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The utility of the repeated-dose liver micronucleus (RDLMN) assay in the detection of a genotoxic hepatocarcinogen was evaluated. In this paper, a rat hepatocarcinogen, 2-nitropropane (2-NP), was administered orally to young adult rats for 14 and 28 days without a partial hepatectomy or a mitogen, and the micronucleus induction in liver was examined using a simple method to isolate hepatocytes. In addition, a bone marrow micronucleus assay was conducted concomitantly. The frequency of micronucleated hepatocytes induced by 2-NP increased significantly in both the 14- and 28-day repeated-dose studies, while the bone marrow micronucleus assays were negative in each study. These results indicate that the RDLMN assay is useful for detecting a genotoxic hepatocarcinogen that is negative in bone marrow micronucleus assays and is a suitable in vivo genotoxicity test method for integration into a repeated-dose general toxicity study., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This paper analyses how the conceptual and therapeutic formation of Japanese traditional medicine (Kampo) has been socially constructed through interactions with popular interpretations of illness. Taking the example of emotion-related disorders, this paper focuses on the changing meaning of constraint (utsu) in Kampo medicine. Utsu was once a name for one of the most frequently cited emotion-related disorders and pathological concerns during the Edo period. With the spread of Western medicine in the Meiji period, neurasthenia replaced utsu as the dominant emotion-related disorder in Japanese society. As a result, post-Meiji doctors developed other conceptual tools and strategies to respond to these new disease categories, innovations that continue to influence contemporary practitioners. I begin this history by focusing on Wada Tōkaku, a Japanese doctor of the Edo period who developed a unique theory and treatment strategy for utsu. Secondly, I examine. Yomuto Kyūshin and Mori Dōhaku, Kampo doctors of the early twentieth century, who privileged neurasthenia over utsu in their medical practice. The paper concludes with a discussion of the flexibility and complexity of Kampo medicine, how its theory and practices have been influenced by cross-cultural changes in medicine and society, while incorporating the popular experience of illness as well.

Maturity-onset diabetes of the young type 3 (MODY3) is caused by heterozygous mutation in the HNF1A gene. Liver adenomatosis has been reported in MODY3 patients. The patient reported in this paper is a Japanese girl who first developed hepatomegaly, fatty liver, and hepatic dysfunction at age 5 years. Liver biopsy demonstrated steatosis and degeneration of hepatocytes. At that time, blood glucose and HbA1c levels were within normal ranges. Elevated HbA1c was noticed 4 years later, but islet cell and glutamic acid decarboxylase antibodies were not detected in the serum. Therefore, MODY3 was suspected and subsequent analysis of the HNF1A gene identified a heterozygous germline splice donor-site mutation in intron 9. MODY3 patients should be screened by non-invasive liver imaging, and careful follow-up of liver disease should be performed.

Introduction: TT virus has been recently isolated in Japan in patients with acute and chronic non-A/non-G hepatitis. Its possible etiopathogenetic role in causing hepatitis has been initially taken in consideration. On the contrary, more recent studies deny the importance of TT virus in causing liver damage. Most of the studies are based on serological data or on viral detection from frozen liver tissue., Aim of the Study: In the present paper we describe a method to detect viral genome from formalin-fixed and paraffin-embedded liver tissue., Materials and Methods: Twelve needle biopsies from liver were studied. Six cases were selected on the basis of serological negativity for HBV and HCV markers. Five cases of HCV-related chronic hepatitis and one HCV- and HIV-positive intravenous drug abuser were also included. All patients underwent liver biopsy, performed with a 14-G needle. Liver specimens were formalin-fixed and paraffin-embedded as routine. From each block, sections were cut and stained for histopathologic examination. Additional 5 microns sections were employed to extract DNA for nested PCR., Results: In 2 of 12 cases studied, TT virus genome was found. In both cases the presence of viral DNA was confirmed by sequencing. Both patients were male. The first patient was a 39-year-old HIV- and HCV-positive intravenous drug abuser. The second patient was a 60-year-old heavy alcohol drinker. In both cases the presence of TT virus apparently did not affect the histological picture., Conclusion: It is possible to detect TT virus genome from formalin-fixed and paraffin-embedded tissue. This method offers the possibility to perform retrospective studies.