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1. Effect of the Casein-Derived Peptide Met-Lys-Pro on Cognitive Function in Community-Dwelling Adults Without Dementia: A Randomized, Double-Blind, Placebo-Controlled Trial

Author

Yuda N, Tanaka M, Yamauchi K, Abe F, Kakiuchi I, Kiyosawa K, Miyasaka M, Sakane N, and Nakamura M

Subjects
humans, mkp, cognition, cognitive dysfunction, orientation, alzheimer’s disease, Geriatrics, RC952-954.6
Abstract

Naoki Yuda,1 Miyuki Tanaka,1 Koji Yamauchi,1 Fumiaki Abe,1 Izumi Kakiuchi,2 Kyoko Kiyosawa,2 Mitsunaga Miyasaka,2 Naoki Sakane,3 Masahiko Nakamura4 1Food Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., Zama, Kanagawa, Japan; 2Department of Nursing, Matsumoto Junior College, Matsumoto, Nagano, Japan; 3Division of Preventive Medicine, Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan; 4Matsumoto City Hospital, Matsumoto, Nagano, JapanCorrespondence: Naoki YudaFood Ingredients and Technology Institute, Morinaga Milk Industry Co., Ltd., 1-83, 5-Chome, Higashihara, Zama, Kanagawa, JapanTel +81 46 252 3051Fax +81 46 252 3017Email n-yuda@morinagamilk.co.jpBackground: Preventative measures have recently been taken to reduce the incidence of Alzheimer’s disease worldwide. We previously showed that Met-Lys-Pro (MKP), a casein-derived angiotensin-converting enzyme inhibitory peptide with the potential to cross the blood–brain barrier, attenuated cognitive decline in a mouse model of Alzheimer’s disease. However, the effect of MKP on cognitive function improvement in humans remains unknown. This exploratory study sought to investigate whether MKP intake could improve cognitive function in adults without dementia.Methods: A total of 268 community-dwelling adults without dementia participated in this 24-week randomized controlled trial. Participants were randomly allocated to the MKP (n = 134) or placebo (n = 134) group. The MKP group received four tablets daily, each containing 50 μg MKP, while the placebo group received four dextrin tablets containing no detectable MKP for 24 weeks. Scores on the Japanese version of the cognitive subscale of the Alzheimer’s Disease Assessment Scale (ADAS-cog) were used as the primary outcome to compare cognitive function between the MKP and placebo groups. The study products were also evaluated for safety.Results: The intention-to-treat analysis showed that there was no significant difference between the groups in terms of the ADAS-cog total score. Orientation, as measured by the respective ADAS-cog subscale, was significantly improved compared to placebo at 24 weeks post-MKP administration (P = 0.022). No serious adverse events due to MKP intake were observed.Conclusion: To the best of our knowledge, this is the first study to report the effects of MKP on human cognition. These preliminary results suggested the safety of daily MKP intake and its potential to improve orientation in adults without dementia. Further clinical studies are needed to confirm the present findings and the benefits of MKP on cognitive function.Keywords: humans, MKP, cognition, cognitive dysfunction, orientation, Alzheimer’s disease

Published
2020

9. A case of primary low grade mucosa associated lymphoid tissue (MALT) lymphoma of the oesophagus. (Case Report)

Author

Hosaka, S., Nakamura, N., Akamatsu, T., Fujisawa, T., Ogiwara, Y., Kiyosawa, K., Hidaka, E., Ota, H., Katsuyama, T., and Inagaki, H.

Subjects
Lymphomas -- Identification and classification -- Case studies, Esophageal cancer -- Case studies, Health
Abstract

We report a very rare case of primary low grade mucosa associated lymphoid tissue (MALT) lymphoma of the oesophagus. An 83 year old woman was referred to our hospital in [...]

Published
2002

10. Association between severity of type A hepatitis and nucleotide variations in the 5' non-translated region of hepatitis A virus RNA: strains from fulminant hepatitis have fewer nucleotide substitutions. (Liver and Biliary Disease)

Author

Fujiwara, K., Yokosuka, O., Ehata, T., Saisho, H., Saotome, N., Suzuki, K., Okita, K., Kiyosawa, K., and Omata, M.

Subjects
Hepatitis A -- Genetic aspects, Nucleotides -- Analysis, Health, Analysis, Genetic aspects
Abstract

Background: Type A hepatitis is still a considerable problem in both underdeveloped and developed countries. Why some patients progress to fulminant type A hepatitis and others do not is unclear. [...]

Published
2002

40. Polyenephosphatidylcholine prevents alcoholic liver disease in PPARα-null mice through attenuation of increases in oxidative stress

Author

Okiyama, W, Tanaka, N, Nakajima, T, Tanaka, E, Kiyosawa, K, Gonzalez, FJ, and Aoyama, T

Abstract

Background/Aims: Alcoholic liver disease (ALD) is one of the leading causes of cirrhosis and yet efficient therapeutic strategies are lacking. Polyenephosphatidylcholine (PPC), a major component of essential phospholipids, prevented alcoholic liver fibrosis in baboons, but its precise mechanism remains uncertain. We aimed to explore the effects of PPC on ALD using ethanol-fed peroxisome proliferator-activated receptor α (Ppara)-null mice, showing several similarities to human ALD. Methods: Male wild-type and Ppara-null mice were pair-fed a Lieber-DeCarli control or 4% ethanol-containing diet with or without PPC (30 mg/kg/day) for 6 months. Results: PPC significantly ameliorated ethanol-induced hepatocyte damage and hepatitis in Ppara-null mice. These effects were likely a consequence of decreased oxidative stress through down-regulation of reactive oxygen species (ROS)-generating enzymes, including cytochrome P450 2E1, acyl-CoA oxidase, and NADPH oxidases, in addition to restoration of increases in Toll-like receptor 4 and CD14. PPC also decreased Bax and truncated Bid, thus inhibiting apoptosis. Furthermore, PPC suppressed increases in transforming growth factor-β1 expression and hepatic stellate cell activation, which retarded hepatic fibrogenesis. Conclusions: PPC exhibited anti-inflammatory, anti-apoptotic, and anti-fibrotic effects on ALD as a result of inhibition of the overexpression of ROS-generating enzymes. Our results demonstrate detailed molecular mechanisms of the anti-oxidant action of PPC., Article, Journal of Hepatology 50(6): 1236-1246(2009)

Published
2009

41. Insulin resistance and hepatitis C virus: a case-control study of non-obese, non-alcoholic and non-steatotic hepatitis virus carriers with persistently normal serum aminotransferase

Author

Tanaka, N, Nagaya, T, Komatsu, M, Horiuchi, A, Tsuruta, G, Shirakawa, H, Umemura, T, Ichijo, T, Matsumoto, A, Yoshizawa, K, Aoyama, T, Kiyosawa, K, and Tanaka, E

Abstract

Author Posting. © The Authors 2008 This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Liver International, 28(8):1104-1111. https://doi.org/10.1111/j.1478-3231.2008.01737.x, Article, LIVER INTERNATIONAL. 28(8):1104-1111(2008)

Published
2008

49. 8-year Birth Cohort Study of the Seroepidemiology of Helicobacter pylori infection and Hepatitis A Virus in rural Japan

Author

Malaty, H. M., Tanaka, E., Kumagai, T., Ota, H., Akamatsu, T., Kiyosawa, K., and Graham, D.Y.

Subjects
Hepatitis A -- Research, Helicobacter infections -- Research, Helicobacter pylori -- Research, Gastrointestinal diseases -- Research, Health, Research
Abstract

H.M. Malaty [1] E. Tanaka [2] T. Kumagai [2] H. Ota [2] T. Akamatsu [2] K. Kiyosawa [2] D.Y. Graham [1] [6/05] [*] 8-year Birth Cohort Study of the Seroepidemiology [...]

Published
2001

50. Proceedings of the 69th General Meeting from April 11–13, 1983-Osaka, Japan

Author

Baba, Yoshihiro, Nagata, Kunio, Tsukada, Yoshihisa, Narisawa, Rintaro, Honma, Akira, Hirose, Shinichi, Tomizawa, Mineo, Ozaki, Toshihiko, Ichida, Fumihiro, Tanehiro, Kenji, Kuno, Nobuyoshi, Kurimoto, Kumiko, Yokota, Tetsuo, Kano, Tomoyuki, Kasugai, Tatsuzo, Ueno, Kazuya, Shimakura, Katsuhide, Kakita, Akira, Kambayashi, Masaaki, Takahashi, Tsuyoshi, Sasaki, Eisei, Kasai, Yoichi, Takahashi, Toshihisa, Shimaguchi, S., Ariyama, J., Sumida, Masatoshi, Tsuchiya, Yukihiro, Ohto, Masao, Asagami, Fumio, Fuji, Tadasu, Okabe, Norimasa, Sakurai, Kenji, Miyakawa, Shuichi, Horiguchi, Yuji, Nakano, Hiroshi, Nimura, Yuji, Hayakawa, N., Hasegawa, H., Kamiya, J., Maeda, S., Iyomasa, Y., Matsumoto, Yoshiro, Sugahara, Katsuhiko, Ida, T., Mashimo, R., Wen, Shu Kou, Fujii, H., Wakashiro, S., Isowa, G., Itoh, S., Yamakawa, T., Udaka, Hidenori, Miyamoto, Hideyuki, Tamura, Toshikazu, Hirai, Tsutomu, Okamura, Osamu, Komi, Nobuhiko, Yoshioka, Nobuo, Kawamura, Yoshio, Kojima, Takahiko, Hachiya, Hitoshi, Okumura, Nobuyoshi, Suzuki, Kunihiko, Suzuki, Toshiyuki, Suzuki, Sadasuke, Ozeki, Norishige, Goto, Kazuo, Shiraki, Shigehiro, Takeuchi, Toshihiko, Yamaguchi, Atsumasa, Shibue, Tadashi, Kawaura, Yukimitsu, Iwa, Takashi, Takeda, Isao, Nakano, Satoshi, Kobayashi, Tomoko, Harada, Hideo, Wakabayashi, Tokio, Sawabu, Norio, Naito, Yasuo, Nakazawa, Saburo, Isawa, Tomoaki, Tabata, Ikuo, Sasaki, Yuichi, Yamada, Hideaki, Tatsumi, Shunichi, Kobayashi, Kenzo, Suzuki, Eitaro, Okamoto, Eizo, Matsukawa, Masakatsu, Tabata, Ikuo, Nakanishi, Toshio, Kawakami, Hiroiku, Fujimoto, Sotaro, Nakajima, Masatsugu, Sugihara, Junichi, Saitoh, Yoichi, Matsushiro, Takashi, Nagashima, Hideyuki, Yamamoto, Kyoji, Nakamura, Ryuji, Tanaka, Junichi, Shimizu, Fumito, Toshima, Takashi, Hariu, Tuneo, Nagakawa, Takukazu, Suzuki, Noriyoshi, Takahashi, Wataru, Uematsu, Ikunoshin, Sato, Toshio, Egami, K., Tajiri, T., Aoki, N., Yamaguchi, K., Yamakawa, H., Watanabe, A., Yano, M., Hatta, S., Yoshioka, M., Miki, M., Shirota, A., Morimoto, Koji, Furukawa, Masato, Nakata, Toshinori, Yamada, Ryuhei, Ito, Shinichiro, Maeda, Shigeru, Morinaga, Toshinori, Tanigawa, Makota, Fujio, Toshiyuki, Inui, Hiroshi, Kinoshita, Hiroaki, Yamasaki, Osamu, Nagata, Eiichi, Hirohashi, Kazuhiro, Sakai, Katsuz8i, Takada, Tadahiro, Yasuda, Hideki, Shishikura, Makoto, Uchiyama, Katsuhiro, Ogura, Yoshifumi, Mizumoto, Ryuji, Nakazawa, Kazuomi, Sato, Shunichi, Kaito, Isamu, Suzuki, Hiroshi, Ohtsuki, Masao, Goto, Yoshio, Nomoto, M., Yunoue, K., Soga, K., Ichida, F., Koike, Y., Kiyosawa, K., Akahane, Y., Kamijyo, K., Suzuki, Y., Yamamura, S., Komatsu, T., Nagata, A., Furuta, S., Hayashi, Shigeki, Ohta, Yasuhiko, Fujiwara, Kenji, Sato, Yuzuru, Ogata, Itsuro, Takatsuki, Katsuyoshi, Mishiro, Shunji, Oka, Hiroshi, Furube, Masaru, Yamada, Nobuo, Shibata, Hisao, Shibuya, Akitaka, Hijikata, Eishi, Kokubu, Shigenobu, Ishii, Kohdo, Okabe, Haruya, Sasaki, Kenichi, Takada, Akira, Takeuchi, Jugoro, Ohta, Yasuyuki, Tsujii, Tadashi, Ikegame, Fumiaki, Unoura, Masashi, Furusawa, Akihiko, Tanaka, Nobuyoshi, Kato, Yasuhiro, Kobayashi, Kenichi, Hattori, Nobu, Tameda, Yukihiko, Kakiuchi, Satoshi, Kosaka, Yoshitane, Harihara, Shigeyoshi, Yamamoto, Sukeo, Yamada, Gotaro, Nagashima, Hideo, Onji, Morikazu, Yamashita, Yoshimasa, Horiike, Norio, Ohta, Yasuyuki, Abe, Hirohiko, Hino, Kazuhiko, Kojima, Masaru, Noguchi, Kazunori, Ueda, Hiromu, Aritaka, Tomoki, Maruyama, Naoto, Motoori, Hitoshi, Yamauchi, Kazuaki, Setoyama, Hiroshi, Sata, Michio, Kubo, Yasuhiko, Tanikawa, Kyuichi, Munehisa, Tatsuo, Nakata, Keisuke, Kono, Kenzo, Muro, Toyoichi, Sato, Akira, Furukawa, Ryuji, Ishii, Nobuko, Kusumoto, Yukio, Koji, Toshihiko, Nagataki, Shigenobu, Nakao, Norio, Miura, Kohi, Sato, Y., Ohta, Y., Ogata, I., Hayashi, S., Fujiwara, K., Oka, H., Furui, S., Iio, M., Ikeda, Kenji, Oyake, Eiji, Takeuchi, Kazuo, Kumada, Hiromitsu, Nakajima, Masao, Yoshiba, Akira, Irimoto, Masahiro, Kobayashi, Toshio, Ohto, Masao, Satoh, Morio, Yamada, Ryusaku, Nakatsuka, Haruki, Yamada, Ryusaku, Kubo, Yasuhiko, Hirai, Kenji, Kumagai, Masanobu, Yamaguchi, Genjiro, Tanaka, Masatoshi, Abe, Masanobu, Tanikawa, Kyuichi, Ando, Keijiro, Shingai, Yasushi, Okita, Kiwamu, Takemoto, Tadayoshi, Tarao, Kazuo, Iwamura, Kenichiro, Soga, Kenji, Honma, Akira, Nomoto, Minoru, Takagi, Hitoshi, Ichida, Fumihiro, Ichida, Takafumi, Higashi, Shunsaku, Noguchi, Takashi, Mizumoto, Ryuji, Kanematsu, Takashi, Takenaka, Kenji, Matsumata, Takashi, Sonoda, Takashi, Furuta, Toshiya, Sugimachi, Keizo, Inokuchi, Kiyoshi, Yamasaki, Susumu, Hasegawa, Hiroshi, Makuuchi, Masatoshi, Nakanishi, Yoshimi, Kakita, Akira, Sano, Hidekazu, Konno, Tetsuro, Sano, Fumio, Kasai, Yoichi, Tsuzuki, Toshiharu, Iida, Shuhei, Yamanaka, Naoki, Okamoto, Eizo, Kuwata, Keiji, Toyosaka, Akihiro, Tanaka, Nobutaka, Fujiwara, Shiro, Yamazaki, Hajime, Hirohashi, Kazuhiro, Kinoshita, Hiroaki, Sakai, Katsuji, Ono, Tokio, Yamada, Hiroaki, Tada, Masahiro, Asakura, Hitoshi, Kobayashi, Kensuke, Morishita, Tetsuo, Tsuchiya, Masaharu, Sato, Nobutaka, Hiratsuka, Hideo, Ueda, N., and Harada, K.

Published
1984
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