Normalization of Pulmonary Hypertension by the Use of Left Ventricular Assist Device in Patients with End-stage Heart Failure: A Possible Contribution to Donor Pool Expansion in Lung Transplantation

SummaryHeart transplantation alone has been recognized to be contraindicated when pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) are irreversible, irrespective of any medical intervention by the use of inotropic agents or pulmonary vasodilators, because such patients are at an increased risk of post-transplantation right ventricular failure and mortality. Therefore, end-stage heart failure patients with concomitant fixed PH and irreversibly high PVR are considered to be heart–lung transplant candidates. Recently, left ventricular assist device (LVAD) therapy has been reported to normalize PVR through persistent unloading of the left ventricle, even in patients with medically refractory PH. Therefore, LVAD therapy could make such patients suitable for “heart-only” transplants, which contributes to appropriate donor lung allocation for lung-only candidates. We review the literature regarding LVAD use for secondary PH and present a case with end-stage heart failure that could avoid a heart–lung transplant owing to LVAD therapy

Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma including after treatment with sorafenib : Real-world evidence and in vitro assessment via protein phosphorylation array

The efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line LEN treatment, investigated the sensitivity of a SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and assessed their signal transduction pathways by protein array analysis. We retrospectively enrolled 57 patients with unresectable HCC. Fifty-three radiologically evaluated patients comprised 34 molecular-targeted agent (MTA)-naive (first-line), nine intolerant to SOR (second-line), and 10 resistant to regorafenib (third-line). The objective response rates (ORRs) were 61.8% in first-line, 33.3% in second-line, and 20.0% in third-line groups. The overall survival (OS) in the first-line was significantly longer than that in the third-line group (p < 0.05). Patients with better liver functional reserves (child score, ALBI grade) exhibited higher ORR and longer OS. The IC50 of LEN against PLC/PRF5-R2 was significantly higher than that against PLC/PRF5. LEN significantly inhibited more LEN-related signal transduction pathways in PLC/PRF5 than in PLC/PRF5-R2 cells. This suggests that LEN is active and safe as a second/third-line treatment for unresectable HCC. LEN seems more effective for patients with HCC with better hepatic reserve functions or before MTA-resistance is acquired because of the partial cross-resistance to SOR

X-Ray Analysis Literatures 2011

2011年に出版されたX線分析関連文献，X線に関連した情報のなかで，編集委員がX線分析技術の発展に寄与し重要であると選抜した文献を総説としてまとめた．調査対象はe-ジャーナル，web マガジンを含む学術誌20誌，制定された規格およびX線関連メーカーの新技術情報である．各雑誌について，全体的な論評，X線分析に関する傾向から，いくつかの論文について論評を記した．The selected literatures about advances in X-ray analysis and X-ray analysis-related informations published in 2011 were reviewed on the basis of analytical chemistry, physics, techniques, optics, instrumentation and so forth. The 20 kinds of academic journals including web-magagines, Japanease Industrial Standard (JIS), and websites of companies related with X-ray tools and/or X-ray apparatus were researched. The trend of publications related to X-ray analysis for each journal was overviewed, and some of noticeable literatures were commented

X-Ray Analysis Literatures 2010

本総説は，2010年に学術雑誌に掲載されたX線分析関連の論文において，注目すべき論文を厳選し紹介する．調査した学術雑誌は19件（和雑誌2件含む）であり，X線分析の発展に寄与しているものを対象としているが，分析化学の分野だけでなく，分光学や物理学の分野も網羅している．各雑誌に関して，X 線分析手法や測定された試料の傾向，分析技術や要素開発に関するトピックスの他に，特筆すべき論文には論評も記している．日本工業規格（JIS）におけるX線分析関連の規格の制定や改訂についてまとめている．X線関連メーカーのウェブサイトを紹介し，掲載している技術レポートの情報も得られる．　In this article, the interesting X-ray analysis-related literatures, which are published on academic journals during the year 2010, are summarized. The number of the researched journals is 19, including two Japanese journals, which contribute the advance of the X-ray analysis in the field not only of analytical chemistry but also of spectroscopy and physics. In every journal, the trend of the X-ray analysis methods and of the measured specimens, the topics of analytical technique and of the developed components of the X-ray analysis apparatus, and the comments for the nortable articles are mentioned. The constitution and revision of standards of X-ray analysis on Japanease Industrial Standard (JIS) are shown. The websites of the company related with X-ray tools or X-ray apparatus are also shown, and the information on technical reports is available

肝硬変例における呼吸同期肝イメージングおよびフーリエ解析による肝運動性評価の試み

金沢大学大学院医学系研究

Loss of NSD2 causes dysregulation of synaptic genes and altered H3K36 dimethylation in mice

Background: Epigenetic disruptions have been implicated in neurodevelopmental disorders. NSD2 is associated with developmental delay/intellectual disability; however, its role in brain development and function remains unclear.Methods: We performed transcriptomic and epigenetic analyses using Nsd2 knockout mice to better understand the role of NSD2 in the brain.Results and discussion: Transcriptomic analysis revealed that the loss of NSD2 caused dysregulation of genes related to synaptic transmission and formation. By analyzing changes in H3 lysine 36 dimethylation (H3K36me2), NSD2-mediated H3K36me2 mainly marked quiescent state regions and the redistribution of H3K36me2 occurred at transcribed genes and enhancers. By integrating transcriptomic and epigenetic data, we observed that H3K36me2 changes in a subset of dysregulated genes related to synaptic transmission and formation. These results suggest that NSD2 is involved in the regulation of genes important for neural function through H3K36me2. Our findings provide insights into the role of NSD2 and improve our understanding of epigenetic regulation in the brain

Transgenic Monkey Model of the Polyglutamine Diseases Recapitulating Progressive Neurological Symptoms

Age-associated neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and the polyglutamine (polyQ) diseases, are becoming prevalent as a consequence of elongation of the human lifespan. Although various rodent models have been developed to study and overcome these diseases, they have limitations in their translational research utility owing to differences from humans in brain structure and function and in drug metabolism. Here, we generated a transgenic marmoset model of the polyQ diseases, showing progressive neurological symptoms including motor impairment. Seven transgenic marmosets were produced by lentiviral introduction of the human ataxin 3 gene with 120 CAG repeats encoding an expanded polyQ stretch. Although all offspring showed no neurological symptoms at birth, three marmosets with higher transgene expression developed neurological symptoms of varying degrees at 3–4 months after birth, followed by gradual decreases in body weight gain, spontaneous activity, and grip strength, indicating time-dependent disease progression. Pathological examinations revealed neurodegeneration and intranuclear polyQ protein inclusions accompanied by gliosis, which recapitulate the neuropathological features of polyQ disease patients. Consistent with neuronal loss in the cerebellum, brain MRI analyses in one living symptomatic marmoset detected enlargement of the fourth ventricle, which suggests cerebellar atrophy. Notably, successful germline transgene transmission was confirmed in the second-generation offspring derived from the symptomatic transgenic marmoset gamete. Because the accumulation of abnormal proteins is a shared pathomechanism among various neurodegenerative diseases, we suggest that this new marmoset model will contribute toward elucidating the pathomechanisms of and developing clinically applicable therapies for neurodegenerative diseases.ArticleeNeuro.4(2):e0250(2017)journal articl

コウトウ キョウイク カイカク ノ ソウゴ コウイ ブンセキ : ビデオ エスノグラフィー ケンキュウ ノ ネライ ト コウガクブ トシ コウガク エンシュウ ノ ジッサイ

ビデオエスノグラフィーは、当事者的知識を十分に摂取しながら行うビデオ分析であり、我々は この方法で、高等教育改革の現場を研究した。生涯学習社会の到来を受けて、日本の高等教育は現在第 2 次世界大戦直後以来の改革期にある。すなわち、「知識」より「生涯学習能力」の獲得を志向した、 自発性を尊重するような様々な取り組みがなされ始めている。この高等教育の現場に対し、ワークプレ ース研究を行った。Ｂ大学工学部都市工学演習α班を分析対象とした調査の結果、①演習の課題解釈に は「従来の指標の相対化の要求の程度」を巡って２つの解釈があり得たこと、②班内にはその２種類の 解釈に対応した葛藤・対立的相互行為が存在したこと、③にもかかわらず、班内葛藤を生きる当事者が ともに専門性（「都市工学」）を志向していたこと、④したがって、課題理解のいかんにかかわらず、 班活動の全体が「都市工学演習」と呼び得るものになっていたこと、⑤その一方で、最終審査会場（ジ ュリー）ではこの２重性が十分レリバントなものとして浮かび上がって来ていなかったこと、これらの ことがわかった。諸結果を総合すると、学生の自主的活動を尊重するタイプの、新しい学習方法の吟味・ 評価のためには、学生によるその方法の実践状況の分析が有意義であるだろうこと、また、それは、場 合によっては教員の評価のパラダイムを変える力を持つだろうことなどが予測された。なお、本報告は、 文科省科学研究費補助金「高等教育改革のコミュニケーション分析－現場における文化変容の質的検討 －」（基盤研究（Ｂ）、 課題番号 １８３３０１０５、研究代表者：樫田美雄）ほかによる研究成果 の一部である

Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquito Anopheles gambiae

With the spread of resistance to long-established insecticides targeting Anopheles malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13 Anopheles gambiae nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Agα1, Agα2, Agα3, Agα8 and Agβ1 subunits in Xenopus laevis oocytes, the Drosophila melanogaster orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Agα2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Agα3 subunit increases it. Crystal structures of the acetylcholine binding protein (AChBP), an established surrogate for the ligand-binding domain, with dinotefuran bound, shows a unique target site interaction through hydrogen bond formation and CH-N interaction at the tetrahydrofuran ring. This is of interest as dinotefuran is also under trial as the toxic element in baited traps. Multiple regression analyses show a correlation between the efficacy of neonicotinoids for the Agα1/Agα2/Agα8/Agβ1 nAChR, their hydrophobicity and their rate of knockdown of adult female An. gambiae, providing new insights into neonicotinoid features important for malaria vector control

Observation of the acceleration of a single bunch by using the induction device in the kek proton synchrotron

A single rf bunch in the KEK proton synchrotron was accelerated with an induction acceleration method from the injection energy of 500 MeV to 5 GeV.</p