KEIO JOURNAL OF MEDICINE最新文献

{"title":"Dr. Seiji Ogawa and the Past, Present, and Future of Functional MRI Research.","authors":"Hideyuki Okano","doi":"10.2302/kjm.68-4_Editorial","DOIUrl":"https://doi.org/10.2302/kjm.68-4_Editorial","url":null,"abstract":"In basic brain science and clinical investigations of psychiatric/neurological diseases, it is very important to be able to measure the functional state of the brain noninvasively. Dr. Seiji Ogawa worked on this issue for many years and succeeded in developing a novel imaging method of brain function based on the vascular response to functional activation of the brain. Remarkably, in the early 1990s, he developed a technique for detecting magnetic resonance imaging (MRI) signals that depend on blood oxygenation levels in the brain. He named these signals BOLD (for blood oxygen level dependent) and showed that BOLD signals can be used for functional mapping of the human brain following sensory stimulation, thereby establishing the basic principles underlying functional MRI (fMRI).1,2 This method enabled the noninvasive mapping of human brain activity without the use of radioactive isotopes.3 Currently, various noninvasive methods for evaluating functional brain activities have been developed and applied, including electroencephalography (EEG) and magnetoencephalography (MEG). Although fMRI does not directly detect the electrophysiological or electrochemical activity of the brain, fMRI has the advantage of being able to localize the functioning site of the whole brain with high resolution, compared to other noninvasive methods including EEG and MEG.4 In fact, Dr. Ogawa’s pioneering work has inspired the widespread use of fMRI by researchers and physicians in the field of basic and clinical brain science. For example, fMRI techniques are applied to determine which part of the brain is activated when performing a task (task-based fMRI) and to investigate functional brain connectivity in the resting state [resting state fMRI (rsfMRI)]. fMRI is now combined with more recent technologies such as optogenetics. By taking advantage of this combined method [integrated optogenetics and BOLD-fMRI (ofMRI)], Drs. Jin Hyung Lee and Karl Deisseroth at Stanford University observed that BOLD signals are positively induced in the mouse brain on activating a specific subset of neurons (i.e., local CaMKIIα-expressing excitatory neurons) and clearly showed that widely applied fMRI BOLD signals could provide a suitable tool for functional circuit analysis as well as for the global phenotyping of dysfunctional circuitry.5 Dr. Kenji Tanaka and our collaborative team at Keio University recently took advantage of ofMRI and found that optogenetic astrocyte activation evokes BOLD fMRI responses that accompany oxygen consumption without the modulation of neuronal activity.6 Evidently, fMRI is an indispensable methodology for elucidating functional networks in the brain and for analyzing various brain functions and behavioral mechanisms of action in normal subjects and in patients with neurodevelopmental disorders and psychiatric disorders. Comprehensive brain mapping in humans and model animals is generating increasing interest worldwide.7,8 In world-class brain projects, incl","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 4","pages":"71-72"},"PeriodicalIF":2.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37489158","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":"Organoids: Avatars for Personalized Medicine.","authors":"Hans C Clevers","doi":"10.2302/kjm.68-006-ABST","DOIUrl":"https://doi.org/10.2302/kjm.68-006-ABST","url":null,"abstract":"<p><p>Stem cells are the foundation of all mammalian life. Stem cells build and maintain our bodies throughout life. Two types of stem cells are discerned.1) Embryonic stem cells (ES cells) are briefly present in the early human or mouse embryo, a few days after fertilization. These ES cells can be grown indefinitely in the lab and have the potential to build each and every tissue in our body. Because of this 'pluripotency', ES cells hold great promise for therapeutic application in the field of regenerative medicine. It is also possible to take skin cells (or other cells) from adults and convert these in the lab into cells with ES properties, so called iPS cells. Many of the hurdles that ES cell technology have faced, do not exist for iPS cells.2) Adult stem cells. Every organ in our body is believed to harbor its own dedicated stem cells. These adult stem cells replace tissue that is lost due to wear and tear, trauma and disease. Adult stem cells are highly specialized and can only produce the tissue in which they reside; they are 'multipotent'. Examples are bone marrow stem cells that make all blood cells, skin stem cells and gut stem cells. Even the brain is now known to harbor its specialized stem cells. The adult stem cells allow us to live 80-90 years, but this comes at a cost: they are the cells that most easily transform into cancer cells.Both types of stem cells can be used to establish 'organoids', 3D structures established in a dish, that recapitulate many aspects of the organ they represent. Pluripotent stem cells can be taken through the developmental steps that establish organs during embryogenesis. This has worked particularly well for parts of the the central nervous system, the kidney and GI organs. We have shown that adult epithelial stem cells carrying the generic Lgr5 marker can be cultured under tissue-repair conditions and generate epithelial organoids directly from healthy and diseased organs such as the gut, the liver, the lung and the pancreas. Organoid technology opens a range of avenues for the study of development, physiology and disease, for drug development and for personalized medicine. In the long run, cultured mini-organs may replace transplant organs from donors and hold promise in gene therapy.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 4","pages":"95"},"PeriodicalIF":2.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.68-006-ABST","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37489159","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":"Exploration of Microbial Diversity to Discover Novel Molecular Technologies.","authors":"Feng Zhang","doi":"10.2302/kjm.68-002-ABST","DOIUrl":"10.2302/kjm.68-002-ABST","url":null,"abstract":"<p><p>Many powerful molecular biology tools have their origin in nature. From restriction enzymes to CRISPR-Cas9, microbes utilize a diverse array of systems to get ahead evolutionarily. We are exploring this natural diversity through bioinformatics, biochemical, and molecular work to better understand the fundamental ways in which microbes and other living organisms sense and respond to their environment and as possible to develop these natural systems as molecular tools and to improve human health. Building on our demonstration that Cas9 can be repurposed for precision genome editing in mammalian cells, we look for novel CRISPR-Cas systems that are different and may have other useful properties. This led to the discovery of several new CRISPR systems, including the CRISPR-Cas13 family that target RNA, rather than DNA. We have developed a toolbox for RNA modulation based on Cas13, including methods for precision base editing, adding to our robust toolbox for DNA based on Cas9 and Cas12. We are expanding our biodiscovery efforts to search for new microbial proteins that may be adapted for applications beyond genome and transcriptome modulation, capitalizing on the growing volume of microbial genomic sequences. We are particularly interested in identifying new therapeutic modalities and vehicles for delivering them into patients. We hope that additional robust tools and delivery options will further accelerate research into human disease and open up new therapeutic possibilities.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 1","pages":"26"},"PeriodicalIF":2.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.68-002-ABST","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37086674","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":"Human Amniotic Fluid Stem Cells: Therapeutic Potential for Perinatal Patients with Intractable Neurological Disease.","authors":"Daigo Ochiai,&nbsp;Hirotaka Masuda,&nbsp;Yushi Abe,&nbsp;Toshimitsu Otani,&nbsp;Marie Fukutake,&nbsp;Tadashi Matsumoto,&nbsp;Kei Miyakoshi,&nbsp;Mamoru Tanaka","doi":"10.2302/kjm.2017-0019-IR","DOIUrl":"https://doi.org/10.2302/kjm.2017-0019-IR","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) have generated great interest in the fields of regenerative medicine and immunotherapy because of their unique biological properties. Among MSCs, amniotic fluid stem cells (AFS) have a number of characteristics that make them attractive candidates for tissue engineering and cell replacement strategies, particularly for perinatal medicine. If various neonatal conditions, including birth asphyxia, preterm birth, and congenital abnormalities, which result in long-lasting severe impairments, could be predicted during pregnancy, it would allow collection of small samples of amniotic fluid cells by amniocentesis. In vitro culture of these autologous AFS during pregnancy would make them available for use soon after birth. Hypoxic-ischemic encephalopathy (HIE) and myelomeningocele (MMC) are neonatal conditions that cause permanent neurological disability, for which the treatment options are extremely limited. Experiments using animal models of HIE and MMC and human clinical trials have demonstrated that MSCs, including AFS, have beneficial effects on the central nervous system through paracrine influences, indicating that autologous AFS treatment may be applicable for intractable neurological diseases, including HIE and MMC, during the perinatal period. In this review, we focus on recent research related to the therapeutic potential of AFS for perinatal neurological diseases such as HIE and MMC.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"67 4","pages":"57-66"},"PeriodicalIF":2.0,"publicationDate":"2018-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2017-0019-IR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35893800","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":"Midline Extraperitoneal Approach for Obturator Hernia Repair.","authors":"Yuji Otsuki,&nbsp;Hirofumi Konn,&nbsp;Keisa Takeda,&nbsp;Masahiko Koike","doi":"10.2302/kjm.2017-0014-OA","DOIUrl":"https://doi.org/10.2302/kjm.2017-0014-OA","url":null,"abstract":"<p><p>Obturator hernia (OH) is a rare condition that accounts for 0.073-1% of abdominal hernias and 0.48% of bowel obstructions. OH frequently occurs in elderly women, with an incidence that increases with age. The only treatment for OH is surgical intervention, and the approaches used vary greatly. Consequently, a well-defined consensus has not yet emerged. We assessed the efficiency and safety of the midline extraperitoneal approach for OH. Six patients with OH repaired using the midline extraperitoneal approach at KKR Sapporo Medical Center between April 2011 and January 2016 were included in the study. We retrospectively evaluated the patient characteristics, intraoperative findings, and the postoperative course. All patients were elderly women [median age, 90 (range, 79-92) years], with a median body mass index of 17.0 (range, 15.6-18.3) kg/m² at presentation. All had symptoms associated with bowel obstruction: two patients presenting with leg pain had the Howship-Romberg sign. In two patients, bowel resection was required because of irreversible ischemic changes. Five patients had coexisting femoral and inguinal hernias that were repaired by bilateral mesh repair. One patient had aspiration pneumonia as a postoperative complication. All patients were discharged alive, without infection or recurrence. OH can be efficiently and safely repaired using the midline extraperitoneal approach. This approach establishes the diagnosis of OH, avoids injuring obturator vessels, gives improved exposure of the obturator canal, enables identification and simultaneous repair of other pelvic hernias, and facilitates bowel resection. This approach reduces the risk of mesh infection in patients undergoing bowel resection.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"67 4","pages":"67-71"},"PeriodicalIF":2.0,"publicationDate":"2018-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2017-0014-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35915339","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":"Perspective of junior doctors on the cost and value in e-learning.","authors":"Kieran Walsh","doi":"10.1136/bmjstel-2017-000262","DOIUrl":"10.1136/bmjstel-2017-000262","url":null,"abstract":"","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"8 1","pages":"59-60"},"PeriodicalIF":1.1,"publicationDate":"2018-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90381906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression in Cancer Care.","authors":"Daisuke Fujisawa","doi":"10.2302/kjm.2017-0010-IR","DOIUrl":"https://doi.org/10.2302/kjm.2017-0010-IR","url":null,"abstract":"<p><p>Depression is common among cancer patients and their families, and may lead to substantial clinical consequences. Clinicians should routinely screen cancer patients for comorbid depression and should provide appropriate care at both primary and specialized care levels. Good quality care is beneficial not only for cancer patients themselves but also for their family members. It includes good communication between patients and health providers, and addressing of unmet needs of cancer patients. Specialized care comprises pharmacotherapy and psychotherapy. The advancement of psychotherapy for cancer patients parallels the advancement of general psychotherapy. Among the many types of psychotherapies, mindfulness-based interventions have been attracting growing attention. Some relevant studies that have been conducted in Keio University Hospital are described herein.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"67 3","pages":"37-44"},"PeriodicalIF":2.0,"publicationDate":"2018-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2017-0010-IR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35609384","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":"The Efficacy of Transcorneal Electrical Stimulation for the Treatment of Primary Open-angle Glaucoma: A Pilot Study.","authors":"Yuka Ota,&nbsp;Naoki Ozeki,&nbsp;Kenya Yuki,&nbsp;Daisuke Shiba,&nbsp;Itaru Kimura,&nbsp;Kazushige Tsunoda,&nbsp;Kei Shinoda,&nbsp;Hisao Ohde,&nbsp;Kazuo Tsubota","doi":"10.2302/kjm.2017-0015-OA","DOIUrl":"https://doi.org/10.2302/kjm.2017-0015-OA","url":null,"abstract":"<p><p>The aim of this study was to evaluate the effects of transcorneal electrical stimulation in subjects with primary open-angle glaucoma. Five eyes of four male subjects with primary open-angle glaucoma (average age: 52.25 ± 14.68 years) were enrolled. The subjects underwent transcorneal electrical stimulation every 3 months according to the following procedure. A Dawson-Trick-Litzkow electrode was placed on the cornea, and biphasic electric current pulses (10 ms, 20 Hz) were delivered using a stimulator (BPG-1,BAK Electronics) and a stimulus isolation unit (BSI-2). A current that evoked a phosphene that the subject perceived in the whole visual area was delivered continuously for 30 min. Humphrey visual field testing was performed after every third transcorneal electrical stimulation treatment. Changes in mean deviation (MD) values were evaluated with a linear regression model. Transcorneal electrical stimulation was performed 18.2 ± 9.4 times over a period of 49.8 ± 23.0 months. The average pretranscorneal electrical stimulation intraocular pressure, best corrected visual acuity, and MD values were 11.8 ± 1.79 mmHg, 0.14 ± 0.19 (logMAR) and -17.28 ± 6.24 dB, respectively. No significant differences were observed in intraocular pressure before and after transcorneal electrical stimulation. However, there was a significant positive linear relationship between changes in MD values and the number of transcorneal electrical stimulation treatments (R² = 0.176, P = 0.005, Spearman correlation R =0.294, P = 0.008). Transcorneal electrical stimulation treatment may improve glaucomatous visual field defects in subjects with primary open-angle glaucoma. Large-scale studies are necessary to confirm these preliminary findings.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"67 3","pages":"45-53"},"PeriodicalIF":2.0,"publicationDate":"2018-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2017-0015-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35806367","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":"Correlation of the Blood Test Results Obtained between Assays Using Microliter-scale Fingertip Blood Samples Collected with a Novel Blood Collection Device and Conventional Venous Blood Assays: a Secondary Publication in English.","authors":"Hajime Iwasawa,&nbsp;Tomoaki Nishimura,&nbsp;Shota Nemoto,&nbsp;Naoki Aikawa,&nbsp;Kiyoaki Watanabe","doi":"10.2302/kjm.2017-0009-OA","DOIUrl":"https://doi.org/10.2302/kjm.2017-0009-OA","url":null,"abstract":"<p><p>In this study, we investigated the correlations between biochemical and hematological test results obtained using microliter-scale fingertip blood samples collected with a newly developed blood collection device and those obtained using conventional venous blood. Eighty volunteer subjects were enrolled in this study. Blood samples were drawn from the fingertip of the ring finger by a single puncture, and 60-µL samples were promptly and accurately aspirated into a blood collection chip. Then the chip was tightly sealed in a chip container and was shaken to mix the contents without dispersion. For biochemical tests other than that for HbA1c, blood was collected without anticoagulant and centrifuged to obtain 15 µL of serum which was then diluted with 190 µL of physiological saline for the assay. For hematological tests and the test for HbA1c, the sample was assayed with blood collected using EDTA-2 K. Good correlations were obtained between the test results of the assay using fingertip blood and that using venous blood. The correlation coefficients were ≥0.97 for TG, T-CHO, HDL-C, LDL-C, GLU, ALT, γ-GTP, UA, BUN, and HbA1c and ≥0.95 for WBC, RBC, Hgb, and Hct. These results suggest that our microliter-scale blood testing system is comparable to assays using venous blood and may be useful as a rapid and simple test to determine basic clinical parameters that are close to the reference intervals.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"67 2","pages":"26-34"},"PeriodicalIF":2.0,"publicationDate":"2018-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2017-0009-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35574167","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":"The History and Future of Unlinked Total Elbow Arthroplasty.","authors":"Takuji Iwamoto,&nbsp;Hiroyasu Ikegami,&nbsp;Taku Suzuki,&nbsp;Satoshi Oki,&nbsp;Noboru Matsumura,&nbsp;Masaya Nakamura,&nbsp;Morio Matsumoto,&nbsp;Kazuki Sato","doi":"10.2302/kjm.2017-0007-IR","DOIUrl":"https://doi.org/10.2302/kjm.2017-0007-IR","url":null,"abstract":"<p><p>Unlinked total elbow arthroplasty (TEA), which has no mechanical connection between the humeral and ulnar components, has theoretical advantages based on its near-normal elbow kinematics and the preservation of bone stock. Unlinked TEA is appropriate only for patients who have limited bone loss or limited deformity and good ligamentous function. This is because postoperative instability has been a major complication of unlinked prostheses. The concept and goal of unlinked TEA is to share the loading stress on the bone implant interface with the surrounding tissues. Although the loosening rate of unlinked prostheses theoretically should be lower than that of linked prostheses (which have a mechanical connection between the humeral and ulnar components), there is no clear evidence that unlinked TEAs are superior to linked TEAs in this respect. However, we believe that primary TEA should be performed using an unlinked TEA, especially for younger patients, because revision surgery for unlinked TEA results in longer prosthesis survival than revision surgery for linked TEA. Improvement of the design of unlinked prostheses and the introduction of less invasive surgical techniques are required to reduce postoperative instability.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"67 2","pages":"19-25"},"PeriodicalIF":2.0,"publicationDate":"2018-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2017-0007-IR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35294208","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}