| 1.
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Asano, Krisana ; Nakane, Akio
概要:
Autophagy, a cellular homeostatic pathway, is emerged as an innate immune response against intracellularpathogens. It ca
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n directly eliminate invading bacteria by mediating their delivery to lysosomes. However, successfulintracellular pathogens have developed mechanism（s） to escape or subvert autophagy for their intracellular niches.Studies on interplay between autophagy and intracellular pathogens are very important for understanding howinfections occur. Particularly, Staphylococcus aureus is an important opportunistic pathogen that causes a wide rangeof infections. Classically, S. aureus is considered as an extracellular pathogen, but cumulative evidence indicates thatthis bacterium invades epithelial cells and replicates intracellularly which is relevant to intracellular persistence andchronic infections. A serious therapeutic problem of staphylococcal infections is caused by antibiotic resistant strainswhich have emerged increasingly in recent years. Thus, new insights in the strategy of S. aureus to interplay withautophagy is urgently required. This review highlights an impact of S. aureus toxins on autophagy. Alpha-hemolysinactivates autophagy and prevents lysosome-autophagosome fusion, whereas toxic shock syndrome toxin-1 suppressesautophagosome formation. This opposite function indicates a complicated relationship between autophagy andintracellular adaptation of S. aureus. The possible effects of these toxins on S. aureus infections are also addressed in this review.
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| 2.
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Nozaki, Shuhei ; Ogata, Yoshiki ; Yonekura, Manabu ; Han, Chong ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Hirota, Kazuyoshi ; Matsuzaki, Yasushi ; Tomita, Hirofumi ; Imaizumi, Tadaatsu ; Itagaki, Shirou ; Sawamura, Daisuke ; Murakami, Manabu
概要:
We analyzed the effects of halothane as an inhalational anesthetic agent on electrocardiogram （ECG）parameters in C57/BL6
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mice. Following induction of anesthesia using 2% halothane, the ECGs showed a regularpattern and the heart rate （HR） was within an acceptable range （~500 bpm）. The HR decreased with increasinghalothane concentration in a concentration-dependent fashion. The frequency domain analysis showed that the high-frequency （HF） component decreased and the lowfrequency（LF） component increased in a concentration-dependent fashion. Therefore, the LF/HF ratio increasedwith increasing halothane concentration, suggesting effects on the autonomic nervous system. We analyzed the pharmacological response to sympathetic blockade with propranolol, a typical adrenergicβ-blocker, under halothane anesthesia. Propranolol administration resulted in a decreased HR; interestingly,intraperitoneal injection of propranolol （120 μg/kg body weight） resulted in arrhythmia （sick sinus syndrome）during anesthesia with 3% halothane. Our results indicate the importance of selecting a suitable anesthetic agent for C57/BL6 mice in pharmacological studies
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| 3.
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津山, 博匡 ; 中川, 潤一 ; 細井, 一広 ; 照井, 一史 ; 兵藤, 塁 ; 上野, 桂代 ; 早狩, 誠
概要:
本研究ではバイオ医薬品の純度について検討し，その安全性を評価することを目的とした。 糖鎖の付加がない単純タンパクである顆粒球コロニー刺激因子（granulocyte-colony stimulating factor, G-CSF）製剤では
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，バイオシミラー（ 2 社製）も含め純度について比較検討した．その結果，SDS-PAGE 法，HPLC 法，SELDI-TOFMS 法において，先行品およびバイオシミラーは高純度のG-CSF を含んでいることが明らかとなり，安全性は問題がないことが明らかとなった。 また，バイオ医薬品の1 つであるキメラ型抗体製剤（infliximab）のエピトープマッピングを行い，投与患者に産生される中和抗体に対する抗原部位を検索した．その結果，少なくとも3 箇所に抗原部位を認め，中和抗体のマルチタイプの検索が今後の薬物療法への重要な指標となることを明らかにした。
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| 4.
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韓, 沖 ; 瀬谷, 和彦 ; 小潟, 佳輝 ; 野崎, 修平 ; 米倉, 学 ; 村上, 学
概要:
新生仔マウス初代培養心筋細胞法は1960年代に確立された。しかし，多数の新生仔が必要であり，遺伝子改変動物に応用するためには問題も多い。今回我々は，野生型57BL/6J 系マウス新生仔を用い，心筋保護剤であるブタンジオンモノオキシム存在下，
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2 段階の酵素処理（トリプシン処理（約2 時間），コラゲナーゼ-ディスパーゼ処理（約1 時間））約5 時間で単離し，初代培養できる手法を考案した。得られた初代培養心筋細胞は，培養開始後約12時間で拍動を開始し，1 週間継続した。また，交感神経刺激薬を用いた生理学・薬理学的検討でも心筋細胞機能が従来法で得た細胞と変わらないことを確認した。以上の結果は，本改良法が少数の個体しか得られない遺伝子改変マウス新生仔にも適用し得る事を示唆している。
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| 5.
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Ogata, Yoshiki ; Yonekura, Manabu ; Yamaki, Rouichi ; Han, Chong ; Fujiwara, Tomonori ; Seya, Kazuhiko ; Niwa, Hidetoshi ; Kushikata, Tetsuya ; Imaizumi, Tadaatsu ; Hirota, Kazuyoshi ; Tomita, Hirofumi ; Murakami, Manabu
概要:
We examined the effects of enflurane anesthesia on the mouse cardiac autonomic nervous system usingelectrocardiogram（ EC
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G） analysis. Enflurane had a lower effect on heart rate（ HR） compared to isoflurane, which ismore widely used in small animal studies. Under anesthesia with 3 or 4% of enflurane, administration of propranololhad a significant effect on HR. Enflurane increased R-R interval length in a dose-dependent fashion, and the R-Rinterval became unstable at high concentrations. Although HR decreased with high doses of enflurane, we observednormal sinus rhythm and no arrhythmia. These results suggest that the effect of enflurane anesthesia is acceptableeven though the drug can lead to cardiac instability. No remarkable changes were observed in HR frequency. These results suggest that enflurane anesthesia may be suitable for cardiac autonomic nervous system analysis.
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| 6.
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Fukuda, Wakako ; Chiyoya, Mari ; Saito, Yoshiaki ; Taniguchi, Satoshi ; Daitoku, Kazuyuki ; Fukuda, Ikuo
概要:
Background: Retrievable inferior vena cava （IVC） filter devices have been developed to overcome thelong-term complicatio
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ns of permanent filters. It is of interest to evaluate the retrievability of retrievable IVC filtersand how safely the IVC filters indwelled for a long period of time can be retrieved. We reviewed a group of 44patients, who were selected for ALN retrievable filter implantation and reviewed the indications, efficacy as well ascomplications.Material and Methods: 300 venous thromboembolism （VTE） patients were treated in our institution between2003 and 2014. IVC filters were inserted in 84 cases （28%） and 44 of 84 patients received ALN retrievable filterimplantation. We retrospectively reviewed the indications, efficacy and complications of 44 patients with ALN filters.Results: All 44 patients had deep vein thrombosis（ DVT） and 39 patients（ 88.6%） also had pulmonary embolism（ PE）.The most frequent associated risk factor for DVT was cancer（ n=19）. The filter was implanted for a median durationof 708.8 days（ range 68-1717）. While the filter was in place, at least one venous thromboembolic event occurred in 4.5%（2 of 44 patients）. Filter retrieval was attempted in 8 patients（ 18.2%） after a median period of 271.9 days（ range 79- 559）. Filter retrievals were successful in all cases.Conclusion: This study showed the efficacy of ALN filter. It also demonstrated the safety of retrieval after a longterm placement.
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Nagawa, Yonmi ; Tsushima, Eiki
概要:
We conducted an observational gait assessment and examined the relationship of gait deviations withphysical function and
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walking ability. A total of 57 stroke patients admitted to a rehabilitation unit, who could walkunaided or under close supervision, were enrolled in the study （37 men; 20 women; 62.2±11.2 years of age; elapsedtime since the onset of stroke: 90.9±39.9 days）. We combined and partially modified several assessment formsused for gait evaluation. With regard to physical functions, we assessed: lower limb paralysis, sensory impairment,lower limb spasticity, range of motion, lower limb muscle strength, lower limb weight-bearing, and standing balance.We conducted a 10-meter walk test to assess patients’ walking ability. In order to identify variables that affectthe total gait assessment score, a multiple regression analysis was performed. The following parameters werestatistically associated with gait deviations: number of steps required to walk 10 meters（ standard partial regressioncoefficient=0.68）, affected side hip abductor strength （–0.23）, ankle plantar flexor spasticity （0.18）, and maximumweight-bearing rate on the unaffected side （0.16）. We established the relationship of gait deviations with physical function and walking ability.
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| 8.
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宇佐美, 真一
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| 9.
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小笠原, 望
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| 10.
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今村, 憲市
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