To comprehensively characterize the contribution of virological factors as well as interleukin 28B (IL28B) single nucleotide polymorphisms (SNPs) in determining treatment responses in pegylated-interferon plus ribavirin (PEG-IFN/RBV) therapy for chronic hepatitis C virus (HCV)-1b infection, we undertook a retrospective cohort analysis for the pretreatment dominant complete HCV open reading frame (ORF) amino acid sequence study in consecutive 103 HCV-1b Japanese patients. The dominant HCV sequences classified by the response were subjected to systematic sliding window comparison analysis to characterize response-specific viral sequences along with IL28B SNPs analyses (rs8099917). In each comparison of the patients between with and without rapid viral response (RVR), non-early viral response (nEVR), sustained virological response (SVR) or relapse, following regions were extracted as most significantly associated with the different responses respectively: NS5A aa.2224-2248(p=1.2E-07), core aa.70 (p=4E-04), NS5A aa.2340-2382(p=7.0E-08) and NS5A aa.2360-2377(p=1.1E-05). Those NS5A regions nearly coincided with the interferon sensitivity-determining region (ISDR, NS5A aa.2209-2248) and the IFN/RBV resistance-determining region (IRRDR, NS5A aa.2339-2379). In a multivariate analysis, the IL28B SNP (OR 16.8, p=0.009) and NS5A aa.2340-2382 (OR 13.8, p=0.0003) were extracted as the two most significant independent variables contributing to the final outcome.(HEPATOLOGY 2012.).

We synthesized superconducting fullerene nanowhiskers (C(60)NWs) by potassium (K) intercalation. They showed large superconducting volume fractions, as high as 80%. The superconducting transition temperature at 17 K was independent of the K content (x) in the range between 1.6 and 6.0 in K-doped C(60) nanowhiskers (K(x)C(60)NWs), while the superconducting volume fractions changed with x. The highest shielding fraction of a full shielding volume was observed in the material of K(3.3)C(60)NW by heating at 200 °C. On the other hand, that of a K-doped fullerene (K-C(60)) crystal was less than 1%. We report the superconducting behaviors of our newly synthesized K(x)C(60)NWs in comparison to those of K(x)C(60) crystals, which show superconductivity at 19 K in K(3)C(60). The lattice structures are also discussed, based on the x-ray diffraction (XRD) analyses.

Human lymph nodes excised from cancer patients during lymphadenectomy can contain small clinically-important metastatic regions that can be missed because conventional histopathology methods do not allow nodes to be examined over their entire volume. In this study, more than 250 lymph nodes were scanned in 3D using a 26-MHz ultrasound transducer before histology processing. Acquired radio-frequency data were processed using 3D regions-of-interest to yield thirteen quantitative ultrasound (QUS) estimates. The QUS estimates are related to tissue microstructure and are hypothesized to be different in normal nodal tissue and metastatic tissue. Four QUS estimates were obtained from backscattered spectra and the remaining nine were derived from envelope statistics. Following ultrasound scanning, serial-section histology was performed at 50-μm intervals to depict cancer foci in 3D. Classification based on QUS estimates was performed using linear-discriminant analyses in a step-wise approach, and areas under ROC curves (AUCs) were computed. The AUC for the linear combination of four QUS estimates was 0.87 for a dataset of 95 breast-cancer nodes. Similarly, using only two QUS estimates, an AUC of 0.95 was obtained for a dataset of 160 gastrointestinal-cancer nodes. These results suggest that QUS may provide an effective tool for detecting metastatic foci in lymph nodes.

Hepatitis is a growing health concern and early disease detection is critical. Ultrasound is ideally suited for real-time imaging of liver, but typical ultrasound images do not display quantitative tissue information because it is first necessary to understand the complex interaction between ultrasound and tissue and scattering models based on tissue properties must be devised. Towards this aim, speed-of-sound (SOS) and attenuation from three types of rat livers (normal, fatty, and fibrosis) were measured with a scanning acoustic microscope using transducers with center frequencies from 1-MHz to over 100-MHz. Results indicated that SOS and attenuation measured with each transducer showed the following trend. Variability in SOS and attenuation values of normal liver was much smaller than other livers at any frequencies. In the fatty liver, SOS was 20 m/s slower and the attenuation was 1.0 dB/cm/MHz larger than in the normal liver. In fibrosis, SOS and attenuation had values between those of normal and fatty liver. Additionally, the relation between the pathologic state of liver and SOS and attenuation was investigated. Correlation between the ultrasound wavelength and the distribution and size of fat or fiber deposits in the liver was investigated using the corresponding stained histology photomicrograph.

Acoustic properties of living tissues are an important parameter for quantitative estimation of the tissue structure. It is very important to determine the relationship between the physical and the chemical change of tissue structure and the change of acoustic properties. We have developed ultrasonic tissue imaging system (UTIS) to measure the special distribution of acoustic properties at frequencies form 3 MHz to 50 MHz. The speed and attenuation of sound were measured by the noncontact technique based on frequency-time analysis of a reflected pulse response. From rat tissues measurement, The speed of sound in normal tissues varied minimally between individuals and was not related to body weight or age. The relationship between speed of sound and density in normal, fatty and cirrhotic livers can be fitted well on the line which is estimated using the immiscible liquid model assuming a mixture of normal liver and fat tissues. We have also measured the distribution of acoustic properties in human tissues, and obtained relationship between the sound speed and the attenuation of tissue. These findings of the relationship between tissue structure and acoustic structure are used for development of a quantitative diagnosis technique.

This paper presents an experimental demonstration to determine electron temperature (T(e)) with unknown spectral sensitivity (transmissivity) in a Thomson scattering system. In this method, a double-pass scattering configuration is used and the scattered lights from each pass (with different scattering angles) are measured separately. T(e) can be determined from the ratio of the signal intensities without knowing a real chromatic dependence in the sensitivity. Note that the wavelength range for each spectral channel must be known. This method was applied to the TST-2 Thomson scattering system. As a result, T(e) measured from the ratio (T(e,r)) and T(e) measured from a standard method (T(e,s)) showed a good agreement with 〈∣T(e,r)- T(e,s)∣∕T(e,s)〉 = 7.3%.

Yokukansan (YKS), a traditional Japanese medicine, is composed of seven kinds of dried herbs. It is widely prescribed in clinical situation for treating psychiatric disorders such as aggressiveness in patients with dementia. We previously demonstrated that YKS and Uncaria hook (UH), which is a constituent herb of YKS, had a partial agonistic effect to 5-HT(1A) receptors in vitro. However, it has still been unclear whether this in vitro effect is reflected in in vivo, and what the active ingredients are. The purpose of the present study is to find the active ingredient in YKS and to demonstrate the effect in in vivo. In the present study, we first studied the effect of YKS and UH on aggressiveness and sociality in socially isolated mice. YKS and UH ameliorated the isolation-induced increased aggressiveness and decreased sociality, and these ameliorative effects were counteracted by coadministration of 5-HT(1A) receptor antagonist WAY-100635, or disappeared by eliminating UH from YKS. These results suggest that the effect of YKS is mainly attributed to UH, and the active ingredient is contained in UH. To find the candidate ingredients, we examined competitive binding assay and [(35)S] guanosine 5'-O-(3-thiotriphosphate)(GTPγS) binding assay of seven major alkaloids in UH using Chinese hamster ovary cells expressing 5-HT(1A) receptors artificially. Only geissoschizine methyl ether (GM) among seven alkaloids potently bound to 5-HT(1A) receptors and acted as a partial agonist. This in vitro result on GM was further demonstrated in the socially isolated mice. As did YKS and UH, GM ameliorated the isolation-induced increased aggressiveness and decreased sociality, and the effect was counteracted by coadministration of WAY-100635. These lines of results suggest that GM in UH is potent 5-HT(1A) receptor agonist and a candidate for pharmacological effect of YKS on aggressiveness and sociality in socially isolated mice.

We investigated the efficacy of cord blood transplantation (CBT) for adult acute lymphoblastic leukemia (ALL) by reviewing medical records of 256 patients reported to the Japan Cord Blood Bank Network between June 1997 and August 2006. Cumulative incidence of neutrophil engraftment at day 100 was 78%. Infused CD34-positive cell dose (>1 × 10(5) cells/kg) was associated with successful neutrophil engraftment. Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) at day 100 was 37%. A 2-year disease-free and overall survival (OS) rates were 36% and 42%, respectively. Multivariate analysis showed that age (51 or older vs younger than 50)(hazard ratio 1.9, 95% confidence interval (CI), 1.3-2.8, P=0.001), disease status (non-remission vs remission)(hazard ratio 2.2, 95% CI, 1.5-3.2, P<0.0001), grade III-IV acute GVHD (hazard ratio 2.0, 95% CI, 1.2-3.2, P=0.006) and absence of chronic GVHD (hazard ratio 2.4, 95% CI, 1.1-5.1, P=0.02) were negatively associated with OS. CBT is effective for some patients with advanced ALL. It is worth considering for further evaluation.Leukemia advance online publication, 31 January 2012; doi:10.1038/leu.2012.11.

Neutron spin echo measurements of monolayer and capillary condensed heavy water (D(2)O) confined in MCM-41 C10 (pore diameter 2.10 nm) were performed in a temperature range of 190-298 K. The intermediate scattering functions were analyzed by the Kohlrausch-Williams-Watts stretched exponential function. The relaxation times of confined D(2)O in the capillary condensed state follow remarkably well the Vogel-Fulcher-Tammann equation between 298 and 220 K, whereas below 220 K they show an Arrhenius type behavior. That is, the fragile-to-strong (FTS) dynamic crossover occurs, which has never been seen in experiments on bulk water. On the other hand, for monolayer D(2)O, the FTS dynamic crossover was not observed in the temperature range measured. The FTS dynamic crossover observed in capillary condensed water would take place in the central region of the pore, not near the pore surface. Because the tetrahedral-like water structure in the central region of the pore is more preserved than that near the pore surface, the FTS dynamic crossover would be concerned with the tetrahedral-like water structure.