検索結果 18181 件
| 著者 | 齋藤 昇| |
|---|---|
| 発行日 | 2014-04 |
| 出版物タイトル | 岡山実験動物研究会報 |
| 巻 | 30巻 |
| 資料タイプ | その他 |
| 著者 | 織田 銑一| |
|---|---|
| 発行日 | 2014-04 |
| 出版物タイトル | 岡山実験動物研究会報 |
| 巻 | 30巻 |
| 資料タイプ | その他 |
| 著者 | 平井 成幸| |
|---|---|
| 発行日 | 1996-03 |
| 出版物タイトル | 中部日本整形外科災害外科学会雑誌 |
| 巻 | 39巻 |
| 号 | 2号 |
| 資料タイプ | 学術雑誌論文 |
| 著者 | 吉村 一穂| |
|---|---|
| 発行日 | 1992-09 |
| 出版物タイトル | 中部日本整形外科災害外科学会雑誌 |
| 巻 | 35巻 |
| 号 | 5号 |
| 資料タイプ | 学術雑誌論文 |
| 著者 | Fujiwara, Masaru| Hamatake, Yuko| Arimoto, Sakae| Okamoto, Keinosuke| Suzuki, Toshinori| Negishi, Tomoe| |
|---|---|
| 発行日 | 2011-08-12 |
| 出版物タイトル | Genes and Environment |
| 巻 | 33巻 |
| 号 | 3号 |
| 資料タイプ | 学術雑誌論文 |
| 著者 | Fang, Xing| Nunoshiba, Tatsuo| Yoshida, Midori| Nishikawa, Akiyoshi| Nemoto, Kiyomitsu| Degawa, Masakuni| Arimoto, Sakae| Okamoto, Keinosuke| Takahashi, Eizo| Negishi, Tomoe| |
|---|---|
| 発行日 | 2014-02-28 |
| 出版物タイトル | Genes and Environment |
| 巻 | 36巻 |
| 号 | 1号 |
| 資料タイプ | 学術雑誌論文 |
| JaLCDOI | 10.18926/bgeou/52429 |
|---|---|
| タイトル（別表記） | Proton Magnetic Resonance Spectroscopy in Patients with Migration Disorders |
| フルテキストURL | 110_0029_0034.pdf |
| 著者 | 眞田 敏| 浅野 孝| 岡 鍈次| 河原 道子| 栄 勝美| 平木 祥夫| 大田原 俊輔| |
| 抄録 | Proton Magnetic Resonance Spectroscopy (1H-MRS) can be used to detect cerebral metabolites including N-acetylaspartate (NAA)，creatine (Cr) and choline (Ch). Hence，clinical applications of this method for neuropediatric diseases can be expected. However，regarding neuronal migration disorders，there have been only a few reported studies. We therefore examined the lH-MRS in six patients with migration disorders，ages ranged from 8months to 28years 10months with a mean of 10years 10months. Investigation was performed using Magnetom H15 (Siemens) with a repetition time of 1500 msec and an echo time of 270msec. The ratio of NAA/Cr，Ch/Cr were examined. The volume of interest with the size of 2 × 2 × 2 ～ 3 × 3 × 5cm3 was chosen in the area including lesions，and a contralateral area without lesions was also investigated. Results were as follows. 1) The ratio of NAA/Cr was low in the area with lesions in all 6cases; 1.41，1.95，2.27 and 1.71 in cases with heterotopic gray matter，0.99 in one case with polymicrogyria，an d 1.30 in one case with hemimegalencephaly，contrasted with a contralataral area without lesions: 1.89， 2.89，2.87，2.55，3.26，2.03，respectively. 2) The ratio of Ch/Cr showed no consistent difference between the area including lesions and contralataral area without lesions. Our findings of a decreased NAA/Cr ratio can be inferred to reflect the decreased numbers of neuronal cell population，or reduced metabolism in the lesions. |
| キーワード | MR spectroscopy migration disorder heterotopic gray matter polymicrogyria hemimegalencephaly |
| 出版物タイトル | 岡山大学教育学部研究集録 |
| 発行日 | 1999-03-15 |
| 巻 | 110巻 |
| 開始ページ | 29 |
| 終了ページ | 34 |
| ISSN | 0471-4008 |
| 言語 | 日本語 |
| 論文のバージョン | publisher |
| NAID | 120005425646 |
| JaLCDOI | 10.18926/bgeou/52428 |
|---|---|
| タイトル（別表記） | Assessment of the brain function by evoked potentials: analysis of the late components of visual evoked potentials recorded from the vertex |
| フルテキストURL | 116_0091_0095.pdf |
| 著者 | 眞田 敏| 柳原 正文| 林 優子| |
| 抄録 | Visual evoked potentials recorded from the vertex were studied in seventy four individuals with mental retardation，ranging from l old to 50 years old. They were classified into 4 groups according to the level of IQ/DQ，and the relation between the late components and the intellectual level was exarnined. In 9 of 74 cases(12.2%)，la tency of the N130 component was prolonged and in 7 of 74 cases (9.6%)，the P190 component was prolonged. There was，however，no correlation between the number of the cases with prolonged N130 or P190 latency and the level of IQ/DQ. Cases with prolongation in N130 and/or Pl90 were almost exclusively found among those with such complications as cerebral palsy and/or epilepsy，while few cases without complications showed prolongation. From these results，it is suggested that the prolongation in the late components developes reflecting the presence of the organic lesions that have a common causative potent producing cerebral palsy and/or epilepsy. |
| キーワード | brain function mental retardation visual evoked potentials cerebral palsy epilepsy |
| 出版物タイトル | 岡山大学教育学部研究集録 |
| 発行日 | 2001-03-15 |
| 巻 | 116巻 |
| 開始ページ | 91 |
| 終了ページ | 95 |
| ISSN | 0471-4008 |
| 言語 | 日本語 |
| 論文のバージョン | publisher |
| NAID | 120005425645 |
| JaLCDOI | 10.18926/bgeou/52425 |
|---|---|
| タイトル（別表記） | Suggestions for Safe Motorchair Football. |
| フルテキストURL | 120_0087_0092.pdf |
| 著者 | 眞田 敏| 目時 英治| 柳原 正文| |
| 抄録 | 本研究は電動車椅子サッカーの岡山県における活動状況を把握し，このスポーツを安全に行う方法について検討することを目的とした。対象は脊髄損傷(A群)，脳性麻痺(B群)，筋ジストロフイー(C群)の選手各々4名， 5名および4名の計13名で，平成13年8月24日から平成13年12月23日までに行なわれた計8日の練習および試合をビデオカメラを用いて撮影し分析した。平成13年12月14日までの練習状況から電動車椅子同士の衝突により生じるスピン，身体接触，電動車椅子の浮揚の危険な衝突に着目し，平成13年12月23日に行なわれた3試合，計120分のなかで危険な衝突に関して分析を行った。その結果， A群では 危険な衝突が19回， BおよびC群でも計19回みられた。それらの内，衝突後の防御姿勢の有無に関してA群は認められた回数が17回，認められなかった回数が2回であった。B群およびC群では，認められた回数がl回，認められなかった回数が18回であった。A群とB・C群間での防御姿勢の有無に関する差異は有意(x2検定， p < 0.01) であった。以上より障害種別によるクラス分けの必要性が明らかになった。さらにヘルメットやプロテクターの着用の重要性に関しての指摘も行い，指導員の養成の必要性についても考察した。 |
| キーワード | 電動車椅子サッカー 脊髄損傷 脳性麻痺 筋ジストロフィー |
| 出版物タイトル | 岡山大学教育学部研究集録 |
| 発行日 | 2002-07-15 |
| 巻 | 120巻 |
| 開始ページ | 87 |
| 終了ページ | 92 |
| ISSN | 0471-4008 |
| 言語 | 日本語 |
| 論文のバージョン | publisher |
| NAID | 120005425643 |
| 著者 | Sakata, Kenichiro| Furumatsu, Takayuki| Miyazawa, Shinichi| Okada, Yukimasa| Fujii, Masataka| Ozaki, Toshifumi| |
|---|---|
| 発行日 | 2013-01 |
| 出版物タイトル | International Orthopaedics |
| 巻 | 37巻 |
| 号 | 1号 |
| 資料タイプ | 学術雑誌論文 |
| 著者 | Putranto, Endy Widya| Murata, Hitoshi| Yamamoto, Ken-Ichi| Kataoka, Ken| Yamada, Hidenori| Futami, Jun-Ichiro| Sakaguchi, Masakiyo| Huh, Nam-Ho| |
|---|---|
| 発行日 | 2013-10 |
| 出版物タイトル | International Journal of Molecular Medicine |
| 巻 | 32巻 |
| 号 | 4号 |
| 資料タイプ | 学術雑誌論文 |
| JaLCDOI | 10.18926/bgeou/52411 |
|---|---|
| フルテキストURL | 129_117_122.pdf |
| 著者 | Sanada, Satoshi| Chumioque, Cecilia| |
| 抄録 | The differences and similarities between the Japanese and Peruvian Special Education practice，considering aspects like，educational approaches used，communication strategies to deal with non-verbal students and the education system in general，were explored. Teachers of intellectual disabled children in Japan (30) and Peru (30) were the participants who completed a questionnaire developed by the researcher to determine the different ways of teaching in both countries. Results indicate important differences in the practice of special education between the groups，but some coincidences in the limitations teachers have in this field. The importance of inclusion doctrine in both countries and the role it plays in thespecial education system was found to be considerable. Implications include the need of an individualized education for students with special educational needs. |
| キーワード | educational approaches inclusion applied behavior analysis (ABA) TEACCH picture exchange communication system (PECS) |
| 出版物タイトル | 岡山大学教育学部研究集録 |
| 発行日 | 2005-07-15 |
| 巻 | 129巻 |
| 開始ページ | 117 |
| 終了ページ | 122 |
| ISSN | 0471-4008 |
| 言語 | 英語 |
| 論文のバージョン | publisher |
| NAID | 120005425634 |
| フルテキストURL | Talanta_122_240–245.pdf |
|---|---|
| 著者 | Higashidani, Naoki| Kaneta, Takashi| Takeyasu, Nobuyuki| Motomizu, Shoji| Okibe, Naoko| Sasaki, Keiko| |
| キーワード | Thermoacidophilic iron-oxidizing archaeon Acidianus brierleyi Arsenic Speciation Inductively coupled plasma–optical emission spectroscopy Flow injection pretreatment |
| 発行日 | 2014-05 |
| 出版物タイトル | Talanta |
| 巻 | 122巻 |
| 出版者 | Elsevier |
| 開始ページ | 240 |
| 終了ページ | 245 |
| ISSN | 00399140 |
| NCID | AA00856594 |
| 資料タイプ | 学術雑誌論文 |
| 言語 | 英語 |
| OAI-PMH Set | 岡山大学 |
| 著作権者 | © 2014 Elsevier B.V. All rights reserved |
| 論文のバージョン | author |
| PubMed ID | 24720990 |
| DOI | 10.1016/j.talanta.2014.01.057 |
| Web of Science KeyUT | 000335636700037 |
| 関連URL | isVersionOf https://doi.org/10.1016/j.talanta.2014.01.057 |
| JaLCDOI | 10.18926/AMO/52409 |
|---|---|
| フルテキストURL | 68_2_125.pdf |
| 著者 | Young Jin Chang| Wol Seon Jung| Woon Rak Son| Youn Yi Jo| |
| 抄録 | A 47-year-old woman with amyotrophic lateral sclerosis was scheduled for total thyroidectomy with cervical node dissection. During anesthetic management by total intravenous anesthesia using remifentanil, propofol, and rocuronium, train-of-four (TOF) monitoring findings were not consistent with clinical signs. Sugammadex successfully reversed shallow respiration. |
| キーワード | amyotrophic lateral sclerosis train-of-four sugammadex |
| Amo Type | Case Report |
| 出版物タイトル | Acta Medica Okayama |
| 発行日 | 2014-04 |
| 巻 | 68巻 |
| 号 | 2号 |
| 出版者 | Okayama University Medical School |
| 開始ページ | 125 |
| 終了ページ | 127 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| 資料タイプ | 学術雑誌論文 |
| 言語 | 英語 |
| 著作権者 | CopyrightⒸ 2014 by Okayama University Medical School |
| 論文のバージョン | publisher |
| 査読 | 有り |
| PubMed ID | 24743788 |
| Web of Science KeyUT | 000334652700008 |
| JaLCDOI | 10.18926/AMO/52408 |
|---|---|
| フルテキストURL | 68_2_119.pdf |
| 著者 | Takeda, Akiko| Shimada, Akira| Hamamoto, Kazuko| Yoshino, Syuuji| Nagai, Tomoko| Fujii, Yousuke| Yamada, Mutsuko| Nakamura, Yoshimi| Watanabe, Toshiyuki| Watanabe, Yuki| Yamamoto, Yuko| Sakakibara, Kanae| Oda, Megumi| Morishima, Tsuneo| |
| 抄録 | Acute megakaryocytic leukemia (AMKL) with t(1;22)(p13;q13) is a distinct category of myeloid leukemia by WHO classification and mainly reported in infants and young children. Accurate diagnosis of this type of AMKL can be difficult, because a subset of patients have a bone marrow (BM) blast percentage of less than 20% due to BM fibrosis. Therefore, it is possible that past studies have underestimated this type of AMKL. We present here the case of a 4-month-old female AMKL patient who was diagnosed by presence of the RBM15-MKL1 (OTT-MAL) fusion transcript by RT-PCR. In addition, we monitored RBM15-MKL1 fusion at several time points as a marker of minimal residual disease (MRD), and found that it was continuously negative after the first induction chemotherapy even by nested RT-PCR. Detection of the RBM15-MKL1 fusion transcript thus seems to be useful for accurate diagnosis of AMKL with t(1;22)(p13;q13). We recommend that the RBM15-MKL1 fusion transcript be analyzed for all suspected AMKL in infants and young children. Furthermore, monitoring of MRD using this fusion transcript would be useful in treatment of AMKL with t(1;22)(p13;q13). |
| キーワード | AMKL infant RBM15-MKL1 OTT-MAL |
| Amo Type | Case Report |
| 出版物タイトル | Acta Medica Okayama |
| 発行日 | 2014-04 |
| 巻 | 68巻 |
| 号 | 2号 |
| 出版者 | Okayama University Medical School |
| 開始ページ | 119 |
| 終了ページ | 123 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| 資料タイプ | 学術雑誌論文 |
| 言語 | 英語 |
| 著作権者 | CopyrightⒸ 2014 by Okayama University Medical School |
| 論文のバージョン | publisher |
| 査読 | 有り |
| PubMed ID | 24743787 |
| Web of Science KeyUT | 000334652700007 |
| JaLCDOI | 10.18926/AMO/52407 |
|---|---|
| フルテキストURL | 68_2_111.pdf |
| 著者 | Shirakawa, Yasuhiro| Noma, Kazuhiro| Maeda, Naoaki| Katsube, Ryoichi| Tanabe, Shunsuke| Ohara, Toshiaki| Sakurama, Kazufumi| Fujiwara, Toshiyoshi| |
| 抄録 | Thoracoscopic esophagectomy in the prone position (TEPP) might enable solo-surgery in cases requiring resection of the esophagus and the surrounding lymph nodes due to the associated advantages of good exposure of the surgical field and ergonomic considerations for the surgeon. However, no one approach can be for all patients requiring extensive lymphadenectomy. We recently developed an assistant-based procedure to standardize exposure of the surgical field. Patients were divided into 1 of 2 groups:a pre-standardization group (n＝37) and a post-standardization group (n＝28). The thoracoscopic operative time was significantly shorter (p＝0.0037) in the post-standardization group (n＝28; 267±31min) than in the pre-standardization group (n＝37;301±53min). Further, learning curve analysis using the moving average method showed stabilization of the thoracoscopic operative time after the standardization. No significant differences were found in the number of mediastinal lymph nodes dissected or intraoperative blood loss between the 2 groups. There were also no significant differences in the complication rate. Assistant-based surgery and standardization of the procedure resulted in a well-exposed and safe surgical field. TEPP decreased the operative time, even in patients requiring extensive lymphadenectomy. |
| キーワード | thoracoscopic esophagectomy prone position standardization |
| Amo Type | Original Article |
| 出版物タイトル | Acta Medica Okayama |
| 発行日 | 2014-04 |
| 巻 | 68巻 |
| 号 | 2号 |
| 出版者 | Okayama University Medical School |
| 開始ページ | 111 |
| 終了ページ | 117 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| 資料タイプ | 学術雑誌論文 |
| 言語 | 英語 |
| 著作権者 | CopyrightⒸ 2014 by Okayama University Medical School |
| 論文のバージョン | publisher |
| 査読 | 有り |
| PubMed ID | 24743786 |
| Web of Science KeyUT | 000334652700006 |
| JaLCDOI | 10.18926/AMO/52406 |
|---|---|
| フルテキストURL | 68_2_101.pdf |
| 著者 | Izutsu, Masato| Suzuki, Etsuji| Izutsu, Yukako| Doi, Hiroyuki| |
| 抄録 | The aim of this study was to examine trends in the geographic distribution of nursing staff in Japan from 2000 to 2010. We examined time trends in the rates of nursing staff per 100,000 population across 349 secondary health service areas. Using the Gini coefficient as a measure of inequality, we separately analyzed the data of 4 nursing staff types:public health nurses (PHN), midwives (MW), nurses (NS), and associate nurses (AN). Then, using multilevel Poisson regression models, we calculated the rate ratios (RRs) and their 95% confidence intervals (CIs) for each type of nursing staff per 1-year change. Overall, the distribution of PHN, MW, and NS improved slightly in terms of the Gini coefficient. After adjusting for prefectural capital and population density, PHN, MW, and NS significantly increased;the RRs per 1-year increment were 1.022 (95% CI:1.020-1.023), 1.021 (95% CI:1.019-1.022), and 1.037 (95% CI:1.037-1.038), respectively. In contrast, AN significantly decreased;the RR per 1-year increment was 0.993 (95% CI:0.993-0.994). Despite the considerable increase in the absolute number of nursing staff in Japan (excluding AN), this increase did not lead to a sufficient improvement in distribution over the last decade. |
| キーワード | health policy inequality Japan multilevel Poisson model nursing staff |
| Amo Type | Original Article |
| 出版物タイトル | Acta Medica Okayama |
| 発行日 | 2014-04 |
| 巻 | 68巻 |
| 号 | 2号 |
| 出版者 | Okayama University Medical School |
| 開始ページ | 101 |
| 終了ページ | 110 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| 資料タイプ | 学術雑誌論文 |
| 言語 | 英語 |
| 著作権者 | CopyrightⒸ 2014 by Okayama University Medical School |
| 論文のバージョン | publisher |
| 査読 | 有り |
| PubMed ID | 24743785 |
| Web of Science KeyUT | 000334652700005 |
| 関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/52523 |
| JaLCDOI | 10.18926/AMO/52405 |
|---|---|
| フルテキストURL | 68_2_89.pdf |
| 著者 | Sako, Shinichi| Kariyama, Reiko| Mitsuhata, Ritsuko| Yamamoto, Masumi| Wada, Koichiro| Ishii, Ayano| Uehara, Shinya| Kokeguchi, Susumu| Kusano, Nobuchika| Kumon, Hiromi| |
| 抄録 | We conducted a study on molecular epidemiology and clinical implications of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa isolated from urine. Over a 10-year period from 2001 through 2010, a total of 92 MBL-producing P. aeruginosa urine isolates were collected from patients (one isolate per patient) who were admitted to 5 hospitals in Okayama Prefecture, Japan. When cross-infection was suspected in the hospital, pulsed-field gel electrophoresis was performed. In the resulting dendrogram of 79 MBL-producing P. aeruginosa urine isolates, no identical isolates and 7 pairs of isolates with ≥80% similarity were found. The biofilm-forming capabilities of 92 MBL-producing P. aeruginosa urine isolates were significantly greater than those of 92 non-MBL-producing urine isolates in a medium of modified artificial urine. The imipenem resistance transferred in 16 of 18 isolates tested, and these frequencies were in the range of 10－3 to 10－9. All of 18 isolates tested belonged to internationally spread sequence type 235 and had 3 gene cassettes of antimicrobial resistance genes in the class 1 integron. The strong biofilm-forming capabilities of MBL-producing P. aeruginosa urine isolates could be seriously implicated in nosocomial infections. To prevent spread of the organism and transferable genes, effective strategies to inhibit biofilm formation in medical settings are needed. |
| キーワード | Pseudomonas aeruginosa metallo-β-lactamase molecular epidemiology biofilm urinary tract infection |
| Amo Type | Original Article |
| 出版物タイトル | Acta Medica Okayama |
| 発行日 | 2014-04 |
| 巻 | 68巻 |
| 号 | 2号 |
| 出版者 | Okayama University Medical School |
| 開始ページ | 89 |
| 終了ページ | 99 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| 資料タイプ | 学術雑誌論文 |
| 言語 | 英語 |
| 著作権者 | CopyrightⒸ 2014 by Okayama University Medical School |
| 論文のバージョン | publisher |
| 査読 | 有り |
| PubMed ID | 24743784 |
| Web of Science KeyUT | 000334652700004 |
| 関連URL | http://ousar.lib.okayama-u.ac.jp/metadata/52504 |
| JaLCDOI | 10.18926/AMO/52404 |
|---|---|
| フルテキストURL | 68_2_79.pdf |
| 著者 | Mu-Mu-Shwe| Harano, Teruo| Okada, Shigeru| Aye-Aye-Win| Khin-Saw-Aye| Hlaing-Myat-Thu| Mo-Mo-Win| Khin-Khin-Oo| Myo-Khin| |
| 抄録 | This study aimed to determine the prevalence of normal and abnormal cervical cytology in women who attended the cervical cancer screening clinic of the Department of Medical Research in Lower Myanmar, and to determine the proportion of high-risk (HR) human papillomavirus (HPV) infection and HPV genotypes in women with normal and abnormal cervical cytology. A total of 1,771 women were screened from 2010 to 2011. Among them, 762 women (43.0%) had a normal smear, and 866 (48.9%) and 87 (4.9%) were diagnosed with inflammatory smears and atypical squamous cells of undetermined significance (ASCUS), respectively. Diagnoses of low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL) numbered 42 (2.3%) and 11 (0.6%) respectively. Three cases of squamous cell carcinoma (SCC) (0.2%) were detected. Cervical swabs were collected from 96 women with abnormal cervical cytology and 20 with normal cytology. HR-HPV DNA testing was performed by polymerase chain reaction (PCR) with pU1M/pU2R primers. HR-HPV were identified in 35.5% (22/62) of inflammatory smears, 60% (6/10) of ASCUS, 86.7% (13/15) of LSIL, 50% (3/6) of HSIL, 100% (3/3) of SCC and 5% (1/20) of normal cytology. In PCR-positive cases, HPV genotyping was analyzed by the cleaved amplification polymorphism method. The most prevalent HPV genotypes were HPV-16 (60.4%) followed by HPV-31 (14.6%), HPV-18 (12.5%) and HPV-58 (12.5%). Women with abnormal cervical cytology were 10 times more likely to be HR-HPV positive than those with normal cytology (p＝0.0001). This study suggests that the implementation of a cervical cytology screening program and routine vaccination against HPV in preadolescent and adolescent groups are needed to reduce the burden of HPV-associated cervical cancer. |
| キーワード | human papillomavirus cervical neoplasia genotyping Myanmar |
| Amo Type | Original Article |
| 出版物タイトル | Acta Medica Okayama |
| 発行日 | 2014-04 |
| 巻 | 68巻 |
| 号 | 2号 |
| 出版者 | Okayama University Medical School |
| 開始ページ | 79 |
| 終了ページ | 87 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| 資料タイプ | 学術雑誌論文 |
| 言語 | 英語 |
| 著作権者 | CopyrightⒸ 2014 by Okayama University Medical School |
| 論文のバージョン | publisher |
| 査読 | 有り |
| PubMed ID | 24743783 |
| Web of Science KeyUT | 000334652700003 |
| JaLCDOI | 10.18926/AMO/52403 |
|---|---|
| フルテキストURL | 68_2_63.pdf |
| 著者 | Fujii, Yasuyuki| Hoshino, Tyuji| Kumon, Hiromi| |
| 抄録 | Dickkopf (DKK) proteins interact with low-density lipoprotein receptor-related protein 5/6 (LRP5/6) to modulate WNT signaling. The interaction is mediated by a cysteine-rich domain (C2) in the DKK protein and β-propeller domains (PD) of LRP5/6. However, the third member of the DKK family (DKK3) does not bind to LRP5/6. To determine why DKK3 does not bind to the receptor domains, we performed a molecular modeling simulation study including homology modeling, protein-protein docking and molecular dynamics (MD). The computed affinities (ΔGbinding) between the C2 and PD models were consistent with the previously reported experimental results. The C2 model of DKK3 showed the lowest affinity for PD models. Multiple sequence alignment of C2 domains revealed that the DKK3 genes have a unique 7-amino-acid insertion (L249-E255 in human DKK3) and P258 in a finger loop 1 (FL1). Interestingly, the insertion sequence is evolutionally conserved. MD simulations of high-affinity complex models of C2 and PD showed that FL1 directly interacts with the PD models and stabilizes the complex models. We also built a 7-amino-acid-deletion/P258G mutant model of DKK3C2 and estimated its affinities for the PD models. The affinity for human LRP5PD2 was increased by the substitution (ΔGbinding＝－48.9kcal/mol) and the affinity was compatible with that of high-affinity ligands. The results suggested that the lack of affinity between human DKK3 and human LRP5/6 results from: i) insertion of the 7 amino acids, and ii) P258 in human DKK3. The sequence differences thus suggest an explanation for this unique property of DKK3. |
| キーワード | DKK3 molecular modeling protein-protein docking LRP5/6 |
| Amo Type | Original Article |
| 出版物タイトル | Acta Medica Okayama |
| 発行日 | 2014-04 |
| 巻 | 68巻 |
| 号 | 2号 |
| 出版者 | Okayama University Medical School |
| 開始ページ | 63 |
| 終了ページ | 78 |
| ISSN | 0386-300X |
| NCID | AA00508441 |
| 資料タイプ | 学術雑誌論文 |
| 言語 | 英語 |
| 著作権者 | CopyrightⒸ 2014 by Okayama University Medical School |
| 論文のバージョン | publisher |
| 査読 | 有り |
| PubMed ID | 24743782 |
| Web of Science KeyUT | 000334652700002 |