Policy Responses to the Post-bubble Adjustments in Japan: A Tentative Review

This paper provides a very tentative review of the monetary and prudential policy responses to the post-bubble adjustments in Japan. The adjustments after the collapse of the bubble have been prolonged due to (1) the rapid downward revision of the expected economic growth rate; (2) balance-sheet adjustments on the part of firms; and (3) the malfunctioning of the financial intermediary system stemming from its nonperforming-asset problem. We use four yardsticks, Marshallian k, Taylor rule, the equity yield spread, and the short-term real interest rate for assessing the monetary easing. The results suggest that the timing of policy reversal was swift and the magnitude of easing in the early phase could be viewed as broadly adequate for dealing with a normal business cycle. It is possible to argue that the effects of the bursting of the bubble might have not been sufficiently taken into account. It should be noted the outcome would not have differed greatly even if the drastic monetary easing that eventually took place had been decided at an earlier point in time without a fundamental cure of the nonperforming- asset problem. A considerable achievement of prudential policy in the period under review is that systemic risk was avoided with the cost being delayed in establishing a legal framework for handling troubled financial institutions and in organizing a comprehensive safety net. As a result of this delay, it took a long time to deal with the nonperforming- asset problem. This, in turn, posed a serious drag on the economy. Our preliminary conclusion about the lesson we should draw from this experience is the importance for the Bank of Japan of identifying the precise impacts of shocks on the economy as well as their transmission mechanism promptly and thereby minimizing adjustment costs. It should also be conducive for the Bank to address actively structural issues that may influence the effectiveness of its policy measures.

Heat shock protein 90 inhibitor NVP-AUY922 exerts potent activity against adult T-cell leukemia?lymphoma cells

Adult T-cell leukemia-lymphoma (ATL), an aggressive neoplasm etiologically associated with HTLV-1, is a chemoresistant malignancy. Heat shock protein 90 (HSP90) is involved in folding and functions as a chaperone for multiple client proteins, many of which are important in tumorigenesis. In this study, we examined NVP-AUY922 (AUY922), a second generation isoxazole-based non-geldanamycin HSP90 inhibitor, and confirmed its effects on survival of ATL-related cell lines. Analysis using FACS revealed that AUY922 induced cell-cycle arrest and apoptosis; it also inhibited the growth of primary ATL cells, but not of normal PBMCs. AUY922 caused strong upregulation of HSP70, a surrogate marker of HSP90 inhibition, and a dose-dependent decrease in HSP90 client proteins associated with cell survival, proliferation, and cell cycle in the G1 phase, including phospho-Akt, Akt, IKKα, IKKβ, IKKγ, Cdk4, Cdk6, and survivin. Interestingly, AUY922 induced downregulation of the proviral integration site for Moloney murine leukemia virus (PIM) in ATL cells. The PIM family (PIM-1, -2, -3) is made up of oncogenes that encode a serine/threonine protein kinase family. As PIM kinases have multiple functions involved in cell proliferation, survival, differentiation, apoptosis, and tumorigenesis, their downregulation could play an important role in AUY922-induced death of ATL cells. In fact, SGI-1776, a pan-PIM kinase inhibitor, successfully inhibited the growth of primary ATL cells as well as ATL-related cell lines. Our findings suggest that AUY922 is an effective therapeutic agent for ATL, and PIM kinases may be a novel therapeutic target. This report first describes the effectiveness of a novel HSP90 inhibitor NVP-AUY922 to adult T-cell leukemia-lymphoma (ATL) cells

RELEVANCE OF MOLECULAR TESTS FOR HTLV-1 INFECTION AS CONFIRMATORY TESTS AFTER THE FIRST SERO-SCREENING

The diagnosis of human T-cell leukemia virus type-1 (HTLV-1) infection has been widely examined by serologics. In the first screening tests, serological false negative and positive samples have been reduced thanks to advances in assay techniques that apply new emission agents and sensors. On the other hand, western blot (WB) remains problematic. For example, WB analysis yields many samples equivalent to antibody positive ones. To reduce the need for WB, an alternative testing strategy is required to detect HTLV-1 infection. Polymerase chain reaction (PCR) for the HTLV-1 provirus has recently been recommended for a final diagnosis of infection. However, although PCR is thought to be one element, the validation of detection performance for HTLV-1 infection between serological and molecular testing is not always clear. Thus, this study aimed to evaluate the accuracy and test the validity of an improved methodology for serological detection of HTLV-infection, as well as that of PCR. In conclusion, the high values of kappa-statistics are expected to deliver high quality in chemiluminescent enzyme immunoassay (or chemiluminescent immunoassay), while the problems with WB assays remain to be elucidated. As an alternative to WB, a combination of real-time qPCR and nested PCR is proposed as a suitable confirmatory test

Molecular analysis of the BCR-ABL1 kinase domain in chronic-phase chronic myelogenous leukemia treated with tyrosine kinase inhibitors in practice: Study by the Nagasaki CML Study Group

An appropriate trigger for BCR-ABL1 mutation analysis has not yet been established in unselected cohorts of chronic-phase chronic myelogenous leukemia patients. We examined 92 patients after 12 months of tyrosine kinase inhibitor (TKI) treatment in Nagasaki Prefecture, Japan. Univariate analysis revealed that significant factors associated with not attaining a major molecular response (MMR) were the presence of the minor BCR-ABL1 fusion gene, a low daily dose of TKI, and the emergence of BCR-ABL1 kinase domain mutations conferring resistance to imatinib. Factors associated with the loss of sustained MMR were a low daily dose of TKI and the emergence of alternatively spliced BCR-ABL1 mRNA with a 35-nucleotide insertion. Taken together, our results suggest that the search for BCR-ABL1 mutations should be initiated if patients have not achieved MMR following 12 months of TKI treatment

A survey of the international use of yen

This paper focuses on the yen's role as a currency of invoice and financial asset. Further aspects of the internationalisation of the yen (e.g. non-resident borrowing in yen) are not dealt with directly. The relatively small importance of the yen in trade invoicing suggests that the "transaction balance" portion of yen holdings has been small. This argument is further reinforced by the fact that the growth of non-resident holdings of yen assets has been closely related to the development of the exchange rate, coupled with the low level of yen sight accounts with Japanese banks. This implies that the advantage that the Japanese economy would enjoy from internationalisation is small, since the major advantage to the home country of an international currency is that it can fund part of its imports with non- or low-interest bearing liabilities. Furthermore, the exchange rate has been made more vulnerable to external shocks, although direct disturbance on of the domestic financial market has so far not been too serious.