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Eiichi Kodama

Section

International Research Institute of Disaster Science

Job title

Professor

Degree

博士（医学）（福島県立医科大学）

researchmap

https://researchmap.jp/7000005426

J-GLOBAL ID

201301075761064283

Research History 12

2020/08 - Present

Tohoku University
2020/08 - Present

東北大学病院　兼務教授
2020/08 - Present

東北メディカル・メガバンク機構
2016/06 - Present

Tohoku University
2013/04 - 2016/03

Tohoku University
2013/01 - 2013/03

Tohoku University
2009/04 - 2012/12

東北大学病院　内科総合感染症科　助教
1999/09 - 2009/03

Kyoto University　Institute for Virus Research
1998/04 - 1999/08

Fukushima Medical University
1996/05 - 1998/03

NIH/NCL　レトロウイルス部門
1995/10 - 1996/04

アラバマ州立大学　小児科学講座
1994/04 - 1995/09

Fukushima Medical University

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Education 2

Fukushima Medical University

1990/04 - 1994/03
Fukushima Medical University　Faculty of Medicine

- 1990/03/31

Professional Memberships 9

国際抗ウイルス学会
Association for Antiviral Therapy
JAPANESE SOCIETY FOR CHEMICAL BIOLOGY
THE JAPANESE SOCIETY FOR AIDS RESEARCH
THE JAPANESE BIOLOGICAL SAFETY ASSOCIATION
Japanese Association for Disaster Medicine
JAPANESE SOCIETY FOR INFECTION PREVENTION AND CONTROL
THE JAPANESE ASSOCIATION FOR INFECTIOUS DISEASES
THE JAPANESE SOCIETY FOR VIROLOGY

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Research Interests 5

感染制御
抗菌剤
resistance
anti-cncer agents
Antivira agents

Research Areas 4

Life sciences / Pharmaceuticals - chemistry and drug development /
Life sciences / Healthcare management, medical sociology /
Life sciences / Infectious disease /
Life sciences / Virology /

Papers 187

Elucidation of Postfusion Structures of the Measles Virus F Protein for the Structure-Based Design of Fusion Inhibitors. International-journal

Aoi Takahara, Toru Nakatsu, Kazushige Hirata, Hironori Hayashi, Kumi Kawaji, Keisuke Aoki, Shinsuke Inuki, Hiroaki Ohno, Hiroaki Kato, Eiichi Kodama, Shinya Oishi

Journal of medicinal chemistry　2025/01/31

DOI： 10.1021/acs.jmedchem.4c02337 　

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Measles is a highly infectious disease and remains a major cause of childhood mortality worldwide. In some cases, the measles virus (MV) induces subacute sclerosing panencephalitis within several years of the acute infection. The infection of the target cells by MV is mediated by the F protein, in which two heptad repeat regions, HR1 and HR2, form a six-helix bundle before membrane fusion. We previously reported anti-MV peptides, which were designed from the HR region of the MV F protein. Here, we characterized the essential interactions between the HR1 and HR2 regions on the postfusion six-helix bundles of synthetic HR1 and HR2 peptides by crystallographic studies. Based on the crystal structures, we identified the minimal α-helix sequence for antiviral activity. Additionally, optimizing HR2 peptides by introducing α-helix-inducible motifs and maintaining key hydrogen bond networks at the N- and C-terminal regions led to the identification of highly potent antiviral peptides.
Association Between Sodium- and Potassium-Related Urinary Markers and the Prevalence of Atrial Fibrillation.

Sayuri Tokioka, Naoki Nakaya, Rieko Hatanaka, Kumi Nakaya, Mana Kogure, Ippei Chiba, Masato Takase, Kotaro Nochioka, Kai Susukita, Hirohito Metoki, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Satoshi Nagaie, Soichi Ogishima, Yoko Izumi, Nobuo Fuse, Shinichi Kuriyama, Satoshi Yasuda, Atsushi Hozawa

Circulation journal : official journal of the Japanese Circulation Society　2025/01/11

DOI： 10.1253/circj.CJ-24-0780 　

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BACKGROUND: The primary prevention of atrial fibrillation (AF), which increases mortality through complications including stroke and heart failure, is important. Excessive salt intake and low potassium intake are risk factors for cardiovascular disease; however, their association with AF remains inconclusive. This study investigated the association between sodium- and potassium-related urinary markers and AF prevalence. METHODS AND RESULTS: Data from the Tohoku Medical Megabank Project Community-based Cohort Study were used in this cross-sectional study. The urinary sodium-to-potassium (Na/K) ratio and estimated 24-h sodium and potassium excretion were calculated using spot urine samples and categorized into quartiles (Q1-Q4). The prevalence of AF was the primary outcome. Of the 26,506 participants (mean age 64.8 years; 33.2% males) included in this study, 630 (2.4%) had AF. Using Q1 as the reference group, the odds ratios for AF prevalence in Q4 were 1.35 (95% confidence interval [CI] 1.07-1.73) and 1.59 (95% CI 1.20-2.12) for 24-h estimated urinary Na/K ratio and estimated 24-h sodium excretion, respectively. Estimated 24-h potassium excretion was not associated with AF prevalence. CONCLUSIONS: AF prevalence was positively associated with the urinary Na/K ratio and estimated 24-h urinary sodium excretion, but not with estimated 24-h urinary potassium excretion. Although further prospective studies are warranted, the findings of this study suggest that salt intake may be a modifiable risk factor for AF.
Analyzing Trends in the Medical Community During the Spanish Flu Pandemic in Japan with the Comprehensive Knowledge of Humanities and Sciences: A Case Study of the Medical Journal, The Japan Medical World

Atsushi Kawauchi, Natsuko Chubachi, Yasuhiro Miki, Kiyoshi Ito, Eiichi N. Kodama

Journal of Disaster Research　19　(6)　921-934　2024/12/01
Publisher: Fuji Technology Press Ltd.
DOI： 10.20965/jdr.2024.p0921 　

ISSN： 1881-2473

eISSN： 1883-8030

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This study aimed to examine the trends in the medical community in Japan during the Spanish flu pandemic by analyzing The Japan Medical World (JMW), a medical journal of modern Japan. The analysis included 3,856 articles published in issues Nos.228–279, from January 1918 to March 1919. Three key issues emerged from this analysis. First, the tone of the JMW’s discourse may have been influenced by the prevailing medical situation or may have placed emphasis on specific aspects of the situation. Second, the JMW and the medical community in Japan initially neglected the influenza pandemic until the autumn of 1918, when the Spanish flu became widespread in Japan. Third, complex factors, such as academic factionalism and conflicts within the pharmaceutical industries, influenced the Japanese medical community, particularly the bacteriological scientific community during the Spanish flu pandemic. Therefore, “a comprehensive approach” to understanding the period, including not only medical knowledge but also critical reading skills of humanities and social sciences, is indispensable for analyzing the trends in the Japanese medical community during the Spanish flu pandemic. Attention should be paid to these factors when examining the trends in the medical community in Japan at that time.
SHIN-2 exerts potent activity against VanA-type vancomycin-resistant Enterococcus faecium in vitro by stabilizing the active site loop of serine hydroxymethyltransferase. International-journal

Hironori Hayashi, Erika Saijo, Kazushige Hirata, Shumei Murakami, Haruka Okuda, Eiichi N Kodama, Kazuya Hasegawa, Kazutaka Murayama

Archives of biochemistry and biophysics　110160-110160　2024/09/21

DOI： 10.1016/j.abb.2024.110160 　

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Novel classes of antibiotics are needed to improve the resilience of the healthcare system to antimicrobial resistance (AMR), including vancomycin resistance. vanA gene cluster is a cause of vancomycin resistance. This gene cluster is transferred and spreads vancomycin resistance from Enterococcus spp. to Staphylococcus aureus. Therefore, novel antibacterial agents are required to combat AMR, including vanA-type vancomycin resistance. Serine hydroxymethyltransferase (SHMT) is a key target of antibacterial agents. However, the specific binding mechanisms of SHMT inhibitors remain unclear. Detailed structural information will contribute to understanding these mechanisms. In this study, we found that (+)-SHIN-2, the first in vivo active inhibitor of human SHMT, is strongly bound to the Enterococcus faecium SHMT (efmSHMT). Comparison of the crystal structures of apo- and (+)-SHIN-2-boud efmSHMT revealed that (+)-SHIN-2 stabilized the active site loop of efmSHMT via hydrogen bonds, which are critical for efmSHMT inhibition. Additionally, (+)-SHIN-2 formed hydrogen bonds with serine, forming the Schiff's base with pyridoxal 5'-phosphate, which is a co-factor of SHMT. Furthermore, (+)-SHIN-2 exerted biostatic effects on vancomycin-susceptible and vanA-type vancomycin-resistant E. faecium in vitro, indicating that SHMT inhibitors do not induce cross-resistance to vanA-type vancomycin. Overall, these findings can aid in the design of novel SHMT inhibitors to combat AMR, including vancomycin resistance.
Genetic Risk, Lifestyle Adherence, and Risk of Developing Hyperuricaemia in a Japanese Population

Masato Takase, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Sayuri Tokioka, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Akira Narita, Taku Obara, Mami Ishikuro, Hisashi Ohseto, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Biobank Japan Project; Koichi Matsuda, Yoko Izumi, Kengo Kinoshita, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

Rheumatology　2024/09/13
Publisher: Oxford University Press (OUP)
DOI： 10.1093/rheumatology/keae492 　

ISSN： 1462-0324

eISSN： 1462-0332

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Abstract Objective To investigate the inter-relationships among genetic risk, healthy lifestyle adherence, and hyperuricaemia susceptibility. Methods This prospective cohort study was conducted with 7,241 hyperuricaemia-free individuals aged ≥ 20 years from the Tohoku Medical Megabank Community-based cohort study. A comprehensive lifestyle score included body mass index, smoking, drinking, and physical activity, and a polygenic risk score (PRS) was constructed based on uric acid loci from a previous genome-wide association study meta-analysis. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and hyperuricaemia incidence and calculate the area under the receiver operating characteristic curve (AUROC). Hyperuricaemia was defined as a uric acid level ≥7.0 mg/dl or a self-reported history of hyperuricaemia. Results Of the 7,241 adults (80.7% females; mean [SD] age: 57.7 [12.6] years), 217 (3.0%) developed hyperuricaemia during 3.5 years of follow-up. Genetic risk correlated with hyperuricaemia development (P for interaction = 0.287), and lifestyle risks were independently associated. Those with a high genetic risk and poor lifestyle had the highest risk (odds ratio: 5.34; 95% confidence interval [CI]: 2.61–12.10). Although not statistically significant, incorporating the PRS in the model with lifestyle information improved predictive ability (AUROC = 0.771, 95% CI: 0.736–0.806 for lifestyle; AUROC = 0.785, 95% CI: 0.751–0.819 for lifestyle and PRS; p = 0.07). Conclusion : A healthy lifestyle to prevent hyperuricaemia, irrespective of genetic risk, may mitigate the genetic risk. Genetic risk may complement lifestyle factors in identifying individuals at a heightened hyperuricaemia risk.
Janus-Type Immunofluorescent Probes and a Quantitative Immunoassay System. International-journal Peer-reviewed

Hiroshi Yabu, Misako Suzuki, Kazushige Matsukawa, Ikuma Maeda, Sigeo Ihara, Koshiro Yaegashi, Kentaro Totsu, Hironori Hayashi, Eiichi Kodama

Langmuir : the ACS journal of surfaces and colloids　2024/08/15

DOI： 10.1021/acs.langmuir.4c01911 　

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To realize highly sensitive immunoassays, high optical density probes conjugated with antibodies for target antigens have been demanded in order to increase the visibility of antigen-antibody complex formation. We herein demonstrate the development of an immunoassay system using magnetic and fluorescent Janus particles as probes in conjunction with an antibody-immobilized microfluidic device. The concentration of the detection limit at which there was a significant difference between SARS-CoV-2 and human coronavirus 229E antigens was 3.1 ng/mL, and the standard deviation of the signal was less than 5%. The immunofluorescent probe and immunoassay system developed in this study are expected to be applicable not only to SARS-CoV-2 but also to the quantitative measurement of various other disease marker proteins and biomolecules.
The association of birth weight and current BMI on the risk of hypertension: the Tohoku medical megabank community-based cohort study. International-journal

Hiromi Himuro, Mana Kogure, Naoki Nakaya, Tomohiro Nakamura, Rieko Hatanaka, Ippei Chiba, Kumi Nakaya, Naho Tsuchiya, Takumi Hirata, Masatsugu Orui, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Akira Uruno, Nobuo Fuse, Satoshi Nagaie, Soichi Ogishima, Mami Ishikuro, Taku Obara, Yoko Izumi, Masatoshi Saito, Shinichi Kuriyama, Atsushi Hozawa, Junichi Sugawara

Hypertension research : official journal of the Japanese Society of Hypertension　2024/08/08

DOI： 10.1038/s41440-024-01827-z 　

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This study aimed to investigate the association of combination of birth weight and current body mass index (BMI) with the risk of hypertension in adulthood. This cross-sectional study used data from the Tohoku Medical Megabank Community-based Cohort Study conducted in Japan. A total of 10,688 subjects aged ≥20 years were eligible. We calculated the least square (LS) means of systolic blood pressure (SBP) and trend tests were performed to evaluate the linear relationships between birth weight categories and SBP. We also used a multivariate logistic regression analysis to assess the risk of hypertension associated with the combination of birth weight and current BMI. There was a statistically inverse association between birth weight and SBP in the 20-64 age group, but no significant association in the ≥65 age group. Low birth weight (LBW) with normal BMI group had a higher risk of hypertension than the normal or high birth weight groups with normal BMI. Furthermore, the group with LBW and BMI ≥25.0 kg/m2 was the highest risk for hypertension (adjusted odds ratio: 2.73; 95% CI, 2.04-3.65) compared to the reference group (birth weight 2500-3499 g and BMI 18.5-24.9 kg/m2). There was a significant association between LBW and subsequent risk of hypertension. In addition, participants with lower birth weights had a higher risk of hypertension than those with higher birth weights. However, even in participants with a lower birth weight, the risk of hypertension could be reduced when they maintained an optimal BMI.
2′-β-Methylselenyl nucleos(t)ide analogs as reverse transcriptase inhibitors against diverse HIV mutants Peer-reviewed

Yuki Yoshida, Yushi Niimi, Daichi Fushihara, Hideo Katakura, Ryusuke Fukui, Hirotaka Murase, Fumiaki Tomoike, Fumitaka Hashiya, Tsutomu Murakami, Eiichi N. Kodama, Tetsuro Suzuki, Kiyoshi Yasukawa, Yasuaki Kimura, Hiroshi Abe

Bioorganic & Medicinal Chemistry　110　117813-117813　2024/08
Publisher: Elsevier BV
DOI： 10.1016/j.bmc.2024.117813 　

ISSN： 0968-0896
Urgent Notification Intervention of Home Blood Pressure in Cohort Studies of the Tohoku Medical Megabank Project.

Eiichi N Kodama, Makiko Taira, Hideyasu Kiyomoto, Tomohiro Nakamura, Satoshi Nagaie, Shinichi Kuriyama, Atsushi Hozawa, Junichi Sugawara, Fuji Nagami, Akira Uruno, Jun Nakaya, Hirohito Metoki, Masaki Sakaida, Masahiro Kikuya, Yoichi Suzuki, Kiyoshi Ito, Yohei Hamanaka, Kichiya Suzuki, Shigeo Kure, Nobuo Yaegashi, Nobuo Fuse, Ritsuko Shimizu, Masayuki Yamamoto

JMA journal　7　(3)　342-352　2024/07/16

DOI： 10.31662/jmaj.2023-0215 　

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INTRODUCTION: The Tohoku Medical Megabank (TMM) was established for creative reconstruction from the Great East Japan Earthquake and tsunami in 2011. Two prospective genome cohort studies in Miyagi prefecture have successfully recruited approximately 127,000 participants. The health status of these individuals was evaluated at the initial recruitment, and follow-up health checkups have been conducted every 5 years. During these health checkups, unexpected critical values were encountered, which prompted us to develop an urgent notification system. METHODS: We analyzed the frequency of critical values observed in home blood pressure (HBP) test in an urgent notification office (UNO). We returned the critical values by urgent notification before the notifications of regular results. In addition, the impact of the TMM urgent notification on the participants was evaluated. RESULTS: We issued urgent notifications of the critical values of extremely high HBP. Of the 21,061 participants who underwent HBP measurements, 256 (1.2%) met the criteria for urgent notification. It was found that abnormalities in blood sugar levels, renal function, and lipid values were frequently concurrent with the abnormal HBP readings. Annual questionnaires administered after the urgent notification, approximately 60% of those went to hospitals or clinics. CONCLUSIONS: The urgent notification system for hypertensive emergency with HBP in the TMM was well accepted by the participants and encouraged them to seek medical care. The system has been useful in addressing the prolonged healthcare problems and in promoting health care in large-scale disaster damaged areas.
Depressive symptoms as risk factors for the onset of home hypertension: a prospective cohort study. International-journal

Sayuri Tokioka, Naoki Nakaya, Rieko Hatanaka, Kumi Nakaya, Mana Kogure, Ippei Chiba, Kotaro Nochioka, Hirohito Metoki, Takahisa Murakami, Michihiro Satoh, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Satoshi Nagaie, Soichi Ogishima, Yoko Izumi, Nobuo Fuse, Shinichi Kuriyama, Atsushi Hozawa

Hypertension research : official journal of the Japanese Society of Hypertension　2024/07/10

DOI： 10.1038/s41440-024-01790-9 　

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Depression is comorbid with somatic diseases; however, the relationship between depressive symptoms and hypertension (HT), a risk factor for cardiovascular events, remains unclear. Home blood pressure (BP) is more reproducible and accurately predictive of cardiovascular diseases than office BP. Therefore, we focused on home BP and investigated whether depressive symptoms contributed to the future onset of home HT. This prospective cohort study used data from the Tohoku Medical Megabank Community-Cohort Study (conducted in the Miyagi Prefecture, Japan) and included participants with home normotension (systolic blood pressure (SBP) < 135 mmHg and diastolic blood pressure (DBP) < 85 mmHg). Depressive symptoms were evaluated using the Center for Epidemiologic Studies Depression Scale-Japanese version at the baseline survey. In the secondary survey, approximately 4 years later, the onset of home HT was evaluated (SBP ≥ 135 mmHg or DBP ≥ 85 mmHg) and was compared in participants with and without depressive symptoms. Of the 3 082 (mean age: 54.2 years; females: 80.9%) participants, 729 (23.7%) had depressive symptoms at the baseline survey. During the 3.5-year follow-up, 124 (17.0%) and 388 (16.5%) participants with and without depressive symptoms, respectively, developed home HT. Multivariable adjusted odds ratios were 1.37 (95% confidence interval (CI): 1.02-1.84), 1.18 (95% CI: 0.86-1.61), and 1.66 (95% CI: 1.17-2.36) for home, morning, and evening HT, respectively. This relationship was consistent in the subgroup analyses according to age, sex, BP pattern, and drinking habit. Depressive symptoms increased the risk of new-onset home HT, particularly evening HT, among individuals with home normotension. This prospective cohort study revealed that depressive symptoms are risk factors for new-onset home hypertension, particularly evening hypertension among individuals with home normotension. Assessing home blood pressure in individuals with depressive symptoms is important for the prevention of hypertension and concomitant cardiovascular diseases.
Associations of combined genetic and lifestyle risks with hypertension and home hypertension. International-journal

Masato Takase, Takumi Hirata, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Akira Narita, Hirohito Metoki, Michihiro Satoh, Taku Obara, Mami Ishikuro, Hisashi Ohseto, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

Hypertension research : official journal of the Japanese Society of Hypertension　2024/06/24

DOI： 10.1038/s41440-024-01705-8 　

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No study, to our knowledge, has constructed a polygenic risk score based on clinical blood pressure and investigated the association of genetic and lifestyle risks with home hypertension. We examined the associations of combined genetic and lifestyle risks with hypertension and home hypertension. In a cross-sectional study of 7027 Japanese individuals aged ≥20 years, we developed a lifestyle score based on body mass index, alcohol consumption, physical activity, and sodium-to-potassium ratio, categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score was constructed with the target data (n = 1405) using publicly available genome-wide association study summary statistics from BioBank Japan. Using the test data (n = 5622), we evaluated polygenic risk score performance and examined the associations of combined genetic and lifestyle risks with hypertension and home hypertension. Hypertension and home hypertension were defined as blood pressure measured at a community-support center ≥140/90 mmHg or at home ≥135/85 mmHg, respectively, or self-reported treatment for hypertension. In the test data, 2294 and 2322 participants had hypertension and home hypertension, respectively. Both polygenic risk and lifestyle scores were independently associated with hypertension and home hypertension. Compared with those of participants with low genetic risk and an ideal lifestyle, the odds ratios for hypertension and home hypertension in the low genetic risk and poor lifestyle group were 1.94 (95% confidence interval, 1.34-2.80) and 2.15 (1.60-2.90), respectively. In summary, lifestyle is important to prevent hypertension; nevertheless, participants with high genetic risk should carefully monitor their blood pressure despite a healthy lifestyle.
Genetic Risk, Healthy Lifestyle Adherence, and Risk of Developing Diabetes in the Japanese Population.

Masato Takase, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Akira Narita, Taku Obara, Mami Ishikuro, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Koichi Matsuda, Yoko Izumi, Kengo Kinoshita, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

Journal of atherosclerosis and thrombosis　2024/06/22

DOI： 10.5551/jat.64906 　

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AIM: This study examined the relationship between genetic risk, healthy lifestyle, and risk of developing diabetes. METHODS: This prospective cohort study included 11,014 diabetes-free individuals ≥ 20 years old from the Tohoku Medical Megabank Community-based cohort study. Lifestyle scores, including the body mass index, smoking, physical activity, and gamma-glutamyl transferase (marker of alcohol consumption), were assigned, and participants were categorized into ideal, intermediate, and poor lifestyles. A polygenic risk score (PRS) was constructed based on the type 2 diabetes loci from the BioBank Japan study. A multiple logistic regression model was used to estimate the association between genetic risk, healthy lifestyle, and diabetes incidence and to calculate the area under the receiver operating characteristic curve (AUROC). RESULT: Of the 11,014 adults included (67.8% women; mean age [standard deviation], 59.1 [11.3] years old), 297 (2.7%) developed diabetes during a mean 4.3 (0.8) years of follow-up. Genetic and lifestyle score is independently associated with the development of diabetes. Compared with the low genetic risk and ideal lifestyle groups, the odds ratio was 3.31 for the low genetic risk and poor lifestyle group. When the PRS was integrated into a model including the lifestyle and family history, the AUROC significantly improved to 0.719 (95% confidence interval [95% CI]: 0.692-0.747) compared to a model including only the lifestyle and family history (0.703 [95% CI, 0.674-0.732]). CONCLUSION: Our findings indicate that adherence to a healthy lifestyle is important for preventing diabetes, regardless of genetic risk. In addition, genetic risk might provide information beyond lifestyle and family history to stratify individuals at high risk of developing diabetes.
Association of physiological factors with grip and leg extension strength: tohoku medical megabank community-based cohort study. International-journal

Yoshiaki Noji, Rieko Hatanaka, Naoki Nakaya, Mana Kogure, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Tomohiro Nakamura, Naho Tsuchiya, Haruki Momma, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Ryoichi Nagatomi, Nobuo Fuse, Shinichi Kuriyama, Atsushi Hozawa

BMC public health　24　(1)　714-714　2024/03/05

DOI： 10.1186/s12889-024-18244-z 　

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BACKGROUND: Upper and lower extremity muscle strength can be used to predict health outcomes. However, the difference between the relation of upper extremity muscle and of lower extremity muscle with physiological factors is unclear. This study aimed to evaluate the association between physiological data and muscle strength, measured using grip and leg extension strength, among Japanese adults. METHODS: We conducted a cross-sectional study of 2,861 men and 6,717 women aged ≥ 20 years living in Miyagi Prefecture, Japan. Grip strength was measured using a dynamometer. Leg extension strength was measured using a hydraulic isokinetic leg press machine. Anthropometry and physiological data, including blood pressure, calcaneal ultrasound bone status, pulmonary function, carotid echography, and blood information, were assessed. We used a general linear model adjusted for age, body composition, and smoking status to evaluate the association between muscle strength and physiological factors. RESULTS: Grip and leg extension strength were positively associated with bone area ratio, vital capacity, forced vital capacity, forced expiratory volume in one second, and estimated glomerular filtration rate, and negatively associated with waist circumference and percentage body fat mass in both the sexes. Diastolic blood pressure was positively associated with grip strength in both the sexes and leg extension strength in men, but not women. High-density lipoprotein cholesterol and red blood cell counts were positively associated with grip and leg extension strength in women, but not men. In both the sexes, pulse rate, total cholesterol, and uric acid were consistently associated with only leg extension strength, but not grip strength. In women, glycated hemoglobin demonstrated negative and positive associations with grip and leg extension strength, respectively. CONCLUSIONS: Grip and leg extension strength demonstrated similar associations with anthropometry, pulmonary function, and estimated glomerular filtration rate, but the associations with the other factors were not always consistent.
The Association of Urinary Sodium-to-Potassium Ratio and Estimated Urinary Sodium Excretion with Atrial Fibrillation among Participants without Hypertension(タイトル和訳中)

時岡紗由理, 中谷直樹, 畑中里衣子, 中谷久美, 千葉一平, 小暮真奈, 後岡広太郎, 大類真嗣, 宇留野晃, 小林朋子, 児玉栄一, 濱中洋平, 布施昇男, 寳澤篤

日本循環器学会学術集会抄録集　88回　PJ005-4　2024/03
Publisher: (一社)日本循環器学会
Relationship between traditional risk factors for hypertension and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study. International-journal

Masato Takase, Naoki Nakaya, Kozo Tanno, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Tomohiro Nakamura, Takumi Hirata, Taku Obara, Mami Ishikuro, Yuka Kotozaki, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Hideki Ohmomo, Nobuo Fuse, Junichi Sugawara, Atsushi Shimizu, Yoko Izumi, Shinichi Kuriyama, Atsushi Hozawa

Hypertension research : official journal of the Japanese Society of Hypertension　2024/02/29

DOI： 10.1038/s41440-024-01582-1 　

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Risk factors for hypertension have been emphasized in the Japanese Society of Hypertension Guidelines for the Management of Hypertension. However, large-scale studies on the association of smoking, potassium excretion, and gamma-glutamyl transferase level with BP in the Japanese population are limited. We conducted a cross-sectional study to examine the association between hypertension risk factors and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study (23,446 men and 38,921 women aged ≥20 years). A model adjusted for age, body mass index, smoking status, drinking status, estimated daily salt intake, potassium excretion, (or urinary sodium-to-potassium ratio), gamma-glutamyl transferase, physical activity, education level, status of damage to homes during the Great East Japan Earthquake, and residential areas was used. The average age and systolic blood pressure were 62.5 (10.3) years for men and 59.6 (11.3) years for women, 128.9 (16.7) mmHg for men and 124.7 (17.5) mmHg for women, respectively. Body mass index estimated daily salt intake, urinary sodium-to-potassium ratio and gamma-glutamyl transferase levels were positively associated with systolic blood pressure. Compared with never-drinkers, current drinkers who consumed 23-45 g/day and ≥46.0 g/day had significantly increased systolic blood pressure. Conversely, current smokers (1-10 cigarettes/day and 11-20 cigarettes/day) were inversely associated with systolic blood pressure compared to never-smokers. Overall, systolic blood pressure was associated with gamma-glutamyl transferase and hypertension risk factors, including body mass index, alcohol consumption, estimated daily salt intake, urinary sodium-to-potassium ratio, and potassium excretion. Our findings support the notion that lifestyle modifications should be attempted to prevent hypertension.
Progress report of the Tohoku Medical Megabank Community-Based Cohort Study: Study profile of the repeated center-based survey during second period in Miyagi Prefecture.

Atsushi Hozawa, Kumi Nakaya, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Ikumi Kanno, Junichi Sugawara, Eiichi Kodama, Yohei Hamanaka, Tomoko Kobayashi, Akira Uruno, Naho Tsuchiya, Takumi Hirata, Akira Narita, Akito Tsuboi, Toru Tamahara, Akihito Otsuki, Maki Goto, Makiko Taira, Ritsuko Shimizu, Kichiya Suzuki, Taku Obara, Masahiro Kikuya, Hirohito Metoki, Mami Ishikuro, Inaho Danjoh, Soichi Ogishima, Satoshi Nagaie, Naoko Minegishi, Masahiro Hiratsuka, Kazuki Kumada, Ichiko Nishijima, Takahiro Nobukuni, Yumi Yamaguchi-Kabata, Fuji Nagami, Shigeo Kure, Nobuo Fuse, Kengo Kinoshita, Yoko Izumi, Shinichi Kuriyama, Masayuki Yamamoto

Journal of epidemiology　2024/02/24

DOI： 10.2188/jea.JE20230241 　

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BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.
Helical peptides with disordered regions for measles viruses provide new generalized insights into fusion inhibitors. International-journal

Kazushige Hirata, Aoi Takahara, Satoshi Suzuki, Shumei Murakami, Kumi Kawaji, Akie Nishiyama, Mina Sasano, Mariko Shoji-Ueno, Emiko Usui, Kazutaka Murayama, Hironori Hayashi, Shinya Oishi, Eiichi N Kodama

iScience　27　(2)　108961-108961　2024/02/16

DOI： 10.1016/j.isci.2024.108961 　

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Despite effective vaccines, measles virus (MeV) outbreaks occur sporadically. Therefore, developing anti-MeV agents remains important for suppressing MeV infections. We previously designed peptide-based MeV fusion inhibitors, M1 and M2, that target MeV class I fusion protein (F protein). Here, we developed a novel fusion inhibitor, MEK35, that exerts potent activity against M1/M2-resistant MeV variants. Comparing MEK35 to M1 derivatives revealed that combining disordered and helical elements was essential for overcoming M1/M2 resistance. Moreover, we propose a three-step antiviral process for peptide-based fusion inhibitors: (i) disordered peptides interact with F protein; (ii) the peptides adopt a partial helical conformation and bind to F protein through hydrophobic interactions; and (iii) subsequent interactions involving the disordered region of the peptides afford a peptide-F protein with a high-affinity peptide-F protein interaction. An M1-resistant substitution blocks the second step. These results should aid the development of novel viral fusion inhibitors targeting class I F protein.
Relationships of Fat Mass Index and Fat-Free Mass Index with Low-Density Lipoprotein Cholesterol Levels in the Tohoku Medical Megabank Community-Based Cohort Study.

Masato Takase, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Taku Obara, Mami Ishikuro, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Yoko Izumi, Shinichi Kuriyama, Atsushi Hozawa

Journal of atherosclerosis and thrombosis　2024/02/06

DOI： 10.5551/jat.64535 　

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AIMS: Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the f at mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. RESULTS: Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. CONCLUSIONS: Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.
Improving diagnostic accuracy of blood culture-positive cases in a cancer center via an antimicrobial stewardship program and infectious disease consultations. International-journal

Naoya Itoh, Nana Akazawa, Takanori Kawabata, Makoto Yamaguchi, Eiichi N Kodama, Norio Ohmagari

Scientific reports　14　(1)　2869-2869　2024/02/04

DOI： 10.1038/s41598-024-53543-w 　

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The direct impact of antimicrobial stewardship programs (ASP) and infectious disease (ID) consultations on patients' clinical diagnoses remains unknown. We assessed their influence on improving the diagnostic accuracy of blood culture-positive inpatients at a Japanese cancer center. Our single-center, retrospective observational study was conducted from April 1, 2018 to March 31, 2022 to evaluate two phases: pre-intervention (notification of antimicrobials by the infection control team) and post-intervention (ASP implementation and ID consultation service establishment). There were 42,514 inpatients: 22,096 during the pre-intervention and 20,418 during the intervention periods. A total of 939 blood culture-positive episodes (pre-intervention, n = 434; post-intervention, n = 505) were analyzed. During the pre-intervention period, 28.1% of the patients had an unknown diagnosis, which decreased significantly to 1.2% post-intervention. Furthermore, hepatobiliary tract and other infections increased significantly post-intervention, and the mortality rate due to Staphylococcus aureus infection decreased from 28.6% pre-intervention to 10.4% post-intervention. The trend and level of the total number of culture specimens submitted per 1000 patient days for all culture specimens increased significantly post-intervention. Notably, the two-set rate of monthly blood cultures increased significantly. In conclusion, improving the overall diagnostic process with ASP and ID consultations at cancer centers could lead to the optimization of patient care.
尿中ナトリウム/カリウム比と心房細動の関連の検討

時岡紗由理, 中谷直樹, 畑中里衣子, 千葉一平, 中谷久美, 小暮真奈, 大類正嗣, 宇留野晃, 小林朋子, 児玉栄一, 濱中洋平, 布施昇男, 寳澤篤

Journal of Epidemiology　34　(Suppl.)　122-122　2024/01
Publisher: (一社)日本疫学会
ISSN： 0917-5040

eISSN： 1349-9092
Synthesis and Cytotoxicity of Cyclic Octapeptide Surugamides with Varied N-Acyl Moieties.

Kenichi Matsuda, Shinya Niikura, Rintaro Ichihara, Kei Fujita, Anna M Strasser, Rokusuke Yoshikawa, Jiro Yasuda, Yoshiki Hiramatsu, Hironori Hayashi, Eiichi N Kodama, Toshiyuki Wakimoto

Chemical & pharmaceutical bulletin　72　(9)　826-830　2024

DOI： 10.1248/cpb.c24-00533 　

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Surugamides are a group of non-ribosomal peptides produced by Streptomyces spp. Several derivatives possess acyl groups, which are proposed to be attached to a lysine side chain after backbone-macrocyclization during biosynthesis. To date, five different acyl groups have been identified in nature, yet their impacts on biological activity remain underexplored. Here we synthesized surugamide B derivatives with varied acyl moieties. Biological evaluations revealed that larger hydrophobic acyl groups on lysine ε-NH2 enhance cytotoxicity.
Real-world effectiveness of full and booster mRNA vaccination for coronavirus disease 2019 against disease severity during the delta- and omicron-dominant phases: A propensity score-matched cohort study using the nationwide registry data in Japan. International-journal

Tetsuya Suzuki, Yusuke Asai, Shinya Tsuzuki, Hidetoshi Nomoto, Nobuaki Matsunaga, Eiichi N Kodama, Kayoko Hayakawa, Norio Ohmagari

Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi　2023/12/10

DOI： 10.1016/j.jmii.2023.12.002 　

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BACKGROUND: To date, few studies from the Asian region have reported the effectiveness of messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccines against disease progression and death after hospitalization. METHODS: We evaluated the data from the COVID-19 registry in Japan during the delta- and omicron-dominant phases. A propensity score-matched cohort study was conducted between the incompletely (0-1 dose) and fully (2 doses) vaccinated groups during the delta-dominant phase and among the incompletely, fully, and booster (3 doses) vaccinated groups during the omicron-dominant phase. RESULTS: In the delta-dominant phase, 411 pairs were matched. The fully vaccinated group showed a significantly lower oxygen supplementation rate (24.1 % vs. 41.1 %, p < 0.001) but little difference in the mortality rate (2.2 % vs. 2.9 %, p = 0.66). In the omicron-dominant phase, 1494 pairs from the incompletely and fully vaccinated groups, and 425 pairs from the fully and booster vaccinated groups were matched. Full vaccination reduced both the oxygen supplementation rate (18.6 % vs 25.7 %, p < 0.001) and mortality rate (0.7 % vs 2.3 %, p < 0.001). Booster vaccination showed little difference in either the rate of oxygen supplementation (21.2 % vs. 24.7 %, p = 0.25) or mortality (1.2 % vs. 2.6 %, p = 0.21) compared with full vaccination. CONCLUSIONS: Full vaccination reduced disease severity during the delta- and omicron-dominant phases; booster vaccination did not further enhance the protective effects against disease progression during the omicron-dominant phase compared to full vaccination. Future vaccine strategies and policy decisions should consider preventing infection or disease progression in the target population, as well as the characteristics of the dominant variant in that phase.
The association between depressive symptoms and masked hypertension in participants with normotension measured at research center. International-journal

Sayuri Tokioka, Naoki Nakaya, Kumi Nakaya, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Hirohito Metoki, Takahisa Murakami, Michihiro Satoh, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Yohei Hamanaka, Masatsugu Orui, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Satoshi Nagaie, Soichi Ogishima, Yoko Izumi, Nobuo Fuse, Shinichi Kuriyama, Atsushi Hozawa

Hypertension research : official journal of the Japanese Society of Hypertension　2023/10/31

DOI： 10.1038/s41440-023-01484-8 　

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Masked hypertension is a risk factor for cardiovascular diseases. However, masked hypertension is sometimes overlooked owing to the requirement for home blood pressure measurements for diagnosing. Mental status influences blood pressure. To reduce undiagnosed masked hypertension, this study assessed the association between depressive symptoms and masked hypertension. This cross-sectional study used data from the Tohoku Medical Megabank Project Community-Based Cohort Study (conducted in Miyagi Prefecture, Japan, from 2013) and included participants with normotension measured at the research center (systolic blood pressure<140 mmHg and diastolic blood pressure <90 mmHg). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (Japanese version). Masked hypertension was defined as normotension measured at the research center and home hypertension (home systolic blood pressure ≥135 mmHg or home diastolic blood pressure ≥85 mmHg). The study comprised 6705 participants (mean age: 55.7 ± 13.7 years). Of these participants, 1106 (22.1%) without depressive symptoms and 393 (23.2%) with depressive symptoms were categorized to have masked hypertension. Sex-specific and age-adjusted least mean squares for home blood pressure, not for research blood pressure were significantly higher in the group with depressive symptoms in both sex categories. The multivariate odds ratio for masked hypertension in the patients with depressive symptoms was 1.72 (95% confidence interval: 1.26-2.34) in male participants and 1.30 (95% confidence interval: 1.06-1.59) in female ones. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at the research center. Depressive symptoms may be one of the risk factors for masked hypertension. Depressive symptoms were associated with masked hypertension in individuals with normotension measured at research center.
The risk of withdrawal from hypertension treatment in coastal areas after the Great East Japan Earthquake: the TMM CommCohort Study. International-journal

Rieko Hatanaka, Naoki Nakaya, Mana Kogure, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Hideaki Hashimoto, Tomohiro Nakamura, Kotaro Nochioka, Taku Obara, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Akira Uruno, Eiichi N Kodama, Nobuo Fuse, Shinichi Kuriyama, Atsushi Hozawa

Hypertension research : official journal of the Japanese Society of Hypertension　2023/10/13
Publisher: Springer Science and Business Media LLC
DOI： 10.1038/s41440-023-01454-0 　

ISSN： 0916-9636

eISSN： 1348-4214

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Abstract This study aimed to examine whether risk of withdrawal from HTTx was higher in coastal areas that were severely damaged by tsunami than in inland areas. We conducted a cross-sectional study of 9218 participants aged ≥20 years in Miyagi, Japan. The odds ratios (ORs) and confidence interval (CI) for withdrawal from HTTx in coastal and inland groups were compared using multivariate logistic regression analysis, adjusting for potential confounders. In total, 194 of 5860 and 146 of 3358 participants in the inland and coastal groups, respectively, withdrew from HTTx treatment. OR (95%CI) of withdrawal from HTTx in the coastal group was 1.46 (1.14–1.86) compared to the inland group. According to housing damage, ORs (95% CI) in the no damage, partially destroyed, and more than half destroyed coastal groups compared with the no damage inland group were 1.62 (1.04–2.50), 1.69 (1.17–2.45), and 1.08 (0.71–1.65), respectively. In conclusion, the risk of HTTx withdrawal for participants whose homes in coastal areas were relatively less damaged was significantly higher compared with those in inland areas, while the risk of HTTx withdrawal for participants whose homes were more than half destroyed was not. Post-disaster administrative support for disaster victims is considered vital for continuation of their treatment.
Influence of Diabetes Family History on the Associations of Combined Genetic and Lifestyle Risks with Diabetes in the Tohoku Medical Megabank Community-Based Cohort Study.

Masato Takase, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Akira Narita, Taku Obara, Mami Ishikuro, Akira Uruno, Tomoko Kobayashi, Eiichi N Kodama, Yohei Hamanaka, Masatsugu Orui, Soichi Ogishima, Satoshi Nagaie, Nobuo Fuse, Junichi Sugawara, Shinichi Kuriyama, Ichiro Tsuji, Gen Tamiya, Atsushi Hozawa, Masayuki Yamamoto

Journal of atherosclerosis and thrombosis　2023/10/06

DOI： 10.5551/jat.64425 　

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AIM: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. METHODS: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. RESULTS: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. CONCLUSIONS: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.
Association of Central Blood Pressure and Carotid Intima Media Thickness with New-Onset Hypertension in People with High Normal Blood Pressure.

Sayuri Tokioka, Naoki Nakaya, Kumi Nakaya, Masato Takase, Mana Kogure, Rieko Hatanaka, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Hirohito Metoki, Takahisa Murakami, Michihiro Satoh, Tomohiro Nakamura, Taku Obara, Yohei Hamanaka, Tomoko Kobayashi, Akira Uruno, Junichi Sugawara, Eiichi N Kodama, Soichi Ogishima, Yoko Izumi, Nobuo Fuse, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

Journal of atherosclerosis and thrombosis　2023/07/05

DOI： 10.5551/jat.64151 　

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AIM: People with high normal blood pressure (BP) have a higher risk of cardiovascular events than those with normal BP; therefore, progression to hypertension (HT) should be prevented. We aimed to assess the HT risk using central BP and carotid intima media thickness (CIMT) in people with high normal BP. METHODS: This prospective cohort study used the Tohoku Medical Megabank Community-Based Project Cohort Study (conducted from 2013 in Miyagi Prefecture in Japan). The participants had a high normal BP, defined as a systolic BP of 120-139 mmHg and diastolic BP ＜90 mmHg using brachial BP measurement during the baseline survey. The outcome was new-onset HT during the secondary survey, conducted four years after the baseline survey. RESULTS: Overall, 4,021 participants with high normal BP during the baseline survey, with an average age of 58.7 years, were included; 1,030 (26%) were diagnosed with new-onset HT during the secondary survey, 3.5± 0.7 years after the baseline survey. The multivariable odds ratio (95% confidence interval) for HT in the highest versus lowest quartile of central BP was 1.7 (1.2-2.4, p=0.0030), and that of CIMT was 1.8 (1.4-2.4, p＜0.001). Subgroup analysis according to age (＜60 and ≥ 60 years) and sex revealed that the central BP was influential in groups with younger age and female individuals; CIMT was influential in all groups. CONCLUSIONS: Higher central BP and thicker CIMT at the baseline were correlated with new-onset HT in individuals with high normal BP, independent of brachial systolic BP and other cardiovascular risk factors.
Rapid Detection of SARS-CoV-2 RNA Using Reverse Transcription Recombinase Polymerase Amplification (RT-RPA) with Lateral Flow for N-Protein Gene and Variant-Specific Deletion-Insertion Mutation in S-Protein Gene. International-journal

Jose L Malaga, Monica J Pajuelo, Michiko Okamoto, Emmanuel Kagning Tsinda, Kanako Otani, Pablo Tsukayama, Lucero Mascaro, Diego Cuicapuza, Masamichi Katsumi, Kazuhisa Kawamura, Hidekazu Nishimura, Akie Sakagami, Yo Ueki, Suguru Omiya, Satoshi Okamoto, Asami Nakayama, Shin-Ichi Fujimaki, Chuyao Yu, Sikandar Azam, Eiichi Kodama, Clyde Dapat, Hitoshi Oshitani, Mayuko Saito

Viruses　15　(6)　2023/05/26

DOI： 10.3390/v15061254 　

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Rapid molecular testing for severe acute respiratory coronavirus 2 (SARS-CoV-2) variants may contribute to the development of public health measures, particularly in resource-limited areas. Reverse transcription recombinase polymerase amplification using a lateral flow assay (RT-RPA-LF) allows rapid RNA detection without thermal cyclers. In this study, we developed two assays to detect SARS-CoV-2 nucleocapsid (N) gene and Omicron BA.1 spike (S) gene-specific deletion-insertion mutations (del211/ins214). Both tests had a detection limit of 10 copies/µL in vitro and the detection time was approximately 35 min from incubation to detection. The sensitivities of SARS-CoV-2 (N) RT-RPA-LF by viral load categories were 100% for clinical samples with high (>9015.7 copies/µL, cycle quantification (Cq): < 25) and moderate (385.5-9015.7 copies/µL, Cq: 25-29.9) viral load, 83.3% for low (16.5-385.5 copies/µL, Cq: 30-34.9), and 14.3% for very low (<16.5 copies/µL, Cq: 35-40). The sensitivities of the Omicron BA.1 (S) RT-RPA-LF were 94.9%, 78%, 23.8%, and 0%, respectively, and the specificity against non-BA.1 SARS-CoV-2-positive samples was 96%. The assays seemed more sensitive than rapid antigen detection in moderate viral load samples. Although implementation in resource-limited settings requires additional improvements, deletion-insertion mutations were successfully detected by the RT-RPA-LF technique.
Mental Health Problems among University Students under the Prolonged COVID-19 Pandemic in Japan: A Repeated Cross-Sectional Survey.

Moe Seto, Hitomi Usukura, Yasuto Kunii, Yumiko Hamaie, Eiichi N Kodama, Yuko Makino, Yoshitaka Kinouchi, Chihiro Ito, Tadayoshi Ikeda, Hiroaki Tomita

The Tohoku journal of experimental medicine　260　(1)　1-11　2023/05/01

DOI： 10.1620/tjem.2023.J012 　

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Numerous studies have investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health among university students within a year of its onset, but few have examined the impact of a prolonged pandemic on university life. This study aimed to evaluate the impact of the COVID-19 pandemic on the mental health of students in a large university community. Online questionnaire surveys were conducted on students from March 24 to April 14 (first survey, n = 3,357) and December 2-23, 2021 (second survey, n = 2,604). The questionnaires included items on demographic data, living conditions, and mental health status as measured using the Patient Health Questionnaire-9 for depressive symptoms and the Generalized Anxiety Disorder-7 scale for anxiety symptoms. The results showed that, compared with undergraduate students, graduate students, except those in Medicine, Dentistry, and Pharmaceutical Science courses, had more anxiety symptoms. Furthermore, among undergraduate students, depressive and anxiety symptoms were significantly higher in fourth- than in first-year students. Logistic regression analyses of data from both surveys revealed the seven risk factors associated with depressive or anxiety symptoms that affected the mental health of university students throughout the COVID-19 pandemic: 1) female or nonbinary gender, 2) graduate student, 3) quarantine experience due to COVID-19, 4) isolation from friends and acquaintances, 5) disorganized pattern of daily life, 6) worse financial situation, and 7) no availability of consultations regarding health, life, and finances. These findings suggest that mental health measures for university students need to be designed specific to each course.
Combined fat mass and fat-free mass indices and lung function among Japanese population: The Tohoku Medical Megabank Community-based Cohort Study.

Masato Takase, Mitsuhiro Yamada, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

Journal of epidemiology　2023/04/08

DOI： 10.2188/jea.JE20220355 　

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BACKGROUND: Although fat mass index (FMI) and fat-free mass index (FFMI) affect lung function, FMI and FFMI are not independent of each other since FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. We aimed to examine the association of combined FMI and FFMI with lung function. METHODS: In this cross-sectional study, lung function was evaluated using forced expiratory volume at 1 s and forced vital capacity was measured using spirometry. Both FMI and FFMI were classified into sex-specific quartiles (16 groups). Analysis of covariance was used to assess the associations of combined FMI and FFMI with lung function. The trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1-4 (lowest-highest), and entering the number as a continuous term in the regression model. RESULTS: This study included 3,736 men and 8,821 women aged ≥20 years living in Miyagi Prefecture, Japan. The mean FEV1 (standard deviation) was 3.0 (0.7) L for men and 2.3 (0.5) L for women. The mean FVC was 3.8 (0.7) L for men and 2.8 (0.5) L for women. The FMI was inversely associated with lung function among all FFMI subgroups in both sexes. Conversely, FFMI was positively associated with lung function in all FMI subgroups in both sexes. CONCLUSIONS: Higher FMI was associated with lower lung function independent of FFMI; higher FFMI was associated with higher lung function independent of FMI. Reducing FMI and maintaining FFMI might be important for respiratory health.
Association between lung function and hypertension and home hypertension in a Japanese population: the Tohoku Medical Megabank Community-Based Cohort Study. International-journal

Masato Takase, Mitsuhiro Yamada, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

Journal of hypertension　41　(3)　443-452　2023/03/01

DOI： 10.1097/HJH.0000000000003356 　

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BACKGROUND: Although several studies have shown an inverse association between lung function and hypertension, few studies have examined the association between lung function and hypertension among never-smokers, and no study has investigated the association between lung function and home hypertension. We investigated the associations between lung function and hypertension in a Japanese population. INDIVIDUALS AND METHODS: We conducted a cross-sectional study of 3728 men and 8795 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was assessed using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC), measured by spirometry. Hypertension was defined as a casual blood pressure at least 140/90 mmHg and/or self-reported treatment for hypertension. Home hypertension was defined as morning home blood pressure at least 135/85 mmHg and/or self-reported treatment for hypertension. Multivariate logistic regression models adjusted for potential confounders were used to assess the association between lung function and hypertension. RESULTS: The mean ages (±SD) of men and women were 60.1 (±14.0) years and 56.2 (±13.4) years, respectively, and 1994 (53.5%) men and 2992 (34.0%) women had hypertension. In the multivariable models, FEV1 and FVC were inversely associated with hypertension. Inverse associations between lung function and hypertension were observed even among never-smokers. Furthermore, reduced lung function was associated with higher prevalence of home hypertension in men and women. CONCLUSION: Reduced lung function was associated with higher prevalence of hypertension, independent of smoking status. Assessment of the lung function or blood pressure may be required in individuals with reduced lung function or hypertension.
Nasopharyngeal SARS-CoV-2 may not be dispersed by a high-flow nasal cannula. International-journal

Tetsuya Suzuki, Shinichiro Morioka, Kei Yamamoto, Sho Saito, Shun Iida, Katsuji Teruya, Jin Takasaki, Masayuki Hojo, Kayoko Hayakawa, Satoshi Kutsuna, Sho Miyamoto, Seiya Ozono, Tadaki Suzuki, Eiichi N Kodama, Norio Ohmagari

Scientific reports　13　(1)　2669-2669　2023/02/15

DOI： 10.1038/s41598-023-29740-4 　

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A high-flow nasal cannula (HFNC) therapy plays a significant role in providing respiratory support to critically ill patients with coronavirus disease 2019 (COVID-19); however, the dispersion of the virus owing to aerosol generation is a matter of concern. This study aimed to evaluate if HFNC disperses the virus into the air. Among patients with COVID-19 admitted to private rooms with controlled negative pressure, we enrolled those admitted within 10 days of onset and requiring oxygenation through a conventional nasal cannula or HFNC therapy. Of the 17 patients enrolled, we obtained 22 samples (11 in the conventional nasal cannula group and 11 in the HFNC group). Viral RNA was detected in 20 nasopharyngeal swabs, and viable viruses were isolated from three nasopharyngeal swabs. Neither viral RNA nor viable virus was detected in the air sample at 0.5 m regardless of the oxygen-supplementation device. We detected viral RNA in two samples in the conventional nasal cannula group but not in the HFNC therapy group in gelatin filters located 3 m from the patient and the surface of the ventilation. This study directly demonstrated that despite viral RNA detection in the nasopharynx, viruses may not be dispersed by HFNC therapy. This warrants further research to determine if similar results can be obtained under different conditions.
Carotid Intima Media Thickness and Risk Factor for Atherosclerosis: Tohoku Medical Megabank Community-Based Cohort Study.

Masato Takase, Naoki Nakaya, Tomohiro Nakamura, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ippei Chiba, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

Journal of atherosclerosis and thrombosis　2023/02/11

DOI： 10.5551/jat.64039 　

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AIM: We examined the association between the carotid intima medica thickness (cIMT) and risk factors for atherosclerosis based on the Japan Atherosclerosis Society 2022 Atherosclerosis Prevention Guideline. METHODS: Using data from the Tohoku Medical Megabank Community-based Cohort Study, we performed a cross-sectional study that enrolled 13,366 participants (age ≥ 20 years) with an analysis of covariance to assess associations between cIMT and risk factors for atherosclerosis. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. Analysis was conducted in the model adjusted for age, sex, smoking status, drinking status, body mass index (BMI), systolic blood pressure (SBP), glycated hemoglobin (HbA1c), high-density lipoprotein-cholesterol (HDL-C), non-high-density lipoprotein-cholesterol (non-HDL-C), and height. RESULTS: In this study cohort, the average age and cIMT were 57.3 (13.8) years and 0.61 (0.13) mm, respectively, which included 3,988 males (29.8%). Males had a higher cIMT than did the females. Age, height, BMI, SBP, HbA1c, and non-HDL-C were positively associated with cIMT. HDL-C was inversely associated with cIMT. Compared with never drinkers, current drinkers (≥ 46.0 g/day) had a significantly decreased cIMT. CONCLUSIONS: The cIMT was associated with atherosclerosis risk factors including age, sex, BMI, SBP, HbA1c, non-HDL-C, and HDL-C, and adequate control of risks in high-risk individuals might be required to prevent atherosclerotic cardiovascular diseases.
タンパク質間相互作用を標的とするRSウイルスの新薬更補創出

鈴木聡志, 天野陽斗, 薄井友輔, 河治久実, 笹野美奈, 西山瑛絵, 平松佳樹, 橋本浩一, 村山和隆, 児玉栄一, 大石真也, 林宏典

日本小児科学会雑誌　127　(2)　231-231　2023/02
Publisher: (公社)日本小児科学会
ISSN： 0001-6543
新型コロナウイルスへの創薬に応用できるタンパク質間相互作用

鈴木聡志, 黒田実央, 河治久実, 村山和隆, 林宏典, 大石真也, 児玉栄一

日本小児科学会雑誌　127　(2)　235-235　2023/02
Publisher: (公社)日本小児科学会
ISSN： 0001-6543
Report of Research on the Actual Situation in Psychiatric Wards in Large-Scale Earthquake Disasters and Countermeasures for Infectious Diseases in Times of Disaster

3　(36)　37-45　2023/02

ISSN： 2436-1437
Design and Progress of Child Health Assessments at Community Support Centers in the Birth and Three-Generation Cohort Study of the Tohoku Medical Megabank Project.

Tomoko Kobayashi, Mika Kobayashi, Naoko Minegishi, Masahiro Kikuya, Taku Obara, Mami Ishikuro, Chizuru Yamanaka, Tomomi Onuma, Keiko Murakami, Fumihiko Ueno, Aoi Noda, Akira Uruno, Junichi Sugawara, Kichiya Suzuki, Eiichi N Kodama, Yohei Hamanaka, Naho Tsuchiya, Mana Kogure, Naoki Nakaya, Makiko Taira, Mika Sakurai-Yageta, Toru Tamahara, Junko Kawashima, Maki Goto, Akihito Otsuki, Ritsuko Shimizu, Soichi Ogishima, Hiroaki Hashizume, Fuji Nagami, Tomohiro Nakamura, Atsushi Hozawa, Tadao Kobayashi, Nobuo Fuse, Shinichi Kuriyama, Shigeo Kure, Masayuki Yamamoto

The Tohoku journal of experimental medicine　259　(2)　93-105　2023/01/20

DOI： 10.1620/tjem.2022.J103 　

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The Tohoku Medical Megabank Project (TMM) has been conducting a birth and three-generation cohort study (the BirThree Cohort Study). We recruited 73,529 pregnant women and their family members for this cohort study, which included 23,143 newborns and 9,459 of their siblings. We designed and are in the process of conducting three-step health assessments for each newborn at approximately ages of 5, 10 and 16. These health assessments are administered at seven community support centers. Trained genome medical research coordinators conduct physical examinations of and collect biological specimens from each participant. The Sendai Children's Health Square has been established as the headquarters for these child health assessments and is utilized to accumulate knowledge that can facilitate the proper practice of child health assessments. We designed all the relevant health assessments facilities to allow parents and their children to participate in the health assessments concomitantly. Our centers serve as places where child participants and their parents can feel at ease as a result of the implementation of safety measures and child hospitality measures. The TMM BirThree Cohort Study is in the process of conducting strategically detailed health assessments and genome analysis, which can facilitate studies concerning the gene-environment interactions relevant to noncommunicable diseases. Through these operations, our study allows for a significant depth of data to be collected in terms of the number of biospecimens under study and the comprehensiveness of both basic and clinical data alongside relevant family information.
Helix-based screening with structure prediction using artificial intelligence has potential for the rapid development of peptide inhibitors targeting class I viral fusion

Satoshi Suzuki, Mio Kuroda, Keisuke Aoki, Kumi Kawaji, Yoshiki Hiramatsu, Mina Sasano, Akie Nishiyama, Kazutaka Murayama, Eiichi N. Kodama, Shinya Oishi, Hironori Hayashi

RSC Chemical Biology　2023
Publisher: Royal Society of Chemistry (RSC)
DOI： 10.1039/d3cb00166k 　

eISSN： 2633-0679

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Peptide inhibitors against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are designed using a screening system for peptide-based inhibitors containing an α-helix region (SPICA) and structures predicted by AlphaFold2.
Investigation of oral macrolide prescriptions in Japan using a retrospective claims database, 2013-2018. International-journal

Satoshi Ide, Masahiro Ishikane, Kensuke Aoyagi, Akane Ono, Yusuke Asai, Shinya Tsuzuki, Yoshiki Kusama, Yoshiaki Gu, Eiichi Kodama, Norio Ohmagari

PloS one　18　(6)　e0287297　2023

DOI： 10.1371/journal.pone.0287297 　

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Macrolide usage in Japan exceeds that in Europe and the United States. Investigating the actual conditions in which macrolides are used is important for identifying further interventions for appropriate antimicrobial use; however, this situation has not been evaluated in Japan. Therefore, we aimed to clarify the number of macrolide prescriptions and their changes before and after implementation of the Antimicrobial Resistance (AMR) Action Plan. In addition, we also investigated the names of diseases for which macrolides have been prescribed and the number of days of prescription. A retrospective observational study was conducted using JMDC claims data from January 2013 to December 2018. The proportion of all oral antimicrobials and macrolides used during this period and the diseases for which macrolides were used in the 3 years before and after the AMR Action Plan were determined separately for acute (< 14 prescription days) and chronic (> 14 prescription days) diseases. The number of prescriptions for macrolides constituted approximately 30% of those for all oral antimicrobials; of these, clarithromycin accounted for approximately 60%. Most prescriptions for acute diseases were for common cold, whereas allergic and dermatological diseases were included among chronic diseases. The names of these illnesses did not change before and after the AMR Action Plan. Overall, these results indicate that appropriate macrolide use involves a review of their use for common cold along with appropriate evaluation of their long-term use for skin and allergic diseases. They also indicate the need for further fact-finding studies and ongoing AMR measures.
Reduction strategies for inpatient oral third-generation cephalosporins at a cancer center: An interrupted time-series analysis. International-journal

Naoya Itoh, Takanori Kawabata, Nana Akazawa, Daichi Kawamura, Hiromi Murakami, Yuichi Ishibana, Eiichi N Kodama, Norio Ohmagari

PloS one　18　(2)　e0281518　2023

DOI： 10.1371/journal.pone.0281518 　

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Oral third-generation cephalosporins (3GCs) are not recommended for use owing to their low bioavailability and the risk of emergence of resistant microorganisms with overuse. A standardized and effective method for reducing their use is lacking. Here, in a 60-month, single-institution, interrupted time-series analysis, which was retrospectively conducted between April 1, 2017, and March 31, 2022, we evaluated the effectiveness of a four-phase intervention to reduce the use of 3GCs in patients at a cancer center: Phase 1 (pre-intervention), Phase 2 (review of clinical pathways), Phase 3 (establishment of infectious disease consultation service and implementation of antimicrobial stewardship program), and Phase 4 (educational lecture and pop-up displays for oral antimicrobials at the time of ordering). Although no significant changes were observed in Phases 3 and 4, the first intervention resulted in a significant decrease in the trend and level of days of therapy (DOT) for 3GCs. The level for cephalexin DOT and the trend for sulfamethoxazole-trimethoprim DOT increased in Phase 4, and the trend for amoxicillin and amoxicillin-clavulanate DOT increased in Phase 3. Macrolide DOT showed a decreasing trend in Phases 2 and 4 and decreasing and increased levels in Phases 3 and 4, respectively; no change was observed for quinolones. Actual and adjusted purchase costs of 3GCs decreased significantly during all study periods, while those for oral antimicrobials decreased in Phase 2, and actual purchase costs increased in Phases 3 and 4. No significant reduction in resistant organisms, length of hospital stay, or mortality was observed. This is the first study on the effects of oral 3GC reduction strategies in patients with cancer. We conclude that even facilities that substantially use antimicrobials can efficiently reduce the use of 3GCs.
Lessons learned from an outbreak of COVID-19 in the head and neck surgery ward of a Japanese cancer center during the sixth wave by Omicron. International-journal

Naoya Itoh, Nana Akazawa, Masahiro Ishikane, Takanori Kawabata, Daichi Kawamura, Tomoyuki Chikusa, Eiichi N Kodama, Norio Ohmagari

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy　28　(12)　1610-1615　2022/12
Publisher: Elsevier BV
DOI： 10.1016/j.jiac.2022.08.010 　

ISSN： 1341-321X

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INTRODUCTION: We describe a coronavirus disease (COVID-19) outbreak in a cancer center's head and neck surgery ward and the interventions to halt ongoing exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers and patients with cancer. METHODS: Case definition included all healthcare workers and all patients associated to the ward from January 27 to January 31, 2022 with a positive SARS-COV-2 antigen test. This retrospective descriptive study was conducted between January 27, 2022, and February 14, 2022. RESULTS: From January 28, 2022, to February 9, 2022, 84 cases (36 healthcare workers, 48 patients) were screened, and 26 (12 healthcare workers, 14 patients) were identified as SARS-CoV-2-positive. The proportion of healthcare providers who performed aerosol generating procedures on positive patients was 91% for positive cases and 49% for non-cases. Room sharing with patients with COVID-19 was 64% for positive cases and 21% for non-cases (57% vs. 21% with positive tracheostomy patients; 43% vs. 9% with positive cases using a nebulizer; 50% vs. 15% with positive cases requiring sputum suctioning, respectively). Compliance with the universal masking policy for patients was 36% of positive cases and 79% of non-cases. CONCLUSIONS: This is the first report of a nosocomial outbreak of COVID-19 in a head and neck surgery ward during the Omicron pandemic. Notably, there were a high number of positive cases among healthcare workers who performed aerosol generating procedures for positive patients and patients who shared the room with a patient with COVID-19 with the potential to generate aerosols.
The Association of Lung Function and Carotid Intima-Media Thickness in a Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

Masato Takase, Mitsuhiro Yamada, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Tomoko Kobayashi, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Atsushi Hozawa

Journal of atherosclerosis and thrombosis　2022/11/04

DOI： 10.5551/jat.63826 　

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AIM: Impaired lung function is associated with atherosclerotic vascular events. Carotid intima-media thickness (cIMT) is a marker for subclinical atherosclerosis. However, few studies have examined the association between lung function and cIMT among never smokers or individuals stratified by age. We investigated the association between lung function and cIMT in the Japanese population. METHODS: We conducted a cross-sectional study of 3,716 men and 8,765 women aged 20 years or older living in Miyagi Prefecture, Japan. Lung function was evaluated using forced expiratory volume at 1 s (FEV1) and forced vital capacity (FVC) was measured using spirometry. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between lung function and cIMT and adjusted for potential confounders. A linear trend test was conducted by scoring the categories from 1 (lowest) to 4 (highest) and entering the score as a continuous term in the regression model. RESULTS: After adjusting for potential confounders including passive smoking, lower FEV1 and FVC were associated with higher cIMT in both men and women (P＜0.001 for linear trend). This association was confirmed even when we restricted our study to never smokers. Furthermore, even when we stratified by age, an inverse association between lung function and cIMT was confirmed in middle-aged (40-64 years) and elderly participants (65-74 years). CONCLUSIONS: Lower lung function was associated with higher cIMT in the Japanese population independent of age and smoking. Assessment of atherosclerosis or lung function may be required for individuals with lower lung function or atherosclerosis.
Impact of the COVID-19 pandemic on racial and ethnic minorities in Japan. International-journal

Hidetoshi Nomoto, Yusuke Asai, Kayoko Hayakawa, Nobuaki Matsunaga, Satoshi Kutsuna, Eiichi N Kodama, Norio Ohmagari

Epidemiology and infection　1-35　2022/10/26

DOI： 10.1017/S0950268822001674 　
Comparison of sputum specimens and nasopharyngeal swab specimens for diagnosis of acute human metapneumovirus-related lower respiratory tract infections in adults

Takehiro Yajima, Hiroshi Takahashi, Nozomu Kimura, Kosuke Sato, Daisuke Jingu, Satoshi Ubukata, Makoto Shoji, Hiroshi Watanabe, Eiichi N. Kodama, Hidekazu Nishimura

JOURNAL OF CLINICAL VIROLOGY　154　2022/09

DOI： 10.1016/j.jcv.2022.105238 　

ISSN： 1386-6532

eISSN： 1873-5967
Interferon lambda 3 in the early phase of coronavirus disease-19 can predict oxygen requirement. International-journal

Tetsuya Suzuki, Noriko Iwamoto, Shinya Tsuzuki, Yuko Kakumoto, Michiyo Suzuki, Shinobu Ashida, Yusuke Oshiro, Takeshi Nemoto, Kohei Kanda, Ayako Okuhama, Gen Yamada, Makoto Inada, Lubna Sato, Yusuke Miyazato, Yutaro Akiyama, Sho Saito, Shinichiro Morioka, Mugen Ujiie, Kayoko Hayakawa, Masaya Sugiyama, Masashi Mizokami, Eiichi N Kodama, Norio Ohmagari

European journal of clinical investigation　52　(9)　e13808　2022/09

DOI： 10.1111/eci.13808 　
COVID-19 in a Hairy Cell Leukemia Patient: A Rare Case Report.

Hirohito Sano, Koji Murakami, Hisayuki Yokoyama, Chie Suzuki, Yudai Iwasaki, Eiichi Kodama, Hisatoshi Sugiura

The Tohoku journal of experimental medicine　258　(1)　63-68　2022/08/10

DOI： 10.1620/tjem.2022.J058 　

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The detailed clinical course of coronavirus disease 2019 (COVID-19) in patients with hairy cell leukemia (HCL) is rarely reported. We report the first case of HCL diagnosed with prolonged pancytopenia after COVID-19 infection in Japan. We describe the case of a 56-year-old man who was diagnosed with COVID-19. Computed tomography revealed ground-glass opacities in the bilateral lung lobes as well as splenomegaly. Remdesivir and dexamethasone were administered for the treatment of COVID-19. Since the pancytopenia persisted, bone marrow examination was performed, and he was diagnosed with HCL. Although pancytopenia can occur with COVID-19 alone, clinicians should be alerted regarding the presence of hematologic malignancies in patients in whom pancytopenia persists after COVID-19 treatment or in those with splenomegaly. Further, the condition of all previously reported patients with COVID-19 associated with HCL was severe enough to require mechanical ventilation. This is the first case in which the disease was not severe. The interleukin-6 (IL-6) level was lower in this case than in previous cases, suggesting that racial differences in IL-6 production may have contributed to COVID-19 severity.
Serine hydroxymethyltransferase as a potential target of antibacterial agents acting synergistically with one-carbon metabolism-related inhibitors. International-journal

Yuko Makino, Chihiro Oe, Kazuya Iwama, Satoshi Suzuki, Akie Nishiyama, Kazuya Hasegawa, Haruka Okuda, Kazushige Hirata, Mariko Ueno, Kumi Kawaji, Mina Sasano, Emiko Usui, Toshiaki Hosaka, Yukako Yabuki, Mikako Shirouzu, Makoto Katsumi, Kazutaka Murayama, Hironori Hayashi, Eiichi N Kodama

Communications biology　5　(1)　619-619　2022/06/23

DOI： 10.1038/s42003-022-03555-x 　

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Serine hydroxymethyltransferase (SHMT) produces 5,10-methylenetetrahydrofolate (CH2-THF) from tetrahydrofolate with serine to glycine conversion. SHMT is a potential drug target in parasites, viruses and cancer. (+)-SHIN-1 was developed as a human SHMT inhibitor for cancer therapy. However, the potential of SHMT as an antibacterial target is unknown. Here, we show that (+)-SHIN-1 bacteriostatically inhibits the growth of Enterococcus faecium at a 50% effective concentration of 10-11 M and synergistically enhances the antibacterial activities of several nucleoside analogues. Our results, including crystal structure analysis, indicate that (+)-SHIN-1 binds tightly to E. faecium SHMT (efmSHMT). Two variable loops in SHMT are crucial for inhibitor binding, and serine binding to efmSHMT enhances the affinity of (+)-SHIN-1 by stabilising the loop structure of efmSHMT. The findings highlight the potency of SHMT as an antibacterial target and the possibility of developing SHMT inhibitors for treating bacterial, viral and parasitic infections and cancer.
Associations between the Combined Fat Mass Index and Fat-Free Mass Index with Carotid Intima-Media Thickness in a Japanese Population: The Tohoku Medical Megabank Community-Based Cohort Study.

Masato Takase, Tomohiro Nakamura, Naoki Nakaya, Mana Kogure, Rieko Hatanaka, Kumi Nakaya, Ikumi Kanno, Kotaro Nochioka, Naho Tsuchiya, Takumi Hirata, Yohei Hamanaka, Junichi Sugawara, Kichiya Suzuki, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Shigeo Kure, Atsushi Hozawa

Journal of atherosclerosis and thrombosis　30　(3)　255-273　2022/05/26

DOI： 10.5551/jat.63523 　

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AIM: Although many epidemiological studies have shown that obesity assessed by body mass index is associated with carotid intima-media thickness (cIMT), few studies have evaluated fat-free mass, which is a component of body composition. We investigated the associations between the combined fat mass index (FMI) and fat-free mass index (FFMI) with cIMT. METHODS: We conducted a cross-sectional study of 3,873 men and 9,112 women aged 20 years or older who lived in Miyagi prefecture, Japan. The FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. The indices were classified into sex-specific quartiles and were combined into 16 groups. The maximum common carotid artery was measured using high-resolution B-mode ultrasound. An analysis of covariance was used to assess associations between the combined FMI and FFMI with cIMT adjusted for age and smoking status. The linear trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1 (lowest) to 4 (highest), and entering the number as a continuous term in the regression model. RESULTS: In multivariable models, a higher FMI was not related to higher cIMT in men and women in most FFMI subgroups. Conversely, a higher FFMI was related to higher cIMT in all FMI subgroups (p＜0.001 for linear trend). CONCLUSIONS: FMI was not associated with cIMT in most FFMI subgroups. Conversely, FFMI was positively associated with cIMT independently of FMI.
Antiviral Activity and Resistance Profile of the Novel HIV-1 Non-Catalytic Site Integrase Inhibitor JTP-0157602. International-journal

Yoshitsugu Ohata, Mitsunori Tomonaga, Yasuo Watanabe, Keiko Tomura, Koji Kimura, Tatsuo Akaki, Kaoru Adachi, Eiichi N Kodama, Yuji Matsuzaki, Hironori Hayashi

Journal of virology　96　(6)　e0184321　2022/03/23

DOI： 10.1128/JVI.01843-21 　

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HIV-1 integrase (IN) is an essential enzyme for viral replication. Non-catalytic site integrase inhibitors (NCINIs) are allosteric HIV-1 IN inhibitors and a potential new class of antiretrovirals. In this report, we identified a novel NCINI, JTP-0157602, with an original scaffold. JTP-0157602 exhibited potent antiviral activity against HIV-1 and showed a serum-shifted EC90 of 138 nM, which is comparable to the FDA-approved IN strand transfer inhibitors (INSTIs). This compound was fully potent against a wide range of recombinant viruses with IN polymorphisms, including amino acids 124/125, a hot spot of IN polymorphisms. In addition, JTP-0157602 retained potent antiviral activity against a broad panel of recombinant viruses with INSTI-related resistant mutations, including multiple substitutions that emerged in clinical studies of INSTIs. Resistance selection experiments of JTP-0157602 led to the emergence of A128T and T174I mutations, which are located at the lens epithelium-derived growth factor/p75 binding pocket of IN. JTP-0157602 inhibited HIV-1 replication mainly during the late-phase of the replication cycle, and HIV-1 virions produced by reactivation from HIV-1 latently-infected Jurkat cells in the presence of JTP-0157602 were non-infectious. These results suggest that JTP-0157602 and analog compounds can be used to treat HIV-1 infectious diseases. IMPORTANCE Non-catalytic site integrase inhibitors (NCINIs) are allosteric HIV-1 integrase (IN) inhibitors that bind to the lens epithelium-derived growth factor (LEDGF)/p75 binding pocket of IN. NCINIs are expected to be a new class of anti-HIV-1 agents. In this study, we present a novel NCINI, JTP-0157602, which has potent activity against a broad range of HIV-1 strains with IN polymorphisms. Furthermore, JTP-0157602 shows strong antiviral activity against IN strand transfer inhibitor-resistant mutations, suggesting JTP-0157602 and its analogs are potential agents to treat HIV-1 infections. Structural modeling indicated that JTP-0157602 binds to the LEDGF/p75 binding pocket of IN, and the results of in vitro resistance induction revealed the JTP-0157602-resistance mechanism of HIV-1. These data shed light on developing novel NCINIs, which exhibit potent activity against HIV-1 with broad IN polymorphisms and multi-drug resistant HIV-1 variants.
Disseminated tuberculosis with paradoxical reactions caused by a Mycobacterium tuberculosis strain belonging to the Indo-Oceanic lineage: An imported case in Japan. International-journal

Kengo Oshima, Chie Nakajima, Kazushige Hirata, Hironori Hayashi, Eiichi N Kodama, Yukari Fukushima, Yasuhiko Suzuki, Hajime Kanamori, Hiroaki Baba, Tetsuji Aoyagi, Koichi Tokuda, Mitsuo Kaku

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy　28　(7)　965-970　2022/03/04

DOI： 10.1016/j.jiac.2022.02.008 　

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Tuberculosis remains a major public health concern. Millions of tuberculosis cases and associated deaths have been reported worldwide. The Indo-Oceanic lineage Mycobacterium tuberculosis is common in Southeast Asia and causes extrapulmonary lesions. Only a few case studies on this lineage with genetic analysis using whole-genome sequencing have been reported in the literature. We present a case of disseminated tuberculosis, characterized by a variety of extrapulmonary lesions and paradoxical reactions, caused by the Indo-Oceanic lineage M. tuberculosis in a woman in Myanmar. A 22-year-old Burmese woman had arthritis in the right knee, with unknown aetiology, and was referred to our hospital. Computed tomography of the trunk revealed multiple nodular shadows in both lungs; swollen mediastinal lymph nodes; and small, low-density areas in the spleen. M. tuberculosis was detected in the sputum sample, joint aspirate, subcutaneous tumor, and exudate. She experienced a variety of paradoxical reactions together with aggressive tuberculosis dissemination in all areas of the body. Whole-genome sequencing of the DNA of MTB obtained from sputum and the right cervical subcutaneous abscess confirmed the Indo-Oceanic lineage of M. tuberculosis, the predominant strain in Myanmar. The Indo-Oceanic lineage M. tuberculosis causes disseminated tuberculosis all over the body including the periungual region. When patients show unusual symptoms, physicians should consider the introduction of new strains from foreign countries. Genetic analyses of the strains are recommended to define and confirm the lineages.
Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan International-journal Peer-reviewed

Nobuo Fuse, Miyuki Sakurai, Ikuko N. Motoike, Kaname Kojima, Takako Takai-Igarashi, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Mami Ishikuro, Taku Obara, Akiko Miyazawa, Kei Homma, Keisuke Ido, Makiko Taira, Tomoko Kobayashi, Ritsuko Shimizu, Akira Uruno, Eiichi N. Kodama, Kichiya Suzuki, Yohei Hamanaka, Hiroaki Tomita, Junichi Sugawara, Yoichi Suzuki, Fuji Nagami, Soichi Ogishima, Fumiki Katsuoka, Naoko Minegishi, Atsushi Hozawa, Shinichi Kuriyama, Nobuo Yaegashi, Shigeo Kure, Kengo Kinoshita, Masayuki Yamamoto

Ophthalmology Science　2　(1)　100113-100113　2022/03
Publisher: Elsevier BV
DOI： 10.1016/j.xops.2022.100113 　

ISSN： 2666-9145

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PURPOSE: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. DESIGN: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). PARTICIPANTS: In total, 33 483 participants aged > 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. METHODS: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. MAIN OUTCOME MEASURES: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. RESULTS: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. CONCLUSIONS: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL.
Change in use of pediatric oral antibiotics in Japan, pre- and post-implementation of an antimicrobial resistance action plan. International-journal

Noriko Iwamoto, Naho Morisaki, Kazuhiro Uda, Masashi Kasai, Eiichi N Kodama, Norio Ohmagari, Isao Miyairi

Pediatrics international : official journal of the Japan Pediatric Society　64　(1)　e15197　2022/01

DOI： 10.1111/ped.15197 　

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BACKGROUND: Most antimicrobials are prescribed to outpatients, making outpatient antibiotic prescription an important target for antibiotic stewardship. A national antimicrobial resistance (AMR) action plan was developed in 2016 by the Japanese government with various antimicrobials steawardship activities for pediatric outpatients. We aimed to evaluate changes in antibiotic use pre- and post-implementation of the AMR action plan. METHODS: All antimicrobials prescribed to pediatric outpatients in Japan from 2011 to 2018 were retrospectively analyzed using data from a national database. Antimicrobials dispensed for patients aged ≤19 years were reviewed. Antimicrobial use was surveyed by age, year of use, type of antimicrobial prescribed, and prescribing facility. Five cities were selected as pilot areas to investigate the variations, based on the clinical specialties of the prescribing physicians. RESULTS: Antimicrobial usage varied with age. Specifically, usage decreased post-AMR in patients aged ≤8 years and increased in those aged >15 years. Further, antimicrobial prescriptions tended to decrease after 2016 in primary care clinics and hospitals. In the pilot areas of the study, 35% of all oral antimicrobials were prescribed in otolaryngology departments, and 8% were prescribed in dermatology clinics. Notably, antimicrobial prescriptions from both departments showed an upward trend from 2011 to 2018. CONCLUSION: The use of antimicrobial agents decreased in children younger than 8 years in pediatric clinics, hospitals, and internal medicine clinics. However, use increased in children older than 15 years and in other specialty clinics. Settings with an increasing use of antimicrobials are potential targets for the next antibiotic stewardship program and should be investigated in detail.
Factors Associated With Prolonged Psychological Distress Among Nurses and Physicians Engaged in COVID-19 Patient Care in Singapore and Japan. International-journal

Shinichiro Morioka, Ban Hock Tan, Hiroe Kikuchi, Yusuke Asai, Tetsuya Suzuki, Shinobu Ashida, Satoshi Kutsuna, Sho Saito, Kayoko Hayakawa, Thuan Tong Tan, Eiichi Kodama, Norio Ohmagari

Frontiers in psychiatry　13　781796-781796　2022

DOI： 10.3389/fpsyt.2022.781796 　

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This study explores the factors contributing to the prolonged psychological distress of frontline nurses and physicians caring for COVID-19 patients in hospitals in Singapore and Japan. A cross-sectional survey between September and December 2020 yielded 1,644 responses (23.8%), from 62 nurses and 64 physicians in Singapore and 1,280 nurses and 238 physicians in Japan. Multivariate logistic regression analysis revealed that significant risk factors for prolonged psychological distress included being a frontline nurse [adjusted odds ratio (aOR) = 2.40, 95% confidence interval (CI): 1.24-4.66], having an underlying medical condition (aOR = 1.74, 95% CI: 1.22-2.46), experiencing prejudice because they undertook COVID-19 patient care (aOR = 3.05, 95% CI: 2.23-4.18), having trouble dealing with panicked or uncooperative patients (aOR = 2.36, 95% CI: 1.71-3.25), and experiencing an outbreak of COVID-19 in the hospital (aOR = 2.05, 95% CI: 1.38-3.04). Factors inversely associated with psychological distress included age (OR = 0.98, 95% CI: 0.97-1.00), number of beds in the hospital (aOR = 0.73, 95% CI: 0.57-0.94), clinical practice of carefully putting on and taking off personal protective equipment in daily COVID-19 patient care (aOR = 0.52, 95% CI: 0.37-0.73), and knowledge on COVID-19 (aOR = 0.82, 95% CI: 0.72-0.94). These results could help us identify vulnerable healthcare providers who need urgent mental care during the COVID-19 pandemic. Measures that may reduce psychological strain include adequate supply of medical resources, education on precautionary measures, and communication strategies to combat discrimination against frontline healthcare providers.
Effects of infectious disease consultation and antimicrobial stewardship program at a Japanese cancer center: An interrupted time-series analysis. International-journal

Naoya Itoh, Nana Akazawa, Eri Kanawaku, Hiromi Murakami, Yuichi Ishibana, Daichi Kawamura, Takanori Kawabata, Keita Mori, Eiichi N Kodama, Norio Ohmagari

PloS one　17　(1)　e0263095　2022

DOI： 10.1371/journal.pone.0263095 　

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In cancer patients, appropriate diagnosis and management of infection are frequently challenging owing to subtle or atypical presentation. We investigated the effectiveness of infectious disease (ID) consultations and the Antimicrobial Stewardship Program (ASP) in a Japanese cancer center. This 36-month-period, single-institution, interrupted time series analysis was retrospectively conducted during April 1, 2018-March 31, 2021, to evaluate a two-phase intervention: Phase 1 (notification of antimicrobials by the infection control team) and Phase 2 (establishing an ID consultation service and implementing ASP). Among 32,202 patients hospitalized, 22,096 and 10,106 hospitalizations occurred at baseline and during intervention period, respectively. The Antimicrobial Stewardship Team (AST) provided feedback on specific broad-spectrum antimicrobials in 913 instances (347 appropriate [38%]; 566 inappropriate [62%]), and 440 ID consultations were completed, with a 75% overall acceptance rate for AST suggestions. In Phase 2, monthly carbapenem days of therapy (CAR-DOT) decreased significantly, and narrow-spectrum antibiotic usage increased significantly in both trend and level; monthly DOT of antipseudomonal agents decreased significantly in trend. The results of these analyses of antimicrobial use are consistent with the DOT-based data based on antimicrobial use density (AUD). The total number of inpatient specimens increased significantly; the trend of multidrug-resistant Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus infections decreased, without changes in the incidence of other resistant organisms, all-cause in-hospital mortality, and length of stay. Actual and adjusted CAR purchase costs per patient-day decreased without significant changes in the actual and adjusted purchase cost per patient-day for all intravenous antimicrobials. Combining ID consultation and ASP reduced carbapenem use without negative patient outcomes. Their implementation could facilitate establishment of safe cancer treatment facilities in Japan and improve prognosis in cancer patients.
Association between fat mass index, fat-free mass index and hemoglobin A1c in a Japanese population: The Tohoku Medical Megabank Community-based Cohort Study.

Masato Takase, Tomohiro Nakamura, Takumi Hirata, Naho Tsuchiya, Mana Kogure, Fumi Itabashi, Naoki Nakaya, Yohei Hamanaka, Junichi Sugawara, Kichiya Suzuki, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Shigeo Kure, Atsushi Hozawa

Journal of diabetes investigation　13　(5)　858-867　2021/12/03

DOI： 10.1111/jdi.13729 　

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AIMS/INTRODUCTION: Fat mass and fat-free mass affect glycated hemoglobin A1c (HbA1c) levels and blood glucose levels, respectively. The aim of the present study was to examine the association between the fat mass index and fat-free mass index with HbA1c. MATERIALS AND METHODS: We carried out a cross-sectional study that included 3,731 men and 9,191 women aged ≥20 years, living in Miyagi Prefecture, Japan, who were not treated for diabetes. The fat mass index and fat-free mass index were calculated as fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into sex-specific quartiles and combined into 16 groups. An analysis of covariance was used to assess associations between the combined fat mass index and fat-free mass index with HbA1c adjusted for potential confounders. The linear trend test was carried out by stratifying the fat mass index and fat-free mass index, entering the number as a continuous term in the regression model. RESULTS: In multivariable models, a higher fat mass index was related to higher HbA1c levels in men and women in all fat-free mass index subgroups (P < 0.001 for linear trend). When we excluded the participants who had been identified as having diabetes, the fat-free mass index was also related to higher HbA1c levels in most fat mass index subgroups (P < 0.05 for linear trend). CONCLUSIONS: Fat mass index was positively related to HbA1c levels. The fat-free mass index was also related to HbA1c levels when we excluded participants who had been identified as having have diabetes.
Genetic loci for lung function in Japanese adults with adjustment for exhaled nitric oxide levels as airway inflammation indicator. International-journal

Mitsuhiro Yamada, Ikuko N Motoike, Kaname Kojima, Nobuo Fuse, Atsushi Hozawa, Shinichi Kuriyama, Fumiki Katsuoka, Shu Tadaka, Matsuyuki Shirota, Miyuki Sakurai, Tomohiro Nakamura, Yohei Hamanaka, Kichiya Suzuki, Junichi Sugawara, Soichi Ogishima, Akira Uruno, Eiichi N Kodama, Naoya Fujino, Tadahisa Numakura, Tomohiro Ichikawa, Ayumi Mitsune, Takashi Ohe, Kengo Kinoshita, Masakazu Ichinose, Hisatoshi Sugiura, Masayuki Yamamoto

Communications biology　4　(1)　1288-1288　2021/11/15

DOI： 10.1038/s42003-021-02813-8 　

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Lung function reflects the ability of the respiratory system and is utilized for the assessment of respiratory diseases. Because type 2 airway inflammation influences lung function, genome wide association studies (GWAS) for lung function would be improved by adjustment with an indicator of the inflammation. Here, we performed a GWAS for lung function with adjustment for exhaled nitric oxide (FeNO) levels in two independent Japanese populations. Our GWAS with genotype imputations revealed that the RNF5/AGER locus including AGER rs2070600 SNP, which introduces a G82S substitution of AGER, was the most significantly associated with FEV1/FVC. Three other rare missense variants of AGER were further identified. We also found genetic loci with three candidate genes (NOS2, SPSB2 and RIPOR2) associated with FeNO levels. Analyses with the BioBank-Japan GWAS resource revealed genetic links of FeNO and asthma-related traits, and existence of common genetic background for allergic diseases and their biomarkers. Our study identified the genetic locus most strongly associated with airway obstruction in the Japanese population and three genetic loci associated with FeNO, an indicator of type 2 airway inflammation in adults.
Development of robust isothermal RNA amplification assay for lab-free testing of RNA viruses. International-journal

Radhika Biyani, Kirti Sharma, Kenji Kojima, Madhu Biyani, Vishnu Sharma, Tarun Kumawat, Kevin Maafu Juma, Itaru Yanagihara, Shinsuke Fujiwara, Eiichi Kodama, Yuzuru Takamura, Masahiro Takagi, Kiyoshi Yasukawa, Manish Biyani

Scientific reports　11　(1)　15997-15997　2021/08/06

DOI： 10.1038/s41598-021-95411-x 　

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Simple tests of infectiousness that return results in minutes and directly from samples even with low viral loads could be a potential game-changer in the fight against COVID-19. Here, we describe an improved isothermal nucleic acid amplification assay, termed the RICCA (RNA Isothermal Co-assisted and Coupled Amplification) reaction, that consists of a simple one-pot format of 'sample-in and result-out' with a primary focus on the detection of low copy numbers of RNA virus directly from saliva without the need for laboratory processing. We demonstrate our assay by detecting 16S rRNA directly from E. coli cells with a sensitivity as low as 8 CFU/μL and RNA fragments from a synthetic template of SARS-CoV-2 with a sensitivity as low as 1740 copies/μL. We further demonstrate the applicability of our assay for real-time testing at the point of care by designing a closed format for paper-based lateral flow assay and detecting heat-inactivated SARS-COV-2 virus in human saliva at concentrations ranging from 28,000 to 2.8 copies/μL with a total assay time of 15-30 min.
Association between the combined fat mass and fat-free mass index and hypertension: The Tohoku Medical Megabank Community-based Cohort Study. International-journal

Masato Takase, Tomohiro Nakamura, Naho Tsuchiya, Mana Kogure, Fumi Itabashi, Akira Narita, Takumi Hirata, Naoki Nakaya, Yohei Hamanaka, Junichi Sugawara, Kichiya Suzuki, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Shigeo Kure, Atsushi Hozawa

Clinical and experimental hypertension (New York, N.Y. : 1993)　43　(7)　1-12　2021/07/06

DOI： 10.1080/10641963.2021.1925681 　

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BACKGROUND: A higher body fat percentage is associated with hypertension, even in non-obese individuals. The difference in body composition may be related to hypertension. The fat mass index (FMI) and fat-free mass index (FFMI) are proposed indicators of body composition. This study aimed to examine the relationship of a combination of FMI and FFMI with hypertension. METHODS: We conducted a cross-sectional study of 5,058 men and 11,842 women aged ≥ 20 years in the Miyagi Prefecture, northeastern Japan. The FMI and FFMI were calculated as the fat mass and fat-free mass divided by the height squared, respectively. The indices were classified into quartiles and combined into 16 groups. Hypertension was defined as casual blood pressure ≥ 140/90 mmHg and/or self-reported treatment for hypertension. Multivariable logistic regression models, adjusted for potential confounders, were used to assess the relationship of a combination of FMI and FFMI with hypertension. RESULTS: Higher FMI was associated with hypertension in most of the FFMI subgroups. Similarly, a higher FFMI was associated with hypertension in most of FMI subgroups. For men, the association between FFMI and hypertension in the lowest FMI group was not significant. CONCLUSIONS: Reducing the FMI and FFMI may be important in preventing hypertension. For men, the relationship between the FFMI and hypertension in the lowest FMI group might be weak.
A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan. International-journal

Sho Saito, Kayoko Hayakawa, Shinya Tsuzuki, Masahiro Ishikane, Maki Nagashima, Kazuhisa Mezaki, Yuko Sugiki, Taichi Tajima, Nobuaki Matsunaga, Satoshi Ide, Noriko Kinoshita, Yoshiki Kusama, Yumiko Fujitomo, Takato Nakamoto, Yuta Toda, Mitsuo Kaku, Eiichi N Kodama, Norio Ohmagari

Antimicrobial agents and chemotherapy　65　(3)　2021/02/17

DOI： 10.1128/AAC.01483-20 　

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IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included; they were matched with patients with carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition for the CRE and CSE groups and mortality rates, which were calculated using multivariate logistic regression models with weighting according to the inverse probability of propensity scores, were compared. In total, 192 patients (96 patients each in the CRE and CSE groups, with 130 Enterobacter cloacae isolates and 62 Klebsiella sp. isolates) were included. The IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1 each; 31 patients with CRE (32.3%) and 34 with CSE (35.4%) developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad-spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. In propensity score-adjusted analysis, mortality rates for the CRE and CSE groups were similar (15.0% and 19.5%, respectively). We found that IMP-CRE may not contribute to worsened clinical outcomes, compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.
A small molecule compound with an indole moiety inhibits the main protease of SARS-CoV-2 and blocks virus replication. International-journal

Shin-Ichiro Hattori, Nobuyo Higashi-Kuwata, Hironori Hayashi, Srinivasa Rao Allu, Jakka Raghavaiah, Haydar Bulut, Debananda Das, Brandon J Anson, Emma K Lendy, Yuki Takamatsu, Nobutoki Takamune, Naoki Kishimoto, Kazutaka Murayama, Kazuya Hasegawa, Mi Li, David A Davis, Eiichi N Kodama, Robert Yarchoan, Alexander Wlodawer, Shogo Misumi, Andrew D Mesecar, Arun K Ghosh, Hiroaki Mitsuya

Nature communications　12　(1)　668-668　2021/01/28

DOI： 10.1038/s41467-021-20900-6 　

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Except remdesivir, no specific antivirals for SARS-CoV-2 infection are currently available. Here, we characterize two small-molecule-compounds, named GRL-1720 and 5h, containing an indoline and indole moiety, respectively, which target the SARS-CoV-2 main protease (Mpro). We use VeroE6 cell-based assays with RNA-qPCR, cytopathic assays, and immunocytochemistry and show both compounds to block the infectivity of SARS-CoV-2 with EC50 values of 15 ± 4 and 4.2 ± 0.7 μM for GRL-1720 and 5h, respectively. Remdesivir permitted viral breakthrough at high concentrations; however, compound 5h completely blocks SARS-CoV-2 infection in vitro without viral breakthrough or detectable cytotoxicity. Combination of 5h and remdesivir exhibits synergism against SARS-CoV-2. Additional X-ray structural analysis show that 5h forms a covalent bond with Mpro and makes polar interactions with multiple active site amino acid residues. The present data suggest that 5h might serve as a lead Mpro inhibitor for the development of therapeutics for SARS-CoV-2 infection.
Study Profile of the Tohoku Medical Megabank Community-Based Cohort Study.

Atsushi Hozawa, Kozo Tanno, Naoki Nakaya, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Akira Narita, Mana Kogure, Kotaro Nochioka, Ryohei Sasaki, Nobuyuki Takanashi, Kotaro Otsuka, Kiyomi Sakata, Shinichi Kuriyama, Masahiro Kikuya, Osamu Tanabe, Junichi Sugawara, Kichiya Suzuki, Yoichi Suzuki, Eiichi N Kodama, Nobuo Fuse, Hideyasu Kiyomoto, Hiroaki Tomita, Akira Uruno, Yohei Hamanaka, Hirohito Metoki, Mami Ishikuro, Taku Obara, Tomoko Kobayashi, Kazuyuki Kitatani, Takako Takai-Igarashi, Soichi Ogishima, Mamoru Satoh, Hideki Ohmomo, Akito Tsuboi, Shinichi Egawa, Tadashi Ishii, Kiyoshi Ito, Sadayoshi Ito, Yasuyuki Taki, Naoko Minegishi, Naoto Ishii, Masao Nagasaki, Kazuhiko Igarashi, Seizo Koshiba, Ritsuko Shimizu, Gen Tamiya, Keiko Nakayama, Hozumi Motohashi, Jun Yasuda, Atsushi Shimizu, Tsuyoshi Hachiya, Yuh Shiwa, Teiji Tominaga, Hiroshi Tanaka, Kotaro Oyama, Ryoichi Tanaka, Hiroshi Kawame, Akimune Fukushima, Yasushi Ishigaki, Tomoharu Tokutomi, Noriko Osumi, Tadao Kobayashi, Fuji Nagami, Hiroaki Hashizume, Tomohiko Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Ryujin Endo, Satoshi Nishizuka, Ichiro Tsuji, Jiro Hitomi, Motoyuki Nakamura, Kuniaki Ogasawara, Nobuo Yaegashi, Kengo Kinoshita, Shigeo Kure, Akio Sakai, Seiichiro Kobayashi, Kenji Sobue, Makoto Sasaki, Masayuki Yamamoto

Journal of epidemiology　31　(1)　65-76　2021/01/05

DOI： 10.2188/jea.JE20190271 　

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BACKGROUND: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases. METHODS: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely. RESULTS: As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex. CONCLUSION: This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.
Implementation of evacuation measures during natural disasters under conditions of the novel coronavirus (COVID-19) pandemic based on a review of previous responses to complex disasters in Japan. International-journal

Masashi Sakamoto, Daisuke Sasaki, Yuichi Ono, Yuko Makino, Eiichi N Kodama

Progress in disaster science　8　100127-100127　2020/12

DOI： 10.1016/j.pdisas.2020.100127 　

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We aimed to investigate how evacuation measures could be effectively implemented in the event of multiple disasters caused by natural hazards under conditions of the novel coronavirus infection (COVID-19) pandemic, which is rapidly spreading worldwide. We conducted a review of literature focusing on complex disasters, entailing natural disasters in combination of outbreaks or endemics of infectious diseases. Using the Google Scholar search engine, we identified and reviewed 24 papers sourced from academia, governments, and concerned organizations, and associated data on such disasters, commencing with the Great Hanshin-Awaji Earthquake, which occurred in 1995. In light of our review, we developed a summary of correspondences and problems linked to compound disasters involving conjunctions of outbreaks/endemics and natural disasters that could offer insights for developing measures to deal with natural disasters that occur in the context of the COVID-19 pandemic. We subsequently attempted to differentiate the characteristics of evacuation measures relating to COVID-19 from those relating to other infectious diseases using three sets of extracted keywords: (1) surveillance and information sharing, (2) evacuation center environment and stockpiled supplies, and (3) community disaster risk reduction and community leadership. We identified issues relating to evacuation measures that would need to be explored further to improve disaster management and preparedness in the future.
【新型コロナウイルス感染症(COVID-19)と精神科病院】宮城県精神科医療機関新型コロナウイルス感染症対策ネットワークにおける対策指針策定の経緯と意義コロナ禍が精神医療にもたらした教訓

富田博秋, 佐藤博俊, 角藤芳久, 國井泰人, 佐久間篤, 牧野祐子, 児玉栄一, 徳田浩一, 鈴木陽, 吉田眞紀子, 賀来満夫, 押谷仁, 小坂健

日本精神科病院協会雑誌　39　(11)　1125-1130　2020/11
Publisher: (公社)日本精神科病院協会
ISSN： 1347-4103
【新型コロナウイルス感染症(COVID-19)と精神科病院】宮城県精神科医療機関新型コロナウイルス感染症対策ネットワークにおける対策指針策定の経緯と意義コロナ禍が精神医療にもたらした教訓

富田博秋, 佐藤博俊, 角藤芳久, 國井泰人, 佐久間篤, 牧野祐子, 児玉栄一, 徳田浩一, 鈴木陽, 吉田眞紀子, 賀来満夫, 押谷仁, 小坂健

日本精神科病院協会雑誌　39　(11)　1125-1130　2020/11
Publisher: (公社)日本精神科病院協会
ISSN： 1347-4103
Maternal Baseline Characteristics and Perinatal Outcomes: the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

Junichi Sugawara, Mami Ishikuro, Taku Obara, Tomomi Onuma, Keiko Murakami, Masahiro Kikuya, Fumihiko Ueno, Aoi Noda, Satoshi Mizuno, Tomoko Kobayashi, Yohei Hamanaka, Kichiya Suzuki, Eiichi Kodama, Naho Tsuchiya, Akira Uruno, Yoichi Suzuki, Osamu Tanabe, Hideyasu Kiyomoto, Akito Tsuboi, Atsushi Shimizu, Seizo Koshiba, Naoko Minegishi, Soichi Ogishima, Gen Tamiya, Hirohito Metoki, Atsushi Hozawa, Nobuo Fuse, Kengo Kinoshita, Shigeo Kure, Nobuo Yaegashi, Shinichi Kuriyama, Masayuki Yamamoto

Journal of epidemiology　32　(2)　69-79　2020/10/10

DOI： 10.2188/jea.JE20200338 　

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BACKGROUND: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study was launched in 2013 to evaluate the complex interactions of genetic and environmental factors in multifactorial diseases. The present study describes the maternal baseline profile and perinatal data of participating mothers and infants. METHODS: Expectant mothers living in Miyagi prefecture were recruited from obstetric facilities or affiliated centers between 2013 and 2017. Three sets of self-administered questionnaires were collected, and the medical records were reviewed to obtain precise information about each antenatal visit and each delivery. Biospecimens, including blood, urine, umbilical cord blood, and breast milk, were collected for the study biobank. The baseline maternal sociodemographic characteristics, results of screening tests, and obstetric outcomes were analyzed according to the maternal age group. RESULTS: A total of 23 406 pregnancies involving 23 730 fetuses resulted in 23 143 live births. Younger maternal participants had a tendency toward a higher incidence of threatened abortion and threatened premature labor, while older age groups exhibited a significantly higher rate of low lying placenta, placenta previa, gestational diabetes and hypertensive disorders of pregnancy. CONCLUSIONS: The present study clearly shows the distribution of maternal baseline characteristics and the range of perinatal outcomes according to maternal age group. This cohort study can provide strategic information for creating breakthroughs in the pathophysiology of perinatal, developmental, and noncommunicable diseases by collaborative data visiting or sharing.
Pyrimidine Analogues as a New Class of Gram-Positive Antibiotics, Mainly Targeting Thymineless-Death Related Proteins. International-journal Peer-reviewed

Chihiro Oe, Hironori Hayashi, Kazushige Hirata, Kumi Kawaji, Fusako Hashima, Mina Sasano, Maaya Furuichi, Emiko Usui, Makoto Katsumi, Yasuhiko Suzuki, Chie Nakajima, Mitsuo Kaku, Eiichi N Kodama

ACS infectious diseases　6　(6)　1490-1500　2020/06/12

DOI： 10.1021/acsinfecdis.9b00305 　

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Multidrug-resistant (MDR) bacteria are widespread throughout the world and pose an increasingly serious threat to human and animal health. Besides implementing strict measures to prevent improper antibiotic use, it remains essential that novel antibiotics must be developed. These antibiotics need to exert their activity via mechanisms different from those employed by currently approved antibiotics. In this study, we used several 5-fluorouracil (5-FU) analogues as chemical probes and investigated the potential of these pyrimidine analogues as antibacterial agents. Several 5-FU derivatives exerted potent activity against strains of Gram-positive cocci (GPC) that are susceptible or resistant toward approved antibiotics, without showing cross-resistance. Furthermore, we have provided evidence that the pyrimidine analogues exerted anti-GPC activity via thymineless death by inhibition of thymidylate synthetase (ThyA) and/or inhibition of RNA synthesis. Interestingly, whole genome resequencing of in vitro-selected, pyrimidine analogue-resistant Staphylococcus aureus mutants indicated that S. aureus strains with pyrimidine-analogue resistance induced an amino acid (AA) substitution, deletion, and/or insertion into thymineless-death related proteins except for ThyA, or enhanced the ThyA transcription level. Thus, S. aureus may avoid altering the ThyA function by introducing an AA substitution, suggesting that the pyrimidine analogues, which directly bind to ThyA without phosphorylation, may be more effective and show a higher genetic barrier than the pyrimidines that depend on phosphorylation for activity. The findings of this study may assist in the future development of a novel class of antibiotics for combating MDR GPC, including methicillin-resistant S. aureus and vancomycin-resistant Enterococci.
Design and Progress of Oral Health Examinations in the Tohoku Medical Megabank Project. Peer-reviewed

Akito Tsuboi, Hiroyuki Matsui, Naru Shiraishi, Takahisa Murakami, Akihito Otsuki, Junko Kawashima, Tomomi Kiyama, Toru Tamahara, Maki Goto, Shihoko Koyama, Junichi Sugawara, Eiichi N Kodama, Hirohito Metoki, Atsushi Hozawa, Shinichi Kuriyama, Hiroaki Tomita, Masahiro Kikuya, Naoko Minegishi, Kichiya Suzuki, Seizo Koshiba, Gen Tamiya, Nobuo Fuse, Yuichi Aoki, Takako Takai-Igarashi, Soichi Ogishima, Tomohiro Nakamura, Mika Sakurai-Yageta, Fuji Nagami, Kengo Kinoshita, Shigeo Kure, Ritsuko Shimizu, Keiichi Sasaki, Masayuki Yamamoto

The Tohoku journal of experimental medicine　251　(2)　97-115　2020/06

DOI： 10.1620/tjem.251.97 　

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In order to assess the long-term impact of the Great East Japan Earthquake on the oral health of disaster victims and to evaluate gene-environmental interactions in the development of major oral diseases and oral-systemic associations, the oral part of two large-scale genome cohort studies by the Tohoku Medical Megabank Organization (ToMMo), including the Community-based cohort (CommCohort) study and the Birth and Three-Generation cohort (BirThree) study, have been conducted. The study population comprised 32,185 subjects, including 16,886 participants in the CommCohort study and 15,299 participants in the BirThree cohort study, recruited from 2013 to 2017. The oral studies consist of a questionnaire regarding oral hygiene behavior, clinical examinations by dentists, and oral plaque and saliva sampling for microbiome analyses, which were carried out at seven community support centers in Miyagi prefecture. The median age of all participants was 55.0 years, and 66.1% of participants were women. Almost all participants reported that they brushed their teeth more than once a day. The median number of present teeth was 27.0, and the decayed, missing and filled tooth number was 16.0, with a significant difference according to age and sex. The median periodontal pocket and clinical attachment level was 2.48 mm and 4.00 mm, respectively. Periodontal parameters increased significantly according to age, except for the accumulation of dental calculus. The oral part of these extensive cross-sectional studies provides a unique and important platform for future studies on oral health and diseases that elicit through interactions with systemic diseases, lifestyles, life events and genetic backgrounds, and contributes to researches clarifying the long-term effects of disasters on oral health.
Synthetic biology based construction of biological activity-related library of fungal decalin-containing diterpenoid pyrones. International-journal Peer-reviewed

Kento Tsukada, Shono Shinki, Akiho Kaneko, Kazuma Murakami, Kazuhiro Irie, Masatoshi Murai, Hideto Miyoshi, Shingo Dan, Kumi Kawaji, Hironori Hayashi, Eiichi N Kodama, Aki Hori, Emil Salim, Takayuki Kuraishi, Naoya Hirata, Yasunari Kanda, Teigo Asai

Nature communications　11　(1)　1830-1830　2020/04/14

DOI： 10.1038/s41467-020-15664-4 　

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A synthetic biology method based on heterologous biosynthesis coupled with genome mining is a promising approach for increasing the opportunities to rationally access natural product with novel structures and biological activities through total biosynthesis and combinatorial biosynthesis. Here, we demonstrate the advantage of the synthetic biology method to explore biological activity-related chemical space through the comprehensive heterologous biosynthesis of fungal decalin-containing diterpenoid pyrones (DDPs). Genome mining reveals putative DDP biosynthetic gene clusters distributed in five fungal genera. In addition, we design extended DDP pathways by combinatorial biosynthesis. In total, ten DDP pathways, including five native pathways, four extended pathways and one shunt pathway, are heterologously reconstituted in a genetically tractable heterologous host, Aspergillus oryzae, resulting in the production of 22 DDPs, including 15 new analogues. We also demonstrate the advantage of expanding the diversity of DDPs to probe various bioactive molecules through a wide range of biological evaluations.
フルオロウラシル誘導体は新規作用機序であるピリミジン代謝阻害によって薬剤耐性グラム陽性球菌に優れた抗菌活性を示す

大江千紘, 林宏典, 平田和成, 勝見真琴, 賀来満夫, 児玉栄一

感染症学雑誌　94　(臨増)　301-301　2020/03
Publisher: (一社)日本感染症学会
ISSN： 0387-5911

eISSN： 1884-569X
Cohort Profile: Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study): rationale, progress and perspective. International-journal Peer-reviewed

Shinichi Kuriyama, Hirohito Metoki, Masahiro Kikuya, Taku Obara, Mami Ishikuro, Chizuru Yamanaka, Masato Nagai, Hiroko Matsubara, Tomoko Kobayashi, Junichi Sugawara, Gen Tamiya, Atsushi Hozawa, Naoki Nakaya, Naho Tsuchiya, Tomohiro Nakamura, Akira Narita, Mana Kogure, Takumi Hirata, Ichiro Tsuji, Fuji Nagami, Nobuo Fuse, Tomohiko Arai, Yoshio Kawaguchi, Shinichi Higuchi, Masaki Sakaida, Yoichi Suzuki, Noriko Osumi, Keiko Nakayama, Kiyoshi Ito, Shinichi Egawa, Koichi Chida, Eiichi Kodama, Hideyasu Kiyomoto, Tadashi Ishii, Akito Tsuboi, Hiroaki Tomita, Yasuyuki Taki, Hiroshi Kawame, Kichiya Suzuki, Naoto Ishii, Soichi Ogishima, Satoshi Mizuno, Takako Takai-Igarashi, Naoko Minegishi, Jun Yasuda, Kazuhiko Igarashi, Ritsuko Shimizu, Masao Nagasaki, Osamu Tanabe, Seizo Koshiba, Hiroaki Hashizume, Hozumi Motohashi, Teiji Tominaga, Sadayoshi Ito, Kozo Tanno, Kiyomi Sakata, Atsushi Shimizu, Jiro Hitomi, Makoto Sasaki, Kengo Kinoshita, Hiroshi Tanaka, Tadao Kobayashi, Shigeo Kure, Nobuo Yaegashi, Masayuki Yamamoto

International journal of epidemiology　49　(1)　18-19　2020/02/01

DOI： 10.1093/ije/dyz169 　

ISSN： 0300-5771
Mitochondrial dysfunction underlying sporadic inclusion body myositis is ameliorated by the mitochondrial homing drug MA-5. International-journal

Yoshitsugu Oikawa, Rumiko Izumi, Masashi Koide, Yoshihiro Hagiwara, Makoto Kanzaki, Naoki Suzuki, Koichi Kikuchi, Tetsuro Matsuhashi, Yukako Akiyama, Mariko Ichijo, Shun Watanabe, Takafumi Toyohara, Takehiro Suzuki, Eikan Mishima, Yasutoshi Akiyama, Yoshiaki Ogata, Chitose Suzuki, Hironori Hayashi, Eiichi N Kodama, Ken-Ichiro Hayashi, Eiji Itoi, Masashi Aoki, Shigeo Kure, Takaaki Abe

PloS one　15　(12)　e0231064　2020

DOI： 10.1371/journal.pone.0231064 　

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Sporadic inclusion body myositis (sIBM) is the most common idiopathic inflammatory myopathy, and several reports have suggested that mitochondrial abnormalities are involved in its etiology. We recruited 9 sIBM patients and found significant histological changes and an elevation of growth differential factor 15 (GDF15), a marker of mitochondrial disease, strongly suggesting the involvement of mitochondrial dysfunction. Bioenergetic analysis of sIBM patient myoblasts revealed impaired mitochondrial function. Decreased ATP production, reduced mitochondrial size and reduced mitochondrial dynamics were also observed in sIBM myoblasts. Cell vulnerability to oxidative stress also suggested the existence of mitochondrial dysfunction. Mitochonic acid-5 (MA-5) increased the cellular ATP level, reduced mitochondrial ROS, and provided protection against sIBM myoblast death. MA-5 also improved the survival of sIBM skin fibroblasts as well as mitochondrial morphology and dynamics in these cells. The reduction in the gene expression levels of Opa1 and Drp1 was also reversed by MA-5, suggesting the modification of the fusion/fission process. These data suggest that MA-5 may provide an alternative therapeutic strategy for treating not only mitochondrial diseases but also sIBM.
Application of human lymphoid cells for the evaluation of antivirals against human adenovirus type 19: Zalcitabine has superior activity compared to cidofovir

Kohsuke Nakagawara, Hironori Hayashi, Kumi Kawaji, Mina Sasano, Eiichi N Kodama

Antiviral Chemistry and Chemotherapy　28　204020662092131-204020662092131　2020/01
Publisher: SAGE Publications
DOI： 10.1177/2040206620921319 　

ISSN： 2040-2066

eISSN： 2040-2066

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Human adenovirus type 19 (HAdV-19) is a major cause of the epidemic keratoconjunctivitis. Outbreaks of keratoconjunctivitis are problematic to human health, especially for infants, the elderly, and immunocompromised individuals. However, the development of anti-HAdV drugs has been hampered by inconvenient screening systems; therefore, development of a simple screening method is highly desirable. In this study, we identified that HAdV-19 can infect a human lymphoid cell line transformed with human T-cell leukemia virus (MT-2 cells). MT-2 cells supported HAdV-19 replication and showed apparent cytopathic effects within five days post-infection. Using a thiazolyl blue tetrazolium bromide (MTT)-based colorimetric assay on MT-2 cells, we were able to detect the anti-HAdV-19 activities of previously reported nucleoside/tide compounds, including (S)-1–(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (cidofovir), 2′,3′-dideoxycytidine (zalcitabine) and 3′-deoxy-3′-fluorothymidine (trifluridine). Compared with previous methods, this system represents a more simple and rapid method to screen anti-HAdV-19 agents.
東日本大震災と熊本地震の比較分析による精神科病棟における被災時感染症対策の実態についての研究

野崎裕之, 児玉栄一

Japanese Journal of Disaster Medicine　24　(3)　392-392　2019/12
Publisher: (一社)日本災害医学会
ISSN： 2189-4035

eISSN： 2434-4214
Construction of a Meroterpenoid-Like Compounds Library Based on Diversity-Enhanced Extracts. International-journal Peer-reviewed

Haruhisa Kikuchi, Kosuke Kawai, Yota Nakashiro, Takayuki Yonezawa, Kumi Kawaji, Eiichi N Kodama, Yoshiteru Oshima

Chemistry (Weinheim an der Bergstrasse, Germany)　25　(4)　1106-1112　2019/01/18

DOI： 10.1002/chem.201805417 　

ISSN： 0947-6539

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The structural diversity of natural products and their derivatives have long contributed to the development of new drugs. However, the difficulty in obtaining compounds bearing skeletally novel structures has recently led to a decline of pharmaceutical research into natural products. This paper reports the construction of a meroterpenoid-like library containing 25 compounds with diverse molecular scaffolds obtained from diversity-enhanced extracts. This method constitutes an approach for increasing the chemical diversity of natural-product-like compounds by combining natural product chemistry and diversity-oriented synthesis. Extensive pharmacological screening of the library revealed promising compounds for anti-osteoporotic and anti-lymphoma/leukemia drugs. This result indicates that the use of diversity-enhanced extracts is an effective methodology for producing chemical libraries for the purpose of drug discovery.
Identification of human immunodeficiency virus type-1 Gag-TSG101 interaction inhibitors by high-throughput screening. International-journal Peer-reviewed

Lowela Siarot, Nopporn Chutiwitoonchai, Hirotaka Sato, Hao Chang, Hironori Sato, Masayuki Fujino, Tsutomu Murakami, Toshihiro Aono, Eiichi Kodama, Kazumichi Kuroda, Masami Takei, Yoko Aida

Biochemical and biophysical research communications　503　(4)　2970-2976　2018/09/18
Publisher: Elsevier BV
DOI： 10.1016/j.bbrc.2018.08.079 　

ISSN： 0006-291X

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The interaction between viral protein Gag and cellular protein tumor susceptibility gene 101 (TSG101) is a crucial step in the HIV-1 replication cycle. This interaction initiates the viral assembly/budding via the cellular endosomal sorting complexes required for transport (ESCRT) pathway, making it a potential target for antiviral therapy. Here we developed a simple, robust, and reliable high-throughput screening (HTS) system based on enzyme-linked immunosorbent assay (ELISA) to identify compounds that inhibit HIV-1 replication by targeting Gag-TSG101 interaction. Through screening of the 9600-compound library using the established HTS system, several hit compounds, which inhibited Gag-TSG101 interaction, were identified. Subsequent assays revealed two hit compounds, HSM-9 and HSM-10, which have antiviral activity against CD4+ T cell-tropic NL4-3 and macrophage-tropic JR-CSF HIV-1 strains. These results suggest that our established HTS system is an indispensable tool for the identification of HIV-1 Gag-TSG101 interaction inhibitors.
Structural basis of HIV inhibition by translocation-defective RT inhibitor 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA). International-journal Peer-reviewed

Zhe Li Salie, Karen A Kirby, Eleftherios Michailidis, Bruno Marchand, Kamalendra Singh, Lisa C Rohan, Eiichi N Kodama, Hiroaki Mitsuya, Michael A Parniak, Stefan G Sarafianos

Proceedings of the National Academy of Sciences of the United States of America　113　(33)　9274-9　2016/08/16

DOI： 10.1073/pnas.1605223113 　

ISSN： 0027-8424
A Novel Peptide Derived from the Fusion Protein Heptad Repeat Inhibits Replication of Subacute Sclerosing Panencephalitis Virus In Vitro and In Vivo. International-journal Peer-reviewed

Masahiro Watanabe, Koichi Hashimoto, Yusaku Abe, Eiichi N Kodama, Ryota Nabika, Shinya Oishi, Shinichiro Ohara, Masatoki Sato, Yukihiko Kawasaki, Nobutaka Fujii, Mitsuaki Hosoya

PloS one　11　(9)　e0162823　2016

DOI： 10.1371/journal.pone.0162823 　

ISSN： 1932-6203
A Cinnamon-Derived Procyanidin Compound Displays Anti-HIV-1 Activity by Blocking Heparan Sulfate- and Co-Receptor- Binding Sites on gp120 and Reverses T Cell Exhaustion via Impeding Tim-3 and PD-1 Upregulation. International-journal Peer-reviewed

Bridgette Janine Connell, Sui-Yuan Chang, Ekambaranellore Prakash, Rahima Yousfi, Viswaraman Mohan, Wilfried Posch, Doris Wilflingseder, Christiane Moog, Eiichi N Kodama, Pascal Clayette, Hugues Lortat-Jacob

PloS one　11　(10)　e0165386　2016

DOI： 10.1371/journal.pone.0165386 　

ISSN： 1932-6203
Histone chaperone CAF-1 mediates repressive histone modifications to protect preimplantation mouse embryos from endogenous retrotransposons. International-journal Peer-reviewed

Yuki Hatanaka, Kimiko Inoue, Mami Oikawa, Satoshi Kamimura, Narumi Ogonuki, Eiichi N Kodama, Yasuyuki Ohkawa, Yu-ichi Tsukada, Atsuo Ogura

Proceedings of the National Academy of Sciences of the United States of America　112　(47)　14641-6　2015/11/24

DOI： 10.1073/pnas.1512775112 　

ISSN： 0027-8424
Use of a biosynthetic intermediate to explore the chemical diversity of pseudo-natural fungal polyketides. International-journal Peer-reviewed

Teigo Asai, Kento Tsukada, Satomi Ise, Naoki Shirata, Makoto Hashimoto, Isao Fujii, Katsuya Gomi, Kosuke Nakagawara, Eiichi N Kodama, Yoshiteru Oshima

Nature chemistry　7　(9)　737-43　2015/09

DOI： 10.1038/nchem.2308 　

ISSN： 1755-4330

eISSN： 1755-4349
Inhibition of the DNA polymerase and RNase H activities of HIV-1 reverse transcriptase and HIV-1 replication by Brasenia schreberi (Junsai) and Petasites japonicus (Fuki) components. Peer-reviewed

Tetsuro Hisayoshi, Mayu Shinomura, Kanta Yokokawa, Ikumi Kuze, Atsushi Konishi, Kumi Kawaji, Eiichi N Kodama, Keishi Hata, Saori Takahashi, Satoru Nirasawa, Shohei Sakuda, Kiyoshi Yasukawa

Journal of natural medicines　69　(3)　432-40　2015/07

DOI： 10.1007/s11418-015-0885-9 　

ISSN： 1340-3443

eISSN： 1861-0293
Anti-HIV-1 activity determined by β-galactosidase activity in the multinuclear activation of an indicator assay is comparable with that by a conventional focus counting method. International-journal Peer-reviewed

Fusako Miyamoto, Kumi Kawaji, Shinya Oishi, Nobutaka Fujii, Mitsuo Kaku, Eiichi N Kodama

Antiviral chemistry & chemotherapy　24　(2)　77-82　2015/04
Publisher: SAGE Publications Inc.
DOI： 10.1177/2040206615614164 　

ISSN： 0956-3202
Synthesis of a Vpr-Binding Derivative for Use as a Novel HIV-1 Inhibitor. International-journal Peer-reviewed

Kyoji Hagiwara, Hideki Ishii, Tomoyuki Murakami, Shin-nosuke Takeshima, Nopporn Chutiwitoonchai, Eiichi N Kodama, Kumi Kawaji, Yasumitsu Kondoh, Kaori Honda, Hiroyuki Osada, Yasuko Tsunetsugu-Yokota, Masaaki Suzuki, Yoko Aida

PloS one　10　(12)　e0145573　2015

DOI： 10.1371/journal.pone.0145573 　

ISSN： 1932-6203
4 '-Ethynyl-2-fluoro-2 '-deoxyadenosine (EFdA) Inhibits HIV-1 Reverse Transcriptase with Multiple Mechanisms Peer-reviewed

Eleftherios Michailidis, Andrew D. Huber, Emily M. Ryan, Yee T. Ong, Maxwell D. Leslie, Kayla B. Matzek, Kamalendra Singh, Bruno Marchand, Ariel N. Hagedorn, Karen A. Kirby, Lisa C. Rohan, Eiichi N. Kodama, Hiroaki Mitsuya, Michael A. Parniak, Stefan G. Sarafianos

JOURNAL OF BIOLOGICAL CHEMISTRY　289　(35)　24533-24548　2014/08

DOI： 10.1074/jbc.M114.562694 　

ISSN： 0021-9258

eISSN： 1083-351X
エピジェネティックな二次代謝活性化法を利用するイチイ内生糸状菌からの新規生物活性物質の探索

布木純, 浅井禎吾, 山下幸和, 河治久実, 児玉栄一, 大島吉輝

日本薬学会年会要旨集　134年会　(2)　151-151　2014/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Delayed emergence of HIV-1 variants resistant to 4 '-ethynyl-2-fluoro-2 '-deoxyadenosine: comparative sequential passage study with lamivudine, tenofovir, emtricitabine and BMS-986001 Peer-reviewed

Kenji Maeda, Darshan V. Desai, Manabu Aoki, Hirotomo Nakata, Eiichi N. Kodama, Hiroaki Mitsuya

ANTIVIRAL THERAPY　19　(2)　179-189　2014

DOI： 10.3851/IMP2697 　

ISSN： 1359-6535
Effects of Substitutions at the 4 ' and 2 Positions on the Bioactivity of 4 '- Ethynyl-2-Fluoro-2 '-Deoxyadenosine

Karen A. Kirby, Eleftherios Michailidis, Tracy L. Fetterly, Musetta A. Steinbach, Kamalendra Singh, Bruno Marchand, Maxwell D. Leslie, Ariel N. Hagedorn, Eiichi N. Kodama, Victor E. Marquez, Stephen H. Hughes, Hiroaki Mitsuya, Michael A. Parniak, Stefan G. Sarafianos

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　57　(12)　6254-6264　2013/12

DOI： 10.1128/AAC.01703-13 　

ISSN： 0066-4804

eISSN： 1098-6596
Evaluation of Combinations of 4 '-Ethynyl-2-Fluoro-2 '-Deoxyadenosine with Clinically Used Antiretroviral Drugs Peer-reviewed

Atsuko Hachiya, Aaron B. Reeve, Bruno Marchand, Eleftherios Michailidis, Yee Tsuey Ong, Karen A. Kirby, Maxwell D. Leslie, Shinichi Oka, Eiichi N. Kodama, Lisa C. Rohan, Hiroaki Mitsuya, Michael A. Parniak, Stefan G. Sarafianos

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　57　(9)　4554-4583　2013/09

DOI： 10.1128/AAC.00283-13 　

ISSN： 0066-4804

eISSN： 1098-6596
HIV-1 Resistance Mechanism to an Electrostatically Constrained Peptide Fusion Inhibitor That Is Active against T-20-Resistant Strains Peer-reviewed

Kazuki Shimane, Kumi Kawaji, Fusako Miyamoto, Shinya Oishi, Kentaro Watanabe, Yasuko Sakagami, Nobutaka Fujii, Kazuya Shimura, Masao Matsuoka, Mitsuo Kaku, Stefan G. Sarafianos, Eiichi N. Kodama

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　57　(8)　4035-4038　2013/08

DOI： 10.1128/AAC.00237-13 　

ISSN： 0066-4804
Hypersusceptibility mechanism of Tenofovir-resistant HIV to EFdA Peer-reviewed

Eleftherios Michailidis, Emily M. Ryan, Atsuko Hachiya, Karen A. Kirby, Bruno Marchand, Maxwell D. Leslie, Andrew D. Huber, Yee T. Ong, Jacob C. Jackson, Kamalendra Singh, Eiichi N. Kodama, Hiroaki Mitsuya, Michael A. Parniak, Stefan G. Sarafianos

Retrovirology　10　(1)　doi:10.1186/1742-4690-10-65-doi:10.1186/1742-4690-10-65　2013/06/24

DOI： 10.1186/1742-4690-10-65 　

ISSN： 1742-4690
Mechanism of resistance to S138A substituted enfuvirtide and its application to peptide design Peer-reviewed

Kazuki Izumi, Kumi Kawaji, Fusasko Miyamoto, Kazuki Shimane, Kazuya Shimura, Yasuko Sakagami, Toshio Hattori, Kentaro Watanabe, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka, Mitsuo Kaku, Stefan G. Sarafianos, Eiichi N. Kodama

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY　45　(4)　908-915　2013/04

DOI： 10.1016/j.biocel.2013.01.015 　

ISSN： 1357-2725
Development of Small Molecule HIV-1 Fusion Inhibitors: Linking Biology to Chemistry Peer-reviewed

Fusako Miyamoto, Eiichi N. Kodama

CURRENT PHARMACEUTICAL DESIGN　19　(10)　1827-1834　2013/03

ISSN： 1381-6128
HIV-1 Reverse Transcriptase (RT) Polymorphism 172K Suppresses the Effect of Clinically Relevant Drug Resistance Mutations to Both Nucleoside and Non-nucleoside RT Inhibitors Peer-reviewed

Atsuko Hachiya, Bruno Marchand, Karen A. Kirby, Eleftherios Michailidis, Xiongying Tu, Krzysztof Palczewski, Yee Tsuey Ong, Zhe Li, Daniel T. Griffin, Matthew M. Schuckmann, Junko Tanuma, Shinichi Oka, Kamalendra Singh, Eiichi N. Kodama, Stefan G. Sarafianos

JOURNAL OF BIOLOGICAL CHEMISTRY　287　(35)　29988-29999　2012/08

DOI： 10.1074/jbc.M112.351551 　

ISSN： 0021-9258
A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats Peer-reviewed

Xiaoguang Li, Hua Qian, Fusako Miyamoto, Takeshi Naito, Kumi Kawaji, Kazumi Kajiwara, Toshio Hattori, Masao Matsuoka, Kentaro Watanabe, Shinya Oishi, Nobutaka Fujii, Eiichi N. Kodama

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS　424　(2)　257-261　2012/07

DOI： 10.1016/j.bbrc.2012.06.097 　

ISSN： 0006-291X
Development and application of fluorescent SDF-1 derivatives Peer-reviewed

Ryo Masuda, Shinya Oishi, Noriko Tanahara, Hiroaki Ohno, Akira Hirasawa, Gozoh Tsujimoto, Eiichi Kodama, Masao Matsuoka, Nobutaka Fujii

Future Medicinal Chemistry　4　(7)　837-844　2012/05

DOI： 10.4155/fmc.12.31 　

ISSN： 1756-8919 1756-8927
In vitro and in vivo resistance to human immunodeficiency virus type 1 entry inhibitors Peer-reviewed

Yosuke Maeda, Kazuhisa Yoshimura, Fusako Miyamoto, Eiichi Kodama, Shigeyoshi Harada, Yuzhe Yuan, Shinji Harada, Keisuke Yusa

Journal of AIDS and Clinical Research　3　(2)　2012

DOI： 10.4172/2155-6113.S2-004 　

ISSN： 2155-6113
Potent anti-HIV-1 activity of N-HR-derived peptides including a deep pocket-forming region without antagonistic effects on T-20 Peer-reviewed

Kazuki Izumi, Kentaro Watanabe, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka, Stefan G. Sarafanos, Eiichi N. Kodama

Antiviral Chemistry and Chemotherapy　22　(1)　51-55　2012

DOI： 10.3851/IMP1836 　

ISSN： 0956-3202
EFFECT OF TRANSLOCATION DEFECTIVE REVERSE TRANSCRIPTASE INHIBITORS ON THE ACTIVITY OF N348I, A CONNECTION SUBDOMAIN DRUG RESISTANT HIV-1 REVERSE TRANSCRIPTASE MUTANT Peer-reviewed

E. Michailidis, K. Singh, E. M. Ryan, A. Hachiya, Y. T. Ong, K. A. Kirby, B. Marchand, E. N. Kodama, H. Mitsuya, M. A. Parniak, S. G. Sarafianos

CELLULAR AND MOLECULAR BIOLOGY　58　(1)　187-195　2012

DOI： 10.1170/T940 　

ISSN： 0145-5680

eISSN： 1165-158X
Biochemical, inhibition and inhibitor resistance studies of xenotropic murine leukemia virus-related virus reverse transcriptase Peer-reviewed

Tanyaradzwa P. Ndongwe, Adeyemi O. Adedeji, Eleftherios Michailidis, Yee Tsuey Ong, Atsuko Hachiya, Bruno Marchand, Emily M. Ryan, Devendra K. Rai, Karen A. Kirby, Angela S. Whatley, Donald H. Burke, Marc Johnson, Shilei Ding, Yi-Min Zheng, Shan-Lu Liu, Ei-Ichi Kodama, Krista A. Delviks-Frankenberry, Vinay K. Pathak, Hiroaki Mitsuya, Michael A. Parniak, Kamalendra Singh, Stefan G. Sarafianos

NUCLEIC ACIDS RESEARCH　40　(1)　345-359　2012/01

DOI： 10.1093/nar/gkr694 　

ISSN： 0305-1048

eISSN： 1362-4962
K70Q Adds High-Level Tenofovir Resistance to "Q151M Complex" HIV Reverse Transcriptase through the Enhanced Discrimination Mechanism Peer-reviewed

Atsuko Hachiya, Eiichi N. Kodama, Matthew M. Schuckmann, Karen A. Kirby, Eleftherios Michailidis, Yasuko Sakagami, Shinichi Oka, Kamalendra Singh, Stefan G. Sarafianos

PLOS ONE　6　(1)　e16242-e16242　2011/01

DOI： 10.1371/journal.pone.0016242 　

ISSN： 1932-6203
THE SUGAR RING CONFORMATION OF 4 '-ETHYNYL-2-FLUORO-2 '-DEOXYADENOSINE AND ITS RECOGNITION BY THE POLYMERASE ACTIVE SITE OF HIV REVERSE TRANSCRIPTASE Peer-reviewed

K. A. Kirby, K. Singh, E. Michailidis, B. Marchand, E. N. Kodama, N. Ashida, H. Mitsuya, M. A. Parniak, S. G. Sarafianos

CELLULAR AND MOLECULAR BIOLOGY　57　(1)　40-46　2011

DOI： 10.1170/T900 　

ISSN： 0145-5680

eISSN： 1165-158X
Epigallocatechin gallate inhibits the HIV reverse transcription step Peer-reviewed

Shenwei Li, Toshio Hattori, Eiichi N. Kodama

Antiviral Chemistry and Chemotherapy　21　(6)　239-243　2011

DOI： 10.3851/IMP1774 　

ISSN： 0956-3202
The N348I Mutation at the Connection Subdomain of HIV-1 Reverse Transcriptase Decreases Binding to Nevirapine Peer-reviewed

Matthew M. Schuckmann, Bruno Marchand, Atsuko Hachiya, Eiichi N. Kodama, Karen A. Kirby, Kamalendra Singh, Stefan G. Sarafianos

JOURNAL OF BIOLOGICAL CHEMISTRY　285　(49)　38700-38709　2010/12

DOI： 10.1074/jbc.M110.153783 　

ISSN： 0021-9258
Resistance Profiles of Novel Electrostatically Constrained HIV-1 Fusion Inhibitors Peer-reviewed

Kazuya Shimura, Daisuke Nameki, Keiko Kajiwara, Kentaro Watanabe, Yasuko Sakagami, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka, Stefan G. Sarafianos, Eiichi N. Kodama

JOURNAL OF BIOLOGICAL CHEMISTRY　285　(50)　39471-39480　2010/12

DOI： 10.1074/jbc.M110.145789 　

ISSN： 0021-9258
Affinity selection and sequence-activity relationships of HIV-1 membrane fusion inhibitors directed at the drug-resistant variants Peer-reviewed

Shinya Oishi, Kentaro Watanabe, Saori Ito, Michinori Tanaka, Hiroki Nishikawa, Hiroaki Ohno, Kazuki Shimane, Kazuki Izumi, Yasuko Sakagami, Eiichi N. Kodama, Masao Matsuoka, Akira Asai, Nobutaka Fujii

MEDCHEMCOMM　1　(4)　276-281　2010/10

DOI： 10.1039/c0md00091d 　

ISSN： 2040-2503
Rev-derived peptides inhibit HIV-1 replication by antagonism of Rev and a co-receptor, CXCR4 Peer-reviewed

Kazuki Shimane, Eiichi N. Kodama, Ikuhiko Nakase, Shiroh Futaki, Yasuteru Sakurai, Yasuko Sakagami, Xiaoguang Li, Toshio Hattori, Stefan G. Sarafianos, Masao Matsuoka

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY　42　(9)　1482-1488　2010/09

DOI： 10.1016/j.biocel.2010.05.005 　

ISSN： 1357-2725
Characterization of HIV-1 resistance to a fusion inhibitor, N36, derived from the gp41 amino-terminal heptad repeat Peer-reviewed

Kazuki Izumi, Shota Nakamura, Hiroaki Nakano, Kazuya Shimura, Yasuko Sakagami, Shinya Oishi, Susumu Uchiyama, Tadayasu Ohkubo, Yuji Kobayashi, Nobutaka Fujii, Masao Matsuoka, Eiichi N. Kodama

ANTIVIRAL RESEARCH　87　(2)　179-186　2010/08

DOI： 10.1016/j.antiviral.2010.04.011 　

ISSN： 0166-3542
Synthesis and biological evaluation of selective CXCR4 antagonists containing alkene dipeptide isosteres Peer-reviewed

Tetsuo Narumi, Ryoko Hayashi, Kenji Tomita, Kazuya Kobayashi, Noriko Tanahara, Hiroaki Ohno, Takeshi Naito, Eiichi Kodama, Masao Matsuoka, Shinya Oishi, Nobutaka Fujii

ORGANIC & BIOMOLECULAR CHEMISTRY　8　(3)　616-621　2010

DOI： 10.1039/b917236j 　

ISSN： 1477-0520
Procyanidin B1 purified from Cinnamomi cortex suppresses hepatitis C virus replication Peer-reviewed

Shenwei Li, Eiichi N. Kodama, Yuuki Inoue, Hideki Tani, Yoshiharu Matsuura, Jing Zhang, Takashi Tanaka, Toshio Hattori

Antiviral Chemistry and Chemotherapy　20　(6)　239-248　2010

DOI： 10.3851/IMP1597 　

ISSN： 0956-3202
Binding of Multivalent Anionic Porphyrins to V3 Loop Fragments of an HIV-1 Envelope and Their Antiviral Activity Peer-reviewed

Kenji Watanabe, Shigeru Negi, Yukio Sugiura, Akiko Kiriyama, Akino Honbo, Katsumi Iga, Eiichi N. Kodama, Takeshi Naitoh, Masao Matsuoka, Koji Kano

CHEMISTRY-AN ASIAN JOURNAL　5　(4)　825-834　2010

DOI： 10.1002/asia.200900465 　

ISSN： 1861-4728

eISSN： 1861-471X
Bioorganic synthesis of a recombinant HIV-1 fusion inhibitor, SC35EK, with an N-terminal pyroglutamate capping group Peer-reviewed

Kazumi Kajiwara, Kentaro Watanabe, Rei Tokiwa, Tomoko Kurose, Hiroaki Ohno, Hiroko Tsutsumi, Yoji Hata, Kazuki Izumi, Eiichi Kodama, Masao Matsuoka, Shinya Oishi, Nobutaka Fujii

BIOORGANIC & MEDICINAL CHEMISTRY　17　(23)　7964-7970　2009/12

DOI： 10.1016/j.bmc.2009.10.017 　

ISSN： 0968-0896
Mechanism of Inhibition of HIV-1 Reverse Transcriptase by 4 '-Ethynyl-2-fluoro-2 '-deoxyadenosine Triphosphate, a Translocation-defective Reverse Transcriptase Inhibitor Peer-reviewed

Eleftherios Michailidis, Bruno Marchand, Eiichi N. Kodama, Kamlendra Singh, Masao Matsuoka, Karen A. Kirby, Emily M. Ryan, Ali M. Sawani, Eva Nagy, Noriyuki Ashida, Hiroaki Mitsuya, Michael A. Parniak, Stefan G. Sarafianos

JOURNAL OF BIOLOGICAL CHEMISTRY　284　(51)　35681-35691　2009/12

DOI： 10.1074/jbc.M109.036616 　

ISSN： 0021-9258

eISSN： 1083-351X
Bioorganic synthesis of end-capped anti-HIV peptides by simultaneous cyanocysteine-mediated cleavages of recombinant proteins Peer-reviewed

Michinori Tanaka, Kazumi Kajiwara, Rei Tokiwa, Kentaro Watanabe, Hiroaki Ohno, Hiroko Tsutsumi, Yoji Hata, Kazuki Izumi, Eiichi Kodama, Masao Matsuoka, Shinya Oishi, Nobutaka Fujii

BIOORGANIC & MEDICINAL CHEMISTRY　17　(21)　7487-7492　2009/11

DOI： 10.1016/j.bmc.2009.09.015 　

ISSN： 0968-0896
X-ray Crystallographic Study of an HIV-1 Fusion Inhibitor with the gp41 S138A Substitution Peer-reviewed

Tsuyoshi Watabe, Yukihiro Terakawa, Kentaro Watanabe, Hiroaki Ohno, Hiroaki Nakano, Toru Nakatsu, Hiroaki Kato, Kazuki Izumi, Eiichi Kodama, Masao Matsuoka, Kazuo Kitaura, Shinya Oishi, Nobutaka Fujii

JOURNAL OF MOLECULAR BIOLOGY　392　(3)　657-665　2009/09

DOI： 10.1016/j.jmb.2009.07.027 　

ISSN： 0022-2836
Design and synthesis of membrane fusion inhibitors against the feline immunodeficiency virus Peer-reviewed

Shinya Oishi, Yasuyo Kodera, Hiroki Nishikawa, Hirotaka Kamitani, Tsuyoshi Watabe, Hiroaki Ohno, Tadafumi Tochikura, Kazuki Shimane, Eiichi Kodama, Masao Matsuoka, Fuminori Mizukoshi, Hajime Tsujimoto, Nobutaka Fujii

BIOORGANIC & MEDICINAL CHEMISTRY　17　(14)　4916-4920　2009/07

DOI： 10.1016/j.bmc.2009.06.001 　

ISSN： 0968-0896

eISSN： 1464-3391
Clinical relevance of substitutions in the connection subdomain and RNase H domain of HIV-1 reverse transcriptase from a cohort of antiretroviral treatment-naive patients Peer-reviewed

Atsuko Hachiya, Kazuki Shimane, Stefan G. Sarafianos, Eiichi N. Kodama, Yasuko Sakagami, Fujie Negishi, Hirokazu Koizumi, Hiroyuki Gatanaga, Masao Matsuoka, Masafumi Takiguchi, Shinichi Oka

ANTIVIRAL RESEARCH　82　(3)　115-121　2009/06

DOI： 10.1016/j.antiviral.2009.02.189 　

ISSN： 0166-3542

eISSN： 1872-9096
Electrostatically constrained alpha-helical peptide inhibits replication of HIV-1 resistant to enfuvirtide Peer-reviewed

Hiroki Nishikawa, Shota Nakamura, Efichi Kodama, Saori Ito, Keiko Kajiwara, Kazuki Izumi, Yasuko Sakagami, Shinya Oishi, Tadayasu Ohkubo, Yuji Kobayashi, Akira Otaka, Nobutaka Fujii, Masao Matsuoka

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY　41　(4)　891-899　2009/04

DOI： 10.1016/j.biocel.2008.08.039 　

ISSN： 1357-2725
Synonymous mutations in stem-loop III of Rev responsive elements enhance HIV-1 replication impaired by primary mutations for resistance to enfuvirtide Peer-reviewed

Mariko Ueno, Eiichi N. Kodama, Kazuya Shimura, Yasuteru Sakurai, Keiko Kajiwara, Yasuko Sakagami, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka

ANTIVIRAL RESEARCH　82　(1)　67-72　2009/04

DOI： 10.1016/j.antiviral.2009.02.002 　

ISSN： 0166-3542
Elvitegravir: a new HIV integrase inhibitor. Peer-reviewed

Shimura Kazuya, Kodama Eiichi N

Antivir Chem Chemother　20　(2)　79-85　2009/04

DOI： 10.3851/IMP1397 　
SC29EK, a Peptide Fusion Inhibitor with Enhanced alpha-Helicity, Inhibits Replication of Human Immunodeficiency Virus Type 1 Mutants Resistant to Enfuvirtide Peer-reviewed

Takeshi Naito, Kazuki Izumi, Eiichi Kodama, Yasuko Sakagami, Keiko Kajiwara, Hiroki Nishikawa, Kentaro Watanabe, Stefan G. Sarafianos, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　53　(3)　1013-1018　2009/03

DOI： 10.1128/AAC.01211-08 　

ISSN： 0066-4804
Design of Peptide-based Inhibitors for Human Immunodeficiency Virus Type 1 Strains Resistant to T-20 Peer-reviewed

Kazuki Izumi, Eiichi Kodama, Kazuya Shimura, Yasuko Sakagami, Kentaro Watanabe, Saori Ito, Tsuyoshi Watabe, Yukihiro Terakawa, Hiroki Nishikawa, Stefan G. Sarafianos, Kazuo Kitaura, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka

JOURNAL OF BIOLOGICAL CHEMISTRY　284　(8)　4914-4920　2009/02

DOI： 10.1074/jbc.M807169200 　

ISSN： 0021-9258
Development of a novel fusion inhibitor against T-20-resistant HIV-1. Peer-reviewed

Oishi S, Ito S, Nishikawa H, Tanaka M, Ohno H, Otaka A, Izumi K, Kodama E, Matsuoka M, Fujii N

Advances in experimental medicine and biology　611　389-391　2009

DOI： 10.1007/978-0-387-73657-0_170 　

ISSN： 0065-2598
Peptide bond mimicry by (E)-alkene and (Z)-fluoroalkene peptide isosteres: synthesis and bioevaluation of alpha-helical anti-HIV peptide analogues Peer-reviewed

Shinya Oishi, Hirotaka Kamitani, Yasuyo Kodera, Kentaro Watanabe, Kazuya Kobayashi, Tetsuo Narumi, Kenji Tomita, Hiroaki Ohno, Takeshi Naito, Eiichi Kodama, Masao Matsuoka, Nobutaka Fujii

ORGANIC & BIOMOLECULAR CHEMISTRY　7　(14)　2872-2877　2009

DOI： 10.1039/b907983a 　

ISSN： 1477-0520
Novel screening systems for HIV-1 fusion mediated by two extra-virion heptad repeats of gp41 Peer-reviewed

Hiroki Nishikawa, Eiichi Kodama, Ayako Sakakibara, Ayako Fukudome, Kazuki Izumi, Shinya Oishi, Nobutaka Fujii, Masao Matsuoka

ANTIVIRAL RESEARCH　80　(1)　71-76　2008/10

DOI： 10.1016/j.antiviral.2008.05.006 　

ISSN： 0166-3542
Identification of minimal sequence for HIV-1 fusion inhibitors Peer-reviewed

Hiroki Nishikawa, Shinya Oishi, Mizuno Fujita, Kentaro Watanabe, Rei Tokiwa, Hiroaki Ohno, Eiichi Kodama, Kazuki Izumi, Keiko Kajiwara, Takeshi Naitoh, Masao Matsuoka, Akira Otaka, Nobutaka Fujii

BIOORGANIC & MEDICINAL CHEMISTRY　16　(20)　9184-9187　2008/10

DOI： 10.1016/j.bmc.2008.09.018 　

ISSN： 0968-0896
Identification of novel non-peptide CXCR4 antagonists by ligand-based design approach Peer-reviewed

Satoshi Ueda, Manabu Kato, Shinsuke Inuki, Hiroaki Ohno, Barry Evans, Zi-xuan Wang, Stephen C. Peiper, Kazuki Izumi, Eiichi Kodama, Masao Matsuoka, Hideko Nagasawa, Shinya Oishi, Nobutaka Fujii

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　18　(14)　4124-4129　2008/07

DOI： 10.1016/j.bmcl.2008.05.092 　

ISSN： 0960-894X
Novel inhibition mechanism and potent activity of trans location-deficient reverse transcriptase inhibitors Peer-reviewed

Michailidis Lefteris, Marchand Bruno, Kodama Ei-Ichi, Fopoussi Amelie, Olga Mafotsing, Sawani Ali, Ryan Emilie, Eisele Nicholas, Matsuoka Masao, Ashida Noriyuki, Nagy Eva, Parniak Michael, Mitsuya Hiroaki, Sarafianos Stefan

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES　12　S24-S25　2008/06

DOI： 10.1016/S1201-9712(08)60058-2 　

ISSN： 1201-9712
Synthesis and application of fluorescein- and biotin-labeled molecular probes for the chemokine receptor CXCR4 Peer-reviewed

Shinya Oishi, Ryo Masuda, Barry Evans, Satoshi Ueda, Yukiko Goto, Hiroaki Ohno, Akira Hirasawa, Gozoh Tsujimoto, Zixuan Wang, Stephen C. Peiper, Takeshi Naito, Eiichi Kodama, Masao Matsuoka, Nobutaka Fujii

CHEMBIOCHEM　9　(7)　1154-1158　2008/05

DOI： 10.1002/cbic.200700761 　

ISSN： 1439-4227
Amino acid mutation N348I in the connection subdomain of human immunodeficiency virus type 1 reverse transcriptase confers multiclass resistance to nucleoside and nonnucleoside reverse transcriptase inhibitors Peer-reviewed

Atsuko Hachiya, Eiichi N. Kodama, Stefan G. Sarafianos, Matthew M. Schuckmann, Yasuko Sakagami, Masao Matsuoka, Masafumi Takiguchi, Hiroyuki Gatanaga, Shinichi Oka

JOURNAL OF VIROLOGY　82　(7)　3261-3270　2008/04

DOI： 10.1128/JVI.01154-07 　

ISSN： 0022-538X
Dual-reporter phenotypic assay for human immunodeficiency viruses Peer-reviewed

Keiko Kajiwara, Eiichi Kodama, Yasuko Sakagami, Takeshi Naito, Masao Matsuoka

JOURNAL OF CLINICAL MICROBIOLOGY　46　(2)　792-795　2008/02

DOI： 10.1128/JCM.01470-07 　

ISSN： 0095-1137
Design of a novel HIV-1 fusion inhibitor that displays a minimal interface for binding affinity Peer-reviewed

Shinya Oishi, Saori Ito, Hiroki Nishikawa, Kentaro Watanabe, Michinori Tanaka, Hiroaki Ohno, Kazuki Izumi, Yasuko Sakagami, Eiichi Kodama, Masao Matsuoka, Nobutaka Fujii

JOURNAL OF MEDICINAL CHEMISTRY　51　(3)　388-391　2008/02

DOI： 10.1021/jm701109d 　

ISSN： 0022-2623
Broad Antiretroviral activity and resistance profile of the novel human immunodeficiency virus integrase inhibitor elvitegravir (JTK-303/GS-9137) Peer-reviewed

Kazuya Shimura, Eiichi Kodama, Yasuko Sakagami, Yuji Matsuzaki, Wataru Watanabe, Kazunobu Yamataka, Yasuo Watanabe, Yoshitsugu Ohata, Satoki Doi, Motohide Sato, Mitsuki Kano, Satoru Ikeda, Masao Matsuoka

JOURNAL OF VIROLOGY　82　(2)　764-774　2008/01

DOI： 10.1128/JVI.01534-07 　

ISSN： 0022-538X

eISSN： 1098-5514
Heptad repeat-derived peptides block protease-mediated direct entry from the cell surface of severe acute respiratory syndrome coronavirus but not entry via the endosomal pathway Peer-reviewed

Makoto Ujike, Hiroki Nishikawa, Akira Otaka, Naoki Yamamoto, Norio Yamamoto, Masao Matsuoka, Eiichi Kodama, Nobutaka Fujii, Fumihiro Taguchi

JOURNAL OF VIROLOGY　82　(1)　588-592　2008/01

DOI： 10.1128/JVI.01697-07 　

ISSN： 0022-538X
Binding modes of two novel non-nucleoside reverse transcriptase inhibitors, YM-215389 and YM-228855, to HIV type-1 reverse transcriptase Peer-reviewed

Eiichi Kodoma, Masaya Orita, Naoyuki Masuda, Osamu Yamamoto, Masahiro Fujii, Tetsuro Ohgami, Shunji Kageyama, Mitsuaki Ohta, Toshifumi Hatta, Hiroshi Inoue, Hiroshi Suzuki, Kenji Sudo, Yasuaki Shimizu, Masao Matsuoka

Antiviral Chemistry and Chemotherapy　19　(3)　133-141　2008

ISSN： 0956-3202
2 '-deoxy-4 '-C-ethynyl-2-halo-adenosines active against drug-resistant human immunodeficiency virus type 1 variants Peer-reviewed

Atsushi Kawamoto, Eiichi Kodama, Stefan G. Sarafianos, Yasuko Sakagami, Satoru Kohgo, Kenji Kitano, Noriyuki Ashida, Yuko Iwai, Hiroyuki Hayakawa, Hirotomo Nakata, Hiroaki Mitsuya, Eddy Arnold, Masao Matsuoka

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY　40　(11)　2410-2420　2008

DOI： 10.1016/j.biocel.2008.04.007 　

ISSN： 1357-2725
Activity against human immunodeficiency virus type 1, intracellular metabolism, and effects on human DNA Polymerases of 4 '-ethynyl-2-fluoro-2 '-deoxyadenosine Peer-reviewed

Hirotorao Nakata, Masayuki Amano, Yasuhiro Koh, Eiichi Kodama, Guangwei Yang, Christopher M. Bailey, Satoru Kohgo, Hiroyuki Hayakawa, Masao Matsuoka, Karen S. Anderson, Yung-Chi Cheng, Hiroaki Mitsuya

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　51　(8)　2701-2708　2007/08

DOI： 10.1128/AAC.00277-07 　

ISSN： 0066-4804
2 '-deoxy-4 '-C-ethynyl-2-fluoroadenosine: A nucleoside reverse transcriptase inhibitor with highly potent activity against wide spectrum of hiv-1 strains, favorable toxic profiles, and stability in plasma Peer-reviewed

Hiroshi Ohrui, Satoru Kohgo, Hiroyuki Hayakawa, Eiichi Kodama, Masao Matsuoka, Tomohiro Nakata, Hiroaki Mitsuya

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS　26　(10-12)　1543-1546　2007

DOI： 10.1080/15257770701545218 　

ISSN： 1525-7770
A high collusion-resistant approach to distributed privacy-preserving data mining. Peer-reviewed

Shintaro Urabe, Jiahong Wang, Eiichiro Kodama, Toyoo Takata

Proceedings of the IASTED International Conference on Parallel and Distributed Computing and Networks, as part of the 25th IASTED International Multi-Conference on Applied Informatics, February 13-15 2007, Innsbruck, Austria　307-312　2007
Publisher: IASTED/ACTA Press
Structural basis for the interaction of CCR5 with a small molecule, functionally selective CCRS agonist Peer-reviewed

Yuji Saita, Eiichi Kodama, Masaya Orita, Mitsuhiro Kondo, Takahiro Miyazaki, Kenji Sudo, Keiko Kajiwara, Masao Matsuoka, Yasuaki Shimizu

JOURNAL OF IMMUNOLOGY　177　(5)　3116-3122　2006/09

ISSN： 0022-1767

eISSN： 1550-6606
P-39 2'-DEXY-4'-C-ETHYNYL-2-FLUOROADENOSINE, A NRTI THAT COULD BE AN IDEAL DRUG FOR BOTH HIV-AND HBV-INFECTIONS

Ohrui Hiroshi, Kohgo Satoru, Hayakawa Hiroyuki, Kodama Eiichi, Matsuoka Masao, Mitsuya Hiroaki

International Symposium on the Chemistry of Natural Products　2006　"P-39"　2006/07/23
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/intnaturalprod.2006.0__P-39_ 　
2'-Deoxy-4'-C-ethynyl-2-fluoroadenosine: a nucleoside reverse transcriptase inhibitor with highly potent activity against all HIV-1 strains, favorable toxic profiles and stability in plasma. Peer-reviewed

Ohrui Hiroshi, Kohgo Satoru, Hayakawa Hiroyuki, Kodama Eiichi, Matsuoka Masao, Nakata Tomohiro, Mitsuya Hiroyuki

Nucleic Acids Symp Ser (Oxf)　(50)　1-2　2006/04

DOI： 10.1093/nass/nrl001 　
Novel HIV-1 integrase inhibitors derived from quinolone antibiotics Invited Peer-reviewed

M Sato, T Motomura, H Aramaki, T Matsuda, M Yamashita, Y Ito, H Kawakami, Y Matsuzaki, W Watanabe, K Yamataka, S Ikeda, E Kodama, M Matsuoka, H Shinkai

JOURNAL OF MEDICINAL CHEMISTRY　49　(5)　1506-1508　2006/03

DOI： 10.1021/jm0600139 　

ISSN： 0022-2623
Creation of low toxic reverse-transcriptase inhibitory nucleosides that prevent the emergence of drug-resistant HIV variants Peer-reviewed

Hiroshi Ohrui, Hiroyuki Hayakawa, Satoru Kohgo, Masao Matsuoka, Eiichi Kodama, Hiroaki Mitsuya

Yuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry　64　(7)　716-723　2006
Publisher: Society of Synthetic Organic Chemistry
DOI： 10.5059/yukigoseikyokaishi.64.716 　

ISSN： 0037-9980
A novel colorimetric assay for CXCR4 and CCR5 tropic human immunodeficiency viruses Peer-reviewed

Keiko Kajiwara, Eiichi Kodama, Masao Matsuoka

Antiviral Chemistry and Chemotherapy　17　(4)　215-223　2006
Publisher: International Medical Press Ltd
DOI： 10.1177/095632020601700405 　

ISSN： 0956-3202
A Scalable Sequential Pattern Mining Algorithm. Peer-reviewed

Jiahong Wang, Yoshiaki Asanuma, Eiichiro Kodama, Toyoo Takata

2006 IEEE/ACS International Conference on Computer Systems and Applications (AICCSA 2006), March 8-11, Dubai/Sharjah, UAE　437-444　2006
Publisher: IEEE Computer Society
DOI： 10.1109/AICCSA.2006.205128 　
Halogenated thymidine analogues restore the expression of silenced genes without demethylation Peer-reviewed

J Fan, E Kodama, Y Koh, N Nakao, M Matsuoka

CANCER RESEARCH　65　(15)　6927-6933　2005/08

DOI： 10.1158/0008-5472.CAN-04-3495 　

ISSN： 0008-5472
RNase S complex bearing arginine-rich peptide and anti-HIV activity Peer-reviewed

S Futaki, Nakase, I, T Suzuki, D Nameki, EI Kodama, M Matsuoka, Y Sugiura

JOURNAL OF MOLECULAR RECOGNITION　18　(2)　169-174　2005/03

DOI： 10.1002/jmr.725 　

ISSN： 0952-3499
Mutations conferring resistance to human immunodeficiency virus type 1 fusion inhibitors are restricted by gp41 and Rev-responsive element functions Peer-reviewed

Daisuke Nameki, Eiichi Kodama, Mieko Ikeuchi, Naoto Mabuchi, Akira Otaka, Hirokazu Tamamura, Mutsuhito Ohno, Nobutaka Fujii, Masao Matsuoka

Journal of Virology　79　(2)　764-770　2005/01

DOI： 10.1128/JVI.79.2.764-770.2005 　

ISSN： 0022-538X
Mutations conferring resistance to human immunodeficiency virus type 1 fusion inhibitors are restricted by gp4l and rev-responsive element functions Peer-reviewed

D Nameki, E Kodama, M Ikeuchi, N Mabuchi, A Otaka, H Tamamura, M Ohno, N Fujii, M Matsuoka

JOURNAL OF VIROLOGY　79　(2)　764-770　2005/01

DOI： 10.1128/JVI.79.2.764-770.2005 　

ISSN： 0022-538X
Studies of nonnueleoside HIV-1 reverse transcriptase inhibitors. Part 1: Design and synthesis of thiazolidenebenzenesulfonamides Peer-reviewed

N Masuda, O Yamamoto, M Fujii, T Ohgami, J Fujiyasua, T Kontani, A Moritomo, M Orita, H Kurihara, H Koga, H Nakahara, S Kageyama, M Ohta, H Inoue, T Hatta, H Suzuki, K Sudo, Y Shimizu, E Kodama, M Matsuoka, M Fujiwara, T Yokota, S Shigeta, M Baba

BIOORGANIC & MEDICINAL CHEMISTRY　12　(23)　6171-6182　2004/12

DOI： 10.1016/j.bmc.2004.08.050 　

ISSN： 0968-0896
Novel patterns of nevirapine resistance-associated mutations of human immunodeficiency virus type 1 in treatment-naive patients Peer-reviewed

A Hachiya, H Gatanaga, E Kodama, M Ikeuchi, M Matsuoka, S Harada, H Mitsuya, S Kimura, S Oka

VIROLOGY　327　(2)　215-224　2004/10

DOI： 10.1016/j.virol.2004.07.001 　

ISSN： 0042-6822
Design, efficient synthesis, and anti-HIV activity of 4 '-C-cyano- and 4 '-C-ethynyl-2 '-deoxy purine nucleosides Peer-reviewed

S Kohgo, K Yamada, K Kitano, Y Iwai, S Sakata, N Ashida, H Hayakawa, D Nameki, E Kodama, M Matsuoka, H Mitsuya, H Ohrui

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS　23　(4)　671-690　2004/04

DOI： 10.1081/NCN-120037508 　

ISSN： 1525-7770
Application of oligoarginine for the delivery of protein complexes into living cells Peer-reviewed

Futaki Shiroh, Nakase Ikuhiko, Niwa Miki, Suzuki Tomoki, Nameki Daisuke, Kodama Ei-ichi, Matsuoka Masao, Sugiura Yukio

Peptide Revolution: Genomics, Proteomics & Therapeutics　791-792　2004
Attempt to reduce cytotoxicity by synthesizing the L-enantiomer of 4′-C-ethynyl-2′-deoxypurine nucleosides as antiviral agents against HIV and HBV Peer-reviewed

Kenji Kitano, Satoru Kohgo, Kohei Yamada, Shinji Sakata, Noriyuki Ashida, Hiroyuki Hayakawa, Daisuke Nameki, Eiichi Kodama, Masao Matsuoka, Hiroaki Mitsuya, Hiroshi Ohrui

Antiviral Chemistry and Chemotherapy　15　(3)　161-167　2004
Publisher: International Medical Press Ltd
DOI： 10.1177/095632020401500306 　

ISSN： 0956-3202
Broad spectrum anti-RNA virus activities of titanium and vanadium substituted polyoxotungstates Peer-reviewed

S Shigeta, S Mori, E Kodama, J Kodama, K Takahashi, T Yamase

ANTIVIRAL RESEARCH　58　(3)　265-271　2003/05

DOI： 10.1016/S0166-3542(03)00009-3 　

ISSN： 0166-3542
Development of Fusion-inhibiting Anti-HIV-1 Peptides Based on the Structure of Molecular Complex Involved in HIV-1-cell Fusion Peer-reviewed

Akira Otaka, Miki Nakamura, Eiichi Kodama, Syota Nakamura, Hiroaki Nakano, Susumu Uchiyama, Hirokazu Tamamura, Masao Matsuoka, Yuji Kobayashi, Nobutaka Fujii

Peptide Science 2002　Vol.2002　(No.0)　65-68　2003/02/01

ISSN： 1344-7661
Synthesis of 4'-C-ethynyl and 4'-C-cyano purine nucleosides from natural nucleosides and their anti-HIV activity Peer-reviewed

S Kohgo, K Yamada, K Kitano, S Sakata, H Hayakawa, D Nameki, E Kodama, M Matsuoka, H Mitsuya, H Ohrui

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS　22　(5-8)　887-889　2003

DOI： 10.1081/NCN-120022678 　

ISSN： 1525-7770
Assuring interoperability in heterogeneous, autonomous and decentralized multi-agent systems Peer-reviewed

H Suguri, E Kodama, M Miyazaki

ISADS 2003: SIXTH INTERNATIONAL SYMPOSIUM ON AUTONOMOUS DECENTRALIZED SYSTEMS, PROCEEDINGS　17-24　2003

DOI： 10.1109/ISADS.2003.1193928 　
Design and Synthesis of Highly Active Anti-HIV Peptide Based on gp41-C34 Peptide Peer-reviewed

Miki Nakamura, Akira Otaka, Eiichi Kodama, Masao Matsuoka, Susumu Uchiyama, Syota Nakamura, Yuji Kobayashi, Hirokazu Tamamura, Nobutaka Fujii

Peptide Science 2001　Vol.2001　(No.0)　73-76　2002/03/01

ISSN： 1344-7661
Artificial Remodeling of gp41-C34 Peptide Leads to Effective HIV Fusion Inhibitor with High anti-HIV Activity Peer-reviewed

Akira Otaka, Miki Nakamura, Eiichi Kodama, Susumu Uchiyama, Hirokazu Tamamura, Yuji Kobayashi, Masao Matsuoka, Nobutaka Fujii

Peptide 2002　838-839　2002
Remodeling of gp41-C34 peptide leads to highly effective inhibitors of the fusion of HIV-1 with target cells Peer-reviewed

A Otaka, M Nakamura, D Nameki, E Kodama, S Uchiyama, S Nakamura, H Nakano, H Tamamura, Y Kobayashi, M Matsuoka, N Fujii

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION　41　(16)　2938-2940　2002

DOI： 10.1002/1521-3773(20020816)41:16<2937::AID-ANIE2937>3.0.CO;2-J 　

ISSN： 1433-7851
Assuring interoperability between heterogeneous multi-agent systems with a gateway agent Peer-reviewed

H Suguri, E Kodama, M Miyazaki, Kaji, I

7TH IEEE INTERNATIONAL SYMPOSIUM ON HIGH ASSURANCE SYSTEMS ENGINEERING, PROCEEDINGS　167-170　2002

DOI： 10.1109/HASE.2002.1173118 　
Development of specific CXCR4 inhibitors possessing high selectivity indexes as well as complete stability in serum based on an anti-HIV peptide T140 Peer-reviewed

H Tamamura, A Omagari, K Hiramatsu, K Gotoh, T Kanamoto, YN Xu, E Kodama, M Matsuoka, T Hattori, N Yamamoto, H Nakashima, A Otaka, N Fujii

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS　11　(14)　1897-1902　2001/07

DOI： 10.1016/S0960-894X(01)00323-7 　

ISSN： 0960-894X
4 '-ethynyl nucleoside analogs: Potent inhibitors of multidrug-resistant human immunodeficiency virus variants in vitro Peer-reviewed

EI Kodama, S Kohgo, K Kitano, H Machida, H Gatanaga, S Shigeta, M Matsuoka, H Ohrui, H Mitsuya

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　45　(5)　1539-1546　2001/05

DOI： 10.1128/AAC.45.5.1539-1546.2001 　

ISSN： 0066-4804
4′-Ethynyl nucleoside analogues: Potent inhibitors active against multi-drug-resistant HIV variants Peer-reviewed

E. Kodama, M. Matsuoka, H. Ohrui, H. Mitsuya

International Antiviral News　9　(8)　128-132　2001
Syntheses of 4 '-C-ethynyl-beta-D-arabino- and 4'-C-ethynyl-2'-deoxy-beta-D-ribo-pentofuranosylpyrimidines and -purines and evaluation of their anti-HIV activity Peer-reviewed

H Ohrui, S Kohgo, K Kitano, S Sakata, E Kodama, K Yoshimura, M Matsuoka, S Shigeta, H Mitsuya

JOURNAL OF MEDICINAL CHEMISTRY　43　(23)　4516-4525　2000/11

DOI： 10.1021/jm000209n 　

ISSN： 0022-2623
140(P-96) Development of Nucleosides Highly Potent Against Multi-drug Resistant HIV

Kohgo Satoru, Ohrui Hiroshi, Kitano Kenji, Kodama Eiichi, Mitsuya Hiroaki

Symposium on the Chemistry of Natural Products, symposium papers　(42)　835-840　2000/10/01
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.42.0_835 　

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4'-C-Ethynyl-β-D-arabino- and 4'-C-ethyny1-2'-deoxy-β-D-ribo-pentofuranosyl pyrimidine and purine nucleosides were synthesized, and evaluated for their in vitro anti-HIV activity. The key intermediate, 4-C-ethynyl or 4-C-triethylsilylethynyl-α-D-ribo-pentofuranose, was prepared from D-glucose and glycosidated with various pyrimidine or purine bases. The arabino pyrimidine derivatives were prepared from the corresponding ribo derivatives via O^2-2'-cyclonucleosides. The 2'-deoxyribo derivatives were synthesized by radical reduction of 2'-bromo or 2'-phenoxythio-carbonyloxy nucleosides. These 4'-C-ethynyl nucleosides were proved to be potent against HIV-1 in vitro with EC_<50> values ranging 0.0003 to 0.61μM. These compounds also exerted an activity against multi-dideoxynucleoside-resistant HIV-1 strains with comparable EC_<50> values.
Interactions of conformationally biased north and south 2 '-fluoro-2 ',3 '-dideoxynucleoside 5 '-triphosphates with the active site of HIV-1 reverse transcriptase Peer-reviewed

L Mu, SG Sarafianos, MC Nicklaus, P Russ, MA Siddiqui, H Ford, H Mitsuya, R Le, E Kodama, C Meier, T Knispel, L Anderson, JJ Barchi, VE Marquez

BIOCHEMISTRY　39　(37)　11205-11215　2000/09

DOI： 10.1021/bi001090n 　

ISSN： 0006-2960
Synthesis of 4'-ethynyl-purine nucleosides possessing anti-HIV activity. Peer-reviewed

Kitano K, Sakata S, Kohgo S, Matsuoka M, Kodama E, Mitsuya H, Ohrui H

Nucleic Acids Symp Ser　(44)　105-106　2000/04
Antileukemic activity and mechanism of action of cordycepin against terminal deoxynucleotidyl transferase-positive (TdT(+)) leukemic cells Peer-reviewed

EN Kodama, RP McCaffrey, K Yusa, H Mitsuya

BIOCHEMICAL PHARMACOLOGY　59　(3)　273-281　2000/02

DOI： 10.1016/S0006-2952(99)00325-1 　

ISSN： 0006-2952
Natural language programming for multimedia information Peer-reviewed

E Kodama, K Sato, M Miyazaki

SEVENTH INTERNATIONAL CONFERENCE ON PARALLEL AND DISTRIBUTED SYSTEMS: WORKSHOPS, PROCEEDINGS　167-172　2000

DOI： 10.1109/PADSW.2000.884533 　
Characterization of human immunodeficiency virus type 1 strains resistant to the non-nucleoside reverse transcriptase inhibitor RD4-2217 Peer-reviewed

M Fujiwara, EN Kodama, M Okamoto, K Tokuhisa, T Ide, Y Hanasaki, K Katsuura, H Takayama, N Aimi, H Mitsuya, S Shigeta, K Konno, T Yokota, M Baba

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY　10　(6)　315-320　1999/11

ISSN： 0956-3202
In vitro induction of human immunodeficiency virus type 1 variants resistant to phosphoralaninate prodrugs of Z-methylenecyclopropane nucleoside analogues Peer-reviewed

K Yoshimura, R Feldman, E Kodama, MF Kavlick, YL Qiu, J Zemlicka, H Mitsuya

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　43　(10)　2479-2483　1999/10

ISSN： 0066-4804
Significance of endogenous heat shock protein in adjuvant arthritis Peer-reviewed

M Miyata, H Sato, H Sato, Y Sato, E Kodama, R Kasukawa

JOURNAL OF RHEUMATOLOGY　26　(10)　2210-2214　1999/10

ISSN： 0315-162X
Anti-herpesvirus activities and cytotoxicities of 2-thiopyrimidine nucleoside analogues in vitro Peer-reviewed

S Shigeta, S Mori, T Kira, K Takahashi, E Kodama, K Konno, T Nagata, H Kato, T Wakayama, N Koike, M Saneyoshi

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY　10　(4)　195-209　1999/07

DOI： 10.1177/095632029901000404 　

ISSN： 0956-3202
In vitro anti-human immunodeficiency virus activities of Z- and E-methylenecyclopropane nucleoside analogues and their phosphoro-L-alaninate diesters Peer-reviewed

H Uchida, EN Kodama, K Yoshimura, Y Maeda, P Kosalaraksa, Maroun, V, YL Qiu, J Zemlicka, H Mitsuya

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY　43　(6)　1487-1490　1999/06

ISSN： 0066-4804
Synthesis of 4'-substituted nucleosides and their biological evaluation. Peer-reviewed

Kohgo S, Kodama E, Shigeta S, Saneyoshi M, Machida H, Ohrui H

Nucleic Acids Symp Ser　(42)　127-128　1999/04
Inhibition of human immunodeficiency virus replication by RD6-Y664, a novel benzylhydroxylamine derivative Peer-reviewed

M Okamoto, M Fujiwara, E Kodama, O Yamamoto, S Shigeta, H Mitsuya, K Konno, T Yokota, M Baba

ANTIVIRAL CHEMISTRY & CHEMOTHERAPY　10　(2)　71-77　1999/03

ISSN： 0956-3202
Marine microalgal polysaccharide induces apoptosis in human lymphoid cells Peer-reviewed

K Sogawa, E Kodama, M Matsuda, S Shigeta, K Okutani

JOURNAL OF MARINE BIOTECHNOLOGY　6　(1)　35-38　1998

ISSN： 0941-2905
Application of a gastric cancer cell line (MKN-28) for anti-adenovirus screening using the MTT method Peer-reviewed

E Kodama, S Shigeta, T Suzuki, E DeClercq

ANTIVIRAL RESEARCH　31　(3)　159-164　1996/07

DOI： 10.1016/0166-3542(96)06966-5 　

ISSN： 0166-3542
Evaluation of antiherpetic compounds using a gastric cancer cell line: Pronounced activity of BVDU against herpes simplex virus replication Peer-reviewed

E Kodama, A Igarashi, S Mori, KI Hashimoto, T Suzuki, E DeClercq, S Shigeta

MICROBIOLOGY AND IMMUNOLOGY　40　(5)　359-363　1996

ISSN： 0385-5600
Antiviral activity of a sulphated polysaccharide extracted from the marine Pseudomonas and marine plant Dinoflagellata against human immunodeficiency viruses and other enveloped viruses Peer-reviewed

K. Hashimoto, E. Kodama, S. Mori, J. Watanabe, M. Baba, K. Okutani, M. Matsuda, S. Shigeta

Antiviral Chemistry and Chemotherapy　7　(4)　189-196　1996
Publisher: International Medical Press Ltd
DOI： 10.1177/095632029600700403 　

ISSN： 0956-3202
Analysis of human 65 kD heat shock protein mRNA using polymerase chain reaction in synovia of rheumatoid arthritis patients. Peer-reviewed

Kodama E, Kasukawa R, Miyata M, Shigeta S, Ito M

Fukushima J Med Sci　41　(2)　95-102　1995/12
Publisher: Fukushima Medical University
ISSN： 0016-2590
DETECTION OF ANTIBODIES TO 65 KD HEAT-SHOCK PROTEIN AND TO HUMAN SUPEROXIDE-DISMUTASE IN AUTOIMMUNE HEPATITIS-MOLECULAR MIMICRY BETWEEN 65 KD HEAT-SHOCK PROTEIN AND SUPEROXIDE-DISMUTASE Peer-reviewed

M MIYATA, A KOGURE, H SATO, E KODAMA, H WATANABE, H OHIRA, M KURODA, T TAKAGI, Y SATO, R KASUKAWA

CLINICAL RHEUMATOLOGY　14　(6)　673-677　1995/11

ISSN： 0770-3198
ANALYSIS OF MUTATIONS IN THE THYMIDINE KINASE GENE OF VARICELLA TESTER VIRUS-ASSOCIATED WITH RESISTANCE TO 5-IODO-2'-DEOXYURIDINE AND 5-BROMO-2'-DEOXYURIDINE Peer-reviewed

E KODAMA, S MORI, S SHIGETA

ANTIVIRAL RESEARCH　27　(1-2)　165-170　1995/05

DOI： 10.1016/0166-3542(94)00077-L 　

ISSN： 0166-3542
ANTIBODIES TO 65KD HEAT-SHOCK PROTEIN WERE ELEVATED TO RHEUMATOID-ARTHRITIS Peer-reviewed

A ODA, M MIYATA, E KODAMA, H SATOH, Y SATO, T NISHIMAKI, H NOMAGUCHI, R KASUKAWA

CLINICAL RHEUMATOLOGY　13　(2)　261-264　1994/06

ISSN： 0770-3198
DETECTION OF HEPATITIS-C VIRUS GENOME IN HUMAN SERUM BY MULTITARGETED POLYMERASE CHAIN-REACTION Peer-reviewed

M OKAMOTO, M BABA, E KODAMA, K SEKINE, T TAKAGI, R KASUKAWA, S SHIGETA

JOURNAL OF MEDICAL VIROLOGY　41　(1)　6-10　1993/09

DOI： 10.1002/jmv.1890410103 　

ISSN： 0146-6615
A case report of transverse myelopathy associated with systemic lupus erythematosus with positive antiphospholipid antibody Peer-reviewed

Hiroshi Watanabe, Hironobu Ochiai, Eiichi Kodama, Shuzoh Suzuki, Isao Takeda, Noriya Watanabe, Shigeaki One, Shunji Kaise, Tomoe Nishimaki, Reiji Kasukawa

Japanese Journal of Clinical Immunology　15　(4)　385-390　1992

DOI： 10.2177/jsci.15.385 　

ISSN： 1349-7413 0911-4300

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Novel Design Strategy of DNA-Artificial Nucleic Acid Chimera Toward Enhancement of Target RNA Cleavage Activities: Modification Effects of DNA Moiety upon Complex Stabilities and Activity

石渡望, 稲垣雅仁, 西嶋政樹, 林宏典, 荒木保幸, 児玉栄一, 和田健彦

日本化学会春季年会講演予稿集(Web)　103rd　2023
Novel Design Strategy of DNA-Artificial Nucleic Acid Chimera Toward Enhancement of Target RNA Cleavage Activities: Application for COVID-19 Therapeutics

石渡望, 藤田一寿, 堀内結翔, 林宏典, 稲垣雅仁, 稲垣雅仁, 西嶋政樹, 荒木保幸, 児玉栄一, 和田健彦

日本核酸医薬学会年会講演要旨集(CD-ROM)　7th　2022
Structure-based design and optimization of novel measles virus fusion inhibitors

山口夕貴, 高原葵, 青木啓輔, 青木啓輔, 中津亨, 中津亨, 平田和成, 鈴木聡志, 林宏典, 河治久実, 井貫晋輔, 大野浩章, 加藤博章, 村山和隆, 児玉栄一, 大石真也, 大石真也

メディシナルケミストリーシンポジウム講演要旨集　39th (CD-ROM)　2022

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大規模自然災害の被災地における感染制御支援マニュアル2021

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日本環境感染学会誌　36　(5)　i,S1,np1-S173,np1　2021/09
Publisher: (一社)日本環境感染学会
ISSN： 1882-532X

eISSN： 1883-2407
令和パンデミックの今、大正パンデミックを計量書誌学的に考察する

三木康宏, 中鉢奈津子, 川内淳史, 児玉栄一, 伊藤潔

日本生殖内分泌学会雑誌　26　36-38　2021/08
Publisher: 日本生殖内分泌学会
ISSN： 1348-8031
新型コロナウイルス感染症(COVID-19)の第1報から1年半

児玉栄一

宮城県医師会報　(905)　379-380　2021/06
Publisher: (公社)宮城県医師会
腸内常在菌が宿主粘膜恒常性に与える影響

大久朋子, 工藤逸美, 江口修平, 岡健太郎, 高橋志達, 賀来満夫, 児玉栄一

日本臨床腸内微生物学会誌　23　(1)　77-77　2021/06
Publisher: 日本臨床腸内微生物学会
令和パンデミックの今、大正パンデミックを計量書誌学的に考察する

三木康宏, 中鉢奈津子, 川内淳史, 児玉栄一, 伊藤潔

日本内分泌学会雑誌　96　(4)　1065-1065　2021/04
Publisher: (一社)日本内分泌学会
ISSN： 0029-0661

eISSN： 2186-506X
災害時の業務継続に向けて取り組むべき対策熊本地震による病院被害と診療体制への影響の分析

伊山聡子, 前田ひとみ, 松本智晴, 南家貴美代, 児玉栄一

日本看護研究学会雑誌　43　(4)　769-777　2020/09
Publisher: (一社)日本看護研究学会
ISSN： 0285-9262

eISSN： 2189-6100
成人ヒトボカウイルス関連肺炎の2例

矢島剛洋, 佐藤幸佑, 神宮大輔, 生方智, 庄司淳, 高橋洋, 西村秀一, 児玉栄一

感染症学雑誌　94　(臨増)　280-280　2020/03
Publisher: (一社)日本感染症学会
ISSN： 0387-5911
フルオロウラシル誘導体は新規作用機序であるピリミジン代謝阻害によって薬剤耐性グラム陽性球菌に優れた抗菌活性を示す

大江千紘, 林宏典, 平田和成, 勝見真琴, 賀来満夫, 児玉栄一

感染症学雑誌　94　(臨増)　301-301　2020/03
Publisher: (一社)日本感染症学会
ISSN： 0387-5911
熊本地震と東日本大震災の比較分析による精神科病棟における災害時感染症対策の実態に関する研究

野崎裕之, 吉村直仁, 村田ひとみ, 北田志郎, 杉森裕樹, 児玉栄一

日本環境感染学会総会プログラム・抄録集　35回　P21-5　2020/02
Publisher: (一社)日本環境感染学会
経腟超音波検査装置の微生物汚染に関する検討

千田貴恵, 金森肇, 石川恵子, 池田しのぶ, 勝見真琴, 児玉栄一, 徳田浩一, 林宏典

日本環境感染学会総会プログラム・抄録集　35回　P62-6　2020/02
Publisher: (一社)日本環境感染学会
Synthetic study on carbocyclic-2’-deoxynucleoside-synthesis of carbocyclic-2’-deoxy-7-deazaadenosine-

水石彩菜, 斎藤智亜季, 目黒公太郎, 植松明星, 原島利彰, 林宏典, 児玉栄一, 三澤隆史, 出水庸介, 栗原正明, 紺野奇重

日本薬学会年会要旨集(CD-ROM)　140th　2020
Synthetic study on carbocyclic-2’-deoxynucleoside-synthesis of carbocyclic-2’-deoxyuridine

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日本薬学会年会要旨集(CD-ROM)　140th　2020
東日本大震災と熊本地震の比較分析による精神科病棟における被災時感染症対策の実態についての研究

野崎裕之, 児玉栄一

Japanese Journal of Disaster Medicine　24　(3)　392-392　2019/12
Publisher: (一社)日本災害医学会
ISSN： 2189-4035

eISSN： 2434-4214
二量体化HIV-1膜融合阻害剤の作用機構

村上努, 海老原健人, 小早川拓也, 藤野真之, 児玉栄一, 玉村啓和

日本エイズ学会誌　21　(4)　427-427　2019/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
アカデミアで創薬研究を継続させるヒント

児玉栄一, 児玉栄一, 児玉栄一, 児玉栄一

創薬懇話会講演要旨集　2019　1‐2　2019/06/20
ウイルスタンパク質の活性をトリガーとした新規不可逆阻害剤の開発

福井竜介, 新美結士, 片倉秀雄, 鈴木哲郎, 村上努, 児玉栄一, 木村康明, 阿部洋

日本薬学会年会要旨集　139年会　(2)　103-103　2019/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
細胞治療を指向したエクソソーム分泌細胞封入ゲルの技術開発

平野まみ, 萩原将也, ベイリー小林菜穂子, 吉田徹彦, 児玉栄一, 中瀬生彦

日本薬学会年会要旨集　139年会　(2)　236-236　2019/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
細胞治療を指向したエクソソーム分泌細胞封入ゲルの技術開発

平野まみ, 萩原将也, ベイリー小林菜穂子, ベイリー小林菜穂子, 吉田徹彦, 吉田徹彦, 児玉栄一, 中瀬生彦, 中瀬生彦

日本薬学会年会要旨集(CD-ROM)　139th　(2)　ROMBUNNO.22R‐pm21S-236　2019/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
ウイルスタンパク質の活性をトリガーとした新規不可逆阻害剤の開発

福井竜介, 新美結士, 片倉秀雄, 鈴木哲郎, 村上努, 児玉栄一, 木村康明, 阿部洋

日本薬学会年会要旨集(CD-ROM)　139th　(2)　ROMBUNNO.23K‐pm11-103　2019/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
2’‐βセレノ核酸アナログによるウイルス逆転写酵素の不可逆阻害

木村康明, 新美結士, 片倉秀雄, 友池史明, 鈴木哲朗, 村上努, 児玉栄一, 阿部洋, 阿部洋

日本化学会春季年会講演予稿集(CD-ROM)　99th　ROMBUNNO.1PC‐122　2019/03/01
急性期病院で分離されたカルバペネム耐性腸内細菌科細菌(CRE)の解析

牧野祐子, 金森肇, 遠藤史郎, 馬場啓聡, 大江千紘, 吉田眞紀子, 大島謙吾, 青柳哲史, 徳田浩一, 児玉栄一, 矢野寿一, 賀来満夫

感染症学雑誌　93　(1)　74-75　2019/01
Publisher: (一社)日本感染症学会
ISSN： 0387-5911

eISSN： 1884-569X
ウイルスポリメラーゼの不可逆阻害を目指した新規2′‐&βセレノ核酸アナログの創製

村上努, 木村康明, 新美結士, 藤野真之, 片倉秀雄, 鈴木哲朗, 児玉栄一, 阿部洋

日本エイズ学会誌　20　(4)　468-468　2018/11/20
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
ウイルスポリメラーゼの不可逆阻害を目指した新規2'-&βセレノ核酸アナログの創製

村上努, 木村康明, 新美結士, 藤野真之, 片倉秀雄, 鈴木哲朗, 児玉栄一, 阿部洋

日本エイズ学会誌　20　(4)　468-468　2018/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
Gag-TSG101相互作用を標的とする新規HIV-1阻害薬の特徴(Characterization of novel HIV-1 inhibitors targeting Gag-TSG101 interaction)

Lowela Siarot, Nopporn Chutiwitoonchai, 佐藤洋隆, Hao Chang, 小谷治, 横山勝, 佐藤裕徳, 藤野真之, 村上勉, 近藤恭光, 本田香り, 長田裕之, 上田一樹, 伊藤嘉浩, 青野俊裕, 児玉栄一, 黒田和道, 武井正美, 間陽子

日本エイズ学会誌　20　(4)　522-522　2018/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
Gag-TSG101相互作用を標的とする新規HIV-1阻害薬の特徴(Characterization of novel HIV-1 inhibitors targeting Gag-TSG101 interaction)

Lowela Siarot, Nopporn Chutiwitoonchai, 佐藤洋隆, Hao Chang, 小谷治, 横山勝, 佐藤裕徳, 藤野真之, 村上勉, 近藤恭光, 本田香り, 長田裕之, 上田一樹, 伊藤嘉浩, 青野俊裕, 児玉栄一, 黒田和道, 武井正美, 間陽子

日本エイズ学会誌　20　(4)　522-522　2018/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
生合成経路の再構築と再設計による糸状菌ジテルペノイドピロンライブラリーの構築と生物活性評価

塚田健人, 塚田健人, 金子秋穂, 新木翔之, 河治久実, 児玉栄一, 倉石貴透, 村上一馬, 入江一浩, 平田尚也, 諫田泰成, 浅井禎吾

メディシナルケミストリーシンポジウム講演要旨集　36th　48　2018/11/01

ISSN： 0919-214X
ウイルスポリメラーゼを標的とした不可逆阻害剤の開発

新美結士, 片倉秀雄, 鈴木哲郎, 村上努, 児玉栄一, 木村康明, 阿部洋

メディシナルケミストリーシンポジウム講演要旨集　36th　151　2018/11/01

ISSN： 0919-214X
生合成経路の再構築と再設計による糸状菌ジテルペノイドピロンライブラリーの構築と生物活性評価

塚田健人, 塚田健人, 金子秋穂, 新木翔之, 河治久実, 児玉栄一, 倉石貴透, 村上一馬, 入江一浩, 平田尚也, 諫田泰成, 浅井禎吾

メディシナルケミストリーシンポジウム講演要旨集　36th　58　2018/11/01

ISSN： 0919-214X
これからの抗ウイルス療法抗ウイルス薬の開発の将来展望

児玉栄一, 林宏典, 臼井恵美子

臨床と微生物　45　(6)　685-688　2018/11
Publisher: (株)近代出版
ISSN： 0910-7029
急性期病院で分離されたカルバペネム耐性腸内細菌科細菌(CRE)の解析

牧野祐子, 金森肇, 遠藤史郎, 馬場啓聡, 大江千紘, 吉田眞紀子, 大島謙吾, 青柳哲史, 徳田浩一, 児玉栄一, 矢野寿一, 賀来満夫

日本感染症学会東日本地方会学術集会・日本化学療法学会東日本支部総会合同学会プログラム・抄録集　67th-65th　136　2018/10
大規模災害時の避難施設におけるウイルス性疾患対策~ワクチンと予防投与に期待されること~

児玉栄一

日本環境感染学会総会・学術集会(Web)　33回　96-96　2018/02
Publisher: (一社)日本環境感染学会
創薬からアウトブレイクを制御する

児玉栄一

東北医学雑誌　129　(2)　161-162　2017/12
Publisher: 東北医学会
ISSN： 0040-8700
ゲンボイヤ配合錠(GEN;EVG/COBI/FTC/TAF)投与時の耐性発現症例の検討

田沼順子, 潟永博之, 岡慎一, 児玉栄一, 中本泰充, 池田篤史, 小倉直樹, ABRAM ME, MARGOT NA, COX S, CALLEBAUT C, DAS M

日本エイズ学会誌　19　(4)　450-450　2017/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
飛躍的に発展を見せる抗ウイルス薬 1.抗ウイルス薬の開発―今後のアプローチ―

児玉栄一, 児玉栄一, 児玉栄一

化学療法の領域　33　(1)　26‐31　2016/12/25

DOI： 10.20837/2201701026 　

ISSN： 0913-2384
【飛躍的に発展を見せる抗ウイルス薬】抗ウイルス薬の開発今後のアプローチ

児玉栄一

化学療法の領域　33　(1)　26-31　2016/12
Publisher: (株)医薬ジャーナル社
ISSN： 0913-2384
感染症治療の新戦略新たな抗ウイルス薬の開発とその将来展望

児玉栄一

感染症学雑誌　90　(臨増)　186-186　2016/03
Publisher: (一社)日本感染症学会
ISSN： 0387-5911
マウス着床前胚におけるレトロトランスポゾン抑制制御機構の解明

畑中勇輝, 井上貴美子, 及川真実, 上村悟, 越後貫成美, 児玉栄一, 大川恭行, 束田裕一, 小倉淳郎

日本生化学会大会・日本分子生物学会年会合同大会講演要旨集　88回・38回　[4T20L-09(3P0928)]　2015/12
Publisher: (公社)日本生化学会
糖尿病啓発イベントからみえる糖尿病と歯周病の関連

山田紗智子, 由浪有希子, 児玉栄一, 伊藤恵美, 小関健由, 清元秀康, 石井正

宮城県糖尿病看護研究会　10回　13-13　2014/06
Publisher: 宮城県糖尿病看護研究会
ISSN： 2187-2511
結核は一般病院でみる普通の病気になれるか? 県内一ヶ所の結核病棟を持つ病院の現状(宮城県の場合)

内山美寧, 平潟洋一, 菅野剛, 金森肇, 児玉栄一

結核　89　(3)　298-298　2014/03
Publisher: (一社)日本結核病学会
ISSN： 0022-9776

eISSN： 1884-2410
MAGI細胞による薬剤screeningにおいて酵素法がヒット化合物検出に優れる

児玉栄一

日本エイズ学会誌　15　(4)　521-521　2013/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
ToMMoクリニカルフェローによる循環型地域支援の報告(第一期、第二期)

阿部倫明, 田中淳一, 高山真, 金村政輝, 奈良正之, 目時弘仁, 関口敦, 児玉栄一, 坪井明人, 瀧靖之, 菅原準一, 石井正, 清元秀泰, 八重樫伸生

日本医療・病院管理学会誌　50　(Suppl.)　272-272　2013/08
Publisher: (一社)日本医療・病院管理学会
ISSN： 1882-594X

eISSN： 2185-422X
【抗ウイルス療法の現状と今後の展望】新しい抗ウイルス薬開発の考え方

児玉栄一, 宮本総子

臨床と微生物　40　(1)　009-013　2013/01
Publisher: (株)近代出版
ISSN： 0910-7029
サハラ以南アフリカにおけるエイズ・結核研究ネットワーク構築の試み

服部俊夫, 鈴木定彦, 山岡昇司, 井戸栄治, 一瀬休生, 仲宗根正, 久保亨, 臼澤基紀, 垣本和宏, 福本学, 児玉栄一

日本国際保健医療学会学術大会プログラム・抄録集　27th　123　2012/11/02
EFdAおよびEdDAPに対する耐性変異が耐性度と複製能力に及ぼす影響

宮本総子, 満屋裕明, 児玉栄一

日本エイズ学会誌　14　(4)　388-388　2012/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
Novel HIV-1 fusion inhibition peptides: Designing the next generation of drugs

Fusako Miyamoto, Eiichi N Kodama

Antiviral Chemistry and Chemotherapy　22　(4)　151-158　2012

DOI： 10.3851/IMP1930 　

ISSN： 0956-3202
膜融合蛋白(F蛋白)を標的とした新規ペプチドによる亜急性硬化性全脳炎の新たな治療戦略

WATABE MASAHIRO, HASHIMOTO KOICHI, ABE YUSAKU, OHARA SHIN'ICHIRO, SATO AKISATO, KAWASAKI YUKIHIKO, KODAMA EIICHI, OISHI SHIN'YA, HOSOYA MITSUAKI

Neuroinfection　16　(2)　152　2011/10/21

ISSN： 1348-2718
がん遺伝子治療に向けた新しいPETレポーター/治療遺伝子の開発(Development of new PET reporter/ therapy gene for cancer gene therapy)

渡邊夕紀子, 児玉栄一, 堀江佐知子, 高地崇, サックス・ニコラ, 柳下陽子, 陳鋭, 李麗, 服部俊夫, 森士朗, 小玉哲也

日本癌学会総会記事　69回　366-366　2010/08
Publisher: 日本癌学会
ISSN： 0546-0476
新規抗HIV薬の開発特集・抗ウイルス薬物療法の現状と今後の展望 (医薬ジャーナル)

児玉栄一

医薬ジャーナル　46　97-102　2010/04
【抗ウイルス薬物療法の現状と今後の展望】抗HIV薬新規抗HIV薬の開発 (医薬ジャーナル)

児玉栄一

医薬ジャーナル　46　(2)　729-734　2010/02
Publisher: (株)医薬ジャーナル社
ISSN： 0287-4741
新規抗HIV薬の開発 (特集抗ウイルス薬物療法の現状と今後の展望) -- (抗HIV薬)

児玉栄一

医薬ジャ-ナル　46　(2)　97-102　2010/02
Publisher: 医薬ジャ-ナル社
ISSN： 0287-4741
The crystal structure of EFdA-resistant HIV-1 reverse transcriptase reveals structural changes in the polymerase active site

B. Marchand, K. A. Kirby, D. Sietsema, E. N. Kodama, H. Mitsuya, M. A. Parniak, S. G. Sarafianos

ANTIVIRAL THERAPY　15　A10-A10　2010

ISSN： 1359-6535
The crystal structure of EFdA-resistant HIV-1 reverse transcriptase reveals structural changes in the polymerase active site

B. Marchand, K. A. Kirby, D. Sietsema, E. N. Kodama, H. Mitsuya, M. A. Parmak, S. G. Sarafianos

ANTIVIRAL THERAPY　15　(4)　A10-A10　2010

ISSN： 1359-6535
アルケン型ジペプチドイソスターの合成とケモカイン受容体CXCR4拮抗剤の構造活性相関研究への応用

HAYASHI RYOKO, OISHI SHIN'YA, TOMITA KENJI, NARUMI TETSUO, TANAHARA NORIKO, ONO HIROAKI, NAITO TAKESHI, KODAMA EIICHI, MATSUOKA MASAO, FUJII NOBUTAKA

メディシナルケミストリーシンポジウム講演要旨集　28th　116-117　2009/11/10

ISSN： 0919-214X
Focus on the Effector Site of the Antiviral Agent

Kodama Eiichi, Hattori Toshio

Nihon Naika Gakkai Zasshi　98　(11)　2754-2761　2009/11/10
Publisher: The Japanese Society of Internal Medicine
DOI： 10.2169/naika.98.2754 　

ISSN： 0021-5384

More details Close

HIVは後天性免疫不全症候群（acquired immunodeficiency syndrome；AIDS）を引き起こすウイルスであり，また一方で遺伝子導入・治療のベクターとして用いられることから幅広い研究の対象となっている．抗レトロウイルス剤の作用やその耐性機序を知る上で複製機構の理解は必須である．本稿では現在臨床使用されている薬剤と治験中の薬剤がウイルス複製のどのステップを抑えているかを侵入，逆転写反応，組込み，転写，アッセンブリ，出芽の6ステップに分けて要約した．<br>
HAARTによるオステオポンチンの誘導の意義に関する検討

Haorile Chagan-Yasutan, 齋藤弘樹, 芦野有悟, 児玉栄一, 服部俊夫

日本エイズ学会誌　11　(4)　575-575　2009/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
HIV感染と増殖のメカニズム-抗ウイルス剤の作用点を中心に (日本内科学会雑誌)

児玉栄一, 服部俊夫

日本内科学会雑誌　98　(11)　2754-2761　2009/11
Publisher: (一社)日本内科学会
DOI： 10.2169/naika.98.2754 　

ISSN： 0021-5384

eISSN： 1883-2083
エンドキャップ抗HIV活性ペプチドSC35EKの合成

KAJIWARA KAZUMI, TOKIWA REI, WATANABE KENTARO, ONO HIROAKI, IZUMI KAZUKI, KODAMA EIICHI, MATSUOKA MASAO, OISHI SHIN'YA, FUJII NOBUTAKA

日本薬学会年会要旨集　129th　(2)　186　2009/03/05

ISSN： 0918-9823
Identification of Novel HIV-1 Fusion Inhibitors by Template-Assisted Peptide Aldehyde Ligation

TANAKA Michinori, WATANABE Kentaro, OHNO Hiroaki, IZUMI Kazuki, KODAMA Eiichi, MATSUOKA Masao, OISHI Shinya, FUJII Nobutaka

2008　361-362　2009/03/01

ISSN： 1344-7661
Structure Activity Relationship Study of the Helix-inducible Motifs in HIV Fusion Inhibitors

WATANABE Kentaro, ITO Saori, OHNO Hiroaki, IZUMI Kazuki, KODAMA Eiichi, MATSUOKA Masao, OISHI Shinya, FUJII Nobutaka

2008　257-258　2009/03/01

ISSN： 1344-7661
Bioorganic Synthesis of End-capped HIV-1 Fusion Inhibitor SC35EK

KAJIWARA Kazumi, TOKIWA Rei, WATANABE Kentaro, OHNO Hiroaki, IZUMI Kazuki, KODAMA Eiichi, MATSUOKA Masao, OISHI Shinya, FUJII Nobutaka

2008　203-204　2009/03/01

ISSN： 1344-7661
X-ray Crystallographic Study of the HIV-1 Fusion Inhibitor against the Drug-Resistant N43D Variant

WATABE Tsuyoshi, OISHI Shinya, WATANABE Kentaro, OHNO Hiroaki, NAKANO Hiroaki, NAKATSU Toru, KATO Hiroaki, IZUMI Kazuki, KODAMA Eiichi, MATSUOKA Masao, FUJII Nobutaka

2008　229-232　2009/03/01

ISSN： 1344-7661
HIV‐1 Rev‐derived peptideはRevとCXCR4のdual‐target inhibitorとして作用する

SHIMANE KAZUKI, KODAMA EIICHI, MATSUOKA MASAO

日本エイズ学会誌　10　(4)　539-539　2008/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
逆転写酵素connectionとRNase H subdomainの多様性と薬剤感受性に及ぼす影響

蜂谷敦子, 嶋根和毅, 児玉栄一, 小泉寛和, 潟永博之, 松岡雅雄, 滝口雅文, 岡慎一

日本エイズ学会誌　10　(4)　422-422　2008/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
ヘリックス誘起モチーフを導入した抗HIVペプチドのデザインと合成

WATANABE KENTARO, OISHI SHIN'YA, ITO SAORI, TANAKA MASANORI, NISHIKAWA HIROKI, WATABE TAKESHI, IZUMI KAZUKI, SAKAGAMI YASUKO, KODAMA EIICHI, MATSUOKA MASAO, ONO HIROAKI, FUJII NOBUTAKA

日本薬学会年会要旨集　128th　(2)　49　2008/03/05

ISSN： 0918-9823
Synthesis and Application of Novel Fluorescence-Labeled CXCR4 Antagonists

MASUDA Ryo, OISHI Shinya, UEDA Satoshi, GOTO Yukiko, OHNO Hiroaki, EVANS Barry, PEIPER Stephen C., HIRASAWA Akira, TSUJIMOTO Gozoh, KODAMA Eiichi, MATSUOKA Masao, FUJII Nobutaka

2007　403-404　2008/03/01

ISSN： 1344-7661
Helix Inducible Motifs Affect Helicity and Bioactivity of Anti-HIV Peptides

WATANABE Kentaro, ITO Saori, NISHIKAWA Hiroki, TANAKA Michinori, OISHI Shinya, OHNO Hiroaki, IZUMI Kazuki, KODAMA Eiichi, MATSUOKA Masao, FUJII Nobutaka

2007　311-312　2008/03/01

ISSN： 1344-7661
Chemical Virologyを基盤とする新興・再興ウイルス侵入阻害剤の開発研究

FUJII NOBUTAKA, OISHI SHIN'YA, NISHIKAWA HIROKI, WATANABE TSUYOSHI, ONO HIROAKI, UJIIE MAKOTO, TAGUCHI FUMIHIRO, KODAMA EIICHI, MATSUOKA MASAO

ケミカルバイオロジーシンポジウム発表要旨集第4回化学-生物融合領域創成の軌跡理研シンポジウム平成20年　41　2008
T‐20(Fuzeon)耐性HIV‐1変異株における6‐ヘリカルバンドル構造のX線構造解析

渡部毅, 大石真也, 西川裕輝, 渡辺健太郎, 中野博明, 中津亨, 大野浩章, 加藤博章, 児玉栄一, 松岡雅雄, 藤井信孝

日本化学会講演予稿集,88th,2,878　2008
Elvitegravir: An emerging HIV integrase inhibitor

Kazuya Shimura, Eiichi Kodama

Future HIV Therapy　2　(5)　411-418　2008

DOI： 10.2217/17469600.2.5.411 　

ISSN： 1746-9600
インテグレース阻害剤に対する耐性HIVの誘導とその複製能の比較

SHIMURA KAZUYA, KODAMA EIICHI, IKEDA RYO, MATSUOKA MASAO

日本エイズ学会誌　9　(4)　405-405　2007/11/20
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
核酸系(NRTI)および非核酸系逆転写酵素阻害剤(NNRTI)に対する多剤耐性変異N348Iについて~その1/基礎的検討

蜂谷敦子, 児玉栄一, 潟永博之, 松岡雅雄, 滝口雅文, 岡慎一

日本エイズ学会誌　9　(4)　508-508　2007/11/20
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
核酸系(NRTI)および非核酸系逆転写酵素阻害剤(NNRTI)に対する多剤耐性変異N348Iについて~その2/臨床解析

蜂谷敦子, 児玉栄一, 潟永博之, 松岡雅雄, 滝口雅文, 岡慎一

日本エイズ学会誌　9　(4)　508-508　2007/11/20
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
T‐20誘導体の抗HIV効果

SHIMANE KAZUKI, IZUMI KAZUKI, KODAMA EIICHI, OISHI SHIN'YA, FUJII NOBUTAKA, MATSUOKA MASAO

日本エイズ学会誌　9　(4)　403　2007/11/20

ISSN： 1344-9478
EKコンセプトを利用した高活性HIV膜融合阻害剤の創製研究

ITO SAORI, OISHI SHIN'YA, NISHIKAWA YUKI, TANAKA MASANORI, WATANABE KENTARO, IZUMI KAZUKI, KODAMA EIICHI, MATSUOKA MASAO, ONO HIROAKI, FUJII NOBUTAKA

日本薬学会年会要旨集　127年会　(4)　117-117　2007/03
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Development of a novel fusion inhibitor against t-20-resistant HIV-1

S. Oishi, S. Ito, H. Nishikawa, M. Tanaka, H. Ohno, A. Otaka, K. Izumi, E. Kodama, M. Matsuoka, N. Fujii

BIOPOLYMERS　88　(4)　524-524　2007

ISSN： 0006-3525
HIV インチグレース阻害剤Elvitegravir (JTK-303/GS-9137) の抗ウイルス活性および耐性機序の解析 Peer-reviewed

志村和也, 児玉栄一, 阪上泰子, 松崎裕児, 渡辺渡, 山高一修, 佐藤元秀, 加納光記, 池田了, 松岡雅雄

第17 回抗ウイルス療法研究会、高松、2007 年5 月25 日-26 日　2007
C29 水溶性誘導体 SC29EK の抗HIV 効果 Peer-reviewed

内藤武志, 泉和樹, 西川裕輝, 児玉栄一, 大石真也, 藤井信孝, 松岡雅雄

第21 回日本エイズ学会学術集会・総会、広島、2007 年11月28-30 日　2007
T-20 耐性変異を利用した融合阻害薬の開発 Peer-reviewed

泉和樹, 児玉栄一, 志村和也, 大石真也, 藤井信孝, 松岡雅雄

第21回日本エイズ学会学術集会・総会、広島、2007 年11月28-30 日　2007
T-20 耐性HIV-1 に対して有効な融合阻害薬の開発 Peer-reviewed

泉和樹, 西川裕輝, 伊藤紗織, 児玉栄一, 志村和也, 大石真也, 藤井信孝, 松岡雅雄

第17 回抗ウイルス療法研究会、香川、 2007 年5 月25-26 日　2007
NRTIを含む治療中に誘導された新しいネビラピン(NVP)耐性変異

蜂谷敦子, 潟永博之, 児玉栄一, 松岡雅雄, 滝口雅文, 岡慎一

日本エイズ学会誌　8　(4)　411-411　2006/11/20
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
EKコンセプトを利用した高活性HIV膜融合阻害剤の創製研究

ITO SAORI, OISHI SHIN'YA, NISHIKAWA HIROKI, TANAKA MICHINORI, IZUMI KAZUKI, KODAMA EIICHI, MATSUOKA MASAO, ONO HIROAKI, FUJII NOBUTAKA

メディシナルケミストリーシンポジウム講演要旨集　25th　62-63　2006/11/10

ISSN： 0919-214X
SARSコロナウイルススパイク(S)蛋白質のHeptad Repeat由来Peptide(HR‐p)は細胞表面からのウイルス侵入を効果的に抑制する

UJIIE MAKOTO, NISHIKAWA YUKI, OTAKA AKIRA, YAMAMOTO NAOKI, YAMAMOTO NORIO, MATSUOKA MASAO, KODAMA EIICHI, FUJII NOBUTAKA, TAGUCHI FUMIHIRO

日本ウイルス学会学術集会プログラム・抄録集　54th　168　2006/11/01
2'-Deoxy-4'-C-ethynyl-2-fluoroadenosine(E2 FdA)の細胞内代謝とDNAポリメラーゼに対する阻害作用の検討

中田浩智, 天野将之, こう康博, 満屋裕明, 児玉栄一, Yang Guangwei, 向後悟, 早川弘之, 大類洋, 松岡雅雄, Chen Yung-Chi

感染症学雑誌　80　(6)　803-803　2006/11
Publisher: (一社)日本感染症学会
ISSN： 0387-5911
サイエンスが直面する難題を有機化学の基本でブレークスルーするPartII,画期的抗HIVヌクレオシドの創製

大類洋, 向後悟, 早川弘之, 児玉栄一, 松岡雅雄, 満屋裕明

天然有機化合物討論会講演要旨集　48th　(48)　547-552　2006/09/15
Publisher: Symposium on the chemistry of natural products
DOI： 10.24496/tennenyuki.48.0_547 　
サイエンス(人類)が直面する難題を有機化学でブレークスルーしよう!―エイズとB型肝炎の夢の治療薬の開発!?―

大類洋, 向後悟, 早川弘之, 児玉栄一, 松岡雅雄, 満屋裕明

万有生命科学振興国際交流財団仙台シンポジウム　17th　61　2006/06/24
Research on building an HIV test system. B. Study on more effective HIV follow-up systems for caring HIV-positive people (infected). B-4. Drug resistance test with newly infected patients and non-subtype-B and collection of sensitivity test data.

HACHIYA ATSUKO, NEGISHI FUJIE, KATANAGA HIROYUKI, KIMURA SATOSHI, OKA SHIN'ICHI, KODAMA MASAKAZU, MATSUOKA MASAO

HIV検査体制の構築に関する研究平成15-17年度総合研究報告書　256-262　2006
Establishing HIV screening program. B. Effective HIV follow up screening program for HIV positive patients. B-4. Drug resistance trial and sensitivity testing of Non-subtype B HIV-1.

HACHIYA ATSUKO, NEGISHI FUJIE, KODAMA MASAKAZU, MATSUOKA MASAO, OKA SHIN'ICHI, KIMURA SATOSHI

HIV検査体制の構築に関する研究平成17年度研究報告書　242-246　2006
In Vitro Antiviral Activity and Resistance Profile of a Novel HIV Integrase Inhibitor JTK-303/GS-9137. Peer-reviewed

Kodama E, Shimura K, Sakagami Y, Matsuzaki Y, Watanabe W, Yamataka K, Sato M, Kano M, Ikeda S, Matsuoka M

46th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, Sep 27-30, 2006.　2006
新規HIV インチグレース阻害剤JTK-303/GS-9137の抗HIV 活性および耐匪機序の解析 Peer-reviewed

志村和也, 児玉栄一, 池田了, 松岡雅雄

第20 回日本エイズ学会学術集会・総会、東京、2006年11月30 日-12 月2日　2006
膜融合阻害ペプチドN36 に対する耐匪HIVの誘導と解析 Peer-reviewed

泉和樹, 児玉栄一, 藤井信孝, 松岡雅雄

第9 回白馬シンポジウム、京都、2006 年10 月12-13 日　2006
強力な抗HIV活性を示す2’‐Deoxy4’‐C‐ethynyl‐2‐haloadenosine誘導体の設計と合成

KOGO SATORU, IWAI YUKO, ASHIDA NORIYUKI, HAYAKAWA HIROYUKI, KAWAMOTO ATSUSHI, KODAMA EIICHI, MATSUOKA MASAO, MITSUYA HIROAKI, ORUI HIROSHI

メディシナルケミストリーシンポジウム講演要旨集　24th　56-57　2005/11/10

ISSN： 0919-214X
融合阻害剤T-20(Fuzeon)に対する耐性HIVの解析 Peer-reviewed

上野真理子, 梶原慶子, 志村和也, 児玉栄一, 松岡雅雄

日本エイズ学会誌　7　(4)　360-360　2005/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
核酸系逆転写酵素阻害剤 2'-Deoxy-4'-C-ethynyl-2-fluoro-adenosine(E2FdA)の細胞内動態の検討

中田浩智, 天野将之, こう康博, 児玉栄一, Yang Guangwei, 向後悟, 早川弘之, 大類洋, 松岡雅雄, Chen Yun-Chi, 満屋裕明

日本エイズ学会誌　7　(4)　423-423　2005/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
核酸系逆転写酵素阻害剤 4'-ethynyl-2-halo-deoxyadenosine誘導体の耐性HIV複製阻害活性の検討 Peer-reviewed

川本敦司, 児玉栄一, 大類洋, 満屋裕明, 松岡雅雄

日本エイズ学会誌　7　(4)　423-423　2005/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
水溶性C34誘導体の抗HIV効果

児玉栄一, 梶原慶子, 大高章, 藤井信孝, 松岡雅雄

日本エイズ学会誌　7　(4)　418-418　2005/11
Publisher: 日本エイズ学会
ISSN： 1344-9478
アマンタジン誘導体の抗HIV活性

CHIBA TAKUO, KODAMA EIICHI, MATSUOKA MASAO

化学系学協会東北大会プログラムおよび講演予稿集　2005　291　2005/09/15
広いスペクトラムのHIVに著効を示す低毒性ヌクレオシド誘導体の開発:特に3’‐OHの生物活性に対する役割について

ORUI HIROSHI, MUKAJIRI SATORU, MUKAJIRI SATORU, HOKUNO KENJI, ASHIDA NORIYUKI, HAYAKAWA HIROYUKI, KODAMA EIICHI, MATSUOKA MASAO, MITSUYA HIROAKI

日本農芸化学会大会講演要旨集　2005　181　2005/03/05
4 '-C-ethynyl-2 '-deoxy-2-fluoroadenosine, a nucleoside derivative potent against HIV-1 with no acute mouse toxicity: Highlights of the role of 3 '-OH for biological activity

H Ohrui, S Kohgo, K Kitano, N Ashida, H Hayakawa, E Kodama, M Matsuoka, H Mitsuya

ANTIVIRAL RESEARCH　65　(3)　A42-A42　2005/03

ISSN： 0166-3542
HIV-1 Acquires Resistance to New NNRTI, Thiazol Derivatives, through Steric Hindrance with Multiple Mutations. Peer-reviewed

Kodama E, Masuda N, Orita M, Yamamoto O, Fujii M, Kageyama S, Ohta M, Hatta T, Inoue H, Suzuki H, Sudo K, Shimizu Y, Matsuoka M

12th conference on retroviruses and opportunistic infections. Boston, MA, Feb 22-25, 2005.　2005
MTT 法を用いたCXCR4 およびCCR5 トロピックHIV-1 に対する薬剤感受性試験法 Peer-reviewed

梶原慶子, 児玉栄一, 松岡雅雄

第19 回日本エイズ学会学術集会・総会、熊本、2005 年 12 月1-3 日　2005
ELISAを応用した迅速なHIV‐fusion inhibitor screening法の確立

児玉栄一, 榊原綾子, 大高章, 藤井信孝, 松岡雅雄

日本エイズ学会誌　6　(4)　514-514　2004/11/20
Publisher: 日本エイズ学会
ISSN： 1344-9478
HIV侵入の動的超分子機構を標的とした膜融合阻害剤の創製

NISHIKAWA YUKI, OTAKA AKIRA, TAMAMURA HIROKAZU, FUJII NOBUTAKA, MATSUOKA MASAO, KODAMA EIICHI

日本薬学会年会要旨集　124th　(2)　44-44　2004/03/05
Publisher: (公社)日本薬学会
ISSN： 0918-9823
A GENERAL STRATEGY FOR DEVELOPMENT OF ANTI-VIRUS PEPTIDES BASED ON X-EE-XX-KK CONCEPT FOR THE ALPHA-HELICAL ENV SEQUENCE: PRACTICE IN AIDS AND SARS

A. Otaka, N. Yamamoto, E. Kodama, H. Tamamura, M. Matsuoka, N. Yamamoto, N. Fujii

JOURNAL OF PEPTIDE SCIENCE　10　112-112　2004

ISSN： 1075-2617
Potential of 4′-C-substituted nucleosides for the treatment of HIV-1

Hiroyuki Hayakawa, Satoru Kohgo, Kenji Kitano, Noriyuki Ashida, Eiichi Kodama, Hiroaki Mitsuya, Hiroshi Ohrui

Antiviral Chemistry and Chemotherapy　15　(4)　169-187　2004
Publisher: International Medical Press Ltd
DOI： 10.1177/095632020401500401 　

ISSN： 0956-3202
Peptide fusion inhibitor C34に対する耐性機序の解析

児玉栄一, 大高章, 藤井信孝, 松岡雅雄

日本エイズ学会誌　5　(4)　403-403　2003/11/20
Publisher: 日本エイズ学会
ISSN： 1344-9478
C34誘導体SC34およびSC34EKはfusion inhibitor耐性ウイルスに効果を示す

行木大輔, 児玉栄一, 大高章, 藤井信孝, 松岡雅雄

日本エイズ学会誌　5　(4)　324　2003/11/20

ISSN： 1344-9478
Oligoarginine-mediated Delivery of Bioactive Peptides into Living cells

FUTAKI Shiroh, NAKASE Ikuhiko, NIWA Miki, SUZUKI Tomoki, NAMEKI Daisuke, KODAMA Ei-ichi, MATSUOKA Masao, SUGIURA Yukio

2002　73-76　2003/02/01

ISSN： 1344-7661
HIV感染に関与するヘリックスバンドルのX線結晶構造決定と熱力学的解析

中村昇太, 中野博明, 内山進, 大高章, 藤井信孝, 松岡雅雄, 児玉栄一, 山県ゆり子, 小林祐次

生化学　74　(11)　1405-1405　2002/11/25
Publisher: (公社)日本生化学会
ISSN： 0037-1017
多剤耐性HIVにも有効な4′位置換プリンヌクレオシド天然ヌクレオシドからの合成とその評価

KITANO KENJI, KOGO SATORU, SAKATA SHINJI, HAYAKAWA HIROYUKI, NAMEKI DAISUKE, KODAMA EIICHI, MATSUOKA MASAO, MITSUYA HIROAKI, ORUI HIROSHI

メディシナルケミストリーシンポジウム・日本薬学会医薬化学部会年会講演要旨集　22nd-11th　74-76　2002/11/05

ISSN： 0919-214X
HIV-1 gp41C末端由来ペプチドC34による耐性化機序の解明

行木大輔, 児玉栄一, 松岡雅雄

日本エイズ学会誌　4　(4)　294-294　2002/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
新規感染患者から検出された新たなネビラピン(NVP)耐性変異について

蜂谷敦子, 児玉栄一, 松岡佐織, 土屋亮人, 立川夏夫, 安岡彰, 満屋裕明, 松岡雅雄, 木村哲, 岡慎一

日本エイズ学会誌　4　(4)　296-296　2002/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
α‐helix形成モチーフ導入型HIV‐1‐細胞膜融合阻害剤の創製

OTAKA AKIRA, NAKAMURA MIKI, KODAMA EIICHI, NAKAMURA SHOTA, NAKANO HIROAKI, TAMAMURA HIROKAZU, KOBAYASHI YUJI, MATSUOKA MASAO, FUJII NOBUTAKA

反応と合成の進歩シンポジウム講演要旨集　28th　130-131　2002/10/15

ISSN： 0919-2123
【HIV/AIDS研究の進歩】抗HIV薬・ワクチンの開発研究の進歩新しい逆転写酵素阻害剤 (日本臨床)

児玉栄一

日本臨床　60　(4)　775-779　2002/04
HIV感染初期過程に関わる6‐helical‐bundle構造を標的とした高活性膜融合阻害剤(SC34)の創出とその応用研究

NAKAMURA MIKI, OTAKA AKIRA, KODAMA EIICHI, MATSUOKA MASAO, UCHIYAMA SUSUMU, NAKAMURA SHOTA, KOBAYASHI YUJI, TAMAMURA YOSHIKAZU, FUJII NOBUTAKA

日本薬学会年会要旨集　122nd　(2)　183-183　2002/03/05
Publisher: (公社)日本薬学会
ISSN： 0918-9823
HIV感染に関与するヘリックスバンドルの熱力学的解析

NAKAMURA SHOTA, NAKANO HIROAKI, UCHIYAMA SUSUMU, OKUBO TADAYOSHI, MATSUOKA MASAO, KODAMA EIICHI, NAKAMURA MIKI, FUJII NOBUTAKA, KOBAYASHI YUJI

日本薬学会年会要旨集　122nd　(3)　23-23　2002/03/05
Publisher: (公社)日本薬学会
ISSN： 0918-9823
Arginine‐richペプチドを用いたRNase S複合体の細胞内導入

FUTAKI SHIRO, NAKASE ARIHIKO, SUZUKI TOMOKI, NIWA MIKI, NAMEKI DAISUKE, KODAMA EIICHI, MATSUOKA MASAO, SUGIURA YUKIO

日本薬学会年会要旨集　122nd　(2)　177-177　2002/03/05
Publisher: (公社)日本薬学会
ISSN： 0918-9823
新規の核酸系逆転写酵素阻害剤(4′‐ethynyl nucleoside)に対するHIV‐1の耐性化機序の解析

KODAMA EIICHI, MITSUYA HIROAKI, MATSUOKA MASAO

日本エイズ学会誌　3　(4)　388-388　2001/11/20
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
HIV‐1 gp41N末端由来のペプチドN36による耐性化機序の解明

NAMEKI DAISUKE, KODAMA EIICHI, MATSUOKA MASAO

日本エイズ学会誌　3　(4)　389-389　2001/11/20
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
抗HIVペプチドN36耐性株から誘導されたC34KQとN36の複合体のX線結晶解析

中村昇太, 中野博明, 内山進, 大高章, 藤井信孝, 松岡雅雄, 児玉栄一, 山県ゆり子, 小林祐次

日本生物物理学会年会講演予稿集　39th　2001

ISSN： 0582-4052
Crystal structure of potent anti-HIV peptide, N36 complexed with C34KQ derived from N36-resistant strain

Nakamura S, Nakano H, Uchiyama S, Otaka A, Nakamura M, Fujii N, Matsuoka M, Kodama E, Yamagata Y, Ohkubo T, Kobayashi Y

Seibutsu Butsuri　41　(0)　S34　2001
Publisher: 一般社団法人日本生物物理学会
DOI： 10.2142/biophys.41.S34_1 　
8th Conference on Retroviruses and Opportunistic Infections

KODAMA Eiichi

The Journal of AIDS Research　3　(3)　175-177　2001
Publisher: The Japanese Society for AIDS Research
DOI： 10.11391/aidsr1999.3.175 　

ISSN： 1344-9478
4'-Ethynyl nucleosides 多剤耐性HIVに著効する新規nucleoside reverse transcriptase inhibitor(NRTI)

児玉栄一, 大類洋, 茂田士郎, 満屋裕明, 松岡雅雄

日本エイズ学会誌　2　(4)　456-456　2000/11
Publisher: (一社)日本エイズ学会
ISSN： 1344-9478
抗ウイルス薬の進歩 (日本医事新報)

茂田士郎, 児玉栄一, 橋本浩一

日本医事新報　(3730)　26-30　1995/10

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Books and Other Publications 2

Revを標的とした新規抗HIV療法の確立

児玉栄一(ウィルス学, 京都大学ウイルス研究所

[児玉栄一]　2007
ウイルス感染症との闘い

茂田士郎, 満屋裕明, ds, 児玉栄一, 松岡雅雄, 満屋裕明

医薬ジャーナル社　2001/07

Presentations 22

4'-Ethynyl-核酸誘導体に対するHIV-1及びHIV-2の耐性機序

宮本総子, 服部俊夫, 児玉栄一

第２５回日本エイズ学会学術集会・総会　2011/11/30
HIV-1 Reverse Transcriptase (RT) Polymorphism 172K Suppresses the Effect of Clinically Relevant Drug Resistance Mutations to Both Nucleoside and Nonnucleoside RT Inhibitors. International-presentation

Atsuko Hachiya, Bruno Marchand, Karen A. Kirby, Eleftherios Michailidis, Xiongying Tu, Yee Tsuey Ong, Daniel T. Griffin, Matthew M. Schuckmann, Junko Tanuma, Shinichi Oka, Kamalendra Singh, Eiichi N. Kodama, Stefan G. Sarafianos

12th Annual Symposium on Antiviral Drug Resistance　2011/11/06
Development of HIV-1 fusion inhibitors active ,to enfuvirtide (T-20) resistant variants International-presentation

児玉栄一

U.S-Japan cooperative Medical Sciences Panel　2010/12/08
HAART施行中の薬剤副作用に対するRaltegravirへの薬剤変更を行った10例

齋藤弘樹, 芦野有悟, 児玉栄一, 服部俊夫

第24回日本エイズ学会　2010/11/24
当院におけるHAART施行中の手術症例

芦野有悟, 齋藤弘樹, 児玉栄一, 服部俊夫

第24回日本エイズ学会　2010/11/24
カテキン2量体procyanidin B1はHCV複製を抑制する

児玉栄一, Li Schenwei, 服部俊夫

第２０回日本抗ウイルス療法研究会　2010/05/19
Retroviral Integrase Inhibitor,elvitegravir(JK-303/GS9137)Mechanism of action and resistance.

児玉栄一

International Symposium on AIDS & TUBERCULOSIS　2010/01/13
Procyanidin B-1 suppresses HCV replication

Shenwei Li, 児玉栄一, Zhang Jing, 服部俊夫

第５７回ウイルス学会学術集会　2009/10/25
Drugs design for resistant HIV

Kodama E

Kumamoto AIDS Seminar Satellite Symposium　2009/09/30
Retroviral integrase inhibitor, elvitegravir(JTK-303/GS9137) International-presentation

児玉栄一

the Korea-Japan basic scientific cooperation program　2007/12/05
A Novel Mutations,N3481 in HIV-1 Reverse transcriptase Induced by NRTI Treatment,Confers Nevirapine Resistance. International-presentation

Hachiya A, Kodama E, Sarafianos SG, Schuckmann M, Matsuoka M, Takiguchi, Gatanaga H, Oka S

The 14th Conference on Retroviruses and Opportunistic Infections.　2007/02/25
In Vitro Antiviral Activity and Resistance profile of a Novel HIV Integrase Inhibitor JTK-303/GS-9137 International-presentation

Kodama E, SHimura K, Sakagami Y, Matsuzaki Y, Watanabe W, Yamataka K, Sato M, Kano M, Ikeda S, Matsuoka M

The 46th Interscience Conference on Antimicrobial Agents and Chemotherapy　2006/09/27
Mutations Conferring Resistance to HIV-1 Fusion Unhibitors are Restricted by gp41 and rev responsive Element Functions.

Kodama E, Mabuchi N, Otaka A, Ohno M, Fujii M, Matsuoka M

The 7th International Congress on AIDS in Asia and the pacific.　2005/07/01
HIV-1 Acquires Resistance to New NNRT1,Thiazol Derivatives,through Steric hindrance with Multiple Mutations. International-presentation

Kodama E, masuda N, Orita M, Yamamoto O, Fujii M, Kageyama S, Ohta M, Hatta T, Inoue H, Suzuki H, Sudo K, Shimizu Y, Matsuoka M

The 12th Conference on Retroviruses and Opportunistic Infections.　2005/02/22
HIV-1 fusion inhibitor-resistance and development of the new inhibitors.

Kodama E

The Japan-Korea Basic Scientific Cooperation Program　2004/11/17
Resistant mutations to HIV-1 fusion inhibitors are restricted by gp41 and Rev responsive element functioins. International-presentation

Kodama E, Ikeuchi M, Mabuchi N, Otaka A, Ohno M, Fujii N, Matsuoka M

The11th Conference on Retroviruses and Opportunistic Infections.　2004/02/08
Development of a novel fusion inhibitor,SC34EK International-presentation

Kodama E, Nameki D, Ikeuchi M, Otaka A, Tamamura H, Fujii N, Matsuoka M

The10th Conference on Retroviruses and Opportunistic Infections.　2003/02/10
Generation of HIV variants resistant to 4'-ethynyl-2'-deoxynucleosides. International-presentation

Kodama E, ikeuchi M, Matsuoka M, mitsuya M

The 9th Conference on Retroviruses and Opportunisyic Infections.　2002/02/24
4'-Ethynyl nucleoside analogs International-presentation

Kodama E, Ohrui H, Gatanaga H, Shigeta S, matsuoka M, Miysuya H

The 8th Conference on Retroviruses and Opportunistic Infections.　2001/02/04
4'-Ethynyl nucleoside analogs

kodama E, Ohrui H, Gatanaga H, Sigeta S, Matsuoka M, mitsuya H

The 8th International Antiviral Symposium and Workshop　2000/11/19
In vitro Anti-HIV-1activity of and virsl drug resistance profiles against phosphoralaninate diesters of Z-and E-methylene cyclopropene analogues. International-presentation

Yoshimura K, uchida H, Kodama E, maeda Y, Feldman R, Qiu Y-L, Zemlicka j, mitsuya H

The 5th Conference on Retroviruses and Opportunistic Infections.　1998/02/01
Analysis of mutation in the thymidine kinase gene of varicella zoster virus associated with resistance to5-iodo-2'-deoxyuridine and 5-bromo-2'-deoxyuridine. International-presentation

Kodama E, Mori S, Shigeta S

The 8th International Conference on Antiviral Reserch.　1995/04/23

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Industrial Property Rights 12

4’−C−置換−2−ハロアデノシン誘導体

向後悟, 大類洋, 児玉栄一, 松岡雅雄, 満屋裕明

特許第5213194号

Property Type: Patent
修飾ペプチド及びその製造方法

藤井信孝, 松岡雅雄, 児玉栄一, 大石真也, 田中理紀, 秦洋二, 堤浩子, 梶原一美, 常磐礼

Property Type: Patent
エプスタイン・バールウイルス関連疾患に対する薬剤およびそのスクリーニング法

児玉栄一

Property Type: Patent
4’−C−エチニルヌクレオシド化合物

大類洋, 向後悟, 児玉栄一, 松岡雅雄, 満屋裕明

Property Type: Patent
抗HIV剤

藤井信孝, 大石真也, 松岡雅雄, 児玉栄一

Property Type: Patent
抗HIV剤

藤井信孝, 大石真也, 松岡雅雄, 児玉栄一

Property Type: Patent
N36結合ペプチドの製造方法

堤浩子, 石田博樹, 久田博元, 水本真紀子, 秦洋二, 藤井信孝, 松岡雅雄, 児玉栄一, 大石真也

Property Type: Patent
4’−C−置換−2−ハロアデノシン誘導体

向後悟, 大類洋, 児玉栄一, 松岡雅雄, 満屋裕明

Property Type: Patent
4’−C−シアノ−2’−デオキシプリンヌクレオシド

向後悟, 山田浩平, 坂田紳二, 大類洋, 児玉栄一

Property Type: Patent
4’−C−エチニルプリンヌクレオシド化合物

大類洋, 向後悟, 児玉栄一, 松岡雅雄, 満屋裕明

特許第4076114号

Property Type: Patent
4’−C−エチニルピリミジンヌクレオシド化合物

大類洋, 向後悟, 児玉栄一, 茂田士郎, 満屋裕明

特許第4039790号

Property Type: Patent
エプスタイン・バールウイルス関連疾患に対する薬剤およびそのスクリーニング法

児玉栄一, 松岡雅雄, 芦田則之

特許第5326173号

Property Type: Patent

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Research Projects 18

呼吸器ウイルス感染症における重症化抑制に関する研究

菊地章子, 山谷睦雄, 児玉栄一, 高山真, 西村秀一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北大学

2023/04/01 - 2028/03/31
高活性触媒的標的RNA切断機能付与型人工核酸の構築と新興感染症等治療基盤の創製

和田健彦, 林宏典, 児玉栄一, 稲垣雅仁, 西嶋政樹, 荒木保幸

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(A)

Institution: 東北大学

2023/04/01 - 2026/03/31
新規免疫抑制分子Plet-1の機能解析と革新的なARDS治療薬の開発

笠松純, 佐藤光, 児玉栄一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 基盤研究(C)

Institution: 東北大学

2022/04/01 - 2025/03/31
コロナウイルス制圧のための新規膜融合阻害ペプチドの創出と合理的な設計法の確立

児玉栄一, 大石真也

Offer Organization: 日本学術振興会

System: 科学研究費助成事業

Category: 挑戦的研究(萌芽)

Institution: 東北大学

2021/07/09 - 2024/03/31

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本研究は、ウイルス膜融合をモデルとしてヘリックス相互作用を阻害することによって効率的で汎用性の高いタンパク機能阻害剤の開発方法を提案することを目的にしている。方法論の確立に加えて迅速な社会実装を踏まえ、昨今のパンデミックをおこした新型コロナウイルスをモデルとしている。本ウイルスの侵入機序はClass I膜融合である。この膜融合にスパイクタンパクC末端側に位置するウイルスエンベロープ貫通ドメインを有するウイルス融合タンパク（FP）が重要な役割を果たす。このFPには特徴的な2つのヘリックス構造があり、このヘリックス相互作用によるFPの構造変化が侵入に大切である。この構造変化阻害のためFPを標的としたペプチド設計法とin vitro 耐性誘導を組み合わせ、１）設計-２）評価-３）耐性ウイルス誘導-４）耐性機序の解明-５）耐性機序を利用したペプチド創製（最終段階の５）は１）の設計につながる）といった 4 工程を繰り返すことにより、より強力で薬剤耐性を生じにくい阻害剤を効果的にかつ短期間に開発することを目指す。本年度は、効率的な抗ウイルス活性の評価方法として非感染系で迅速にハイスループットが期待できる独自のELISA法を開発した。さらに培養細胞と感染性ウイルスを用いる従来評価法を応用し、より安全で短期間にできるMTT色素法を組み合わせた培養評価系も確立した。これらを駆使し、ウイルス感染を抑制しうる重要なアミノ酸配列の同定、複数の候補ペプチド配列を同定している。また、新たなウイルスパネルも構築しつつある。本年度の進捗は順調である。
Development of a gel encapsulating cells capable of secreting functional exosomes for cell therapy

Nakase Ikuhiko

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Challenging Research (Pioneering)

Institution: Osaka Prefecture University

2019/06/28 - 2022/03/31

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The purpose of this research project is to establish an intracellular encapsulation gel system capable of secreting functional exosomes as a new technique that can contribute to cell therapy. Using agarose gel, secretory exosomes pass through, but the mother cells do not pass through to create cell inclusions, and the relatively high cell viability of the gel-encapsulating cells and the exosome secretion that maintains the properties from the cell-encapsulating gel. It was shown that exosomes are effectively taken up by surrounding cancer cells after secretion. Furthermore, we have succeeded in constructing a technology that can bind to secretory exosomes in gels using antibodies that can target cancer cells. The construction of our basic technology is considered to be as a new cell therapy technology that can target secretory exosomes to targeted disease-related cells.
Development of therapeutics for intractable infections using diverse natural products combined with stress-inductive biosynthesis and chemical modification

Kodama Eiichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2019/04/01 - 2022/03/31

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Molecular and structural diversities of natural compound have been required to expand for drug development. Here, we produced novel natural derivatives by the biosynthetic pathway remodeled by genome mining technology and identified novel anti-HIV agent. We established a simple and rapid screening method to develop antiviral agents against adenovirus, which caused epidemic keratoconjunctivitis. Additionally, we also identified several novel classes of antibacterial agents, which blocked uridine kinase, thymidine synthetase and serine hydroxymethyl transferase. Moreover, anti-viral and -bacterial mechanisms of compounds we identified were analyzed by time-of-addition method and crystal structural analysis. These results are important not only to expand molecular and structural diversities of natural compounds but also to develop therapeutic agents against antimicrobial resistances, unpredictable outbreaks and wildly destructive health consequences.
Novel screenings for unmet medical needs with innovative new natural product derived compounds

Kodama Eiichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2016/04/01 - 2019/03/31

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In the project, we have successfully established unique and divergent chemical libraries with innovative natural products under up-regulation of the synthetic enzymes and/or pathways of plants or microbes by various anti-silencing agents. Further chemical modifications have been applied to the isolated products and determined chemical structures with nuclear magnetic resonance analysis. In addition, we have also established several novel screening methods for unmet medical needs. Some compounds show new biological activities, such as anti-osteoporosis, anti-cancers associated with virus infections, and anti-viruses. These valuable achievements were published and presented in scientific meetings elsewhere. Our innovative libraries and novel screening systems based on chemical biology may contribute to rational drug designs and developments.
Development of antiviral agents targeting ATP-mediated excision

Kodama Eiichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research

Category: Grant-in-Aid for Challenging Exploratory Research

Institution: Tohoku University

2013/04/01 - 2016/03/31

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In this study, we tried to expand our findings of ATP-medicated nucleotide excision inhibition, to biochemical, pharmacological, and structural aspects of DNA polymerases, via HIV reverse transcriptase as a model enzyme. We have established a novel assay system and screened over 5000 chemical compounds developed in the Tohoku University. Employing the identified several hits, structure-activity relation analysis is now in progress. In addition, we demonstrated that inhibitors for HIV reverse transcriptase appear to be experimentally suitable candidate to control differention process of mouse oocyte. Here we demonstrate that antiviral agents are useful for wide-range chemical biology tools as well as medical purpose.
Development of anti-HIV agents that exert synergism with host immune pressure

KODAMA Eiichi, UENO Takamasa

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)

Category: Grant-in-Aid for Scientific Research (B)

Institution: Tohoku University

2012/04/01 - 2015/03/31

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Treatment of HIV, so far, remains to be insufficient. Therefore, development of efficient and safe therapy for HIV infection is urgently needed. Here, we focus on one of essential accessary viral proteins, Nef that has povital role in escape from host immune system, through immunological, rational drug design, and structural features. We newly identified novel domains for down regulation of MHC class I, and HIV receptors CD4 and CCR5, and established a screening system for Nef antagonists. Furthermore, we revealed impaired Nef functions in the elite controllers. Our findings will provide insights into further successful therapies and development of effective vaccines.
Clinical Utilities of new biomarker for dengue virus infection

HATTORI Toshio, NIKI Toshiro, HIRASHIMA Mitsuomi, HAORILE Chagan-Yasutan, KUBO Toru

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)

Category: Grant-in-Aid for Scientific Research (A)

Institution: Tohoku University

2011/04/01 - 2015/03/31

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Matricellular proteins of galectin-9 (Gal-9) and osteopontin (OPN) were studied in plasma from 65 dengue virus (DENV) infected patients. During the critical phase, Gal-9 levels were significantly higher in DENV infected patients compared to control groups. The highest Gal-9 levels were observed in dengue hemorrhagic fever (DHF) patients (DHF: 2464pg/ml; dengue fever (DF): 1407pg/ml). In the recovery phase, Gal-9 levels significantly declined from peak levels in those patients. Gal-9 levels tracked viral load, and were associated with monocyte frequencies and hematologic variables of coagulation. Plasma levels of OPN were significantly elevated in the critical phase in both of DF and DHF as compared with healthy. During the recovery phase, OPN levels declined while thrombin cleaved OPN levels increased dramatically in both of DF and DHF patients. Thus, Gal-9 and OPN appears to track DENV inflammatory responses and it could serve as an important novel biomarker of acute DENV infection..
Mechanism of resistance to translocation defective reverse transcriptase inhibitors

ASHINO Yugo, KODAMA Eiichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2011/04/28 - 2014/03/31

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A novel nucleoside reverse transcriptase (RT) inhibitor, 4'-ethynyl-2-fluoro-deoxyadenosine (EFdA) inhibits translocation activity of RT. To elucidate mechanism of the action in detail, resistant HIV-1 and -2 variants to EFdA were induced in vitro. M184I/V in the RT was identified as the primary mutation, while A158T and T165M/R were considered as the secondary mutations. M184I/V much reduced replication kinetics of HIV, but some of the secondary mutations improved the reduced replication. Data obtained from enzymatic assays with recombinant RT well supported those from viral assays. In this study, we provide crucial information of key amino aicds for tranlocation activity and of drug design for novel inhibitors.
Effect of a novel resistance associated mutation, N348I, which has been identified in Japanese HIV-1 infected patients, on the reverse transcriptase activity.

KODAMA Eiichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Tohoku University

2009 - 2011

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Effect of a novel resistance associated mutation, N348I, which has been identified in Japanese HIV-1 infected patients, on the reverse transcriptase activity.
Establishment of Rev based anti-HIV therapy.

KODAMA Eiichi

Offer Organization: Japan Society for the Promotion of Science

System: Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)

Category: Grant-in-Aid for Scientific Research (C)

Institution: Kyoto University

2005 - 2006

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Even under highly active anti-retroviral therapy using extensive combination of inhibitors to reverse transcriptase and/or protease, eradication of human immunodeficiency virus (HIV) remains to be achieved. Thus, development of new inhibitors that block new targets as well as reverse transcriptase or protease is urgently required. In this project, the principal investigator focuses on a viral accessory protein, Rev that is essential for HIV replication and has developed peptide based Rev inhibitors. The investigator found that a peptide containing 10 to 63 amino acids of Rev transduced cells were resistant to HIV infection, suggesting that the region contains an HIV inhibitory peptide sequence. To identify the region, expression vectors containing peptide sequences in various size and region of Rev 10 to 63 were constructed. Among them, a peptide containing arginine rich 34 to 50 amino acid sequence showed inhibitory effect. Addition of four alanines that stabilize α-helical structure enhances the inhibitory effect. Human T-cell leukemia virus Rex, a homolog of Rev also has arginine rich domain. This region also showed inhibitory effect to HIV infection. Synthetic peptides also block HIV infections through its binding to CXCR4, not through suppression of Rev function, indicating that enhancement of peptide penetration efficiency into cells is needed. Further study is needed to develop clinically useful Rev inhibitors.
ヘルペスウイルスを標的とした新規治療薬開発による難治性腫瘍克服

松岡雅雄, 児玉栄一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業萌芽研究

Category: 萌芽研究

Institution: 京都大学

2003 - 2004

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内在性thymidine kinase(TK)欠損細胞株であるヒト骨肉腫細胞株143BにEBV-TK,KSHV-TK、ヒトTK遺伝子を発現させ、この細胞株に様々な核酸化合物を添加しMTTアッセイで細胞傷害作用を確認することによりTKでリン酸化される化合物をスクリーニングした。核酸系化合物をスクリーニングすることによりEBV-TK,KSHV-TK特異的に阻害効果を有する化合物を同定した.EBV-TK発現細胞株に対するEC50は0.049μg/mlであり、KSHV-TK発現細胞株に対するEC50は0.64μg/mlであった。EBV感染細胞株RPMI8866を用いてDNAメチル化阻害剤である5-aza-deoxy-cytidine (5-azaCdR)、Histone deacethylase阻害剤であるTrichostatin A(TSA)、butylateで処理することによって化合物に対する感受性の亢進を認めた。またEBV初感染により引き起こされるChronic EBV infectionに対する治療効果を確認するために末梢血リンパ球にB958より分離したEBVを感染させる系に薬剤を加え、その抑制効果を解析した。本化合物を加えることによりMTTアッセイで細胞数の減少を認め、primary infectionに対しても有効である可能性が示唆された。
ヒト免疫不全症ウイルス・細胞融合機構の解明と治療への応用

児玉栄一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業若手研究(B)

Category: 若手研究(B)

Institution: 京都大学

2003 - 2004

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In vitroにおけるgp41由来ペプチドに対する耐性機序を明らかにするため、gp41C末端heptad repeat由来ペプチドC34耐性HIV-1株を作製し、その耐性機序を解析した。その耐性ウイルスのgp120では連続する5アミノ酸が欠失しており(ΔFNSTW)、またgp41では計7つのアミノ酸置換が認められた(A30V、D36G、Q39H、I37T、I37K、N126K、L2041)。このうちI37T、I37KおよびN126Kは耐性化に関与しており、その中でもI37Kが耐性責任変異であったが、I37Kのみでは十分なC34耐性を得られず、高度耐性を獲得するためにはアミノ酸変異の蓄積が必要であることが示された。一方、A30V、D36GおよびL2041は複製能の向上に、gp120に認められたΔFNSTWは耐性度の上昇と複製能の向上の両方に関与していた。本研究の結果から、耐性に直接寄与する変異がまず導入されるが、それらは同時に複製能を低下させてしまうため複製能を向上させる変異が出現し、それらが交互に追加されてゆくことが示された。また、耐性責任変異であるI37KはC34との結合力を弱めるが、N126Kは、I37Kを有する変異N-HRとの結合力を回復させることを明らかとした。A30とD36における塩基置換は、ウイルスゲノムRNAを細胞核外へ輸送するRevタンパクが結合するRev responsive element (RRE)領域中に存在し、I37の置換によって変化したRREの2次構造を補正していた。さらにgp41コード領域はRREのみならず、tatやrevの一部をコードしていることから、HIVは融合阻害剤に対する変異を容易に導入することはできないと推測された。これらの結果は、HIV-1の融合阻害がHIV-1の化学療法における有効な標的の一つであることを示唆している。
新規HIV複製ステップの同定及びその阻害剤開発への応用

児玉栄一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究(A)

Category: 特定領域研究(A)

Institution: 京都大学

2001 - 2001

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研究代表者は、Human immunodeficiency virus (HIV)の薬剤耐性化を克服するために新規阻害ステップの同定および新規核酸系逆転写酵素阻害剤の関発を行った。今年度は野耐性ウイルスを含めたHIV-1のみならず、HIV-2にも効果を示す核酸誘導体、4'-ethynyl-2'-deoxynucleoside(4'-E-dN)を同定した。4'-E-dNは今までに報告のある主な薬剤耐性株(AZT、ddI、ddC、d4T、3-TC耐性株)に対しても強い抗ウイルス効果を維持しており、多剤併用療法(HAART)施行後問題となっている多剤耐性臨床分離HIVの複製も野生株同様に阻害した。特に4'-E-2'-deoxycytidine、4'-E-2'-deoxyadenosine(4'-E-dA)、4'-E-2'-deoxyribofuranosyl-2,6-diaminopurineが強い抗HIV効果を示した。これらの薬剤が核酸系逆転写酵素阻害剤として作用していることを明らかとした。この作用機序をさらに解明するために4'-E-dA耐性ウイルスの誘導を試みたところ、約80倍耐性を示すウイルスを分離することができた。4'-E-dA耐性ウイルスの逆転写酵素領域の塩基配列を解析したところ、逆転写酵素領域にI142V/T165R/M184Vといった新規変異を見出した。4'-E-dAとその誘導体および3-TCに対してのみ交叉耐性を示した。種々の組み合わせの分子クローンを用いて解析したところ、T165RとM184Vが主な耐性責任変異であった。単一変異では耐性は獲得されていなかった。これらアミノ酸変異部位は現在報告されている逆転写酵素立体構造においてすべてRT活性中心近傍に位置し、特にT165はM184と対をなしており、sterichindranceによって耐性化することを明らかとした。
薬剤耐性HIVに著効を示す新規核酸誘導体の開発

児玉栄一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業奨励研究(A)

Category: 奨励研究(A)

Institution: 京都大学

2000 - 2001

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研究代表者は、Human immunodeficiency virus(HIV)の薬剤耐性化を克服するために耐性ウイルスを含めたHIV-1のみならず、HIV-2にも効果を示す核酸誘導体、4'-ethyny1-2'-deoxynucleoside(4'-E-dN)を同定した。4'-E-dNは今までに報告のある主な薬剤耐性株(AZT、ddI、ddC、d4T、3-TC耐性株)に対しても強い抗ウイルス効果を維持しており、多剤併用療法(HAART)施行後問題となっている多剤耐性臨床分離HIVの複製も野生株同様に阻害した。特に4'-E-2'-deoxycytidine、4,-E-2'-deoxyadenosine(4'-E-dA)、4'-E-2'-deoxyribofuranosyl-2,6-diaminopurineが強い抗HIV効果を示した。これらの薬剤が核酸系逆転写酵素阻害剤として作用していることを明らかとした。この作用機序をさらに解明するために4'-E-dA耐性ウイルスの誘導を試みたところ、約80倍耐性をホすウイルスを分離することができた4'-E-dA耐性ウイルスの逆転写酵素領域の塩基配列を解析したところ、逆転写酵素領域にI142V/T165R/M184Vといった新規変異を見出した。4'-E-dAとその誘導体および3-TCに対してのみ交叉耐性を示した。種々の組み合わせの分子クローンを用いて解析したところ、T165RとM184Vが主な耐性責任変異であった。単一変異では耐性は獲得されていなかうた。これらアミノ酸変異部位は現在報告されている逆転写酵素立体構造においてすべてRT活性中心近傍に位置し、特にT165はM184と対をなしており、steric hindranceによって耐性化することを明らかとした。
新規HIV複製ステップの同定及びその阻害剤開発への応用

児玉栄一

Offer Organization: 日本学術振興会

System: 科学研究費助成事業特定領域研究(A)

Category: 特定領域研究(A)

Institution: 京都大学

2000 - 2000

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研究代表者は今まで同定されていないHIV複製ステップを阻害する薬剤(Y-664)を発見、報告した。Y-664はAZTとの併用で相乗効果が認められ、治療上問題となる多剤耐性HIVに対しても野生株と同様な効果を示した。また、Y-664は宿主細胞への吸着、進入および逆転写反応を阻害しないが、宿主細胞内でのウイルスDNAの合成を濃度依存的に阻害した。作用機序解明のためY-664に対する耐性HIVをin vitroで誘導し、約4倍の耐性度を示すHIVを分離した。このHIVの複製能は野生株と比べ低下していた。その変異部位をplasmid cloneであるpNL4-3と組み替え、解析したところpolおよびvifをコードする部位が耐性に関与していることが判明し、現在その詳細な解析を行っている。さらに作用機序が未だ解明されていない薬剤を18種同定し、そのうち14種類が宿主細胞への吸着からprovirus組み込みまでに関与していることを明らかとした。この研究で確立した方法を用い、耐性株に対して効果を示す新規核酸誘導体の作用機序を解明したところ、逆転写酵素阻害剤であると同定でき、その結果を論文にまとめることが可能であった。

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安全かつ効果的な抗HIV療法開発のための研究

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安全かつ効果的な抗HIV療法開発のための研究
人獣共通感染症病因の生態と病原性の分子基盤

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人獣共通感染症の制圧に向けた基礎研究
人獣共通感染症病因の生態と病原性の分子基盤

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