions for charged and neutral B-->eta(c)K decays where the eta(c) meson is reconstructed in the K(0)(S)K+/-pi(-/+), K+K-pi(0), K(*0)K-pi(+), and pp; decay channels. The neutral B0 channel is a CP eigenstate and can be used to measure the CP violation parameter sin(2phi(1). We also report the first observation of the B0-->eta(c)K(*0) mode. The results are based on an analysis of 29.1 fb(-1) of data collected by the Belle detector at KEKB.

Journal Article↗
PubMed2003

Measurement of the electroweak penguin process B-->X(s)l+l-.

We report the first measurement of the branching fraction for the inclusive decay B-->X(s)l(+)l(-), where l is either an electron or a muon, and X(s) is a hadronic recoil system that contains an s quark. We analyzed a data sample of 65.4 x 10(6) B meson pairs collected with the Belle detector at the KEKB e(+)e(-) asymmetric-energy collider. We find B(B-->X(s)l(+)l(-))=[6.1 +/-1.4(stat) +1.4-1.1(syst)] x 10(-6) for dilepton masses greater than 0.2 GeV/c(2).

Journal Article↗