Japan's Deflation, Problems in the Financial System, and Monetary Policy

This paper offers three analyses of Japan's macroeconomic experience during the post-1990 period. First, we analyze various facets of deflation during the period, arguing that the deflation of general prices has by no means been a major factor for the stagnating economy. In contrast, the deflation of asset prices was closely related to the economic difficulty of the period. In particular, the negative shocks generated by sharp declines in asset prices in the early 1990s have been propagated and amplified by their interaction with the deterioration in the condition of the financial system. Some statistical evidence supports this view. Second, we analyze the effects of monetary policy adopted by the Bank of Japan (BOJ) to fight deflation since the late 1990s. Given that short-term interest rates were already nearly zero in the mid-1990s, policy measures have focused on creating monetary easing effects beyond those created by zero interest rates alone. We show that the zero interest rate policy, which includes a commitment to maintain a zero interest rate for a longer period than that suggested by a baseline monetary policy rule, has produced strong effects on expected future short-term interest rates and thus the entire yield curve. Third, we argue that the BOJ has successfully prevented a repetition of the 1997-98 type liquidity crisis by directing market operations at addressing the financial-sector problems. These operations have taken the form of containing risk and liquidity premiums, particularly in the money market, through proactive provision of liquidity as well as the BOJ's own risk- taking activity.

"In vivo cryotechnique" for paradigm shift to "living morphology" of animal organs

The morphological study has been one of the major approaches in medical and biological fields. For the last century, the conventional chemical fixation and alcohol dehydration were commonly used as an easy preparation method, but it was frequently pointed out that they usually yield many structural artifacts during their preparation processes. Although both conventional quick-freezing and high-pressure freezing methods, by which animal tissues are resected and frozen for physical fixation,can reduce such structural artifacts, the tissues have to be removed from living animal organs for the freezing. Therefore, such specimens are inevitably exposed to noxious stresses of anoxia and ischemia, exhibiting only dead morphological states of animal tissues without blood circulation. To the contrary, our "in vivo cryotechnique", by which all cells and tissues in animal bodies are cryofixed in vivo, can prevent such artifacts of resected specimens. By means of the cryotechnique, it is now possible to reveal the in vivo morphology of cells and tissues in living animal organs. Actually, it has been already applied to several animal organs, such as kidney, liver, intestine, cerebellum, eye ball, blood vessel, and joint cartilage, and brought new morphological findings, reflecting their physiological significance, which had been difficult to demonstrate by the conventional preparation methods. Moreover, its application to immunohistochemistry has also revealed more precise immunolocalizations of dynamically changing molecules in living animal organs, easily translocated by ischemic stresses and anoxia caused during the tissue resection. The "in vivo cryotechnique" allows us to perform novel morphological investigations of "living" morphological states, and develops new medical and biological fields with "living morphology" during this 21st century.Biomedical Reviews 2004; 15: 1-19

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy