Dynamic collision behavior between osteoblasts and tumor cells regulates the disordered arrangement of collagen fiber/apatite crystals in metastasized bone

Bone metastasis is one of the most intractable bone diseases; it is accompanied with a severe mechanical dysfunction of bone tissue. We recently discovered that the disorganized collagen/apatite microstructure in cancer-bearing bone is a dominant determinant of the disruption of bone mechanical function; disordered osteoblast arrangement was found to be one of the principal determinants of the deteriorated collagen/apatite microstructure. However, the precise molecular mechanisms regulating the disordered osteoblast arrangement triggered by cancer invasion are not yet understood. Herein, we demonstrate a significant disorganization of bone tissue anisotropy in metastasized bone in our novel ex vivo metastasis model. Further, we propose a novel mechanism underlying the disorganization of a metastasized bone matrix: A dynamic collision behavior between tumor cells and osteoblasts disturbs the osteoblast arrangement along the collagen substrate.Matsugaki A., Harada T., Kimura Y., et al. Dynamic collision behavior between osteoblasts and tumor cells regulates the disordered arrangement of collagen fiber/apatite crystals in metastasized bone. International Journal of Molecular Sciences, 19, 11, 3474. https://doi.org/10.3390/ijms19113474

Impaired alignment of bone matrix microstructure associated with disorganized osteoblast arrangement in malignant melanoma metastasis

Malignant melanoma favors spreading to bone, resulting in a weakened bone with a high fracture risk. Here, we revealed the disorganized alignment of apatite crystals in the bone matrix associated with the homing of cancer cells by developing an artificially controlled ex vivo melanoma bone metastasis model. The ex vivo metastasis model reflects the progressive melanoma cell activation in vivo, resulting in decreased bone mineral density and expression of MMP1-positive cells. Moreover, less organized intercellular connections were observed in the neighboring osteoblasts in metastasized bone, indicating the abnormal and randomized organization of bone matrix secreted by disconnected osteoblasts. Our study revealed that the deteriorated microstructure associated with disorganized osteoblast arrangement was a determinant of malignant melanoma-related bone dysfunction.Matsugaki A., Kimura Y., Watanabe R., et al. Impaired alignment of bone matrix microstructure associated with disorganized osteoblast arrangement in malignant melanoma metastasis. Biomolecules, 11, 2, 1. https://doi.org/10.3390/biom11020131

Nucleophilic allylation of N,O-acetals with allylic alcohols promoted by Pd/Et3B and Pd/Et2Zn systems

Pd/Et3B and Pd/Et2Zn systems promote the nucleophilic allylations of 2-aminotetrahydrofuran and 2-aminotetrahydropyran with allylic alcohols to provide ω-hydroxyhomoallylamines in high yields. The transformation is applicable to the allylation of non-protective carbohydrates, such as ribose and deoxyribose

病院外来部のウェイファインディング・デザインに関する研究

Among the hospital departments, outpatient department should be the one where many patients could wander from the right path. The purpose of this study is to find out the guidelines for the planning of the safe and comfortable way-finding environment for the outpatient department. First, 190 Japanese hospitals built after 1985 with 300 or more beds were classified by the space components of the outpatient department from the way-finding design point of view. Next, comparative analysis was made on the information signs for the patients at 5 hospitals. These 5 hospitals had different kinds of space components. It was found that the visual acknowledgment by the patients heavily depends on the amount of information gathered from the space components as well as from the information signs. Therefore, by the good utilization of such space elements as light court and well space, we could reduce the stray patients even with less number of information signs

母児同室における初産婦のニーズと支援について─ KJ 法を用いた分析（第2報）─

　「母乳育児成功のための10か条」はWHO/UNICEF が1989年に発表した「母乳育児の保護，推進，支援，産科医 療施設の特別な役割」の要約である．これは「Baby Friendly Hospital Initiative：赤ちゃんにやさしい病院運動」の 基本方針でもあり，母児同室を推奨している． 　今回，個室にて母児同室を開始した初産婦の語りをKJ 法で分析し，ニーズと看護支援について検討した． 　その結果，看護者に期待する支援の内容は《常に気にかけて訪室してくれる》《頻回に言葉をかけてほしい》《看 護者たちの指導力や十分な心遣い》の3つのカテゴリーで構成された．《常に気にかけて訪室してくれる》は〈もっ と来て声をかけてほしい〉〈呼ばなくても見に来てくれる〉〈夜も目を向けてほしい〉のサブカテゴリー，《頻回に 訪室してくれる》は〈言いたくても自分だけかと躊躇する〉〈初産婦の特性〉のサブカテゴリーで，また《看護者 たちの指導力や十分な心遣い》は〈指導以外でも看護者の心遣いを感じる〉〈看護者から学ぶことが多い〉の2つの サブカテゴリーで構成されていた．母親たちの殆どは，初産のため些細な不安で看護者を呼ぶのを躊躇していた． 母親たちにとって指導のほか，看護者がすることをまねて学ぶとことも大きかった． 　看護者は常に意識を離さず，母親たちに対してプロの目があることを伝え，支え見守っているという保証を示す ことが重要である．“10 Steps to Successful Breast-feeding” is a summary of“ Protecting, promoting and supporting breast-feeding: the special role of maternity services” which was published by WHO/UNICEF in 1989 and is the basic policy of“ Baby Friendly Hospital Initiative”, which recommends rooming-in. In this study, the support from nurses to their needs described by primiparas who started rooming-in with the mother was analyzed using the KJ method. Results showed that the detailed expected support provided by nurses were broken down into the following three categories:“ Nurses often visit rooms with care”,“ Mothers wish for nurses to frequently speak to them”, and“ Nurses’ leadership and substantial care”. Each category consisted of the subcategories:‘ Visit more often’,‘ Visit without asking’, and‘ Watch at night as well’ in“ Nurses often visit rooms with care”;‘ Hesitate to call thinking that I am only one to do so’ and‘ Characteristic of primiparas’ in“ Mothers wish for nurses to frequently speak to them”;‘ Feel care from nurses other than guidance’ and‘ Learn many things from nurses’ in “Nurses’ leadership and substantial care”. Most mothers were hesitant to call nurses for trivial concerns due to it being their first deliveries. Mothers often learned by copying what nurses did, in addition to learning from guidance. It was suggested that it was important to give assurance that nurses were supporting and keeping a constant eye on the mothers, and to communicate to mothers that they were being supported by professionals

初産婦が感じた母児同室のメリット─ KJ 法を用いた分析（第1報）─

1989年のWHO/UNICEF による「母乳育児の保護，推進，支援，産科医療施設の特別な役割」の中で，母児同室 での感染予防や母乳育児のメリットを提唱している． 　今回個室で分娩後2時間より母児同室を開始した，初産婦がとらえた母児同室制についての語りをKJ 法にて分 析し，メリットについて検討した．その結果，抽出されたメリットは《大変さを乗り越える試練》《見守り寄り添 う看護》《愛着形成の場である》の3つのカテゴリーで構成された．《大変さを乗り越える試練》は〈大変でも退院 までの練習期間である〉〈自信をもって退院できる〉，《見守り寄り添う看護》は〈いつでもフォローしてくれる〉 〈自立性が芽生える〉，また《愛着形成の場である》は〈子どもが側にいるということ〉〈常に子どもと共にすごし ている〉のサブカテゴリーから構成されていた．出産前に母児同室制について十分に理解できないまま出産して戸 惑っていた母親も，母児同室で育児することは退院してからの生活の予測が立ち，看護者に聞いて疑問などを解決 して自信をもって育児できる体験と前向きにとらえていた．この背景には看護者の見守り，母親に対する気配り， 常にフォローできることを伝え，個室での母児同室で初産婦が陥りがちな問題を予測してケアをしており，看護者 として母親の状況を察知して頻回訪室の重要性が示唆された．　“Protecting, promoting and supporting breast-feeding: the special role of maternity services”, a joint WHO/UNICEF statement published in 1989, asserted the protection against infection and the benefits of breast-feeding brought about by rooming-in. 　In this study the advantages described by primiparas who started rooming-in with the mother two hours after delivery were analyzed using the KJ method and merit to be provided by nurses were considered. 　As a result, the extracted advantages were broken down into the following 3 categories:“ Challenge to overcome difficulties”,“ Nursing by watching carefully and staying close by”, and“ Opportunity to develop affection”. Each category consisted of the subcategories:‘ Although it is difficult, it is a training period until discharge’ and‘ I can leave the hospital with confidence’ in“ Challenge to overcome difficulties”;‘ Support is available anytime’ and‘ Independence is developed’ in“ Nursing by watching carefully and staying close by”; and‘ My child is nearby’ and‘ I always stay with my child’ in“ Opportunity to develop affection”. Even mothers who were confused by rooming-in because they did not have enough knowledge about it prior to giving birth had positive thoughts about the Rooming-in experience and found it useful in foreseeing life after discharge and in raising their child with confidence, since they could solve questions with the help of nurses. As a backdrop to the rooming-in environment, it was deemed important for nurses to care for new mothers by predicting problems that tended to occur with primiparas mothers and by assuring the mothers that nurses were there to watch over them and provide support at any time, and to frequently visit the rooms and, as assigned nurses, be conscientious of the mother's situations

Effect of Salivation by Facial Somatosensory Stimuli of Facial Massage and Vibrotactile Apparatus

We studied the effects of salivary promotion of fluid secretion after hand massage, and the apparatus of vibrotactile stimulation (89 Hz frequency, 15 min) in normal humans. Personal massage cannot be performed on handicap and stroke patients, and then giving hand massage to them for 5 min massage gives a tired feeling. So, we focused 3 min stranger massage. Salivary glands can discharge the accumulated saliva by extrusion from the acinus glands’ massages as described in the recent Japanese textbook. We think that this method may not produce realistic recovery. Our aim ideas are to relieve stress and increase temperature with lightly touch massage of the skin and for a 1 cycle of 1 s. We recorded RR interval of ECG, total salivation, facial skin temperature, OxyHb of fNIRS on the frontal cortex, and amylase activity for the autonomic changes. In increased 2°C of the facial skin temperature, the hand massage had a need for 3 min and the vibrotactile stimulation for 15 min. Increase from 700 to 1000 ms of RR intervals had a need for 3 min in the hand massage and had 15 min in the vibrotactile stimulation. Although vibrotactile stimulation needs long time of 4–7 years as effective recovery, hand massage may have more effect with a repetition of day after day

Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3.

植物由来成分であるプテロシンBはSIK3を阻害し変形性関節症の治療薬開発のリード化合物となる. 京都大学プレスリリース. 2016-03-31.Yahara, Y., Takemori, H., Okada, M. et al. Correction: Corrigendum: Pterosin B prevents chondrocyte hypertrophy and osteoarthritis in mice by inhibiting Sik3. Nat Commun 7, 12117 (2016).Osteoarthritis is a common debilitating joint disorder. Risk factors for osteoarthritis include age, which is associated with thinning of articular cartilage. Here we generate chondrocyte-specific salt-inducible kinase 3 (Sik3) conditional knockout mice that are resistant to osteoarthritis with thickened articular cartilage owing to a larger chondrocyte population. We also identify an edible Pteridium aquilinum compound, pterosin B, as a Sik3 pathway inhibitor. We show that either Sik3 deletion or intraarticular injection of mice with pterosin B inhibits chondrocyte hypertrophy and protects cartilage from osteoarthritis. Collectively, our results suggest Sik3 regulates the homeostasis of articular cartilage and is a target for the treatment of osteoarthritis, with pterosin B as a candidate therapeutic

Analysis of nivolumab related interstitial lung disease in patient with non-small-cell lung cancer.

ニボルマブに関連した間質性肺疾患（以下，ILD）の発現については，死亡例が報告され注意喚起がなされている。ILD 等の異常が認められた場合には，ニボルマブを中止し副腎皮質ステロイド剤の投与等の処置を行うこととされているが，十分なデータが得られているとは言えない。平成28年１～12月の間に非小細胞肺癌に対してニボルマブ投与を開始した患者の中でGrade 2及びGrade 3のILD各１名を経験し，メチルプレドニゾロンコハク酸エステルナトリウム１ g/day ×３日間投与後，経口プレドニゾロン投与し漸減することで軽快した。ILD の発現時期については，ニボルマブ２～ 12回目の投与時（中央値８回目）に発現しており定まっていなかった。今回経験したGrade ２以上の症例においては，副腎皮質ステロイドに対する反応性を認めた。The attention is given to Nivolumab induced interstitial lung disease （refered to as ILD）. In some cases, even deaths have been reported. The standard protocol is that once a sign of ILD is seen, stop Nivolumab and switch to corticosteriod, but there is no enough data to back up this protocol. Among the non-small cell lung cancer patients who were given Nivolumab between January 2016 and December 2016, there was one patient who experienced grade 2 ILD and another patient with grade 3 ILD. Both of these patients’ symptoms of ILD were mostly contained after given 1g/day of Methyprednisolone Soduim Succinate for 3 days, then oral prednisolones with gradually decreasing the dosage of it. Regarding the manifestation of ILD, it varied and it was somewhere bewteen second to 12th doses of Nivolumab with the median of 8th doses. This study was able to confirm the effective response to corticosteriod for grade 2 or higher cases of ILD

ヒマラヤ・ラダーク地方における高所適応とその変容 (1) 生業と食を中心に

　高所では一般に、エネルギー摂取量が低い一方、運動量が多いため、糖尿病や高血圧などの生活習慣病はもともと少ないと考えられてきた。しかし、生活スタイルの変化によって、近年、急激に生活習慣病が顕在化してきた。そこで、本研究では、インド・ラダーク地方に焦点を絞り、文化人類学と栄養学と医学の共同により、高所環境に対する人間の医学生理的適応と生態・文化的適応を明らかにし、そして、近年の変化によって適応のバランスがどのように崩れ、それが高所住民にどのような影響を及ぼしているかを明らかにすることを主な目的とした。　本稿では、まず、ラダークの都市レー（標高3600m）の概要、チャンタン高原（標高4200-4900m）の遊牧民とドムカル谷（標高3000-3800m）の農民・農牧民の伝統的生活とその変化、及びその背景について論じる。つぎに、それぞれの地域で実施した健診調査のうち、栄養学調査の結果、および分析について論じる。　チャンタン高原の人びとは、以前はヤクとヤギ・ヒツジの遊牧と交易によって生計を立ててきた。遊牧については、基本的に固有のシステムが継承されている。一方、かつて行われていた、北のチベット、西のザンスカル等との長距離のキャラバン交易は、消滅した。　ドムカル谷では、農耕とともに、ヤク、ゾモ（ウシとヤクの交雑種）、ゾー（ゾモの雄）、バラン（在来ウシ）などの移牧が行われてきた。ドムカルにおける農牧複合は、この地方の厳しい自然環境に適応した、独自の特徴を持っている。それは相互扶助などの社会システムによって支えられてきた。しかし、若者が軍関係の仕事につくため、村外に出ることが多くなり、家畜の飼養は急激に減少し、むらの生活も近代化して大きく変化してきた。その背景には、中国との国境紛争、舗装道路の開通、政府による食糧配給による援助、さらに、レーの都市の拡大・観光化や軍の需要などによる市場経済化などがある。　ラダークにおける食事調査により、高所環境という食料入手の困難な環境を反映した、質・量ともに乏しい栄養状態を明らかにした一方、レーやドムカルでは過栄養やこれに関わる生活習慣病も見過ごせない問題となっていることが明らかになった。さらに、栄養摂取と糖尿病との関連を分析すると、エネルギー摂取量の多い人だけではなく、少ない人にも糖尿病がみられた。エネルギー摂取量の少ない人では、食品摂取の多様性が少なく、炭水化物に偏った食事内容になっていることも要因の一つと考察できる。　現在の人々の食の嗜好からも食事の変化をみてとることができた。特に大麦から米・小麦への主食の転換は、元来の高所住民の伝統的な食生活の中心を大きく変えるものであり、生活習慣病の増加の一因となることが懸念される。伝統的な食生活を見直すこと加え、野菜などの摂取頻度の少ない食品群の補強がうまく行われること、さらに健康に関する知識の向上が今後ますます重要になると考えられる