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Tomohiro Yan, Yukinao Sakai, Kohsuke Terada, Sho Okano, Sayuri Kawasaki, Tetsuya Kashiwagi, Masato Iwabu Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, Tokyo, JapanCorrespondence: Yukinao Sakai, Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo, 113-8603, Japan, Tel +81-03-3822-2131, Fax +81-3-3822-4865, Email y-sakai@nms.ac.jpBackground: There are numerous causes of liver function disorder in patients undergoing peritoneal dialysis (PD). Infection with the Hepatitis E virus (HEV) is a rare cause of liver injury, and the behavior of HEV in patients with PD is unclear. Since patients undergoing dialysis are frequently polypharmatic, liver injury caused by HEV infection may be misdiagnosed as drug-induced liver injury.Case Presentation: A 61-year-old woman with PD developed abrupt elevation of blood transaminase levels on a routine outpatient session. Since the patient has been receiving tolvaptan as the only new medication, we suspected tolvaptan induced liver injury. In further investigating the cause of liver injury, the blood screening test was found to be positive for HEV-IgA. The patient was diagnosed with HEV infection, and had a self-limited course.Conclusion: When encountered with patients developing liver injury during PD, HEV infection should be included in the differential diagnosis.Keywords: peritoneal dialysis, hepatitis E virus, HEV infection, liver injury

Atsushi Sobajima,1 Hisao Haniu,1,2 Hiroki Nomura,1 Manabu Tanaka,1 Takashi Takizawa,1 Takayuki Kamanaka,1 Kaoru Aoki,1,3 Masanori Okamoto,1 Kazushige Yoshida,1 Jun Sasaki,1 Kumiko Ajima,2 Chika Kuroda,1,2 Haruka Ishida,2 Satomi Okano,2 Katsuya Ueda,2 Hiroyuki Kato,1 Naoto Saito1,21Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 2Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University School of Medicine, Matsumoto, Nagano, Japan; 3Department of Applied Physical Therapy, Shinshu University School of Health Sciences, Matsumoto, Nagano, JapanPurpose: Multiwalled carbon nanotubes (MWCNTs) have been known to enter the circulatory system via the lungs from inhalation exposure; however, its carcinogenicity and subsequent accumulation in other organs have not been adequately reported in the literature. Moreover, the safety of MWCNTs as a biomaterial has remained a matter of debate, particularly when the material enters the circulatory system. To address these problems, we used carcinogenic rasH2 transgenic mice to intravenously administer highly dispersed MWCNTs and to evaluate their carcinogenicity and accumulation in the organs.Methods: Two types of MWCNTs (thin- and thick-MWCNTs) were intravenously administered at a high dose (approximately 0.7 mg per kg body weight) and low dose (approximately 0.07 mg per kg body weight).Results: MWCNTs showed pancreatic accumulation in 3.2% of mice administered with MWCNTs, but there was no accumulation in other organs. In addition, there was no significant difference in the incidence of tumor among the four MWCNTs-administered groups compared to the vehicle group without MWCNTs administration. Blood tests revealed elevated levels in mean red blood cell volume and mean red blood cell hemoglobin level for the MWCNTs-administered group, in addition to an increase in eotaxin.Conclusion: The present study demonstrated that the use of current technology to sufficiently disperse MWCNTs resulted in minimal organ accumulation with no evidence of carcinogenicity.Keywords: multiwalled carbon nanotubes, rasH2 transgenic mouse, carcinogenicity, organ accumulation, dispersion

Kazushige Yoshida,1 Masanori Okamoto,1 Jun Sasaki,1 Chika Kuroda,2 Haruka Ishida,2 Katsuya Ueda,2 Satomi Okano,2 Hirokazu Ideta,1 Takayuki Kamanaka,1 Atsushi Sobajima,1 Takashi Takizawa,1 Munehisa Kito,1 Kaoru Aoki,3 Takeshi Uemura,2 Hisao Haniu,2 Hiroyuki Kato,1 Naoto Saito2 1Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Japan; 2Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, Japan; 3Physical Therapy Division, School of Health Sciences, Shinshu University School of Medicine, Matsumoto, Japan Purpose: Although both anti-PD-1 antibody and treatments using anti-PD-L1 antibody are currently in clinical use, their therapeutic effects vary according to cancer type. One of the factors accounting for this variability is the expression level of the immune checkpoint molecule that differs between cancer types; thus, it is important to clarify the relationship between clinical outcomes and immune checkpoint molecules for all types of human cancer. The purpose of this study is to evaluate the clinical outcome of osteosarcoma in relation to PD-L1, PRF, GZMB, and IFNγ expression. Methods: Using 19 clinical specimens of osteosarcoma, we examined the expression of PD-L1, PRF, GZMB, and IFNγ in relation to their clinical outcomes. Results: PD-L1 expression correlated with early metastatic formation in clinical specimens of osteosarcoma, and the group with highly expressed functional markers for T cells such as PRF and GZMB resulted in a long overall survival time. Conclusion: This is the first study to elucidate the clinical outcomes of osteosarcoma in relation to PD-L1, PRF, GZMB, and IFNγ expression. This study provides valuable information regarding the clinical indication and prediction of effect for anti-PD-1 antibody in osteosarcoma. Keywords: anti-PD-1 antibody, perforin, granzyme B, IFNγ, osteosarcoma, clinical outcome

Chika Kuroda,1,2,* Katsuya Ueda,1,3,* Hisao Haniu,1,3–5 Haruka Ishida,1,4 Satomi Okano,1,4 Takashi Takizawa,5 Atsushi Sobajima,5 Takayuki Kamanaka,5 Kazushige Yoshida,5 Masanori Okamoto,5 Tamotsu Tsukahara,6 Yoshikazu Matsuda,7 Kaoru Aoki,8 Hiroyuki Kato,5 Naoto Saito1,3–5 1Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Asahi, Matsumoto, Nagano, Japan; 2Department of Orthopaedic Surgery, Graduate School of Medicine, Shinshu University, Asahi, Matsumoto, Nagano, Japan; 3Department of Biomedical Engineering, Graduate School of Science and Technology, Shinshu University, Asahi, Matsumoto, Nagano, Japan; 4Department of Biomedical Engineering, Graduate School of Medicine, Science and Technology, Shinshu University, Asahi, Matsumoto, Nagano, Japan; 5Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi, Matsumoto, Nagano, Japan; 6Department of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, Bunkyo-machi, Nagasaki, Japan; 7Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Komuro, Ina-machi, Saitama, Japan; 8Physical Therapy Division, School of Health Sciences, Shinshu University, Asahi, Matsumoto, Nagano, Japan *These authors contributed equally to this work Introduction: Carbon nanotubes (CNTs) have various shapes, including needle-like shapes and curled shapes, and the cytotoxicity and carcinogenicity of CNTs differ depending on their shapes and surface modifications. However, the biological responses induced by CNTs and related mechanisms according to the dispersion state of CNTs have not been extensively studied.Materials and methods: We prepared multiwalled CNTs (MWCNTs) showing different dispersions and evaluated these MWCNTs in RAW264 cells to determine cytotoxicity, cellular uptake, and immune responses. Furthermore, RAW264 cells were also used to compare the cellular uptake and cytotoxicity of fibrous MWCNTs and spherical carbon nanohorns (CNHs) exhibiting the same degree of dispersion.Results: Our analysis showed that the cellular uptake, localization, and inflammatory responses of MWCNTs differed depending on the dispersion state. Moreover, there were differences in uptake between MWCNTs and CNHs, even showing the same degree of dispersion. These findings suggested that receptors related to cytotoxicity and immune responses differed depending on the aggregated state of MWCNTs and surface modification with a dispersant. Furthermore, our results suggested that the receptors recognized by the cells differed depending on the particle shape.Conclusion: Therefore, to apply MWCNTs as a biomaterial, it is important to determine the carcinogenicity and toxicity of the CNTs and to examine different biological responses induced by varying shapes, dispersion states, and surface modifications of particles. Keywords: multiwalled carbon nanotubes, aggregation, carbon nanohorns, cytotoxicity, immune response, cellular uptake

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.icarus.2005.08.006 Byline: S. Takahashi (a)(b), H. Misawa (b), H. Nozawa (c), A. Morioka (b), S. Okano (b), R. Sood (d) Keywords: Io; Satellites; atmospheres; Jupiter; Magnetosphere Abstract: We report on two-dimensional imaging observations of D-line emissions from the extended distribution of iogenic sodium atoms with two fields of view ([+ or -]20 R.sub.J (narrow FOV) and [+ or -]400 R.sub.J (wide FOV)) simultaneously by using a portable small telescope or camera lens. We derived dynamic feature of the band-shaped and spray-shaped distributions near Io's orbit by means of continuous observation. The observations confirm the phenomenological behavior of the sodium cloud on two spatial scales, as previously observed by Pilcher et al. [Pilcher, C.B., Smyth, W.H., Combi, M.R., Fertel, J.H., 1984. Astrophys. J. 287, 427-444], Schneider et al. [Schneider, N.M., Trauger, J.T., Wilson, J.K., Brown, D.I., Evans, R.W., Shemansky, D.E., 1991. Science 253, 1394-1397], and Mendillo et al. [Mendillo, M., Baumgartner, J., Flynn, B., Hughes, W.S., 1990. Nature 348, 312-314]. We also confirm an elongated oval emission distribution of the sodium nebula and derivation of its detailed east-west asymmetry depending on Io's phase angle, which was first noted by Flynn et al. [Flynn, B., Mendillo, M., Baumgartner, J., 1994. J. Geophys. Res. 99, 8403-8409]. We then did model analyses to investigate the source process for sodium atoms and the dynamics behind their distribution. We conclude that the essential of molecular ion mechanisms to the band-shaped distribution is in agreement with Wilson and Schneider [Wilson, J.K., Schneider, N.M., 1999. J. Geophys. Res. 104, 16567-16583]. We differ from Wilson et al. [Wilson, J.K., Mendillo, M., Baumgartner, J., Schneider, N.M., Trauger, J.T., Flynn, B., 2002. Icarus 157, 476-489] in finding that charge exchange process contributes more to the spray-shaped distribution and sodium nebula than sputtering does. These results derived the double-peaked velocity distribution of released sodium atoms, and re-confirmed the source rates in agreement with past studies. Author Affiliation: (a) Information and Mathematical Science Laboratory, Inc., Tokyo, Japan (b) Planetary Plasma and Atmospheric Research Center, Tohoku University, Sendai, Japan (c) Department of Physics, Rikkyo University, Tokyo, Japan (d) School of Physics, ADFA, University of New South Wales, Canberra, Australia Article History: Received 14 September 2004; Revised 17 August 2005