K. Abe, T. Shimura, T. Takenouchi, Yuka W. Iwasaki, H. Ishizu, Y. Uwamino, S. Uno, Jun Gotoh, N. Tachikawa, Y. Takeuchi, Junpei Katayama, H. Nozaki, Susumu Fujii, S. Seki, Morio Nakamura, Kazuhiro Uda, T. Misumi, J. Ishihara, Kenichiro Yamada, Toshio Kanai, S. Murai, Kazuhiro Araki, T. Ebihara, Haruhiko Shiomi, N. Hasegawa, Y. Kitagawa, M. Amagai, M. Suematsu, K. Kosaki
{"title":"Identification of B.1.346 lineage of SARS-CoV-2 in Japan: Genomic evidence of re-entry of Clade 20C","authors":"K. Abe, T. Shimura, T. Takenouchi, Yuka W. Iwasaki, H. Ishizu, Y. Uwamino, S. Uno, Jun Gotoh, N. Tachikawa, Y. Takeuchi, Junpei Katayama, H. Nozaki, Susumu Fujii, S. Seki, Morio Nakamura, Kazuhiro Uda, T. Misumi, J. Ishihara, Kenichiro Yamada, Toshio Kanai, S. Murai, Kazuhiro Araki, T. Ebihara, Haruhiko Shiomi, N. Hasegawa, Y. Kitagawa, M. Amagai, M. Suematsu, K. Kosaki","doi":"10.1101/2021.01.29.21250798","DOIUrl":"https://doi.org/10.1101/2021.01.29.21250798","url":null,"abstract":"Objectives Whole SARS-CoV-2 genome sequencing from COVID-19 patients is useful for infection control and regional trends evaluation. We report a lineage data collected from hospitals in the Kanto region of Japan. Methods We performed whole genome sequencing in specimens of 198 COVID-19 patients at 13 collaborating hospitals in the Kanto region. Phylogenetic analysis and fingerprinting of the nucleotide substitutions underwent to differentiate and classify the viral lineages. Results More than 90% of the strains belonged to Clade 20B and two lineages (B.1.1.284 and B.1.1.214) have been detected predominantly in the Kanto region. However, one sample from a COVID-19 patient in November 2020, belonged to the B.1.346 lineage of Clade 20C, which has been prevalent in western United States. The patient had no history of overseas travel and no contact with anyone who had travelled abroad, suggesting that this strain appeared likely to have been imported from western United States, across the strict quarantine barrier. Conclusion B.1.1.284 and B.1.1.214 have been identified predominantly in the Kanto region and B.1.346 of clade 20C in one patient was probably imported from western United States. These results illustrate that a decentralized network of hospitals can be significantly advantageous for monitoring regional molecular epidemiologic trends.","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"1 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2021-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44109120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Outbreak of Health Care-associated Novel Coronavirus (SARS-coV-2) COVID-19 infections in the Spring of 2020.","authors":"Yuko Kitagawa","doi":"10.2302/kjm.kjm-covid19-01","DOIUrl":"https://doi.org/10.2302/kjm.kjm-covid19-01","url":null,"abstract":"<p><p>As the Director General of Keio University Hospital, I hereby document the recent outbreak of health care-associated novel coronavirus (SARS-CoV-2) COVID-19 infections at our hospital in the spring of 2020.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"70 1","pages":"1-6"},"PeriodicalIF":2.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25523284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypertrophic Cardiomyopathy: Diverse Pathophysiology Revealed by Genetic Research, Toward Future Therapy.","authors":"Takeharu Hayashi","doi":"10.2302/kjm.2019-0012-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0012-OA","url":null,"abstract":"<p><p>Hypertrophic cardiomyopathy (HCM) is an intractable disease that causes heart failure mainly due to unexplained severe cardiac hypertrophy and diastolic dysfunction. HCM, which occurs in 0.2% of the general population, is the most common cause of sudden cardiac death in young people. HCM has been studied extensively using molecular genetic approaches. Genes encoding cardiac β-myosin heavy chain, cardiac myosin-binding protein C, and troponin complex, which were originally identified as causative genes, were subsequently reported to be frequently implicated in HCM. Indeed, HCM has been considered a disease of sarcomere gene mutations. However, fewer than half of patients with HCM have mutations in sarcomere genes. The others have been documented to have mutations in cardiac proteins in various other locations, including the Z disc, sarcoplasmic reticulum, plasma membrane, nucleus, and mitochondria. Next-generation sequencing makes it possible to detect mutations at high throughput, and it has become increasingly common to identify multiple cardiomyopathy-causing gene mutations in a single HCM patient. Elucidating how mutations in different genes contribute to the disease pathophysiology will be a challenge. In studies using animal models, sarcomere mutations generally tend to increase myocardial Ca<sup>2+</sup> sensitivity, and some mutations increase the activity of myosin ATPase. Clinical trials of drugs to treat HCM are ongoing, and further new therapies based on pathophysiological analyses of the causative genes are eagerly anticipated.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 4","pages":"77-87"},"PeriodicalIF":2.0,"publicationDate":"2020-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0012-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37782488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Antifungal Agent Luliconazole Inhibits the Growth of Mouse Glioma-initiating Cells in Brain Explants.","authors":"Hideaki Nagashima, Naoyoshi Koike, Kazunari Yoshida, Hideyuki Saya, Oltea Sampetrean","doi":"10.2302/kjm.2020-0001-OA","DOIUrl":"https://doi.org/10.2302/kjm.2020-0001-OA","url":null,"abstract":"<p><p>Imidazole antifungal compounds exert their antipathogenic effects through inhibition of sterol biosynthesis. These drugs have also recently been identified as candidate anticancer agents for several solid tumors including glioblastoma. However, their effects on glioma-initiating cells (GICs), i.e., glioma cells with stemlike properties that are able to initiate tumors, remain unclear. Consequently, we examined the effects of the optically active imidazole compound luliconazole on mouse GICs and GIC-based tumors. Luliconazole impaired in a concentration-dependent manner the growth of spheres formed by GICs in vitro. In contrast to the inhibitory effects of ionizing radiation and temozolomide on sphere growth, that of luliconazole was attenuated by the addition of exogenous cholesterol. Exposure to luliconazole of brain slices derived from mice with orthotopic GIC implants for 4 days in culture resulted in a marked increase in the number of tumor cells positive for cleaved caspase-3, but without a similar effect on normal cells. Furthermore, in brain slices, luliconazole inhibited the expansion of GIC-based tumors and the parenchymal infiltration of tumor cells. Our findings therefore indicate that luliconazole effectively targets GICs, thereby providing further support for the antitumorigenic effects of imidazole antifungal compounds.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 4","pages":"97-104"},"PeriodicalIF":2.0,"publicationDate":"2020-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38227292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Circulating microRNAs: Next-generation Cancer Detection.","authors":"Juntaro Matsuzaki, Takahiro Ochiya","doi":"10.2302/kjm.2019-0011-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0011-OA","url":null,"abstract":"<p><p>Early detection of cancer is crucial for its ultimate control and the prevention of malignant progression. In Japan, a nationwide project was conducted between 2014 and 2019 to develop novel cancer detection tools using serum microRNAs (miRNAs). Using the National Cancer Center Biobank, we collected more than 10,000 serum samples from patients with malignant diseases, including rare cancers such as ovarian cancer, gliomas, and sarcomas. Subsequently, comprehensive miRNA microarray analyses were performed for all samples. This serum miRNA database provides insights regarding miRNA biomarker candidates for each cancer type. Here, we summarize the major achievements of this national project. Notably, although circulating miRNAs packaged in extracellular vesicles are thought to be a cell-to-cell communication tool, the functional characteristics of the miRNAs listed in the project are still unknown. We hope that our findings will help elucidate the biological functions of circulating miRNAs.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 4","pages":"88-96"},"PeriodicalIF":2.0,"publicationDate":"2020-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0011-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37931655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Body Motion and Rowing Performance: Association between Hip Angle and Rowing Performance: A Pilot Study.","authors":"Masato Fumoto, Yasushi Sera, Koichiro Azuma, Kazuki Sato, Hideo Matsumoto","doi":"10.2302/kjm.2019-0007-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0007-OA","url":null,"abstract":"<p><p>The importance of aerobic fitness in rowing has been widely studied, and it is accepted that aerobic fitness is a key factor in rowing performance. In contrast, the impact of rowing efficacy, especially rowing form, on rowing performance has not yet been fully elucidated. The present study aimed to investigate this subject via the analysis of hip kinematics and the association of this variable with 2000 m ergometer rowing test performance. Eleven adult male rowers underwent a 2000 m rowing test on an ergometer and the exhaled gas was analyzed. The hip joint angle, the pelvic rotation, and the knee joint angle were measured at the catch position throughout the test. Peak VO<sub>2</sub> was strongly associated with the time taken to complete the test (ρ=-0.96, P<0.01), thereby confirming the importance of aerobic capacity in rowing performance. The variance of the hip joint angle of each rower was associated with peak VO<sub>2</sub>, lean mass, and test time (ρ=-0.72, -0.84, and 0.66, respectively, all P<0.05). Greater knee flexion was accompanied by larger posterior rotation of the pelvis (ρ=0.74, P<0.05), and was negatively associated with hip flexion (ρ=-0.76, P<0.05). Although we cannot confirm whether the consistency of the hip joint angle actually leads to better rowing performance, our results suggest that there are associations between the consistency of the hip joint angle, aerobic capacity, lean mass, and the time taken to complete the 2000 m ergometer rowing test.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 3","pages":"66-75"},"PeriodicalIF":2.0,"publicationDate":"2020-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0007-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37569846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Direct Cardiac Reprogramming for Cardiovascular Regeneration and Differentiation.","authors":"Taketaro Sadahiro, Masaki Ieda","doi":"10.2302/kjm.2019-0008-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0008-OA","url":null,"abstract":"<p><p>Cardiovascular disease is the leading cause of death worldwide. Cardiomyocytes have limited regenerative capacity; consequently, regenerative therapies are in high demand. There are currently several potential strategies for heart regeneration, with one approach involving in situ generation of new cardiomyocytes from endogenous cell sources. Direct cardiac reprogramming has emerged as a novel therapeutic approach to regenerating the damaged heart by directly converting endogenous cardiac fibroblasts into cardiomyocyte-like cells. Following our first report of direct cardiac reprogramming, significant advances have elucidated the molecular mechanisms associated with cardiac reprogramming. These advances have also improved cardiac-reprogramming efficiency by enabling direct in vivo cardiac reprogramming. Moreover, progress has been made in cardiac reprogramming of human fibroblasts. Although basic research has supported substantial progress in this field, numerous challenges remain in terms of clinical application. Here, we review the current state of cardiac reprogramming as a new technology for understanding and treating cardiovascular diseases.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 3","pages":"49-58"},"PeriodicalIF":2.0,"publicationDate":"2020-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0008-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37524244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takuma Ohnishi, Yoshinori Mishima, Shohei Takizawa, Kentaro Tsutsumi, Atsuko Amemiya, Nao Akiyama, Yukiko Kanna, S. Asato, Mizue Tomita, M. Ikemiyagi, Nobuaki Shikoro, Maki Nakazawa, Nobuyoshi Kurihara, I. Kamimaki
{"title":"Clinical Features of Febrile Urinary Tract Infection Caused by Extended-spectrum Beta-lactamase-producing Escherichia Coli in Children.","authors":"Takuma Ohnishi, Yoshinori Mishima, Shohei Takizawa, Kentaro Tsutsumi, Atsuko Amemiya, Nao Akiyama, Yukiko Kanna, S. Asato, Mizue Tomita, M. Ikemiyagi, Nobuaki Shikoro, Maki Nakazawa, Nobuyoshi Kurihara, I. Kamimaki","doi":"10.2302/kjm.2019-0005-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0005-OA","url":null,"abstract":"The global prevalence of infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli has been increasing. In children, ESBL-producing E. coli manifest mostly as febrile urinary tract infections (fUTIs). This study aimed to elucidate the clinical features of fUTI resulting from ESBL-producing E. coli in Japanese patients. The clinical features of children with E. coli-related fUTI were retrospectively examined. These children underwent treatment at the National Hospital Organization Saitama Hospital, Japan, between May 2010 and April 2018. Urine specimens were obtained by either bladder catheterization or the clean-catch method. All children having positive urine cultures (≥104 colony-forming unit/mL for catheter specimens and ≥105 colony forming unit/mL for clean-catch specimens) and a fever of ≥38°C were considered to have fUTI. During the study period, 171 patients were diagnosed with E. coli-related fUTI. Among these, 17 (9.9%) fUTI cases were caused by ESBL-producing E. coli. A significant difference was noted in the median age of the populations having ESBL-producing E. coli and non-ESBL-producing E. coli infections (2 and 5 months, respectively); other characteristics were not significantly different between the two patient groups. ESBL-producing E. coli infections markedly increased in our hospital between 2013 and 2018. In the present study, young age was the only risk factor for fUTI caused by ESBL-producing E. coli identified in Japanese children.","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2020-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0005-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46467692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Organ Fabrication Using Pigs as An in Vivo Bioreactor.","authors":"E. Kobayashi, S. Tohyama, K. Fukuda","doi":"10.2302/kjm.2019-0006-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0006-OA","url":null,"abstract":"We present the most recent research results on the creation of pigs that can accept human cells. Pigs in which grafted human cells can flourish are essential for studies of the production of human organs in the pig and for verification of the efficacy of cells and tissues of human origin for use in regenerative therapy. First, against the background of a worldwide shortage of donor organs, the need for future medical technology to produce human organs for transplantation is discussed. We then describe proof-of-concept studies in small animals used to produce human organs. An overview of the history of studies examining the induction of immune tolerance by techniques involving fertilized animal eggs and the injection of human cells into fetuses or neonatal animals is also presented. Finally, current and future prospects for producing pigs that can accept human cells and tissues for experimental purposes are discussed.","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2020-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0006-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46631085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}