National Institute of Health SciencesTokyo

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National Institute of Health SciencesTokyo

Japan
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Zhang H.,Beijing Forestry University | Zhang H.,Gifu University | Zhang H.,Tokyo University of Agriculture | Taya K.,Gifu University | And 5 more authors.
Environmental Pollution | Year: 2017

4-nitrophenol (PNP), isolated from diesel exhaust particles, has estrogenic and anti-androgenic activities, and affects the hypothalamus-pituitary-gonad axis in male rats. However, the effect of PNP on the reproduction of the female rats is still unknown. The aim of the study was to investigate the effect of neonatal PNP exposure on the ovarian function of female rats. The neonatal female rats were exposed to PNP (10 mg/kg, subcutaneously injection), the ovary and serum samples were collected at postnatal day (PND) 7, 14 and 21. The results showed that the ratio of primordial and primary follicles increased whereas the ratio of antral follicles decreased in the PNP treated ovaries at PND21. Even though no abnormality was observed in cyclicity, there was a significantly delayed timing of vaginal opening in PNP treated rats. The ovarian expression of steroidogenic enzymes including StAR, P450scc, P450c17 and P450arom increased at PND14 in the PNP treated rats compared with the control rats. In consistent with the gene expression, the concentration of estradiol-17β showed the similar pattern. However, PNP exposure failed to cause any significant change in the expression of steroidogenic enzymes in cultured neonatal ovaries. Furthermore, PNP suppressed the expression of estrogen receptor β (ERβ), but not estrogen receptor α (ERα), in cultured ovaries or developmental ovaries. These results suggested that PNP might directly affect the expression of ERβ in the rat ovaries, resulting in the disrupted steroidogenesis during ovarian development and the delayed puberty. © 2017 Elsevier Ltd


Yahata Y.,National Institute of Infectious DiseasesTokyo | Sugita-Konishi Y.,Azabu UniversityKanagawa | Ohnishi T.,National Institute of Health SciencesTokyo | Toyokawa T.,Okinawa Prefectural Nanbu Medical Center | And 3 more authors.
Japanese Journal of Infectious Diseases | Year: 2015

Raw fish consumption is increasing worldwide. Since around the year 2000, western regions of Japan have reported a foodborne disease of unknown cause that occurred after the consumption of flounder. In October 2010, a particularly large outbreak was reported in these regions among in-dividuals who consumed flounder fish that had been raised in aquaculture systems. The median incuba-tion period was 5 h (range, 4–19 h), and the most frequently reported symptom was diarrhea (80z). The risk estimate of the consumption of flounder was significantly higher than that of the development of symptoms (odds ratio = 9.50; 95z confidence interval, 1.59–/). According to a trace-back investigation, all of the flounder responsible for the outbreak were raised in aquaculture systems. Microscopic examination revealed that the median amount of Kudoa septempunctata present in the muscle of flounder fish from the aquaculture farm was 4.5 × 103 spores/g (range, 1.0 × 103 -9.6 × 106 spores/ g). The number of K. septempunctata spores required for the development of illness, as estimated using the Monte Carlo simulation, was 7.2 × 107 spores/g; therefore, thus this might be the minimum ingestion threshold for the development of gastrointestinal symptoms. As a public health measure, the cur-rent study results should be referred to for the prevention of the gastrointestinal symptoms related to the consumption of flounder; the national public health authority has disseminated these results. We con-cluded that K. septempunctata-contaminated flounder fish were associated with the gastrointestinal symptoms of this recent outbreak. © 2015, National Institute of Health. All rights reserved.


Koba Y.,Nagasaki University | Hirata Y.,Nagasaki University | Ueda A.,Nagasaki University | Oba M.,Nagasaki University | And 4 more authors.
Biopolymers | Year: 2016

Chiral five-membered carbocyclic ring amino acids bearing various diol acetal moieties were synthesized starting from l-malic acid, and homo-chiral homopeptides composed of cyclic amino acid (S)-Ac5c3EG bearing an ethylene glycol acetal, up to an octapeptide, were prepared. A conformational analysis revealed that (S)-Ac5c3EG homopeptides formed helical structures. (S)-Ac5c3EG homopeptides, up to hexapeptides, formed helical structures without controlling the helical screw direction, while (S)-Ac5c3EG hepta- and octapeptides formed helical structures with a preference for the left-handed (M) helical-screw direction. © 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 555–562, 2016. © 2015 Wiley Periodicals, Inc.


Demizu Y.,National Institute of Health SciencesTokyo | Yamashita H.,National Institute of Health SciencesTokyo | Yamashita H.,Tokyo Institute of Technology | Doi M.,Osaka University of Pharmaceutical Sciences | And 5 more authors.
Journal of Organic Chemistry | Year: 2015

We designed and synthesized two dodecapeptides, Boc-(l-Leu-l-Leu-Aib-d-Leu-d-Leu-Aib)2-OMe (5) and Boc-l-Leu-l-Leu-Aib-(d-Leu-d-Leu-Aib)2-l-Leu-l-Leu-Aib-OMe (6), that contain equal amounts of l-Leu, d-Leu, and achiral Aib residues. The conformations of peptides 5 and 6 in the crystalline state were studied using X-ray crystallographic analysis. Peptide 5 formed a left-handed (M) α-helical structure, whereas peptide 6 was composed of a combination of fused (M) α-helical and right-handed (P) 310-helical structures. In solution, roughly equivalent amounts of (P) and (M) helices were present in 5, whereas the (M) α-helix was present in 6 as its dominant conformation. © 2015 American Chemical Society.


Demizu Y.,National Institute of Health SciencesTokyo | Shibata N.,National Institute of Health SciencesTokyo | Hattori T.,National Institute of Health SciencesTokyo | Ohoka N.,National Institute of Health SciencesTokyo | And 5 more authors.
Bioorganic and Medicinal Chemistry Letters | Year: 2016

The manipulation of protein stability with small molecules has great potential as a technique for aiding the development of clinical therapies, including treatments for cancer. In this study, BCR-ABL protein degradation inducers called SNIPER(ABL) (Specific and Non-genetic inhibitors of apoptosis protein [IAP]-dependent Protein Erasers) were developed. The designed molecules contained two biologically active scaffolds: one was an imatinib derivative that binds to BCL-ABL and the other was a methyl bestatin that binds to cellular IAP 1 (cIAP1). The hybrid molecules, SNIPER(ABL), were expected to recruit BCR-ABL to cIAP1 for removal by proteasomes. In fact, SNIPER(ABL) induced the degradation of BCR-ABL protein and a subsequent reduction in cell growth. Thus, the degradation of BCR-ABL by SNIPER(ABL) is one potential strategy for treating BCR-ABL driven chronic myelogenous leukemia. © 2016 Elsevier Ltd

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