ABO-Incompatible Kidney Transplantation

Previously, ABO-incompatible kidney transplantation (KTx) was believed to be a “taboo” for immunological reasons. In Japan, the Tokyo Women’s Medical University reported the first successful case of such transplantation, performed on January 19, 1989. Since then, we have been striving to improve the outcome of ABO-incompatible transplantation for a quarter of a century

Clinical Feature of Men Who Benefit from Dose Escalation of Naftopidil for Lower Urinary Tract Symptoms: A Prospective Study

Objectives. To examine the feature of men who benefit from dose escalation of naftopidil for lower urinary tract symptoms (LUTSs). Methods. Based on the IPSS, men reporting LUTS were prospectively studied using 50 mg/day of naftopidil for the first 4 weeks; satisfied patients continued its 50 mg/day (n = 11), and those reporting unsatisfactory improvement received its 75 mg/day (n = 35) for the next 4 weeks. Results. The 75 mg group showed improvement in the total IPSS and QOL score in a dose-dependent manner (at 4 weeks: P < .001, at 4 weeks versus 8 weeks: P < .05). In the 50 mg group, both scores reduced at 4 weeks, thereafter unchanged. The baseline slow stream score alone was higher in the 75 mg group (P = .013). The rate of change in the QOL score during the initial 4 weeks (ΔQOL) and Δnocturia was smaller in the 75 mg group (P < .05). Conclusions. Men with high slow stream score and unsatisfactory improvement in nocturia may benefit from dose escalation of naftopidil

Long-term CMV monitoring and chronic rejection in renal transplant recipients

IntroductionCytomegalovirus (CMV) is well established to be an independent risk factor for graft loss after kidney transplantation (KTx). Monitoring for CMV in the chronic phase is not defined in the current guideline. The effects of CMV infection, including asymptomatic CMV viremia, in the chronic phase are unclear.MethodsWe performed a single-center retrospective study to investigate incidence of CMV infection in the chronic phase, defined as more than 1 year after KTx. We included 205 patients who received KTx between April 2004 and December 2017. The CMV pp65 antigenemia assays to detect CMV viremia were continuously performed every 1–3 months.ResultsThe median duration of the follow-up was 80.6 (13.1–172.1) months. Asymptomatic CMV infection and CMV disease were observed in 30.7% and 2.9% in the chronic phase, respectively. We found that 10–20% of patients had CMV infections in each year after KTx which did not change over 10 years. The history of CMV infection in the early phase (within 1 year after KTx) and chronic rejection were significantly associated with CMV viremia in the chronic phase. CMV viremia in the chronic phase was significantly associated with graft loss.DiscussionThis is the first study to examine the incidence of CMV viremia for 10 years post KTx. Preventing latent CMV infection may decrease chronic rejection and graft loss after KTx

AQT-D: Demonstration of the Water Resistojet Propulsion System by the ISS-Deployed CubeSat

AQT-D (AQua Thruster-Demonstrator) is a 3U CubeSat for a demonstration of a water resistojet propulsion system developed by The University of Tokyo. AQT-D installed the 1U propulsion system using water as a propellant, named AQUARIUS-1U (AQUA ResIstojet propUlsion System 1U). We completed the design and assembly of the AQT-D flight model. AQUARIUS-1U was fired on a pendulum-type thrust balance, and its performance was directly characterized in both a stand-alone test and an integrated test using an entire spacecraft system. AQT-D is currently scheduled to be delivered to JAXA in July 2019 and launched to the International Space Station (ISS) in the middle of 2019 by the H-IIB rocket. AQT-D will be deployed from the Japanese Experiment Module (JEM), known as Kibo, and demonstrate water propulsion technology

Derivation of induced pluripotent stem cells in Japanese macaque (Macaca fuscata)

Non-human primates are our closest relatives and are of special interest for ecological, evolutionary and biomedical research. The Japanese macaque (Macaca fuscata) has contributed to the progress of primatology and neurosciences over 60 years. Despite this importance, the molecular and cellular basis of the Japanese macaque remains unexplored since useful cellular tools are lacking. Here we generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of the Japanese macaque with Sendai virus or plasmid vectors. The Japanese macaque iPSCs (jm-iPSCs) were established under feeder-free culture conditions, but feeder cells turned out to be essential for their maintenance. The jm-iPSCs formed human iPSC-like flat colonies which were positive for pluripotent antigens including alkaline phosphatase, SSEA4, and TRA-1-81. They also expressed endogenous OCT3/4, SOX2, L-MYC, and KLF4 and other pluripotent marker genes. The potential to differentiate into all three germ layers and neural stem cells was confirmed by embryoid body and neurosphere formation, respectively. The jm-iPSCs will provide a robust in vitro tool for investigating the underlying mechanisms of development and physiology studies with the Japanese macaque

Basic assessment on adding platelet measurement to legal health checkup in Japan: A cross-sectional and 20-year longitudinal study

BackgroundIn Japan, health checkups for workers are legally compulsory. Considering legal health checkup items are important for Japanese workers' health problems. To date, the legal health checkup items for blood cell counts include only red blood cell counts and hemoglobin but not platelet counts. This study aimed to investigate the significance of measuring platelets in workers by showing the association between the FIB-4 index (FIB-4), which can be easily calculated from factors including platelet counts and viral hepatitis infection.MethodBoth cross-sectional and longitudinal analyses were conducted on the comprehensive medical examinations of male workers. In fiscal year (FY) 2019, a logistic regression model was applied to 12,918 examinees. For 13,459 examinees (mean age = 47.5 ± 9.3 SD), FY2000 was set to be followed until FY2019. A total of 149,956 records between FY2000 and FY2019 were analyzed cross-sectionally, and 8,038 men who were consecutively examined to FY2019 at the longest were analyzed longitudinally. Receiver operating characteristic (ROC) curve–area under the ROC curve (ROC–AUC) and Cox proportional methods were used to examine the association between platelet-related indices and viral hepatitis infection.ResultsLogistic regression showed that the risk of FIB-4 ≥ 2.67 was mostly associated with hepatitis C virus antibody (HCVAb) positivity [odds ratio (OR) = 2.51, 95% confidence interval (CI) = 1.08–5.86], while negatively associated with body mass index (BMI) (OR = 0.54, 95% CI = 0.30–0.97), and not associated with the presence of fatty liver. To detect HVC Ab positivity, ROC–AUC showed more effectiveness in FIB-4 than in the AST/ALT ratio (0.776, 95% CI = 0.747–0.773 vs. 0.552; 95% CI = 0.543–0.561). The Cox analysis showed that the risk of FIB-4 ≥ 2.67 was closely associated with hepatitis B virus surface antigen (HBsAg) [hazard ratio (HR) = 3.1, 95% CI = 2.0–4.6] and HCV Ab positivity (HR = 3.2, 95% CI = 2.0–5.0).ConclusionOur results suggest that it might be worth considering that usage of information on platelets in legal health checkups could be some help not to overlook workers with hepatitis virus carriers as a complementary countermeasure, although further investigations are needed into its practical application

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Redox regulation of hepatitis C in nonalcoholic and alcoholic liver

Hepatitis C virus (HCV) is an RNA virus of the Flaviviridae family that is estimated to have infected 170 million people worldwide. HCV can cause serious liver disease in humans, such as cirrhosis, steatosis, and hepatocellular carcinoma. HCV induces a state of oxidative/nitrosative stress in patients through multiple mechanisms, and this redox perturbation has been recognized as a key player in HCV-induced pathogenesis. Studies have shown that alcohol synergizes with HCV in the pathogenesis of liver disease, and part of these effects may be mediated by reactive species that are generated during hepatic metabolism of alcohol. Furthenriore, reactive species and alcohol may influence HCV replication and the outcome of interferon therapy. Alcohol consumption has also been associated with increased sequence heterogeneity of the HCV RNA sequences, suggesting multiple modes of interaction between alcohol and HCV. This review summarizes the current understanding of oxidative and nitrosative stress during HCV infection and possible combined effects of HCV, alcohol, and reactive species in the pathogenesis of liver disease. (c) 2007 Elsevier Inc. All rights reserved

Visual crypsis as a possible function of polymorphic shell coloration in the infaunal clam Ruditapes philippinarum

The infaunal clam Ruditapes philippinarum exhibits highly polymorphic shell coloration, but the function of the coloration remains uncertain. Here, a hypothesis that such shell coloration functions to enhance visual crypsis (i.e., background color matching) in juveniles (<15 mm in shell length) was tested with a combination of a field survey and laboratory experiments. Shell and background colorations were expressed as mean brightness values. Firstly, the association between shell and background brightness was investigated. For this, a field survey for two sympatric subpopulations with distinct substrates was conducted on an intertidal sandflat in western Kyushu, Japan. Secondly, the visual-crypsis hypothesis was tested experimentally using half-valve clam shells filled with paste of raw clam meat as prey and the pufferfish Takifugu niphobles as a visually hunting predator, in a tank with one to two dark-colored substrates and one light-colored substrate. The field survey showed that shell brightness significantly differed between the two sympatric subpopulations of juvenile clams and was positively associated with background brightness. The laboratory experiments indicated that prey items with comparatively light (dark) coloration on dark- (light-) colored substrate were consumed by predators more immediately and at a higher rate than in the color-matched combinations. Consequently, shell?background color matching could help juvenile clams avoid attack from visually hunting predators. The results provide a new insight into effective management planning for this clam species, creating sand habitats with a more matched coloration