Identification and functional characterization of uric acid transporter Urat1 (Slc22a12) in rats

AbstractUric acid transporter URAT1 contributes significantly to reabsorption of uric acid in humans to maintain a constant serum uric acid (SUA) level. Since alteration of SUA level is associated with various diseases, it is important to clarify the mechanism of change in SUA. However, although expression of mRNA of an ortholog of URAT1 (rUrat1) in rats has been reported, functional analysis and localization have not been done. Therefore, rat rUrat1 was functionally analyzed using gene expression systems and isolated brush-border membrane vesicles (BBMVs) prepared from rat kidney, and its localization in kidney was examined immunohistochemically. Uric acid transport by rUrat1 was chloride (Cl−) susceptible with a Km of 1773μM. It was inhibited by benzbromarone and trans-stimulated by lactate and pyrazinecarboxylic acid (PZA). Cl− gradient-susceptible uric acid transport by BBMVs showed similar characteristics to those of uric acid transport by rUrat1. Moreover, rUrat1 was localized at the apical membrane in proximal tubular epithelial cells in rat kidney. Accordingly, rUrat1 is considered to be involved in uric acid reabsorption in rats in the same manner as URAT1 in humans. Therefore, rUrat1 may be a useful model to study issues related to the role of human URAT1

The effects of herring-roe lyophilized powder on lipid metabolism

AbstractHerring-roe, which contains large amounts of docosahexaenoic acid and eicosapentaenoic acid, has anti-dyslipidemia effects. Here, we evaluated the effects of herring-roe on lipid metabolism in 33 adult subjects in a randomized, double-blind, placebo-controlled study. We divided the subjects into a test group that ingested herring-roe lyophilized powder (herring-roe powder) and a placebo group that ingested non-herring-roe powder, with each member of each group ingesting 15 g daily for 8 weeks. Hematological tests and body composition measurements were performed before and after 4, 6, and 8 weeks of the study period. Although no significant differences in low density lipoprotein were observed, high density lipoprotein was found to be increased in subjects who ingested herring-roe powder. In addition, the level of free fatty acid was significantly improved in the herring-roe powder group. These results suggest that ingestion of herring-roe could influence lipid metabolism

What was Keizaigaku to wa Nan Daro ka [What is Economics]?

本稿の目的は、佐和隆光『経済学とは何だろうか』（1982）という書物の同時代受容とその含意をめぐる経済思想史的検討にある。『けいなん』は経済学の〈制度化〉という視点から「経済理論の社会的〈文脈〉への依存性」を強調したものであり、経済学史・経済思想史研究に親和的なものでありながら、これまで十分な検討がなされていなかった。本稿では、第２節で『けいなん』の背景とその基本的な主張を明らかにし、第３節では、一般の読者層、経済学者たち、さらに経済学史・経済思想史研究者の出版当時の受容と反応のあり方を検討し、第４節では『けいなん』の登場と受容の歴史的・社会的〈文脈〉となる「ポスト・クーン」「ポスト・ラディカルズ」という問題系について論じた。本稿を通じて『けいなん』の登場と受容の社会的〈文脈〉としての1970年代の日本の経済学者たちによる科学史・科学哲学の参照や「経済学の内省」ともいえる動向の存在とその含意について明らかにした。植村邦彦先生退職記念

Setting the criterion for fall risk screening for healthy community-dwelling elderly

金沢大学人間社会研究域人間科学系This study aimed to develop a criterion for screening high risk elderly using Demura\u27s fall risk assessment chart (DFRA), compared with the Tokyo Metropolitan Institute of gerontology (TMIG) fall risk assessment chart. Participants included 1122 healthy elderly individuals aged 60 years and over (380 males and 742 females) 15.8% of whom had experienced a fall. We assessed fall risk of the elderly by DFRA and TMIG. To develop a criterion for screening high fall risk subjects among community-dwelling elderly, receiver-operating-characteristic (ROC) analysis was conducted using fall experience (separated into the categories of faller and non-faller) and the following fall risk scale scores: (1) TMIG score, (2) DFRA score, and (3) potential for falling score according to the DFRA (summing the scores of three items). In ROC analyses, the area under the ROC curve (AUC) for evaluating the potential for falling gave a value of 0.797 (95% CI = 0.759-0.834) which proved better than the evaluation of the overall TMIG (0.654, 95% CI = 0.600-0.706) and DFRA scores (0.680, 95% CI = 0.633-0.727). Assessment of the potential for falling and fall experience are of benefit in screening for elderly persons deemed to be at a high fall risk. Further examinations based on the prospective data setting will be required. © 2011 Elsevier Ireland Ltd. All rights reserved

Evidence for hydrogen generation in laser- or spark-induced cavitation bubbles

The growing use of focused lasers or electric sparks to generate cavitation bubbles raises concerns about the possible alteration of gas content during the initiation process and its effect on bubble dynamics. We provide experimental evidence that hydrogen molecules are produced for such plasma-induced bubbles. We performed spectral analysis of the light emitted by the plasma and monitored the dissolved hydrogen concentration in water. The mass of dissolved hydrogen was found proportional to the potential energy of the rebound bubble for both laser and spark methods. Nevertheless, hydrogen concentration was found 2.7 times larger with the spark

Requisite role of vasohibin‐2 in spontaneous gastric cancer formation and accumulation of cancer‐associated fibroblasts

The vasohibin (VASH) family consists of two genes, VASH1 and VASH2. VASH1 is mainly expressed in vascular endothelial cells and suppresses angiogenesis in an autocrine manner, whereas VASH2 is mainly expressed in cancer cells and exhibits pro‐angiogenic activity. Employing adenomatous polyposis coli gene mutant mice, we recently reported on the role of Vash2 in the spontaneous formation of intestinal tumors. In this study, we used K19‐Wnt1/C2mE (Gan) mice and examined the role of Vash2 in spontaneous gastric cancer formation. Gan mice spontaneously develop gastric tumors by activation of Wnt and prostaglandin E2 signaling pathways in gastric mucosa after 30 weeks of age. Expression of Vash2 mRNA was significantly increased in gastric tumor tissues compared with normal stomach tissues. When Gan mice were crossed with the Vash2‐deficient (Vash2 LacZ/LacZ) strain, gastric cancer formation was significantly suppressed in Vash2 LacZ/LacZ Gan mice. Normal composition of gastric mucosa was partially maintained in Vash2 LacZ/LacZ Gan mice. Knockout of Vash2 caused minimal reduction of tumor angiogenesis but a significant decrease in cancer‐associated fibroblasts (CAF) in tumor stroma. DNA microarray analysis and real‐time RT‐PCR showed that mRNA levels of epiregulin (Ereg) and interleukin‐11 (Il11) were significantly downregulated in gastric tumors of Vash2 LacZ/LacZ Gan mice. Furthermore, conditioned medium of gastric cancer cells stimulated migration of and α‐smooth muscle actin expression in fibroblasts, whereas conditioned medium of VASH2 knockdown cells attenuated these effects in vitro. These results suggest that VASH2 plays an important role in gastric tumor progression via the accumulation of CAF accompanying upregulation of EREG and IL‐11 expression

Naturalness Improvement Algorithm for Reconstructed Glossectomy Patient's Speech Using Spectral Differential Modification in Voice Conversion

In this paper, we propose an algorithm to improve the naturalness of the reconstructed glossectomy patient's speech that is generated by voice conversion to enhance the intelligibility of speech uttered by patients with a wide glossectomy. While existing VC algorithms make it possible to improve intelligibility and naturalness, the result is still not satisfying. To solve the continuing problems, we propose to directly modify the speech waveforms using a spectrum differential. The motivation is that glossectomy patients mainly have problems in their vocal tract, not in their vocal cords. The proposed algorithm requires no source parameter extractions for speech synthesis, so there are no errors in source parameter extractions and we are able to make the best use of the original source characteristics. In terms of spectrum conversion, we evaluate with both GMM and DNN. Subjective evaluations show that our algorithm can synthesize more natural speech than the vocoder-based method. Judging from observations of the spectrogram, power in high-frequency bands of fricatives and stops is reconstructed to be similar to that of natural speech

A Suzaku Observation of the Low-Ionization Fe-Line Emission from RCW 86

The newly operational X-ray satellite Suzaku observed the southwestern quadrant of the supernova remnant (SNR) RCW 86 in February 2006 to study the nature of the 6.4 keV emission line first detected with the Advanced Satellite for Cosmology and Astronomy (ASCA). The new data confirm the existence of the line, localizing it for the first time; most of the line emission is adjacent and interior to the forward shock and not at the locus of the continuum hard emission. We also report the first detection of a 7.1 keV line that we interpret as the K-beta emission from low-ionization iron. The Fe-K line features are consistent with a non-equilibrium plasma of Fe-rich ejecta with n_{e}t <~ 10^9 cm^-3 s and kT_{e} ~ 5 keV. This combination of low n_{e}t and high kT_{e} suggests collisionless electron heating in an SNR shock. The Fe K-alpha line shows evidence for intrinsic broadening, with a width of 47 (34--59) eV (99% error region). The difference of the spatial distributions of the hard continuum above 3 keV and the Fe-K line emission support a synchrotron origin for the hard continuum.Comment: 6 pages with 6 figures. Accepted for PASJ Suzaku Special Issue (vo. 58, sp.1

HLA-A*0201-restricted CTL epitope of a novel osteosarcoma antigen, papillomavirus binding factor

<p>Abstract</p> <p>Background</p> <p>To develop peptide-based immunotherapy for osteosarcoma, we previously identified papillomavirus binding factor (PBF) as a CTL-defined osteosarcoma antigen in the context of HLA-B55. However, clinical application of PBF-based immunotherapy requires identification of naturally presented CTL epitopes in osteosarcoma cells in the context of more common HLA molecules such as HLA-A2.</p> <p>Methods</p> <p>Ten peptides with the HLA-A*0201 binding motif were synthesized from the amino acid sequence of PBF according to the BIMAS score and screened with an HLA class I stabilization assay. The frequency of CTLs recognizing the selected PBF-derived peptide was determined in peripheral blood of five HLA-A*0201⁺patients with osteosarcoma using limiting dilution (LD)/mixed lymphocyte peptide culture (MLPC) followed by tetramer-based frequency analysis. Attempts were made to establish PBF-specific CTL clones from the tetramer-positive CTL pool by a combination of limiting dilution and single-cell sorting. The cytotoxicity of CTLs was assessed by ⁵¹Cr release assay.</p> <p>Results</p> <p>Peptide PBF A2.2 showed the highest affinity to HLA-A*0201. CD8+ T cells reacting with the PBF A2.2 peptide were detected in three of five patients at frequencies from 2 × 10^-7to 5 × 10^-6. A tetramer-positive PBF A2.2-specific CTL line, 5A9, specifically lysed allogeneic osteosarcoma cell lines that expressed both PBF and either HLA-A*0201 or HLA-A*0206, autologous tumor cells, and T2 pulsed with PBF A2.2. Five of 12 tetramer-positive CTL clones also lysed allogeneic osteosarcoma cell lines expressing both PBF and either HLA-A*0201 or HLA-A*0206 and T2 pulsed with PBF A2.2.</p> <p>Conclusion</p> <p>These findings indicate that PBF A2.2 serves as a CTL epitope on osteosarcoma cells in the context of HLA-A*0201, and potentially, HLA-A*0206. This extends the availability of PBF-derived therapeutic peptide vaccines for patients with osteosarcoma.</p

Subsequent chemotherapy with paclitaxel plus cetuximab-based chemotherapy following immune checkpoint inhibitor in recurrent or metastatic squamous cell carcinoma of the head and neck

BackgroundImmune checkpoint inhibitors (ICIs) are essential in treating recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). However, the overall response rate (ORR) is limited to 10-20%, and subsequent chemotherapy is critical to maximizing the subjects’ prognosis.MethodsWe retrospectively reviewed 59 patients with R/M SCCHN treated with paclitaxel+cetuximab (PE)-based chemotherapy (PCE, paclitaxel+carboplatin+cetuximab; or PTX+Cmab, paclitaxel+cetuximab) following disease progression after either pembrolizumab or nivolumab monotherapy.ResultsOf 59 patients, 15 were treated with pembrolizumab, with an ORR of 13.3%, and the remaining 44 with nivolumab, with an ORR of 11.4%. All patients in the pembrolizumab cohort had platinum-sensitive disease. Following ICI treatment, 19 patients were treated with PCE and the remaining 40 with PTX+Cmab. PE-based chemotherapy induced favorable and prompt tumor shrinkage even in cases where ICI was not effective, with a median change in the summed dimensions of target lesions of -43.4%, resulting in an ORR of 62.7%. Median time to response was 1.8 months. The patients in the pembrolizumab cohort appeared to have a numerically higher response rate than those receiving nivolumab (80.0% vs. 56.8%). For the 59 patients, progression-free survival and overall survival, calculated from the initiation of PE-based chemotherapy, were 4.6 months and 17.1 months, respectively. Grade ≥3 adverse events occurred in 40.7%, and no treatment-related death was observed.ConclusionPE-based chemotherapy following ICI is encouraging for its robust antitumor efficacy in R/M SCCHN