Effects of Switching from Treatment with Amlodipine and Atorvastatin Using Two Pills to an Equal Dose of Single-Pill Therapy in Japanese Outpatients

This study examined whether switching from amlodipine and atorvastatin treatment using two pills to an equal dose of single-pill therapy is useful in Japanese outpatients. We retrospectively reviewed data obtained from 94 outpatients for whom treatment with two pills, namely amlodipine and atorvastatin, was switched to an equal dose of single-pill therapy in 11 hospitals. The criterion for enrollment in this study was that patients had switched their medication without changing other anti-hypertensive or anti-cholesterol drugs. Neither systolic nor diastolic blood pressure changed significantly after switching to an equal dose of single-pill therapy, whereas low-density lipoprotein (LDL) cholesterol levels significantly decreased after the medication was switched from 94±24 mg/dl to 89±17 mg/dl (p=0.015). A switch from medication with two separate pills of amlodipine and atorvastatin to an equal dose of single-pill therapy resulted in an overall decrease in LDL cholesterol. The results indicated that the switch to single-pill therapy might be a useful treatment

Effect of Taurine on Acinar Cell Apoptosis and Pancreatic Fibrosis in Dibutyltin Dichloride-induced Chronic Pancreatitis

The relationship between pancreatic fibrosis and apoptosis of pancreatic acinar cells has not been fully elucidated. We reported that taurine had an anti-fibrotic effect in a dibutyltin dichloride (DBTC)-chronic pancreatitis model. However, the effect of taurine on apoptosis of pancreatic acinar cells is still unclear. Therefore, we examined apoptosis in DBTC-chronic pancreatitis and in the AR42J pancreatic acinar cell line with/without taurine. Pancreatic fibrosis was induced by a single administration of DBTC. Rats were fed a taurine-containing diet or a normal diet and were sacrificed at day 5. The AR42J pancreatic acinar cell line was incubated with/without DBTC with taurine chloramines. Apoptosis was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay. The expression of Bad and Bcl-2 proteins in the AR42J cells lysates was detected by Western blot analysis. The apoptotic index of pancreatic acinar cells in DBTC-administered rats was significantly increased. Taurine treatment inhibited pancreatic fibrosis and apoptosis of acinar cells induced by DBTC. The number of TUNEL-positive cells in the AR42J pancreatic acinar cell lines was significantly increased by the addition of DBTC. Incubation with taurine chloramines ameliorated these changes. In conclusion, taurine inhibits apoptosis of pancreatic acinar cells and pancreatitis in experimental chronic pancreatitis

食道痛細胞におけるWntのベータカテ二ンTCF経路の活性化の検討

Although, accumulation of nuclear and cytoplasmic beta-catenin has been observed in ESCCs, mutation of APC and beta-catenin are not found in ESCCs. Therefore, another mechanism for cytoplasmic beta- catenin accumulation might exist in ESCCs. Materials and Methods: Human ESCCs cell lines and the 293 stable transfectants expressing Wnt-1, Wnt-5A, and Wnt-7A were cultured under standard conditions. The TOPFlash or FOPFlash reporter plasmids were transfected. Results: Transfected mutant beta-catenin as well as an axin fragment harbing the GSK3 beta interaction domain, the latter a potent GSK3 beta inhibitor. both robustly activated pTOPFlash in ESCCs cells. When pTOPFlash/pFOPFlash reporters were transfected in ESCCs cell lines followed by cocultivation with 293 cells that stably express Wnt -1, all cell lines except one demonstrated TCF mediated transcriptional. But, cells were co- cultured, Wnt - 7A or Wnt - 5A did not activate TCF mediated transcription in a cell number dependent fashion. Discussion; We report the activation of TCF promoter gene by extemal Wnt stimuli in ESCCs cells.背景:食道癌細胞にベータカテニンの蓄積があることは報告されているが,大腸癌とことなり,ベータカテニン,Axin,APC変異の報告がなく,そのメカニズムは不明である｡ 方法:8種類の食道癌細胞株において,3種類のWntの刺激によるベータカテニンTCF系の活性化への影響をTCFプロモーターを持つルシュフフェラーゼプラスミドを癌細胞にトランスフェクションして検討した｡ 結果:代表的な食道癌細胞は変異ベータカテニン,変異APC,変異Axinのいずれも,TCFの活性化をおこした｡8種類中7種類の癌細胞はWnt1により量依存性のTCFの活性化が認められたが,Wnt5A,Wnt7Aでは活性化が認められなかった｡ 結語:食道癌の進展にWnt1の関与が示唆された

Concordance of acquired mutations between metastatic lesions and liquid biopsy in metastatic colorectal cancer

Aim: To evaluate whether PCR-reverse sequence-specific oligonucleotide can examine the concordance between liquid biopsy and metastatic lesions with acquired resistance. Materials & methods: We examined acquired mutations in chemoresistant lesions and blood obtained from four patients with RAS wildtype metastatic colorectal cancer who underwent treatment with anti-epidermal growth factor receptor antibodies. Results: In one patient, metastatic lesions harbored diverse acquired mutations in KRAS in all seven metastases; the two acquired mutations were detectable in blood collected after the patient acquired resistance. None of the other patients exhibited liquid biopsy mutations, except one, with a BRAF mutation confirmed in primary tumor and peritoneal dissemination. Conclusion: Liquid biopsy based on PCR-reverse sequence-specific oligonucleotide is a successful procedure for capturing acquired mutations with precise information on the RAS mutational spectrum

Prevalence and Outcomes of Acute Hepatitis B in Okayama, Japan, 2006-2010

Hepatitis B virus (HBV) is one of the major viruses causing acute hepatitis. Recently, the incidence of acute hepatitis with genotype A has been increasing in Japan. The aim of this study was to investigate acute hepatitis B (AHB) in Okayama prefecture, with special attention to HBV genotype A. AHB patients who visited one of 12 general hospitals in Okayama prefecture between 2006 and 2010 were retrospectively analyzed. Over the course of the study period, 128 patients were diagnosed with AHB. Sexual transmission was supposed in the majority of patients (78 patients, 61%), including 59 (76%) having sex with heterosexual partners. The genotypes of HBV were assessed in 90 patients (70%), of whom 27 patients were infected with genotype A, 5 with genotype B, and 58 with genotype C. The prevalence of genotype A was significantly higher among male patients (28.7%), aged 20-29 (35.6%, p＜0.01), among men who had sex with men (100%, p＜0.005), and among patients having sex with unspecified partners (44.8%, p＜0.005). Genotype A was not a significant factor associated with delayed HBsAg disappearance. Caution should be exercised with regard to sexually transmissible diseases in order to slow the pandemic spread of AHB due to genotype A

Impact of Gender on In-hospital Mortality in Patients with Acute Myocardial Infarction in Nagasaki

Acute myocardial infarction (AMI) is one of the leading causes of death in Japan. Immediate reperfusion therapy, includingcoronary intervention, improves patient prognosis. Despite this, females are said to be more prone to poor prognosis. A regional AMI registry in Nagasaki prefecture has been instituted recently that will evaluate whether female gender might predict short-term in-hospital death. Seventeen regional AMI centers enrolled all AMI patients from September 2014 through March 2016. A propensity score (PS) was derived using logistic regression to model the probability of females as a total function of the potential confounding covariates. Two types of PS techniques were used: PS matching and PS stratification. The consistency of in-hospital death was determined between PS matched patients of both genders. Based on PS, patients were ranked and stratified into five groups for the PS stratification. Out of 996 patients, 67 (6.7%) died during hospitalization: 31 (10.4%) out of 298 females and 36 (5.2%) out of 698 males (p < 0.0025). The proportion of cardiac and non-cardiac related death was almost same between genders (25 and 6 in female, 29 and 7 in male, respectively). Among 196 PS matched patients, there was a consistency between genders regarding in-hospital deaths (McNemar test, p = 0.6698). The 717 propensity scored patients had no significant differences between genders among propensity quintiles (Cochran-Mantel-Heanszel test, p = 0.7117). We found that gender alone is not an indicator of short-term in-hospital death in acute myocardial infarction patients

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Search for eccentric black hole coalescences during the third observing run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass M&gt;70 M⊙) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities 0&lt;e≤0.3 at 0.33 Gpc−3 yr−1 at 90\% confidence level

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM