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K Hara

Publications and source records attributed to K Hara.

At least 19 recordsLinked to original sources
PubMed2006

Inhibitory effect of gabapentin on N-methyl-D-aspartate receptors expressed in Xenopus oocytes.

BACKGROUND: Gabapentin (GBP) is a prescription drug used for the treatment of neuropathic and post-operative pain. However, the mechanism by which it exerts its analgesic action is not well understood. Because intrathecal administration of GBP has been shown to exert antinociceptive effects in animal studies, we hypothesized that the spinal cord may be a plausible action site. METHODS: We examined the effects of GBP on neurotransmitter-gated ion channels and G protein-coupled inwardly rectifying potassium (GIRK) channels distributed in the spinal cord and involved in pain modulation. Recombinant human NR1/NR2A N-methyl-D-aspartate (NMDA), alpha(1)beta(2)gamma(2S)gamma-aminobutyric acid type A (GABA(A)) or alpha(1) glycine receptors, or GIRK1/GIRK2 channels were expressed in Xenopus laevis oocytes and the effects of GBP (0.1-1000 microM) on them were assessed using a two-electrode, voltage-clamp system. RESULTS: GABA(A) and glycine receptors and GIRK channels were not affected by GBP, even at the highest concentrations. Conversely, NMDA receptors were inhibited by GBP in a concentration-dependent manner, with significant inhibition observed at 10 microM. At 30 microM, GBP inhibited the glutamate-concentration response curve without changing the half-maximal effective concentration or the Hill coefficient, indicating a non-competitive inhibition. Glycine decreased the inhibitory effect in a concentration-dependent manner. CONCLUSIONS: These findings suggest that the inhibitory effect of GBP on NMDA receptors may play an important role in the antinociceptive property of GBP; however, it does not appear that GABA(A) and glycine receptors or GIRK channels contribute to the pharmacological properties of GBP.

Amines↗
PubMed2006

Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase.

Target of Rapamycin (TOR), a giant protein kinase expressed by all eucaryotic cells, controls cell size in response to nutrient signals. In metazoans, cell and organismal growth is controlled by nutrients and the insulin/insulin-like growth factor (IGF) system, and the understanding of how these inputs coordinately regulate TOR signaling has advanced greatly in the past 5 years. In single-cell eucaryotes and Caenorhabditis elegans, TOR is a dominant regulator of overall mRNA translation, whereas in higher metazoans, TOR controls the expression of a smaller fraction of mRNAs that is especially important to cell growth. TOR signals through two physically distinct multiprotein complexes, and the control of cell growth is mediated primarily by TOR complex 1 (TORC1), which contains the polypeptides raptor and LST8. Raptor is the substrate binding element of TORC1, and the ability of raptor to properly present substrates, such as the translational regulators 4E-BP and p70 S6 kinase, to the TOR catalytic domain is essential for their TOR-catalysed phosphorylation, and is inhibited by the Rapamycin/FKBP-12 complex. The dominant proximal regulator of TORC1 signaling and kinase activity is the ras-like small GTPase Rheb. Rheb binds directly to the mTOR catalytic domain, and Rheb-GTP enables TORC1 to attain an active configuration. Insulin/IGF enhances Rheb GTP charging through the ability of activated Akt to inhibit the Rheb-GTPase-activating function of the tuberous sclerosis heterodimer (TSC1/TSC2). Conversely, energy depletion reduces Rheb-GTP charging through the ability of the adenosine monophosphate-activated protein kinase to phosphorylate TSC2 and stimulate its Rheb-GTPase activating function, as well as by HIFalpha-mediated transcriptional responses that act upstream of the TSC1/2 complex. Amino-acid depletion inhibits TORC1 acting predominantly downstream of the TSC complex, by interfering with the ability of Rheb to bind to mTOR. The components of the insulin/IGF pathway to TORC1 are now well established, whereas the elements mediating the more ancient and functionally dominant input of amino acids remain largely unknown.

Animals↗
PubMed2006

Finasteride 1 mg has no inhibitory effect on omeprazole metabolism in extensive and poor metabolizers for CYP2C19 in Japanese.

OBJECTIVE: To examine the inhibitory effect of finasteride 1 mg on the metabolism of omeprazole in genetically determined extensive (EMs) and poor metabolizers (PMs) for CYP2C19 in young healthy Japanese male subjects. METHODS: Twenty-four volunteers participated in this study, among whom 12 were homozygous EMs and 12 were PMs for CYP2C19. A single center, controlled, randomized, open, crossover study with a 5 day washout between the two study periods was performed. Each of the six EMs and PMs received a single oral 20 mg dose of omeprazole on day 1 (treatment I). After a 5 day washout period, these subjects received 1 mg of finasteride once a day for three consecutive days, and a single oral 20 mg dose of omeprazole was co-administered on day 3 (treatment II). The 12 other EMs and PMs received treatments I and II in reverse. Plasma samples were collected for up to a 12 hours postdose of omeprazole, and the pharmacokinetic parameters of omeprazole were determined. RESULTS: The geometric mean ratio (GMR) for the AUC((0-12 hr)) of omeprazole when co-administered with finasteride/omeprazole alone is 1.13 (90%CI, 1.03, 1.25) and 0.96 (0.88, 1.05) in EMs and PMs, respectively. Finasteride did not significantly alter C(max), T(max) and t(1/2) in both genotypes. CONCLUSION: Finasteride 1 mg, widely used for the treatment of androgenetic alopecia in men, did not meaningfully increase omeprazole exposure (20 mg) in both EMs and PMs for CYP2C19. These results indicate that finasteride does not meaningfully inhibit CYP2C19 activity in vivo at the dose of 1 mg.

Adult↗
PubMed2006

Measurement of the branching fraction, polarization, and asymmetry for decays, and determination of the Cabibbo-Kobayashi-Maskawa phase.

We have measured the branching fraction , longitudinal polarization fraction f(L), and CP asymmetry coefficients A and S for B(0) --> rho(+) rho(-) decays with the Belle detector at the KEKB e(+) e(-) collider using 253 Fb(-1) of data. We obtain B = [22.8 +/- 3.8(stat)(+2.3)(-2.6)(syst)] x 10(-6), f(L) = 0.941 (+0.034)(-0.040)(stat) +/- 0.030(syst). A = 0.00 +/- 0.30(stat) +/- 0.09(syst) and S = 0.08 +/- 0.09(syst). These values are used to constrain the Cabibbo-Kobayashi-Maskawa phase ; the solution consistent with the standard model is phi(2) = (88 +/- 17) degrees or 59 degrees < phi(2) < 115 degrees at 90% C.L.

Journal Article↗
PubMed2006

New HSN2 mutation in Japanese patient with hereditary sensory and autonomic neuropathy type 2.

The authors report a Japanese patient with hereditary sensory and autonomic neuropathy type 2 (HSAN2) who has a new mutation of the HSN2 gene. The pathologic findings of the patient matched those of Canadian patients. They identified a homozygous 1134-1135 ins T mutation, resulting in a frameshift, and the subsequent premature stop codon at residue 378. These observations support the hypothesis that HSN2 is a causative gene for HSAN2.

Adult↗
PubMed2006

The value of multichannel MEG and EEG in the presurgical evaluation of 70 epilepsy patients.

OBJECTIVE: To evaluate the sensitivity of a simultaneous whole-head 306-channel magnetoencephalography (MEG)/70-electrode EEG recording to detect interictal epileptiform activity (IED) in a prospective, consecutive cohort of patients with medically refractory epilepsy that were considered candidates for epilepsy surgery. METHODS: Seventy patients were prospectively evaluated by simultaneously recorded MEG/EEG. All patients were surgical candidates or were considered for invasive EEG monitoring and had undergone an extensive presurgical evaluation at a tertiary epilepsy center. MEG and EEG raw traces were analysed individually by two independent reviewers. RESULTS: MEG data could not be evaluated due to excessive magnetic artefacts in three patients (4%). In the remaining 67 patients, the overall sensitivity to detect IED was 72% (48/67 patients) for MEG and 61% for EEG (41/67 patients) analysing the raw data. In 13% (9/67 patients), MEG-only IED were recorded, whereas in 3% (2/67 patients) EEG-only IED were recorded. The combined sensitivity was 75% (50/67 patients). CONCLUSION: Three hundred and six-channel MEG has a similarly high sensitivity to record IED as EEG and appears to be complementary. In one-third of the EEG-negative patients, MEG can be expected to record IED, especially in the case of lateral neocortical epilepsy and/or cortical dysplasia.

Adolescent↗
PubMed2006

Detection of pattern of myocardial fibrosis by contrast-enhanced MRI: is redefinition of uremic cardiomyopathy necessary for management of patients?

Cardiac magnetic resonance imaging (CMR) can detect cardiac tissue components for several kinds of cardiac myopathies. Mark et al. found two patterns of late gadolinium enhancement (LGE) in patients with uremic cardiomyopathy: focal LGE and diffuse LGE. The impact of these contrast-enhanced CMR findings on clinical outcomes warrants assessment in future studies.

Cardiomyopathies↗
PubMed2005

Improved evidence for direct CP violation in B0-->pi+pi- decays and model-independent constraints on phi2.

We present a new measurement of the time-dependent CP-violating parameters in B(0)--> pi(+)pi(-) decays with 275 x 10(6) BB pairs collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider operating at the Gamma(4S) resonance. We find 666 +/- 43 B(0) --> pi(+)pi(-) events and measure the CP-violating parameters: S(pipi) = -0.67 +/- 0.16(stat) +/- 0.06(syst) and A(pipi) = +0.56 +/- 0.12(stat) +/- 0.06(syst). We find evidence for large direct CP violation with a significance greater than 4 standard deviations for any S(pipi) value. Using isospin relations, we obtain 95.4% confidence intervals for the Cabibbo-Kobayashi-Maskawa quark-mixing matrix angle phi(2) of 0 degree < phiv(2) < 19 degrees and 71 degrees < phi(2) < 180 degrees.

Journal Article↗
PubMed2005

Studies of CP violation in B-->J/PsiK* decays.

CP violation in B-->J/PsiK* decays is studied using an angular analysis in a data sample of 253 fb(-1) recorded with the Belle detector at the KEKB e(+)e(-) collider. The flavor separated measurements of the decay amplitudes indicate no evidence for direct CP violation. T-odd CP violation is studied using the asymmetries in triple product correlations, and the results are consistent with the standard model null predictions. The time-dependent angular analysis gives the following values of CP-violating parameters: sin(2phi(1) = 0.24 +/- 0.31 +/- 0.05 and cos(2phi(1)=0.56 +/- 0.79 +/- 0.11.

Journal Article↗
PubMed2005

Measurement of time-dependent CP-violating asymmetries in B0 --> K(s)0K(s)0K(s)0 decay.

We present a measurement of CP-violation parameters in the B0 --> K(s)0K(s)0K(s)0 decay based on a sample of 275 x 10(6) BB pairs collected at the upsilon(4S) resonance with the Belle detector at the KEKB energy-asymmetric e+e- collider. One neutral B meson is fully reconstructed in the decay B0 --> K(s)0K(s)0K(s)0, and the flavor of the accompanying B meson is identified from its decay products. CP-violation parameters are obtained from the asymmetry in the distributions of the proper-time interval between the two B decays: S = +1.26 +/- 0.68(stat) +/- 0.20(syst) and [symbol: see text] = +0.54 +/- 0.34(stat) +/- 0.09(syst).

Journal Article↗
PubMed2005

Measurement of the time-dependent CP-violating asymmetry in B(0)-->K(0)(S)pi(0)gamma decays.

We present a new measurement of CP-violation parameters in B(0)-->K(0)(S)pi(0)gamma decay based on a sample of 275 x 10(6) BB pairs collected at the Gamma(4S) resonance with the Belle detector at the KEKB energy-asymmetric e(+)e(-) collider. One of the B mesons is fully reconstructed in the B(0)-->K(0)(S)pi(0)gamma decay. The flavor of the accompanying B meson is identified from its decay products. CP-violation parameters are obtained from the asymmetry in the distribution of the proper time intervals between the two B decays. We obtain SK(0)(S)(pi(0)gamma) = -0.58(+0.46)(-0.38)(stat) +/- 0.11(syst) and AK(0)(S)(pi(0)gamma) = +0.03 +/- 0.34(stat) +/- 0.11(syst), for the K(0)(S)pi(0) invariant mass covering the full range up to 1.8 GeV/c2. We also measure the CP-violation parameters for the case B(0)-->K(*0)(-->K(0)(S)pi(0))gamma and obtain S(K(*0)gamma) = -0.79(+0.63)(-0.50)(stat) +/- 0.10(syst) for A(K(*0)gamma) fixed at 0.

Journal Article↗
PubMed2005

Absence of an association between the polymorphisms in the genes encoding adiponectin receptors and type 2 diabetes.

AIMS/HYPOTHESIS: Secreted by adipocytes, adiponectin is a hormone that acts as an antidiabetic and anti-atherogenic adipokine. We recently cloned the genes encoding two adiponectin receptors (ADIPOR1 and ADIPOR2). The aim of this study was to examine whether ADIPOR1 and/or ADIPOR2 play a major role in genetic susceptibility to insulin resistance or type 2 diabetes in the Japanese population. METHODS: By direct sequencing and a search of public databases, we identified single nucleotide polymorphisms (SNPs) in ADIPOR1 and ADIPOR2, and investigated whether these SNPs are associated with insulin resistance and type 2 diabetes in the Japanese population. RESULTS: The linkage disequilibrium (LD) in the chromosomal region of ADIPOR1 was almost completely preserved, whereas the LD in ADIPOR2 was less well preserved. None of the SNPs in ADIPOR1 or ADIPOR2 were significantly associated with insulin resistance or type 2 diabetes. No differences in ADIPOR1 or ADIPOR2 haplotype frequencies were observed between type 2 diabetic and non-diabetic subjects. CONCLUSIONS/INTERPRETATION: Genetic variations in ADIPOR1 or ADIPOR2 are unlikely to lead to a common genetic predisposition to insulin resistance or type 2 diabetes in the Japanese population.

Diabetes Mellitus, Type 2↗
PubMed2005

Light source position and reflectance estimation from a single view without the distant illumination assumption.

Several techniques have been developed for recovering reflectance properties of real surfaces under unknown illumination. However, in most cases, those techniques assume that the light sources are located at inifinity, which cannot be applied safely to, for example, reflectance modeling of indoor environments. In this paper, we propose two types of methods to estimate the surface reflectance property of an object, as well as the position of a light source from a single view without the distant illumination assumption, thus relaxing the conditions in the previous methods. Given a real image and a 3D geometric model of an object with specular reflection as inputs, the first method estimates the light source position by fitting to the Lambertian diffuse component, while separating the specular and diffuse components by using an iterative relaxation scheme. Our second method extends that first method by using as input a specular component image, which is acquired by analyzing multiple polarization images taken from a single view, thus removing its constraints on the diffuse reflectance property. This method simultaneously recovers the reflectance properties and the light source positions by optimizing the linearity of a log-transformed Torrance-Sparrow model. By estimating the object's reflectance property and the light source position, we can freely generate synthetic images of the target object under arbitrary lighting conditions with not only source direction modification but also source-surface distance modification. Experimental results show the accuracy of our estimation framework.

Algorithms↗
PubMed2005

Effect of additives in lidocaine spray on postoperative sore throat, hoarseness and dysphagia after total intravenous anaesthesia.

BACKGROUND: Laryngo-tracheal lidocaine spray before intubation is associated with an increased risk of postoperative throat problems. Our study investigated the effect of additives contained in lidocaine spray on postoperative sore throat, hoarseness and dysphagia. METHODS: We compared the incidence and severity of postoperative throat complications after laryngo-tracheal application of lidocaine spray (40 mg), lidocaine (40 mg) or normal saline as placebo during laryngoscopy with total intravenous anaesthesia in 122 ASA I-III patients aged 15-87 years in a double-blinded, placebo-controlled study. The incidence and severity of postoperative sore throat, hoarseness and dysphagia were evaluated on the day of and the day after surgery. RESULTS: Sore throat and dysphagia were significantly more severe after lidocaine spray was used than after lidocaine or placebo was used. However, there was no significant difference in the incidence or severity of postoperative sore throat, hoarseness or dysphagia between the lidocaine group and the placebo group throughout the study. CONCLUSION: These results suggest that additives in lidocaine spray, not lidocaine itself, contribute to the increase in postoperative throat problems. Therefore, lidocaine spray should be avoided to prevent these unnecessary complications. Our findings also confirm that laryngo-tracheal lidocaine application does not prevent sore throat, hoarseness or dysphagia after total intravenous anaesthesia.

Adolescent↗
PubMed2005

Exfoliation of Helicobacter pylori from gastric mucin by glycopolypeptides from buttermilk.

In the human stomach, Helicobacter pylori, an ulcer pathogenic bacterium, colonizes the gastric mucosal layer primarily. The ability of glycopolypeptides (GPP) prepared from buttermilk to exfoliate H. pylori bound to gastric mucin was investigated. The GPP were prepared from buttermilk by digestion with trypsin, papain, pancreatin, bromelain, or pepsin. Helicobacter pylori ATCC 43504T and 43579 adhered more strongly to all of the GPP tested than to whole buttermilk, the soluble fraction of buttermilk, gastric mucin prepared from mouse stomach, or commercial pig gastric mucin. The GPP digested with trypsin, papain, or pancreatin were significantly more adherent. When the GPP concentration was 10 mg/mL, bound H. pylori ATCC 43504T, 43579, and 5 clinical isolates were exfoliated markedly from immobilized porcine gastric mucin following treatment with GPP digested with trypsin or pancreatin. This ability of GPP did not correlate with sialic acid content, indicating that sialic acid content is not important in the exfoliation of this microorganism. Such an ability may depend on the structure or number of sugar chains, or the position of sialic acid. We conclude that GPP promote the exfoliation of H. pylori bound to gastric mucin and prevent the de novo adherence of this microorganism. As such, GPP are a promising food material for preventing H. pylori infection.

Animals↗
PubMed2004

Study of time-dependent CP violation in B0-->J/psipi0 decays.

We report a measurement of CP asymmetry parameters in the decay B0(B (0))-->J/psipi(0), which is governed by the b-->cc d transition. The analysis is based on a 140 fb(-1) data sample accumulated at the Upsilon(4S) resonance by the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B meson in the J/psipi(0) final state is fully reconstructed for events used in this analysis. The accompanying B meson flavor is identified by its decay products. From the distribution of proper-time intervals between the two B decays, we obtain the following CP-violating parameters: S(J/psipi(0))=-0.72+/-0.42(stat)+/-0.09(syst) and A(J/psipi(0))=-0.01+/-0.29(stat)+/-0.03(syst).

Journal Article↗