KEIO JOURNAL OF MEDICINE最新文献

{"title":"Casting Light on Life.","authors":"Atsushi Miyawaki","doi":"10.2302/kjm.69-001-ABST","DOIUrl":"https://doi.org/10.2302/kjm.69-001-ABST","url":null,"abstract":"<p><p>The behavior of biochemical molecules moving around in cells makes me think of a school of whales wandering in the ocean, captured by the Argus system on the artificial satellite. When bringing a whale back into the sea --- with a transmitter on its dorsal fin, every staff member hopes that it will return safely to a school of its species. A transmitter is now minute in size, but it was not this way before. There used to be some concern that a whale fitted with a transmitter could be given the cold shoulder and thus ostracized by other whales for \"wearing something annoying.\" How is whale's wandering related to the tide or a shoal of small fish? What kind of interaction is there among different species of whales? We human beings have attempted to fully understand this fellow creature in the sea both during and since the age of whale fishing.In a live cell imaging experiment, a luminescent probe replaces a transmitter. We put a luminescent probe on a specific region of a biological molecule and bring it back into a cell. We can then visualize how the molecule behaves in response to external stimulation. Since luminescence is a physical phenomenon, we can extract various kinds of information by making full use of its characteristics.Cruising inside cells in a supermicro corps, gliding down in a microtubule like a roller coaster, pushing our ways through a jungle of chromatin while hoisting a flag of nuclear localization signal --- we are reminded to retain a playful and adventurous perspective at all times. What matters is mobilizing all capabilities of science and giving full play to our imagination. We believe that such serendipitous findings can arise out of such a sportive mind, a frame of mind that prevails when enjoying whale-watching.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 4","pages":"105"},"PeriodicalIF":2.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38774738","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":"Cell Atlases as Roadmaps in Health and Disease.","authors":"Aviv Regev","doi":"10.2302/kjm.69-002-ABST","DOIUrl":"https://doi.org/10.2302/kjm.69-002-ABST","url":null,"abstract":"<p><p>The recent advent of methods for high-throughput single-cell and spatial profiling have opened the way to complete the 150-year-old endeavor of identifying all cell types in the human body, by their distinctive molecular profiles, and to relate this information to other cellular descriptions, physiological phenotypes, molecular mechanisms and functions. Our effort to build a comprehensive reference map of the molecular state of cells in healthy human tissues is propelling the systematic study of physiological states, developmental trajectories, regulatory circuitry and interactions of cells, provides a framework for understanding cellular dysregulation in human disease, and suggests the possibility of predicting cell types and behaviors, towards a \"periodic table of our cells\". In this talk, I describe our foundational work underlying single cell genomics and the conceptual framework and impact of our understanding of cell and tissue biology in health, as well as how we use it to shed light on rare disease, cancer, and COVID-19.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"69 4","pages":"105"},"PeriodicalIF":2.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38774736","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":"Incidence, Clinical Characteristics, and Long-term Outcome of the Dilated Phase of Hypertrophic Cardiomyopathy.","authors":"Yoshiyasu Aizawa,&nbsp;Yoko Tanimoto,&nbsp;Yoshiko Hirata,&nbsp;Taishi Fujisawa,&nbsp;Ryoma Fukuoka,&nbsp;Kazuaki Nakajima,&nbsp;Yoshinori Katsumata,&nbsp;Takahiko Nishiyama,&nbsp;Takehiro Kimura,&nbsp;Shinsuke Yuasa,&nbsp;Takashi Kohno,&nbsp;Shun Kohsaka,&nbsp;Mitsushige Murata,&nbsp;Yuichiro Maekawa,&nbsp;Yoshiko Furukawa,&nbsp;Seiji Takatsuki,&nbsp;Keiichi Fukuda","doi":"10.2302/kjm.2018-0004-OA","DOIUrl":"https://doi.org/10.2302/kjm.2018-0004-OA","url":null,"abstract":"<p><p>Some patients with hypertrophic cardiomyopathy (HCM) develop systolic dysfunction, called the dilated phase of HCM (d-HCM), which is associated with increased morbidity and mortality. We conducted a retrospective study using an HCM database to clarify the incidence, clinical characteristics, and long-term outcomes of d-HCM. We analyzed an HCM cohort consisting of 434 patients (273 with apical HCM and 161 with non-apical HCM; 18 had obstructive HCM, 16 had dilated HCM, and 127 had other HCM) diagnosed by echocardiography in our hospital between 1991 and 2010. The follow-up period was 8.4 ± 6.7 years. The mean age at final follow-up was 67 ± 14 years, and 304 patients (70%) were men. The mean age of the 16 d-HCM patients at the initial visit was 45 ± 17 years, the age at final follow-up was 59 ± 18 years, and 13 were men. Thirteen d-HCM patients developed atrial fibrillation and six patients developed ischemic stroke. Twelve d-HCM patients were implanted with cardiac devices: one pacemaker, nine implantable cardioverter-defibrillators, and two cardiac resynchronization therapy with defibrillator. Five patients died of progressive heart failure at the age of 61 ± 23 years. The age at the initial visit and final follow-up were lower and the NYHA class, brain natriuretic peptide levels, and left ventricular function at initial evaluation were worse in the d-HCM group. Univariate analysis demonstrated that a lower age at the initial visit was associated with d-HCM (hazard ratio 0.955/1 year increase; 95% CI 0.920-0.991, P = 0.015). In our HCM cohort, the incidence of d-HCM was 4%. A high prevalence of atrial fibrillation and cerebral infarction and poor prognosis were noted in this group, despite patients undergoing medication and device implantation.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 4","pages":"87-94"},"PeriodicalIF":2.0,"publicationDate":"2019-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2018-0004-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36831825","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":"Selected Topics Relating to Functional MRI Study of the Brain.","authors":"Seiji Ogawa,&nbsp;Yul-Wan Sung","doi":"10.2302/kjm.2018-0011-OA","DOIUrl":"https://doi.org/10.2302/kjm.2018-0011-OA","url":null,"abstract":"<p><p>The authors selected some interesting current topics among many in the field of functional MRI (fMRI) of the brain. The selection was based on authours' immediate interests in exploring these aspects further; the topics are presented and discussed along with their perspectives. If progress can be made in these areas, it would be very advantageous to the field of brain research. The topics are (I) Detectable MRI signals in response to functional activity of the brain, including the current status of neurocurrent MRI; (II) Vascular-dependent and vascular-independent MRI signals, leading to the distinction of functional and structural MRI; (III) Functional specificity and functional connectivity of local sites, including differences between task-fMRI and resting state fMRI; (IV) Functional networks: an example of application to assessing the vocational aptitude test by fMRI; (V) Neural oscillation relevant to the formation of fMRI signals and of networks; (VI) Upgrading fMRI to \"information-content-reflecting\" fMRI, discussed as one of the prospects of near-future fMRI.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 4","pages":"73-86"},"PeriodicalIF":2.0,"publicationDate":"2019-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2018-0011-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37141043","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":"Rivaroxaban Promotes Reduction of Embolus Size within Cerebrocortical Microvessels in a Mouse Model of Embolic Stroke.","authors":"Masahiro Katsumata,&nbsp;Koichi Oki,&nbsp;Naoki Tsukada,&nbsp;Takato Abe,&nbsp;Yoshiaki Itoh,&nbsp;Shinichi Takahashi,&nbsp;Norihiro Suzuki","doi":"10.2302/kjm.2018-0010-OA","DOIUrl":"https://doi.org/10.2302/kjm.2018-0010-OA","url":null,"abstract":"<p><p>Previous reports have suggested that direct oral anticoagulants exert a prothrombolytic effect against intracardiac thrombi. We hypothesized that these anticoagulants may also help recanalize occluded intracranial arteries via prothrombolytic effects. In this study, we evaluated the effects of rivaroxaban, a direct oral anticoagulant, on fibrin emboli within the cerebrocortical microvessels in a mouse model of embolic stroke. Fibrin emboli prepared ex vivo were injected into the common carotid artery of male C57BL/6 mice, and embolization in the microvessels on the brain surface was observed through a cranial window. Oral administration of rivaroxaban was initiated a week before injection of the emboli. The number and sizes of the emboli were measured at two time points: immediately after and 3 h after the embolus injection in the rivaroxaban-treated mice (n =6) and untreated mice (n =7). The rates of recanalization and change in the embolus size were analyzed between the two groups. Complete recanalization was observed only in the rivaroxaban group (three mice in the rivaroxaban group compared with none in the control group). A significantly higher rate of reduction of the embolus size was observed in the rivaroxaban group than in the control group (P=0.0216). No significant differences between the two groups were observed in the serum levels of the following coagulation markers: thrombin-antithrombin III complexes, D-dimers, or plasmin-α2-plasmin inhibitor complex. Our findings indicate that rivaroxaban may promote reduction in the size of stagnated fibrin emboli in cerebrocortical microvessels in cases of embolic stroke.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 3","pages":"45-53"},"PeriodicalIF":2.0,"publicationDate":"2019-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2018-0010-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36741317","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":"Prevalence of Metabolic Syndrome and Lifestyle Characteristics by Business Type among Japanese Workers in Small- and Medium-sized Enterprises.","authors":"Hiroko Hozawa,&nbsp;Ayano Takeuchi,&nbsp;Yuko Oguma","doi":"10.2302/kjm.2018-0007-OA","DOIUrl":"https://doi.org/10.2302/kjm.2018-0007-OA","url":null,"abstract":"<p><p>This cross-sectional study investigated the associations of business type with the prevalence of metabolic syndrome (MetS) and lifestyle characteristics among workers in small- and medium-sized enterprises. In total, data from 167,736 workers (114,746 men and 52,990 women) who participated in health checkups in 2013 were analyzed using multilevel logistic regression models. The odds ratios (ORs) of having MetS, defined based on the criteria of the joint interim statement, were significantly higher in employees of transportation businesses (reference OR =1) than in other business types among men (OR: 0.67-0.85) and similar result was observed among women (OR: 0.70-0.88). The prevalence of a smoking habit was significantly higher in transportation workers than in employees of other businesses for both men and women. Furthermore, male transportation workers were more likely to skip breakfast, engage in <1 h/day of walking, walk at a slower speed, and eat dinner just before going to bed. Female transportation workers were more likely to have gained 10 kg since the age of 20 years. In conclusion, the prevalence of MetS was higher in transportation workers than in workers from other businesses; the associated risk factors may also vary by sex. To effectively promote public health, the labor environment, such as the business type, should be considered.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 3","pages":"54-67"},"PeriodicalIF":2.0,"publicationDate":"2019-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2018-0007-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36830152","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":"Regulatory T Cells: Pathophysiological Roles and Clinical Applications.","authors":"R. Sakai, Kyoko Komai, Mana Iizuka-Koga, A. Yoshimura, Minako Ito","doi":"10.2302/kjm.2019-0003-OA","DOIUrl":"https://doi.org/10.2302/kjm.2019-0003-OA","url":null,"abstract":"Inflammation and immune responses after tissue injury play pivotal roles in the resolution of inflammation, tissue recovery, fibrosis, and remodeling. Regulatory T cells (Tregs) are responsible for immune tolerance and are usually activated in secondary lymphatic tissues. Activated Tregs subsequently regulate effector T cell and dendritic cell activation. For clinical applications such as the suppression of both autoimmune diseases and the rejection of transplanted organs, methods to generate stabilized antigen-specific Tregs are required. For this purpose, transcriptional and epigenetic regulation of Foxp3 expression has been investigated. In addition to conventional Tregs, there are some Tregs that reside in tissues and are called tissue Tregs. Tissue Tregs exhibit tissue-specific functions that contribute to the maintenance of tissue homeostasis and repair. Such tissue Tregs could also be useful for Treg-based cell therapy. We recently discovered brain Tregs that accumulate in the brain during the chronic phase of ischemic brain injury. Brain Tregs resemble other tissue Tregs, but are unique in expressing neural cell-specific genes such as the serotonin receptor (Htr7); consequently, brain Tregs respond to serotonin. Here, we describe our experiences in the use of Tregs to suppress graft-versus-host disease and to promote neural recovery after stroke.","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"1 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2019-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2019-0003-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42756457","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":"A Case of Renal Oncocytoma with Renal Venous Tumor Thrombus.","authors":"Hideyuki Kondo,&nbsp;Takashi Okabe,&nbsp;Yoshitaka Okada,&nbsp;Takahiro Hasebe,&nbsp;Suguru Shirotake,&nbsp;Masafumi Oyama,&nbsp;Koshiro Nishimoto","doi":"10.2302/kjm.2017-0012-CR","DOIUrl":"https://doi.org/10.2302/kjm.2017-0012-CR","url":null,"abstract":"<p><p>Renal oncocytoma is generally regarded as a benign renal tumor. We herein report a case of large renal oncocytoma with renal venous tumor thrombus. The patient may need to be carefully followed up because hematogenous metastasis may occur.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 2","pages":"39-41"},"PeriodicalIF":2.0,"publicationDate":"2019-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2017-0012-CR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36713876","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":"Regenerative Therapy for Patients with Congenital Heart Disease.","authors":"Naritaka Kimura","doi":"10.2302/kjm.2018-0002-IR","DOIUrl":"https://doi.org/10.2302/kjm.2018-0002-IR","url":null,"abstract":"<p><p>Congenital heart disease (CHD) is the most common birth defect, affecting 1 in 100 babies. Among CHDs, single ventricle (SV) physiologies, such as hypoplastic left heart syndrome and tricuspid atresia, are particularly severe conditions that require multiple palliative surgeries, including the Fontan procedure. Although the management strategies for SV patients have markedly improved, the prevalence of ventricular dysfunction continues to increase over time, especially after the Fontan procedure. At present, the final treatment for SV patients who develop heart failure is heart transplantation; however, transplantation is difficult to achieve because of severe donor shortages. Recently, various regenerative therapies for heart failure have been developed that increase cardiomyocytes and restore cardiac function, with promising results in adults. The clinical application of various forms of regenerative medicine for CHD patients with heart failure is highly anticipated, and the latest research in this field is reviewed here. In addition, regenerative therapy is important for children with CHD because of their natural growth. The ideal pediatric cardiovascular device would have the potential to adapt to a child's growth. Therefore, if a device that increases in size in accordance with the patient's growth could be developed using regenerative medicine, it would be highly beneficial. This review provides an overview of the available regenerative technologies for CHD patients.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 2","pages":"29-38"},"PeriodicalIF":2.0,"publicationDate":"2019-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2018-0002-IR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36242981","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":"Distinctive Roles of D-Amino Acids in the Homochiral World: Chirality of Amino Acids Modulates Mammalian Physiology and Pathology.","authors":"Jumpei Sasabe,&nbsp;Masataka Suzuki","doi":"10.2302/kjm.2018-0001-IR","DOIUrl":"https://doi.org/10.2302/kjm.2018-0001-IR","url":null,"abstract":"<p><p>Living organisms enantioselectively employ L-amino acids as the molecular architecture of protein synthesized in the ribosome. Although L-amino acids are dominantly utilized in most biological processes, accumulating evidence points to the distinctive roles of D-amino acids in non-ribosomal physiology. Among the three domains of life, bacteria have the greatest capacity to produce a wide variety of D-amino acids. In contrast, archaea and eukaryotes are thought generally to synthesize only two kinds of D-amino acids: D-serine and D-aspartate. In mammals, D-serine is critical for neurotransmission as an endogenous coagonist of N-methyl D-aspartate receptors. Additionally, D-aspartate is associated with neurogenesis and endocrine systems. Furthermore, recognition of D-amino acids originating in bacteria is linked to systemic and mucosal innate immunity. Among the roles played by D-amino acids in human pathology, the dysfunction of neurotransmission mediated by D-serine is implicated in psychiatric and neurological disorders. Non-enzymatic conversion of L-aspartate or L-serine residues to their D-configurations is involved in age-associated protein degeneration. Moreover, the measurement of plasma or urinary D-/L-serine or D-/L-aspartate levels may have diagnostic or prognostic value in the treatment of kidney diseases. This review aims to summarize current understanding of D-amino-acid-associated biology with a major focus on mammalian physiology and pathology.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 1","pages":"1-16"},"PeriodicalIF":2.0,"publicationDate":"2019-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2018-0001-IR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36125655","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}