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Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathologic events (e.g., epilepsy, ischemia, and axotomy). The roles of galanin in brain development under both normal and pathologic conditions have been hypothesized, but the question of how galanin is involved in fetal and early postnatal brain development remains largely unanswered. In this study, using granule cell migration in the cerebellum of early postnatal mice (both sexes) as a model system, we examined the role of galanin in neuronal cell migration during normal development and after brain injury. Here we show that, during normal development, endogenous galanin participates in accelerating granule cell migration via altering the Ca2+ and cAMP signaling pathways. Upon brain injury induced by the application of cold insults, galanin levels decrease at the lesion sites, but increase in the surroundings of lesion sites. Granule cells exhibit the following corresponding changes in migration: (1) slowing down migration at the lesion sites; and (2) accelerating migration in the surroundings of lesion sites. Experimental manipulations of galanin signaling reduce the lesion site-specific changes in granule cell migration, indicating that galanin plays a role in such deficits in neuronal cell migration. The present study suggests that manipulating galanin signaling may be a potential therapeutic target for acutely injured brains during development.SIGNIFICANCE STATEMENT Deficits in neuronal cell migration caused by brain injury result in abnormal development of cortical layers, but the underlying mechanisms remain to be determined. Here, we report that on brain injury, endogenous levels of galanin, a neuropeptide, are altered in a lesion site-specific manner, decreasing at the lesion sites but increasing in the surroundings of lesion sites. The changes in galanin levels positively correlate with the migration rate of immature neurons. Manipulations of galanin signaling ameliorate the effects of injury on neuronal migration and cortical layer development. These results shed a light on galanin as a potential therapeutic target for acutely injured brains during development.

DOI： 10.1523/JNEUROSCI.0900-15.2021

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Airway and intestinal epithelial permeability barriers are crucial in epithelial homeostasis. High mobility group box 1 (HMGB1), increased by various stimuli, is involved in the induction of airway inflammation, as well as the pathogenesis of inflammatory bowel disease. HMGB1 enhances epithelial hyperpermeability. Two-and-a-half dimensional (2.5D) culture assays are experimentally convenient and induce cells to form a more physiological tissue architecture than 2D culture assays for molecular transfer mechanism analysis. In 2.5D culture, treatment with HMGB1 induced permeability of FITC-dextran into the lumen formed by human lung, nasal and intestinal epithelial cells. The tricellular tight junction molecule angulin-1/LSR is responsible for the epithelial permeability barrier at tricellular contacts and contributes to various human airway and intestinal inflammatory diseases. In this review, we indicate the mechanisms including angulin-1/LSR and multiple signaling in dysfunction of the epithelial permeability barrier induced by HMGB1 in 2.5D culture of human airway and intestinal epithelial cells.

DOI： 10.1080/21688370.2021.1972760

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Withdrawal from contact inhibition is necessary for epithelial cancer precursor cells to initiate cell growth and motility. Nevertheless, little is understood about the mechanism for the sudden initiation of cell growth under static conditions. We focused on cellular junctions as one region where breaking out of contact inhibition occurs. In well-differentiated endometrial cancer cells, Sawano, the ligand administration for tricellular tight junction protein LSR, which transiently decreased the robust junction property, caused an abrupt increase in cell motility and consequent excessive multilayered cell growth despite being under contact inhibition conditions. We observed that macropinocytosis essentially and temporarily occurred as an antecedent event for the above process at intercellular junctions without disruption of the junction apparatus but not at the apical plasma membrane. Collectively, we concluded that the formation of macropinocytosis, which is derived from tight junction-mediated signaling, was triggered for the initiation of cell growth in static precancerous epithelium.

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1096/fj.202100299R

DOI： 10.1096/fj.202100299R

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This study aimed to examine the effects of voluntary wheel running on cancer cachexia-induced mitochondrial alterations in mouse skeletal muscle. Mice bearing colon 26 adenocarcinoma (C26) were used as a model of cancer cachexia. C26 mice showed a lower gastrocnemius and plantaris muscle weight, but 4 weeks of voluntary exercise rescued these changes. Further, voluntary exercise attenuated observed declines in the levels of oxidative phosphorylation proteins and activities of citrate synthase and cytochrome c oxidase in the skeletal muscle of C26 mice. Among mitochondrial morphology regulatory proteins, mitofusin 2 (Mfn2) and dynamin-related protein 1 (Drp1) were decreased in the skeletal muscle of C26 mice, but exercise resulted in similar improvements as seen in markers of mitochondrial content. In isolated mitochondria, 4-hydroxynonenal and protein carbonyls were elevated in C26 mice, but exercise blunted the increases in these markers of oxidative stress. In addition, electron microscopy revealed that exercise alleviated the observed increase in the percentage of damaged mitochondria in C26 mice. These results suggest that voluntary exercise effectively counteracts mitochondrial dysfunction to mitigate muscle loss in cachexia.

DOI： 10.14814/phy2.15016

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The epithelial-mesenchymal transition (EMT) is an essential step in cancer progression. Epithelial cells possess several types of cell-cell junctions, and tight junctions are known to play important roles in maintaining the epithelial program. EMT is characterized by a loss of epithelial markers, including E-cadherin and tight junction proteins. Somewhat surprisingly, the evidence is accumulating that upregulated expression of tight junction proteins plays an important role in the EMT of cancer cells. Tight junctions have distinct tissue-specific and cancer-specific regulatory mechanisms, enabling them to play different roles in EMT. Tight junctions and related signaling pathways are attractive targets for cancer treatments; signal transduction inhibitors and monoclonal antibodies for tight junction proteins may be used to suppress EMT, invasion, and metastasis. Here we review the role of bicellular and tricellular tight junction proteins during EMT. Further investigation of regulatory mechanisms of tight junctions during EMT in cancer cells will inform the development of biomarkers for predicting prognosis as well as novel therapies.

DOI： 10.1016/j.bbamem.2020.183503

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The force-length relation of the skeletal muscles is an important factor influencing the joint torque at a given joint angle. We aimed to clarify the relationship between the resting sarcomere length and knee joint angle in the vastus intermedius (VI) and to compare it with that of the vastus lateralis (VL). The left and right legs were fixed at knee joint angles of 0° and 90°, respectively, in seven cadavers (age at the time of death: 70-91 years). Muscle tissues were dissected by necropsy of the VL and the VI, and electron microscopy images were obtained to calculate the sarcomere length. At knee joint angles of 0° and 90°, the VL sarcomere length was 2.28 ± 0.49 μm and 2.30 ± 0.48 μm, respectively, and the VI sarcomere length was 2.19 ± 0.35 μm and 2.46 ± 0.53 μm, respectively, with a significant difference between the two (p = 0.028). The magnitude of sarcomere length changes with knee joint angle changes was significantly greater for the VI (0.27 ± 0.20 μm) than for the VL (0.02 ± 0.09 μm) (p = 0.009). Thus, knee joint angle changes may affect the passive and active tension produced by the VI more than those produced by the VL.

DOI： 10.14814/phy2.14771

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High mobility group box 1 protein (HMGB1) is involved in the pathogenesis of inflammatory bowel disease (IBD). Patients with IBD develop zinc deficiency. However, the detailed roles of HMGB1 and zinc deficiency in the intestinal epithelial barrier and cellular metabolism of IBD remain unknown. In the present study, Caco-2 cells in 2D culture and 2.5D Matrigel culture were pretreated with transforming growth factor-β (TGF-β) type 1 receptor kinase inhibitor EW-7197, epidermal growth factor receptor (EGFR) kinase inhibitor AG-1478 and a TNFα antibody before treatment with HMGB1 and inflammatory cytokines (TNFα and IFNγ). EW-7197, AG-1478 and the TNFα antibody prevented hyperpermeability induced by HMGB1 and inflammatory cytokines in 2.5D culture. HMGB1 affected cilia formation in 2.5D culture. EW-7197, AG-1478 and the TNFα antibody prevented the increase in cell metabolism induced by HMGB1 and inflammatory cytokines in 2D culture. Furthermore, ZnSO4 prevented the hyperpermeability induced by zinc chelator TPEN in 2.5D culture. ZnSO4 and TPEN induced cellular metabolism in 2D culture. The disruption of the epithelial barrier induced by HMGB1 and inflammatory cytokines contributed to TGF-β/EGF signaling in Caco-2 cells. The TNFα antibody and ZnSO4 as well as EW-7197 and AG-1478 may have potential for use in therapy for IBD.

DOI： 10.3390/ijms21228434

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Apoptosis-stimulating p53 protein 2 (ASPP2) is an apoptosis inducer that acts via binding with p53 and epithelial polarity molecule PAR3. Lipolysis-stimulated lipoprotein receptor (LSR) is an important molecule at tricellular contacts, and loss of LSR promotes cell migration and invasion via Yes-associated protein (YAP) in human endometrial cancer cells. In the present study, to find how ASPP2 suppression promotes malignancy in human endometrial cancer, we investigated its mechanisms including the relationship with LSR. In endometriosis and endometrial cancers (G1 and G2), ASPP2 was observed as well as PAR3 and LSR in the subapical region. ASPP2 decreased in G3 endometrial cancer compared to G1. In human endometrial cancer cell line Sawano, ASPP2 was colocalized with LSR and tricellulin at tricellular contacts and binding to PAR3, LSR, and tricellulin in the confluent state. ASPP2 suppression promoted cell migration and invasion, decreased LSR expression, and induced expression of phosphorylated YAP, claudin-1, -4, and -7 as effectively as the loss of LSR. Knockdown of YAP prevented the upregulation of pYAP, cell migration and invasion induced by the ASPP2 suppression. Treatment with a specific antibody against ASPP2 downregulated ASPP2 and LSR, affected F-actin at tricellular contacts, upregulated expression of pYAP and claudin-1, and induced cell migration and invasion via YAP. In normal human endometrial epithelial cells, ASPP2 was in part colocalized with LSR at tricellular contacts and knockdown of ASPP2 or LSR induced expression of claudin-1 and claudin-4. ASPP2 suppression promoted cell invasion and migration via LSR and YAP in human endometrial cancer cells.

DOI： 10.1007/s00418-020-01876-8

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Epithelial integrity and barrier function are maintained during cytokinesis in vertebrate epithelial tissues. The changes in localization and the roles of tricellular tight junction molecule lipolysis-stimulated lipoprotein receptor (LSR) during cytokinesis are not well known, although new tricellular tight junctions form at the flank of the midbody during cytokinesis. In this study, we investigated the changes in localization and the role of LSR at the midbody and centrosome during cytokinesis using human endometrial carcinoma cell line Sawano, comparing the tricellular tight junction molecule tricellulin; bicellular tight junction molecules occludin, claudin-7, zonula occludens-1, and cingulin; and the epithelial polarized related molecules apoptosis-stimulating of p53 protein 2, PAR3, and yes-associated protein. During cytokinesis induced by treatment with taxol, the epithelial barrier was maintained and the tricellular tight junction molecules LSR and tricellulin were concentrated at the flank of the acetylated tubulin-positive midbody and in γ-tubulin-positive centrosomes with the dynein adaptor Hook2, whereas the other molecules were localized there as well. All the molecules disappeared by knockdown using small interfering RNAs. Furthermore, by the knockdown of Hook2, the epithelial barrier was maintained and most of the molecules disappeared from the centrosome. These findings suggest that LSR may play crucial roles not only in barrier function but also in cytokinesis.

DOI： 10.1369/0022155419886263

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Lipolysis-stimulated lipoprotein receptor (LSR)/angulin-1 is a crucial molecule of tricellular contacts in the epithelial barrier of normal cells and the malignancy of cancer cells. To investigate whether LSR/angulin-1 affects the epithelial barrier and malignancy in human pancreatic cancer, human pancreatic cancer cell line HPAC was used. Treatment with EGF or TGF-β increased the expression of LSR, but not tricellulin (TRIC), and induced the localization of LSR and TRIC to bicellular tight junctions from tricellular tight junctions. TGF-β receptor type-1 inhibitor EW-7197 prevented changes of the distribution and the barrier function of LSR by TGF-β. Knockdown of LSR increased cell migration, invasion, proliferation and EGF ligand amphiregulin expression and decreased the epithelial barrier. Treatment with amphiregulin induced cell migration and invasion and knockdown of amphiregulin prevented the increases of cell migration, invasion and proliferation caused by knockdown of LSR. Treatment with LSR ligand peptide angubindin-1 decreased the epithelial barrier and the expression of LSR, but not TRIC, and increased cell invasion. Knockdown of TRIC decreased cell migration and the epithelial barrier. In immunohistochemical analysis of human pancreatic cancer tissues, LSR and TRIC were found to be localized at the cell membranes of normal pancreatic ducts and well-differentiated pancreatic ductal adenocarcinomas (PDAC), whereas in poorly differentiated PDAC, LSR was weakly detected in the cytoplasm. Amphiregulin was highly expressed in the cytoplasm of well- and poorly differentiated PDAC. In pancreatic cancer, LSR contributes to the epithelial barrier and malignancy via growth factors and may be a potential targeting molecule in the therapy.

DOI： 10.1007/s00418-019-01821-4

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Angulin-1/LSR is a tricellular tight junction molecule, that plays an important role in maintaining the epithelial and endothelial barriers. The actin cytoskeleton at tricellular contacts also contributes to the maintenance of the epithelial barrier. Loss of angulin-1/LSR enhances the migration of various cancer cells. Angubindin-1 is a novel binder to angulin-1/LSR and angulin-3. It is a peptide generated from the angulin-1 binding site of Clostridium perfringens iota toxin, which affects the actin cytoskeleton and decreases the epithelial and endothelial barrier functions. However, its regulatory mechanisms are not well understood. To investigate the regulatory mechanisms of the epithelial barrier dysfunction and cell migration induction by angubindin-1, we used human endometrial cancer cell line Sawano, which has high LSR expression and the epithelial barrier function. Angubindin-1 decreased LSR expression and the epithelial barrier function and increased cell migration. It inhibited the recovery of the epithelial barrier function in a Ca-switch model. At tricellular contacts, sinking of the membrane and an increase of actin fibers near the junctions were caused by angubindin-1. It dynamically changed F-actin from lines to dot-like structures at tricellular contacts. Angubindin-1 transiently increased the phosphorylation of cofilin and JNK, which are involved in the regulation of the intracellular actin cytoskeleton. Furthermore, knockdown of JNK and the JNK inhibitor SP600125 prevented the decrease of the epithelial barrier function and the increase of cell migration induced by angubindin-1. These findings suggest that angubindin-1 might reversibly regulate the epithelial barrier and cell migration at tricellular contacts via JNK/cofilin/actin cytoskeleton dynamics.

DOI： 10.1080/21688370.2019.1695475

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Language：Japanese   Publisher：東北連合産科婦人科学会・北日本産科婦人科学会  

Ichushi

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Primary cilia, regulated via distinct signal transduction pathways, play crucial roles in various cellular behaviors. However, the full regulatory mechanism involved in primary cilia development during cellular differentiation is not fully understood, particularly for the sensory hair cells of the mammalian cochlea. In this study, we investigated the effects of the Rho-kinase inhibitor Y27632 and PKCα inhibitor GF109203X on primary cilia-related cell behavior in undifferentiated and differentiated temperature-sensitive mouse cochlear precursor hair cells (the conditionally immortalized US/VOT-E36 cell line). Our results indicate that treatment with Y27632 or GF109203X induced primary cilia elongation and tubulin acetylation in both differentiated and undifferentiated cells. Concomitant with cilia elongation, Y27632 treatment also increased Hook2 and cyclinD1 expression, while only Hook2 expression was increased after treatment with GF109203X. In the undifferentiated cells, we observed an increase in the number of S and G2/M stage cells and a decrease of G1 cells after treatment with Y27632, while the opposite was observed after treatment with GF109203X. Finally, while both treatments decreased oxidative stress, only treatment with Y27632, not GF109203X, induced cell cycle-dependent cell proliferation and cell migration.

DOI： 10.1369/0022155419841013

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The underlying therapeutic mechanism of renal tubular epithelium repair of diabetic nephropathy (DN) by bone marrow-derived mesenchymal stem cells (BM-MSCs) has not been fully elucidated. Recently, mitochondria (Mt) transfer was reported as a novel action of BM-MSCs to rescue injured cells. We investigated Mt transfer from systemically administered BM-MSCs to renal proximal tubular epithelial cells (PTECs) in streptozotocin (STZ)-induced diabetic animals. BM-MSCs also transferred their Mt to impaired PTECs when co-cultured in vitro, which suppressed apoptosis of impaired PTECs. Additionally, BM-MSC-derived isolated Mt enhanced the expression of mitochondrial superoxide dismutase 2 and Bcl-2 expression and inhibited reactive oxygen species (ROS) production in vitro. Isolated Mt also inhibited nuclear translocation of PGC-1α and restored the expression of megalin and SGLT2 under high glucose condition (HG) in PTECs. Moreover, isolated Mt directly injected under the renal capsule of STZ rats improved the cellular morphology of STZ-PTECs, and the structure of the tubular basement membrane and brush border in vivo. This study is the first to show Mt transfer from systemically administered BM-MSCs to damaged PTECs in vivo, and the first to investigate mechanisms underlying the potential therapeutic effects of Mt transfer from BM-MSCs in DN.

DOI： 10.1038/s41598-019-40163-y

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Cobalt is a trace element that localizes in the human body as cobalamin, also known as vitamin B12. Excessive cobalt exposure induces a peripheral neuropathy, the mechanisms of which are yet to be elucidated. We investigated how cobalt may affect mitochondrial motility in primary cultures of rat dorsal root ganglion (DRG). We observed mitochondrial motility by time-lapse imaging after DsRed2 tagging via lentivirus, mitochondrial structure using transmission electron microscopy (TEM), and axonal swelling using immunocytochemical staining. The concentration of cobaltous ion (Co2+) required to significantly suppress mitochondrial motility is lower than that required to induce axonal swelling following a 24-h treatment. Exposure to relatively low concentrations of Co2+ for 48 h suppressed mitochondrial motility without leading to axonal swelling. TEM images indicated that Co2+ induces mitochondrial destruction. Our results show that destruction of the axonal mitochondria precedes the axonal degeneration induced by Co2+ exposure.

DOI： 10.1007/s10565-017-9402-0

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DOI： 10.1038/s41598-017-11481-w

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DOI： 10.1371/journal.pone.0182291

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DOI： 10.1111/nyas.13362

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Language：Japanese   Publisher：公益社団法人 日本皮膚科学会  

<p>クラウドを流れる情報を，どの様に活用するかが重要である．そこで，原点に戻り，情報の定義を「人の心を動かすもの」とすると，分子生物学的に「細胞を動かすもの」といえ，医療に活用できるところから「情報薬」という発想に辿り着いた．例えば，医療情報の氾濫による弊害は一種の社会病であり，「情報薬」により予防できる．そこでクラウド活用のためのワイドスペクトラムな「情報薬」について説明し，その応用について述べる．</p>

DOI： 10.14924/dermatol.127.2455

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DOI： 10.1007/s00418-014-1300-4

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DOI： 10.1124/mol.114.096982

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DOI： 10.1007/s00401-014-1354-3

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Language：Japanese   Publisher：(一社)日本解剖学会  

Ichushi

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DOI： 10.1369/jhc.2010.956326

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DOI： 10.1002/jcp.22273

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DOI： 10.1679/aohc.73.81

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DOI： 10.1007/s00795-009-0470-y

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DOI： 10.1007/s00441-008-0635-3

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DOI： 10.1007/s10735-008-9162-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：1  

DOI： 10.1298/jjpta.11.23

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DOI： 10.1016/j.pediatrneurol.2004.1

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：5  

DOI： 10.11251/ojjscn1969.35.380

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J-GLOBAL

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Other Link:： http://search.jamas.or.jp/link/ui/2017085857

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J-GLOBAL

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Language：Japanese   Publisher：The Institute of Electronics, Information and Communication Engineers  

Other Link:： http://search.jamas.or.jp/link/ui/2014391796

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Language：Japanese   Publisher：バイオメカニズム学会  

戦略防衛構想(SDI : Strategic Defense Initiative) では，IT をフル利活用しミサイルが飛んで来るのを逸早く察知して，その軌道を綿密にすばやく計算し，タイミングよく空中で破壊する。このことにより積極的な攻撃は行わず，究極の防衛を実現している。このことにヒントを得て，医療系で実現しようというものが，我々の提案している戦略的防衛医療構想(SDMCI :Strategic Defensive Medica1-Care Initiative) である。 超予防医療としてのこの構想は，Ver.1.0 から始まり，現在では，Ver.3.0 に達している。これらを推進し実現する為の強力な武器は「情報薬」で，IT 及び情報科学との融合が，これからの21 世紀の医療には必須のものとなる。その要素としてのゼロクリック，どこでも逆ナースコール，そして，ユビキタスセンサーネットワークの解説と、その応用例を示した。

DOI： 10.3951/sobim.35.113

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DOI： 10.15114/bshs.13.21

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DOI： 10.15114/bshs.13.13

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Language：English   Publishing type：Research paper, summary (international conference)  

DOI： 10.1016/j.neures.2011.07.1007

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DOI： 10.1016/j.neures.2010.07.1069

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Language：Japanese   Publisher：Japanese Physical Therapy Association (JPTA)  

Purpose: Ataxia-oculomotor apraxia type 1 (AOA1) is responsible for the mutation of aprataxin gene. The aprataxin gene, located on chromosome 9p13.3, has seven exons. Alternative splicing in exon 3 generates two distinct isoforms, the longer transcript encodes for a 342 amino acid protein, while the shorter one encodes a 174 amino acid protein. The function of aprataxin is considered to play an important role in single-strand break repair. Clinical features of AOA1 patients show ataxic gait before 10 years of age; slowly progressive cerebellar dysfunction including nystagmus and dysarthria. The peripheral neuropathy has been disclosed with aging. Evaluation of peripheral neuropathy is important to perform physical therapy in AOA1 patients. Method: In this study, we evaluated involvement of peripheral neuropathy by motor nerve conduction velocity, Neuropathy Disability Score and Medical Research Council sum-score and cerebellar dysfunction by International Cooperative Ataxia Rating Scale in two patients with AOA1. Result: The motor nerve conduction velocity was slightly delayed on thirty-age, moderately on forty-age, respectively. Severe cerebellar dysfunction and muscle weakness and atrophy of distal lower extremities due to peripheral neuropathy were disclosed. Conclusions: It is important to perform physical therapy for cerebellar dysfunction and peripheral neuropathy in young age patients with AOA1.

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DOI： 10.15114/smj.77.1

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Language：Japanese   Publisher：公益社団法人日本理学療法士協会  

【諸言】常染色体劣性遺伝性脊髄小脳変性症のひとつである、眼球運動失行を伴う失調症（AOA1）はaprataxin遺伝子の変異により起こる疾患である。この遺伝子の翻訳するタンパクは一本鎖遺伝子損傷修復機能を有することが確認されている。疾患の発症時期は10歳以前であり、発症早期より失調症状が認められ、その後、疾患の進行とともに末梢神経障害が著明となる。成人期AOA1患者の小脳症状と末梢神経障害の臨床症状を知ることは、予後を予測した理学療法を行うために重要である。また、一過性の過負荷の運動は遺伝子やタンパクの損傷を引き起こし、逆に規則的で適度な運動は損傷を一定に保つか減少させることが知られており、AOA1患者の臨床症状における遺伝子損傷レベルを知ることは適切な運動量・強度の処方の上で重要な指標となる。<BR>【方法】対象はAOA1患者（689insT）の姉妹（44歳、48歳）であった。末梢神経症状の量的評価として運動神経伝導速度の計測を行った。対象神経は、上肢は尺骨神経、下肢は腓骨神経とした。重症度は厚生省運動失調調査研究班によるSCDの重症度分類、小脳症状はInternational Cooperative Ataxia Rating Scale、末梢神経症状はNeuropathy Disability Score、筋力評価はMedical Research Council sum score（MRCS）を用い、質的評価を行った。遺伝子損傷レベルの測定は平常時の尿中8-ヒドロキシデオキシグアノシン（以下8-OHdG）濃度測定を行い、40代女性10名（43.3±2.1歳；41～46歳）を対照群とした。各被検者に対し、本研究の説明を行い、書面にて同意を得た。<BR>【結果】神経伝導速度は、尺骨神経では21.2m/s、20.5 m/s、腓骨神経では計測不能で、尺骨神経では20歳代から40歳代の約15年で20m/s程度の低下が認められた。質的評価により、重度の小脳失調と、特に末梢部・下肢に強い筋力低下が認められることが明らかとなった。尿中8-OHdGでは、対照群は3.7±1.2ng/mg、AOA1患者はそれぞれ4.0ng/mg、7.3ng/mgであり、対照群との差は認められなかった。<BR>【考察】成人期AOA1患者の臨床症状の評価により、より早期に小脳症状に対する理学療法のみでなく、末梢神経障害を考慮した身体局所の選択的筋力強化、関節変形・拘縮の予防的運動療法などの理学療法を行うことが重要になると考えられた。平常時の尿中8-OHdGは対照群との差が認められなかったが、過負荷な運動はAOA1患者の病状の進行を助長してしまう可能性があることを考慮すると、今後、理学療法前後の尿中8-OHdGの測定を行う必要があると考える。

DOI： 10.14900/cjpt.2007.0.B1567.0

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Language：Japanese   Publisher：文光堂  

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Language：English  

DOI： 10.1298/jjpta.11.23

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Language：Japanese  

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Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

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Language：Japanese   Publisher：日本重症心身障害学会  

Ichushi

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Language：Japanese   Publisher：公益社団法人日本理学療法士協会  

DOI： 10.14900/cjpt.2005.0.B0212.0

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Language：Japanese   Publisher：公益社団法人 日本理学療法士協会  

【はじめに】&lt;BR&gt; 先天性筋強直性ジストロフィー症（congenital myotonic dystrophy;以下CDM）は常染色体優性遺伝疾患で、生下時のリスクと尖足もしばしば指摘される。しかし、新生児期を乗り越えた後は、緩やかに運動発達し歩行を獲得する症例が多い。そのため足部に対しての治療は重要となってくる。今回、足部変形が運動発達を阻害していた為、手術が施行されたCDM児2例の理学療法経過を報告する。&lt;BR&gt;【症例1】&lt;BR&gt; 39週5日3270gで出生、男児。母親は成人型筋強直性ジストロフィー（myotonic dystrophy;以下DM）を発症。生下時より両側内反尖足を認めていたが、全身状態不良にて殆ど未治療。生後8ヶ月よりPT介入を開始、運動発達は進み掴まり立ちを意欲的に行うも、変形は進行し足関節背屈角度は右-30°左-60°、足背接地する様になる。2歳6ヶ月で、足関節周囲筋解離術を施行、術後療法の後3歳で独歩獲得。その後、足部背屈角度は、右30°左25°迄拡大しているが、外反扁平足を呈する。その後走行、ジャンプも可能となる。&lt;BR&gt;【症例2】&lt;BR&gt; 31週1866gで出生、男児。母親はDMを発症。呼吸窮迫症候群により74日間人工換気。生後8か月 PT介入を開始、足背屈角度は右15°左30°であった。4歳で独歩獲得するも、右足部は外反尖足に移行し、右足背屈角度は-30°で踵接地不能、膝反張して歩行。4才9ヶ月時に、右足関節周囲筋解離術を施行した。術後療法の後、右足背屈角度は5°、装具装着で歩容の改善を見る。&lt;BR&gt;【考察】&lt;BR&gt;CDM児の足部変形においては、早期の装具・徒手的アプローチは有効とされるが、生下時リスクにより介入が遅れた場合、変形は進行していく。今回一側足部と両足部の違いはあったが、機能的なアライメントの獲得に向けて最小限の筋解離術及び術後療法へと転換し、良好な経過が得られた。いかなる場合でも、介入開始からの可動域管理と体幹機能を含む粗大運動全般の発達支援の継続は必須である。&lt;BR&gt; 2症例とも、発達指標の時期については類似が見られ、手術の時期に関わらず独歩を獲得した。しかし、手術時期が遅い例の方が、早い例に比べ、約1年の遅れが見られた。運動発達は独歩を目標として積極的に行い、足部の状態に応じて手術も選択肢に入れ適宜方向修正していくことが望ましい。&lt;BR&gt; CDMは、第19染色体長腕にある3塩基対反復配列数が増加しており、これに発症年齢・重症度は関連するとされている。親から子に伝わった場合のリピート数が増加する（anticipation効果）傾向にあり、本2症例も母親はDM患者である。母親の症状の程度によっては、養育環境での運動発達支援が非常に大変になる事があるので、家族状況を含めて、身体・精神面両方に考慮したアプローチが重要になると考える。

DOI： 10.14900/cjpt.2005.0.B0212.0

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Language：English   Publishing type：Research paper, summary (international conference)  

Web of Science

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Language：Japanese   Publisher：日本重症心身障害学会  

Ichushi

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Language：Japanese   Publisher：Sapporo Medical University  

DOI： 10.15114/smj.74.39

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Language：Japanese   Publisher：公益社団法人日本理学療法士協会  

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Language：Japanese   Publisher：公益社団法人日本理学療法士協会  

DOI： 10.14900/cjpt.2004.0.B0261.0

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Language：English  

DOI： 10.1016/j.pediatrneurol.2004.1

Web of Science

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Language：Japanese   Publisher：医学書院  

DOI： 10.11477/mf.1552100047

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Language：Japanese   Publisher：Sapporo Medical University  

DOI： 10.15114/bshs.6.43

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Language：Japanese   Publisher：Sapporo Medical University  

DOI： 10.15114/bshs.6.49

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Language：Japanese  

DOI： 10.11251/ojjscn1969.35.380

PubMed

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Language：Japanese  

DOI： 10.11251/ojjscn1969.35.380

PubMed

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