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Aim Recent studies have indicated that hepatocellular adenoma (HCA) is a heterogenous group of benign tumors with various genetic and clinicopathological characteristics. We delineated the clinicopathological characteristics of HCA subtypes and evaluated the expression of transporter protein OATP1B3 in HCA. Methods HCA in 34 Japanese patients were investigated immunohistochemically and classified into four subtypes (HNF1α-inactivated type, H-HCA; β-catenin-activated type, b-HCA; inflammatory type, I-HCA; unclassified type, u-HCA). Immunostaining of OATP1B3 protein in HCA tissue sections was performed to determine the association between OATP1B3 expression and HCA subtypes. Results HCA was categorized into the following four subtypes and two combined subtypes: 10 H-HCA (29%), 10 I-HCA (29%), seven b-HCA (21%), two b-HCA/H-HCA (6%), two b-HCA/I-HCA (6%) and three u-HCA (9%). The male-to-female ratio was 18:16. Oral contraceptive use was rare but seven HCA were found in patients with glycogen storage disease, congenital absence of the portal vein and idiopathic portal hypertension. OATP1B3 expression was decreased in 24 HCA but was preserved or increased in 10 HCA. All nine HCA with nuclear staining for β-catenin showed preserved or enhanced OATP1B3 expression, indicating a significant association between nuclear β-catenin accumulation and OATP1B3 expression in HCA. Conclusion HCA subtype classification was validated in 91% of our Japanese subjects although their clinical backgrounds including rare contraceptive use were different from European subjects. A close association between preserved or enhanced OATP1B3 expression and b-HCA subtype indicated important modalities for clinical decisions in the treatment and follow up of patients with HCA.

In December 2005, Japan experienced a major outage in Niigata Kaetsu area due to a large amount of wet snow mixed with sea-salt accreted on several transmission line insulators. To clarify the causes of the snow-induced outage and increase reliability of the networks, a 154 kV class full-scale snow test procedure to evaluate various insulator designs was developed, and artificial flashover voltage tests of snow accreted insulators were carried out. High voltage flashover tests showed that the flashover voltage of both long-rod and cap & pin insulators was decreased with the increase of snow conductivity. Also, cap & pin insulators showed significantly higher flashover voltage than long-rod insulators. Thus substitution of long-rod insulators with cap & pin insulators appears to be reasonable as a countermeasure against snow induced flashovers.

This paper presents evaluation of snow accretion properties of long-rod and cap & pin insulators focusing on the phenomena found in the snowstorm in 2005, which related to wet snow accretion packed with sea-salt. Field observations at severe natural environment and laboratory tests under defined conditions were parallelly carried out in order to clarify wet snow accretion process under various conditions. In field observations, it was confirmed that snow easily accreted on insulators at temperature range especially between 0 and +1.0°C. The long-rod insulator's sheds were bridged more easily than that of cap & pin type because of its narrower shed spacing. In laboratory tests, cylindrical snow accretion, which was found in the snowstorm in 2005, was achieved. The mechanisms on explaining snow accretion on long-rod insulators were found to be similar to those confirmed for wires. The laboratory simulations agree well with the field observations. In order to estimate the amount of snow flux on insulators caused by a snow event for given climatic conditions, an index called the snow accretion potential ability (SAP) was proposed. SAP is defined by using the snow flux and associated with the weight term in the index for the snow stress product (SSP). SAP was adopted to evaluate snow accretion characteristics by field observations and laboratory tests, and the snow accretion phenomenon during a snowstorm in 2005 was discussed.

This paper presents the flashover characteristics of snow-bridged insulators, and the related discharge propagation phenomena in the presence of salt contaminated snowstorms. Two types of flashover tests, a) Snow accretion without voltage application, then apply the voltage after snow accretion, b) Snow accretion during voltage application, were carried out on a 33 kV long rod insulator with the snow conductivity controlled between 180 and 980 μS/cm. Method a simulates the "cold switch-on" situations. In this case, the flashover voltage is found to be inversely proportional to the fifth root of the snow conductivity. Further, the flashover voltage showed a relation to the leakage resistance of snow-bridged insulators. Method b simulates energized situations during a snowstorm. The concept of Method b is equivalent to the “Ice Progressive Stress (IPS)” method described in the IEEE Std. 1783-2009. In this case, partial arc discharges gradually increase owing to the development of snow accretion. Flashovers are mostly induced during the period of snowstorm suspension, because the arc discharge can develop into a flashover without the cooling effect of the blizzard. Melting snow by heating of electric power does affect flashover characteristics. The minimum flashover stress by Method b is lower than that by Method a. However, in particular case of Method b with higher snow conductivity, too much discharge activities prevent snow accretion on the insulator. This leads to snow melting or snow shedding.

Few studies have investigated the effects of Japanese herbal medicines on nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). To the best of our knowledge, only one study has examined whether high-fat (HF) diet-fed db/db mice are appropriate animal models of NASH. We investigated the effects of four types of Japanese herbal medicines (shosaikoto (TJ-9), inchinkoto (TJ-135), juzentaihoto (TJ-48), and keishibukuryogan (TJ-25)) on hepatic lesions of HF diet-fed db/db mice. Db/db mice were divided into six groups: control diet (control); HF diet (HF); and HF diet supplemented with TJ-9, TJ-135, TJ-48, or TJ-25 (TJ-9, TJ-135, TJ-48, and TJ-25, respectively). Mice were killed after 6 weeks of treatment, and biochemical and pathological analyses were performed. Mice in the HF group consistently developed histopathological features consistent with definite NASH, and marked necroinflammation occurred. Serum alanine aminotransferase levels in the TJ-9, TJ-135, and TJ-48 groups were significantly improved compared with those in the HF group. With regard to liver histology, TJ-9 and TJ-48 significantly improved lobular inflammation, and TJ-135 significantly improved ballooning degeneration. We have shown that HF diet-fed db/db mice are animal models that correctly recapitulate the histopathology of human NASH and that TJ-9, TJ-135, and TJ-48 inhibit necroinflammatory activity in this model.

Hydrogen storage and release properties of composites were compared: lithium hydride with conjugated macromolecules of polyacetylene (PA), poly(p-phenylene) (PPP), and poly(diphenylacetylene) (PDPA). Cyclic hydrogen absorption and desorption experiments showed that LiH–PPP has better durability than either LiH–PA or LiH–PDPA, probably because the higher structural stability of PPP prevented unfavorable side reactions that might inactivate LiH. Mechanistic investigations of hydrogen release reactions on LiH–PPP were conducted using isotopic tracer experiments, electrical conductivity measurements, and IR and NMR spectroscopy. Those results indicate that the hydrogen release reaction proceeded via electron transfer from hydride ion to conjugation systems of polymer molecules. This proposed mechanism is identical to those for the LiH–PA composite.

a b s t r a c t Objective: We examined the appropriate measurement for pathological tumor size by comparing radio- logical and pathological tumor size of resected lung adenocarcinoma in FSE. Materials and methods: We reviewed records of 59 resected specimens of lung adenocarcinoma for FSE from January to December 2008. Specimens were well-inflated with saline by using an injector before cutting into segments. After selecting the tumor segment of maximal diameter, we compared three ways of measuring pathological tumor size by using paired t-test: (I) macroscopic tumor size (MTS), measured with a metal straight ruler, (II) microscopic frozen section tumor size (FSTS), and (III) microscopic paraffin section tumor size (PSTS). We compared each discrepancy rate (DR) (DR = (CT tumor size − pathological tumor size)/CT tumor size × 100) (%) between tumors that were air-containing type and solid-density type on CT scans, and also compared the tumors with lepidic component rates (LCR) ≥50% and LCR

In-plane uniaxial anisotropic CoPd-CaF 2 nanogranular soft magnetic films for gigahertz applications were prepared using RF tandem-sputtering deposition with substrate revolution. Strong anisotropy with a large anisotropy field exceeding 50 kA/m was achieved in the centrifugal-centripetal direction of the substrate revolution, regardless of the presence or absence of an applied external dc field for induced anisotropy. X-ray pole-figure analysis demonstrated that the crystalline orientation of CoPd111 as a crystallographically magnetic easy axis corresponds to the easy axis of the films. Thus, the soft magnetic properties and uniaxial anisotropy of nanogranular films are determined by both random-magnetocrystalline and shape anisotropies. Complex permeabilities indicated high ferromagnetic resonance frequency exceeding 5GHz with a low Gilbert damping factor of 0.06 for the nanogranular films, and the applied field caused a change in the damping factor. Thus, the magnetic properties of the films can be controlled by the substrate motion and the applied field under tandem-sputtering conditions.

Solitary pulmonary capillary hemangioma (SPCH) is a rare benign lung tumor that must be distinguished from small and early lung cancers. Here, we report a case of SPCH for which we performed frozen section diagnosis. The patient was a 55-year-old Japanese woman. Five years before the operation, mixed ground-glass opacity was detected by computed tomography in the left posterior basal segment of the lower lobe (S10). Because the interior tumor density of the ground-glass opacity increased slightly, video-assisted thoracic surgery wedge resection was performed. Frozen section diagnosis revealed a benign tumor without proliferation of atypical epithelial cells. The tumor had narrow alveolar lumens, thickened alveolar septa and a clear boundary separating it from normal lung tissue. The proliferated lumens varied in size and were lined with single layers of flat cells. After the operation, immunohistochemical staining of a paraffin section revealed that the thickened alveolar septa resulted from the proliferation of capillary vessels, the flat cells of which were positive for CD31 and CD34 and negative for podoplanin; the tumor was diagnosed as SPCH. Here, we discuss the pathological features of SPCH on frozen sections with reference to this case and review previous related reports.

Cervical lymph node metastasis in oral squamous cell carcinoma (OSCC) is recognized as a poor prognostic factor, although its mechanism remains unclear. Recently, cyclo-oxygenase-2 (COX-2) level has been found to correlate highly with vascular endothelial growth factor C (VEGF-C) and lymph node metastasis, as in other solid tumors. However, there has been no report of this correlation in OSCC. Therefore, the aim of this study was to investigate whether COX-2 immunohistochemical expression in OSCC was associated with VEGF-C expression, histopathologic parameters, and lymph node metastasis.Lymphatic vessel density, VEGF-C, and COX-2 immunohistochemical expression were examined pathologically in 60 specimens of invasive OSCC. Relations of histopathologic parameters to lymph node metastasis were analyzed.Expression levels of VEGF-C and COX-2 and lymphatic vessel density in the lymph node metastatic group were significantly higher than in the nonmetastatic group (P.01). A significant correlation was found between the expression levels of VEGF-C and COX-2 (r = 0.512; P.001). COX-2 expression was significantly related to lymph node metastasis (P = .004) and VEGF-C expression (P = .005). Univariate analysis showed that survival time was impaired by higher COX-2 and VEGF-C expression levels. Multivariate survival analysis showed that COX-2 expression was an independent prognostic factor.This study showed that VEGF-C expression was upregulated by COX-2 in OSCC. High VEGF-C expression appears to promote peritumoral lymphangiogenesis. These data indicated that lymph node metastasis is promoted by COX-2 and VEGF-C in OSCC.

The novel antifungal macrocyclic lipopeptidolactone, KB425796-A (1), was isolated from the fermentation broth of bacterial strain 530603, which was identified as a new Paenibacillus species based on morphological and physiological characteristics, and 16S rRNA sequences. KB425796-A (1) was isolated as white powder by solvent extraction, HP-20 and ODS-B column chromatography, and lyophilization, and was determined to have the molecular formula C79H115N19O18. KB425796-A (1) showed antifungal activities against Aspergillus fumigatus and the micafungin-resistant infectious fungi Trichosporon asahii, Rhizopus oryzae, Pseudallescheria boydii and Cryptococcus neoformans.

KB425796-C is a novel antifungal metabolite produced by the newly isolated bacterial strain Paenibacillus sp. No. 530603. This compound is a 40-membered macrocyclic lipopeptidolactone consisting of 12 amino acids and a 3-hydroxy-15-methylpalmitoyl moiety. KB425796-C displayed antifungal activity against micafungin-resistant fungi and was fungicidal to Trichosporon asahii in vitro. In a murine systemic infection model of T. asahii, KB425796-C showed excellent efficacy upon i.p. administration at 32 mg kg(-1). In addition, KB425796-C induced morphological changes in the hyphae of Aspergillus fumigatus and had fungicidal effects in combination with micafungin. In a mouse model of septic A. fumigatus infection, although non-treated mice survived for a maximum of only 6 days, the survival rate of micafungin-treated mice (0.1 mg kg(-1)) increased to 20%, while the survival rate of mice treated with a combination of micafungin (0.1 mg kg(-1)) and KB425796-C (32 mg kg(-1)) increased to 100% during the 31-day post-infection period. Our findings suggest that KB425796-C is a good candidate for the treatment of aspergillosis in combination with micafungin.

Biosensors of single-gene knockout mutants and physical methods using mesh and quartz glass are employed to discriminate plasma agents and assess their lethal effects generated in a Direct-Current atmospheric-pressure oxygen plasma jet. Radicals generated in plasma are determined by optical emission spectroscopy, along with the O3 density measurement by UV absorption spectroscopy. Besides, thermal effect is investigated by an infrared camera. The biosensors include three kinds of Escherichia coli (E. coli) K-12 substrains with their mutants, totalling 8 kinds of bacteria. Results show that oxidative stress plays a main role in the inactivation process. Rather than superoxide O2-, neutral reactive oxygen species such as O3 and O2(a1Δg) are identified as dominant sources for oxidative stress. In addition, DNA damage caused by oxidation is found to be an important destruction mechanism.

Using the high-brilliance synchrotron radiation at super photon ring 8 (SPring-8) we determined the electron escape depths in approximately 1-nm-thick low-temperature oxide layers, which were formed on Si(1 1 1) at 300 ◦ C using three kinds of atomic oxygen, and that in approximately 1-nm-thick thermally grown oxide layer formed in 1 Torr dry oxygen at 900 ◦ C by measuring Si 2p photoelectron spectra at the photon energy of 1050 eV. The results indicated that the electron escape depths in the three kinds of low-temperature oxide layers were 13–21% smaller than that in the thermally grown oxide layer. Furthermore, the electron escape depth in the thermally grown oxide layer, whose thickness was close to that of the structural transition layer, was 19% smaller than that in bulk SiO 2. © 2005 Elsevier B.V. All rights reserved.

Introduction Endoscopic surgery is reportedly associated with smaller scars and greater patient satisfaction. Herein we evaluate the early results of endoscopy-assisted breast-conserving surgery(E-BCS). Methods Between May 2009 and October 2010, 61 women with breast cancer underwent E-BCS. We performed E-BCS on patients with tumors measuring less than 2 cm, without skin or pectoralis muscles invasion. Any patients with microcalcified lesions or axillary lymph node metastasis were excluded. We used an endoscopic vein retractor to dissect the dorsal layer of the mammary gland from a small axillar incision. We dissected the subcutaneous layer and cut the mammary gland vertically from a periareolar incision. We evaluated the clinicopathological characteristics, the surgical outcomes, and early cosmetic results. Results The mean age of the patients was 58.5 years, and the mean tumor size was 1.4 cm. Sentinel node biopsy was positive in seven patients, all of whom underwent axillary node dissection. An additional intraoperative resection of the breast was performed in 12 patients. The mean length of the operation was 167 min, and the mean blood loss was 27 mL. Eight patients received a boost to the tumor bed. The cosmetic results were satisfactory, and the wound scar was inconspicuous in most patients. Conclusion Herein we demonstrate that E-BCS is a feasible and safe procedure for patients with early breast cancer. It allows for a better cosmetic scar location and offers patients favorable aesthetic results in the short-term follow-up results.

Introduction: No studies have shown whether the enhanced recovery after surgery (ERAS) protocol is superior to the conventional protocol after robot-assisted laparoscopic radical prostatectomy (RALP). We compared intestinal function and perioperative parameters of patients with prostate cancer after the ERAS and conventional protocols to determine the superior protocol for recovery of intestinal function. Material and Methods: A retrospective analysis of 198 consecutive patients who underwent RALP between August 2013 and June 2015 was conducted. Our study design included 2 cohorts. Patients underwent conventional care in one group (n = 123) and the ERAS protocol in the other group (n = 75). The primary outcome was the time to first defecation. Secondary outcomes were perioperative parameters and the complication rate. Results: The ERAS group showed a significantly shorter time to first defecation than did the conventional group (p = 0.006). Multivariate analysis showed that selection of the ERAS protocol was significantly associated with the number of days for first time to defecation. Conclusions: Successful application of an ERAS protocol was applied to our patients who underwent RALP and did not have major complications. The ERAS protocol included enhanced intestinal recovery. The ERAS group showed a significantly shorter time to first defecation than did the conventional group.

Background: Neutrophilic airway inflammation has been suggested to play a crucial role in chronic inflammatory airway diseases such as asthma and COPD, and airway epithelial cells are involved in their regulation. growth-related gene α (GROα) has been reported to be expressed in the sputum of COPD patients. However, the role and clinical significance of GROα are poorly understood. Aims: We investigated the regulation of GROα production in human bronchial epithelial cells in vitro . Methods: We stimulated human bronchial epithelial cell line BEAS-2B with exogenous agents such as LPS and house dust mite (HDM) derp1 as well as TNFα. GROα production and expression were determined by ELISA and qRT-PCR. Furthermore, we evaluated the inhibitory effect of therapeutic agents associated with its regulation. Results: LPS and TNFα showed significant concentration-dependent effects on GROα expression and production in human BEAS-2B cells, and fluticasone (FP) suppressed this production. HDM derp1 also showed a significant concentration-dependent effect on GROα production, but the effect was less potent compared with those by LPS and TNFα. Conclusions: LPS and TNFα showed a potent stimulatory effect on GROα expression and production in human BEAS-2B cells. FP suppressed this production, implying that GROα is involved in chronic inflammatory airway diseases where FP show therapeutic effects.

Background: Bronchial asthma (BA) is characterized by chronic airway inflammation. Although a majority of BA patients are controlled by standard treatment containing inhaled corticosteroids, some patients suffer acute exacerbation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells which are involved in the pathogenesis of BA. However, the role of ROS levels as a biomarker in BA patients is not yet clear. Aims and objectives: We tried to determine the role of ROS levels as a biomarker in the clinical settings of BA. Methods: We enrolled patients with BA from 2013 through 2015 at the Department of Respiratory Medicine, Kyorin University Hospital. Pulmonary function tests, FeNO, serum reactive oxygen metabolite (ROM) levels and serum IL-6 and IL-8 were measured. Serum ROM levels were measured by d-ROMs test. Results: A total of 110 patients with BA were recruited. Serum ROM levels correlated with WBC (rs = 0.273, P = 0.004), neutrophil (rs = 0.235, P = 0.014), CRP (rs = 0.403, P P 1 (rs = -0.306, P = 0.001, rs = - 0.240, P = 0.012, respectively). Serum ROM levels were significantly higher in patients with severe exacerbation group than in patients without exacerbation group ( P = 0.025). Receiver-operating characteristics analysis showed that ROM levels associated with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597 to 0.801, P = 0.025). Conclusions: ROM levels might reflect neutrophilic inflammation, and correlated with airway obstruction. This biomarker may be useful for predicting severe exacerbations of BA.

BACKGROUND: The viral infection is one of the main causes of bronchial asthma attack.It has been reported that the serum CCL5 levels during attack increase as compared to stable periods. The airway epithelial cell has a potential to release various chemical mediators as well as a barrier role from the outside world. CCL5, one of chemical mediators, is known to have strong chemotactic activity for eosinophils, and thus might be involved in asthma exacerbation. AIMS: To determine regulation of CCL5 production from the airway epithelial cell at the time of the viral infection. METHODS: BEAS-2B cells were stimulated by poly I:C. CCL5 mRNA levels were evaluated using RT-PCR method and concentrations of CCL5 in the supernatant were measured by ELISA method. A variety of endogenous agents such as IL-4, IL-13, IL-33, IL-37 and Clara cell 16 kD protein (CC16) were co-stimulated to investigate the roles of these factors in endogenouscontrol of CCL5 production. RESULTS: CCL5 production and mRNA levels were significantly increased by poly I:C stimulation (∼50-fold increase and∼80-fold increase, p DISCUSSION: Airway epithelial cells act as potent sources of CCL5 upon viral infection, and IL-13 was suggested to play a role in airway inflammatory exacerbation in coordinated fashion during viral infection. Therefore, targeting IL-13 might be useful for the management of the asthma exacerbation at the time of the viral infection.

Previous study has demonstrated that erythrocyte-rich thrombi contain more inflammatory cells and reflect high thrombus burden, leading to impaired myocardial reperfusion in myocardial infarction. The aim of this study is to investigate the utility of quantified frequency domain optical coherence tomography (FD-OCT) signal analysis in evaluating the erythrocyte-rich thrombus with ex-vivo materials. We evaluated 54 specimens of coronary artery thrombus obtained by thrombectomy catheter from 8 patients who underwent primary percutaneous coronary intervention. The thrombi were immersed in saline immediately after thrombectomy and FD-OCT image acquisition was performed ex-vivo. Quantitative analysis for all contiguous frames was performed by the dedicated automated software (OCT system software, Light Lab Inc.). For the maximum thrombus area, mean signal intensity (MSI) and normalized standard deviation of signal (NSD) was evaluated. All thrombi were stained using double staining of phosphotungstic acid—hematoxylin and eosin to enable automatic extraction of erythrocyte from fibrin. Computer-assisted analysis was performed using dedicated image processing software (WinROOF, Mitani Corp., Tokyo, Japan) for color identification of the erythrocyte area. Erythrocyte-rich thrombus, defined as % erythrocyte [(erythrocyte area/total thrombus area) × 100] ≥ 10%, showed significantly lower MSI [4.39 ± 0.24 vs. 4.74 ± 0.35, p = 0.002] than that of

Fe3O4 has been known to have attractive physical properties for spintronic applications such as half-metallicity, however, its complicated magnetism has yet to be elucidated fully. We investigated the sputtered polycrystalline Fe3O4 thin film in which Ge was added for stabilization of the spinal structure. From X-ray photoelectron and Raman spectroscopies, major part of added Ge is found to be quadrivalent and considered to be incorporated in the spinel structure. Out-of-plane alignment of the local moment was confirmed by conversion electron Mössbauer spectroscopy and magnetization measurements with an applied field up to 70 kOe also support it. The Pawley refinement of the X-ray diffraction profile with a series of possible space groups in the spinel structure suggests that the crystal symmetry is reduced from cubic to tetragonal or orthorhombic spinels with (100) or (010) strains up to -0.231%. The uniaxial anisotropy constants K(u) for the tetragonally distorted cases estimated from the evaluated strains and the ab-initio calculation were found to be around 1.05 x 10(6) erg/cm3. We consider that the magnetic anisotropy induced by the lattice distortion contributes to the out-of-plane alignment of local moments in addition to the previously reported effect by the exchange coupling across crystallographic defects of the antiphase boundaries.

Monoclonal gammopathy of undetermined significance (MGUS) is the common pre-malignant B cell disorders with a general prevalence of 3–5 % at age over 50. Because of the potential malignant transformation and immune insufficiency, pre-transplant MGUS recipient should be carefully followed after allograft transplantation. The post-transplant prognosis and quality of life (QOL) in patient with MGUS have not yet been fully determined. The aim of this study is to evaluate function and pathology of the renal allograft and self-assessment QOL changes during 2 years after transplantation in our case of MGUS-bearing recipient. We here studied the clinical course and QOL improvement before and 20 months after transplant in a 56-year-old woman, who had pre-existing MGUS and underwent living donor kidney transplantation. After the renal allograft transplant, the patients maintained normal GFR and had neither acute rejections nor histologic evidence of renal injuries related to the monoclonal gammopathy on the protocol biopsy of 1 year post-transplant. During further 20 months follow-up, the pre-transplant MGUS remained uneventful without any hematologic abnormalities and other medical complications, i.e., infection. Evaluation of QOL using a self-assessment questionnaire showed significant improvement for physical and mental items on both 6 and 18 months post-transplant. The renal transplant thus successfully provided a greater satisfaction for the recipient on both physical and mental health aspects. Our observations suggest that renal transplantation is beneficial even in those who had pre-existing MGUS if managed and followed carefully, which ultimately could significantly improve the patient QOL.

Assessment of oxaliplatin-associated hepatotoxicity in patients receiving oxaliplatin, fluorouracil and leucovorin chemotherapy (FOLFOX) for colorectal cancer remains controversial. The aims of this study were to clarify which variables are indicators of such hepatotoxicity.Twenty-seven patients who were to receive FOLFOX for colorectal cancer were included in this study. A range of liver function tests, including serum hyaluronic acid (HA) and type IV collagen concentrations, indocyanine green (ICG) retention rate at 15 min (ICGR15) and splenic volume were assessed before commencement of chemotherapy and after four cycles of FOLFOX.No significant changes were found in conventional liver function tests or splenic volume. Significant changes pre- and post-FOLFOX were found in type IV collagen concentrations and ICGR15. Correlation analyses showed that the following two factors were associated with significant changes in ICGR15 after four cycles of FOLFOX: platelet count (p = 0.028, correlation coefficient 0.423), and type IV collagen concentration (p0.001, correlation coefficient 0.830). The regression line between type IV collagen concentration and ICGR15 was Y = 2.70 + 0.84 x X.Serum type IV collagen concentration is an indicator of oxaliplatin-associated hepatotoxicity and correlates with significant changes in ICGR15 in patients receiving FOLFOX.

Background The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression. Methods Ninety‐four HCC lesions no larger than 8 cm from 94 patients were immuno‐histochemically studied using two hepatocyte markers (Hep par 1 and α‐fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c‐Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, < 2.0 cm; S2, 2.0–5.0 cm; S3, 5.0–8.0 cm. The tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined. Results The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c‐Kit). Conclusion Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression.

Background and Purpose Bronchial asthma (BA) is a chronic airway disease characterized by airway hyperresponsiveness and remodeling, which are intimately linked to chronic airway inflammation. Reactive oxygen species (ROS) such as hydrogen peroxide are generated by inflammatory cells that are involved in the pathogenesis of BA. However, the role of ROS in the management of BA patients is not yet clear. We attempted to determine the role of ROS as a biomarker in the clinical setting of BA. Subjects and Methods We enrolled patients with BA from 2013 through 2015 and studied the degrees of asthma control, anti-asthma treatment, pulmonary function test results, fractional exhaled nitric oxide (FeNO), serum reactive oxygen metabolite (ROM) levels, and serum levels of interleukin (IL)-6 and IL-8. Results We recruited 110 patients with BA. Serum ROM levels correlated with white blood cell (WBC) count (rs = 0.273, p = 0.004), neutrophil count (rs = 0.235, p = 0.014), CRP (rs = 0.403, p < 0.001), and IL-6 (rs = 0.339, p < 0.001). Serum ROM levels and IL-8 and CRP levels negatively correlated with %FEV1 (rs = -0.240, p = 0.012, rs = -0.362, p < 0.001, rs = -0.197, p = 0.039, respectively). Serum ROM levels were significantly higher in patients who experienced severe exacerbation within 3 months than in patients who did not (339 [302–381] vs. 376 [352–414] CARR U, p < 0.025). Receiver-operating characteristics analysis showed that ROM levels correlated significantly with the occurrence of severe exacerbation (area under the curve: 0.699, 95% CI: 0.597–0.801, p = 0.025). Conclusions Serum levels of ROM were significantly associated with the degrees of airway obstruction, WBC counts, neutrophil counts, IL-6, and severe exacerbations. This biomarker may be useful in predicting severe exacerbations of BA.

Objectives To elucidate the significance of intrarenal reflux. Methods We retrospectively analyzed 276 patients (age

A study to evaluate WT1 mRNA expression levels in peripheral blood (PB) and bone marrow aspirate (BM) was conducted in 172 patients, including 115 with myelodysplastic syndromes (MDS), in Japan. The level of WT1 mRNA expression was evaluated according to the French – American – British (FAB) and World Health Organization (WHO) classifi cations (2001, 2008) and using the International Prognostic Scoring System and the WHO Prognostic Scoring System scales. WT1 mRNA expression levels in PB and BM were well correlated ( r 0.85), and they tended to increase with disease stage progression and in those at higher risk of leukemic transformation. WT1 mRNA expression can be a useful marker for the diagnosis and risk evaluation of MDS.

Although allogeneic hematopoietic cell transplantation (HCT) from a related donor is effective therapy for younger patients with AML, it remains unknown how the availability of a related donor affects the outcome when unrelated HCT is a treatment option for patients without a related donor. To address this issue, we retrospectively analyzed 605 cytogenetically non-favorable AML patients younger than 50 years for whom a related donor search was performed during first CR (CR1). The 4-year OS was 62% in 253 patients with a related donor and 59% in 352 patients without a related donor (P=0.534). Allogeneic HCT was performed during CR1 in 62% and 41% of patients with and without a related donor, respectively. Among patients transplanted in CR1, the cumulative incidence of non-relapse mortality was significantly higher in patients without a related donor (P=0.022), but there was no difference in post-transplant OS between the groups (P=0.262). These findings show the usefulness of unrelated HCT in younger patients with cytogenetically non-favorable AML who do not have a related donor. The extensive use of unrelated HCT for such patients may minimize the potential disadvantage of lacking a related donor.

Two cases of rheumatoid nodules evaluated by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and video-assisted thoracic surgery (VATS) biopsy are reported. The first case was that of a 44-year-old woman who presented with a cavitated nodule with intense standardized uptake values (SUVs) both in the early (max 3.4) and delayed (max 4.4) phases, suggesting malignancy. However, after VATS biopsy, she was diagnosed as having a rheumatoid nodule with vasculitis. The second case was that of a 74-year-old woman admitted with bilateral lung nodules, two of which showed intense early (max 2.2) and delayed (max 6.0) phase SUVs, and mild early (max 0.6) and delayed (max 0.9) phase SUVs. These two nodules were finally proven to be a lung cancer and rheumatoid nodule without vasculitis, respectively. These cases show that rheumatoid nodules with an enhanced inflammatory process, such as vasculitis, can appear false-positive for malignancy on FDG-PET/CT scan images.

Dynamic recrystallization (DRX) behavior in a coarse columnar-grained Cu-0.65Sn-0.025P and Cu-0.025P (mass%) alloys were systematically investigated by compression tests at temperatures between 1073 K and 1253 K and at true strain rates from 2 x 10-4s-1to 2 x 10-1s-1in vacuum. As a model sample, an orientation-controlled bicrystal having [0 1 twist 18oboundary was prepared and also hot deformed. Appearance of the peaks stress, where DRX onsets, was much delayed in Cu-Sn-P alloy compared with that in Cu-0.025P alloy. The onset of DRX was, therefore, obviously impeded by the small addition of Sn to Cu-P. While nucleation of new grains took place almost at random in Cu-Sn-P when strain rate was high enough, it tended to appear more preferentially at grain boundary with decreasing strain rate and with increasing temperature. The most of new grains were annealing twins formed behind the migrating grain boundary. Because grain boundary migration took place more extensively with increasing temperature and with decreasing strain rate, the preferential nucleation at grain boundary became more significant.

We synthesized new vitamin K analogues with demethylation or reduction of the double bonds of the side chain of menaquinone-4 (MK-4) and evaluated their SXR-mediated transcriptional activity as well as the extent of their conversion to MK-4. The results indicated that the analogue with the methyl group deleted at the 7' site of the side chain part affected conversion activity to MK-4. In contrast, a decrease in the number of the double bonds in the side chain moiety appeared to decrease the SXR-mediated transcriptional activity.

High dose chemotherapy followed by autologous stem cell transplantation (SCT) has been shown to be effective therapy for patients with relapsed lymphoma responsive to standard-dose salvage chemotherapy. Here we report a patient in second complete remission (CR) from relapsed follicular lymphoma (grade 3) who was successfully treated with peripheral blood stem cells (PBSC) that had been harvested in first CR 10 years before. One of six frozen bags was thawed and submitted for progenitor cell assays. Because the number of progenitors was considered to be sufficient for engraftment, autologous SCT was performed without further stem cell harvest. At infusion, the viability of all nucleated cells (ANC) of the 5 remaining bags was 61.4%. She was expected to receive 2.87

Pinch dynamics of the imploding plasma and its relations with the 13.5 nm extreme ultraviolet (EUV) emissions have been experimentally investigated for a laser assisted Sn based discharge produced plasma (LA-DPP) EUV source. Plasma behaviors during the discharge are clarified using the laser aided shadowgraphic technique. Temporally and spatially resolved electron density distributions obtained by using Nomarski interferometry reveal that the maximum EUV emission corresponds to the electron density of (2.0–3.0)×1018 cm−3. The ion fraction and electron temperature of the pre-pinch plasma are estimated using a stationary collisional-radiative model.

We have investigated the influence of HF, (NH4)2S and Hexa Methy Disilazane (HMDS) treatments on thermal stability of high-k/In0.53Ga0.47As interface and the chemical bonding states at high-k/In0.53Ga0.47As interface by the X-ray (hv= 1486.6eV) photoemission spectroscopy. The control of the oxide formation on In0.53Ga0.47As surface was tried by surface treatment. Analyses of As 3d, Ga 3p, In 3d, S 1s, Si 2p, N 1s, O 1s and C 1s spectra show that the oxidation of In0.53Ga0.47As was suppressed by various surface treatments.

Vitamin K(2) has been demonstrated to induce gene expression related to bone formation through a nuclear steroid and xenobiotic receptor (SXR). We synthesized new vitamin K analogues with the same isoprene side chains symmetrically introduced at the 2 and 3 positions of 1,4-naphthoquinone and evaluated the transcriptional activity of the target gene. The transcriptional activity was related to the length of the side chain which allowed optimal interaction with ligand-binding domain of SXR.

Purpose To evaluate the possibility of immediate mandibular reconstruction using particulate cancellous bone and marrow (PCBM), platelet-rich plasma (PRP), and a tray, we compared the postsurgical infection rate and bone formation in patients who received mandibular reconstruction with this method using either an intraoral or extraoral approach. Patients and Methods We conducted a retrospective study of a series of 18 patients who underwent the mandibular reconstruction procedure using a mesh tray with PCBM and PRP, all performed by 1 surgeon. These cases were further divided into those treated by the intraoral approach and those treated by the extraoral approach. Clinical data, postoperative bone formation, and complications in the 2 groups were evaluated. The χ 2 examination and the Mann-Whitney U test were used for statistical analysis. Results We could not detect any statistically significant differences in clinical data between the 2 groups, except for the timing of reconstruction. There were postoperative complications such as wound dehiscence and tray exposure, as well as infection of the reconstructed bone. The overall complication rate of the recipient sites in the intraoral group was 30% (3 of 10), whereas in the extraoral group, it was 0%. However, satisfactory bone formation was seen in all cases in the intraoral group (100% [10 of 10]) but only 87.5% (7 of 8) in the extraoral group. Conclusion We conclude that mandibular reconstruction using a tray with PCBM and PRP is a safe and reliable method for cases of benign tumor and trauma, even if immediate reconstruction is performed by an intraoral approach.

Vitamin K(2) is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. We synthesized vitamin K(2) analogues with hydroxyl or phenyl groups at the ω-terminal of the side chain. The up-regulation of SXR-mediated transcription of the target gene by the analogues was dependent on the length of the side chain and the hydrophobicity of the ω-terminal residues. Phenyl analogue menaquinone-3 was as active as the known SXR ligand rifampicin.

Tob belongs to the anti-proliferative Tob/BTG protein family. The expression level of Tob family proteins is strictly regulated both transcriptionally and through post-translational modification. Ubiquitin (Ub)/proteosome-dependent degradation of Tob family proteins is critical in controlling cell cycle progression and DNA damage responses. Various Ub ligases (E3s) are responsible for degradation of Tob protein. Here, we show that Tob family proteins undergo monoubiquitination even in the absence of E3s in vitro. Determination of the ubiquitination site(s) in Tob by mass spectrometric analysis revealed that two lysine residues (Lys48 and Lys63) located in Tob/BTG homology domain are ubiquitinated. A mutant Tob, in which both Lys48 and Lys63 are substituted with alanine, is more strongly polyubiquitinated than wild-type Tob in vivo. These data suggest that monoubiquitination of Tob family proteins confers resistance against polyubiquitination, which targets proteins for degradation. The strategy for regulating the stability of Tob family proteins suggests a novel role for monoubiquitination.

Malignant fibrous histiocytoma (MFH) originates from primitive mesenchymal cells and has the capacity for dual histiocytic and fibroblastic differentiation. We report on an MFH of the left maxilla that developed in a 79-year old woman 20 years after surgery and radiation for squamous cell carcinoma (SCC). Postoperative radiotherapy with 70 Gy was administered for a primary neoplasm of SCC of the left maxilla to a localized field through two lateral ports. This secondary neoplasm arose at the site of tumor resection (partial maxillectomy) within the irradiated field, and was resected. The development of sarcomas is a recognized complication of radiation therapy. The final diagnosis after the operation was MFH. The patient died of tumor recurrence at the skull base and within the cranium, 19 months after the operation. Radiation-induced sarcoma is well known, but radiation-induced MFH is relatively rare in the head and neck region. The details of this case are presented with a review of literature.

The anti-tumor effect of a cyclooxygenase (COX)-2 selective inhibitor or a non-specific immunostimulant (PSK) alone, as well as the anti-tumor effect of their combined administration were examined on a hepatic metastasis model of colon cancer using a colon 26 cell line (CT26) and its highly metastatic variant. Anti-tumor effects were assessed by the number of hepatic metastases. Serum MMP-9, TGF-β and IL-6 were also measured. In a preliminary experiment, cells (5×10(5)) of a mouse colon cancer 26 cell line (CT26) and its highly metastatic variant were implanted below the splenic capsule in BALB/c and CDF1 mice. The number of hepatic metastatic CT26 cell lesions in the CDF1 mice of the non-spleen-removed group at 2 weeks was found to be optimum for the experiments. Although no significant difference was found, etodolac treatment showed the highest inhibitory effect on the number of hepatic metastases at a concentration of 30 mg/kg. In contrast, intraperitoneal administration of 50 mg/kg PSK showed an inhibitory effect on hepatic metastases, but a significant difference was not observed. PSK (p=0.002) or the combined use of etodolac and PSK (p=0.001) exhibited a significant inhibition of the number of hepatic metastases. In addition, MMP-9 was significantly inhibited by the single use of etodolac or PSK, and was inhibited with an additive effect by the combined use of etodolac and PSK. IL-6 and TGF-β were significantly inhibited following the combined use of etodolac and PSK. In conclusion, etodolac did not exhibit any significant hepatic metastasis inhibitory effect, whereas it significantly reduced the MMP-9 level. PSK reduced both the number of hepatic metastases and MMP-9. Combined use of etodolac and PSK did not show any additive effect in the inhibition of the number of hepatic metastases, whereas it inhibited MMP-9, TGF-β and IL-6, suggesting the benefit of a combined effect.

Dynamics of the imploding plasma and its relations to the 13.5 nm EUV emissions have been experimentally investigated for a laser-assisted Sn based discharge-produced plasma EUV source. The behaviours and two-dimensional electron density distributions of the EUV-emitting plasma were obtained using the time-resolved shadowgraph and Nomarski interferometric techniques. Observation of the plasma piston in the prepinch phase justified the validity of the zero-dimensional thin-shell model, from which the ion charge state of the prepinch plasma in the cathode region was estimated. The sausage (m = 0) instability that usually enhances the EUV emission was observed, with the radial electron density distribution that displays a concave shape at the crest of the plasma and a bell shape at the neck; the maximum of the electron density is located at one peak of the concave distribution at the crest instead of the neck. Intense EUV emission was produced by the Z-pinch plasma with the electron density (2.0–3.0) × 1018 cm−3. Moreover, the shock waves generated in the anode region can also produce in-band EUV emission with the intensity of 30% of that from the Z-pinch plasma.

The benefits of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with acute myelogenous leukemia (AML) in first complete remission (CR1) have mostly been evaluated in younger patients. Although favorable outcomes of allo-HCT over chemotherapy have been reported with the use of reduced-intensity conditioning (RIC) regimens in elderly patients with AML in CR1, information is still limited, especially on the effects of cytogenetic risks and donor sources. We collected data from AML patients aged 50 to 70 years who achieved CR1, and compared the outcome in 152 patients who underwent allo-HCT in CR1 (HCT group) to that in 884 patients who were treated with chemotherapy (CTx group). The cumulative incidence of relapse in the HCT group was significantly lower than that in the CTx group (22% versus 62%). Both overall survival (OS) and relapse-free survival (RFS) were significantly improved in the HCT group (OS: 62% versus 51%, P = .012), not only in the whole population, but also in the intermediate-risk group. Among patients who had a suitable related donor, the outcomes in the HCT group were significantly better than those in the CTx group. The introduction of appropriate treatment strategies that include allo-HCT may improve the outcome in elderly patients with AML in CR1.

Various prospective trials have been performed to assess the roles of allogeneic hematopoietic cell transplantation (allo-HCT) and chemotherapy in patients with acute myeloid leukemia (AML) in first complete remission (CR1). However, the results have not always been consistent, and there has been a limited evaluation of quality of life (QOL) in these postremission strategies. We performed a Markov decision analysis that enabled us to compare survival outcomes with a QOL evaluation using a database of 2029 adult AML patients who achieved CR1. The Markov decision model compared 2 strategies: allo-HCT or chemotherapy in CR1. Patients who had intermediate- or unfavorable-risk AML had a longer life expectancy when they received allo-HCT in CR1 than patients treated with chemotherapy alone. Likewise, patients who had a suitable related donor who received allo-HCT in CR1 had a longer life expectancy. The life expectancy was shortened to a greater degree by adjustment for QOL in the allo-HCT group. Nevertheless, QOL-adjusted life expectancies in most of the subgroups remained longer in the allo-HCT group than in the chemotherapy group. Our results showed that older patients with a related donor and younger patients with unfavorable cytogenetics benefited the most from allo-HCT in CR1.