Biochemical and histological effects of heat stress on experimental animals

暑熱環境が生体の生化学的変化に及ぼす影響について検討した。暑熱影響を生化学的観点からみると､肝臓における酸素ラジカルの生成が注目される。酸素ラジカルによる生体高分子との反応による脂質過酸化は生体膜や酵素の変性に結びつくため重要な障害反応と考えられるためである。ラット肝臓の脂質過酸化反応生成物の指標であるチオバルビツール酸反応生成物(TBARS)の濃度変化をみると､30℃では変化がなかった生成も､35℃の暑熱負荷では急激に増加した。ラットとモルモットを比較すると､モルモットは30℃においても若干の増加が認められ､35℃では顕著な増加が認められた。モルモットは暑熱への耐性が弱く暑熱負荷の長期的な実験は困難であった。肝臓細胞内小器官の脂質過酸化は若齢では影響を受けていなかったが､高齢・老齢ラットのミトコンドリア､ミクロゾームでは脂質過酸化が著しく誘導されていた。ラットでは肝臓の細胞質グルタチオンペルオキシダーゼは高体温症で強く誘導されたが､モルモットでは誘導がみられなかった。肝臓カタラーゼ活性は若齢のラットでは暑熱ストレスによる影響を受けていなかったが､高齢・老齢ラットは肝臓､腎臓のいずれの臓器においても減少していた。高齢・老齢ラットにおける肝細胞の小胞体は暑熱ストレスにより変形していたため､ミクロゾームの電子伝達系酵素のアミノピリン脱メチル化酵素やTMPDペルオキシダーゼ活性について検討した。その結果､加齢につれていずれの酵素も活性の低下がみられ､週齢の高いラットでは暑熱暴露によりさらに活性が低下した。暑熱ストレスにより合成する蛋白質の立体構造形成が不安定化することを防ぐ分子シャペロンとしての機能を示す熱ショックタンパク誘導にはモルモットとラットで種差があり､モルモットでは核とミトコンドリアで90-kDaの熱ショックタンパクの誘導が認められ､ラットの単離細胞においては70-kDaの熱ショックタンパクの合成促進が観察された。両種において暑熱ストレスによる細胞機能の変調に対して､分子シャペロン機能を示す防御系が活性化したと考えられる。実験動物に暑熱ストレスを加え､臓器・組織を光学顕微鏡と電子顕微鏡を用いて観察した結果､肝臓､腎臓､心臓､呼吸器系､内分泌系､免疫系などにおいて､暑熱ストレスにより組織的変化が認められた。特徴的な組織的変化は肝臓の静脈周辺細胞の空胞変性､脂質過酸化物に起因するとみられる脂肪顆粒の貯留､欝血などであった。さらに動物の加齢により暑熱ストレスの影響が増強し､適応性が低下していると考えられる老齢期ラットでは顕著に暑熱ストレスの影響があらわれた。35℃の暑熱環境下では､暴露期間が長くなるほど病理組織学的な諸変化が増強していた。臓器・組織における最も顕著な変化は静脈系の拡張であった。心筋の空胞変性とともに､肝臓､腎臓､心臓､肺および骨髄などに欝血の傾向が認められた。この研究により､暑熱ストレスが組織学的変化を伴う生体組織の障害を引き起こすことが判明した。暑熱ストレスの増大は生体諸機能の低下している高齢者や高齢の動物に対し深刻な影響を及ぼすと予想される

<症例>マムシ (Agkistrodon halys Blomhoffii) 咬傷における少量抗毒素血清投与の経験 : 43症例の検討

Forty-three consecutive patients of venomous snakebite by the Japanese viper (Agkistrodon halys Blomhoffii, "Mamushi" in Japanese) were treated with an uniformly scheduled therapy from 1990 and 1994. The therapy was mainly composed of minimal dose of antivenin, methylprednisolon and cepharanthin. There were two clinical courses, i.e., the minimal envenomation course (Group A, n=14) and the severe one (Group B, n=29). Our treatment was so satisfactory that all patients of both groups fully recovered activities of daily living with neither organic disorders nor sequelae of the bitten extremities. The high appearance ratio of atypical lymphocytes (P < 0. 05) and the increased ratio of lymphocyte count to White blood cell count (P<0. 02) could be indicators that predict hich clinical courses the patients take.1990年から1994年までの5年間に当院で治療したマムシ咬傷43例について検討した. 当院では原則として抗毒素血清, ステロイド, セファランチンの投与を行っているが, 死亡例はなく, 咬傷部の機能障害を示した症例もなかった. 4例（9. 3%）に即効型過敏反応が認められた. 1例は anaphylaxy shock を呈したが治療により即時改善をみた. 遅延型血清病は入院期間中観察されなかった. McCollough らの分類により軽症例（n=14）と重症例（n=29）に分け予後因子を検討した. 治療開始前の WBC, CPK, LDH, BUN, Cr はいずれも重症化指標とはなりえなかったが, 白血球中のリンパ球比率（P<0. 02）, 異型リンパ球出現率（P<0. 05）が高い程, 重症化することが示唆された. 死亡報告が散見されるマムシ咬傷に対し受傷早期の抗毒素血清投与は有用であり, 即効型過敏反応に即座に対応すれば比較的安全に投与できるものと考えられた. しかし, 軽症例に対しての抗毒素血清投与には疑問が残り, 今後は重症化が危倶される症例を的確に選択する必要があると思われた

CTを用いた成人日本人における股関節寛骨臼計測の基準値の性差および加齢が計測値に与える影響

Background: It is very important to understand the acetabular morphology of the normal hip joint to assist in diagnosis and surgical planning of hip disorders. The purpose of the present study was to obtain gender-based reference values for the acetabular measurements of a normal hip using computed tomography data and investigate the effect of aging on the measurement values. Methods: We measured acetabular parameters (center-edge angle, Sharp angle, vertical center anterior angle, acetabular anteversion) on computed tomography corrected for changing the obliquity, rotation, and tilt of the pelvis. We performed measurements in 245 patients (490 joints; 120 men [240 joints] and 125 women [250 joints]). The mean age was 64.7 ± 14.3 (31-88) years for men and 63.2 ± 15.2 (30-88) years for women. Results: In men and women, the mean center-edge angle was 31.8° ± 6.4° and 30.6° ± 6.5°, the mean Sharp angle was 38.6° ± 3.2° and 40.6° ± 3.8°, the mean vertical center anterior angle was 44.3° ± 7.9° and 40.0° ± 8.5°, and the mean acetabular anteversion angle was 14.3° ± 5.2° and 18.8° ± 5.4°, respectively. All differences were statistically significant. The center-edge angle increased with age in women; however, such an effect was not observed in men. The other measurements showed a similar trend, such as larger vertical center anterior angle and smaller Sharp and acetabular anteversion angles, with aging in both men and women. Conclusions: We used computed tomography data to quantitatively assess the coverage and shape of the acetabulum in adult Japanese subjects and obtain the estimated reference ranges by gender. The results also proved that the measurements changed with aging in both sexes. These facts must be taken into account during the diagnosis of hip disease and planning of surgery.博士（医学）・甲第784号・令和3年3月15日© 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved

Pre-DECIGO can get the smoking gun to decide the astrophysical or cosmological origin of GW150914-like binary black holes

Pre-DECIGO consists of three spacecraft arranged in an equilateral triangle with 100km arm lengths orbiting 2000km above the surface of the earth. It is hoped that the launch date will be in the late 2020s. Pre-DECIGO has one clear target: binary black holes (BBHs) like GW150914 and GW151226. Pre-DECIGO can detect $\sim 30M_\odot-30M_\odot$ BBH mergers up to redshift $z\sim 30$. The cumulative event rate is $\sim 1.8\times 10^{5}\,{\rm events~yr^{-1}}$ in the Pop III origin model of BBHs like GW150914, and it saturates at $z\sim 10$, while in the primordial BBH (PBBH) model, the cumulative event rate is $\sim 3\times 10^{4}\,{\rm events~ yr^{-1}}$ at $z=30$ even if only $0.1\%$ of the dark matter consists of PBHs, and it is still increasing at $z=30$. In the Pop I/II model of BBHs, the cumulative event rate is $(3-10)\times10^{5}\,{\rm events~ yr^{-1}}$ and it saturates at $z \sim 6$. We present the requirements on orbit accuracy, drag free techniques, laser power, frequency stability, and interferometer test mass. For BBHs like GW150914 at 1Gpc, SNR$\sim 90$ is achieved with the definition of Pre-DECIGO in the $0.01-100$Hz band. Pre-DECIGO can measure the mass spectrum and the $z$-dependence of the merger rate to distinguish various models of BBHs like GW150914. Pre-DECIGO can also predict the direction of BBHs at $z=0.1$ with an accuracy of $\sim 0.3\,{\rm deg}^2$ and a merging time accuracy of $\sim 1$s at about a day before the merger so that ground-based GW detectors further developed at that time as well as electromagnetic follow-up observations can prepare for the detection of merger in advance. For intermediate mass BBHs at a large redshift $z > 10$, the QNM frequency after the merger can be within the Pre-DECIGO band so that the ringing tail can also be detectable to confirm the Einstein theory of general relativity with SNR$\sim 35$. [abridged]Comment: 17 pages, 10 figures, added some references, modifications to match the published version in PTE

The shape of the emotion

　The emotion is an active reaction with being eloquent of the emotions such as the change of the look with the physiological reaction which is strong in the automatic nerves system, the immune system, the endocrine system which occurs with the organolepty which the creature felt.However, the definition of the emotion is ambiguous.　It is different roughly every learning field and for it, there is not a strict distinction of the emotion and the feelings.　The handling depends on the interval of the research area and the researcher.There seems to be possibility to complicate the discussion of the concerning with anxiety, theamygdala which is the nucleus of the fear and a cerebral limbic system for the ambiguousness of the definition and to make difficult.　Therefore, we made a chart with the emotion , feelings and the mood, placing as the differentreaction. In the tunnel of the tube-like of the comparatively gently long lasting mood, the feelings were wavering but supposed that doing of the eloquent of the emotion which is a physiological reaction and an active reaction didn\u27t accompany.　On the other hand, it supposed that an emotion was accompanied by the reaction which is physiological which is strong in the automatic nerves system, the immune system, the endocrine system and doing of the eloquent of the emotion physiological strong, deviating from the feeling control by the ventromedial prefrontal cortex.　Moreover, it considered about the relation, too, about the amygdala which is the existence like a nucleus of the experience like an emotion and the chronic pain

Sialyl LewisX mimic-decorated liposomes for anti-angiogenic everolimus delivery to E-selectin expressing endothelial cells

In this study, we developed novel E-selectin-targeting liposomes, i.e., 3′-(1-carboxy)ethyl sialyl LewisX (3′-CE sLeX) mimic liposomes, for targeted delivery of everolimus (EVE) in anti-angiogenic therapy. We investigated the uptake and efficacy of these E-selectin targeting liposomes in inflammatory cytokine-treated human umbilical vein endothelial cells (HUVECs). The uptake of EVE in 3′-CE sLeX mimic liposomes increased steadily and almost caught up with the uptake of plain EVE at 3 h, which was higher than that in PEGylated liposomes (PEG-liposomes). Inhibition of uptake by anti-E-selectin antibody suggested involvement of E-selectin-mediated endocytotic processes. Migration in cells treated with EVE/3′-CE sLeX mimic liposomes was suppressed by more than half when compared to the control. This treatment was also seen to significantly inhibit the formation of capillary tubes and networks. In addition, Thr389 phosphorylation of pS6 kinase, as a marker of mTOR activity, was remarkably suppressed to less than endogenous levels by EVE/3′-CE sLeX mimic liposomes. In conclusion, the present study demonstrated that EVE/3′-CE sLeX mimic liposomes were intracellularly taken up by E-selectin and prompted anti-angiogenic effects of EVE involved in the mTOR signaling pathway. However, moderate retention of EVE in the liposomes might limit the targeting ability of 3′-CE sLeX mimic liposomes

Inferior Vena Caval Thrombosis After Traumatic Liver Injury

We report here the case of a 35-year-old man who presented with inferior vena cava thrombosis (IVCT) after blunt hepatic trauma. The IVCT was incidentally detected by computed tomography (CT) 35 days after deep parenchymal suturing and suture approximation for liver lacerations. The patient denied any symptoms of thrombophlebitis. However, he had presented with significantly elevated values of FDP-D-dimer and a modest increase in plasminogen concentration, which indicated that he had been in a hypercoagulable and hypofibrinolytic state after the operation. He had not undergone any prophylactic anticoagulant therapy because of his concomitant subarachnoid hemorrhage and huge hepatic hematoma. The patient was treated with an emercy thrombectomy. Posttraumatic IVCT is extremely rare phenomenon. We should consider IVCT in patients with a severe hepatic injury, particularly if their coagulation system change into hypercoagulable and hypofibrinolytic state. Additionally, this case made us reflect on the treatment of traumatic liver injury