著者

Takanori Honda Sanmei Chen Jun Hata Daigo Yoshida Yoichiro Hirakawa Yoshihiko Furuta Mao Shibata Satoko Sakata Takanari Kitazono Toshiharu Ninomiya

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.61960, (Released:2021-01-22)

参考文献数

33

被引用文献数

23

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Aim: To develop and validate a new risk prediction model for predicting the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) in Japanese adults. Methods: A total of 2,454 participants aged 40–84 years without a history of cardiovascular disease (CVD) were prospectively followed up for 24 years. An incident ASCVD event was defined as the first occurrence of coronary heart disease or atherothrombotic brain infarction. A Cox proportional hazards regression model was used to construct the prediction model. In addition, a simplified scoring system was translated from the developed prediction model. The model performance was evaluated using Harrell's C statistics, a calibration plot with the Greenwood-Nam-D'Agostino test, and a bootstrap validation procedure. Results: During a median of a 24-year follow-up, 270 participants experienced the first ASCVD event. The predictors of the ASCVD events in the multivariable Cox model included age, sex, systolic blood pressure, diabetes, serum high-density lipoprotein cholesterol, serum low-density lipoprotein cholesterol, proteinuria, smoking habits, and regular exercise. The developed models exhibited good discrimination with negligible evidence of overfitting (Harrell's C statistics: 0.786 for the multivariable model and 0.789 for the simplified score) and good calibrations (the Greenwood-Nam-D'Agostino test: P=0.29 for the multivariable model, 0.52 for the simplified score). Conclusion: We constructed a risk prediction model for the development of ASCVD in Japanese adults. This prediction model exhibits great potential as a tool for predicting the risk of ASCVD in clinical practice by enabling the identification of specific risk factors for ASCVD in individual patients.

著者

Mayumi Nagano Kuniyoshi Shimizu Ryuichiro Kondo Chickako Hayashi Daigo Sato Katsuyuki Kitagawa Koichiro Ohnuki

出版者

Biomedical Research Press

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.31, no.4, pp.231-237, 2010 (Released:2010-09-08)

参考文献数

27

被引用文献数

31 73 24

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Hericium erinaceus, a well known edible mashroom, has numerous biological activities. Especially hericenones and erinacines isolated from its fruiting body stimulate nerve growth factor (NGF) synthesis, which expects H. erinaceus to have some effects on brain functions and autonomic nervous system. Herein, we investigated the clinical effects of H. erinaceus on menopause, depression, sleep quality and indefinite complaints, using the Kupperman Menopausal Index (KMI), the Center for Epidemiologic Studies Depression Scale (CES-D), the Pittsburgh Sleep Quality Index (PSQI), and the Indefinite Complaints Index (ICI). Thirty females were randomly assigned to either the H. erinaceus (HE) group or the placebo group and took HE cookies or placebo cookies for 4 weeks. Each of the CES-D and the ICI score after the HE intake was significantly lower than that before. In two terms of the ICI, “insentive” and “palpitatio”, each of the mean score of the HE group was significantly lower than the placebo group. “Concentration”, “irritating” and “anxious” tended to be lower than the placebo group. Our results show that HE intake has the possibility to reduce depression and anxiety and these results suggest a different mechanism from NGF-enhancing action of H. erinaceus.

著者

Mayu Higashioka Satoko Sakata Takanori Honda Jun Hata Daigo Yoshida Yoichiro Hirakawa Mao Shibata Kenichi Goto Takanari Kitazono Haruhiko Osawa Toshiharu Ninomiya

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.51961, (Released:2019-11-11)

参考文献数

39

被引用文献数

49

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Aims: This study aims to investigate the association between serum small dense low-density lipoprotein (sdLDL) cholesterol level and the development of coronary heart disease (CHD) in a Japanese community. Methods: A total of 3,080 participants without prior cardiovascular disease, aged 40 years or older, were followed up for 8 years. The participants were divided into the quartiles of serum sdLDL cholesterol levels. The risk estimates were computed using a Cox proportional hazards model. Results: During the follow-up period, 79 subjects developed CHD. Subjects in the highest quartile had a 5.41- fold (95% confidence interval, 2.12–13.82) higher risk of CHD than those in the lowest quartile after controlling for confounders. In the analysis classifying the participants into four groups according to the levels of serum sdLDL cholesterol and serum low-density lipoprotein (LDL) cholesterol levels, the risk of CHD almost doubled in subjects with sdLDL cholesterol of ≥ 32.9 mg/dL (median), regardless of serum LDL cholesterol levels, as compared with subjects with serum sdLDL cholesterol of <32.9 mg/dL and serum LDL cholesterol of <120.1 mg/dL (median). When serum sdLDL cholesterol levels were incorporated into a model with known cardiovascular risk factors, c-statistics was significantly increased (from 0.77 to 0.79; p=0.02), and the net reclassification improvement was also significant (0.40; p<0.001). Conclusions: The present findings suggest that the serum sdLDL cholesterol level is a relevant biomarker for the future development of CHD that offers benefit beyond the serum LDL cholesterol level and a possible therapeutic target to reduce the burden of CHD in a Japanese community.

著者

Nobutaka Nagano Atsuko Muranaka Ryo Nishikawa Wataru Ohwada Hidemichi Kouzu Naoyuki Kamiyama Takefumi Fujito Atsushi Mochizuki Daigo Nagahara Mitsuhiro Nakanishi Yukiko Ohkubo Shin Hisahara Satoshi Nakao Nagaaki Katoh Aki Ishikawa Akihiro Sakurai Toshiyuki Yano

出版者

International Heart Journal Association

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

vol.63, no.1, pp.168-175, 2022-01-29 (Released:2022-01-29)

参考文献数

35

被引用文献数

7

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Diagnostic strategies for symptomatic transthyretin (ATTR) cardiac amyloidosis showing typical morphological features such as increased ventricular wall thickness and myocardial injury such as an elevation in serum troponin T level have been established, but those for subclinical cardiac amyloidosis are limited. In the era when effective therapies to suppress/delay progression of ATTR cardiac amyloidosis are available, early detection of cardiac involvement plays a crucial role in appropriate decision-making for treatment in TTR mutation carriers who have a family history of heart failure and death due to ATTR amyloidosis. Findings of three cases with known pathogenic transthyretin (TTR) mutations (p.Ser70Arg, p.Phe53Val, and p.Val50Met) and family histories of death for amyloidosis were presented. Two cases were asymptomatic, and a case carrying p.Phe53Val had gastrointestinal symptoms and autonomic neuropathy. Levels of plasma N-terminal fragment of pro-B-type natriuretic peptide and troponin T were within normal ranges in all cases, but results of cardiac magnetic resonance (CMR) and bone scintigraphy clearly revealed the presence of cardiac involvement in all cases, even in a case without echocardiographic abnormalities including left ventricular hypertrophy and relative apical sparing of longitudinal strain shown by two-dimensional speckle-tracking echocardiography. Electrocardiography revealed modest abnormalities including reduced R wave amplitude in V2 and a trend toward left axis deviation in all cases. In conclusion, CMR, bone scintigraphy, and electrocardiography are useful for early detection of ATTR cardiac amyloidosis in TTR mutation carriers. The role of comprehensive cardiac assessment in the early detection of cardiac amyloidosis in TTR mutation carriers is discussed.

著者

Kaoru Umehara Naoko Mukai Jun Hata Yoichiro Hirakawa Tomoyuki Ohara Daigo Yoshida Hiro Kishimoto Takanari Kitazono Sumio Hoka Yutaka Kiyohara Toshiharu Ninomiya

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.81, no.9, pp.1315-1321, 2017-08-25 (Released:2017-08-25)

参考文献数

36

被引用文献数

13

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Background:Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations.Methods and Results:We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002–2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH)2D levels (HR 1.54 [95% confidence interval, 1.18–2.01] for the lowest quartile, 1.31 [0.99–1.73] for the 2nd quartile, 0.94 [0.70–1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend <0.001). A similar association was observed for cardiovascular and respiratory infection death (both P for trend <0.01), but not for cancer death or death from other causes. In the stratified analysis, the association between lower serum 1,25(OH)2D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2than in those with eGFR ≥60 mL/min/1.73 m2; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04).Conclusions:The findings suggested that a lower serum 1,25(OH)2D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH)2D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.

著者

醍醐 身奈 押谷 由夫 Daigo Mina Oshitani Yoshio

雑誌

學苑 = GAKUEN (ISSN:13480103)

巻号頁・発行日

vol.848, pp.24-41, 2011-06-01

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Abstract This study considers the relationship between the government mandated yutori curriculum(education which aims at developing individual talent rather than learning by rote)and moral education, which is the basis of the curriculum. In addition, the authors propose some changes in the system of high school moral education. First, the authors point out that moral education played a key role in promoting zest for life among elementary and junior high school students. Second, we point out that establishing their identity is of great importance for high school students, as Eduard Spranger's "Conscience education" suggests. The state of children who have been taught under the yutori curriculum further suggest that high school students need moral education. Erik Erikson's Identity formation theory and Abraham Maslow's desire development theory lend further support. We conclude that high school students, like elementary school students, need overall moral education based on various activities that stress the relationship between students' own experiences and morality.

著者

醍醐 龍馬 DAIGO Ryuma

出版者

名古屋大学博物館

雑誌

名古屋大学博物館報告 (ISSN:13468286)

巻号頁・発行日

no.28, pp.213-219, 2012

著者

Daigo Kachi Tetsumin Lee Michihito Naito Kazuki Matsuda Kodai Sayama Yuki Odanaka Mao Terui Tomoki Horie Shinichiro Okata Masashi Nagase Yuta Taomoto Toru Misawa Ryoichi Miyazaki Masakazu Kaneko Yasutoshi Nagata Toshihiro Nozato Takashi Ashikaga

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0391, (Released:2023-09-09)

参考文献数

1

著者

Satoko Sakata Jun Hata Masayo Fukuhara Koji Yonemoto Naoko Mukai Daigo Yoshida Hiro Kishimoto Toshio Ohtsubo Takanari Kitazono Yutaka Kiyohara Toshiharu Ninomiya

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-16-1306, (Released:2017-06-14)

参考文献数

36

被引用文献数

6

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Background:The association of morning and evening home blood pressures (HBPs) with carotid atherosclerosis has been uncertain in general populations, so we aimed to investigate it in a general Japanese population.Methods and Results:We performed a cross-sectional survey of 2,856 community-dwelling individuals aged ≥40 years to examine the association of morning and evening HBPs with carotid mean intima-media thickness (IMT). The age- and sex-adjusted geometric averages of carotid mean IMT increased significantly with increasing morning HBP (optimal: 0.67 mm; normal: 0.69 mm; high normal: 0.72 mm; grade 1 hypertension: 0.74 mm; and grade 2+3 hypertension: 0.76 mm) and with increasing evening HBP (0.68 mm, 0.71 mm, 0.73 mm, 0.76 mm, and 0.78 mm, respectively) (both P for trend <0.001). These associations remained significant even after adjusting for potential confounding factors. Likewise, both isolated morning hypertension (morning HBP ≥135/85 mmHg and evening HBP <135/85 mmHg) and isolated evening hypertension (evening HBP ≥135/85 mmHg and morning HBP <135/85 mmHg) as well as sustained hypertension (both morning and evening HBP ≥135/85 mmHg) were significantly associated with thicker mean IMT.Conclusions:Our findings suggested that both morning and evening HBPs were significantly associated with carotid atherosclerosis in this general Japanese population.

著者

Kaoru Umehara Naoko Mukai Jun Hata Yoichiro Hirakawa Tomoyuki Ohara Daigo Yoshida Hiro Kishimoto Takanari Kitazono Sumio Hoka Yutaka Kiyohara Toshiharu Ninomiya

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-16-0954, (Released:2017-04-20)

参考文献数

36

被引用文献数

13

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Background:Few studies have investigated the association between serum vitamin D levels and mortality in general Asian populations.Methods and Results:We examined the association of serum 1,25-dihydroxyvitamin D (1,25(OH)2D) levels with the risk of all-cause and cause-specific death in an average 9.5-year follow-up study of 3,292 community-dwelling Japanese subjects aged ≥40 years (2002–2012). The multivariable-adjusted hazard ratio (HR) for all-cause death increased significantly with lower serum 1,25(OH)2D levels (HR 1.54 [95% confidence interval, 1.18–2.01] for the lowest quartile, 1.31 [0.99–1.73] for the 2nd quartile, 0.94 [0.70–1.25] for the 3rd quartile, 1.00 [Ref.] for highest quartile; P for trend <0.001). A similar association was observed for cardiovascular and respiratory infection death (both P for trend <0.01), but not for cancer death or death from other causes. In the stratified analysis, the association between lower serum 1,25(OH)2D levels and the risk of respiratory infection death was stronger in subjects with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2than in those with eGFR ≥60 mL/min/1.73 m2; there was a significant heterogeneity in the association between eGFR levels (P for heterogeneity=0.04).Conclusions:The findings suggested that a lower serum 1,25(OH)2D level is a potential risk factor for all-cause death, especially cardiovascular and respiratory infection death, in the general Japanese population, and that lower serum 1,25(OH)2D levels greatly increase the risk of respiratory infection death in subjects with kidney dysfunction.

著者

中田 大悟 Daigo NAKATA

出版者

創価大学経済学会

雑誌

創価経済論集 (ISSN:09116834)

巻号頁・発行日

vol.47, no.1/2/3/4, pp.67-77, 2018-03-31

著者

Masaki MICHISHITA Namika SAITO Satoshi NOZAWA Rina FURUMOTO Takayuki NAKAGAWA Touko SATO Kazuhiko OCHIAI Daigo AZAKAMI Kinya KATAYAMA Rei NAKAHIRA Hiroyuki TAZAKI Yukino MACHIDA Toshiyuki ISHIWATA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.19-0194, (Released:2019-07-15)

被引用文献数

8

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Cancer consists of heterogeneous cells that contain a small population of cells that possess stem cell properties; these cells, referred to as cancer stem cells (CSCs) or tumor-initiating cells, are involved in tumor progression and metastasis. Using a sphere-forming assay, canine mammary CSCs were found to be similar to human breast CSCs. Metabolic reprogramming has been recognized as a hallmark of various cancers. However, the significance of cellular metabolism in CSCs remains unclear. The aim of this study was to define the metabolic characteristics of CSCs derived from canine mammary tumors and gain an understanding of the maintenance of stemness. We identified metabolite profiles of canine mammary adenocarcinoma cell lines using gas chromatography-mass spectrometry. Metabolites were extracted from both adherent and sphere-forming cells derived from three cell lines. Sphere-forming cells were separated from adherent cells using an orthogonal, partial least squares discriminant analysis. Sphere-forming cells were found to contain high levels of the amino acids alanine, glycine and proline compared with adherent cells. They also had high levels of palmitoleate, palmitate and dihomo-gamma-linolenic acid compared with adherent cells. In a sphere-forming assay, palmitate increased the number of spheres for all cell lines. These results indicate that the sphere-forming cells derived from canine mammary adenocarcinoma cell lines have specific metabolic profiles that may be useful for the development of CSC-specific therapies targeting metabolic pathways and potential stemness biomarkers; these results also clarify the maintenance of stemness in canine mammary CSCs.

著者

Risako KAWATA Tatsuhito II Tatsuya HORI Yukino MACHIDA Kazuhiko OCHIAI Daigo AZAKAMI Toshiyuki ISHIWATA Masaki MICHISHITA

出版者

JAPANESE SOCIETY OF VETERINARY SCIENCE

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

vol.81, no.2, pp.186-189, 2019 (Released:2019-02-09)

参考文献数

17

被引用文献数

1

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A 14-year and 8-month-old intact male Amur tiger presented with an enlarged left testis, measuring 5.7 × 5.5 × 4.5 cm. The cut surface was mottled dark red to reddish brown in color. Microscopically, the enlarged left testis comprised round or polygonal neoplastic cells arranged in a diffuse sheet pattern. These neoplastic cells had a hyperchromatic nucleus and an abundant eosinophilic cytoplasm. Immunohistochemically, these neoplastic cells were positive for vimentin, chromogranin A, synaptophysin, melan-A, inhibin-α, and S100 and negative for desmin and WT-1. Based on these morphological and immunohistochemical findings, the tumor was diagnosed as a Leydig cell tumor.

著者

Takanori Honda Sanmei Chen Jun Hata Daigo Yoshida Yoichiro Hirakawa Yoshihiko Furuta Mao Shibata Satoko Sakata Takanari Kitazono Toshiharu Ninomiya

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.ER61960, (Released:2023-10-24)

被引用文献数

1

著者

Shohei Kataoka Daigo Yagishita Kyoichiro Yazaki Miwa Kanai Shun Hasegawa Morio Shoda Junichi Yamaguchi

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-23-0058, (Released:2023-06-21)

参考文献数

26

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Background: The association between the T-peak to T-end interval (Tp-e) and ventricular arrhythmia (VA) events in cardiac sarcoidosis (CS) is unknown. The purpose of this study was to investigate whether Tp-e was associated with VA events in CS patients with implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds).Methods and Results: We retrospectively studied 50 patients (16 men; mean [±SD] age 56.3±10.5 years) with CS and ICD/CRT-D. The maximum Tp-e in the precordial leads recorded by a 12-lead electrocardiogram after ICD/CRT-D implantation was evaluated. The clinical endpoint was defined as appropriate ICD therapy. During a median follow-up period of 85.0 months, 22 patients underwent appropriate therapy and 10 patients died. Kaplan-Meier analysis revealed that the probability of the clinical endpoint was 28.3% at 2 years and 35.3% at 4 years. The optimal cut-off value of the Tp-e for the prediction of the clinical endpoint was 91 ms, with a sensitivity of 72.7% and a specificity of 87.0% (area under the curve=0.81). Multivariate Cox regression analysis showed that Tp-e ≥91 ms (hazard ratio [HR] 5.10; 95% confidence interval [CI] 1.99–13.1; P<0.001) and a histological diagnosis of CS (HR 3.84; 95% CI 1.28–11.5; P=0.016) were significantly associated with the clinical endpoint.Conclusions: Tp-e ≥91 ms was a significant predictor of VA events in patients with CS and ICD/CRT-D.

著者

Kimitaka Nakamura Daigo Yoshida Takanori Honda Jun Hata Mao Shibata Yoichiro Hirakawa Yoshihiko Furuta Hiro Kishimoto Tomoyuki Ohara Takanari Kitazono Yasuharu Nakashima Toshiharu Ninomiya

出版者

Japan Epidemiological Association

雑誌

Journal of Epidemiology (ISSN:09175040)

巻号頁・発行日

pp.JE20190289, (Released:2020-06-06)

参考文献数

38

被引用文献数

32

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Background: The prevalence of sarcopenia defined by the Asian Working Group for Sarcopenia (AWGS) definition in Asian communities has not been fully addressed. Moreover, few studies have addressed the influence of sarcopenia on mortality.Methods: A total of 1,371 and 1,597 residents aged 65 years or older participated in health surveys in 2012 and 2017. Sarcopenia was determined by the AWGS definition. Factors associated with the presence of sarcopenia were assessed using a logistic regression model in participants in the 2012 survey. Subjects in the 2012 survey were followed-up prospectively for a median of 4.3 years. Mortality risk for subjects with sarcopenia was examined using the Cox proportional hazards model.Results: The crude prevalence of sarcopenia was 7.4% and 6.6% in participants at the 2012 and 2017 surveys, respectively; there was no significant difference between surveys (p = 0.44). The prevalence of sarcopenia increased significantly with age in both sexes (both p for trend < 0.001). Subjects with sarcopenia were more likely to exercise less regularly, to intake less total energy, and to exhibit a disability in activity of daily living than those without. The multivariable-adjusted hazard ratio for all-cause mortality was 2.20 (95% confidence interval, 1.25-3.85) in subjects with sarcopenia, compared to those without.Conclusions: Approximately 7% of older subjects had sarcopenia in a community-dwelling older Japanese population. Moreover, subjects with sarcopenia had an increased mortality risk. Our findings suggest that a public health strategy for sarcopenia is needed to extend healthy life expectancy.

著者

Daigo Ochiai Hirotaka Masuda Yushi Abe Toshimitsu Otani Marie Fukutake Tadashi Matsumoto Kei Miyakoshi Mamoru Tanaka

出版者

The Keio Journal of Medicine

雑誌

The Keio Journal of Medicine (ISSN:00229717)

巻号頁・発行日

pp.2017-0019-IR, (Released:2018-03-06)

参考文献数

51

被引用文献数

10

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Mesenchymal stem cells (MSCs) have generated great interest in the fields of regenerative medicine and immunotherapy because of their unique biological properties. Among MSCs, amniotic fluid stem cells (AFS) have a number of characteristics that make them attractive candidates for tissue engineering and cell replacement strategies, particularly for perinatal medicine. If various neonatal conditions, including birth asphyxia, preterm birth, and congenital abnormalities, which result in long-lasting severe impairments, could be predicted during pregnancy, it would allow collection of small samples of amniotic fluid cells by amniocentesis. In vitro culture of these autologous AFS during pregnancy would make them available for use soon after birth. Hypoxic-ischemic encephalopathy (HIE) and myelomeningocele (MMC) are neonatal conditions that cause permanent neurological disability, for which the treatment options are extremely limited. Experiments using animal models of HIE and MMC and human clinical trials have demonstrated that MSCs, including AFS, have beneficial effects on the central nervous system through paracrine influences, indicating that autologous AFS treatment may be applicable for intractable neurological diseases, including HIE and MMC, during the perinatal period. In this review, we focus on recent research related to the therapeutic potential of AFS for perinatal neurological diseases such as HIE and MMC.

著者

Shota KAWAKAMI Kazuhiko OCHIAI Yuiko KATO Masaki MICHISHITA Hinako HIRAMA Ryo OBARA Daigo AZAKAMI Masami WATANABE Toshinori OMI

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.17-0362, (Released:2017-11-21)

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Gliomas are common intracranial neoplasias in dogs. However, the underlying pathogenic mechanisms remain unclear. In humans, isocitrate dehydrogenase 2 (IDH2) is often mutated in gliomas. Although almost human IDH2 mutations have been identified at the Arg172 codon, few studies have reported structural, functional, or mutational information for canine IDH2. In this study, we cloned the full-length canine IDH2 (cIDH2) cDNA and substituted wild type Arg174 (cIDH2 WT: corresponding to R172 of human IDH2) with Lys (cIDH2 R174K). The cIDH2 WT and R174K proteins were overexpressed in HeLa cells, and their presence was confirmed using an anti-human IDH2-WT mAb (clone: KrMab-3) and an anti-IDH2-R172K mAb (clone: KMab-1). The IDH2 activity between cIDH2 WT and cIDH2 R174K transfectants was compared by measuring the production of NADH and NADPH. NADPH production was lower for cIDH2 R174K than that for cIDH2 WT transfectants. Finally, we detected increased expression of hypoxia inducible factor-1 alpha (HIF-1α) in cIDH2 R174K transfectants. This indicates that mutations at R174 can potentially induce carcinogenesis in canine somatic cells.

著者

Takuya Evan KISHIMOTO Shoko YASHIMA Rei NAKAHIRA Eri ONOZAWA Daigo AZAKAMI Makoto UJIKE Kazuhiko OCHIAI Toshiyuki ISHIWATA Kimimasa TAKAHASHI Masaki MICHISHITA

出版者

公益社団法人 日本獣医学会

雑誌

Journal of Veterinary Medical Science (ISSN:09167250)

巻号頁・発行日

pp.16-0412, (Released:2017-05-21)

被引用文献数

7

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Cancer stem cells or tumor-initiating cells (TICs) are a small subpopulation of cells that have the capacity to self-renew, differentiate and initiate tumors. These cells may function in tumor initiation, aggression and recurrence. Whether spheres derived from canine rhabdomyosarcoma cells have stem cell-like properties is unclear. We induced sphere formation in the canine rhabdomyosarcoma cell lines, CMS-C and CMS-J, and characterized the spheres in vitro and in vivo. Sphere-forming cells were more resistant to vincristine, mitoxantrone and doxorubicin than adherent cells. Xenograft transplantation demonstrated that 1 × 103 sphere-forming cells derived from CMS-C were sufficient for tumor formation. The sphere assay showed that the sphere-forming cells were present in these tumors. These results suggest that the spheres derived from canine rhabdomyosarcoma cells may possess characteristics of TICs. This study provides the foundation for elucidating the contribution of TICs to rhabdomyosarcoma tumorigenesis.

著者

Eisuke KAWANO Taku TORIUMI Shinya IGUCHI Daigo SUZUKI Shuichi SATO Masaki HONDA

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.38, no.2, pp.135-147, 2017-04-01 (Released:2017-04-22)

参考文献数

63

被引用文献数

22

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We previously generated induced pluripotent stem (iPS) cells from human dental pulp cells of deciduous teeth. Neural crest cells (NCCs) play a vital role in the development of the oral and maxillofacial region. Therefore, NCCs represent a cell source for bone, cartilage, and tooth-related tissue engineering. In this study, we examined whether iPS cells are capable of differentiating into NCCs through modification of the human embryonic stem cell protocol. First, iPS cells were dissociated into single cells and then reaggregated in low-cell-adhesion plates with neural induction medium for 8 days in suspension culture to form neurospheres. The neurospheres were transferred to fibronectin-coated dishes and formed rosette structures. The migrated cells from the rosettes abundantly expressed NCC markers, as evidenced by real-time polymerase chain reaction, immunofluorescence, and flow cytometric analysis. Furthermore, the migrated cells exhibited the ability to differentiate into neural crest lineage cells in vitro. They also exhibited tissue-forming potential in vivo, differentiating into bone and cartilage. Collectively, the migrated cells had similar characteristics to those of NCCs. These results suggest that human dental pulp cell-derived iPS cells are capable of differentiating into NCCs. Therefore, iPS cell-derived NCCs represent cell sources for bone and cartilage tissue engineering.