Spiking Expression of μ-Crystallin mRNA during Treatment with Methimazole in Patients with Graves' Hyperthyroidism

μ-Crystallin is an NADPH-dependent cytosolic T3-binding protein. A knockout study in mice showed that μ-crystallin has a physiological function as a reservoir of T3 in the cytoplasm in vivo. Patients with nonsyndromic deafness were reported to have point mutations in the μ-crystallin gene. The expression of μ-crystallin is regulated by multiple factors. The present study was performed to determine whether thyroid function is related to the expression of μ-crystallin mRNA in peripheral mononuclear cells. We examined 23 normal healthy male and female subjects and 15 patients with Graves' disease. μ-Crystallin protein expression was determined immunohistochemically in peripheral mononuclear cells. The expression of μ-crystallin mRNA was assessed by reverse transcription of total RNA from peripheral mononuclear cells followed by quantitative PCR. μ-Crystallin protein was detected in peripheral mononuclear cells. The mRNA expression was negatively correlated with age in normal female subjects. The values in female subjects were significantly higher than those in males. The values were positively correlated with serum TSH concentration. The values of the thyrotoxic patients with Graves' disease were lower than those in healthy subjects. A transient increase in μ-crystallin expression was observed within 14-42 days after the initial treatment with antithyroid medication. Thyroid hormone inversely relates to the expression of μ-crystallin mRNA in euthyroid mononuclear cells. Abrupt suppression of thyroid function leads to overexpression of μ-crystallin mRNA in thyrotoxic mononuclear cells. Thyroid hormone-regulated μ-crystallin expression may control thyroid hormone action via the intracytoplasmic T? capacity.ArticleHORMONE AND METABOLIC RESEARCH. 41(7):548-553 (2009)journal articl

Fluorescence multispectral imaging-based diagnostic system for atherosclerosis

Background: Composition of atherosclerotic arterial walls is rich in lipids such as cholesterol, unlike normal arterial walls. In this study, we aimed to utilize this difference to diagnose atherosclerosis via multispectral fluorescence imaging, which allows for identification of fluorescence originating from the substance in the arterial wall. Methods: The inner surface of extracted arteries (rabbit abdominal aorta, human coronary artery) was illuminated by 405 nm excitation light and multispectral fluorescence images were obtained. Pathological examination of human coronary artery samples were carried out and thickness of arteries were calculated by measuring combined media and intima thickness. Results: The fluorescence spectra in atherosclerotic sites were different from those in normal sites. Multiple regions of interest (ROI) were selected within each sample and a ratio between two fluorescence intensity differences (where each intensity difference is calculated between an identifier wavelength and a base wavelength) from each ROI was determined, allowing for discrimination of atherosclerotic sites. Fluorescence intensity and thickness of artery were found to be significantly correlated. Conclusions: These results indicate that multispectral fluorescence imaging provides qualitative and quantitative evaluations of atherosclerosis and is therefore a viable method of diagnosing the disease

Trends in incidence and mortality of tuberculosis in Japan : a population-based study, 1997–2016

Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (−6.2% and −5.4%, respectively) and women (−5.7% and −4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035

Clinical efficacy and safety of monthly oral ibandronate 100 mg versus monthly intravenous ibandronate 1 mg in Japanese patients with primary osteoporosis

Summary: The MOVEST study evaluated the efficacy and safety of monthly oral ibandronate versus licensed monthly IV ibandronate in Japanese osteoporotic patients. Relative BMD gains after 12 months were 5.22 % oral and 5.34 % IV, showing non-inferiority of oral to IV ibandronate (primary endpoint). No new safety concerns were identified. Introduction: The randomized, phase 3, double-blind MOVEST (Monthly Oral VErsus intravenouS ibandronaTe) study evaluated the efficacy and safety of monthly oral ibandronate versus the licensed monthly intravenous (IV) ibandronate regimen in Japanese patients with osteoporosis. Methods: Ambulatory patients aged ?55 years with primary osteoporosis were randomized to receive oral ibandronate 100 mg/month plus monthly IV placebo, or IV ibandronate 1 mg/month plus monthly oral placebo. The primary endpoint was non-inferiority of oral versus IV ibandronate with respect to bone mineral density (BMD) gains at the lumbar spine after 12 months of treatment. Results: Four hundred twenty-two patients were enrolled with 372 patients in the per-protocol set (183 and 189 in the oral and IV ibandronate groups, respectively). The relative change from baseline in lumbar spine BMD values for the oral and IV ibandronate groups, respectively, was 5.22 % (95 % confidence interval [CI] 4.65, 5.80) and 5.34 % (95 % CI 4.78, 5.90). The least squares mean difference between the two groups was ?0.23 % (95 % CI ?0.97, 0.51), showing non-inferiority of oral ibandronate to IV ibandronate (non-inferiority limit = ?1.60). Changes in BMD values at other sites, and bone turnover marker levels in the oral ibandronate group, were comparable with those of the IV group. The safety profile was similar to that previously demonstrated; no new safety concerns were identified. Conclusions: This study demonstrated the non-inferiority of oral ibandronate 100 mg/month to IV ibandronate 1 mg/month (licensed dose in Japan) in increasing lumbar spine BMD in Japanese patients with primary osteoporosis

Improved measurement of time-dependent CP violation in B0 -> J/Psi pi0 decays

We report improved measurements of time-dependent CP violation parameters for $B^0(\bar{B}^0) \to J/\psi \pi^0$ decay. This analysis is based on 535 million $B\bar{B}$ pairs accumulated at the $\Upsilon(4S)$ resonance with the Belle detector at the KEKB asymmetric-energy e^+e^- collider. From the distribution of proper time intervals between the two B decays, we obtain the following CP violation parameters $\mathcal{S}_{J/\psi \pi^0} = -0.65\pm0.21 (\rm{stat})\pm0.05 (\rm{syst})$ and $\mathcal{A}_{J/\psi \pi^0} = +0.08\pm0.16 (\rm{stat})\pm0.05 (\rm{syst})$, which are consistent with Standard Model expectations.Comment: Resubmitted to PRD(RC), including 4 figures, 6pages Revision has been made according to communication with PRD referee

Observation of B^0 \to D^{*-} \tau^+ \nu_{\tau} decay at Belle

We report an observation of the decay $B^0\to D^{*-} \tau^+ \nu_{\tau}$ in a data sample containing $535\times10^6$ $B\bar{B}$ pairs collected with the Belle detector at the KEKB asymmetric-energy $e^+e^-$ collider. We find a signal with a significance of 5.2 standard deviations and measure the branching fraction $\mathcal{B}(B^0\to D^{*-} \tau ^+ \nu_{\tau})=(2.02 ^{+0.40}_{-0.37} (stat) \pm 0.37 (syst))$. This is the first observation of an exclusive $B$ decay with a $b \to c \tau \nu_{\tau}$ transition.Comment: 6 pages, 3 figures, submitted to Phys. Rev. Let

Treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the effect of radiation therapy

Hypoxia-inducible factor-1 (HIF-1) has been reported to promote tumour radioresistance; therefore, it is recognised as an excellent target during radiation therapy. However, the inhibition of HIF-1 in unsuitable timing can suppress rather than enhance the effect of radiation therapy because its anti-angiogenic effect increases the radioresistant hypoxic fraction. In this study, we imaged changes of HIF-1 activity after treatment with radiation and/or an HIF-1 inhibitor, YC-1, and optimised their combination. Hypoxic tumour cells were reoxygenated 6 h postirradiation, leading to von Hippel-Lindau (VHL)-dependent proteolysis of HIF-1α and a resultant decrease in HIF-1 activity. The activity then increased as HIF-1α accumulated in the reoxygenated regions 24 h postirradiation. Meanwhile, YC-1 temporarily but significantly suppressed HIF-1 activity, leading to a decrease in microvessel density and an increase in tumour hypoxia. On treatment with YC-1 and then radiation, the YC-1-mediated increase in tumour hypoxia suppressed the effect of radiation therapy, whereas on treatment in the reverse order, YC-1 suppressed the postirradiation upregulation of HIF-1 activity and consequently delayed tumour growth. These results indicate that treatment regimen determines whether an HIF-1 inhibitor enhances or inhibits the therapeutic effect of radiation, and the suppression of the postirradiation upregulation of HIF-1 activity is important for the best therapeutic benefit

Search for B -> h(*) nu nubar Decays at Belle

We present a search for the rare decays B -> h(*) nu nubar, where h(*) stands for a light meson. A data sample of 535 million BBbar pairs collected with the Belle detector at the KEKB e+e- collider is used. Signal candidates are required to have an accompanying B meson fully reconstructed in a hadronic mode and signal-side particles consistent with a single h(*) meson. No significant signal is observed and we set upper limits on the branching fractions at 90% confidence level. The limits on B0 -> K*0 nu nubar and B+ -> K+ nu nubar decays are more stringent than the previous constraints, while the first searches for B0 -> K0 nu nubar, pi0 nu nubar, rho0 nu nubar, phi nu nubar and B+ -> K*+ nu nubar, rho+ nu nubar are reported.Comment: 6 pages, 2 figures, submit to PR

Angular analysis of B0→K∗(892)0ℓ+ℓ−B^0 \to K^\ast(892)^0 \ell^+ \ell^-

We present a measurement of angular observables, $P_4'$, $P_5'$, $P_6'$, $P_8'$, in the decay $B^0 \to K^\ast(892)^0 \ell^+ \ell^-$, where $\ell^+\ell^-$ is either $e^+e^-$ or $\mu^+\mu^-$. The analysis is performed on a data sample corresponding to an integrated luminosity of $711~\mathrm{fb}^{-1}$ containing $772\times 10^{6}$ $B\bar B$ pairs, collected at the $\Upsilon(4S)$ resonance with the Belle detector at the asymmetric-energy $e^+e^-$ collider KEKB. Four angular observables, $P_{4,5,6,8}'$ are extracted in five bins of the invariant mass squared of the lepton system, $q^2$. We compare our results for $P_{4,5,6,8}'$ with Standard Model predictions including the $q^2$ region in which the LHCb collaboration reported the so-called $P_5'$ anomaly.Comment: Conference paper for LHC Ski 2016. SM prediction for $P_{6}'$ corrected and reference for arXiv:1207.2753 adde