母体血中における分娩形式による分娩前後の、羊水塞栓症のバイオマーカーとなりうるSCC 抗原の大きな変化

Amniotic fluid embolism (AFE) is a serious disease in which amniotic fluid components enter the maternal systemic circulation, causing cardiopulmonary collapse in pregnant women. It has been previously reported that amniotic fluid contains extremely high levels of squamous cell carcinoma antigen (SCCA), and that pregnant women who do not survive due to AFE have high blood SCCA levels. The aim of the present study was to determine the possible mechanisms through which SCCA in amniotic fluid enters the maternal blood, as well as the potential origin of SCCA. The prospective study included a cohort of 464 women (339 normal vaginal deliveries, 97 cesarean deliveries without labor, and 28 cesarean deliveries with labor). The dynamic changes in maternal serum SCCA levels were determined before and after delivery in relation to the mode of delivery, and SCCA levels were measured in the placenta, fetal skin, amniotic fluid cell components, amniotic fluid and neonatal urine. Serial serum samples collected at the time of admission, at 2 h postpartum, and on postpartum day 3 were quantitatively measured for SCCA by enzyme‑linked immunosorbent assay. Amniotic fluid and neonatal urine SCCA levels were also measured. The protein expression of SCCA in the placenta and fetal skin was assessed by immunohistochemistry. In vaginal deliveries, there was a significant increase in serum SCCA levels from admission to 2 h postpartum, and SCCA levels decreased on postpartum day 3. In cesarean deliveries, the SCCA levels at the time of admission and 2 h postpartum did not differ. The SCCA levels were significantly higher in women who underwent vaginal deliveries compared to those that underwent cesarean deliveries without labor (P=0.033). Immunohistochemical staining revealed no SCCA expression in the placenta and fetal skin. The SCCA levels in neonatal urine immediately after birth were as high as those in the amniotic fluid, suggesting that SCCA may originate from fetal urine. The present study thus suggests that amniotic fluid SCCA levels, which may be derived from fetal urine, can enter the maternal circulation during vaginal delivery. The onset of labor and full cervical dilatation are the main causes of entry of amniotic fluid components into the maternal circulation.博士（医学）・甲第796号・令和3年6月25日Copyright: © Nakano et al. This is an open access article distributed under the terms of Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc-nd/4.0/)

子宮内膜症性嚢胞の悪性転化におけるHO-1発現マクロファージの特徴

Malignant transformation of endometriosis is a rare and still poorly understood event, but is associated with the distortion of the pro-oxidant and anti-oxidant balance. The aim of the present study was to quantify the numbers of macrophages polarized as M1 or M2 phenotypes and the expression of heme oxygenase (HO)-1 in tissue sections from patients with benign ovarian endometrioma (OE) and its malignant transformation (endometriosis-associated ovarian cancer, EAOC). We performed a retrospective study at the Department of Gynecology, Nara Medical University hospital from December 2012 to March 2015. This study included 53 patients with OE (n = 33) and EAOC (n = 20), and we evaluated polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c, CD163 and HO-1. The number of the M1 phenotype (CD11c+, p = 0.001) and the M2 phenotype (CD163+, p = 0.009) was significantly lower in EAOC patients than in OE patients. Analyzing the correlations between the studied markers, the expression of CD68, CD11c, and CD163 proteins significantly correlated with each other (p < 0.001). The number of M2 phenotypes expressing HO-1 was significantly decreased in the EAOC group, compared with the OE group (P < 0.001), demonstrating sustained downregulation of an antioxidant marker, HO-1, in EAOC. In conclusion, reduced number of M2 macrophages expressing HO-1 may have an important role in promoting malignant transformation of OE.博士（医学）・乙第1434号・令和元年9月27日Copyright © 2018. Published by Elsevier GmbH

BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System

Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields

BATTLE: Genetically Engineered Strategies for Split-Tunable Allocation of Multiple Transgenes in the Nervous System

Elucidating fine architectures and functions of cellular and synaptic connections requires development of new flexible methods. Here, we created a concept called the “battle of transgenes,” based on which we generated strategies using genetically engineered battles of multiple recombinases. The strategies enabled split-tunable allocation of multiple transgenes. We demonstrated the versatility of these strategies and technologies in inducing strong and multi-sparse allocations of multiple transgenes. Furthermore, the combination of our transgenic strategy and expansion microscopy enabled three-dimensional high-resolution imaging of whole synaptic structures in the hippocampus with simultaneous visualizations of endogenous synaptic proteins. These strategies and technologies based on the battle of genes may accelerate the analysis of whole synaptic and cellular connections in diverse life science fields

Capsaicin, a TRPV1 Ligand, Suppresses Bone Resorption by Inhibiting the Prostaglandin E Production of Osteoblasts, and Attenuates the Inflammatory Bone Loss Induced by Lipopolysaccharide

Capsaicin, a transient receptor potential vanilloid type 1 (TRPV1) ligand, regulates nerve-related pain-sensitive signals, inflammation, and cancer growth. Capsaicin suppresses interleukin-1-induced osteoclast differentiation, but its roles in bone tissues and bone diseases are not known. This study examined the effects of capsaicin on inflammatory bone resorption and prostaglandin E (PGE) production induced by lipopolysaccharide (LPS) in vitro and on bone mass in LPS-treated mice in vivo. Capsaicin suppressed osteoclast formation, bone resorption, and PGE production induced by LPS in vitro. Capsaicin suppressed the expression of cyclooxygenase-2 (COX-2) and membrane-bound PGE synthase-1 (mPGES-1) mRNAs and PGE production induced by LPS in osteoblasts. Capsaicin may suppress PGE production by inhibiting the expression of COX-2 and mPGES-1 in osteoblasts and LPS-induced bone resorption by TRPV1 signals because osteoblasts express TRPV1. LPS treatment markedly induced bone loss in the femur in mice, and capsaicin significantly restored the inflammatory bone loss induced by LPS in mice. TRPV1 ligands like capsaicin may therefore be potentially useful as clinical drugs targeting bone diseases associated with inflammatory bone resorption

Effects of Aquatic Pole Walking on the Reduction of Spastic Hypertonia in a Patient with Hemiplegia: A Case Study

Here we report an acute effect of aquatic pole walking (PW) training intervention on a 64-year-old male patient with chronic hemiparesis and symptoms of spasticity in the right lower limb. A comparison of over ground walking before and after 20 minutes of aquatic PW training revealed a significant improvement in gait performance. As a main result, the average speed of walking after the intervention was 0.16 m/s after the intervention as compared to 0.04 m/s in the initial condition. The time taken for each stride cycle was drastically decreased, mainly due to shortening of the stance time. Underlying the improved gait performance was the emergence of functional muscle activity in the paralyzed and spastic leg muscles. The result observed in this patient should be further tested among a large population of patients presenting similar symptoms. Moreover, the basic mechanisms underlying aquatic PW intervention should be further elucidated

子宮筋層の内外層に発生する子宮腺筋症おける、それぞれの組織学的特徴

OBJECTIVE: To estimate the phenotypic characterization of fibrotic process in adenomyosis occurring at the inner or the outer myometrium. METHODS: Eight cases of adenomyosis occurring at the inner myometrium (Subtype I) and 10 cases of adenomyosis occurring at the outer myometrium (Subtype II), and 10 normal counterparts were used in this study. A immunohistochemical study for smooth muscle cells (SMCs) was performed using cytoskeletal proteins, Type I and III collagen, TGF-β and its signaling molecules. RESULTS: An increased expression of Type I collagen was observed in the extracellular matrix of adenomyotic foci. In normal uteri, immunostaining of SMC differentiation marker proteins (Desmin, Smoothelin, Myosin heavy chain (MHC)) were absent or only found in low numbers at the inner myometrium, while all of these marker proteins were clearly stained at the outer myometrium. In both types of adenomyotic foci, Desmin, Smoothelin, and MHC commonly showed a negative staining at the adjacent area to the glands. A significant staining of Non-muscle myosin IIB, TGF-β, and phosphorylated TGF-β type I receptors were found only at the SMCs of Subtype II adenomyosis. The Smad3/2 ratio of Subtype II adenomyosis was significantly higher than that of Subtype I. CONCLUSIONS: The inner myometrium of normal uteri was composed of undifferentiated phenotypes of SMCs, while the outer myometrium was composed of terminally differentiated SMCs. Various fibrotic processes have been suggested in the development of uterine adenomyosis. Distinct expression patterns of fibrosis related proteins have been shown to be implicated with differences in the subtypes of adenomyosis.博士（医学）・甲第681号・平成30年3月15日Copyright: © 2017 Kishi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Vitamin B6 in acute encephalopathy with biphasic seizures and late reduced diffusion

Background The initial presentation of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is indistinguishable from that of complex febrile seizures (FS), which poses a great diagnostic challenge for clinicians. Excitotoxicity is speculated to be the pathogenesis of AESD. Vitamin B6 (VB6) is essential for the biosynthesis of gamma-aminobutyric acid, an inhibitory neurotransmitter. The aim of this study is to investigate our hypothesis that VB6 deficiency in the brain may play a role in AESD. Methods We obtained cerebrospinal fluid (CSF) samples from pediatric patients with AESD after early seizures and those with FS. We measured pyridoxal 5′-phosphate (PLP) and pyridoxal (PL) concentrations in the CSF samples using high-performance liquid chromatography with fluorescence detection. Results The subjects were 5 patients with AESD and 17 patients with FS. Age did not differ significantly between AESD and FS. In AESD, CSF PLP concentration was marginally lower (p = 0.0999) and the PLP-to-PL ratio was significantly (p = 0.0417) reduced compared to those in FS. Conclusions Although it is impossible to conclude that low PLP concentration and PLP-to-PL ratio are causative of AESD, this may be a risk factor for developing AESD. When combined with other markers, this finding may be useful in distinguishing AESD from FS upon initial presentation

乳癌術前化学療法において腋窩リンパ節転移が陰性化するための効果予測因子の検討

Purpose: We investigated the role of tumor-infiltrating lymphocytes (TILs) in pretreatment primary breast cancer to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with clinical node-positive disease (cN +). Methods: The subjects of this study were 60 patients with cN + , who received NAC followed by breast surgery with axillary lymph node dissection (ALND). We conducted a semi-quantitative assessment of TILs in pretreatment primary tumors and their association with clinicopathological factors and axillary lymph node metastasis. Results: We observed a higher number of TILs in tumors with negative hormone receptors, positive human epidermal growth factor receptor 2, or high Ki67. TILs were associated with a favorable response to NAC in primary tumors. The rate of axillary pathologic complete response (Ax-pCR) was significantly higher in patients with a high number of TILs than in patients with a low number of TILs (72.0% versus 17.1%, p < 0.001). In multivariable analysis, a high number of TILs was a significant predictor of Ax-pCR as well as of pCR of the primary tumor after NAC. Importantly, all patients with HER2-positive tumors in the high TILs group showed Ax-pCR on ALND. Conclusion: TILs in pretreatment primary breast cancer had the potential to predict therapeutic efficacy of NAC in patients with clinical node-positive disease.博士（医学）・乙第1498号・令和3年3月15日© Springer Nature Singapore Pte Ltd. 2020This is a post-peer-review, pre-copyedit version of an article published in Surgery today. The final authenticated version is available online at: https://doi.org/10.1007/s00595-020-02157-6