研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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Possible involvement of iron-induced oxidative insults in neurodegeneration. 査読有り国際誌

Asano T, Koike M, Sakata S, Takeda Y, Nakagawa T, Hatano T, Ohashi S, Funayama M, Yoshimi K, Asanuma M, Toyokuni S, Mochizuki H, Uchiyama Y, Hattori N, Iwai K

Neuroscience letters 588 巻 ( 1 ) 頁： 29 - 35 2015年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Neuroscience Letters

Involvement of iron in the development of neurodegenerative disorders has long been suggested, and iron that cannot be stored properly is suggested to induce iron toxicity. To enhance iron uptake and suppress iron storage in neurons, we generated transgenic (Tg) mice expressing iron regulatory protein 2 (IRP2), a major regulator of iron metabolism, in a neuron-specific manner. Although very subtle, IRP2 was expressed in all regions of brain examined. In the Tg mice, mitochondrial oxidative insults were observed including generation of 4-hydroxynonenal modified proteins, which appeared to be removed by a mitochondrial quality control protein Parkin. Inter-crossing of the Tg mice to Parkin knockout mice perturbed the integrity of neurons in the substantia nigra and provoked motor symptoms. These results suggest that a subtle, but chronic increase in IRP2 induces mitochondrial oxidative insults and accelerates neurodegeneration in a mouse model of Parkinson's disease. Thus, the IRP2 Tg may be a useful tool to probe the roles of iron-induced mitochondrial damages in neurodegeraration research.

DOI： 10.1016/j.neulet.2014.12.052

MINIMAL INFLAMMOGENICITY OF PRISTINE SINGLE-WALL CARBON NANOTUBES 査読有り国際誌

Shinya Toyokuni, Li Jiang, Ryo Kitaura, Hisanori Shinohara

NAGOYA JOURNAL OF MEDICAL SCIENCE 77 巻 ( 1-2 ) 頁： 195 - 202 2015年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：NAGOYA UNIV, SCH MED

Carbon nanotubes (CNTs) are a novel synthetic material comprising only carbon atoms. Based on its rigidity, its electrical and heat conductivity and its applicability to surface manufacturing, this material is expected to have numerous applications in industry. However, due to the material's dimensional similarity to asbestos fibers, its carcinogenicity was hypothesized during the last decade, and indeed, we have shown that multi- wall CNTs (MWCNTs) of 50 nm in diameter are potently carcinogenic to mesothelial cells after intraperitoneal injection. Additionally, we suggested that inflammogenicity after intraperitoneal injection can predict mesothelial carcinogenesis. However, few data have been published on the intraperitoneal inflammogenicity of single-wall CNTs (SWCNTs). Here, we conducted a series of studies on SWCNTs using both intraperitoneal injection into rats and MeT5A mesothelial cells. Intraperitoneal injection of 10 mg SWCNTs caused no remarkable inflammation in the abdominal cavity, and the exposure of MeT5A cells to up to 25 mu g/cm(2) SWCNTs did not alter proliferation. MWCNTs of 50 nm in diameter were used as a positive control, and tangled MWCNTs of 15 nm in diameter were used as a negative control. The results suggest that SWCNTs are a low- risk material with respect to mesothelial carcinogenesis.

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Minimal inflammogenicity of pristine single-wall carbon nanotubes.

Toyokuni S, Jiang LI, Kitaura R, Shinohara H

Nagoya journal of medical science 77 巻 ( 1-2 ) 頁： 195 - 202 2015年2月

Minimal inflammogenicity of pristine single-wall carbon nanotubes.

Toyokuni S, Jiang LI, Kitaura R, Shinohara H

Nagoya journal of medical science 77 巻 ( 1-2 ) 頁： 195 - 202 2015年2月

MINIMAL INFLAMMOGENICITY OF PRISTINE SINGLE-WALL CARBON NANOTUBES

Toyokuni Shinya, Jiang Li, Kitaura Ryo, Shinohara Hisanori

NAGOYA JOURNAL OF MEDICAL SCIENCE 77 巻 ( 1-2 ) 頁： 195 - 202 2015年2月

Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders. 査読有り

Hattori Y, Mukaide T, Jiang L, Kotani T, Tsuda H, Mano Y, Sumigama S, Hirayama T, Nagasawa H, Kikkawa F, Toyokuni S

Journal of clinical biochemistry and nutrition 56 巻 ( 1 ) 頁： 57 - 63 2015年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Journal of Clinical Biochemistry and Nutrition

Amniotic fluid contains numerous biomolecules derived from fetus and mother, thus providing precious information on pregnancy. Here, we evaluated oxidative stress of human amniotic fluid and measured the concentration of catalytic Fe(II). Amniotic fluid samples were collected with consent from a total of 89 subjects in Nagoya University Hospital, under necessary medical interventions: normal pregnancy at term, normal pregnancy at the 2nd trimester, preterm delivery with maternal disorders but without fetal disorders, congenital diaphragmatic hernia, fetal growth restriction, pregnancy-induced hypertension, gestational diabetes mellitus, Down syndrome and trisomy 18. Catalytic Fe(II) and oxi-dative stress markers (8-hydroxy-2'-deoxyguanosine, 8-OHdG; dityrosine) were determined with RhoNox-1 and specific antibodies, respectively, using plate assays. Levels of 8-OHdG and dityrosine were higher in the 3rd trimester compared with the 2nd trimester in normal subjects, and the abnormal groups generally showed lower levels than the controls, thus suggesting that they represent fetal metabolic activities. In contrast, catalytic Fe(II) was higher in the 2nd trimester than the 3rd trimester in the normal subjects, and overall the abnormal groups showed higher levels than the controls, suggesting that high catalytic Fe(II) at late gestation reflects fetal pathologic alterations. Notably, products of H2O2 and catalytic Fe(II) remained almost constant in amniotic fluid.

DOI： 10.3164/jcbn.14-82

Napsin A is a specific marker for ovarian clear cell adenocarcinoma. 査読有り国際誌

Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, Ito M, Takahashi S

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 28 巻 ( 1 ) 頁： 111 - 7 2015年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Modern Pathology

Ovarian clear cell adenocarcinoma has a relatively poor prognosis among the ovarian cancer subtypes because of its high chemoresistance. Differential diagnosis of clear cell adenocarcinoma from other ovarian surface epithelial tumors is important for its treatment. Napsin A is a known diagnostic marker for lung adenocarcinoma, and expression of napsin A is reported in a certain portion of thyroid and renal carcinomas. However, napsin A expression in ovarian surface epithelial tumors has not previously been examined. In this study, immunohistochemical analysis revealed that in 71 of 86 ovarian clear cell adenocarcinoma patients (83%) and all of the 13 patients with ovarian clear cell adenofibroma, positive napsin A staining was evident. No expression was observed in 30 serous adenocarcinomas, 11 serous adenomas or borderline tumors, 19 endometrioid adenocarcinomas, 22 mucinous adenomas or borderline tumors, 10 mucinous adenocarcinomas, or 3 yolk sac tumors of the ovary. Furthermore, expression of napsin A was not observed in the normal surface epithelium of the ovary, epithelia of the fallopian tubes, squamous epithelium, endocervical epithelium, or the endometrium of the uterus. Therefore, we propose that napsin A is another sensitive and specific marker for distinguishing ovarian clear cell tumors (especially adenocarcinomas) from other ovarian tumors.

DOI： 10.1038/modpathol.2014.61

Chemical conversion of human fibroblasts into neuronal cells: dawn of future clinical trials. 招待有り

Toyokuni S.

J Clin Biochem Nutr 56 巻頁： 165 2015年

Application of intermittent microwave irradiation to western blot analysis. 査読有り

Liu YT, Toyokuni S.

Methods Mol Biol 1314 巻頁： 185-190 2015年

Aging rather than sun exposure is a major determining factor for the density of miR-125b-positive epidermal stem cells in human skin. 査読有り

Toyokuni S, Jiang L, Wang S, Hirao A, Wada T, Soh C, Tohyama K and Kawada A.

Pathol Int 65 巻頁： 415-419 2015年

Malignant mesothelioma as an oxidative stress-induced cancer: An update. 査読有り

Chew SH and Toyokuni S.

Free Radic Biol Med 86 巻頁： 166-178 2015年

Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury. 査読有り

Hattori Y, Kotani T, Tsuda H, Mano Y, Rei T, Li H, Hirako S, Ushida T, Imai K, Nakano T, Sato Y, Miki R, Sumigama S, Iwase A, Toyokuni S and Kikkawa F.

Free Radic Res 49 巻頁： 1026-1037 2015年

Possible involvement of iron-induced oxidative insults in neurodegeneration. 査読有り

Asano T, Koike M, Sakata S, Takeda Y, Nakagawa T, Hatano T, Ohshi S, Funayama M, Yoshimi K, Sanuma M, Toyokuni S, Mochizuki H, Uchiyama Y, Hattori N and Iwai K.

Neurosci Lett 588 巻頁： 29-35 2015年

Receptor role of annexin A2 in the mesothelial endocytosis of crocidolite fibers. 査読有り

Yamashita K, Nagai H and Toyokuni S.

Lab Invest 95 巻頁： 749-764 2015年

Minimal inflammogenicity of pristine single-wall carbon nanotubes. 査読有り

Toyokuni S, Jiang L, Kitaura R and Shinohara S.

Nagoya J Med Sci 77 巻頁： 195-202 2015年

Asbestos and multi-walled carbon nanotubes generate distinct oxidative responses in inflammatory cells. 査読有り

Funahashi F, Okazaki Y, Ito D, Asakawa A, Nagai H, Tajima M and Toyokuni S.

J Clin Biochem Nutr 56: 111-117, 2015. 56 巻頁： 111-117 2015年

Catalytic ferrous iron in amniotic fluid as a predictive marker of human maternal-fetal disorders. 査読有り

Hattori Y, Mukaide T, Jiang L, Kotani T, Tsuda H, Mano Y, Sumigama S, Hirayama T, Nagasawa H, Kikkawa F and Toyokuni S.

J Clin Biochem Nutr 56: 57-63, 2015. 56 巻頁： 57-63 2015年

Napsin A is a specific marker for ovarian clear cell adenocarcinoma. 査読有り

Yamashita Y, Nagasaka T, Naiki-Ito A, Sato S, Suzuki S, Toyokuni S, Ito M and Takahashi S.

Mod Pathol 28 巻頁： 111-117 2015年

A trial to find appropriate animal models of dichloropropane-induced cholangiocarcinoma based on the hepatic distribution of glutathione S-transferases. 査読有り

Zhang L, Zong C, Ichihara S, Naito H, Toyokuni S, Kumagai S, Ichihara G.

J Occup Health. 57 巻 ( 6 ) 頁： 548-554 2015年

A trial to find appropriate animal models of dichloropropane‐induced cholangiocarcinoma based on the hepatic distribution of glutathione S‐transferases 国際誌

Zhang L., Zong C., Ichihara S., Naito H., Toyokuni S., Kumagai S., Ichihara G.

ｊｏｕｒｎａｌ　ｏｆ　Ｏｃｃｕｐａｔｉｏｎａｌ　Ｈｅａｌｔｈ 57 巻 ( 6 ) 頁： 548 - 554 2015年

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：公益社団法人日本産業衛生学会

Determinants of workplace violence against clinical physicians in hospitals: Jeng-Cheng WU, et al. Department of Urology, Taipei Medical University Hospital, Taiwan-Objectives: Workplace violence in the health sector is a worldwide concern. Physicians play an essential role in health-care teamwork; thus, understanding how organizational factors influence workplace violence against physicians is critical. Methods: A total of 189 physicians from three public hospitals and one private hospital in Northern Taiwan completed a survey, and the response rate was 47.1%. This study was approved by the institutional review board of each participating hospital. The 189 physicians were selected from the Taipei area, Taiwan. Results: The results showed that 41.5% of the respondents had received at least one workplace-related physical or verbal violent threat, and that 9.8% of the respondents had experienced at least one episode of sexual harassment in the 3 months before the survey. Logistic regression analysis revealed that physicians in psychiatry or emergency medicine departments received more violent threats and sexual harassment than physicians in other departments. Furthermore, physicians with a lower workplace safety climate (OR=0.89; 95% CI=0.81-0.98) and more job demands (OR=1.15; 95% CI=1.02-1.30) were more likely to receive violent threats. Conclusions: This study found that workplace violence was associated with job demands and the workplace safety climate. Therefore, determining how to develop a workplace safety climate and ensure a safe job environment for physicians is a crucial management policy issue for health-care systems.

DOI： 10.1539/joh.15-0085-oa

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論文 - 豊國 伸哉

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論文 - 豊國　伸哉