Search for a stochastic background of 100-MHz gravitational waves with laser interferometers

This letter reports the results of a search for a stochastic background of gravitational waves (GW) at 100 MHz by laser interferometry. We have developed a GW detector, which is a pair of 75-cm baseline synchronous recycling (resonant recycling) interferometers. Each interferometer has a strain sensitivity of ~ 10^{-16} Hz^{-1/2} at 100 MHz. By cross-correlating the outputs of the two interferometers within 1000 seconds, we found h_{100}^2 Omega_{gw} < 6 times 10^{25} to be an upper limit on the energy density spectrum of the GW background in a 2-kHz bandwidth around 100 MHz, where a flat spectrum is assumed.Comment: Accepted by Phys.Rev.Lett.; 10 pages, 4 figure

Synergistic inhibitory effect of gemcitabine and angiotensin type-1 receptor blocker, losartan, on murine pancreatic tumor growth via anti-angiogenic activities.

Pancreatic cancer is one of the leading causes of cancer death, and represents a challenging chemotherapeutic problem. The crucial role of angiogenesis in tumor growth has been widely recognized, and several reports have revealed that the combination treatment of the conventional chemotherapeutic drugs and anti-angiogenic agents exerted synergistic anti-cancerous effects. It has been reported that the clinically used angiotensin type-1 receptor blocker (ARB) exerted potent anti-angiogenic activity. The aim of our current study was to examine the combination effect of gemcitabine (GEM), a widely used conventional chemotherapeutic drug against pancreas cancer, and losartan (Lo), an ARB, on murine pancreatic tumor growth, especially in conjunction with angiogenesis. When used individually, GEM and Lo at clinically comparable low doses moderately suppressed pancreatic tumor development. The combination treatment with GEM and Lo exerted a marked inhibitory effect as compared with single agent treatments even after the tumor was fully established. Neovascularization and the expression of the vascular endothelial growth factor (VEGF), a central angiogenic factor, in the tumor were both markedly suppressed in a magnitude similar to the inhibitory effects against the tumor growth. Since both agents are widely used in the clinical practice, the combination regimen of GEM and Lo may represent a potential new therapeutic strategy for pancreatic cancer in the future

Increased Interleukin-8 in Epithelial Lining Fluid of Collapsed Lungs During One-Lung Ventilation for Thoracotomy

The present study was designed to evaluate inflammatory changes in collapsed lungs during one-lung ventilation using the assistance of a bronchoscopic microsampling probe. Serial albumin and interleukin (IL)-8 concentrations in epithelial lining fluid (ELF) were measured in seven patients undergoing resection of lung tumors. The samples were taken after induction of anesthesia (baseline), 30 min after one-lung ventilation was started (point 2), just before resuming two-lung ventilation (point 3), and 30 min after two-lung ventilation was restarted (point 4). The albumin and IL-8 concentrations in ELF were significantly increased at point 2 and point 3, respectively, and remained to be high, compared to the baseline. The increase in IL-8 at point 3 was correlated with the interval of one-lung ventilation; however, none developed specific acute lung injury. These findings suggest that inflammatory changes can occur on the epithelium of a collapsed lung even in patients who underwent successful and standard thoracic surgery.ArticleINFLAMMATION. 35(6):1844-1850 (2012)journal articl

Different tumoricidal effects of interferon subclasses and p53 status on hepatocellular carcinoma development and neovascularization.

Interferon (IFN) is known as a multifunctional cytokine. The aim of this study was to examine the different effects of IFN subclass; namely, IFN-α and IFN-β, on hepatocellular carcinoma (HCC) growth especially in conjunction with angiogenesis that is known to play a pivotal role in the tumor growth. Furthermore, we also examined whether the p53 status in the tumor would alter the anti-tumoral effect of IFN against HCC growth since the p53 status reportedly affected the therapeutic effect of anti-angiogenic agents against cancer. When compared with IFN-α, IFN-β exerted a more potent inhibitory effect on HCC growth, even after the tumor was established, along with suppression of neovascularization in the tumor. A single treatment with clinically comparable low doses of IFN-β significantly inhibited HCC growth whereas the same dose of IFN-α did not. IFN-β also significantly suppressed the tumor growth both in the p53-wild and p53-mutant HCC cells. Our in vitro study revealed that IFN-β showed a more potent inhibitory effect on the endothelial cell proliferation than IFN-α as in the in vivo study. Collectively, IFN may be an alternative anti-angiogenic agent against HCC since it exerted a significant tumoricidal effect regardless of the host p53 status even at a low dose. A cautious approach may be also required in the clinical practice since even in a same IFN subclass (class-I), IFN-α and IFN-β exert tumoricidal effects of different magnitudes on HCC

Selective aldosterone blocker ameliorates the progression of non-alcoholic steatohepatitis in rats.

Although non-alcoholic steatohepatitis (NASH) may progress to cirrhosis and hepatocellular carcinoma (HCC), no effective therapeutic modalities have been fully established yet. Recent studies have shown that the renin-angiotensin-aldosterone-system plays an important role in NASH. The aim of our current study was to elucidate the effects of aldosterone (Ald) inhibition on the progression of NASH. In the choline-deficient L-amino acid-defined diet-induced rat NASH model, the effects of a clinically used selective Ald blocker (SAB) were elucidated in conjunction with the activated hepatic stellate cells (HSC) and neovascularization, which are both known to play important roles in liver fibrosis development and hepatocarcinogenesis, respectively. Liver fibrosis development and the glutathione-S-transferase placental form-positive pre-neoplastic lesions were both markedly attenuated by SAB along with the suppression of the activated HSC and neovascularization. SAB inhibited the hepatic expression of transforming growth factor-β 1 and also that of the vascular endothelial growth factor. Our in vitro study showed that SAB also inhibited the Ald-induced HSC proliferation and in vitro angiogenesis in a dose-dependent manner. These results indicated that Ald plays a pivotal role in the progression of NASH. Considering that SAB is already widely used in clinical practice, this drug could represent a potential new strategy against NASH in the future

Outburst of LS V+44 17 Observed by MAXI and RXTE, and Discovery of a Dip Structure in the Pulse Profile

We report on the first observation of an X-ray outburst of a Be/X-ray binary pulsar LS V +44 17/RX J0440.9+4431, and the discovery of an absorption dip structure in the pulse profile. An outburst of this source was discovered by MAXI GSC in 2010 April. It was the first detection of the transient activity of LS V +44 17 since the source was identified as a Be/X-ray binary in 1997. From the data of the follow-up RXTE observation near the peak of the outburst, we found a narrow dip structure in its pulse profile which was clearer in the lower energy bands. The pulse-phase-averaged energy spectra in the 3$-$100 keV band can be fitted with a continuum model containing a power-law function with an exponential cutoff and a blackbody component, which are modified at low energy by an absorption component. A weak iron K$\alpha$ emission line is also detected in the spectra. From the pulse-phase-resolved spectroscopy we found that the absorption column density at the dip phase was much higher than those in the other phases. The dip was not seen in the subsequent RXTE observations at lower flux levels. These results suggest that the dip in the pulse profile originates from the eclipse of the radiation from the neutron star by the accretion column.Comment: 18 pages, 7 figures, accepted for publication in PAS

Losartan, an angiotensin-II type 1 receptor blocker, attenuates the liver fibrosis development of non-alcoholic steatohepatitis in the rat

<p>Abstract</p> <p>Background</p> <p>Apart from simple steatosis, the non-alcoholic steatohepatitis (NASH) can progress into liver fibrosis and cirrhosis. To date, however, no widely accepted therapeutic modalities have been established against NASH in the clinical practice. To find out promising new therapeutic agents, it is important to employ an appropriate experimental model of NASH, such as association with insulin resistance.</p> <p>Findings</p> <p>In the current study, we found that losartan, a clinically used angiotensin-II type 1 receptor blocker, significantly attenuated a choline-deficient L-amino acid-defined (CDAA) diet-induced steatohepatitis in obese diabetic- and insulin resistance-associated Otsuka Long-Evans Tokushima Fatty (OLETF) rats. The transforming growth factor-beta, a well-known major fibrogenic cytokine, was also suppressed in a similar magnitude to that of the fibrosis area. Noteworthy was the finding that these inhibitory effects were achieved even at a clinically comparable low dose.</p> <p>Conclusion</p> <p>Since losartan is widely used without serious side effects in the clinical practice, this agent may be an effective new therapeutic strategy against NASH.</p

Long-term Monitoring of the Black Hole Binary GX 339-4 in the High/Soft State during the 2010 Outburst with MAXI/GSC

We present the results of monitoring the Galactic black hole candidate GX 339-4 with the Monitor of All-sky X-ray Image (MAXI) / Gas Slit Camera (GSC) in the high/soft state during the outburst in 2010. All the spectra throughout the 8-month period are well reproduced with a model consisting of multi-color disk (MCD) emission and its Comptonization component, whose fraction is <= 25% in the total flux. In spite of the flux variability over a factor of 3, the innermost disk radius is constant at R_in = 61 +/- 2 km for the inclination angle of i = 46 deg and the distance of d=8 kpc. This R_in value is consistent with those of the past measurements with Tenma in the high/soft state. Assuming that the disk extends to the innermost stable circular orbit of a non-spinning black hole, we estimate the black hole mass to be M = 6.8 +/- 0.2 M_sun for i = 46 deg and d = 8 kpc, which is consistent with that estimated from the Suzaku observation of the previous low/hard state. Further combined with the mass function, we obtain the mass constraint of 4.3 M_sun < M < 13.3 M_sun for the allowed range of d = 6-15 kpc and i < 60 deg. We also discuss the spin parameter of the black hole in GX 339-4 by applying relativistic accretion disk models to the Swift/XRT data.Comment: 9 pages, 8 figures, accepted for publication in PASJ (Suzaku+MAXI special issue

The efficacy of pancreatic juice cytology with liquid-based cytology for evaluating malignancy in patients with intraductal papillary mucinous neoplasm

Background Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN. Methods We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017. Results Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043). Conclusions LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method