Phase structure of NJL model with weak renormalization group

We analyze the chiral phase structure of the Nambu--Jona-Lasinio model at finite temperature and density by using the functional renormalization group (FRG). The renormalization group (RG) equation for the fermionic effective potential $V(\sigma;t)$ is given as a partial differential equation, where $\sigma:=\bar \psi\psi$ and $t$ is a dimensionless RG scale. When the dynamical chiral symmetry breaking (D$\chi$SB) occurs at a certain scale $t_c$, $V(\sigma;t)$ has singularities originated from the phase transitions, and then one cannot follow RG flows after $t_c$. In this study, we introduce the weak solution method to the RG equation in order to follow the RG flows after the D$\chi$SB and to evaluate the dynamical mass and the chiral condensate in low energy scales. It is shown that the weak solution of the RG equation correctly captures vacuum structures and critical phenomena within the pure fermionic system. We show the chiral phase diagram on temperature, chemical potential and the four-Fermi coupling constant.Comment: 32 pages, 12 figures; Version published in Nuclear Physics

Differential Regulation by IL-1β and EGF of Expression of Three Different Hyaluronan Synthases in Oral Mucosal Epithelial Cells and Fibroblasts and Dermal Fibroblasts: Quantitative Analysis Using Real-Time RT-PCR

Using “real-time RT-PCR”, we assessed the expression of three different hyaluronan synthase genes, HAS1, HAS2, and HAS3, by measuring their mRNA amounts in cultured human oral mucosal epithelial (COME) cells, oral mucosal fibroblasts, and dermal fibroblasts, and investigated the effects of interleukin-1β (IL-1β) and epidermal growth factor (EGF). When COME cells were treated with IL-1β or EGF, early and marked increases and subsequent rapid decreases were observed for all HAS genes and, moreover, actual changes in hyaluronan synthesis subsequently occurred. The effects of IL-1β stimulation were concentration-dependent and the maximal response to the EGF stimulation was observed at a low concentration (0.1 ng per mL). When two different types of fibroblasts were treated with IL-1β or EGF, increased expression with different degrees and rates of three different HAS genes and subsequent increased synthesis of hyaluronan were also observed. In addition, HAS1 gene expression was not detectable in the mucosal fibroblasts, while weak HAS3 gene expression was detected in the dermal fibroblasts. Taken together, it is likely that the regulation of the expression of the three different HAS genes is different between oral mucosa and skin, which may be of significance for elucidating some of the differences between these tissues in wound healing

Trial of Brain Redox Imaging and Estimation of Radiation-Induced Redox Change in Mouse Brain

The in vivo T1-weighted contrasting abilities and signal decay behaviors of several nitroxyl contrast agents, which have been used as redox responsive contrast agents in several magnetic resonance-based imaging modalities, in mouse brain were compared. In addition, daily variations of redox behavior in mouse brain after irradiation of X-ray or carbon-ion beams (C-beam) were tried to estimate based on the in vivo reduction rate of amphiphilic nitroxyl contrast agents.Injection solutions of five types of five-membered-ring nitroxyl contrast agents, i.e. 3-carboxy-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CxP), 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (CmP), 3-methoxy-carbonyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl (MCP), acetoxymethyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl-3-carboxylate (CxP-AM), and 4-(N-methylpiperidine)-2,2,5,5-tetramethylpyrroline-N-oxyl (23c), and a six-membered-ring nitroxyl contrast agent, i.e. 4-hydroxyl-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL), were prepared. The nitroxyl contrast agent was i.v. injected to a mouse through tail vein. Then, the distributions and pharmacokinetics of nitroxyl contrast agents were compared based on the time course of T1-weighted MRI. The MRI experiments using CMP or TEMPOL were repeated for mice irradiated by X-ray or C-beam to their head on several deferent timings, i.e. 1, 2, 4, 8 day(s) after irradiation. C-beam was irradiated at Heavy-Ion Medical Accelerator in Chiba (HIMAC, National Institute of Radiological Sciences/ National Institutes for Quantum and Radiological Science and Technology).The blood-brain-barrier (BBB)-impermeable CxP could not be distributed in the brain. The slightly lipophilic CmP showed slight distribution only in the ventricle, but not in the medulla and cortex. The amphiphilic MCP and TEMPOL had good initial uniform distribution in the brain and showed typical 2-phase signal decay profiles. A brain-seeking nitroxyl probe, CxP-AM, showed an accumulating phase, and then its accumulation was maintained in the medulla and ventricle regions, but not in the cortex. The lipophilic 23c was well distributed in the cortex and medulla, but slightly in the ventricle, and showed relatively rapid linear signal decay.Decay rates of MCP in mouse brain after irradiation of 8 Gy X-ray, 8 Gy C-beam or 16 Gy C-beams did not show marked clear changes, however relatively little decreasing were observed at day 1 and day 2 after irradiation. Decay rates of TEMPOL was increased 1 after irradiation then gradually recovered to the control level. MCP and TEMPOL showed opposite responses but the timing of redox change may be 1 or 2 days after irradiation.Nitroxyl contrast agents equipped with a suitable lipophilic substitution group could be BBB-permeable functional contrast agents. MR redox imaging, which can estimate not only the redox characteristics but also the detailed distribution of the contrast agents, is a good candidate for a theranostic tool. Irradiation of ionized radiation to head could cause alternation of redox status in the brain. Detail of redox mechanisms were still in progress.第7回国際放射線神経生物学会大

Inhibition of RAGE signaling through the intracellular delivery of inhibitor peptides by PEI cationization

The receptor for advanced glycation end products (RAGE) is a multi-ligand cell surface receptor and a member of the immunoglobulin superfamily. RAGE is involved in a wide range of inflammatory, degenerative and hyper-proliferative disorders which span over different organs by engaging diverse ligands, including advanced glycation end products, S100 family proteins, high-mobility group protein B1 (HMGB1) and amyloid beta. We previously demonstrated that the cytoplasmic domain of RAGE is phosphorylated upon the binding of ligands, enabling the recruitment of two distinct pairs of adaptor proteins, Toll-interleukin 1 receptor domain-containing adaptor protein (TIRAP) and myeloid differentiation protein 88 (MyD88). This engagement allows the activation of downstream effector molecules, and thereby mediates a wide variety of cellular processes, such as inflammatory responses, apoptotic cell death, migration and cell growth. Therefore, inhibition of the binding of TIRAP to RAGE may abrogate intracellular signaling from ligand-activated RAGE. In the present study, we developed inhibitor peptides for RAGE signaling (RAGE-I) by mimicking the phosphorylatable cytosolic domain of RAGE. RAGE-I was efficiently delivered into the cells by polyethylenimine (PEI) cationization. We demonstrated that RAGE-I specifically bound to TIRAP and abrogated the activation of Cdc42 induced by ligand-activated RAGE. Furthermore, we were able to reduce neuronal cell death induced by an excess amount of S100B and to inhibit the migration and invasion of glioma cells in vitro. Our results indicate that RAGE-I provides a powerful tool for therapeutics to block RAGE-mediated multiple signaling

Dual Transneuronal Tracing in the Rat Entorhinal-Hippocampal Circuit by Intracerebral Injection of Recombinant Rabies Virus Vectors

Dual transneuronal tracing is a novel viral tracing methodology which employs two recombinant viruses, each expressing a different reporter protein. Peripheral injection of recombinant pseudorabies viruses has been used as a powerful method to define neurons that coordinate outputs to various peripheral targets of motor and autonomic systems. Here, we assessed the feasibility of recombinants of rabies virus (RV) vector for dual transneuronal tracing in the central nervous system. First, we examined whether two different RV-vectors can double label cells in vitro, and showed that efficient double labeling can be realized by infecting targeted cells with the two RV-vectors within a short time interval. The potential of dual transneuronal tracing was then examined in vivo in the entorhinal-hippocampal circuit, using the chain of projections from CA3 pyramidal cells to CA1 pyramidal cells and subsequently to entorhinal cortex. Six days after the injection of two RV-vectors into the left and right entorhinal cortex respectively, double-labeled neurons were observed in CA3 bilaterally. Some double-labeled neurons showed a Golgi-like labeling. Dual transneuronal tracing potentially provides a powerful and sensitive method to study issues such as the amount of convergence and divergence within and between circuits in the central nervous system. Using this sensitive technique, we established that single neurons in CA3 are connected to the entorhinal cortex bilaterally with only one synaptic relay

Dengue virus type 2 unresponsive to the current PCR primer; : construction of a new PCR primer to detect all strains of Dengue virus type 2.

We found that one strain of dengue virus (Trinidad 1751; TR) did not respond to the PCR primer for Jamaica/83. We investigated such property with other 10 strains of dengue virus type 2 and found 2 more unresponsive strains. All 3 strains were isolated from the central America. To detect the envelope gene of those 3 strains by PCR, we synthesized primers based on TR strain as the reference sequence. Using these primers, we could detect the 3 strains by PCR at the usual annealing temperature. We recommed the new primer for diagnosis of DEN 2

Vildagliptin vs liraglutide as a second-line therapy switched from sitagliptin-based regimens in patients with type 2 diabetes: A randomized, parallel-group study

Introduction: A step-up strategy for dipeptidyl peptidase (DPP)-4 inhibitor-based regimens has not yet been established. In addition, similarities and differences between DPP-4 inhibitors and glucagon-like peptide (GLP)-1 receptor agonists remain to be elucidated in humans. We investigated the pleiotropic effects of vildagliptin vs liraglutide in patients with type 2 diabetes on sitagliptin-based regimens in an open-label, randomized, clinical trial. Materials and Methods: A total of 122 patients with type 2 diabetes that was inadequately controlled by sitagliptin-based regimens were randomly assigned to either vildagliptin (50 mg, twice daily) or liraglutide treatment (0.9 mg, once daily) for 12 weeks. The primary outcomes were glycated hemoglobin and body mass index. Results: Both vildagliptin and liraglutide significantly lowered glycated hemoglobin within 12 weeks after switching from sitagliptin, but liraglutide produced a greater reduction (-0.67 ± 0.12% vs -0.36 ± 0.53%). Liraglutide lowered body mass index, whereas vildagliptin did not affect body mass index. Vildagliptin lowered fasting C-peptide immunoreactivity, but liraglutide did not. Vildagliptin increased serum levels of adiponectin, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, whereas liraglutide had no effect on these levels. Quality of life, assessed using the diabetes treatment satisfaction questionnaire, was not impaired in either group. The most common adverse events were gastrointestinal symptoms, which occurred with similar frequencies in both groups. Conclusions: Vildagliptin-mediated improvements in glycemic control did not correlate with indices for insulin secretion and insulin sensitivity. Switching from sitagliptin to liraglutide is useful in managing hyperglycemia and weight. Each agent exerts unique pleiotropic effects. This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (no. 000004953). © 2014 The Authors. Journal of Diabetes Investigation published by Asian Association of the Study of Diabetes (AASD) and Wiley Publishing Asia Pty Ltd

Rituximab-combination chemotherapy achieves a 10th cycle of remission for Burkitt's lymphoma.

A 14-year-old girl with multiple intra-abdominal tumors was diagnosed with stage III Burkitt's lymphoma. She achieved complete remission after multi-drug chemotherapy, but she relapsed after six courses. Autologous peripheral blood stem cells (PBSC) or allogeneic PBSC harvested from an HLA-identical sibling were insufficient, and her family did not agree to bone marrow collection from the sibling. Although the patient relapsed nine times (the relapses involved intra-abdominal organs or bone) during the following 4 years 7 months, treatment with rituximab monotherapy or in combination with ifosphamide, carboplastin, and etoposide, or local irradiation (33.8-40.0 Gy) to treat the bone metastases, proved effective, resulting in complete or partial remission. At the time of writing, the patient was in a 10th cycle of remission lasting 1 year 6 months and had not required transplantation. Thus, a chemotherapy regimen including rituximab might be effective for Burkitt's lymphoma in patients experiencing multiple relapse

韓国における移民関連施策および支援状況に関する実態調査報告(4)

韓国では近年,移民受入れが進み,それに伴って移民政策も急速に整備されてきている。本稿は2010年9月に科学研究費補助金により,日本語教育保障法研究会で実施した韓国における移民関連施策および移民支援の状況に関する現地実態調査の報告後編であり,2009年度調査の報告書から通算すると第4号となる。本稿は,「朝鮮日報」(第2章),「中央日報」(第3章),「韓国日報」(第4章),「戸田郁子氏」(第5章)に対する聞き取り調査報告,および「2009年度,2010年度の韓国現地実態調査から」(第6章)によって構成される

Therapeutic activity of glycoengineered anti-GM2 antibodies against malignant pleural mesothelioma

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive neoplasm that arises from the pleural, pericardial, or peritoneal lining. Although surgery, chemotherapy, radiotherapy, and combinations of these therapies are used to treat MPM, the median survival of such patients is dismal. Therefore, there is a compelling need to develop novel therapeutics with different modes of action. Ganglioside GM2 is a glycolipid that has been shown to be overexpressed in various types of cancer. However, there are no published reports regarding the use of GM2 as a potential therapeutic target in cases of MPM. In this study, we evaluated the efficacy of the anti-GM2 antibody BIW-8962 as an anti-MPM therapeutic using in vitro and in vivo assays. Consequently, the GM2 expression in the MPM cell lines was confirmed using flow cytometry. In addition, eight of 11 cell lines were GM2-positive (73%), although the GM2 expression was variable. BIW-8962 showed a significant antibody-dependent cellular cytotoxicity activity against the GM2-expressing MPM cell line MSTO-211H, the effect of which depended on the antibody concentration and effector/target ratio. In an in vivo orthotropic mouse model using MSTO-211H cells, BIW-8962 significantly decreased the incidence and size of tumors. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. Fifty-eight percent of the MPM tumors were positive for GM2, with individual variation in the intensity and frequency of staining. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. In this study, the anti-GM2 antibody BIW-8962 first showed a significant ADCC activity against malignant pleural mesothelioma (MPM) cell line and therapeutic activity in an in vivo orthotropic mouse model using the cell line. Additionally, the GM2 expression was confirmed in the MPM clinical specimens. These data suggest that anti-GM2 antibodies may become a therapeutic option for MPM patients. © 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association