KEIO JOURNAL OF MEDICINE最新文献

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.

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.

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.

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.

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.

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.

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.