ラット肝腫瘍モデルにおける化学療法の早期効果判定に有用なダイナミック造影超音波のパラメータについて

Objectives: The objective of the study is to determine a parameter on the time-intensity curve (TIC) of dynamic contrast-enhanced ultrasonography (DCE-US) that best correlates with tumor growth and to evaluate whether the parameter could correlate with the early response to irinotecan in a rat liver tumor model. Material and Methods: Twenty rats with tumors were evaluated (control: Saline, n = 6; treatment: Irinotecan, n = 14) regarding four parameters from TIC: Peak intensity (PI), k value, slope (PI × k), and time to peak (TTP). Relative changes in maximum tumor diameter between day 0 and 10, and parameters in the first 3 days were evaluated. The Mann-Whitney U-test was used to compare differences in tumor size and other parameters. Pearson’s correlation coefficients (r) between tumor size and parameters in the control group were calculated. In the treatment group, relative changes of parameters in the first 3 days were compared between responder and non-responder (<20% and ≥20% increase in size on day 10, respectively). Results: PI, k value, PI × k, and TTP significantly correlated with tumor growth (r = 0.513, 0.911, 0.665, and 0.741, respectively). The mean RC in k value among responders (n = 6) was significantly lower than non-responders (n = 8) (mean k value, 4.96 vs. 72.5; P = 0.003). Conclusion: Parameters of DCE-US could be a useful parameter for identifying early response to irinotecan.博士（医学）・甲第879号・令和5年3月15

ラット凍結肩モデルを用いた経カテーテル的動脈塞栓術の効果に関する検討

Purpose: To assess the angiographic findings and the effects of transcatheter arterial embolization on physical activity and histopathology using a frozen shoulder rat model. Materials and methods: First, the angiographic and histopathologic findings of rats in which the shoulder was immobilized with molding plaster for 6 weeks (n = 4) were compared to control rats with normal non-immobilized shoulders (n = 4). Next, a total of 16 frozen shoulder rats were divided into 2 groups. In the transcatheter arterial embolization group (n = 8), imipenem/cilastatin was injected into the left thoracoacromial artery. The changes of physical activity before and after procedures were evaluated and compared with a saline-injected control group (n = 8). Histopathologic findings were also compared between the 2 groups. Results: Angiography revealed abnormal shoulder staining in all of the rats with a frozen shoulder. On histopathology, the numbers of microvessels and mononuclear inflammatory cells in the synovial membrane of the joint capsule were significantly higher compared with the control rats (both P = .03). In the transcatheter arterial embolization group, the running distance and speed were improved (P = .03 and P = .01, respectively), whereas there were no significant differences in the control group. The number of microvessels and mononuclear inflammatory cells in the transcatheter arterial embolization group were significantly lower than the control group (P = .002 and P = .001, respectively). Conclusions: The rat frozen shoulder model revealed the development of neovascularization. Transcatheter arterial embolization decreased the number of blood vessels and inflammatory changes in the frozen shoulder and increased the moving distance and speed of the rats.博士（医学）・甲第789号・令和3年3月15日Copyright © 2020 SIR(Society of Interventional Radiology). Published by Elsevier Inc. All rights reserved

Observation of low-latitude aurora by color digital cameras in Hokkaido

第3回極域科学シンポジウム/第36回極域宙空圏シンポジウム 11月26日（月）、27日（火） 国立極地研究所 2階ラウン

Constitutive Phosphorylation of Aurora-A on Ser51 Induces Its Stabilization and Consequent Overexpression in Cancer

The serine/threonine kinase Aurora-A (Aur-A) is a proto-oncoprotein overexpressed in a wide range of human cancers. Overexpression of Aur-A is thought to be caused by gene amplification or mRNA overexpression. However, recent evidence revealed that the discrepancies between amplification of Aur-A and overexpression rates of Aur-A mRNA were observed in breast cancer, gastric cancer, hepatocellular carcinoma, and ovarian cancer. We found that aggressive head and neck cancers exhibited overexpression and stabilization of Aur-A protein without gene amplification or mRNA overexpression. Here we tested the hypothesis that aberration of the protein destruction system induces accumulation and consequently overexpression of Aur-A in cancer.Aur-A protein was ubiquitinylated by APC(Cdh1) and consequently degraded when cells exited mitosis, and phosphorylation of Aur-A on Ser51 was observed during mitosis. Phosphorylation of Aur-A on Ser51 inhibited its APC(Cdh1)-mediated ubiquitylation and consequent degradation. Interestingly, constitutive phosphorylation on Ser51 was observed in head and neck cancer cells with protein overexpression and stabilization. Indeed, phosphorylation on Ser51 was observed in head and neck cancer tissues with Aur-A protein overexpression. Moreover, an Aur-A Ser51 phospho-mimetic mutant displayed stabilization of protein during cell cycle progression and enhanced ability to cell transformation.Broadly, this study identifies a new mode of Aur-A overexpression in cancer through phosphorylation-dependent inhibition of its proteolysis in addition to gene amplification and mRNA overexpression. We suggest that the inhibition of Aur-A phosphorylation can represent a novel way to decrease Aur-A levels in cancer therapy

Hemodynamic Effects of Positive end-expiratory Pressure on Right Ventricular Diastolic Function in Patients with Acute Myocardial Infarction

The effects of positive end-expiratory pressure (PEEP) on the right ventricular (RV) diastolic function in patients with congestive heart failure (CHF) due to acute myocardial infarction (AMI) are unknown. The aim in this study was to investigate PEEP associated variations in RV diastolic function in CHF due to AMI. The subjects comprised the control group (26 subjects) and the AMI group (36 subjects) classified as 20 patients with pulmonary capillary wedge pressure (PCWP) < 18 mmHg (CHF-low PCWP group) and 16 patients with PCWP≧18mmHg (CHF-high PCWP group). PEEP was applied for 30 minutes at 0, 5, 10 and 15 cmH_20. Two-dimensional echocardiography with continuous and pulse wave Doppler studies was performed. RV diastolic functional parameters included the ratio of peak early tricuspid valve filling and peak atrial filling velocities, the decelation time of the tricuspid E valve and the RV isovolumic relaxation time. In the control and CHF-low PCWP groups, right atrial pressure, mean pulmonary arterial pressure (mPAP), total pulmonary resistance (TPR) and systemic vascular resistance (SVR) increased, output (CO) decreased and RV diastolic functional parameters worsened significantly at the transition from 10 to 15 cmH_20 PEEP. In the CHF-high PCWP group, mPAP, TPR and SVR decreased, while CO increased and RV diastolic functional parameters improved significantly at the transition from 10 to 15 cmH_20 PEEP. From these findings, it is clear that PEEP induced hemodynamic deterioration and reduces RV diastolic function in intact and mildly failing hearts. On the other hand, in severely failing hearts, PEEP effers hemodynamic improvement and ameliorates RV diastolic function. It appears possible to predict responses to PEEP by determining RV diastolic function in CHF. Therefore, we conclude that evaluation of the RV diastolic function during PEEP is highly important in terms of recognizing the effectiveness of PEEP therapy in CHF

マンセイ シンフゼン カンジャ ノ ジュウショウド ニヨル ヤカン ムコキュウ ト テイサンソ ケッショウ ノ ヒカク

慢性心不全(CHF)患者の重症度による夜間の酸素飽和度(SaO_2)と無呼吸の比較について検討を行うために安定した慢性軽症心不全患者6例(男4例,女2例63±5.2歳,左室駆出率:49.8±3.4%,NYHA class:IかII,mild-CHF群)と安定慢性重症心不全患者11例(男9例,女2例,62±11.9歳,左室駆出率:25.6±8.6%,NYHA class:III,severe-CHF群)患者を対象とし,両群を比較することにより検討を行った.全例において室内空気下にパルスオキシメーターを用いて24時間のSaO_2と脈拍数を連続記録した.そして夜間のSaO_2が3%あるいは4%以上低下した1時間あたりの回数(3%ODI,4%ODI),SaO_2の最低値を各々分析した.さらにポリソムノグラフィーを用いてSaO_2と睡眠に関する全てのデータを連続的に記録分析した.その結果,severe-CHF群のODIはmild-CHF群に比して有意に高値であった(4%ODI;5.8±5.1 vs 0.6±0.5,p<O.01.3%ODI;8.6±7.1 vs 1.0±O.9,p<0.01.).severe-CHF群のSaO_2の最低値はmild-CHF群に比して有意に低かった(82.2±7.1 vs 91.7±1.0%,p<0.01).severe-CHF群の夜間無呼吸は全例にみられ,大多数が中枢型であった(74.0±3.6%).以上より安定した重症心不全では夜間に低酸素血症と無呼吸がみられ,これらが臨床病像の悪化に影響していることが示唆される.Background : Patients with chronic heart failure (CHF) commonly experience Cheyne- Stokes respiration, central apnea, or obstructive apnea during sleep associated with oxygen desaturation. Nocturnal oxygen therapy and nasal continuous positive airway pressure (NCPAP) reduce sleep-disordered breathing in stable CHF. However, the relation between sleep apnea and nocturnal desaturation inpatients with severe, stable CHF in Japan is unknown. Objectives : To examine nocturnal oxygen saturation (SaO_2) and sleep apnea in Japanese patients with severe, stable CHF. Methods : The subjects were 11 patients with severe, stable CHF (9 men and 2 women, LVEF=25.6±8.6%, NYHA class=III, severe CHF group) and 6 with mild, stable CHF (4 men and 2 women, LVEF=49.8±3.4 %, NYHA class=I or II, mild CHF group). SaO_2 was continuously recorded with a pulse oximeter under room air, and 4 % and 3 % SaO_2 dip rate per hour (GDIs) and the SaO_2 nadir were analyzed. In addition, SaO_2 and sleep variables were continuously recorded with a polysomnograph. Results : ODI frequency in the severe CHF group was significantly higher than that in the mild CHF group (4% ODI, 5.8±5.1 vs 0.6±0.5 times/hour, respectively, p<0.01;3 % ODI, 8.6±7.1 vs 1.0±0.9 times/hour, respectively, p<0.01.). SaO_2 nadir in the severe CHF group was significantly lower than that in the mild CHF group (82.2±7.1 vs 91.7±1.0 %, p<0.01). All severe patients had sleep apnea, predominantly of the central type (74.0±3.6%). Conclusion : The frequency of nocturnal hypoxemia and apnea increases in patients with severe, stable CHF. Nocturnal hypoxemia and apnea may adversely effect the clinical status of these patients

Screening nad lsolation of Azo Dyes Decolorizing Microorganisms and Analysis of Their Mechanism

A yeast, Candida sp. MK-1, newly isolated from activated sludge as a dye decolorizing microorganism, decolorized Color lndex (C.l.) Reactive orange 16 and C.l. Reactive red 21 on the solid medium. Both azo dyes were also decolorized even in the liquid medium. The decolorizing activity by Candida sp. MK-1 depends on glucose concentration. Textile stained by Reactive orange 16 or Reactive red 21 was decolorized by Candida sp. MK-1. There results suggest that Candida sp. MK-1 has potential applications for the decolorization of textile and for the bioremediation of dye-contaminated wastewater.アゾ染科を脱色する微生物の検索を行い、岡山市旭西浄化センターの活性汚泥サンプルから染科脱色菌1株を単離した。単離菌MK-1株はCandida属に分類される酵母であり、実験に用いた5種のアゾ染科のうちColor Index(C.I.)Reactive orange 16, C.I.Reactive red 21の2種類の染科を効率的に脱色した。脱色機構を検討したところCandida sp.MK-1株による脱色はグルコースんい依存していることが判明した。さらに菌体を用いた染色生体の脱色も可能であった。これらの結果は、今回単離したCandida sp. MK-1株が、抜染法等に応用可能であり、更に染科を多量に含んだ有色廃水の処理等のバイオレメディエーションにも応用できる可能性を示した

Screening nad lsolation of Azo Dyes Decolorizing Microorganisms and Analysis of Their Mechanism

A yeast, Candida sp. MK-1, newly isolated from activated sludge as a dye decolorizing microorganism, decolorized Color lndex (C.l.) Reactive orange 16 and C.l. Reactive red 21 on the solid medium. Both azo dyes were also decolorized even in the liquid medium. The decolorizing activity by Candida sp. MK-1 depends on glucose concentration. Textile stained by Reactive orange 16 or Reactive red 21 was decolorized by Candida sp. MK-1. There results suggest that Candida sp. MK-1 has potential applications for the decolorization of textile and for the bioremediation of dye-contaminated wastewater.アゾ染科を脱色する微生物の検索を行い、岡山市旭西浄化センターの活性汚泥サンプルから染科脱色菌1株を単離した。単離菌MK-1株はCandida属に分類される酵母であり、実験に用いた5種のアゾ染科のうちColor Index(C.I.)Reactive orange 16, C.I.Reactive red 21の2種類の染科を効率的に脱色した。脱色機構を検討したところCandida sp.MK-1株による脱色はグルコースんい依存していることが判明した。さらに菌体を用いた染色生体の脱色も可能であった。これらの結果は、今回単離したCandida sp. MK-1株が、抜染法等に応用可能であり、更に染科を多量に含んだ有色廃水の処理等のバイオレメディエーションにも応用できる可能性を示した