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1. Association of postmenopausal endogenous sex hormones with global methylation level of leukocyte DNA among Japanese women

Author

Iwasaki Motoki, Ono Hiroe, Kuchiba Aya, Kasuga Yoshio, Yokoyama Shiro, Onuma Hiroshi, Nishimura Hideki, Kusama Ritsu, Yoshida Teruhiko, and Tsugane Shoichiro

Subjects
Cross-sectional study, Endogenous sex hormones, Global methylation level, Luminometric methylation assay, Peripheral blood leukocyte DNA, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Although global hypomethylation of leukocyte DNA has been associated with an increased risk of several sites of cancer, including breast cancer, determinants of global methylation level among healthy individuals remain largely unexplored. Here, we examined whether postmenopausal endogenous sex hormones were associated with the global methylation level of leukocyte DNA. Methods A cross-sectional study was conducted using the control group of a breast cancer case–control study in Nagano, Japan. Subjects were postmenopausal women aged 55 years or over who provided blood samples. We measured global methylation level of peripheral blood leukocyte DNA by luminometric methylation assay; estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate, testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex-hormone binding globulin by immunoradiometric assay. A linear trend of association between methylation and hormone levels was evaluated by regression coefficients in a multivariable liner regression model. A total of 185 women were included in the analyses. Results Mean global methylation level (standard deviation) was 70.3% (3.1) and range was from 60.3% to 79.2%. Global methylation level decreased 0.27% per quartile category for estradiol and 0.39% per quartile category for estrone while it increased 0.41% per quartile category for bioavailable estradiol. However, we found no statistically significant association of any sex hormone level measured in the present study with global methylation level of leukocyte DNA. Conclusions Our findings suggest that endogenous sex hormones are not major determinants of the global methylation level of leukocyte DNA.

Published
2012
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2. Comparison of postmenopausal endogenous sex hormones among Japanese, Japanese Brazilians, and non-Japanese Brazilians

Author

Maciel Maria, Nishimoto Ines, Hamada Gerson, Kusama Ritsu, Nishimura Hideki, Onuma Hiroshi, Yokoyama Shiro, Kasuga Yoshio, Iwasaki Motoki, Motola Juvenal, Laginha Fábio, Anzai Roberto, and Tsugane Shoichiro

Subjects
Medicine
Abstract

Abstract Background Differences in sex hormone levels among populations might contribute to the variation in breast cancer incidence across countries. Previous studies have shown higher breast cancer incidence and mortality among Japanese Brazilians than among Japanese. To clarify the difference in hormone levels among populations, we compared postmenopausal endogenous sex hormone levels among Japanese living in Japan, Japanese Brazilians living in the state of São Paulo, and non-Japanese Brazilians living in the state of São Paulo. Methods A cross-sectional study was conducted using a control group of case-control studies in Nagano, Japan, and São Paulo, Brazil. Participants were postmenopausal women older than 55 years of age who provided blood samples. We measured estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone and free testosterone by radioimmunoassay; bioavailable estradiol by the ammonium sulfate precipitation method; and sex hormone-binding globulin (SHBG) by immunoradiometric assay. A total of 363 women were included for the present analyses, comprising 185 Japanese, 44 Japanese Brazilians and 134 non-Japanese Brazilians. Results Japanese Brazilians had significantly higher levels of estradiol, bioavailable estradiol, estrone, testosterone and free testosterone levels, and lower SHBG levels, than Japanese. Japanese Brazilians also had significantly higher levels of bioavailable estradiol, estrone and DHEAS and lower levels of SHBG and androstenedione than non-Japanese Brazilians. Levels of estradiol, testosterone and free testosterone, however, did not differ between Japanese Brazilians and non-Japanese Brazilians. These differences were observed even after adjustment for known breast cancer risk factors. We also found an increase in estrogen and androgen levels with increasing body mass index, but no association for most of the other known risk factors. Conclusions We found higher levels of estrogens and androgens in Japanese Brazilians than in Japanese and levels similar to or higher than in non-Japanese Brazilians. Our findings may help explain the increase in the incidence and mortality rate of breast cancer among Japanese Brazilians.

Published
2011
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4. Fulminant Type 1 Diabetes Caused by DIHS Could Be Affected by the Reactivation of HHV-6.

Author

Makino, Hideichi, Tohyama, Mikiko, Kawamura, Ryoichi, Takata, Yasunori, Osawa, Haruhiko, and Onuma, Hiroshi

Subjects
IMMUNE reconstitution inflammatory syndrome, TYPE 1 diabetes, HUMAN herpesvirus-6, ANTIBODY titer, ETIOLOGY of diabetes
Abstract

Context In the previous issue of this journal, we reported that the incidence of fulminant type 1 diabetes (FT1D) due to the drug-induced hypersensitivity syndrome (DIHS) in Japan is higher than that in the general population and is associated with HLAB62. On the other hand, the reactivation of human herpesvirus 6 (HHV-6), which has been reported to be associated with DIHS, was observed at a higher frequency, but its association with the development of FT1D was unclear. Objective We aimed to clarify the relationship between the onset of FT1D and the reactivation of HHV-6. Methods We conducted a literature search for cases of DIHS-induced FT1D in addition to previously reported cases and investigated the changes in the HHV-6 antibody titer before and after the onset of FT1D. Results The HHV-6 antibody titer was increased just before or after the onset of FT1D in all 8 cases. In 1 case, HHV-6 DNA was also identified shortly before the onset of FT1D. Conclusion These results indicate for the first time that the reactivation of HHV-6 is associated with the onset of FT1D caused by DIHS. [ABSTRACT FROM AUTHOR]

Published
2024
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10. Recurrent Hypoglycemia Due to a High Titer of Insulin Antibody in Response to Exogenous Insulin Administration in Two Cases of Type 1 Diabetes

Author

Kawamura, Ryoichi, primary, Miyao, Satoshi, additional, Onuma, Hiroshi, additional, Uchigata, Yasuko, additional, Kawasaki, Eiji, additional, Ohashi, Jun, additional, Shiraishi, Sanshiro, additional, Nishida, Wataru, additional, Yokomoto-Umakoshi, Maki, additional, Takata, Yasunori, additional, Osawa, Haruhiko, additional, and Makino, Hideichi, additional

Published
2022
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15. Japanese consensus guidelines for pediatric nuclear medicine: Part 1: Pediatric radiopharmaceutical administered doses (JSNM pediatric dosage card). Part 2: Technical considerations for pediatric nuclear medicine imaging procedures

Author

Koizumi, Kiyoshi, Masaki, Hidekazu, Matsuda, Hiroshi, Uchiyama, Mayuki, Okuno, Mitsuo, Oguma, Eiji, Onuma, Hiroshi, Kanegawa, Kimio, Kanaya, Shinichi, Kamiyama, Hiroshi, Karasawa, Kensuke, Kitamura, Masayuki, Kida, Tetsuo, Kono, Tatsuo, Kondo, Chisato, Sasaki, Masayuki, Terada, Hitoshi, Nakanishi, Atsushi, Hashimoto, Teisuke, Hataya, Hiroshi, Hamano, Shin-ichiro, Hirono, Keishi, Fujita, Yukihiko, Hoshino, Ken, Yano, Masayuki, Watanabe, Seiichi, The Japanese Society of Nuclear Medicine, and Optimization Committee for Pediatric Nuclear Medicine Studies

Published
2014
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16. Endoplasmic reticulum stress induced by tunicamycin increases resistin messenger ribonucleic acid through the pancreatic endoplasmic reticulum eukaryotic initiation factor 2α kinase–activating transcription factor 4–CAAT/enhancer binding protein-α homologous protein pathway in THP-1 human monocytes

Author

Hamada, Junpei, Onuma, Hiroshi, Ochi, Fumihiro, Hirai, Hiroki, Takemoto, Koji, Miyoshi, Akiko, Matsushita, Manami, Kadota, Yuko, Ohashi, Jun, Kawamura, Ryoichi, Takata, Yasunori, Nishida, Wataru, Hashida, Seiichi, Ishii, Eiichi, and Osawa, Haruhiko

Published
2016
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21. CDH13 Genotype-dependent association of high-molecular weight adiponectin with all-cause mortality: the J-SHIPP study

Author

Uetani, Eri, Tabara, Yasuharu, Kawamoto, Ryuichi, Onuma, Hiroshi, Kohara, Katsuhiko, Osawa, Haruhiko, and Miki, Tetsuro

Subjects
Cholesterol -- Genetic aspects -- Research, Mortality -- Japan -- Genetic aspects -- Research, Chromosomes -- Genetic aspects -- Research, Health
Abstract

OBJECTIVE Despite its anti-inflammatory and antiatherogenic effects, adiponectin is potentially associated with adverse clinical outcomes, such as all-cause mortality. As plasma adiponectin levels are strongly influenced by single nucleotide polymorphisms [...]

Published
2014
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23. Dietary isoflavone intake and breast cancer risk in case–control studies in Japanese, Japanese Brazilians, and non-Japanese Brazilians

Author

Iwasaki, Motoki, Hamada, Gerson Shigeaki, Nishimoto, Ines Nobuko, Netto, Mario Mourão, Motola, Jr., Juvenal, Laginha, Fábio Martins, Kasuga, Yoshio, Yokoyama, Shiro, Onuma, Hiroshi, Nishimura, Hideki, Kusama, Ritsu, Kobayashi, Minatsu, Ishihara, Junko, Yamamoto, Seiichiro, Hanaoka, Tomoyuki, and Tsugane, Shoichiro

Published
2009
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24. Genetic variation in CDH13 is associated with lower plasma adiponectin levels but greater adiponectin sensitivity in East Asian populations

Author

Gao, He, Kim, Yu-Mi, Chen, Peng, Igase, Michiya, Kawamoto, Ryuichi, Kim, Mi Kyung, Kohara, Katsuhiko, Lee, Jeannette, Miki, Tetsuro, Ong, Rick Twee-Hee, Onuma, Hiroshi, Osawa, Haruhiko, Sim, Xueling, Teo, Yik Ying, Tabara, Yasuharu, Tai, E. Shyong, and van Dam, Rob M.

Subjects
Cadherins -- Research, Health
Abstract

Variants in the CDH13 gene have been identified as determinants of blood levels of adiponectin, an insulin-sensitizing adipokine. However, their association with other metabolic risk factors remains unclear. We examined variants at CDH13 in relation to total and high-molecular-weight (HMW) adiponectin using data from a genome-wide association study performed in 2,434 Singaporean Chinese with replication in up to 3,290 Japanese and 1,610 Koreans. The top signal rs4783244 in CDH13 showed strong associations with total adiponectin (standardized β [β] = -0.34, 95% CI -0.38 to -0.30, P = 2.0 x [10.sup.-70]), HMW adiponectin (β = HMW-to-total adiponectin ratio (β = -0.44, 95% CI -0.49 to -0.40, P = 3.2 x [10.sup.-83]). In the replication study, this single nucleotide polymorphism explained 4.1% of total and 6.5% of HMW adiponectin levels. No association was observed between rs4783244 and metabolic traits associated with insulin resistance before adjustment for HMW adiponectin levels. After adjustment for HMW adiponectin levels, the minor allele was associated with lower BMI (β = -0.15, 95% CI -0.19 to -0.11, P = 3.5 x [10.sup.-14]), homeostasis model assessment-insulin resistance index (β = -0.16, 95% CI -0.20 to -0.12, P = 9.2 x [10.sup.-16]), and triglycerides (β = -0.16, 95% CI -0.19 to -0.12, P = 1.3 x [10.sup.-16]) and with higher HDL (β = 0.16, 95% CI 0.12 to 0.19, P = 2.1 x [10.sup.-17]). CDH13 variants strongly influence plasma total and HMW adiponectin levels in East Asian populations but appear to alter adiponectin sensitivity, resulting in better metabolic health than expected based on circulating adiponectin levels., Adiponectin is a protein abundantly secreted by adipose tissue with anti-inflammatory (1) and insulin-sensitizing properties (2). Blood levels of diponectin are inversely associated with obesity (3), insulin resistance (4), and [...]

Published
2013
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26. Abstract PD1-09: Safety and efficacy results from the phase 1/2 study of U3-1402, a human epidermal growth factor receptor 3 (HER3)-directed antibody drug conjugate (ADC), in patients with HER3-expressing metastatic breast cancer (MBC)

Author

Krop, Ian, primary, Yonemori, Kan, additional, Takahashi, Shunji, additional, Inoue, Kenichi, additional, Nakayama, Takahiro, additional, Iwata, Hiroji, additional, Toyama, Tatsuya, additional, Yamamoto, Yutaka, additional, Takahashi, Masato, additional, Osaki, Akihiko, additional, Saji, Shigehira, additional, Sagara, Yasuaki, additional, O’Shaughnessy, Joyce, additional, Traina, Tiffany, additional, Ohwada, Shoichi, additional, Qi, Zhenhao, additional, Qiu, Yang, additional, Onuma, Hiroshi, additional, Sharma, Om, additional, Mekan, Sabeen, additional, and Masuda, Norikazu, additional

Published
2021
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27. The G/G genotype of a resistin single-nucleotide polymorphism at -420 increases type 2 diabetes mellitus susceptibility by inducing promoter activity through specific binding of Sp1/3

Author

Osawa, Haruhiko, Yamada, Kazuya, Onuma, Hiroshi, Murakami, Akiko, Ochi, Masaaki, Kawata, Hiroko, Nishimiya, Tatsuya, Niiya, Toshiyuki, Shimizu, Ikki, Nishida, Wataru, Hashiramoto, Mitsuru, Kanatsuka, Azuma, Fujii, Yasuhisa, Ohashi, Jun, and Makino, Hideichi

Subjects
Diabetes -- Research, Diabetes -- Genetic aspects, Type 2 diabetes -- Research, Type 2 diabetes -- Genetic aspects, Biological sciences
Published
2004

32. Abstract OT1-07-06: Phase 1/2 first-in-human study of U3-1402, an anti-human epidermal growth factor receptor 3 (HER3) antibody-drug conjugate, in HER3-expressing advanced/unresectable or metastatic breast cancer, including those with triple negative breast cancer (TNBC) or HER3-low disease

Author

Krop, Ian, primary, Masuda, Norikazu, additional, Kogawa, Takahiro, additional, Takahashi, Shunji, additional, Yonemori, Kan, additional, Inoue, Kenichi, additional, Nakayama, Takahiro, additional, Yamamoto, Yutaka, additional, Alvarez, Ricardo, additional, Toyama, Tatsuya, additional, Osaki, Akihiko, additional, Takahashi, Masato, additional, O'Shaughnessy, Joyce, additional, Sagara, Yasuaki, additional, Saji, Shigehira, additional, Kaklamani, Virginia, additional, Oh, Sun Young, additional, Gradishar, William, additional, Haley, Barbara, additional, Iwasa, Tsutomu, additional, Traina, Tiffany, additional, Ueno, Naoto, additional, Isakoff, Steve, additional, Ohwada, Shoichi, additional, Tanaka, Yoshimi, additional, Mekan, Sabeen, additional, Onuma, Hiroshi, additional, Sharma, Om, additional, and Iwata, Hiroji, additional

Published
2020
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34. Isoflavone, polymorphisms in estrogen receptor genes and breast cancer risk in case-control studies in Japanese, Japanese Brazilians and non-Japanese Brazilians

Author

Iwasaki, Motoki, Hamada, Gerson Shigeaki, Nishimoto, Inês Nobuko, Netto, Mario Mourão, Motola, Juvenal, Jr, Laginha, Fábio Martins, Kasuga, Yoshio, Yokoyama, Shiro, Onuma, Hiroshi, Nishimura, Hideki, Kusama, Ritsu, Kobayashi, Minatsu, Ishihara, Junko, Yamamoto, Seiichiro, Hanaoka, Tomoyuki, and Tsugane, Shoichiro

Published
2009
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36. Empirical Research about the Corporate Governance Structure of the Firms Executed by Transfer Pricing Taxation

Author

Sakurada, Joe and Onuma, Hiroshi

Abstract

本研究は移転価格税制(TPTS)の適用を受けた企業の株価が下落する現象を与件としながら、下落する株価の多寡はコーポレート・ガバナンス（CG）の巧拙や財務構成の違いに影響を受けるとの仮説を検証している。TPTSの適用は一種の企業不祥事であり、情報の非対称性の高い租税関連事象であるため、投資家は企業価値の毀損を覚悟するものの、投資家の抱く不安が何によって大きくなり、又逆に和らげられるのかについて本研究では関心があり、解明を試みている。分析の結果としてTPTSが適用された直後は社外取締役を採用した企業ほど失望が大きい反面、外国人持株比率が高い場合や無形資産の保有が高い場合には投資家の不安が抑えられている。またTPTS適用日を挟んで数日間の投資家の反応を観てみると、webによる情報公開に積極的である場合や当座比率が高い場合に投資家の不安が高まることが明らかとなった。これらのことからTPTSのみならず、その他の企業不祥事においてもCGや財務構成によって投資家による企業評価が左右されているのではないかと考えられる。

Published
2016

41. Plasma resistin, associated with single nucleotide polymorphism -420, is correlated with insulin resistance, lower HDL cholesterol, and high-sensitivity C-reactive protein in the Japanese general population

Author

Osawa, Haruhiko, Tabara, Yasuharu, Kawamoto, Ryuichi, Ohashi, Jun, Ochi, Masaaki, Onuma, Hiroshi, Nishida, Wataru, Yamada, Kazuya, Nakura, Jun, Kohara, Katsuhiko, Miki, Tetsuro, and Makino, Hideichi

Subjects
Insulin resistance -- Causes of -- Research -- Risk factors -- Genetic aspects, Genetic susceptibility -- Research -- Health aspects -- Genetic aspects, Single nucleotide polymorphisms -- Research -- Health aspects -- Genetic aspects, Type 2 diabetes -- Risk factors -- Genetic aspects -- Research, Health, Research, Genetic aspects, Risk factors, Causes of, Health aspects
Abstract

OBJECTIVE--Resistin, secreted from adipocytes, causes insulin resistance in rodents. We previously reported that the G/G genotype of a resistin gene promoter single nucleotide polymorphism (SNP) at -420 increases type 2 [...]

Published
2007

46. Hyperglycemia in non-obese patients with type 2 diabetes is associated with low muscle mass: The Multicenter Study for Clarifying Evidence for Sarcopenia in Patients with Diabetes Mellitus

Author

50203104, Sugimoto, Ken, Tabara, Yasuharu, Ikegami, Hiroshi, Takata, Yasunori, Kamide, Kei, Ikezoe, Tome, Kiyoshige, Eri, Makutani, Yukako, Onuma, Hiroshi, Gondo, Yasuyuki, Ikebe, Kazunori, Ichihashi, Noriaki, Tsuboyama, Tadao, Matsuda, Fumihiko, Kohara, Katsuhiko, Kabayama, Mai, Fukuda, Masahiro, Katsuya, Tomohiro, Osawa, Haruhiko, Hiromine, Yoshihisa, Rakugi, Hiromi, 50203104, Sugimoto, Ken, Tabara, Yasuharu, Ikegami, Hiroshi, Takata, Yasunori, Kamide, Kei, Ikezoe, Tome, Kiyoshige, Eri, Makutani, Yukako, Onuma, Hiroshi, Gondo, Yasuyuki, Ikebe, Kazunori, Ichihashi, Noriaki, Tsuboyama, Tadao, Matsuda, Fumihiko, Kohara, Katsuhiko, Kabayama, Mai, Fukuda, Masahiro, Katsuya, Tomohiro, Osawa, Haruhiko, Hiromine, Yoshihisa, and Rakugi, Hiromi

Abstract

AIMS/INTRODUCTION: Hyperglycemia is a risk factor for sarcopenia when comparing individuals with and without diabetes. However, no studies have investigated whether the findings could be extrapolated to patients with diabetes with relatively higher glycemic levels. Here, we aimed to clarify whether glycemic control was associated with sarcopenia in patients with type 2 diabetes. MATERIALS AND METHODS: Study participants consisted of patients with type 2 diabetes (n = 746, the average age was 69.9 years) and an older general population (n = 2, 067, the average age was 68.2 years). Sarcopenia was defined as weak grip strength or slow usual gait speed and low skeletal mass index. RESULTS: Among patients with type 2 diabetes, 52 were diagnosed as having sarcopenia. The frequency of sarcopenia increased linearly with glycated hemoglobin (HbA1c) level, particularly in lean individuals (HbA1c <6.5%, 7.0%, ≥6.5% and <7.0%: 18.5%; HbA1c ≥7.0% and <8.0%: 20.3%; HbA1c ≥8.0%: 26.7%). The linear association was independent of major covariates, including anthropometric factors and duration of diabetes (HbA1c <6.5%: reference; ≥6.5% and <7.0%: odds ratio [OR] 4.38, P = 0.030; HbA1c ≥7.0% and <8.0%: 4.29, P = 0.024; HbA1c ≥8.0%: 7.82, P = 0.003). HbA1c level was specifically associated with low skeletal mass index (HbA1c ≥8.0%: OR 5.42, P < 0.001) rather than weak grip strength (OR 1.89, P = 0.058) or slow gait speed (OR 1.13, P = 0.672). No significant association was observed in the general population with a better glycemic profile. CONCLUSIONS: Poor glycemic control in patients with diabetes was associated with low muscle mass.

Published
2019

47. Differences in the Contribution of HLA-DR and -DQ Haplotypes to Susceptibility to Adult- and Childhood-Onset Type 1 Diabetes in Japanese Patients

Author

Murao, Satoshi, Makino, Hideichi, Kaino, Yukikazu, Konoue, Etsushi, Ohashi, Jun, Kida, Kaichi, Fujii, Yasuhisa, Shimizu, Ikki, Kawasaki, Eiji, Fujiyama, Masao, Kondo, Shiori, Tanaka, Kiyonobu, Tarumi, Yoshinao, Seto, Isamu, Kato, Kenichi, Ohno, Keizo, Kusunoki, Yukiko, Ebisui, Osamu, Takada, Yasuharu, Tanabe, Katsuya, Takemoto, Koji, Onuma, Hiroshi, Nishimiya, Tatsuya, and Osawa, Haruhiko

Published
2004

50. Clinical, Autoimmune, and Genetic Characteristics of Adult-Onset Diabetic Patients With GAD Autoantibodies in Japan (Ehime Study)

Author

Takeda, Haruyo, Kawasaki, Eiji, Shimizu, Ikki, Konoue, Etsushi, Fujiyama, Masao, Murao, Satoshi, Tanaka, Kiyonobu, Mori, Kennichi, Tarumi, Yoshinao, Seto, Isamu, Fujii, Yasuhisa, Kato, Kenichi, Kondo, Shiori, Takada, Yasuharu, Kitsuki, Nobuaki, Kaino, Yukikazu, Kida, Kaichi, Hashimoto, Naotake, Yamane, Yukio, Yamawaki, Takashi, Onuma, Hiroshi, Nishimiya, Tatsuya, Osawa, Haruhiko, Saito, Yasushi, and Makino, Hideichi

Published
2002

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