Zn-induced wipeout effect on Cu NQR spectra in La2−x_{2-x}Srx_xCu1−y_{1-y}Zny_yO4_4

We report a systematic study of Zn-substitution effect on Cu NQR spectrum for high $T_c$ superconductors La$_{2-x}$Sr$_x$Cu$_{1-y}$Zn$_y$O$_4$ from carrier-underdoped to -overdoped regimes (polycrystalline samples, $x$ =0.10, 0.15, and 0.20). We observed no appreciable wipeout effect for the overdoped samples, a gradual and partial wipeout effect below about 80 K for the optimally doped ones, and very abrupt and full wipeout effect below about 40 K for the underdoped ones. The wipeout effect indicates a highly enhanced spectral weight of Cu spin fluctuations at a low frequency. We associate the wipeout effect with a Zn-induced local magnetism far above 40 K and with a localization effect below 40 K.Comment: 2 pages, 3 figures, accepted for publication in Physica C (LT23, Hiroshima 2002

Intersections of ultracold atomic polarons and nuclear clusters: How is a chart of nuclides modified in dilute neutron matter?

Neutron star observations, as well as experiments on neutron-rich nuclei, used to motivate one to look at degenerate nuclear matter from its extreme, namely, pure neutron matter. As an important next step, impurities and clusters in dilute neutron matter have attracted special attention. In this paper, we review in-medium properties of these objects on the basis of the physics of polarons, which have been recently realized in ultracold atomic experiments. We discuss how such atomic and nuclear systems are related to each other in terms of polarons. In addition to the interdisciplinary understanding of in-medium nuclear clusters, it is shown that the quasiparticle energy of a single proton in neutron matter is associated with the symmetry energy, implying a novel route toward the nuclear equation of state from the neutron-rich side.Comment: 28 pages, 2 figure

Beneficial Effect of Brewers' Yeast Extract on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

The aim of this study was to assess the effect of Brewers' yeast extract (BYE) on daily activity in a mouse model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. BYE was orally administered to mice in a dose of 2 g per kg per day for 2 weeks before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving BYE as compared with that in untreated mice. Weekly variation of body weight (BW) and survival in both groups was monitored during the observation period. Spleen weight (SW), SW/BW ratio, percent splenic follicular area and expression levels of interferon-γ (IFN-γ) and interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity during 2 weeks after the second BA injection was significantly higher in the treated group than in the control. There was no difference in BW between both groups through the experimental course. Two mice in the control died 2 and 7 days after the second injection, whereas no mice in the treated group died. Significantly decreased SW and SW/BW ratio were observed in the treated mice together with elevation of splenic follicular area. There were suppressed IFN-γ and IL-10 mRNA levels in spleens from the treated mice. Our results suggest that BYE might have a protective effect on the marked reduction in activity following repeated BA injection via normalization of host immune responses

Absence of germline mono-allelic promoter hypermethylation of the CDH1 gene in gastric cancer patients

<p>Abstract</p> <p>Background</p> <p>Germline mono-allelic promoter hypermethylation of the <it>MLH1 </it>or <it>MSH2 </it>gene in families with hereditary nonpolyposis colorectal cancer has recently been reported. The purpose of this study was to evaluate if germline promoter hypermethylation of the tumor suppressor gene <it>CDH1 </it>(<it>E-cadherin</it>) might cause predisposition to gastric cancer.</p> <p>Methods</p> <p>We prepared two groups of samples, a group of blood samples from 22 patients with familial gastric cancer or early-onset gastric cancer selected from among 39 patients, and a group of non-cancerous gastric tissue samples from 18 patients with sporadic gastric cancer showing loss of CDH1 expression selected from among 159 patients. We then investigated the allele-specific methylation status of the <it>CDH1 </it>promoter by bisulfite sequencing of multiple clones.</p> <p>Results</p> <p>Although there was a difference between the methylation level of the two alleles in some samples, there was no mono-allelic promoter hypermethylation in any of the samples.</p> <p>Conclusion</p> <p>These results suggest that germline mono-allelic hypermethylation of the <it>CDH1 </it>promoter is not a major predisposing factor for gastric cancer.</p

スルフォラファンはNrf2 活性化作用を介し抗酸化ストレス作用、アセトアルデヒド代謝作用およびLPS/TLR4 シグナル経路を阻害することで四塩化炭素およびエタノール投与により誘発されるアルコール肝線維症を改善する

Alcoholic liver disease (ALD)-related fibrosis results from a variety of mechanisms including the accumulation of acetaldehyde, reactive oxygen species, and hepatic overload of endogenous lipopolysaccharide (LPS). Alcohol cessation is the therapeutic mainstay for patients with all stages of ALD, whereas pharmacological strategies for liver fibrosis have not been established. Sulforaphane, a phytochemical found in cruciferous vegetables, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts anticancer, antidiabetic, and antimicrobial effects; however, few studies investigated its efficacy in the development of ALD-related fibrosis. Herein, we investigated the effect of sulforaphane on acetaldehyde metabolism and liver fibrosis in HepaRG and LX-2 cells, human hepatoma and hepatic stellate cell lines, respectively, as well as in a mouse model of alcoholic liver fibrosis induced by ethanol plus carbon tetrachloride (EtOH/CCl₄). Sulforaphane treatment induced the activity of acetaldehyde-metabolizing mitochondrial aldehyde dehydrogenase in HepaRG cells and suppressed the acetaldehyde-induced proliferation and profibrogenic activity in LX-2 cells with upregulation of Nrf2-regulated antioxidant genes, including HMOX1, NQO1, and GSTM3. Moreover, sulforaphane attenuated the LPS/toll-like receptor 4-mediated sensitization to transforming growth factor-β with downregulation of NADPH oxidase 1 (NOX1) and NOX4. In EtOH/CCl₄-treated mice, oral sulforaphane administration augmented hepatic acetaldehyde metabolism. Additionally, sulforaphane significantly inhibited Kupffer cell infiltration and fibrosis, decreased fat accumulation and lipid peroxidation, and induced Nrf2-regulated antioxidant response genes in EtOH/CCl₄-treated mice. Furthermore, sulforaphane treatment blunted hepatic exposure of gut-derived LPS and suppressed hepatic toll-like receptor 4 signaling pathway. Taken together, these results suggest sulforaphane as a novel therapeutic strategy in ALD-related liver fibrosis.博士（医学）・甲第811号・令和4年3月15日© 2020 Elsevier Inc. All rights reserved

レンバチニブは実験的肝線維症において肝星細胞の活性化と類洞毛細血管化を阻害することにより肝線維化を抑制する。

Molecular targeted agents are pharmacologically used to treat liver fibrosis and have gained increased attention. The present study examined the preventive effect of lenvatinib on experimental liver fibrosis and sinusoidal capillarization as well as the in vitro phenotypes of hepatic stellate cells. LX-2, a human stellate cell line, was used for in vitro studies. In vivo liver fibrosis was induced in F344 rats using carbon tetrachloride by intraperitoneal injection for 8 weeks, and oral administration of lenvatinib was started two weeks after initial injection of carbon tetrachloride. Lenvatinib restrained proliferation and promoted apoptosis of LX-2 with suppressed phosphorylation of extracellular signal-regulated kinase 1/2 and AKT. It also down-regulated COL1A1, ACTA2 and TGFB1 expressions by inhibiting the transforming growth factor-β1/Smad2/3 pathway. Treatment with lenvatinib also suppressed platelet-derived growth factor-BB-stimulated proliferation, chemotaxis and vascular endothelial growth factor-A production, as well as basic fibroblast growth factor-induced LX-2 proliferation. In vivo study showed that lenvatinib attenuated liver fibrosis development with reduction in activated hepatic stellate cells and mRNA expression of profibrogenic markers. Intrahepatic neovascularization was ameliorated with reduced hepatic expressions of Vegf1, Vegf2 and Vegfa in lenvatinib-treated rats. Collectively, these results suggest the potential use of lenvatinib as a novel therapeutic strategy for liver fibrosis.博士（医学）・甲第812号・令和4年3月15日© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited

アンジオテンシンII 受容体拮抗薬であるロサルタンは、レンバチニブによるヒト肝癌細胞への 細胞増殖抑制性および血管新生抑制効果の感性を向上させる

Molecular targeted therapy with lenvatinib is commonly offered to advanced hepatocellular carcinoma (HCC) patients, although it is often interrupted by adverse effects which require a reduction in the initial dose. Thus, an alternative lenvatinib-based therapy to compensate for dose reduction is anticipated. This study aimed to assess the effect of combination of low-dose of lenvatinib and the angiotensin-II (AT-II) receptor blocker losartan on human HCC cell growth. In vitro studies found that losartan suppressed the proliferation by inducing G1 arrest and caused apoptosis as indicated by the cleavage of caspase-3 in AT-II-stimulated HCC cell lines (Huh-7, HLE, and JHH-6). Losartan attenuated the AT-II-stimulated production of vascular endothelial growth factor-A (VEGF-A) and interleukin-8 and suppressed lenvatinib-mediated autocrine VEGF-A production in HCC cells. Moreover, it directly inhibited VEGF-mediated endothelial cell growth. Notably, the combination of lenvatinib and losartan augmented the cytostatic and angiostatic effects of the former at a low-dose, reaching those achieved with a conventional dose. Correspondingly, a HCC tumor xenograft assay showed that the oral administration of losartan combined with lenvatinib reduced the subcutaneous tumor burden and intratumor vascularization in BALB/c nude mice. These findings support that this regimen could be a viable option for patients intolerant to standard lenvatinib dosage.博士（医学）・甲第813号・令和4年3月15日© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)

The effect of a prostaglandin E-1 derivative on the symptoms and quality of life of patients with lumbar spinal stenosis

Quality of life (QOL) is a concern for patients with lumbar spinal stenosis (LSS). In this study, QOL was examined using the 5-item EuroQol (EQ-5D). QOL and activities of daily living (ADL) were surveyed for 91 patients who visited 18 medical institutions in our prefecture and were diagnosed with LSS-associated intermittent claudication. A second survey was performed after a parts per thousand yen6 weeks for 79 of the subjects to evaluate therapy with limaprost (an oral prostaglandin E1 derivative) or etodolac (an NSAID). Symptoms, maximum walking time, QOL, ADL items, and relationships among these variables were investigated for all 91 patients. Leg pain, leg numbness, and low back pain while walking were surveyed by use of VAS scores (0-100). Leg pain, leg numbness, and low back pain while walking (VAS a parts per thousand yen25) were present in 83.5, 62.6, and 54.9 % of the patients in the first survey, and approximately half of the patients had a maximum walking time 30 min, showing that maximum walking time affected health-related QOL. Of the 79 patients who completed the second survey, 56 had taken limaprost and 23 (control group) had received etodolac. Limaprost improved possible walking time, reduced ADL interference, and significantly increased the EQ-5D utility score, whereas no significant changes occurred in the control group. Maximum walking time was prolonged by a parts per thousand yen10 min and the EQ-5D utility value was improved by a parts per thousand yen0.1 points in significantly more patients in the limaprost group than in the control group. According to the findings of this survey, at an average of 8 weeks after administration limaprost improved symptoms, QOL, and ADL in LSS patients whereas treatment with an NSAID reduced pain but did not have any other effects.ArticleJOURNAL OF ORTHOPAEDIC SCIENCE. 18(2):208-215 (2013)journal articl