著者

Hiroshi YAMADA Takashi DAIMON Katsuhiko MATSUDA Masayuki YOSHIDA Norikata TAKUMA Yukihiko HARA

出版者

The Japanese Society of Clinical Pharmacology and Therapeutics

雑誌

臨床薬理 (ISSN:03881601)

巻号頁・発行日

vol.38, no.5, pp.323-330, 2007-09-30 (Released:2008-10-31)

参考文献数

30

被引用文献数

11 14

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Experimental studies have revealed that tea catechins prevent influenza virus infection ; however, the clinical effects have been inconclusive. At the onset of the influenza season, a randomized, double-blind, placebo-controlled study was conducted from December 2005 to March 2006 in Japan. A total of 404 healthy volunteers, 20-65 years of age, were enrolled and randomly assigned to two groups : the catechin group gargling with tea catechin extract solution (approximately 400 μg/mL catechins) or the placebo group gargling without tea catechin extracts. In both groups, gargling was performed three times daily for 90 days. All participants were inoculated with the influenza vaccine before participating in the study. The primary outcome measure was the incidence rate of influenza infection during the study identified by a rapid assay for influenza virus antigens. On an intention to treat basis, 195 participants in the catechin group and 200 in the placebo group who started the intervention were included in the analysis. Of the participants, 6 (1.5%) were infected with influenza. The incidence rate of influenza infection in the catechin group (1.0%, 2 participants) was half that in the control group (2.0%, 4 participants), but not significant between the two groups. We could not find significant effects of gargling with tea catechin on prevention of influenza in the healthy adults inoculated with the influenza vaccine of the 2005-2006 season. However, the effects in more susceptible groups, i.e., those not vaccinated against the influenza virus, children, elderly or immunosuppressed people remain inconclusive.

著者

Atsushi Hirayama Shizuya Yamashita Andrea Ruzza Hyoe Inomata Marcoli Cyrille Chen Lu Andrew W. Hamer Masayuki Yoshida Arihiro Kiyosue Tamio Teramoto

出版者

The Japanese Circulation Society

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

vol.83, no.5, pp.971-977, 2019-04-25 (Released:2019-04-25)

参考文献数

11

被引用文献数

1

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Background: Treatment with evolocumab reduces mean low-density lipoprotein cholesterol (LDL-C) up to 75% and cardiovascular events by 16% in the first year and 25% thereafter. Methods and Results: Japanese patients with hypercholesterolemia enrolled in the parent YUKAWA-1-2 studies could enroll, once eligible, in the OSLER studies (n=556). OSLER re-randomized patients 2:1 to evolocumab plus standard of care (SOC; evolocumab+SOC) or SOC alone for 1 year; after year 1, patients could enter the all-evolocumab+SOC open-label extension of OSLER. Patients received evolocumab+SOC from the 2nd year through up to 5 years. Long-term efficacy and safety, including antidrug antibodies, were evaluated. Of 556 patients, 532 continued to the all-evolocumab+SOC extension: mean (standard deviation [SD]) age 61 (10) years, 39% female. A total of 91% of 532 patients completed the studies. Mean (SD) LDL-C change from parent-study baseline with evolocumab from a mean (SD) baseline of 142.3 (21.3) and 105.0 (31.1) mg/dL in OSLER-1 and OSLER-2, respectively, was maintained through the end of the study: −58.0% (19.1%) at year 5 in OSLER-1, −62.7% (25.6%) at year 3 in OSLER-2. The overall safety profile of the evolocumab+SOC periods was similar to that of the year-1 controlled period. Antidrug antibodies were detected transiently in 3 patients. No neutralizing antibodies were detected. Conclusions: Japanese patients who continued evolocumab+SOC for up to 5 years experienced sustained high LDL-C level reduction. Long-term evolocumab+SOC exposure showed no new safety signals.

著者

Miku Toyozaki Mizuko Osaka Kazuo Kondo Masayuki Yoshida

出版者

Japan Oil Chemists' Society

雑誌

Journal of Oleo Science (ISSN:13458957)

巻号頁・発行日

vol.62, no.4, pp.201-205, 2013 (Released:2013-03-28)

参考文献数

20

被引用文献数

3 4

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Recent studies have reported that dipeptidyl-peptitase IV (DPP-IV) is correlated with diabetic conditions and also with dyslipidemia caused by overnutrition, especially a high fat diet. However, the role of DPP-IV in diabetes during dyslipidemia has been unclear. We utilized a lymph fistula rat model to determine whether intestinal lymph, which absorbs dietary fats, is affected by a chronic high-fat and high-cholesterol diet (HFHC). HFHC diet rats showed significantly higher DPP-IV activity in intestinal lymph and plasma compared to rats receiving a normal chow diet. In addition, HFHC diet rats showed significantly increased DPP-IV mRNA expression in the intestine. However, DPP-IV mRNA in the lymphocytes isolated from intestinal lymph and mesenteric lymph nodes did not show significant differences from that in the normal diet rats. In conclusion, HFHC diets increased DPP-IV expression in intestinal lymph; these results indicate the applicability of a previously unrecognized role for DPP-IV in metabolic disorders, including diabetes.

著者

Jiro Aoyama Mizuko Osaka Michiyo Deushi Shoichi Hosoya Akihito Ishigami Taketoshi Maehara Masayuki Yoshida

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.63237, (Released:2021-12-08)

参考文献数

27

被引用文献数

5

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Aims: Vascular inflammation is critical for the development and progression of atherosclerosis. Previously, we reported that neutrophils adhere to the vascular endothelium in low-density lipoprotein receptor null mice fed a high-fat diet through hypercitrullination of histone H3 by peptidylarginine deiminase 4 (PAD4) in neutrophils. However, the involvement of PAD4 and citrullination of proteins other than histone H3 in neutrophil adhesion is not well known. In this study, we investigated the function of PAD4 and identified citrullinated proteins during vascular inflammation. Methods: We pefformed flow assay under physiological flow conditions using differentiated HL-60 (dHL-60) cells stimulated with CXCL1 and human umbilical vein endothelial cells (HUVECs). Furthermore, phalloidin stain for dHL-60 stimulated with CXCL1 to observe F-actin polymerization and immunohistochemistry for the activated β2-integrin was conducted. To identify a target of citrullination in the cytoplasm of dHL-60 cells, liquid chromatography-mass spectrometry (LC-MS/MS) for dHL-60 stimulated with CXCL1 was performed. Results: Inhibition or knockdown of PAD4 significantly decreased adhesion of under physiological flow conditions. Thr-Asp-F-amidine trifluoroacetate salt (TDFA), a PAD4 inhibitor, inhibited cytoplasmic translocation of PAD4 by CXCL1. TDFA or knockdown of PAD4 significantly decreased expression of β2-integrin and F-actin polymerization activated by CXCL1. Moreover, LC-MS/MS identified protein disulfide isomerase A1 (PDIA1) as a target of citrullination in the cytoplasm of dHL-60 cells. Knockdown of PDIA1 significantly decreased adhesion of dHL-60 cells to HUVECs, expression of β2-integrin, and F-actin polymerization. Conclusions: Cytoplasmic translocation of PAD4 by CXCL1 induces neutrophil adhesion to vascular endothelial cells and citrullination of PDIA1.

著者

Mari Hara Nakano Chihiro Udagawa Arata Shimo Yasuyuki Kojima Reiko Yoshie Hisamitsu Zaha Norie Abe Tokiwa Motonari Mikiko Unesoko Kenji Tamura Tatsunori Shimoi Masayuki Yoshida Teruhiko Yoshida Hiromi Sakamoto Ken Kato Taisei Mushiroda Koichiro Tsugawa Hitoshi Zembutsu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b19-00527, (Released:2019-10-09)

参考文献数

42

被引用文献数

14

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Trastuzumab has been administered to patients with HER2-positive cancer, however, the cardiotoxicity is identified as one of the life-threatening toxicities. Clinically useful biomarker for trastuzumab-induced cardiotoxicity has been expected to be developed. To identify a novel genetic marker(s) determining the risk of trastuzumab-induced cardiotoxicity, we performed a first genome-wide association study (GWAS) in Japanese population. We enrolled 481 patients who had been treated with trastuzumab and carried out a GWAS using 11 cases (with cardiotoxicity) and 257 controls (without cardiotoxicity). Top 100 single nucleotide polymorphisms (SNPs) which revealed the smallest P values in GWAS (P = 7.60 x 10-7 - 2.01 x 10-4) were further examined using replication samples consisted of 14 cases and 199 controls. The combined analysis of the GWAS and replication study indicated possible association of five loci with trastuzumab-induced cardiotoxicity (rs9316695 on chromosome 13q14.3, rs28415722 on chromosome 15q26.3, rs7406710 on chromosome 17q25.3, rs11932853 on chromosome 4q25, and rs8032978 on chromosome 15q26.3, Pcombined = 6.00 x 10-6, 8.88 x 10-5, 1.07 x 10-4, 1.42 x 10-4, 1.60 x 10-4, respectively). Furthermore, we developed a risk prediction model for trastuzumab-induced cardiotoxicity using the five marker SNPs. The incidence of trastuzumab-induced cardiotoxicity in patients with risk score ≥ 5 was significantly higher (42.5%) compared to that in patients with score ≤ 4 (1.8%) (P = 7.82 x 10-15, odds ratio = 40.0). These findings suggest the potential to improve the ability of physicians to avoid the trastuzumab-induced cardiotoxicity for patients with HER2-positive cancer.

著者

Hiroshi Yoshida Hayato Tada Kumie Ito Yoshimi Kishimoto Hidekatsu Yanai Tomonori Okamura Katsunori Ikewaki Kyoko Inagaki Tetsuo Shoji Hideaki Bujo Takashi Miida Masayuki Yoshida Masafumi Kuzuya Shizuya Yamashita

出版者

Japan Atherosclerosis Society

雑誌

Journal of Atherosclerosis and Thrombosis (ISSN:13403478)

巻号頁・発行日

pp.50187, (Released:2019-09-05)

参考文献数

26

被引用文献数

28

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Aims: The present study was conducted to establish a practical method for measuring non-cholesterol sterols and reference intervals of serum levels.Methods: Healthy subjects (109 men and 151 women), four patients with sitosterolemia, and 10 heterozygous mutation carriers of ABCG5/ABCG8 genes were investigated. Then, three non-cholesterol sterols (sitosterol, campesterol, and lathosterol) of fasting serum samples were measured via a practical and highly sensitive gas chromatography (GC) method with 0.2 µg/mL as the lower limit of quantification. The coefficient of variation (CV) values for within-run reproducibility were 3.06%, 1.89%, and 1.77% for lathosterol, campesterol, and sitosterol, respectively. The CV values for between-run reproducibility were 2.81%, 2.06%, and 2.10% for lathosterol, campesterol, and sitosterol, respectively.Results: The serum levels of sitosterol and campesterol were significantly higher in women than in men, whereas the serum levels of lathosterol were significantly higher in men than in women. Because of these gender difference, the determination of reference intervals of the three sterol values was performed by considering gender. The reference intervals of sitosterol, campesterol, and lathosterol were 0.99–3.88, 2.14–7.43, and 0.77–3.60 µg/mL in men and 1.03–4.45, 2.19–8.34, and 0.64–2.78 µg/mL in women, respectively. The serum levels of sitosterol and campesterol were higher in patients with sitosterolemia (94.3±47.3 and 66.3±36.6 µg/mL, respectively) than in healthy subjects.Conclusion: These results demonstrate a practical and highly sensitive GC method to measure non-cholesterol sterol levels and gender-segregated reference intervals of sitosterol, campesterol, and lathosterol in Japanese healthy subjects.

著者

Atsushi Hirayama Narimon Honarpour Masayuki Yoshida Shizuya Yamashita Fannie Huang Scott M. Wasserman Tamio Teramoto

出版者

日本循環器学会

雑誌

Circulation Journal (ISSN:13469843)

巻号頁・発行日

pp.CJ-14-0130, (Released:2014-03-21)

参考文献数

38

被引用文献数

30 83 26

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Background: YUKAWA is a 12-week, randomized, double-blind, placebocontrolled, phase 2 study evaluating the efficacy and safety of evolocumab (AMG 145) in statin-treated Japanese patients at high cardiovascular risk. Methods and Results: 310 eligible patients receiving stable statin (±ezetimibe) therapy were randomized to 1 of 6 treatments: placebo every 2 weeks (Q2W) or monthly (QM), evolocumab 70mg or 140mg Q2W, or evolocumab 280mg or 420mg QM. The primary endpoint was the percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) measured by preparative ultracentrifugation (UC). Secondary endpoints included percentage changes in other lipid parameters and the proportion of patients with LDL-C <1.8mmol/L. Mean (SD) age was 62 (10) years; 37% were female; and the mean (SD) baseline LDL-C was 3.7 (0.5) mmol/L (by UC). Mean (SE) changes vs. placebo in LDL-C were greatest in the high-dose groups: −68.6 (3.0) % and −63.9 (3.2) % with 140mg Q2W and 420mg QM dosing, respectively. Up to 96% of evolocumab-treated patients achieved LDL-C <1.8mmol/L. Adverse events (AEs) were more frequent in evolocumab (51%) vs. placebo (38%) patients; 4 patients taking evolocumab discontinued treatment because of an AE. There were no significant differences in AE rates based on dose or dose frequency. Conclusions: In Japanese patients at high cardiovascular risk with hypercholesterolemia on stable statin therapy, evolocumab significantly reduced LDL-C and was well tolerated during this 12-week study.