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大腿骨後顆形状は大腿骨外旋運動に影響する
Get PDF新潟大学Niigata University博士（医学）Purpose The purpose of this study was to identify factors related to the external rotation of the femur during knee flexion. Methods Three-dimensional (3D) digital models of the femur and tibia were reconstructed from computed tomography images of 41 healthy Japanese subjects. Thirteen parameters related to femoral and tibial morphol-ogy and alignment of the lower extremities were evaluated, including the inclination angle of the posterior lateral and medial femoral condyles, the ratio of the medial and lateral posterior condyle radii approximated as spheres, the spherical condylar angle, the posterior condylar angle, the medial and lateral posterior tibial slope, the difference of medial and lateral posterior tibial slope, the tibiofemoral rotation angle, the 3D femorotibial angle, the 3D hip-knee-ankle angle, and the passing point of the weight-bearing line (medial–lateral and anterior–posterior). The rotation angle of the femur relative to the tibia during squatting was investigated using a 3D to 2D image matching technique and the relationships with the13 parameters were determined. Results The femur externally rotated substantially up to 20°of knee flexion (9.2°± 3.7°) and gently rotated after 20°of knee flexion (12.8°± 6.2°). The external rotation angle at 20°–120°of knee flexion correlated with the spherical condylar angle, the tibiofemoral rotation angle and the inclination angle of the posterior medial condyles (correlation coefficient; 0.506, 0.364, 0.337, respectively). Conclusion The parameter that was most related to the external rotation of the femur during knee flexion was the spherical condylar angle.Hijikata, H., Tanifuji, O., Mochizuki, T., Sato, T., Watanabe, S., Katsumi, R., Hokari, S. and Kawashima, H. (2023), The morphology of the femoral posterior condyle affects the external rotation of the femur. J EXP ORTOP, 10: 122. https://doi.org/10.1186/s40634-023-00686-w新大博（医）第1190
Usefulness of human demineralized bone matrix as a scaffold for bone regeneration
Get PDF新潟大学Niigata University博士（歯学）私たちはこれまでに 120 例を超える患者に培養自家骨膜細胞移植材による歯槽骨顎骨再生療法を実施している。 しかし本治療法は自家骨移植に比べ採骨量を 3 分の 1 程度に減量したとはいえ、依然として自家骨と自家 PRP を細胞移植担体として使用することが患者の負担となっている。そのため、細胞との親和性と骨誘導能に優れた自家由来成分に代わる移植材料の使用が課題である。本研究は培養骨膜細胞の移植担体としてヒト脱灰骨基質（DBM : GraftonTM) の可能性について、基礎的な検討を行った。 8週齢雄ヌードラットの頭蓋骨頭頂部に直径 9mm のポリ乳酸樹脂円形皿状シェルを被覆材として、 DBM および対照群として焼成ウシ骨顆粒（Bio-OssTM) を移植した。 それぞれについて培養骨膜細胞投与群［CPC(+),n=3］および 同非投与群［CPC(-)群,n=3］を設定した。 4 週後にマイクロＣＴを撮影 し、 骨形成領域の体積を計測した。また非脱灰凍結切片を作製し、 移植部位の骨形成状態、骨芽細胞および破骨細胞等の組織学的観察を行うととともに、画像解析ソフト ImageJ を用いて組織画像の骨形成領域を計測した。 マイクロＣＴによる移植骨領域の評価では、Bio-OssTM 移植群では移植材の残遺が見られたのみであったのに対し、 DBM 移植群では移植時には存在しない新たな硬組織レベルの不透過像を生じ、 形成骨の誘導が示唆された。 DBM における形成骨の体積計測では、CPC(+)群は CPC(-)群と比較して骨形成体積が有意に大きい傾向を示した。組織学的観察では、 Bio-OssTM 移植群では移植材周囲に形成骨は形成されず、ALP 陽性および TRAP 陽性細胞の誘導も観察されなかった。それに対し、DBM 移植群では骨が形成され、その周囲に明瞭な ALP 活性を示す骨芽細胞のライニングを認めるとともに、TRAP 陽性の破骨細胞の誘導が確認された。 DBM 移植群について、形成骨密度をCPC(+）群と CPC(-) 群で比較した結果において、両者に有意な差は認められなかった。 DBM 移植により短期間で骨形成が得られたことは、同移植材の骨誘導能を示している。それに加えて、培養骨膜細胞との親和性を示唆する結果は、 DBM の骨再生細胞療法における細胞移植担体としての有用性を示唆している。新大院博(歯)第556
ナトリウム磁気共鳴画像法は、糖尿病モデルマウスの腎臓における対向流増幅系の障害を明らかにする
Get PDF新潟大学Niigata University博士（医学）Background Sodium magnetic resonance imaging can noninvasively assess sodium distribution, specifically sodium concentration in the countercurrent multiplication system in the kidney, which forms a sodium concentration gradient from the cortex to the medulla, enabling efficient water reabsorption. This study aimed to investigate whether sodium magnetic resonance imaging can detect changes in sodium concentrations under normal conditions in mice and in disease models, such as a mouse model with diabetes mellitus. Methods We performed sodium and proton nuclear magnetic resonance imaging using a 9.4-T vertical standard-bore superconducting magnet. Results A condition of deep anesthesia, with widened breath intervals, or furosemide administration in 6-week-old C57BL/6JJcl mice showed a decrease in both tissue sodium concentrations in the medulla and sodium concentration gradients from the cortex to the medulla. Furthermore, sodium magnetic resonance imaging revealed reductions in the sodium concentration in the medulla and in the gradient from the cortex to the medulla in BKS.Cg-Leprdb+/+ Leprdb/Jcl mice at very early type 2 diabetes mellitus stages compared with corre-sponding control BKS.Cg-m+/m+/Jcl mice. Conclusions The kidneys of BKS.Cg-Leprdb+/+ Leprdb/Jcl mice aged 6 weeks showed impairments in the countercurrent multiplication system. We propose the utility of 23Na MRI for evaluating functional changes in diabetic kidney disease and not as a marker that reflects structural damage. Thus, 23Na MRI may be a potentially very early marker for structures beyond the glomerulus; this may prompt intervention with novel efficacious tubule-targeting therapies.Nakagawa, Yusuke; Kaseda, Ryohei; Suzuki, Yuya; Watanabe, Hirofumi; Otsuka, Tadashi; Yamamoto, Suguru; Kaneko, Yoshikatsu; Goto, Shin; Terada, Yasuhiko; Haishi, Tomoyuki; Sasaki, Susumu; Narita, Ichiei. Sodium Magnetic Resonance Imaging Shows Impairment of the Counter-current Multiplication System in Diabetic Mice Kidney. Kidney360 4(5):p 582-590, May 2023. | DOI: 10.34067/KID.0000000000000072新大院博（医）第1223
発育性股関節形成不全の3次元的基準は、骨盤前方面を用いるよりも、骨盤機能面を用いる方が有用である
Get PDF新潟大学Niigata University博士（医学）Background: This retrospective cross-sectional study investigated the cutoff values (COVs) for developmental dysplasia of the hip (DDH) using a three-dimensional (3D) pelvic model recon-structed using computed tomography (CT). We included 107 healthy Japanese participants and 73 patients who had undergone curved periacetabular osteotomy (CPO) for DDH between 2012 and 2017. Methods: The hip CT images were adjusted to the anterior pelvic plane (APP), functional pelvic plane (FPP), sagittal anterior center-edge angle (ACEA), and sagittal posterior center-edge angle (PCEA). The lateral center-edge angle (LCEA), acetabular roof obliquity (ARO), anterior acetab-ular sector angle (AASA), and posterior acetabular sector angle (PASA) were measured. Receiver operating characteristic (ROC) curves were used to calculate the COVs, and the association between the parameters was analyzed using multiple logistic regression. Results: The ARO (≥10.2°) and LCEA(≤22.2°) were independent influencing factors for the APP, whereas the AASA (≤53.1°) and LCEA (≤24.5°) were independent influencing factors for the FPP. Conclusions: The 3D criteria for the diagnosis of DDH in Japanese individuals can identify DDH with insufficient anterior coverage, which anteroposterior plain radiographs cannot visualize, and can help determine indications for acetabular osteotomy.Ibuchi, S.; Imai, N.; Horigome, Y.; Suzuki, H.; Kawashima, H. The Three-Dimensional Criteria of Developmental Dysplasia of the Hip Using the Functional Pelvic Plane Is More Useful Than That Using the Anterior Pelvic Plane. J. Clin. Med. 2024, 13, 2536. https://doi.org/10.3390/jcm13092536新大院博（医）第1226
エダラボンによる酸化還元状態の制御が細胞移植部位における骨再生を促進する
Get PDF新潟大学Niigata University博士（歯学）In cell-based bone augmentation, transplanted cell dysfunction and apoptosis can occur due to oxidative stress caused by the overproduction of reactive oxygen species (ROS). Edaravone (EDA) is a potent free radical scavenger with potential medical applications. This study aimed to investigate the effect of controlling oxidative stress on bone regeneration using EDA. Bone marrow-derived cells were collected from 4-week-old rats, and EDA effects on cell viability and osteogenic differentiation were evaluated. Collagen gels containing PKH26-prelabeled cells were implanted into the calvarial defects of 12-week-old rats, followed by daily subcutaneous injections of normal saline or 500 μM EDA for 4 d. Bone formation was examined using micro-computed to-mography and histological staining. Immunofluorescence staining was performed for markers of oxidative stress, macrophages, osteogenesis, and angiogenesis. EDA suppressed ROS production and hydrogen peroxide-induced apoptosis, recovering cell viability and osteoblast differentiation. EDA treatment in vivo increased new bone formation. EDA induced the transition of the macrophage population toward the M2 phenotype. The EDA group also exhibited stronger immunofluorescence for vascular endothelial growth factor and CD31. In addition, more PKH26-positive and PKH26-osteocalcin-double-positive cells were observed in the EDA group, indicating that transplanted cell survival was prolonged, and they differentiated into bone-forming cells. This could be attrib-uted to oxidative stress suppression at the transplantation site by EDA. Collectively, local administration using EDA facilitates bone regeneration by improving the local environment and angiogenesis, prolonging survival, and enhancing the osteogenic capabilities of transplanted cells.Quang Nguyen Van, Yosuke Akiba, Kaori Eguchi, Nami Akiba, Katsumi Uoshima,
Controlling redox state by edaravone at transplantation site enhances bone regeneration,
Biomedicine & Pharmacotherapy,
Volume 177,
2024,
117032,
ISSN 0753-3322,
https://doi.org/10.1016/j.biopha.2024.117032.
(https://www.sciencedirect.com/science/article/pii/S0753332224009168)新大院博(歯)第572
ポリマープリズムを利用した小型表面プラズモン共鳴センサチップの作製と評価
Get PDF新潟大学Niigata University博士（工学）In this research, we developed a miniature surface plasmon resonance (SPR) sensor chip using the Kretschmann configuration with a polymeric prism made from Norland Optical Adhesive 61 (NOA 61). This approach addresses limitations found in conventional SPR spectroscopy. We utilized the confined sessile drop technique to create the NOA 61 polymeric prism, which provides benefits such as simplicity, low-cost fabrication, and precise control over lens parameters. Liquid NOA 61 was dropped directly on a poly(dimethyl siloxane) (PDMS) circular disk with a diameter of 6 mm, resulting in a hemispherical prism after UV curing. A 3 nm-thick chromium (Cr) layer and a 47 nm-thick gold (Au) layer were then deposited onto the planar side of the prism, and the assembly was mounted on a microfluidic cell made with a 3D printer. The SPR excitation curves observed in the visible region showed a refractive index independence sensitivity of 885.4 nm/RIU, and the sensor demonstrated the ability to detect nanomaterials. Building upon this development, we explored dual-mode sensing capabilities to enhance detection sensitivity and selectivity further. In our subsequent study, we fabricated a dual-mode miniature SPR sensor using a polymeric grating prism made from NOA 61 with a soft lithography and confined sessile drop technique. The dual-mode SPR sensor displayed SPR excitation through wavelength modulation at incident angles of 45°to 75° in air, with reflectivity curves covering the vis–NIR region. We identified two SPR modes: prism-coupling SPR mode (PC-SPR) and grating-coupling SPR mode (GC-SPR). The PC-SPR mode was detected at the gold–NOA 61 interface, while the GC-SPR mode was observed at both the gold–air and gold–NOA 61 interfaces. Using different concentrations of ethylene glycol in aqueous solution, the sensor demonstrated refractive index sensitivities of 1,853 and 489.6 nm/RIU for PC-SPR and GC-SPR modes, respectively. This dual-mode SPR sensor, with its enhanced response and significant wavelength amplification, shows promise for advanced sensing and detection applications. Finally, we focused on modifying Au chips with UiO-66-NH2 for heavy metal detection via the surface plasmon resonance (SPR) technique. Two deposition conditions for UiO-66-NH2 were tested: spin-coating immediately after dropping the dispersion solution (0-minute condition) and spin-coating after a 15-minute waiting period. The 0-minute condition produced a more uniform UiO-66-NH2 distribution and was thus chosen for further investigation of heavy metal ion adsorption. The SPR signal revealed a response to As(V) ion adsorption on the UiO-66-NH2 layer in aqueous solution, demonstrating a novel and effective method for detecting As(V) in the 10 to 50 mg/mL range. This modified sensor exhibited significantly greater sensitivity for detecting As(V) ions compared to an unmodified Au chip. By leveraging the advancements made in the previous studies, we demonstrated the practical applicability and enhanced performance of SPR-based sensors in detecting specific analytes.新大院博(工)第566
Development of an avalanche simulation model using the MPS method
Get PDF新潟大学Niigata University博士（学術）雪崩は斜面に降り積もった積雪の重力によって落下しようとする力が，積雪内の雪のせん断強度，積雪と地面との摩擦を上回ることによって流下する現象である．雪崩は規模が大きいほど，速度や流下距離が大きくなり，走路上に人や構造物などがある場合には大きなダメージを与える．雪崩災害は雪崩研究の先進地域であるヨーロッパをはじめ，世界各地でみられ，日本も例外ではない．このような雪崩災害は集落や道路，鉄道などの交通施設，登山やスキーなどの山岳レジャーなどで発生しているが，ソフト対策ではハザードマップや予測など，ハード対策では予防施設や防護施設などの雪崩対策施設の設置などが挙げられる．ハード対策の計画検討では，雪崩の到達範囲や厚さ，速度，衝撃力などの雪崩の運動に関する情報を正確に予測することが重要であり，古くから様々な予測・解析手法が提案されている．古典的な手法としては，統計的手法により到達距離を求める手法や，雪崩を定常流の流体と仮定し，1次元解析により速度や到達距離を推定する手法がある．一方，現在，研究開発が進められている手法では，雪崩を連続体と仮定し，平均深さモデルや深さ積分モデルと呼ばれる運動方程式を基に雪崩の運動を2次元上で解析する数値シミュレーションモデルが主流となっている．このような古典的手法や2次元モデルは計算効率の良い解析手法であるが，雪崩運動の3次元的な情報（高さ方向の速度や圧力分布など）を得ることはできない．しかし，複雑地形上の雪崩運動の把握や対策施設の形状や配置の計画，雪崩衝撃力に対する耐力の照査などでの利用を考えた場合，3次元の情報を得ることができる数値シミュレーションモデルが必要であると考えられる．以上の背景から，本研究は Lagrange 的手法である粒子法の1つで，自由表面流れやマルチフィジックスの解析に強みを持つ Moving Particle Simulation （MPS）法を応用した3次元雪崩シミュレーションモデルの開発を行ったものである．第1章では，研究の背景や既往研究などを整理し，本研究の有益性や既往研究に対する優位性について論じた．第2章では，MPS法に基づき，手法の基本となる理論の解説に加え，非ニュートン流体として振る舞う雪崩運動に適用するための構成式の導入や雪崩走路上の雪の浸食・堆積過程の考慮方法の検討などを論じた．また，オリジナルのMPS法で採用されている半陰解的手法（Semi-Implicit MPS, SI-MPS）を適用したモデルに加え，計算コストや並列コンピューティングへの適用上有利な手法として開発された陽解法MPS法（Explicit MPS, E-MPS）を適用したモデルの検討も行った．第3章では，自然雪と小規模な滑り台を用いた雪崩実験と，開発したシミュレーションモデルによる再現解析を行い，実験と解析の比較により，本モデルの再現性を確認した．第4章では，北海道ニセコ町で実施した人工雪崩実験を対象に再現解析を行ない，実験時にUAVで撮影された動画から解析した雪崩の速度や流下形状，到達距離などとの比較を行った．比較の結果，実験で確認された雪の取り込みを含む雪崩の流下状況を再現できることが確認された．第5章では，新潟県で観測された雪崩事例，および北海道において実際に人的被害があった雪崩災害事例等，自然斜面において発生した3つの雪崩事例を対象に再現解析を行った．解析結果と実際の雪崩や被害状況との比較により，自然斜面で発生する乾雪・湿雪雪崩に対する本モデルの適用性を論じた．第6章では，本モデルの工学的利用における有効性の確認として，山形県の道路で発生した雪崩災害を対象として，再現解析で再現性の高いパラメータの同定した後，対策施設を対象とした予測解析を実施した．解析の結果，本モデルの再現性に加え，解析によって3次元的な形状を持つ対策施設について，効果の評価が可能であることが確認され，工学的利用における解析ツールとしての有効性が示された．第7章では，開発したシミュレーションモデルの実用化を見据え，第2章から第6章の検討結果を基に，解析に用いるパラメータの範囲や，乾雪・湿雪や面発生・点発生などの分類，煙型・流れ型の運動形態など様々な雪崩の現象に対するモデルの適用範囲，雪崩対策検討など工学分野における利用などについて考察した．第8章では，研究の総括，および開発したシミュレーションモデルの予測精度の向上に向けた今後の課題を示した．以上の検討結果，本研究で開発したシミュレーションモデルは，雪崩ダイナミクスの理解や，雪崩災害対策の計画において必要となる雪崩運動の3次元情報を把握するための手法として極めて有益な解析ツールであり，今後の雪崩災害の防止に資するものであると結論された．Avalanches occur when the force of gravity acting on snow accumulated on a slope exceeds the shear strength within the snow or the friction between the snow and the ground. As the scale of the avalanche increases, its speed and travel distance increase, causing significant damage to settlements, roads, and railways, and impeding mountain leisure activities such as skiing and climbing. To mitigate these hazards, non-structural measures such as danger level assessments based on meteorological data and the publishing of hazard maps as well as construction measures such as building protective structures are employed. To plan countermeasures effectively, accurate predictions of avalanche flow speed, runout area, thickness, and impact force are essential. Although statistical methods considering topologic angles have been dominant for a long time, dynamic fluid models have also been developed. Following one-dimensional steady state models, two-dimensional equations, which assume that avalanches behave as continuous media, are becoming more mainstream. These models, known as averaged-depth models, are computationally cost effective but have limitations in estimating avalanche behavior over complex terrains and optimizing the shape and layout of a facility. Based on the above background, this study presents a three-dimensional avalanche simulation model developed using the moving particle simulation (MPS) method. The MPS method is advantageous for free surface flows and multiphysics applications involving large deformations and fragmentation. The model developed here incorporates non-Newtonian fluid behavior (Bingham and dilatant fluids) and snow erosion and deposition processes. Two algorithms were employed: the original semi-implicit MPS (SI-MPS) and the computationally efficient explicit MPS (E-MPS). To validate the accuracy of the model, simulations were conducted and compared with the results of small-scale snow flow experiments, artificial avalanche releases in Niseko, and actual avalanche cases in Hokkaido and Niigata. Although several improvements, including improving the parameter settings, are needed, the calculated results successfully reproduced the experiments and actual avalanche cases with high accuracy. In this study, the model was also applied to reproduce the avalanche and evaluate the effects of countermeasures in the recent case in Yamagata. Based on the results, it can be concluded that the new 3D avalanche model is highly effective in predicting avalanche characteristics, including distributions of flow speed, flow thickness, and runout area. Furthermore, it provides useful information for planning countermeasure structures and contributes significantly to avalanche disaster prevention新大博(学)第76
ハイブリッド神経線維腫／神経鞘腫の再評価 : 神経線維腫の診断おける、CD34陽性に比する病理学的特徴の優位性
Get PDF新潟大学Niigata University博士（医学）Pathological characteristics of schwannomas include both high-cellularity regions (Antoni A area) and hypocellular regions (Antoni B area). Neurofibromas characteristically consist of CD34 positive spindle cells with thin, wavy, nuclei and wavy collagen bands. Previous reports have described segments of schwannomas with neurofibroma features as hy-brid tumors, although hybrid tumors were diagnosed based on partial CD34 positivity in many previous reports. On the other hand, the Antoni B area of some schwannomas was reported to be positive for CD34. Therefore, the definition of a hybrid tumor has not been clear. The objective of this study was to determine whether only CD34 posi-tive findings in schwannomas could be used to define a hybrid tumor. In the analysis of our patient with schwannomatosis caused by a novel LZTR1 germline mutation, part of the tumor had CD34 positive hypocellular regions. These regions contained no thin, wavy, nuclei, indicating an Antoni B area. Laser microdissection was used to investigate the genetic background and differences in molecular mechanisms between CD34 posi-tive and CD34 negative regions. All mutations identified in CD34 positive regions were also found in CD34 negative regions. Our data could not clear the genetic background of Antoni B which was CD34 positive area. We then reviewed the pathologies of 66 sporadic schwannomas. Histopathological examinations of all schwannomas revealed the absence of thin, wavy, nuclei and wavy collagen bands, and no hybrid tumors were found in any of the cases. Ten of 66 patients were randomly selected for CD34 immunostain-ing and positivity was found in all cases. Our data suggest that it is difficult to distinguish schwannomas by staining for CD34 alone, as Antoni B areas can also be positive for CD34. Therefore, CD34 staining alone should not be used to diagnose hybrid tumors in patients with schwannomas.Katsumi T, Hayashi R, Takei S, Ansai O, Takatsuka S, Takenouchi T, et al. Reevaluating hybrid neurofibroma/schwannoma: Predominance of schwannoma features despite CD34 positivity and initial neurofibroma diagnosis. J Dermatol. 2024; 51: 1461–1469. https://doi.org/10.1111/1346-8138.17343This is the peer reviewed version of the following article: Katsumi T, Hayashi R, Takei S, Ansai O, Takatsuka S, Takenouchi T, et al. Reevaluating hybrid neurofibroma/schwannoma: Predominance of schwannoma features despite CD34 positivity and initial neurofibroma diagnosis. J Dermatol. 2024; 51: 1461–1469. https://doi.org/10.1111/1346-8138.17343, which has been published in final form at https://doi.org/10.1111/1346-8138.17343. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.新大院博（医）第1212