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Hiroshi Ito

Publications and source records attributed to Hiroshi Ito.

At least 19 recordsLinked to original sources
PubMed2006

Development of septum-free injector for gas chromatography and its application to the samples with a high boiling point.

A novel apparatus with a simple structure has been developed for introducing samples into the vaporizing chamber of a gas chromatograph. It requires no septum due to the gas sealing structure over the carrier gas supply line. The septum-free injector made it possible to use injection port temperatures as high as 450 degrees C. Repetitive injection of samples with boiling points below 300 degrees C resulted in peak areas with relative standard deviations between 1.25 and 3.28% (n=5) and good linearity (r(2)>0.9942) for the calibration curve. In the analysis of polycyclic aromatic hydrocarbons and a base oil, the peak areas of components with high boiling points increased as the injection port temperature was increased to 450 degrees C.

Calibration↗
PubMed2006

Anti-CD40L monoclonal antibodies can replace anti-CD4 monoclonal antibodies for the nonmyeloablative induction of mixed xenogeneic chimerism.

BACKGROUND: We have previously demonstrated that xenogeneic bone marrow engraftment and donor-specific tolerance can be induced in mice receiving anti-CD4, -CD8, -Thy-1.2, and -NK1.1 monoclonal antibodies (mAbs) on Days -6 and -1, 3 Gy total body irradiation (TBI), and 7 Gy thymic irradiation on Day 0, followed by injection of T-cell depleted (TCD) rat bone marrow cells. We have recently demonstrated that anti-CD40L mAb treatment is sufficient to completely overcome CD4 cell-mediated resistance to allogeneic marrow engraftment and rapidly induce CD4 cell tolerance in an allogeneic combination. METHODS: We investigated the ability of anti-CD40L mAb to promote mixed xenogeneic chimerism and donor-specific tolerance in B6 mice receiving anti-CD8, -Thy1.2 and -NK1.1 mAbs and 3 Gy TBI followed by TCD bone marrow transplantation (BMT) from F344 rats. RESULTS: Administration of anti-CD4 mAb in this model could be completely replaced by one injection of anti-CD40L mAb. Evidence for deletional tolerance was obtained in mixed chimeras prepared with this anti-CD40L-based regimen. However, anti-NK1.1 and anti-Thy1.2 mAb could not be replaced by anti-CD40L mAb. CONCLUSIONS: These results demonstrate that anti-CD40L in combination with xenogeneic BMT can tolerize preexisting peripheral and intrathymic CD4 cells to xenoantigens. However, anti-CD40L does not prevent NK cell and/or gammaDelta cell-mediated rejection of xenogeneic bone marrow.

Animals↗
PubMed2006

Long-term survival of xenogeneic heart grafts achieved by costimulatory blockade and transient mixed chimerism.

BACKGROUND: Xenotransplantation holds great promise in clinical medicine, but is limited by the vigorous rejection response elicited against solid organs transplanted across species barriers. In this study, we investigated the role of anti-CD40L monoclonal antibody (mAb) in inducing xenogeneic mixed chimerism and donor-specific heart transplantation tolerance. METHODS: One day before heart transplantation, mice were injected intraperitoneally with anti-mouse CD8/NK1.1/Thy1.2 mAbs. On day 0, the mice received 3 Gy total body irradiation (TBI), an intravenous injection of unseparated bone marrow (BM) harvested from F344 rats, and an intraperitoneal injection of hamster antimouse CD40L mAb, MR1. Heart grafts from F344 rats were heterotopically transplanted into the abdomen of B6 mouse recipients. Using flow cytometric analysis of peripheral white blood cells, we assessed donor hematopoiesis at various times after bone marrow transplantation (BMT). RESULTS: Chimerism subsided gradually and disappeared completely 18 weeks after BMT. The cardiac graft survived permanently, even after the mixed chimerism disappeared. To determine if the mice acquired donor-specific tolerance, second rat heart grafts were transplanted 120 days after the first heart transplantation. The second transplanted hearts were also accepted over 60 days. Histological analysis revealed no remarkable vasculopathy in the coronary vessels at any stage. CONCLUSIONS: These findings clearly show that costimulatory blockade plays an important role in inducing xenochimerism, and that transient mixed chimerism can induce permanent acceptance of rat to mouse cardiac xenografts. Transplantation of xenogeneic bone marrow cells under costimulatory blockade at the time of heart transplantation may induce transplantation tolerance.

Animals↗
PubMed2006

Marshall vein as arrhythmogenic source in patients with atrial fibrillation: correlation between its anatomy and electrophysiological findings.

BACKGROUND: Atrial fibrillation (AF) may originate from catecholamine-sensitive vein of Marshall (VOM) or its ligament in addition to pulmonary veins (PVs). The anatomy of VOM and its relation to arrhythmogenic foci in the left atrium are unknown. We studied the anatomy of VOM and its relation to foci in patients with AF. METHODS: The study population consisted of 100 patients with AF (mean age, 62 years; chronic AF, n = 15). AF sources were determined at baseline and after isoproterenol administration without sedation. VOM was identified by balloon-occluded coronary sinus (CS) angiography. We determined its anatomy in relation to left PVs. RESULTS: VOM was visualized in 73 patients (73%). Ninety-seven patients had 269 arrhythmogenic foci (PV, n = 77; non-PV, n = 48). Non-PV foci included left atrial posterior wall (24, 9%), left lateral area (12, 4.5%), roof (6, 2.2%), superior vena cava (28, 10.4%), crista terminalis (8, 3.0%), CS (10, 3.7%), and others (10, 3.7%). The incidence of PV foci in the left superior PV (LSPV) was significantly higher in patients with well-developed VOM than in those without (66% vs 42%, P < 0.05). Twenty-eight patients had 30 non-PV foci around the LSPV ostium. We successfully ablated the non-PV foci at the distal end of VOM in 11 patients. The ends of the VOM branches were good markers to search for non-PV foci. Seven of 11 (64%) patients with successful ablation of non-PV foci were free from arrhythmia, whereas only 6 of 17 (35%) were free from arrhythmia in those with residual non-PV foci. CONCLUSIONS: To determine VOM anatomy is important to identify non-PV foci around the ends of VOM.

Atrial Fibrillation↗
PubMed2006

Highly regioselective transformation of out/out-equatorial bis(formylmethano)[60]fullerenes: construction of dissymmetric [60]fullerene-centered triads.

Three kinds of out/out-equatorial bis(formylmethano)[60]fullerenes (1b-d) were obtained by the tether-directed bifunctionalization of [60]fullerene with bis(alpha-formylsulfonium ylide)s. The condensation of aromatic amines with 1b-d proceeded with an unexpectedly high regioselectivity to give one of two possible regioisomers of mono-imines as the main products (the ratio of the regioisomers, up to 97:3). By the transformation of the remaining formyl group in the mono-imines thus obtained, the corresponding dissymmetric bis-imines were efficiently synthesized.

Amines↗
PubMed2006

Identification of a cardiac isoform of the murine calcium channel alpha1C (Cav1.2-a) subunit and its preferential binding with the beta2 subunit.

We describe a cardiac muscle isoform of the voltage-dependent calcium channel alpha1 subunit, which corresponds to the rabbit ortholog of alpha1C-a (Cav1.2a). We also cloned smooth muscle isoforms alpha1C-b (Cav1.2b) and alpha1C-d (Cav1.2d). Differences among these three isoforms lie within the N-terminal region (exon 1A or 1B), the sixth transmembrane segment of domain I (exon 8A or 8B), and the use of exon 10, which forms the intracellular loop between transmembrane domains I and II. Two-hybrid analysis revealed interactions among the three alpha1 isoforms and beta subunits. In vitro overlay and immunoprecipitation analyses revealed preferential binding between alpha1C-a and beta2, which is also expressed at a high level in the heart.

Alternative Splicing↗
PubMed2006

Effects of repetitive transcranial magnetic stimulation on [11C]raclopride binding and cognitive function in patients with depression.

BACKGROUND: Several studies have demonstrated that repetitive transcranial magnetic stimulation (rTMS) elicits moderate antidepressant effects. Several previous studies suggested that the dopaminergic system might be related to this therapeutic action of rTMS. We attempted to determine the effects of chronic rTMS on central dopaminergic function in depression using positron emission tomography (PET) with [11C]raclopride. METHODS: Nine patients with depression were treated with 10 daily sessions of rTMS (10 Hz, 5 s train, 20 trains at 100% motor threshold per session) over the left dorsolateral prefrontal cortex (DLPFC). Each patient underwent two [11C]raclopride PET scans and neuropsychological tests - before rTMS and 1 day after rTMS. RESULTS: In five patients, the Hamilton Rating Scale for Depression (HRSD) significantly decreased. Patients showed significant improvement in verbal memory following rTMS. There were no changes in [11C]raclopride binding in the caudate nucleus and putamen after rTMS treatment. LIMITATIONS: Our sample size was limited, and our study was an open trial lacking sham-treated controls. CONCLUSION: This study suggests that rTMS may be effective for the treatment of depression and also may improve verbal memory function. We observed no changes in [11C]raclopride binding, suggesting that there was no measurable increase in the release of dopamine at the second PET scan. Several animal studies and healthy human studies have indicated that dopamine can be released soon after acute rTMS. Our results suggest that release of striatal dopamine induced by rTMS may be only transient, or that dopamine release may be attenuated following chronic rTMS.

Adult↗
PubMed2006

Dynamical valence fluctuation at the charge-density-wave phase boundary in iodide-bridged Pt compound [Pt(chxn)2I]I2.

We synthesized a novel iodo-bridged linear chain platinum compound, having the quasi-two-dimensional charge-density-wave (CDW) ground state and the smallest band gap. In this compound, we discovered an anomalous valence state in the boundary region at which the CDW phase alternates in the crystal by means of ESR, X-ray diffuse scattering, STM, and electrical resistivity. This anomalous state can be explained by the fast fluctuation between Pt(IV)-I...Pt(II) and Pt(II)...I-Pt(IV) in the double well potential. This is the first observation of the dynamical fluctuation of the CDW phase among the quasi one-dimensional halogen-bridged complexes.

Journal Article↗
PubMed2006

Cerebral vascular mean transit time in healthy humans: a comparative study with PET and dynamic susceptibility contrast-enhanced MRI.

Cerebral vascular mean transit time (MTT), defined as the ratio of cerebral blood volume to cerebral blood flow (CBV/CBF), is a valuable indicator of the cerebral circulation. Positron emission tomography (PET) and dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI) are useful for the quantitative determination of MTT in the clinical setting. The aim of this study was to establish a normal value set of MTT as determined by PET and by DSC-MRI and to identify differences between these methods. Seven healthy volunteers were studied with (15)O-PET (H(2)(15)O and C(15)O) and gradient-echo echo-planar DSC-MRI at 1.5 T. In the DSC-MRI study with bolus injection of contrast agent, deconvolution analysis was performed. Comparison of gray-to-white matter ratios showed fairly good agreement between PET and DSC-MRI for all parameters (relative CBV, relative CBF, and relative MTT), confirming the validity of relative measurements with DSC-MRI. However, quantitative MTT measured by DSC-MRI was significantly shorter than that measured by PET in cerebral cortical regions (2.8 to 3.0 secs for DSC-MRI versus 3.9 to 4.3 secs for PET) and the centrum semiovale (3.5 secs for DSC-MRI versus 4.8 secs for PET). These discrepancies may be because of the differences in the intrinsic sensitivity of each imaging modality to vascular components; whereas PET measurement of CBV is equally sensitive to all vascular components, measurement with DSC-MRI originates from the microvasculature in the vicinity of the brain parenchyma. This underlying difference may influence interpretation of MTT determined by PET or by DSC-MRI for patients with cerebrovascular disease.

Adult↗
PubMed2006

Quantitative analysis for estimating binding potential of the peripheral benzodiazepine receptor with [(11)C]DAA1106.

[(11)C]DAA1106 is a potent and selective ligand for the peripheral benzodiazepine receptor (PBR) with high affinity. It has been reported that the density of PBR is related to brain damage, so a reliable tracer method for the evaluation of PBR would be of use. We evaluated a quantification method of [(11)C]DAA1106 binding in simulated data and human brain data. In the simulation study, the reliability of parameters estimated from the nonlinear least-squares (NLS) method, graphical analysis (GA), and multilinear analysis (MA) was evaluated. In GA, variation of the estimated distribution volume (DV) was small. However, DV was underestimated as noise increased. In MA, bias was smaller, and variation of the estimated DV was larger than in GA. In NLS, although variation was larger than in GA, it was small enough in regions of interest analysis, and not only DV but also binding potential (BP), determined from the k(3)/k(4) without any constraint, could be estimated. The variation of BP estimated with NLS became larger as k(3) or k(4) became smaller. In human studies with normal volunteers, regions of interest were drawn on several brain regions, BP was calculated by NLS, and DV was also estimated by NLS, GA, and MA. As a result, DVs estimated with each method were well correlated. However, there was no correlation between BP with NLS and DV with NLS, GA, and MA, because of the variation of K(1)/k(2) between individuals. In conclusion, BP is estimated most reliably by NLS with the two-tissue compartment model.

Acetamides↗
PubMed2006

HMG-CoA reductase inhibitor fluvastatin prevents angiotensin II-induced cardiac hypertrophy via Rho kinase and inhibition of cyclin D1.

HMG-CoA reductase inhibitors, so called statins, decrease cardiac events. Previous studies have shown that HMG-CoA reductase inhibitors inhibit cardiomyocyte hypertrophy in vitro and in vivo by blocking Rho isoprenylation. We have shown that the G1 cell cycle regulatory proteins cyclin D1 and Cdk4 play important roles in cardiomyocyte hypertrophy. However, the relation between Rho and cyclin D1 in cardiomyocyte is unknown. To investigate whether HMG-CoA reductase inhibitors prevent cardiac hypertrophy through attenuation of Rho and cyclin D1, we studied the effect of fluvastatin on angiotensin II-induced cardiomyocyte hypertrophy in vitro and in vivo. Angiotensin II increased the cell surface area and [(3)H]leucine uptake of cultured neonatal rat cardiomyocytes and these changes were suppressed by fluvastatin treatment. Angiotensin II also induced activation of Rho kinase and increased cyclin D1, both of which were also significantly suppressed by fluvastatin. Specific Rho kinase inhibitor, Y-27632 inhibited angiotensin II-induced cardiomyocyte hypertrophy and increased cyclin D1. Overexpression of cyclin D1 by adenoviral gene transfer induced cardiomyocyte hypertrophy, as evidenced by increased cell size and increased protein synthesis; this hypertrophy was not diminished by concomitant treatment with fluvastatin. Infusion of angiotensin II to Wistar rats for 2 weeks induced hypertrophic changes in cardiomyocytes, and this hypertrophy was prevented by oral fluvastatin treatment. These results show that an HMG-CoA reductase inhibitor, fluvastatin, prevents angiotensin II-induced cardiomyocyte hypertrophy in part through inhibition of cyclin D1, which is linked to Rho kinase. This novel mechanism discovered for fluvastatin could be revealed how HMG-CoA reductase inhibitors are preventing cardiac hypertrophy.

Adenoviridae Infections↗
PubMed2006

Comparison of orifice area by transthoracic three-dimensional Doppler echocardiography versus proximal isovelocity surface area (PISA) method for assessment of mitral regurgitation.

Effective regurgitant orifice area is a useful index of the severity of mitral regurgitation (MR). The calculation of regurgitant orifice area using the proximal isovelocity surface area (PISA) method has some technical limitations. Three-dimensional reconstruction of the MR jet was performed using the Live 3D system on a Sonos 7500 to measure regurgitant orifice area directly in 109 cases of MR. Regurgitant orifice area was also measured by quantitative 2-dimensional echocardiography and by the PISA method. To analyze the shape of the regurgitant orifice, the ratio of the long axis to the short axis of the orifice (the L/S ratio) was calculated. Regurgitant orifice area on 3-dimensional echocardiography showed an almost identical correlation with that obtained by quantitative echocardiography (r = 0.91, p <0.0001, slope = 0.97) regardless of the L/S ratio. It was also significantly correlated with orifice area obtained using the PISA method (r = 0.93, p <0.0001). However, orifice area on 3-dimensional echocardiography was significantly larger than that obtained using the PISA method in the whole study group and in the 62 cases of MR with L/S ratios >1.5, whereas the correlation was almost identical in cases of MR with L/S ratios < or =1.5. Orifice area obtained using the PISA method also underestimated that obtained by quantitative echocardiography in cases of MR with L/S ratios >1.5. Three-dimensional echocardiography provided robust values independent of the eccentricity of the MR jet or of cardiac rhythm. In conclusion, the direct measurement of the regurgitant orifice area of MR with 3-dimensional Doppler echocardiography could be a promising method to overcome the limitations of the PISA method, especially in cases of MR with elliptic orifice shapes.

Aged↗
PubMed2006

Cytokines produced by bone marrow cells can contribute to functional improvement of the infarcted heart by protecting cardiomyocytes from ischemic injury.

It is well known that the implantation of bone marrow mononuclear cells (BM-MNCs) into ischemic hearts can induce angiogenesis and improve cardiac function after myocardial infarction, but the precise mechanisms of these actions are unclear. We hypothesize that the cytokines produced by BM-MNCs play a key role in this cell-based therapy. BM-MNCs from rats were cultured under normoxic or hypoxic (1% O2) conditions for 24 h, and then supernatants were collected for study. ELISA and Western blotting analysis showed that various cytokines, including VEGF, IL-1 beta, PDGF, and IGF-1, were produced from BM-MNCs, some of which were enhanced significantly under hypoxia stimulation. When compared with a control blank medium, the supernatants of BM-MNCs cultured under normoxic or hypoxic conditions inhibited apoptosis significantly and preserved the contractile capacity of isolated adult rat cardiomyocytes in vitro (P < 0.05). Using a rat model of acute myocardial infarction, we injected the supernatants of BM-MNCs or control medium intramyocardially on day 0 and then intraperitoneally on days 2, 4, and 6 after infarction. When compared with the control medium, the supernatants of BM-MNCs cultured under both normoxic or hypoxic conditions increased the microvessel density and decreased the fibrotic area in the infarcted myocardium significantly, contributing to remarkable improvement in cardiac function. Various cytokines were produced by BM-MNCs, and these cytokines contributed to functional improvement of the infarcted heart by directly preserving the contractile capacity of the myocardium, inhibiting apoptosis of cardiomyocytes, and inducing therapeutic angiogenesis of the infarcted heart.

Acute Disease↗
PubMed2006

Changes in growth factor and cytokine expression in biliary obstructed rat liver and their relationship with delayed liver regeneration after partial hepatectomy.

AIM: To study the effects of obstructive jaundice on liver regeneration after partial hepatectomy. METHODS: Hepatocyte growth factor (HGF), its receptor, c-Met, vascular endothelial growth factor (VEGF) and transforming growth factor-beta1 (TGF-beta1) mRNA expression in both liver tissue and isolated liver cells were investigated after biliary obstruction (BO) by quantitative reverse-transcription polymerase chain reaction (RT-PCR) using a LightCycler. Immunohistochemical staining for desmin and alpha-smooth muscle actin (alpha-SMA) was also studied. Regenerating liver weight and proliferating cell nuclear antigen (PCNA) labeling index, and growth factor expression were then evaluated after 70% hepatectomy with concomitant internal biliary drainage in BO rats or sham-operated rats. RESULTS: Hepatic TGF-beta1 mRNA levels increased significantly 14 days after BO, and further increased with duration of cholestasis. Meanwhile, HGF and VEGF tended to increase, but was not significant. In cell isolates, TGF-beta1 mRNA was found mainly in the hepatic stellate cell (HSC) fraction. Immunohistochemical studies revealed an increased number of HSCs (desmin-positive cells) and activated HSCs (alpha-SMA-positive cells) in portal areas after BO. In a hepatectomy model, liver regeneration was delayed in BO rats, as compared to sham-operated rats. TGF-beta1 mRNA was significantly up-regulated up to 48 h after hepatectomy, and the earlier HGF mRNA peak was lost in BO rats. CONCLUSION: BO induces HSCs proliferation and activation, leading to up-regulation of TGF-beta1 mRNA and suppression of HGF mRNA in livers. These altered expression patterns may be strongly involved in delayed liver regeneration after hepatectomy with obstructive jaundice.

Actins↗
PubMed2006

Usefulness of high-resolution real-time three-dimensional echocardiography to visualize the left ventricular endocardial surface in myocardial infarction.

High-resolution real-time 3-dimensional echocardiography (RT3DE) allows observation of the left ventricular endocardial surface in vivo. This study was performed to characterize the endocardial surface structure and its contractile function in the myocardial infarction (MI) zone in relation to the healing stage. RT3DE was performed in 90 subjects: 10 normal subjects, 50 patients with Q-wave MI 2 weeks after onset (acute MI), and 30 patients >2 months after onset (healed MI). Recordings of the left ventricular endocardial surface allowed observation of the endocardial structure in 76 patients (84%) from the apical window. The endocardial surface of normal myocardium has rough muscle folds that shrink during systole, implying endocardial contraction. In acute MI, the endocardial surface had lost systolic contraction, but appeared as normal surface structure and showed normal acoustic intensity. The endocardial surface of healed MI showed loss of systolic contraction, disappearance of folds (smooth surface), and high acoustic intensity. The frequencies of smooth surface and highest acoustic intensity were significantly higher in healed MI than acute MI (72% vs 32%, 68% vs 37%, p <0.05, respectively). Loss of systolic endocardial contraction was a common finding of Q-wave MI irrespective of the healing stage, and we could roughly estimate the size of the MI from the spatial extent of the noncontractile zone with reasonable reproducibility (r = 0.90, p <0.001). In conclusion, RT3DE is a new modality that allows observation of the structure and contraction of the endocardial surface of the left ventricular wall. We can make rough estimation of the size of the MI and its healing stage from endocardial observation with RT3DE.

Adult↗
PubMed2006

Age-related degeneration of corpus callosum measured with diffusion tensor imaging.

The corpus callosum is the major commissure connecting the cerebral hemispheres, and there is evidence of its change with aging. The sub-regions of the corpus callosum (genu, rostral body, anterior midbody, posterior midbody, isthmus, splenium) respectively comprise fibers connecting heteromodal- and unimodal-associated cortical regions, and it is known that abnormalities of the corpus callosum are correlated with abnormalities in cognition and behavior. Yet, little is known about changes in the tissue characteristics of its sub-regions. We assessed age-related changes in fractional anisotropy and mean diffusivity in the sub-regions of the corpus callosum using diffusion tensor imaging. We studied 42 healthy right-handed individuals aged 21-73 years. There were no significant interactions of sex x region. Age has significant negative correlation with fractional anisotropy in the genu (P < 0.001), rostral body (P < 0.001), and isthmus (P = 0.005). Fractional anisotropy of the anterior midbody was correlated negatively with age at a trend level (P = 0.022). Age was significantly positively correlated with mean diffusivity in the genu (P = 0.001), rostral body (P = 0.002), anterior midbody (P = 0.001), and isthmus (P = 0.001). Age-related changes were detected in the sub-regions where their projection areas are thought to be vulnerable to normal aging. This suggested that fractional anisotropy and mean diffusivity values of the corpus callosum sub-regions could serve as markers of disturbance across the respective projection areas.

Adult↗
PubMed2006

Age-related decline of dopamine synthesis in the living human brain measured by positron emission tomography with L-[beta-11C]DOPA.

Loss of dopamine synthesis in the striatum with normal human aging has been observed in the postmortem brain. To investigate whether there is age-associated change in dopamine synthesis in the extrastriatal brain regions similar to that in the striatum, positron emission tomography studies with (11)C-labelled l-DOPA were performed on 21 normal healthy male subjects (age range 20-67 years). Decline in the tissue fraction of gray matter per region of interest was also investigated. The overall uptake rate constant for each region of interest was quantified by the Patlak plot method using the occipital cortex as reference region. Regions of interest were set on the dorsolateral prefrontal cortex, lateral temporal cortex, medial temporal cortex, occipital cortex, parietal cortex, anterior cingulate, thalamus, midbrain, caudate nucleus, and putamen. Test-retest analysis indicated good reproducibility of the overall uptake rate constant. Significant age-related declines of dopamine synthesis were observed in the striatum and extrastriatal regions except midbrain. The decline in the overall uptake rate constant was more prominent than in the tissue fraction of gray matter. These results indicate that the previously demonstrated age-related decline in striatal dopamine synthesis extends to several extrastriatal regions in normal human brain.

Adult↗