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  1. [Asian Harmonization Working Party (AHWP) report]
    Takahashi S
    Nihon Hoshasen Gijutsu Gakkai Zasshi, 2014 Apr;70(4):416-7.
    PMID: 24759223
  2. Contamination of butyltin compounds in Malaysian marine environments
    Sudaryanto A, Takahashi S, Iwata H, Tanabe S, Ismail A
    Environ Pollut, 2004 Aug;130(3):347-58.
    PMID: 15182968
    Concentration of butyltin compounds (BTs), including tributyltin (TBT), dibutyltin (DBT) and monobutyltin (MBT) and total tin (SigmaSn) were determined in green mussel (Perna viridis), 10 species of muscle fish and sediment from coastal waters of Malaysia. BTs were detected in all these samples ranging from 3.6 to 900 ng/g wet wt., 3.6 to 210 ng/g wet wt., and 18 to 1400 ng/g dry wt. for mussels, fish and sediments, respectively. The concentrations of BTs in several locations of this study were comparable with the reported values from some developed countries and highest among Asian developing nations. Considerable concentration of BTs in several locations might have ecotoxicological consequences and may cause concern to human health. The parent compound TBT was found to be highest than those of its degradation compounds, DBT and MBT, suggesting recent input of TBT to the Malaysian marine environment. Significant positive correlation (Spearman rank correlation: r2=0.82, P<0.0001) was found between BTs and SigmaSn, implying considerable anthropogenic input of butyltin compounds to total tin contamination levels. Enormous boating activities may be a major source of BTs in this country, although aquaculture activities may not be ignored.
  3. Crazing Effect on the Bio-Based Conducting Polymer Film
    Wong PY, Takeno A, Takahashi S, Phang SW, Baharum A
    Polymers (Basel), 2021 Oct 06;13(19).
    PMID: 34641240 DOI: 10.3390/polym13193425
    The biodegradability problem of polymer waste is one of the fatal pollutFions to the environment. Enzymes play an essential role in increasing the biodegradability of polymers. In a previous study, antistatic polymer film based on poly(lactic acid) (PLA) as a matrix and polyaniline (PAni) as a conductive filler, was prepared. To solve the problem of polymer wastes pollution, a crazing technique was applied to the prepared polymer film (PLA/PAni) to enhance the action of enzymes in the biodegradation of polymer. This research studied the biodegradation test based on crazed and non-crazed PLA/PAni films by enzymes. The presence of crazes in PLA/PAni film was evaluated using an optical microscope and scanning electron microscopy (SEM). The optical microscope displayed the crazed in the lamellae form, while the SEM image revealed microcracks in the fibrils form. Meanwhile, the tensile strength of the crazed PLA/PAni film was recorded as 19.25 MPa, which is almost comparable to the original PLA/PAni film with a tensile strength of 20.02 MPa. However, the Young modulus decreased progressively from 1113 MPa for PLA/PAni to 651 MPa for crazed PLA/PAni film, while the tensile strain increased 150% after crazing. The significant decrement in the Young modulus and increment in the tensile strain was due to the craze propagation. The entanglement was reduced and the chain mobility along the polymer chain increased, thus leading to lower resistance to deformation of the polymer chain and becoming more flexible. The presence of crazes in PLA/PAni film showed a substantial change in weight loss with increasing the time of degradation. The weight loss of crazed PLA/PAni film increased to 42%, higher than that of non-crazed PLA/PAni film with only 31%. The nucleation of crazes increases the fragmentation and depolymerization of PLA/PAni film that induced microbial attack and led to higher weight loss. In conclusion, the presence of crazes in PLA/PAni film significantly improved enzymes' action, speeding up the polymer film's biodegradability.
  4. Unantimycin A, a new neoantimycin analog isolated from a microbial metabolite fraction library
    Lim CL, Nogawa T, Okano A, Futamura Y, Kawatani M, Takahashi S, et al.
    J Antibiot (Tokyo), 2016 06;69(6):456-8.
    PMID: 26648115 DOI: 10.1038/ja.2015.124
  5. Opantimycin A, a new metabolite isolated from Streptomyces sp. RK88-1355
    Nogawa T, Okano A, Lim CL, Futamura Y, Shimizu T, Takahashi S, et al.
    J Antibiot (Tokyo), 2017 02;70(2):222-225.
    PMID: 27599762 DOI: 10.1038/ja.2016.113
  6. Dihydrolucilactaene, a Potent Antimalarial Compound from Fusarium sp. RK97-94
    A Abdelhakim I, Bin Mahmud F, Motoyama T, Futamura Y, Takahashi S, Osada H
    J Nat Prod, 2022 01 28;85(1):63-69.
    PMID: 34949088 DOI: 10.1021/acs.jnatprod.1c00677
    A recently discovered secondary metabolism regulator, NPD938, was used to alter the secondary metabolite profile in Fusarium sp. RK97-94. Three lucilactaene analogues were detected via UPLC-ESI-MS analysis in NPD938-treated culture. The three metabolites were successfully purified and identified as dihydroNG391 (1), dihydrolucilactaene (2), and 13α-hydroxylucilactaene (3) via extensive spectroscopic analyses. DihydroNG391 (1) exhibited weak in vitro antimalarial activity (IC50 = 62 μM). In contrast, dihydrolucilactaene (2) and 13α-hydroxylucilactaene (3) showed very potent antimalarial activity (IC50 = 0.0015 and 0.68 μM, respectively). These findings provide insight into the structure-activity relationship of lucilactaene and its analogues as antimalarial lead compounds.
  7. RK-1355A and B, novel quinomycin derivatives isolated from a microbial metabolites fraction library based on NPPlot screening
    Lim CL, Nogawa T, Uramoto M, Okano A, Hongo Y, Nakamura T, et al.
    J Antibiot (Tokyo), 2014 Apr;67(4):323-9.
    PMID: 24496142 DOI: 10.1038/ja.2013.144
    Two novel quinomycin derivatives, RK-1355A (1) and B (2), and one known quinomycin derivative, UK-63,598 (3), were isolated from a microbial metabolites fraction library of Streptomyces sp. RK88-1355 based on Natural Products Plot screening. The structural elucidation of 1 and 2 was established through two-dimensional NMR and mass spectrometric measurements. They belong to a class of quinomycin antibiotics family having 3-hydroxyquinaldic acid and a sulfoxide moiety. They are the first examples for natural products as a quinoline type quinomycin having a sulfoxide on the intramolecular cross-linkage. They showed potent antiproliferative activities against various cancer cell lines and they were also found to exhibit moderate antibacterial activity.
  8. Soil contamination by brominated flame retardants in open waste dumping sites in Asian developing countries
    Eguchi A, Isobe T, Ramu K, Tue NM, Sudaryanto A, Devanathan G, et al.
    Chemosphere, 2013 Mar;90(9):2365-71.
    PMID: 23149186 DOI: 10.1016/j.chemosphere.2012.10.027
    In Asian developing countries, large amounts of municipal wastes are dumped into open dumping sites each day without adequate management. This practice may cause several adverse environmental consequences and increase health risks to local communities. These dumping sites are contaminated with many chemicals including brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs). BFRs may be released into the environment through production processes and through the disposal of plastics and electronic wastes that contain them. The purpose of this study was to elucidate the status of BFR pollution in municipal waste dumping sites in Asian developing countries. Soil samples were collected from six open waste dumping sites and five reference sites in Cambodia, India, Indonesia, Malaysia, and Vietnam from 1999 to 2007. The results suggest that PBDEs are the dominant contaminants in the dumping sites in Asian developing countries, whereas HBCD contamination remains low. Concentrations of PBDEs and HBCDs ranged from ND to 180 μg/kg dry wt and ND to 1.4 μg/kg dry wt, respectively, in the reference sites and from 0.20 to 430 μg/kg dry wt and ND to 2.5 μg/kg dry wt, respectively, in the dumping sites. Contamination levels of PBDEs in Asian municipal dumping sites were comparable with those reported from electronic waste dismantling areas in Pearl River delta, China.
  9. Asia-Pacific mussel watch: monitoring of butyltin contamination in coastal waters of Asian developing countries
    Sudaryanto A, Takahashi S, Monirith I, Ismail A, Muchtar M, Zheng J, et al.
    Environ. Toxicol. Chem., 2002 Oct;21(10):2119-30.
    PMID: 12371488
    Butyltin compounds (BTs) including mono-, di-, and tributyltin and total tin (sigmaSn), were determined in green mussels (Perna viridis) from various Asian developing countries, such as Cambodia, China (Hong Kong and southern China), Malaysia, India, Indonesia, the Philippines, and Vietnam, to elucidate the contamination status, distribution, and possible sources and to assess the risks on aquatic organisms and humans. Butyltin compounds were detected in green mussels collected from all the sampling location investigated, suggesting widespread contamination of BTs along the coastal waters of Asian developing countries. Among butyltin derivatives, tributyltin (TBT) was the predominant compound, indicating its ongoing usage and recent exposures in Asian coastal waters. Higher concentrations of BTs were found in mussels collected at locations with intensive maritime activities, implying that the usage of TBT as a biocide in antifouling paints was a major source of BTs. In addition, relatively high concentrations of BTs were observed in mussels from aquaculture areas in Hong Kong and Malaysia, as it has been reported in Thailand. With the recent improvement in economic status in Asia, it is probable that an increase in TBT usage will occur in aquaculture. Although contamination levels were generally low in mussel samples from most of the Asian developing countries, some of those from polluted areas in Hong Kong, India, Malaysia, the Philippines, and Thailand revealed levels comparable to those in developed nations. Furthermore, the concentrations of TBT in some mussels from polluted areas exceeded the threshold for toxic effects on organisms and estimated tolerable average residue levels as seafoods for human consumption. A significant correlation was observed between the concentrations of sigmaBTs and sigmaSn in mussels, and sigmaBTs were made up mostly 100% of sigmaSn in mussels taken from locations having intensive maritime/human activities. This suggests that anthropogenic BTs represent the major source of tin accumulation in mussels. To our knowledge, this is a first comprehensive report on butyltin pollution monitoring in developing countries in the Asia-Pacific region.
  10. Fulltext Controversies with nonoperative management for adolescent idiopathic scoliosis: Study from the APSS Scoliosis Focus Group
    Cheung JPY, Cheung PWH, Shigematsu H, Takahashi S, Kwan MK, Chan CYW, et al.
    J Orthop Surg (Hong Kong), 2020 6 13;28(2):2309499020930291.
    PMID: 32529908 DOI: 10.1177/2309499020930291
    PURPOSE: To determine consensus among Asia-Pacific surgeons regarding nonoperative management for adolescent idiopathic scoliosis (AIS).

    METHODS: An online REDCap questionnaire was circulated to surgeons in the Asia-Pacific region during the period of July 2019 to September 2019 to inquire about various components of nonoperative treatment for AIS. Aspects under study included access to screening, when MRIs were obtained, quality-of-life assessments used, role of scoliosis-specific exercises, bracing criteria, type of brace used, maturity parameters used, brace wear regimen, follow-up criteria, and how braces were weaned. Comparisons were made between middle-high income and low-income countries, and experience with nonoperative treatment.

    RESULTS: A total of 103 responses were collected. About half (52.4%) of the responders had scoliosis screening programs and were particularly situated in middle-high income countries. Up to 34% obtained MRIs for all cases, while most would obtain MRIs for neurological problems. The brace criteria were highly variable and was usually based on menarche status (74.7%), age (59%), and Risser staging (92.8%). Up to 52.4% of surgeons elected to brace patients with large curves before offering surgery. Only 28% of responders utilized CAD-CAM techniques for brace fabrication and most (76.8%) still utilized negative molds. There were no standardized criteria for brace weaning.

    CONCLUSION: There are highly variable practices related to nonoperative treatment for AIS and may be related to availability of resources in certain countries. Relative consensus was achieved for when MRI should be obtained and an acceptable brace compliance should be more than 16 hours a day.

  11. Fulltext Challenges in Global Access to CAR-T cells: an Asian Perspective
    Hwang WY, Takahashi S, Choi B, Huang H, Kawamata S, Ng SC, et al.
    Blood Cell Ther, 2024 Feb 25;7(1):10-13.
    PMID: 38486827 DOI: 10.31547/bct-2023-023
    The use of cell therapy for clinical applications has seen a dramatic increase in recent years, primarily in oncology, especially with the use of chimeric antigen receptor (CAR) T-cell therapies. However, there are some barriers to the widespread adoption of CAR-T cell therapies globally, primarily because of the high cost of manufacturing these cells and clinical infrastructure considerations. We reviewed the different strategies adopted across Asia to implement CAR-T cell therapy and found that these included patient assistance programs, close engagement with funders, cost-effectiveness studies, on-site manufacturing of CAR-T cells, and joint ventures between local partners and foreign pharmaceutical companies. Although on-site manufacturing can reduce the cost of genetic engineering and expansion, it does not address many other hidden costs and quality considerations. Future growth in large-scale regional manufacturing, facilitated by cutting-edge science and innovation, could reduce costs through economies of scale and facilitate the eagerly needed global access.
  12. Fulltext Epidemic dynamics, interactions and predictability of enteroviruses associated with hand, foot and mouth disease in Japan
    Takahashi S, Metcalf CJE, Arima Y, Fujimoto T, Shimizu H, Rogier van Doorn H, et al.
    J R Soc Interface, 2018 09 12;15(146).
    PMID: 30209044 DOI: 10.1098/rsif.2018.0507
    Outbreaks of hand, foot and mouth disease have been documented in Japan since 1963. This disease is primarily caused by the two closely related serotypes of Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CV-A16). Here, we analyse Japanese virologic and syndromic surveillance time-series data from 1982 to 2015. As in some other countries in the Asia Pacific region, EV-A71 in Japan has a 3 year cyclical component, whereas CV-A16 is predominantly annual. We observe empirical signatures of an inhibitory interaction between the serotypes; virologic lines of evidence suggest they may indeed interact immunologically. We fit the time series to mechanistic epidemiological models: as a first-order effect, we find the data consistent with single-serotype susceptible-infected-recovered dynamics. We then extend the modelling to incorporate an inhibitory interaction between serotypes. Our results suggest the existence of a transient cross-protection and possible asymmetry in its strength such that CV-A16 serves as a stronger forcing on EV-A71. Allowing for asymmetry yields accurate out-of-sample predictions and the directionality of this effect is consistent with the virologic literature. Confirmation of these hypothesized interactions would have important implications for understanding enterovirus epidemiology and informing vaccine development. Our results highlight the general implication that even subtle interactions could have qualitative impacts on epidemic dynamics and predictability.
  13. Asian Mussel Watch Program: contamination status of polybrominated diphenyl ethers and organochlorines in coastal waters of Asian countries
    Ramu K, Kajiwara N, Sudaryanto A, Isobe T, Takahashi S, Subramanian A, et al.
    Environ Sci Technol, 2007 Jul 01;41(13):4580-6.
    PMID: 17695900
    Mussel samples were used in this study to measure the levels of polybrominated diphenyl ethers (PBDEs) and organochlorines (OCs) in the coastal waters of Asian countries like Cambodia, China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, the Philippines, and Vietnam. PBDEs were detected in all the samples analyzed, and the concentrations ranged from 0.66 to 440 ng/g lipid wt. Apparently higher concentrations of PBDEs were found in mussels from the coastal waters of Korea, Hong Kong, China, and the Philippines, which suggests that significant sources of these chemicals exist in and around this region. With regard to the composition of PBDE congeners, BDE-47, BDE-99, and BDE-100 were the dominant congeners in most of the samples. Among the OCs analyzed, concentrations of DDTs were the highest followed by PCBs > CHLs > HCHs > HCB. Total concentrations of DDTs, PCBs, CHLs, and HCHs in mussel samples ranged from 21 to 58 000, 3.8 to 2000, 0.93 to 900, and 0.90 to 230 ng/g lipid wt., respectively. High levels of DDTs were found in mussels from Hong Kong, Vietnam, and China; PCBs were found in Japan, Hong Kong, and industrialized/urbanized locations in Korea, Indonesia, the Philippines, and India; CHLs were found in Japan and Hong Kong; HCHs were found in India and China. These countries seem to play a role as probable emission sources of corresponding contaminants in Asia and, in turn, may influence their global distribution.
  14. Asia-Pacific mussel watch: monitoring contamination of persistent organochlorine compounds in coastal waters of Asian countries
    Monirith I, Ueno D, Takahashi S, Nakata H, Sudaryanto A, Subramanian A, et al.
    Mar Pollut Bull, 2003 Mar;46(3):281-300.
    PMID: 12604061
    Contamination of persistent organochlorines (OCs) such as PCBs (polychlorinated biphenyls), DDT and its metabolites (DDTs), HCH (hexachlorocyclohexane) isomers (HCHs), chlordane compounds (CHLs), and HCB (hexachlorobenzene) were examined in mussels collected from coastal waters of Asian countries such as Cambodia, China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Far East Russia, Singapore, and Vietnam in 1994, 1997, 1998, 1999, and 2001 to elucidate the contamination status, distribution and possible pollution sources and to assess the risks on aquatic organisms and human. OCs were detected in all mussels collected from all the sampling sites investigated. Considerable residue levels of p,p(')-DDT and alpha-HCH were found in mussels and the concentrations of DDTs and HCHs found in mussels from Asian developing countries were higher than those in developed nations suggesting present usage of DDTs and HCHs along the coastal waters of Asian developing countries. On the other hand, lower concentrations of PCBs detected in mussels from Asian developing countries than those in developed countries indicate that PCBs contamination in mussels is strongly related to industrial and activities. To our knowledge, this is a first comprehensive report on monitoring OCs pollution in the Asia-Pacific region.
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