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Recently, thermoplastic resins were used as matrix to synthesize carbon fiber‐reinforced thermoplastic (CFRTP) for recycling it easily. In this study, a CFRTP with excellent mechanical properties and heat resistance was synthesized using a polyether ether ketone (PEEK) as a matrix resin. The PEEK resin was modified to form cross‐linked structures through Friedel–Crafts reaction alkylation. The synthesis temperature of CFRTP was optimized considering the mechanical properties of PEEK, and its heat resistance was enhanced because of the cross‐linked structures. Further, the cross‐linked PEEK resin was partially used as a matrix resin, and the mechanical properties of the CFRTP were enhanced. We plan to develop a method for recycling CFRTP using PEEK and crosslinked PEEK for synthesizing C/C composites by focusing on the high heat resistance of the crosslinked PEEK containing a large amount of carbon and reducing mass loss after heat treatment. Highlights: CC bonds were introduced into the polyether ether ketone (PEEK) resin by Friedel–Crafts reaction alkylation.Thermal properties of PEEK were enhanced by hypercrosslinking reaction.Optimization of synthesized temperature was investigated to fabricate carbon fiber‐reinforced thermoplastic (CFRTP).Mechanical properties were enhanced CFRTP modified with hypercrosslinking reaction. [ABSTRACT FROM AUTHOR]

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming. [ABSTRACT FROM AUTHOR]

Polymeric particles less than 100 nm in size (polymer nanoparticles), which are useful in the fields of medicine and so on, are synthesized through emulsion polymerization, wherein surfactants are essential for maintaining their dispersion stability, contaminating particle surfaces and causing high environmental pollution. The soap‐free emulsion polymerization (SFEP) of styrene in a packed reactor using microglass beads enables the synthesis of polymer nanoparticles without surfactants. Ultraviolet irradiation is used for radical polymerization using an initiator during the SFEP of styrene. The reaction space in the packed reactor is controlled by the size of glass beads to be filled in the reactor. A decrease in the size of the glass beads narrows the reaction space, causing the average polystyrene particle size to reach 27.3 nm and suppress convection flow by the wall of the glass beads, thereby limiting particle motion and preventing particle growth through particle collisions. [ABSTRACT FROM AUTHOR]

Background: Various antigen‐presenting cells and tumor cells‐expressing PD‐L1 inhibits antitumor immune responses in the tumor microenvironment. Recently, numerous studies have shown that tumor cell intrinsic PD‐L1 also plays important roles in tumor growth and progression. On the other hand, oral squamous cell carcinoma (OSCC) cells overexpress epidermal growth factor receptor (EGFR) and EGFR signal pathway exacerbates tumor progression. Therefore, this study assessed whether tumor‐intrinsic PD‐L1 facilitates malignant potential of OSCC cells through regulation of EGFR signaling. Methods: Two OSCC cell lines, SAS and HSC‐3, were transfected with PD‐L1 and EGFR‐specific small interfering RNA (siRNA). Influences of PD‐L1 knockdown on malignant potentials of OSCC cells were examined by Cell Counting kit‐8 assay, transwell assay, sphere formation assay, flow cytometry, and Western blot. Effects of PD‐L1 and EGFR knockdown on each expression were examined by quantitative real‐time PCR (qRT‐PCR), Western blot, and flow cytometry. Results: Transfection of an PD‐L1‐siRNA into OSCC cells decreased the abilities of proliferation, stemness, and mobility of these cells significantly. PD‐L1 knockdown also decreased EGFR expression through the promotion of proteasome‐ and lysosome‐mediated degradation and following activation of the EGFR/protekin kinase B (AKT) signal pathway. Meanwhile, EGFR knockdown did not influence PD‐L1 expression in SAS and HSC‐3 cells, but treatment with a recombinant human EGF induced its expression. Treatment with erlotinib and cetuximab suppressed rhEGF‐induced PD‐L1 expression and localization in the cellular membrane of both OSCC cells. Conclusion: OSCC cells‐expressing PD‐L1 induced by EGF stimulation may promote malignancy intrinsically via the activation of the EGFR/AKT signaling cascade. [ABSTRACT FROM AUTHOR]

To feed on prey efficiently, predators must overcome the prey's defensive traits. However, there are fewer reports on the antagonistic traits of predators than there are on the defensive traits of prey.Here, we focus on prey–predator interactions between social aphids and aphidophagous lepidopteran larvae. Larvae of Taraka hamada (Lepidoptera: Lycaenidae) are specialist predators of the social aphid Ceratovacuna japonica (Homoptera: Aphididae), and later instar larvae have long lateral body setae. Because this aphid produces defensive individuals (soldiers), we hypothesised that T. hamada larvae have an antagonistic trait that prevents attacks by soldiers and tested whether that trait might be their lateral body setae.To test whether a larva's lateral body setae constitute an antagonistic trait against the soldier's physical defence, we compared the rate of aphid consumption per unit time and the vulnerability to attack by soldiers between larvae with short lateral body setae and larvae with long lateral body setae in the presence of soldiers.Our results showed that the aphid consumption rate of larvae with long lateral body setae was significantly higher than that of larvae with short lateral body setae. Furthermore, the larvae with short lateral body setae were more vulnerable to soldier attacks than the larvae with long lateral body setae. These results imply that the length of the lateral body setae of T. hamada larvae affects their vulnerability to soldier attacks and that the lateral body setae are an antagonistic trait against the soldiers of this social aphid. [ABSTRACT FROM AUTHOR]

The article discusses the need for correction methods in the evaluation of structural metrics in brain imaging studies. Total intracranial volume (TIV) is a major factor affecting these metrics, and different correction methods have been used with varying results. A recent study evaluated four TIV correction methods and found that the proportion correction method had inconsistent results compared to the other three methods. The study highlights the importance of further research and comparisons with other correction approaches. Additionally, the article mentions the need to consider other sources of fluctuations in brain volume, such as physiological and technical factors, and the use of new brain atlases for quantitative measurements. [Extracted from the article]

Various halogenated mesoionic‐carbene (MIC)‐coordinated palladium complexes (denoted as TAPs and e‐TAPs) were prepared using triazolylidene precursors that were synthesized in only two steps via a click reaction. Among the prepared complexes, 2‐Bromophenyl group substituted e‐TAP (Br‐e‐TAP) showed optimal catalytic activity for the arylation of aldehydes with arylboronic compounds. Additionally, the Br‐e‐TAP catalyst assisted in synthesizing a wide range of functionalized diarylmethanols and arylmethanols in 29–95% yields with loadings of 0.2–0.6 mol% Pd. [ABSTRACT FROM AUTHOR]

Through combined measurements of broadband optical spectroscopy (10 meV to 6 eV), electrical resistivity, and Hall effect, the effects of gamma ray irradiation on electronic and optical properties of gallium‐doped ZnO (GZO) thin films, deposited by ion plating direct‐current arc discharge, are investigated. A significant number of films, deposited at various discharge currents (ID = 100–200 A) and oxygen gas flow rates (OFR = 0–25 sccm), exposed to doses of 15 and 30 kGy of gamma rays, are studied. The results indicate strong resilience of films to irradiation: visible range transparency is reduced by 10–12% and the optical bandgap shifts to lower energies by less than 3%, while electrical resistivity, carrier concentration, and electron mobility remain nearly unchanged. [ABSTRACT FROM AUTHOR]

Periodontal Ehlers–Danlos syndrome (pEDS) is an autosomal‐dominant disorder first described by Stewart in 1977 that is characterized by severe gingival recession and periodontitis that triggers premature loss of permanent teeth and alveolar bone absorption. It was recently shown that pEDS is caused by a heterozygous missense mutation in C1R or C1S, which encode complement 1 proteases. Here, we report a familial case of pEDS with a novel heterozygous missense mutation, c.674G>C (p.R225P), in C1R (NM_001733.4). The case exhibited pretibial hyperpigmentation and extended periodontitis but neither skin extensibility nor joint hypermobility, suggesting that this mutation will expand the definition of pEDS. [ABSTRACT FROM AUTHOR]

1,2‐Addition reactions using organoboron compounds are one of the useful syntheses of various functionalized alcohols, but they generally require a large quantity of bases. In this study, we attempted to solve this problem by synthesizing unsymmetrical 1,3‐diarylimidazoline‐type N‐heterocyclic carbene (NHC)‐coordinated C^C* cyclometalated palladium(II) complexes with bridging hydroxide ligands (CYPOHs) in two steps and one pot from the corresponding Cl bridged dimer and using them as catalysts. 2,6‐di(pentan‐3‐yl)aniline (IPent)‐based NHC coordinated PhS‐IPent‐CYPOH acted as a highly efficient catalyst for the 1,2‐addition of (hetero)arylboronates to a large number of aldehydes and ketones, including unactivated ketones, under base‐free conditions. [ABSTRACT FROM AUTHOR]

Various cell types secrete exosomes into their surrounding extracellular space, which consequently affect the function and activity of recipient cells. Numerous studies have showed that tumor cell‐derived exosomes play important roles in tumor growth and progression. Although a variety of endocytic pathways are reportedly involved in the cellular uptake of exosomes, detailed mechanisms remain unknown. The present study demonstrated that treatment with recombinant epidermal growth factor (EGF) time‐ and dose‐dependently promoted cellular uptake of oral squamous cell carcinoma (OSCC) cell‐derived exosomes into OSCC cells themselves. Conversely, EGF receptor (EGFR) knockdown and treatment with EGFR inhibitors, including erlotinib and cetuximab, abrogated OSCC cell uptake of exosomes. The macropinocytosis inhibitor 5‐(N‐ethyl‐N‐isopropyl) amiloride (EIPA) blocked the effects of active EGF/EGFR signaling on uptake of OSCC cell‐derived exosomes. These EGFR inhibitors also suppressed OSCC cell‐derived exosome‐induced proliferation, migration, invasion, stemness, and chemoresistance of OSCC cells. Taken together, the data presented herein suggest that EGFR inhibitors might inhibit the malignant potential of OSCC cells through direct inhibition of not only EGFR downstream signaling pathway but also cellular uptake of OSCC cell‐derived exosomes through macropinocytosis. [ABSTRACT FROM AUTHOR]

Background: Constitutive activation of STAT3 promotes oncogenesis and growth of oral squamous cell carcinoma (OSCC). We investigated the mechanism of action of suppressor of cytokine signaling 1 (SOCS1), an endogenous inhibitor of JAK, as gene therapy for OSCC. Methods: Antitumor effect of SOCS1 was compared to JAK inhibitor I by cell proliferation assay, cell cycle analysis, and apoptosis analysis in vitro. In addition, antitumor effect was evaluated using xenograft mouse models in vivo. Results: JAK inhibitor I inhibited the proliferation of KOSC2 cl3‐43 or T3M‐1 clone2 OSCC cell lines in vitro. While JAK inhibitor I arrested both cell lines at the G2/M phase, induction of apoptosis was observed in T3M‐1 clone2 cells, but not KOSC2‐cl3‐43 cells. An adenoviral vector expressing SOCS1 (AdSOCS1) significantly decreased the proliferation of both OSCC cell lines and induced G2/M phase cell cycle arrest and apoptosis, suggesting that induction of apoptosis of KOSC2 cl3‐43 cells by AdSOCS1 is regulated by the JAK/STAT independent pathway. Overexpression of SOCS1 inhibited activation of the JAK/STAT and p44/42 MAPK pathways, while JAK inhibitor I inhibited activation of the JAK/STAT pathway only. Consistently, expression of Mcl‐1 was decreased by overexpression of SOCS1, but not JAK inhibitor I. Additionally, KOSC2 cl3‐43 or T3M‐1 clone2 OSCC cells were subcutaneously implanted in the flanks of two xenograft mouse models. As compared to a control adenovirus vector (AdLacZ), intratumor injection of AdSOCS1 significantly decreased the tumor volume and induced apoptosis in vivo. Conclusion: SOCS1 gene therapy may be a beneficial approach for the treatment of OSCC. [ABSTRACT FROM AUTHOR]

Objectives: Gastrointestinal endoscopy (GIE) is useful for the early detection and treatment of many diseases; however, GIE is considered a high‐risk procedure in the coronavirus disease 2019 (COVID‐19) pandemic era. This study aimed to explore the rate of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) positivity in saliva and gastrointestinal fluids to which endoscopy medical staff are exposed. Methods: The study was a single‐center cross‐sectional study. From June 1 to July 31, 2020, all patients who underwent GIE at Yokohama City University Hospital were registered. All patients provided 3 mL of saliva. For upper GIE, 10 mL of gastric fluid was collected through the endoscope. For lower GIE, 10 mL of intestinal fluid was collected through the endoscope. The primary outcome was the positive rate of SARS‐CoV‐2 in saliva and gastrointestinal fluids. We also analyzed serum‐specific antibodies for SARS‐CoV‐2 and patients' background information. Results: A total of 783 samples (560 upper GIE and 223 lower GIE samples) were analyzed. Polymerase chain reaction (PCR) on saliva samples did not show any positive results in either upper or lower GIE samples. However, 2.0% (16/783) of gastrointestinal fluid samples tested positive for SARS‐CoV‐2. No significant differences in age, sex, purpose of endoscopy, medication, or rate of antibody test positivity were found between PCR positive and PCR negative cases. Conclusions: Asymptomatic patients, even those with no detectable virus in their saliva, had SARS‐CoV‐2 in their gastrointestinal tract. Endoscopy medical staff should be aware of infection when performing procedures. The study was registered as UMIN000040587. [ABSTRACT FROM AUTHOR]

The peroxisome proliferator‐activated receptor alpha (PPARα) is a nuclear receptor that has been linked to the modulation of several physiological functions, including the sleep–wake cycle. The PPARα recognizes as endogenous ligands the lipids oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which in turn, if systemically injected, they exert wake‐promoting effects. Moreover, the activation of PPARα by the administration of OEA or PEA increases the extracellular contents of neurotransmitters linked to the control of wakefulness; however, the role of PPARα activated by OEA or PEA on additional biochemicals related to waking regulation, such as acetylcholine (ACh) and 5‐hydroxytryptamine (5‐HT), has not been fully studied. Here, we have investigated the effects of treatments of OEA or PEA on the contents of ACh and 5‐HT by using in vivo microdialysis techniques coupled to HPLC means. For this purpose, OEA or PEA were systemically injected (5, 10 or 30 mg/kg; i.p.), and the levels of ACh and 5‐HT were collected from the basal forebrain, a wake‐related brain area. These pharmacological treatments significantly increased the contents of ACh and 5‐HT as determined by HPLC procedures. Interestingly, PPARα antagonist MK‐886 (30 mg/kg; i.p.) injected before the treatments of OEA or PEA blocked these outcomes. Our data suggest that the activation of PPARα by OEA or PEA produces significant changes on ACh and 5‐HT levels measured from the basal forebrain and support the conclusion that PPARα is a suitable molecular element involved in the regulation of wake‐related neurotransmitters. [ABSTRACT FROM AUTHOR]

Activated carbon was prepared using bagasse and carbon fiber (RCF) recycled from carbon fiber reinforced polymer (CFRP). The RCF surface has a sufficient amount of functional groups and can be used as a catalyst for the hydrolysis of bagasse cellulose. An RCF‐bagasse composite was fabricated by ultrasonic irradiation. During cellulose hydrolysis, carbon from the bagasse was activated with sulfuric acid, which impregnated the cellulose pores. When bagasse was subjected to high temperatures, the impregnated pores decomposed, resulting in micropores. The addition of RCF increased the specific surface area of activated carbon by up to 20 % when heat treatment was performed at a temperature higher than the carbonization temperature of bagasse. [ABSTRACT FROM AUTHOR]

Paraspeckles are constructed by NEAT1_2 architectural long noncoding RNAs. Their characteristic cylindrical shapes, with highly ordered internal organization, distinguish them from typical liquid–liquid phase‐separated condensates. We experimentally and theoretically investigated how the shape and organization of paraspeckles are determined. We identified the NEAT1_2 RNA domains responsible for shell localization of the NEAT1_2 ends, which determine the characteristic internal organization. Using the soft matter physics, we then applied a theoretical framework to understand the principles that determine NEAT1_2 organization as well as shape, number, and size of paraspeckles. By treating paraspeckles as amphipathic block copolymer micelles, we could explain and predict the experimentally observed behaviors of paraspeckles upon NEAT1_2 domain deletions or transcriptional modulation. Thus, we propose that paraspeckles are block copolymer micelles assembled through a type of microphase separation, micellization. This work provides an experiment‐based theoretical framework for the concept that ribonucleoprotein complexes (RNPs) can act as block copolymers to form RNA‐scaffolding biomolecular condensates with optimal sizes and structures in cells. SYNOPSIS: Paraspeckles scaffolded by NEAT1_2 lncRNAs have characteristic shapes and internal structures distinct from typical LLPS droplets. Using soft matter physics theory, this study reveals that they are built as block copolymer micelles, providing a concept that RNPs act as block copolymers. NEAT1_2 RNPs behave as block copolymer and form paraspeckles as micelles.Length of the NEAT1_2 5′ and 3′ terminal domains and transcription rate of NEAT1_2 determine the internal organization, size, number, and shape of the paraspeckle.NEAT1_2 lacking both the 5′ and 3′ terminal domains form large spherical paraspeckles via macroscopic phase separation.RNPs have the potential to form various structures as block copolymer micelles. [ABSTRACT FROM AUTHOR]

Background: Although 7T functional MRI (fMRI) provides better signal‐to‐noise ratio and higher spatial resolution than 3T fMRI, geometric distortions become more challenging because fMRI is more susceptible to distortions than structural MRI. Accurate alignment of 7T fMRI to structural MRI data is critical for precise cortical surface‐based analysis. Purpose: To quantify the effectiveness of distortion corrections of 7T fMRI data. Study Type: Prospective. Subjects: Fifteen healthy individuals aged 19–26 years (mean: 21.9 years). Field Strength/Sequence: Multiband gradient‐echo echo‐planar imaging sequence at 7T; 3D T1/T2‐weighted sequences (magnetization prepared rapid acquisition with gradient echo [MPRAGE] and sampling perfection with application optimized contrast using different flip angle evolution [SPACE]) at 3T. Assessment: fMRI data at 7T were registered to cortical surfaces reconstructed from 3T structural data acquired in the same subjects. Distortions induced by B0 inhomogeneity and gradient nonlinearity (B0 and gradient distortions) were evaluated as cortical fallout (misregistration of noncortical areas) and displacement (misregistration along gray matter). Statistical Tests: Repeated measures analyses of variance with post‐hoc t‐tests with Bonferroni correction. Results: The accuracy of fully corrected fMRI images based on the intensity distribution was 89.2%. Without any corrections, 9.7% of vertices in the whole surfaces were fallout and the average displacement was 0.96 mm for the rest of the vertices. B0 and gradient distortion corrections significantly reduced the fallout (to 2.1% and 8.7%) and displacement (to 0.29 mm and 0.86 mm). These corrections were effective even around regions with moderate distortions (the somatosensory and visual cortices for B0 distortion, and the anterior frontal, inferior temporal, and posterior occipital cortices for gradient distortion). Data Conclusion: B0 distortion correction is crucial for surface‐based analysis of fine‐resolution fMRI at 7T. Gradient distortion correction should be considered when regions of interest include regions distant from the isocenter of scanners. Evidence Level: 1 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

Young, Sutherland, and McCoy indicated that a Go/No‐Go Task (GNG) becomes more difficult as the inter‐stimulus intervals (ISIs) becomes shorter. However, is the number of commission errors under extremely short ISIs a useful metric for assessing response inhibition? This study challenges the assumption that a shorter ISI in the GNG enables better assessment of response inhibition. University students (N = 213) completed the GNG, the Conners Continuous Performance Test 3rd Edition (CCPT), and the Modified Stroop Task. The GNG comprised four blocks of 400, 600, 800, and 1000 ms ISIs, whereas the stimulus presentation was fixed at 250 ms. Consistent with Young et al., shorter ISIs in the GNG resulted in more commission errors. In the block with the shortest ISI, participants also failed more frequently in responses in go trials than in the other blocks, which appears to increase in error variance of commission errors. Consistent with this interpretation, the association between the number of commission errors in the block with 400 ms ISI and CCPT performance was weaker than those between the number of commission errors in other blocks and CCPT performance. It is concluded that using the number of commission errors in the condition with extremely short ISIs in the GNG might be inappropriate for assessing response inhibition. [ABSTRACT FROM AUTHOR]

The synthesis of primary, secondary, and tertiary alcohols by the 1,2‐addition of arylboronic acids or boronates to carbonyl compounds, including unactivated ketones, using novel bulky yet flexible N‐heterocyclic carbene (NHC)‐coordinated 2,6‐di(pentan‐3‐yl)aniline (IPent)‐based cyclometallated palladium complexes (CYPs) as catalysts is reported. The PhS‐IPent‐CYP‐catalyzed reactions are efficient at low catalyst loadings (0.02–0.3 mol% Pd), and the exceptional catalytic activity for 1,2‐addition is attributed to the steric bulk of the NHC ligand. These reactions can yield a wide range of functionalized benzylic alcohols that are difficult to synthesize by classical protocols using highly active organomagnesium or lithium reagents. [ABSTRACT FROM AUTHOR]

We present a review of the case reports of tongue/lingual necrosis caused by systemic vascular diseases. An electronic search of PubMed/MEDLINE was carried out for studies published from January 2009 to December 2018 using the following three keywords: tongue, lingual, and necrosis. The literature analysis identified 32 reports (38 cases) of tongue/lingual necrosis among the 325 studies originally identified by the PubMed/MEDLINE search. In all, 19 of the 38 cases were on vasculitis, followed by 10 on cardiogenic/septic shock, 7 on tongue infarction (due to carotid artery stenosis or systemic thrombosis), and 2 on other causes (systemic lupus erythematosus and systemic vascular amyloidosis). Among the 19 cases on vasculitis, 15 cases were reported about giant cell arteritis; 3 on polyarteritis nodosa; and 1 on necrotizing vasculitis of the tongue secondary to giant cell arteritis. In conclusion, the diagnosis of tongue/lingual necrosis is diverse and challenging because of the polymorphous clinical pattern at onset and similarity with different diseases. Our findings will be useful to clinicians in the differential diagnosis of unusual tongue/lingual necrosis cases. [ABSTRACT FROM AUTHOR]

In the revised World Health Organization classification 2016, anaplastic pleomorphic xanthoastrocytoma (PXA) has been newly defined as a variant of the PXA entity. Furthermore, some anaplastic PXA were reported to have extremely poor prognosis which showed a type of pediatric glioblastoma (GBM) molecular profile. Recent integrated molecular classification for primary central nervous system tumors proposed some differences between histological and molecular features. Herein, in a genome‐wide molecular analysis, we show an extreme aggressive anaplastic PXA that resulted in a pediatric GBM molecular profile. A full implementation of the molecular approach is the key to predict prognosis and decide the treatment strategy for anaplastic PXA. This report suggests that anaplastic PXA consists of clinically and biologically distinct multiple entities, and genome‐wide molecular profiling may help to identify them. This new approach will be useful for predicting prognosis and choosing treatment for anaplastic PXA patients. [ABSTRACT FROM AUTHOR]

We previously reported the efficacy of anti‐cancer therapy with hyperthermia using an alternating magnetic field (AMF) and a magnetic compound. In the course of the study, unexpectedly, we found that an AMF enhances the cytotoxicity of Compound C, an activated protein kinase (AMPK) inhibitor, although this compound is not magnetic. Therefore, we examined the cellular mechanism of AMF‐induced cytotoxicity of Compound C in cultured human glioblastoma (GB) cells. An AMF (280 kHz, 250 Arms) for 30 minutes significantly enhanced the cytotoxicity of Compound C and promoted apoptosis towards several human GB cell lines in vitro. The AMF also increased Compound C‐induced cell‐cycle arrest of GB cells at the G2 phase and, thus, inhibited cell proliferation. The AMF increased Compound C‐induced reactive oxygen species production. Furthermore, the AMF decreased ERK phosphorylation in the presence of Compound C and suppressed the protective autophagy induced by this compound. The application of an AMF in cancer chemotherapy may be a simple and promising method, which might reduce the doses of drugs used in future cancer treatment and, therefore, the associated side effects. The present paper aims to apply an alternating magnetic field (AMF) combined with Compound C, a cell permeable AMPK inhibitor, to a novel glioblastoma (GB) treatment. We believe that this is the first report in which an AMF is applied to treatment of GB in combination with an anti‐tumor agent, Compound C. Our results revealed that AMF further enhanced Compound C‐induced cytotoxicity through de‐phosphorylation of ERK and suppression of autophagy in GB cells. [ABSTRACT FROM AUTHOR]

Summary: We propose a pressure‐based unified solver for gas‐liquid two‐phase flows where compressible and incompressible flows coexist. Unlike the original thermo–Cubic Interpolated Propagation Combined Unified Procedure (CIP‐CUP) method proposed by Himeno et al (Transactions of the Japan Society of Mechanical Engineers, Series B, 2003), we split the advection term of the governing equations into a conservation part and into the rest. The splitting of advection term has two advantages. One is the high degree of freedom in choosing discretization schemes such as central‐difference schemes, upwind schemes, and Total Variation Diminishing (TVD) schemes. The other is the ease of implementation on unstructured grids. The advantages enable the analyses of various flows such as turbulent and supersonic ones in actual complicated boundaries. Therefore, the solver is useful for practical analyses. The solver was validated on the following test cases: subsonic single‐phase flows, incompressible single‐phase turbulent flows, and incompressible gas‐liquid two‐phase flows. With unstructured grids, we obtained the equivalent results as the ones with structured grids. After the validations, subsonic jet impinging on a water pool was calculated and compared with experimental results. It was confirmed that the calculated results were consistent with the experimental ones. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common and devastating type of malignant brain tumor. We recently found that eribulin suppresses glioma growth in vitro and in vivo and that eribulin is efficiently transferred into mouse brain tumors at a high concentration. Eribulin is a non‐taxane microtubule inhibitor approved for breast cancer and liposarcoma. Cells arrested in M‐phase by chemotherapeutic agents such as microtubule inhibitors are highly sensitive to radiation‐induced DNA damage. Several recent case reports have demonstrated the clinical benefits of eribulin combined with radiation therapy for metastatic brain tumors. In this study, we investigated the efficacy of a combined eribulin and radiation treatment on human glioblastoma cells. The glioblastoma cell lines U87MG, U251MG and U118MG, and SJ28 cells, a patient‐derived sphere culture cell line, were used to determine the radiosensitizing effect of eribulin using western blotting, flow cytometry and clonogenic assay. Subcutaneous and intracerebral glioma xenografts were generated in mice to assess the efficacy of the combined treatment. The combination of eribulin and radiation enhanced DNA damage in vitro. The clonogenic assay of U87MG demonstrated the radiosensitizing effect of eribulin. The concomitant eribulin and radiation treatment significantly prolonged the survival of mice harboring intracerebral glioma xenografts compared with eribulin or radiation alone (P < .0001). In addition, maintenance administration of eribulin after the concomitant treatment further controlled brain tumor growth. Aberrant microvasculature was decreased in these tumors. Concomitant treatment with eribulin and radiation followed by maintenance administration of eribulin may serve as a novel therapeutic strategy for glioblastomas. [ABSTRACT FROM AUTHOR]

A gallium nitride (GaN) epitaxial layer with a low density of threading dislocations is successfully grown on a silicon substrate by using in situ gas etching. Silicon nitride (SiNx) film is used as a mask, and ammonia is intermittently supplied in hydrogen ambient during the etching. After etching, high‐density deep pits appeared on the surface of a GaN template layer and corresponded to the threading dislocations in the layer. In this novel method, before growing an additional GaN layer on the template GaN layer, a second SiNx layer is deposited after the etching process, and this layer prevents GaN nuclei from growing on the upper side‐walls of the pits. By using this method, the density of threading dislocations of the GaN surface is reduced to 6.7 × 107 cm−2. This method is cost effective, completing all the necessary processes in one growth run without taking samples out from a metalorganic chemical vapor deposition (MOCVD) reactor. [ABSTRACT FROM AUTHOR]

Abstract: Palladium‐catalyzed amination of aryl(haloaryl)amines with 9H‐carbazole derivatives was investigated. In the amination of (4‐bromophenyl)phenylamine with 9H‐carbazole by the use of Pd2(dba)3/PtBu3/NaOtBu catalyst, the main product was desired 9‐[4‐(phenylamino)phenyl]‐9H‐carbazole in 60% yield with conversion of (4‐bromophenyl)phenylamine >99%, and the concomitant formation of 9‐[4‐[phenyl[4‐(phenylamino)phenyl]amino]phenyl]‐9H‐carbazole (15% yield), which is the consecutive by‐product, was observed. When XPhos was used instead of PtBu3, the desired product was provided in 81% yield and the consecutive by‐product was suppressed to 7.7%. The yield of the desired product reached 98% by the use of tBu‐XPhos. Such excellent yields of the desired product were also obtained with other 2‐di‐tert‐butyl‐ or 2‐di(1‐adamantyl)phosphino‐1,1’‐biaryls. Various 9‐(arylamino)aryl‐9H‐carbazoles could be synthesized from aryl(haloaryl)amines and 9H‐carbazole derivatives in high yields by the use of tBu‐XPhos. The amination of 4‐bromotoluene with a mixture of diphenylamine and 9H‐carbazole gave only 9‐o‐tolyl‐9H‐carbazole with tBu‐XPhos, while the use of PtBu3 or XPhos afforded the mixture of 9‐o‐tolyl‐9H‐carbazole and diphenyl(o‐tolyl)amine, indicating that Pd2(dba)3/tBu‐XPhos/NaOtBu catalyst high selectively favors 9H‐carbazole over diphenylamine as an amination substrate. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To report the efficacy of the predetermined treatment protocol of the Collaborative Bleb‐related Infection Incidence and Treatment Study (CBIITS) for bleb‐related infection (BRI) patients. Methods: A prospective, observational cohort study was conducted at 34 clinical centres in Japan. Nineteen eyes from 19 patients that developed BRI were treated using the CBIITS protocol at 34 clinical centres. The visual acuity (VA) and intraocular pressure (IOP) were monitored for 6 and 12 months after treatment with the predetermined protocol. Results: The logMAR was 0.623 ± 0.748 (mean ± standard deviation) before the infection developed. It was 1.054 ± 1.156 and 0.950 ± 1.168 at 6 months and 12 months post‐infection, respectively. However, in subgroup analyses, there was no significant decrease in post‐infection logMAR in stages I and II. In contrast, decimal VA was decreased ≥2 lines in all four cases in stage III. The IOP did not change after infection. It was 10.2 ± 5.0 mmHg (range, 3–22 mmHg) before the infection developed, and 12.9 ± 5.2 mmHg (5–24 mmHg) and 10.7 ± 4.7 mmHg (3–18 mmHg) at 6 months and 12 months after infection, respectively. Conclusion: Because of the small number of BRI patients, the superiority of the treatment was not definitively determined. However, VA was almost maintained in stages I and II, and the IOP did not change after infection. Although further study is necessary, the treatment protocol shown in the study might be a valuable treatment regime. [ABSTRACT FROM AUTHOR]

Background The rate of childhood cancer survival has recently reached >80%. Various adverse events among childhood cancer survivors (CCS) have been reported. Proton beams are able to avoid unnecessary irradiation to normal/vital organs. We conducted a quality of life (QOL) study for CCS who were treated with proton beam therapy (PBT). Methods We included those patients treated with PBT to the brain, head, or neck and who were ≤15 years old at the University of Tsukuba Hospital between 1983 and 2011. Clinical information was collected from medical records. Questionnaires including the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales (which assess health-related quality of life) were sent to the families/patients. Results Sixty patients were included. Median age at treatment was 6.2 years. The number of patients with status alive/dead/unknown was 32/24/4. Median follow-up period was 63.0 months (range, 48-340 months) for survivors. Questionnaires were sent to 25 families/patients and 19 were returned. PedsQL was assessed for 17 patients. Eleven of 32 living patients had at least one comorbidity grade 3/4. Average QOL score was above that for Japanese schoolchildren and adolescents. There was no correlation with comorbidity, and only longer time from treatment was correlated with a higher PedsQL score ( P = 0.006). Conclusion CCS who were treated with multimodal treatment using PBT had a higher QOL score. Higher score was related to longer time since treatment, regardless of comorbidity. [ABSTRACT FROM AUTHOR]

Objective Withdrawal of cabergoline is generally challenging, especially in patients with large or invasive macroprolactinomas. Therefore, we aimed to assess long-term results of cabergoline therapy for macroprolactinomas and remission achievement results after withdrawal in patients with macroprolactinomas. We also investigated clinical characteristics and factors related to remission after withdrawal. Methods This was an institutional review board-approved retrospective analysis. We studied 46 macroprolactinoma patients who had taken cabergoline during the period from 2003 through 2013. Administration of cabergoline was maintained for 5 years before withdrawal. Results Median follow-up after the initiation of cabergoline therapy was 54·3 (range 5·3 to 137·2) months. Recurrences of hyperprolactinaemia were observed in 3 of 11 (27%) postwithdrawal patients at a median time of 3·0 (range; 2·9-11·2) months, indicating that a high percentage (73%) maintained remission for at least 12 months after cabergoline cessation. Factors significantly associated with remission were analysed in 21 patients receiving long-term cabergoline administration. On multivariate analysis, the absence of cavernous sinus invasion on pretreatment MRI (≥3/4 tumour encasement of the intracavernous internal carotid artery) ( HR; 21·94, 95% CI; 2·06-1071·0, P = 0·006), initial PRL <132·7 ng/ml ( HR; 8·28, 95% CI; 1·24-199·6, P = 0·03) and nadir PRL <1·9 ng/ml during cabergoline therapy ( HR; 5·14, 95% CI; 1·10-39·02, P = 0·04) showed statistically significant correlations with remission after withdrawal. Conclusions Cabergoline therapy can achieve a high percentage (73% in this series) of remission maintenance for at least 12 months after cessation of a 5-year course of therapy, even in patients with macroprolactinomas. The absence of cavernous sinus invasion, serum PRL level lower than 132·7 ng/ml before cabergoline therapy or nadir serum PRL below 1·9 ng/ml were related to more frequent remission after withdrawal of cabergoline in patients receiving this medication for 5 years. [ABSTRACT FROM AUTHOR]

Purpose To report the 5-year incidence of visual impairment after mitomycin C-augmented trabeculectomy ( MMC trabeculectomy) and the risk factors for visual impairment. Methods This is a multicentre prospective observational cohort study. Among glaucoma patients registered in the Collaborative Bleb-related Infection Incidence and Treatment Study performed in Japan, the patients with eyes meeting the following qualifications were included: eyes with primary open-angle glaucoma; eyes with primary angle-closure glaucoma; eyes with exfoliative glaucoma; eyes with ≥3/60 in blindness analysis; and eyes with ≥20/60 in low-vision analysis and visual acuity loss analysis. The patients were followed at 6-month intervals for 5 years. The entry data and follow-up data were analysed to determine the incidence of blindness (<3/60), low vision (≥3/60 and <20/60) and visual acuity loss (≥0.2 log MAR) during the follow-up period. Risk factors for visual impairment were also analysed. Results A total of 694 eyes of 694 or 559 eyes of 559 glaucoma patients were subjected to the blindness analysis or the low-vision and visual acuity loss analysis, respectively. Visual acuity significantly deteriorated (p < 0.0001): 12.2% (95% CI: 9.8-14.7%) of the patients became blind; 12.1% (95% CI: 9.4-14.9%) were judged to have low vision at the final examination; 28.3% (95% CI: 24.5-32.0%) were judged to have visual acuity loss. Glaucoma subtypes, poor preoperative visual function and postoperative complications are the main risk factors for visual impairment. Conclusions Visual acuity was significantly reduced after MMC trabeculectomy in 5 years, and we identified several risk factors associated with this complication. [ABSTRACT FROM AUTHOR]

Purpose To investigate the intra-ocular pressure ( IOP)-lowering effects and safety of 0.4% ripasudil (K-115), a Rho kinase inhibitor, twice daily for 52 weeks, in patients with open-angle glaucoma or ocular hypertension ( OHT). Methods In this multicentre, prospective, open-label study, 388 patients with primary open-angle glaucoma, OHT or exfoliation glaucoma were enrolled and 354 of them were subdivided into four cohorts (monotherapy, 173; additive therapy to prostaglandin analogs, 62; β-blockers, 60; or fixed combination drugs, 59). The IOP reduction at trough and peak from baseline and adverse events was investigated. Results Ripasudil showed IOP-lowering effects over 52 weeks in all the analyses of monotherapy, additive therapy and both subgroups (baseline IOP ≥21 mmHg and <21 mmHg) of monotherapy. The mean IOP reductions at trough and peak at week 52 were −2.6 and −3.7 mmHg for monotherapy, and −1.4 and −2.4, −2.2 and −3.0, and −1.7 and −1.7 mmHg, respectively, for additive therapy described above. The most frequently observed adverse events were conjunctival hyperaemia ( n = 264, 74.6%), blepharitis ( n = 73, 20.6%) and allergic conjunctivitis ( n = 61, 17.2%). Most of the conjunctival hyperaemia findings were mild (97.0%), transient and resolved spontaneously (78.0%). Although 51 patients discontinued from the study due to blepharitis and/or allergic conjunctivitis (blepharitis, 28; allergic conjunctivitis, 17; both, 6), all the events resolved with or without treatment after the discontinuation of ripasudil administration. Conclusion Fifty-two week administration of 0.4% ripasudil revealed IOP-lowering effects and an acceptable safety profile when administered as monotherapy or as additive therapy, in patients with open-angle glaucoma or OHT. [ABSTRACT FROM AUTHOR]

We evaluated the feasibility of 5-aminolevulinic acid (5- ALA)-mediated photodynamic diagnosis ( PDD) in the biopsy for primary central nervous system lymphoma ( PCNSL). 5- ALA (20 mg kg−1) was administered orally 4 hours preoperatively. Forty-one biopsies obtained under PDD in 47 consecutive biopsies (46 patients) that were finally pathologically diagnosed as PCNSL were evaluated. Positive fluorescence was observed in 34 of those 41 biopsies (82.9%). An intraoperative pathological diagnosis ( IOD) of suspected PCNSL was made in 21 of the biopsies with positive fluorescence (61.8%). However, the eight IODs in the remaining 13 biopsies (23.5%) were not correct (atypical cell, 4; high-grade glioma, 1; gliosis, 1; unremarkable, 2). In those 8 biopsies, PCNSL was confirmed by the final pathological diagnosis. There was no difference in the mean Mib-1 labeling index between the biopsies with positive fluorescence (86.5%) and those without positive fluorescence (90.0%). IOD was not performed in 6 biopsies; however, 5 of those biopsies (83.3%) showed positive fluorescence and were finally pathologically diagnosed as PCNSL. Use of PDD in biopsies for patients with suspected PCNSL is a reliable way of obtaining specimens of adequate quality for the final pathological diagnosis and may lead to improved diagnostic yield in the biopsy of PCNSL. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to evaluate the efficacy of proton beam therapy for pediatric patients with ependymoma. Methods Proton beam therapy was conducted for six patients (three boys and three girls; age, 2-6 years; median, 5 years) with ependymoma. The tumors were WHO grades 2 and 3 in two and four patients, respectively. All patients underwent surgery (subtotal and gross total resection in three patients each) and proton beam therapy at doses of 50.4-61.2 GyE (median, 56.7 GyE). The mean doses to normal brain tissue in proton beam therapy and photon radiotherapy were simulated using the same treatment planning computed tomography images. Results All patients completed the planned irradiation. The follow-up period was 13-44 months (median, 24.5 months) from completion of proton beam therapy and all patients were alive at the end of this period. Local recurrence in the treatment field occurred in one patient at 4 months after proton beam therapy at 50.4 GyE. Alopecia and mild dermatitis occurred in all patients, but there was no severe toxicity. One patient had a once-off seizure after proton beam therapy and alopecia persisted in another patient for 31 months, but no patients had difficulty with daily life. The simulation showed that proton beam therapy reduces the dose to normal brain tissue by approximately half compared with photon radiotherapy. Conclusions Proton beam therapy for pediatric ependymoma is safe, does not have specific toxicities, and can reduce irradiation of normal brain tissue. [ABSTRACT FROM AUTHOR]

Purpose To investigate the intra-ocular pressure ( IOP)-lowering effects of a selective Rho kinase inhibitor, ripasudil (K-115), over 24 hr in patients with primary open-angle glaucoma ( POAG) or ocular hypertension ( OHT). Methods In this multicenter, prospective, randomized, open-label, 3-period, Latin-square crossover clinical study, 28 patients with POAG or OHT whose IOP level was 21 mmHg or higher were subdivided into three groups. Each patient was treated with placebo and ripasudil in concentrations of 0.2 and 0.4%, at 9:00 and 21:00 on day 1 through a total of 3 periods separated by washout periods. IOP was measured at 9:00, 10:00, 11:00, 13:00, 16:00, 19:00, 21:00, 22:00 and 23:00 on day 1, and 1:00, 4:00, 7:00 and 9:00 on day 2 in sitting position using Goldmann applanation tonometer. Main outcome measure was the IOP reduction of placebo and ripasudil from baseline. Results The mean IOP reduction was −5.2 mmHg for 0.2%, −6.4 mmHg for 0.4% and −2.0 mmHg for placebo at 2 hr after the first instillation. Also, the corresponding values were −6.8 mmHg for 0.2%, −7.3 mmHg for 0.4% and −4.1 mmHg for placebo at 2 hr after the second instillation. Statistically significant IOP reduction, compared with placebo, was found for both 0.2 and 0.4% from 1 through 7 hr after each instillation. In safety, conjunctival hyperaemia was observed in 22 patients (79%) for 0.2%, 27 patients (96%) for 0.4% and three patients (11%) for placebo. Conclusion Ripasudil is a promising new topical medication to lower IOP for at least 7 hr after instillations in patients with POAG or OHT. [ABSTRACT FROM AUTHOR]

Three stereoselective syntheses and the physicochemical properties of trans, trans-5-(4-ethoxy-2,3-difluorophenyl)-2-(4-propylcyclohexyl)tetrahydropyran, which is an important liquid-crystal compound with a large negative dielectric anisotropy (Δ ε=−7.3), are described. The key step in the construction of the trans-2,5-disubstituted tetrahydropyran ring in the first approach involved a benzylic cation mediated intramolecular olefin cyclization of a 2-allyloxy-1-arylethanol derivative. The second method included the Et2Zn-induced 1,2-aryl shift of a bromohydrin obtained from a hetero-Diels-Alder reaction, followed by stereoselective bromination. The third approach utilized the hetero-Diels-Alder reaction of trans-4-propylcyclohexanecarboxaldehyde and a 2-aryl-3-(trimethylsilyl)oxy-1,3-butadiene, followed by stereoselective protonation. From results obtained by using a quantum chemical calculation method, the reason why the target compound shows a large negative Δ ε value is discussed. [ABSTRACT FROM AUTHOR]

Cyclometallated NHC palladium complexes prepared from palladium(II) acetate [Pd(OAc)2] and unsymmetrical 1,3-diarylimidazolinium salts catalyzed the hydroxymethylation of (hetero)arylboronic acids using an excess amount of formalin to afford (hetero)arylmethanols in good to satisfactory yields. [ABSTRACT FROM AUTHOR]

The article discusses a study on the link of MYD88 (L265P) mutation to poor prognosis and high risk of progression in primary central nervous system lymphoma (PCNSL) patients. Topics covered include the related link of MYD88 mutations to unfavourable outcome of diffuse large B cell lymphoma (DLBCL) and the importance of clinical sequencing in improving prognostic algorithms of PCNSL. Also noted are the possible alternative treatment regimens for PCNSL patients with MYD88 L265P mutation.

. Purpose: To present clinical features and microbial data for bleb-related infections obtained by the 5-year-long Japan Glaucoma Society Survey of Bleb-related Infection (JGSSBI). Methods: This multicentre prospective observational study was conducted in 82 clinical centres in Japan. A total of 170 bleb-related infections developed in 157 eyes of 156 patients during a 5-year period. The ophthalmological and microbial data were analysed. Results: The patient age at first infection was 59.3 ± 17.7 years [mean ± standard deviation (SD)], and the period between the last glaucoma surgery and the first infection was 6.9 ± 5.8 years (mean ± SD; range: 0.3-41 years). Bleb leakage was noted significantly more frequently in eyes with repeated infections. The stage of infection at diagnosis was stage I in 91 infections (54%), stage II in 30 infections (18%), stage IIIa in 18 infections (11%), and stage IIIb in 31 infections (18%). Staphylococcus species were the most frequently isolated microbe (41%), followed by Streptococcus species (32%). Streptococcus species, coagulase-negative Staphylococcus, Haemophilus influenzae, and Enterococcus species were the major bacteria isolated in the late-stage infections. Conclusions: The JGSSBI project has revealed several characteristics of bleb-related infection in Japan, which include the significance of bleb leakage in the development of repeated infections and the distribution of bacterial isolates. [ABSTRACT FROM AUTHOR]

. Purpose: To identify changes in visual acuity and intra-ocular pressure (IOP) 12 months after the development of bleb-related infection. Methods: Data obtained from 146 eyes of 146 patients with bleb-related infection were analyzed as a part of the Japan Glaucoma Society Survey of Bleb-related Infection. Multiple logistic regression analysis was conducted to identify factors associated with poor prognosis in visual acuity and increased IOP and for being stage III. Results: The logMAR increased by a mean of 0.140, 0.440, 1.099 and 1.122 at 12 months postinfection for stage I, II, IIIa and IIIb infections, respectively. The logMAR was significantly worse at 6 and 12 months postinfection in stage IIIb (p = 0.002 and p = 0.003, respectively; Wilcoxon signed-rank test) and at 6 months postinfection in stage IIIa (p = 0.036). The IOP was significantly elevated following infection in both stage IIIa and stage IIIb (p = 0.028 and p = 0.008 at 6 and 12 months, respectively, for stage IIIa; p = 0.002 and p = 0.005 for stage IIIb). The multiple logistic regression analysis revealed that being stage III and positive culture were significant risk factors for poor outcome for visual acuity (Odds ratio: 9.26 and 6.29, respectively) and that being stage III was a prognostic factor for increased IOP (Odds ratio: 8.33). Pseudophakia or aphakia was significantly associated with stage III and stage IIIb infections (Odds ratio: 2.85 and 6.30). Conclusions: Stage III bleb-related infection causes significant visual loss and IOP elevation within 12 months after development. Therefore, preventative measures should be taken, especially in cases that are pseudophakic or aphakic. [ABSTRACT FROM AUTHOR]

Polycrystalline Ga-doped ZnO films (GZO) with different thicknesses ranging from 100 to 400 nm were deposited by ion plating with DC arc discharge at a glass substrate temperature of 200 °C. The dominant role of grain boundary scattering in carrier transport in the films was demonstrated by varying the film thickness and grain size. With increasing film thickness, the grain size increases and the alignment of the c-axis between the columnar grains is improved. A comparison of Hall mobility and optical mobility showed that for GZO films, carrier transport is mainly limited by grain boundary scattering. By comparing a grain-size-effect theory with electrical resistivity data, we found that the grain boundary resistance coefficient deceases with increasing grain size.(© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

ABSTRACT We investigated the correlation between the SOD activity of Helicobacter pylori ( H. pylori) and gastroduodenal diseases and the characteristics of strains exposed to oxidative stress. Two sequenced strains, 26695 and J99, and clinical isolates from 156 Japanese patients with gastroduodenal diseases such as gastric cancer ( n= 59) and non-cancer ( n= 97) were used. SOD activities of all 158 isolates were measured and were divided into three groups: high-SOD activity (>0.22, n= 2), moderate-SOD activity (0.15≦≦0.22, n= 16) and low-SOD activity (<0.15, n= 140). Expressions of H. pylori Fe-SOD were examined by western blotting with anti- H. pylori Fe-SOD antibody prepared inhouse, and the profiles of Fe-SOD activity were investigated by zymogram with activity staining in native-PAGE. The characteristics of strains from high-SOD and low-SOD groups were examined under oxidative stress by paraquat. The average of H. pylori SOD activity was significantly higher in the cancer group than in the non-cancer group ( P < 0.05). However, irrespective of SOD activity level, the amount of Fe-SOD expressed was variable among individual strains. Zymogram revealed a single band in moderate-SOD and low-SOD strains, but multiple bands in high-SOD strains were observed. These bands were confirmed as H. pylori Fe-SOD. Under oxidative stress with paraquat, low-SOD strains were drastically eliminated without inducible SOD activity; however, high-SOD strains were still viable with increased SOD activity. This study is the first to exhibit the characteristics of high-SOD activity strains representing multiple bands in zymograms and the correlation between H. pylori SOD activity and gastric cancer. [ABSTRACT FROM AUTHOR]

Previous population-based, genetic studies have shown that human leukocyte antigen (HLA) class II loci such as HLA-DR4 (DRB1*04) and HLA-DR14 (DRB1*14) alleles are consistently associated with the occurrence of pemphigus vulgaris (PV) in Japanese as well as other ethnic populations. Among PV-related HLA-DRB1 alleles (*0406, *1401, *1405, *1406) in Japan, HLA DRB1*1405 and DRB1*0406 were found to be associated with both PV and pemphigus foliaceus (PF) phenotypes. We report four familial cases of pemphigus in two unrelated families, together with analysis of their HLA-DR and -DQ alleles, and their antibody profiles. One family comprised a woman with PF and her mother with PV: both patients shared a HLA haplotype of A31(19), B54(22), CW1 and DRB1*1405. Another family included two sisters with PF and PV, respectively: both of these patients shared a DRB1*1405-DQA1*0104-DQB1*0503 haplotype. Clinicopathological and serological monitoring revealed that the elder sister with PF presented with a PV phenotype later, and gained anti-desmoglein (Dsg)3 antibodies in addition to having a low titer of anti-Dsg1 antibodies. Conversely, the younger sister with PV developed PF with only anti-Dsg1 antibody detected. These results indicate that an HLA-DRB1*1405 (DQB1*0503) haplotype may confer susceptibility to both PV and PF, and that genetic susceptibility alone is not always responsible for the clinical phenotype and autoantibody profile. [ABSTRACT FROM AUTHOR]

Some members of the Toll-like receptor (TLR) family, which plays key roles in both innate and adaptive immune responses, are involved in the pathogenesis of autoimmune, chronic inflammatory and infectious diseases. However, the role of TLR in the pathogenesis of oral lichen planus (OLP) has not been investigated. The aim of this study was to understand the roles of TLR in OLP. The expression of TLR genes in OLP tissues was analyzed by cDNA microarray and reverse transcription polymerase chain reaction, and TLR protein expression in OLP tissues and peripheral blood monocytes was examined by immunohistochemical analysis and flow cytometry, respectively. Furthermore, TLR ligand-induced cytokine production from peripheral blood monocytes was measured by enzyme-linked immunosorbent assay. Among 10 TLR genes, the average expression ratio of the genes for TLR1, 2, 3, 5, 6 and 10 in OLP tissues compared to that in the normal buccal mucosae was more than 1.0. In contrast, the average ratio of the genes for TLR7, 8 and 9 was less than 1.0. TLR2 but not TLR4 was highly expressed in the cells of the spinous layer and infiltrating monocytes in OLP tissues, and the mean fluorescence intensity of TLR2 on peripheral blood monocytes was significantly higher in OLP patients than in healthy controls. Furthermore, the peripheral blood monocytes from OLP patients produced considerably higher amounts of interleukin (IL)-12 and lower amounts of IL-10 than those from healthy controls. In OLP, the T-helper cell (Th)1/Th2 balance appears to shift toward Th1 dominance, probably depending on the upregulation of TLR2 expression and these alterations in TLR2-mediated immunity may be involved in the pathogenesis and maintenance of OLP. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) repair systems are thought to be associated with the susceptibility of cancer cells to anticancer agents. The present study investigated the relationship between the susceptibility to γ-rays and the mtDNA repair ability of oral squamous cell carcinoma (OSC) cell lines. The levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and mtDNA common deletion in both nuclear and mitochondrial DNA of OSC-2, OSC-3 and OSC-6 cells (radio-sensitive cell lines) after γ-ray-irradiation were higher than those of OSC-1, OSC-4 and OSC-5 cells (radio-resistant cell lines). Compared with OSC-2, OSC-3 and OSC-6 cells, OSC-1, OSC-4 and OSC-5 cells had higher levels of activity of phosphoinositide-3 kinase (PI-3K)/Akt and more strongly expressed 8-hydroxyguanine DNA glycosylase (OGG1), DNA polymerase γ (POLG) and mitochondrial transcription factor A (Tfam). Down-regulation of these mtDNA-repair-associated molecules by the RNA interference technique enhanced the susceptibility of OSC-2 and OSC-5 cells to γ-rays, and the expression of Tfam and POLG was down-regulated by inhibitors of PI-3K/Akt signaling. These results indicate that the inhibition of mtDNA repair capacity by PI-3K/Akt signal inhibitors and OGG1 down-regulator in cancer cells may be a useful strategy for cancer treatment when combined with ionizing irradiation and chemotherapeutic drugs. ( Cancer Sci 2008; 99: 2230–2237) [ABSTRACT FROM AUTHOR]