KEIO JOURNAL OF MEDICINE最新文献

{"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}

{"title":"The Effect of Improving Oral Hygiene through Professional Oral Care to Reduce the Incidence of Pneumonia Post-esophagectomy in Esophageal Cancer.","authors":"Yuka Yamada,&nbsp;Takashi Yurikusa,&nbsp;Kohei Furukawa,&nbsp;Yasuhiro Tsubosa,&nbsp;Masahiro Niihara,&nbsp;Keita Mori,&nbsp;Seiji Asoda,&nbsp;Hiromasa Kawana,&nbsp;Yuko Kitagawa,&nbsp;Taneaki Nakagawa","doi":"10.2302/kjm.2017-0017-OA","DOIUrl":"https://doi.org/10.2302/kjm.2017-0017-OA","url":null,"abstract":"<p><p>Radical esophagectomy for thoracic esophageal cancer is invasive and frequently results in postoperative pulmonary complications. Postoperative pneumonia is the most common such complication and affects hospital mortality and survival rates. Oral care has been very effective in reducing pneumonia. In Japan, preoperative professional oral care is highly recommended. However, there are few studies on the effect of preoperative improvements in oral hygiene as a result of intervention on the incidence of postoperative pneumonia. The primary end-point of this retrospective study was the incidence of postoperative pneumonia after radical esophagectomy. The oral health levels of 46 patients were individually categorized, and then patients were grouped according to whether they maintained or improved their oral hygiene. At the first dental examination, oral health levels were classified as good in 22 patients and bad in 24. Of the 46 patients studied, 39 patients maintained or improved their oral hygiene (good control group), whereas 7 showed no improvement (bad control group). Postoperative pneumonia occurred in eight patients: four in the good control group and four in the bad control group. Statistical analysis with postoperative pneumonia as a dependent variable showed a significant effect of oral hygiene improvement on the incidence of pneumonia. Logistic regression analysis with this factor as an independent variable demonstrated that the risk of postoperative pneumonia was reduced in the good control group (OR 0.086, 95% CI 0.014-0.529). Therefore, preoperative professional oral care may improve oral hygiene and oral health, which may in turn reduce the incidence of postoperative pneumonia.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 1","pages":"17-25"},"PeriodicalIF":2.0,"publicationDate":"2019-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.2017-0017-OA","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36568592","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":"Dementia care and research - What a difference a decade makes?","authors":"L. Robinson","doi":"10.2302/kjm.68-004-abst","DOIUrl":"https://doi.org/10.2302/kjm.68-004-abst","url":null,"abstract":"Dementia care currently costs the UK 21 bn pounds a year, and that doesn't include the huge informal costs of family careers and community support networks. Developing services to meet the needs of patients with complex health problems must involve service users. Professor Robinson has addressed what resources are needed to provide a better quality of care, and how these can be successfully delivered to patients and their family. As Newcastle University's Professor of Primary Care and Ageing, and as a working GP in a Newcastle practice, she is keen to ensure that the benefits of the University's excellent research into ageing and the diseases of old age are translated into high quality treatment and care for older people. She leads the Primary Care Group of the Dementia and Neurodegenerative Diseases Research Network (DeNDRoN), a national network of researchers which aims to explore the whole spectrum of dementia care from diagnosis and early detection, through to advanced dementia and end of life care. Another Professor Robinson's ambitions would be to help create a center of excellence at Newcastle University for training GPs, hospital staff, community nurses and others in all aspects of dementia care. In this lecture, Prof Robinson will talk about how her translational research had influenced UK practice over the last 10+ years and at same time bring in her career development in both clinical and academic field.(Presented at the 1982th Meeting, June 25, 2019).","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 3 1","pages":"68"},"PeriodicalIF":2.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.68-004-abst","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68399514","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":"Surgical training and research in the Netherlands.","authors":"B. Wijnhoven","doi":"10.2302/kjm.68-005-abst","DOIUrl":"https://doi.org/10.2302/kjm.68-005-abst","url":null,"abstract":"In contrast to many other countries, training of medical specialists is funded by the Department of Health. The curriculum of medical specialist training including general surgery is well structured and lasts 6 years. Specialist (trainers) and hospitals involved in surgical training have been accredited by the Dutch Association of Surgeons. Surgical training includes 4 years of general surgery followed by two years of differentiation in one of the sub-specialities. These are gastrointestinal, oncological, vascular, pediatric and trauma surgery. The training program is competency based: there are key procedures and so called EPA (entrusted professional activities) that are defined to monitor the progress of an individual. Unique in the Dutch system is the quality control and governance of surgical training that will be discussed in my lecture.The number of positions available for surgical trainees is limited and determined by the government each year. Hence, to enter surgical training has always been very competitive and not easy for young doctors. This is one of the reasons why many students start a PhD program after medical school and to gain experience in basic or clinical research. These young and talented students usually work for 3-4 years full time and are well capable of coordinating trials. This is just one of the reasons that many clinical (randomised) studies come from the Netherlands. Besides this strong academic environment, lack of private practice, strong multidisciplinary working parties and the geographical situation in our small country facilitates multicenter studies. Some more crucial factors for success will be discussed in the lecture.(Presented at the 1983th Meeting, July 10, 2019).","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 3 1","pages":"68"},"PeriodicalIF":2.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.68-005-abst","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68399578","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":"Discovery of IL-6 and Development of Anti-IL-6R Antibody.","authors":"Tadamitsu Kishimoto","doi":"10.2302/kjm.68-007-ABST","DOIUrl":"https://doi.org/10.2302/kjm.68-007-ABST","url":null,"abstract":"<p><p>A series of our studies on IL-6 have revealed that it has a pleiotropic activity in various tissues and cells and its deregulated expression is responsible for several chronic inflammations and hemopoietic malignancies.Humanized antibody against 80kd IL-6R (Tocilizumab) has shown significant therapeutic effect in RA, JIA, Castleman's diseases and several other autoimmune inflammatory diseases, such as, giant cell arteritis, reactive arthritis, polymyalgia rheumatica and adult still's disease. Cytokine storm induced by CAR-T cell therapy has been shown to be controlled by Tocilizumab.Therapeutic effect of Tocilizumab confirmed that over and constitutive-production of IL-6 is responsible for the pathogenesis of autoimmune diseases.Then, the question to be asked is how is IL-6 production regulated. We identified a novel molecule called Arid5a which binds with the 3'-UTR of IL-6 mRNA and protects its degradation by competing with Regnase-1. Interestingly, this molecule is present in nuclei and inflammatory stimulation induced translocation of Arid5a from nuclei into cytoplasm and it competes with Regnase-1 for the protection of mRNA of IL-6.Our study indicates that Arid5a is one of the key molecules for inflammation as well as the development of septic shock.The results also suggest the therapeutic potential of anti-agonistic agents for Arid5a in the prevention of various inflammatory diseases and septic shock.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 4","pages":"96"},"PeriodicalIF":2.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.68-007-ABST","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37489160","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":"Toward the Mysteries of Sleep.","authors":"Masashi Yanagisawa","doi":"10.2302/kjm.68-001-ABST","DOIUrl":"https://doi.org/10.2302/kjm.68-001-ABST","url":null,"abstract":"<p><p>Although sleep is a ubiquitous behavior in animal species with well-developed central nervous systems, many aspects in the neurobiology of sleep remain mysterious. Our discovery of orexin, a hypothalamic neuropeptide involved in the maintenance of wakefulness, has triggered an intensive research examining the exact role of the orexinergic and other neural pathways in the regulation of sleep/wakefulness. The orexin receptor antagonist suvorexant, which specifically block the endogenous waking system, has been approved as a new drug to treat insomnia. Also, since the sleep disorder narcolepsy-cataplexy is caused by orexin deficiency, orexin receptor agonists are expected to provide mechanistic therapy for narcolepsy; they will likely be also useful for treating excessive sleepiness due to other etiologies.Despite the fact that the executive neurocircuitry and neurochemistry for sleep/wake switching has been increasingly revealed in recent years, the mechanism for homeostatic regulation of sleep, as well as the neural substrate for \"sleepiness\" (sleep need), remains unknown. To crack open this black box, we have initiated a large-scale forward genetic screen of sleep/wake phenotype in mice based on true somnographic (EEG/EMG) measurements. We have so far screened >8,000 heterozygous ENU-mutagenized founders and established a number of pedigrees exhibiting heritable and specific sleep/wake abnormalities. By combining linkage analysis and the next-generation whole exome sequencing, we have molecularly identified and verified the causal mutation in several of these pedigrees. Biochemical and neurophysiological analyses of these mutations are underway. Since these dominant mutations cause strong phenotypic traits, we expect that the mutated genes will provide new insights into the elusive pathway regulating sleep/wakefulness. Indeed, through a systematic cross-comparison of the Sleepy mutants and sleep-deprived mice, we have recently found that the cumulative phosphorylation state of a specific set of mostly synaptic proteins may be the molecular substrate of sleep need.</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 1","pages":"27"},"PeriodicalIF":2.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.68-001-ABST","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37086676","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":"Stem cells of the suture mesenchyme in craniofacial bone development, repair and regeneration.","authors":"Takamitsu Maruyama","doi":"10.2302/kjm.68-003-ABST","DOIUrl":"https://doi.org/10.2302/kjm.68-003-ABST","url":null,"abstract":"<p><p>Development of the skeleton is mediated through two distinct ossification mechanisms. Craniofacial bones are formed mainly through intramembranous ossification, a mechanism different from endochondral ossification required for development of the body skeleton. The skeletal structures are quite distinct between the two, thus they are likely to have their unique stem cell populations. The sutures serve as the growth center critical for healthy development of the craniofacial skeleton. Defects in suture morphogenesis cause its premature closure, resulting in development of craniosynostosis, a devastating disease affecting 1 in ~2,500 individuals. The suture mesenchyme has been postulated to act as the niche of skeletal stem cells essential for calvarial morphogenesis. However, very limited knowledge is available for suture biology and suture stem cells (SuSCs) have yet to be isolated. Here we report the first evidence for identification and isolation of a stem cell population residing in the suture midline. Genetic labeling of SuSCs shows their ability to self-renew and continually give rise to mature cell types over a 1-year monitoring period. They maintain their localization in the niches constantly produce skeletogenic descendants during calvarial development and homeostastic maintenance. Upon injury, SuSCs expand drastically surrounding the skeletogenic mesenchyme, migrate to the damaged site and contribute directly to skeletal repair in a cell autonomous fashion. The regeneration, pluripotency and frequency of SuSCs are also determined using limiting dilution transplantation. In vivo clonal expansion analysis demonstrates a single SuSC capable of generating bones. Furthermore, SuSC transplantation into injured calvaria facilitates the healing processes through direct engraftments. Our findings demonstrate SuSCs are bona fide skeletal stem cells ideally suited for cell-based craniofacial bone therapy as they possess abilities to engraft, differentiate.(Presented at the 1980th Meeting, April 16, 2019).</p>","PeriodicalId":46245,"journal":{"name":"KEIO JOURNAL OF MEDICINE","volume":"68 2","pages":"42"},"PeriodicalIF":2.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2302/kjm.68-003-ABST","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37370644","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":"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}