Lack of Inertia Force of Late Systolic Aortic Flow Is a Cause of Left Ventricular Isolated Diastolic Dysfunction in Patients With Coronary Artery Disease

ObjectivesWe investigated whether a lack of inertia force of late systolic aortic flow and/or apical asynergy provoke early diastolic dysfunction in patients with coronary artery disease (CAD).BackgroundLeft ventricular (LV) isolated diastolic dysfunction is a well-recognized cause of heart failure.MethodsWe evaluated LV apical wall motion and obtained left ventricular ejection fraction (LVEF) by left ventriculography in 101 patients who underwent cardiac catheterization to assess CAD. We also computed the LV relaxation time constant (Tp) and the inertia force of late systolic aortic flow from the LV pressure (P)–first derivative of left ventricular pressure (dP/dt) relation. Using color Doppler echocardiography, we measured the propagation velocity of LV early diastolic filling flow (Vp). Patients with LVEF ≥50% (preserved systolic function [PSF], n = 83) were divided into 2 subgroups: patients with inertia force (n = 53) and without inertia force (n = 30). No patient with systolic dysfunction (SDF) (LVEF <50%) had inertia force (n = 18).ResultsThe Tp was significantly longer in patients with SDF (85.7 ± 21.0 ms) and with PSF without inertia force (81.1 ± 23.6 ms) than in those with PSF with inertia force (66.3 ± 12.8 ms) (p< 0.001). The Vp was significantly less in the former 2 groups than in the last group. In patients with PSF, LV apical wall motion abnormality was less frequently observed in those with inertia force than in those without (p < 0.0001).ConclusionsAn absence of inertia force in patients with PSF is one of the causes of isolated diastolic dysfunction in patients with CAD. Normal LV apical wall motion is substantial enough to give inertia to late systolic aortic flow

Multifrequency VLBI Observations of the Broad Absorption Line Quasar J1020+4320: Recently Restarted Jet Activity?

This paper reports very-long-baseline interferometry observations of the radio-loud broad absorption line (BAL) quasar J1020+4320 at 1.7, 2.3, 6.7, and 8.4 GHz using the Japanese VLBI network (JVN) and European VLBI network (EVN). The radio morphology is compact with a size of ~10 pc. The convex radio spectrum is stable over the last decade; an observed peak frequency of 3.2 GHz is equivalent to 9.5 GHz in the rest frame, suggesting an age of the order of ~100 years as a radio source, according to an observed correlation between linear size and peak frequency of compact steep spectrum (CSS) and giga-hertz peaked spectrum (GPS) radio sources. A low-frequency radio excess suggests relic of past jet activity. J1020+4320 may be one of the quasars with recurrent and short-lived jet activity during a BAL-outflowing phase.Comment: 7 pages, 2 figures, 2 tables, accepted for publication in PAS

Structural insights into the agonists binding and receptor selectivity of human histamine H₄ receptor

慢性アレルギー疾患に関わるヒスタミン受容体の構造解明 --新規アトピー性皮膚炎・喘息治療薬の開発に貢献--. 京都大学プレスリリース. 2023-10-23.Histamine is a biogenic amine that participates in allergic and inflammatory processes by stimulating histamine receptors. The histamine H₄ receptor (H₄R) is a potential therapeutic target for chronic inflammatory diseases such as asthma and atopic dermatitis. Here, we show the cryo-electron microscopy structures of the H₄R-Gq complex bound with an endogenous agonist histamine or the selective agonist imetit bound in the orthosteric binding pocket. The structures demonstrate binding mode of histamine agonists and that the subtype-selective agonist binding causes conformational changes in Phe344[7.39], which, in turn, form the “aromatic slot”. The results provide insights into the molecular underpinnings of the agonism of H₄R and subtype selectivity of histamine receptors, and show that the H₄R structures may be valuable in rational drug design of drugs targeting the H₄R

ユウビン チョウサ カラ ミタ コクサイ ザイム カンリ ト セキニン カイケイ

本稿では、2001年度に実施した日本および韓国企業それぞれに対する予算管理システムと財務管理システムにかんする郵送調査結果のうち、日本企業をとりあげ、海外子会社の国際財務管理と責任会計の動向について分析した。国際財務管理システムとして、企業がグループ全体における資金、為替を集中的に管理し、効率化するために用いるグローバル・キャッシュ・マネジメント・システム(GCMS)に着目した。GCMSは、企業グループ全体の税引後利益の増大を可能とする一方で、個々の子会社の管理指標に影響を与える可能性がある。そこで、グローバル化の成熟度と財務指標の関係、GCMSの採用と財務指標の重視度、海外子会社の資金・為替意識に影響を与える影響について分析した。その結果、グローバル化が成熟するに従って、GCMSの利用が増えること、節税を志向している会社が大半であるものの子会社の業績に悪影響を及ぼしてまで実行している会社が少ないこと等の知見を得た。最後に、アンケート調査の分析に加え欧州の統括会社を対象にヒアリング調査した結果をふまえて、資金だけでなく物流、販売まで含めた集権化と責任会計にかんする研究の必要性を述べる

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development