研究者詳細 - 豊國　伸哉

論文 - 豊國　伸哉

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Allogeneic offspring produced by male germ line stem cell transplantation into infertile mouse testis. 査読有り国際誌 Open Access

Kanatsu-Shinohara M, Ogonuki N, Inoue K, Ogura A, Toyokuni S, Honjo T, Shinohara T

Biology of reproduction 68 巻 ( 1 ) 頁： 167 - 73 2003年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Biology of Reproduction

The testis is one of several immune-privileged organs and is known for its unique ability to support allogeneic or xenogeneic tissue transplants. We investigated the possibility of deriving offspring from mice that underwent transplantation with allogeneic male germ line stem cells in the testis. Although mature adult mice rejected allogeneic germ cells and were infertile, offspring were obtained by intracytoplasmic germ cell injection using partially differentiated donor cells. In contrast, complete spermatogenesis occurred when allogeneic germ cells were transplanted into immature pup testes. Tolerance induction by monoclonal antibody administration allowed the pup transplant recipients to produce allogeneic offspring by natural mating, whereas no spermatozoa were found in the epididymis of untreated recipients. Thus, these results indicate that a histoincompatible recipient can serve as a "surrogate father" to propagate the genetic information of heterologous male donors.

DOI： 10.1095/biolreprod.102.008516

Birth of offspring following transplantation of cyropreserved immature testicular pieces and in-vitro microinsemination 査読有り国際誌

Shinohara T., Inoue K., Ogonuki N., Kanatsu-Shinohara M., Miki H., Nakata K., Kurome M., Nagashima H., Toyokuni S., Kogishi K., Honjo T., Ogura A.

Human Reproduction 17 巻 ( 12 ) 頁： 3039 - 3045 2002年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Human Reproduction

Background: Fertility protection is an urgent clinical problem for prepubertal male oncology patients who undergo either chemotherapy or radiotherapy. As these patients do not have mature sperm to be frozen, there is as yet no effective method to preserve their fertility. Methods and results: Single pieces of immature mouse (1.5 × 1.5 × 1.5 mm) or rabbit (2.0 × 2.0 × ≃3.0 mm) testis were cryopreserved, thawed and transplanted into mouse testes. Histological techniques were used to determine the presence of spermatogenesis, which was restored in both mouse and rabbit testicular pieces, and led to the production of mature sperm after both cryopreservation and syngeneic or xenogeneic transplantation into mouse testes. Using sperm developed in the frozen-thawed transplants, mouse offspring were born after in-vitro microinsemination. Furthermore, rabbit offspring were obtained using rabbit sperm that developed in fresh transplants in a xenogeneic surrogate mouse. Conclusions: This approach of 'testicular tissue banking' is a promising technique for the preservation of fertility in prepubertal male oncology patients. Xenogeneic transplantation into immunodeficient mice may provide a system for study spermatogenic failure in infertile men.

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Birth of offspring following transplantation of cryopreserved immature testicular pieces and in-vitro microinsemination Open Access

Shinohara, T; Inoue, K; Ogonuki, N; Kanatsu-Shinohara, M; Miki, H; Nakata, K; Kurome, M; Nagashima, H; Toyokuni, S; Kogishi, K; Honjo, T; Ogura, A

HUMAN REPRODUCTION 17 巻 ( 12 ) 頁： 3039 - 3045 2002年12月

A novel method of "preparative" myocardial protection using green tea polyphenol in oral uptake

Miwa, S; Saito, M; Yamazaki, K; Toyokuni, S; Hyon, SH; Fujita, M; Komeda, M

CIRCULATION 106 巻 ( 19 ) 頁： 345 - 345 2002年11月

Oxydative stress persists in nearby LV area after myocardial infarction (MI) and shows two peaks

Miwa, S; Toyokuni, S; Tanaka, S; Nishina, T; Nomoto, T; Yamazaki, K; Ueda, K; Nishimura, K

CIRCULATION 106 巻 ( 19 ) 頁： 312 - 312 2002年11月

Oxydative stress persists in nearby LV area after myocardial infarction (MI) and shows two peaks 国際誌

Miwa, S, Toyokuni, S, Tanaka, S, Nishina, T, Nomoto, T, Yamazaki, K, Ueda, K, Nishimura, K

CIRCULATION 106 巻 ( 19 ) 頁： 312 - 312 2002年11月

A novel method of "preparative" myocardial protection using green tea polyphenol in oral uptake 査読有り国際誌

Miwa, S, Saito, M, Yamazaki, K, Toyokuni, S, Hyon, SH, Fujita, M, Komeda, M

CIRCULATION 106 巻 ( 19 ) 頁： 345 - 345 2002年11月

Ex vivo whole-embryo culture of caspase-8-deficient embryos normalize their aberrant phenotypes in the developing neural tube and heart. 査読有り国際誌

Sakamaki K, Inoue T, Asano M, Sudo K, Kazama H, Sakagami J, Sakata S, Ozaki M, Nakamura S, Toyokuni S, Osumi N, Iwakura Y, Yonehara S

Cell death and differentiation 9 巻 ( 11 ) 頁： 1196 - 206 2002年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cell Death and Differentiation

Caspase-8 plays the role of initiator in the caspase cascade and is a key molecule in death receptor-induced apoptotic pathways. To investigate the physiological roles of caspase-8 in vivo, we have generated caspase-8-deficient mice by gene targeting. The first signs of abnormality in homozygous mutant embryos were observed in extraembryonic tissue, the yolk sac. By embryonic day (E) 10.5, the yolk sac vasculature had begun to form inappropriately, and subsequently the mutant embryos displayed a variety of defects in the developing heart and neural tube. As a result, all mutant embryos died at E11.5. Importantly, homozygous mutant neural and heart defects were rescued by ex vivo whole-embryo culture during E10.5-E11.5, suggesting that these defects are most likely secondary to a lack of physiological caspase-8 activity. Taken together, these results suggest that caspase-8 is indispensable for embryonic development.

DOI： 10.1038/sj.cdd.4401090

その他リンク： http://orcid.org/0000-0003-0548-6452

Comparison between high-performance liquid chromatography and enzyme-linked Immunosorbent assay for the determination of 8-hydroxy-2 '-deoxyguanosine in human urine

Shimoi K, Kasai H, Yokota N, Toyokuni S, Kinae N

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION 11 巻 ( 8 ) 頁： 767 - 770 2002年8月

Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress

Kallay E, Bareis P, Bajna E, Kriwanek S, Bonner E, Toyokuni S, Cross HS

FOOD AND CHEMICAL TOXICOLOGY 40 巻 ( 8 ) 頁： 1191 - 1196 2002年8月

Protective effect of colored rice over white rice on fenton reaction-based renal lipid peroxidation in rats (vol 36, pg 583, 2002)

Toyokuni, S; Itani, T; Morimitsu, Y; Okada, K; Ozeki, M; Kondo, S; Uchida, K; Osawa, T; Hiai, H; Tashiro, T

FREE RADICAL RESEARCH 36 巻 ( 8 ) 2002年8月

Comparison between high-performance liquid chromatography and enzyme-linked immunosorbent assay for the determination of 8-hydroxy-2'-deoxyguanosine in human urine. 国際誌

Kayoko Shimoi, Hiroshi Kasai, Naoko Yokota, Shinya Toyokuni, Naohide Kinae

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 11 巻 ( 8 ) 頁： 767 - 70 2002年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

8-Hydroxy-2'-deoxyguanosine (8-OH-dG), which has been regarded as a potential marker of oxidative DNA damage induced by reactive oxygen species, was measured in human urine by a commercial ELISA using a monoclonal antibody N45.1 and by high-performance liquid chromatography (HPLC) coupled to an electrochemical detector (HPLC-ECD) to evaluate whether the ELISA system is applicable to human monitoring studies. The urine samples were collected from 120 healthy men ages 18-58 in a steel-manufacturing company. A good correlation (r = 0.833; P < 0.0001) was observed between the two methods on HPLC-purified 8-OH-dG fractions from 23 urine samples. The mean value (+/-SD) of 8-OH-dG (microg/g creatinine) was 5.47 (+/-2.97) by HPLC-ECD assay and 5.50 (+/-2.36) by ELISA. However, the correlation (r) between the two methods on 120 original urine samples was 0.460 [P < 0.001; mean value (+/-SD) of 8-OH-dG (microg/g creatinine) was 4.46 (+/-2.03) by the HPLC assay and 9.33 (+/-3.23) by ELISA]. ELISA estimates were about 2-fold higher than the HPLC estimates on original urine. For an unknown reason, 10% of the urine samples showed more than a 4-fold increase in value by ELISA. It is suggested that the ELISA system is applicable for comparative human monitoring studies. Prepurification of 'samples is required to determine the absolute value of 8-OH-dG in individual urine samples by ELISA.

PubMed

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Comparison between high-performance liquid chromatography and enzyme-linked immunosorbent assay for the determination of 8-hydroxy-2'-deoxyguanosine in human urine.

Shimoi K, Kasai H, Yokota N, Toyokuni S, Kinae N

Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress 査読有り国際誌

Kallay E, Bareis P, Bajna E, Kriwanek S, Bonner E, Toyokuni S, Cross HS

FOOD AND CHEMICAL TOXICOLOGY 40 巻 ( 8 ) 頁： 1191 - 1196 2002年8月

Erratum: Protective effect of colored rice over white rice on fenton reaction-based renal lipid peroxidation in rats (Free Radical Research vol. 36 (5) (583-592)) 査読有り国際誌

Toyokuni S., Itani T., Morimitsu Y., Okada K., Ozeki M., Kondo S., Uchida K., Osawa T., Hiai H., Tashiro T.

Free Radical Research 36 巻 ( 8 ) 2002年8月

Inhibition of gastric inhibitory polypeptide signaling prevents obesity. 査読有り国際誌

Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T, Seino Y

Nature medicine 8 巻 ( 7 ) 頁： 738 - 42 2002年7月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Nature Medicine

Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance. In contrast, mice lacking the GIP receptor (Gipr−/−) fed a high-fat diet were clearly protected from both the obesity and the insulin resistance. Moreover, double-homozygous mice (Gipr−/−, Lepob/Lepob) generated by crossbreeding Gipr−/− and obese ob/ob (Lepob/Lepob) mice gained less weight and had lower adiposity than Lepob/Lepob mice. The Gipr−/− mice had a lower respiratory quotient and used fat as the preferred energy substrate, and were thus resistant to obesity. Therefore, GIP directly links overnutrition to obesity and it is a potential target for anti-obesity drugs.

DOI： 10.1038/nm727

Vitamin D receptor activity and prevention of colonic hyperproliferation and oxidative stress

Kállay E., Bareis P., Bajna E., Kriwanek S., Bonner E., Toyokuni S., Cross H.

Food and Chemical Toxicology 40 巻 ( 8 ) 頁： 1191 - 1196 2002年6月

記述言語：日本語掲載種別：研究論文（学術雑誌）出版者・発行元：Food and Chemical Toxicology

Unimpaired vitamin D action has been implicated in human cancer prevention. We have previously demonstrated the effectiveness of 1α-dihydroxyvitamin D3 (1,25-D3) to reduce proliferation and increase differentiation in human colon cancer cells. The aim of this study was to investigate, on the one hand, expression of the vitamin D receptor (VDR) and of 25-hydroxyvitamin D3-1α-hydroxylase (1α-hydroxylase) in human normal and malignant colonic tissue and, on the other hand, to determine consequences of reduced or lacking VDR action in a VDR knockout mouse model. In low-grade malignancies of the human colon we found increased VDR and 1α-hydroxylase mRNA expression. However, in late-stage high-grade tumors the vitamin D system is severely compromised. In the mouse colon we found an inverse relationship between VDR levels and proliferation in colon descendens, a tissue known to be specifically affected by nutrients during carcinogenesis. Expression of 8-hydroxy-2′-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, was significantly augmented with complete loss of VDR. These data suggest that genomic 1,25-D3 action is necessary to protect against nutrition-linked hyperproliferation and oxidative DNA damage. © 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0278-6915(02)00030-3

Scopus

Carvedilol decreases elevated oxidative stress in human failing myocardium 査読有り国際誌 Open Access

Nakamura, K; Kusano, K; Nakamura, Y; Kakishita, M; Ohta, K; Nagase, S; Yamamoto, M; Miyaji, K; Saito, H; Morita, H; Emori, T; Matsubara, H; Toyokuni, S; Ohe, T

CIRCULATION 105 巻 ( 24 ) 頁： 2867 - 2871 2002年6月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Circulation

Background - Oxidative stress has been implicated in the pathogenesis of heart failure. However, direct evidence of oxidative stress generation in the human failing myocardium has not been obtained. Furthermore, the effect of carvedilol, a vasodilating β-blocker with antioxidant activity, on oxidative stress in human failing hearts has not been assessed. This study was therefore designed to determine whether levels of lipid peroxides are elevated in myocardia of patients with dilated cardiomyopathy (DCM) and whether carvedilol reduces the lipid peroxidation level. Methods and Results - Endomyocardial biopsy samples obtained from 23 patients with DCM and 13 control subjects with normal cardiac function were studied immunohistochemically for the expression of 4-hydroxy-2-nonenal (HNE)-modified protein, which is a major lipid peroxidation product. Expression of HNE-modified protein was found in all myocardial biopsy samples from patients with DCM. Expression was distinct in the cytosol of cardiac myocytes. Myocardial HNE-modified protein levels in patients with DCM were significantly increased compared with the levels in control subjects (P<0.0001). Endomyocardial biopsy samples from 11 patients with DCM were examined before and after treatment (mean, 9±4 months) with carvedilol (5 to 30 mg/d; mean dosage, 22±8 mg/d). After treatment with carvedilol, myocardial HNE-modified protein levels decreased by 40% (P<0.005) along with amelioration of heart failure. Conclusions - Oxidative stress is elevated in myocardia of patients with heart failure. Administration of carvedilol resulted in a decrease in the oxidative stress level together with amelioration of cardiac function.

DOI： 10.1161/01.CIR.0000018605.14470.DD

Web of Science

Scopus

PubMed

Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver

Kondo S, Toyokuni S, Tsuruyama T, Ozeki M, Tachibana T, Echizenya M, Hiai H, Onodera H, Imamura M

CANCER LETTERS 179 巻 ( 1 ) 頁： 87 - 93 2002年5月

Peroxynitrite-mediated stress is associated with proliferation of human metastatic colorectal carcinoma in the liver.

Kondo S, Toyokuni S, Tsuruyama T, Ozeki M, Tachibana T, Echizenya M, Hiai H, Onodera H, Imamura M

Cancer letters 179 巻 ( 1 ) 頁： 87 - 93 2002年5月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Cancer Letters

3-Nitrotyrosine (3-NT), a product of peroxynitrite reaction, is abundantly observed in hepatocytes adjacent to human metastatic colorectal carcinoma. To elucidate its biological significance, we undertook to identify nitric oxide (NO)-producing cells and apoptosis under oxidative stress. We observed strong inducible NO-synthase (iNOS) immunoreactivity in the hepatocytes adjacent to metastatic tumor, revealing an identical pattern to 3-NT immunostaining. Furthermore, intense 3-NT immunostaining of hepatocytes was associated with apoptosis whereas carcinoma cells near those hepatocytes presented high proliferating-cell nuclear antigen. Our results suggest that contact of metastatic tumor induces apoptosis in adjacent hepatocytes through peroxynitrite, thus permitting the proliferation of cancer cells. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/s0304-3835(01)00859-x

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PubMed

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