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  1. Sakurai K, Onouchi T, Yamada S, Baba Y, Murata T, Tsukamoto T, et al.
    Malays J Pathol, 2019 Dec;41(3):339-343.
    PMID: 31901919
    INTRODUCTION: Cribriform-morular variant (CMV) is a rare variant of papillary thyroid carcinoma. It frequently occurs in association with familial adenomatous polyposis (FAP), although some cases are sporadic. Herein, we report a case of CMV and analyse morule cytohistology.

    CASE REPORT: The patient was a 47-year-old woman with no familial history of FAP. A 3.0-cm unifocal mass was identified in the left thyroidal lobe. Fine-needle aspiration cytology revealed papillary clusters of atypical cells with nuclear grooves, which was suspected to be conventional papillary thyroid carcinoma. Histologically, the tumour comprised a papillary and cribriform growth of atypical cells with cytoplasmic accumulation and nuclear translocation of b-catenin. In addition, frequent morule formation was identified.

    DISCUSSION: In this case, we performed morule analysis through correlative light and electron microscopy (CLEM), and revealed its ultrastructure. Although CMV is a rare form of thyroid carcinoma, it should be considered along with its distinct clinicopathological characteristics.

  2. Sekizuka T, Kai M, Nakanaga K, Nakata N, Kazumi Y, Maeda S, et al.
    PLoS One, 2014;9(12):e114848.
    PMID: 25503461 DOI: 10.1371/journal.pone.0114848
    Mycobacterium abscessus group subsp., such as M. massiliense, M. abscessus sensu stricto and M. bolletii, are an environmental organism found in soil, water and other ecological niches, and have been isolated from respiratory tract infection, skin and soft tissue infection, postoperative infection of cosmetic surgery. To determine the unique genetic feature of M. massiliense, we sequenced the complete genome of M. massiliense type strain JCM 15300 (corresponding to CCUG 48898). Comparative genomic analysis was performed among Mycobacterium spp. and among M. abscessus group subspp., showing that additional ß-oxidation-related genes and, notably, the mammalian cell entry (mce) operon were located on a genomic island, M. massiliense Genomic Island 1 (MmGI-1), in M. massiliense. In addition, putative anaerobic respiration system-related genes and additional mycolic acid cyclopropane synthetase-related genes were found uniquely in M. massiliense. Japanese isolates of M. massiliense also frequently possess the MmGI-1 (14/44, approximately 32%) and three unique conserved regions (26/44; approximately 60%, 34/44; approximately 77% and 40/44; approximately 91%), as well as isolates of other countries (Malaysia, France, United Kingdom and United States). The well-conserved genomic island MmGI-1 may play an important role in high growth potential with additional lipid metabolism, extra factors for survival in the environment or synthesis of complex membrane-associated lipids. ORFs on MmGI-1 showed similarities to ORFs of phylogenetically distant M. avium complex (MAC), suggesting that horizontal gene transfer or genetic recombination events might have occurred within MmGI-1 among M. massiliense and MAC.
  3. Nakayama E, Tajima S, Kotaki A, Shibasaki KI, Itokawa K, Kato K, et al.
    J Travel Med, 2018 01 01;25(1).
    PMID: 29394382 DOI: 10.1093/jtm/tax072
    Background: Due to the huge 2-way human traffic between Japan and Chikungunya (CHIK) fever-endemic regions, 89 imported cases of CHIK fever were confirmed in Japan from January 2006 to June 2016. Fifty-four of 89 cases were confirmed virologically and serologically at the National Institute of Infectious Diseases, Japan and we present the demographic profiles of the patients and the phylogenetic features of 14 CHIK virus (CHIKV) isolates.

    Methods: Patients were diagnosed with CHIK fever by a combination of virus isolation, viral RNA amplification, IgM antibody-, IgG antibody-, and/or neutralizing antibody detection. The whole-genome sequences of the CHIKV isolates were determined by next-generation sequencing.

    Results: Prior to 2014, the source countries of the imported CHIK fever cases were limited to South and Southeast Asian countries. After 2014, when outbreaks occurred in the Pacific and Caribbean Islands and Latin American countries, there was an increase in the number of imported cases from these regions. A phylogenetic analysis of 14 isolates revealed that four isolates recovered from three patients who returned from Sri Lanka, Malaysia and Angola, belonged to the East/Central/South African genotype, while 10 isolates from 10 patients who returned from Indonesia, the Philippines, Tonga, the Commonwealth of Dominica, Colombia and Cuba, belonged to the Asian genotype.

    Conclusion: Through the phylogenetic analysis of the isolates, we could predict the situations of the CHIK fever epidemics in Indonesia, Angola and Cuba. Although Japan has not yet experienced an autochthonous outbreak of CHIK fever, the possibility of the future introduction of CHIKV through an imported case and subsequent local transmission should be considered, especially during the mosquito-active season. The monitoring and reporting of imported cases will be useful to understand the situation of the global epidemic, to increase awareness of and facilitate the diagnosis of CHIK fever, and to identify a future CHIK fever outbreak in Japan.

  4. Higuchi H, Yamakawa N, Imadome KI, Yahata T, Kotaki R, Ogata J, et al.
    Blood, 2018 06 07;131(23):2552-2567.
    PMID: 29685921 DOI: 10.1182/blood-2017-07-794529
    Epstein-Barr virus (EBV) causes various diseases in the elderly, including B-cell lymphoma such as Hodgkin's lymphoma and diffuse large B-cell lymphoma. Here, we show that EBV acts in trans on noninfected macrophages in the tumor through exosome secretion and augments the development of lymphomas. In a humanized mouse model, the different formation of lymphoproliferative disease (LPD) between 2 EBV strains (Akata and B95-8) was evident. Furthermore, injection of Akata-derived exosomes affected LPD severity, possibly through the regulation of macrophage phenotype in vivo. Exosomes collected from Akata-lymphoblastoid cell lines reportedly contain EBV-derived noncoding RNAs such as BamHI fragment A rightward transcript (BART) micro-RNAs (miRNAs) and EBV-encoded RNA. We focused on the exosome-mediated delivery of BART miRNAs. In vitro, BART miRNAs could induce the immune regulatory phenotype in macrophages characterized by the gene expressions of interleukin 10, tumor necrosis factor-α, and arginase 1, suggesting the immune regulatory role of BART miRNAs. The expression level of an EBV-encoded miRNA was strongly linked to the clinical outcomes in elderly patients with diffuse large B-cell lymphoma. These results implicate BART miRNAs as 1 of the factors regulating the severity of lymphoproliferative disease and as a diagnostic marker for EBV+ B-cell lymphoma.
  5. Nongpiur ME, Khor CC, Jia H, Cornes BK, Chen LJ, Qiao C, et al.
    PLoS Genet, 2014 Mar;10(3):e1004089.
    PMID: 24603532 DOI: 10.1371/journal.pgen.1004089
    Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.
  6. Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, et al.
    Nat Genet, 2016 May;48(5):556-62.
    PMID: 27064256 DOI: 10.1038/ng.3540
    Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.
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