KEIO JOURNAL OF MEDICINE最新文献

{"title":"Antifungal Agent Luliconazole Inhibits the Growth of Mouse Glioma-initiating Cells in Brain Explants.","authors":"Hideaki Nagashima,&nbsp;Naoyoshi Koike,&nbsp;Kazunari Yoshida,&nbsp;Hideyuki Saya,&nbsp;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,&nbsp;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":"Historical overview.","authors":"T. Fujino, R. Calderhead","doi":"10.3109/00016486509127779","DOIUrl":"https://doi.org/10.3109/00016486509127779","url":null,"abstract":"","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"50 Suppl 2 1","pages":"11-6"},"PeriodicalIF":2.0,"publicationDate":"2020-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/00016486509127779","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43865655","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,&nbsp;Yasushi Sera,&nbsp;Koichiro Azuma,&nbsp;Kazuki Sato,&nbsp;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 VO₂ 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 VO₂, 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,&nbsp;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}

{"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}

{"title":"COVID-19: Stay Cool toward Corticosteroids.","authors":"Seitaro Fujishima","doi":"10.2302/kjm.2020-0007-LE","DOIUrl":"https://doi.org/10.2302/kjm.2020-0007-LE","url":null,"abstract":"Due to the global COVID-19 pandemic, intensive care units and general wards are packed with infected patients whose conditions are often complicated by sepsis, acute respiratory failure, or acute respiratory distress syndrome (ARDS). Under the current circumstances, in which no established drugs are available, clinicians have been attempting to treat patients with a wide range of existing drugs, including low-to-high doses of corticosteroids, particularly for critically ill patients. Corticosteroid administration often lowers fever and decreases laboratory indices of inflammation; however, these short-term clinical improvements do not necessarily lead to improved long-term outcomes. Because corticosteroids produce a broad spectrum of anti-inflammatory and immunosuppressive effects,1,2 we should be cautious before initiating corticosteroid treatment, especially at a high dose, without the coadministration of antimicrobials for such acute infections. Over the past two decades, corticosteroids have been used to a significant extent to treat patients during epidemics of severe acute respiratory syndrome (SARS)coronavirus (CoV), Middle East respiratory syndrome (MERS)-CoV, and H1N1 influenza. In the initial phase of the SARS epidemic, even high-dose pulse therapy with methylprednisolone (≥500 mg/day) was suggested to be effective.3 However, the efficacy of corticosteroids remains unproven, and an increase in viral load was observed in SARS patients.4,5 With regard to acute respiratory failure or ARDS associated with H1N1 influenza, the efficacy of low-to-moderate dose corticosteroids in combination with oseltamivir was suggested in early reports,6,7 but later larger studies and systematic reviews showed either no efficacy or harmfulness for H1N1 infection and H1N1-associated ARDS.8–10 Corticosteroids were also administered to MERS-CoV patients, but its ineffectiveness and resultant delayed viral clearance were revealed in a recent large-scale multicenter study.11 There are conflicting results regarding COVID-19. A singlecenter retrospective study reported the possible efficacy of corticosteroids for COVID-19-associated ARDS by unadjusted Kaplan–Meier analysis.12 In contrast, another larger single-center cohort study suggested the harmfulness of high-dose corticosteroids by Cox proportional hazards analysis, although the definition of high dose was not clear.13 In a recently published systematic review of coronavirus infection, corticosteroid use was associated with higher mortality.14 COVID-19 infections are often associated with sepsis and ARDS, and the efficacy of corticosteroids for these critical conditions has been assessed by multiple randomized controlled trials. High-dose methylprednisolone treatments using either 30 mg/kg/6 h four times or an initial dose of 30 mg/kg followed by 5 mg/kg/h for 9 h were proven ineffective for both sepsis and ARDS.15–18 Although low-dose hydrocortisone is effective for the reversal of shock, its efficacy in impr","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 2","pages":"27-29"},"PeriodicalIF":2.0,"publicationDate":"2020-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2020-0007-LE","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37993561","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":"Percutaneous Tendon Needling without Ultrasonography for Lateral Epicondylitis.","authors":"Taku Suzuki,&nbsp;Takuji Iwamoto,&nbsp;Noboru Matsumura,&nbsp;Masaya Nakamura,&nbsp;Morio Matsumoto,&nbsp;Kazuki Sato","doi":"10.2302/kjm.2019-0004-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0004-OA","url":null,"abstract":"<p><p>Percutaneous ultrasonic tendon needling has been used to treat persistent lateral epicondylitis, and its efficacy has been demonstrated. However, whether ultrasonography is necessary remains unclear. The purpose of this retrospective study was to evaluate the efficacy of percutaneous tendon needling without ultrasonography for lateral epicondylitis. A total of 36 patients who underwent tendon needling without ultrasonography for lateral epicondylitis were retrospectively included in the study. The tendinotic lesion was needled by fenestration approximately 20-30 times without sonographic assistance. The Visual Analogue Scale (VAS) pain score, the grip strength, and success rates were assessed at baseline and at 1, 3, 6, and 12 months after treatment. The Nirschl tennis elbow score was evaluated at baseline and at 6 and 12 months after the needling procedure. The mean VAS pain score and grip strength at 3, 6, and 12 months significantly improved compared to the baseline values. At 6 and 12 months, the success rates had significantly increased compared to the rates at 1 month. The mean Nirschl scores at 6 and 12 months were significantly better than the baseline value. No severe complications were observed during the study period. Percutaneous tendon needling without ultrasonography is a simple and safe technique. The procedure is effective for lateral epicondylitis that is unresponsive to conventional conservative treatments.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 2","pages":"37-42"},"PeriodicalIF":2.0,"publicationDate":"2020-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0004-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37402372","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":"Physical Parameters, Use of Specific Medical Treatments, Nursing Levels, and Activities of Daily Living Are Potential Indicators for Forgoing Maintenance Hemodialysis.","authors":"Nobuko Yamaguchi,&nbsp;Tadashi Yoshida,&nbsp;Miho Oba,&nbsp;Reiko Nakano,&nbsp;Miwa Saito,&nbsp;Mihoko Hirokawa,&nbsp;Tazuru Shinmi,&nbsp;Chisa Urasawa,&nbsp;Mototsugu Oya","doi":"10.2302/kjm.2019-0001-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0001-OA","url":null,"abstract":"<p><p>Maintenance hemodialysis (HD) therapy is essential for survival in patients with end-stage renal disease (ESRD); however, HD can also be life-threatening in the final stages of ESRD. Currently, no clear indicators and/or biomarkers exist regarding when HD should be forgone. In the present study, we examined temporal changes in multiple clinical parameters, including biochemical data, physical data, the use of specific medical treatments, nursing care levels, and the activities of daily living (ADL) in 47 ESRD patients who underwent maintenance HD and who died in our hospital. We also investigated the status of informed consents regarding the forgoing of HD in these patients. We found that while biochemical parameters were unaltered, physical parameters such as consciousness levels and blood pressure gradually deteriorated during hospitalization. The use of the following specific medical treatments significantly increased over time: vasopressor use, O₂ inhalation, and ventilator use. The need for nursing care increased and the ADL levels decreased toward the time of death. Medical doctors gave information regarding forgoing HD to patients and/or their family/relatives in 55% of cases, obtained agreement to forego HD in 45% of cases, and HD was actually foregone in 38% of cases. Most clinical parameters were not significantly different between the patients whose HD sessions were forgone versus those in whom HD was continued, indicating that HD was foregone in the very last stages of life. The results suggest that physical parameters, the use of specific medical treatments, the levels of nursing care, and ADL are potential indicators for forgoing HD in the final stages of ESRD.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 1","pages":"16-25"},"PeriodicalIF":2.0,"publicationDate":"2020-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0001-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37386274","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}