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Yoshihiko Fujita,Masahiko Kimura,Hiroki Sato,Toshikazu Takata,Nobufumi Ono,Kazuto Nishio 대한약학회 2016 Archives of Pharmacal Research Vol.39 No.6
Rotaxanes comprise a class of interlocked moleculescontaining a wheel threaded onto an axle with blockinggroups on the ends to keep thewheel fromsliding off.Here,weshow that [2][bis(2-(3,5-dimethylphenylcarbonyloxy)ethyl)ammoniumtrifluoromethanesulfonate]-[dibenzo-24-crown-8]rotaxane (TRO-A0001), a rotaxane compound, exerted agrowth inhibitory effect on several human cancer cell lines.AnMTT assay revealed an IC50 of 14-830 nMfor TRO-A0001 inthese cells. Neither the wheel nor the axle part alone inhibitedtumor cell growth, suggesting that the complete rotaxanemolecule with its unique ‘‘intramolecular mobility’’ is requiredto inhibit cell growth. Annexin-V/PI staining provided evidenceof the induction of apoptosis, which was further confirmedby the observation of poly (ADP-ribose) polymerasecleavage. Furthermore, a cell cycle analysis using flowcytometry showed that TRO-A0001 treatment resulted in G1arrest in glioblastoma T98G and melanoma G361 cells. Animmunoblot analysis revealed that in both cell lines, TROA0001treatment caused the induction of p21/Cip1, therebydown-regulating Cdks 2, 4 and 6 and reducing Cyclins D1 andE. The results presented in this study demonstrate cytotoxicityof the rotaxane compound and its potential as a lead compoundfor the development of a chemotherapeutic agent againstcancer.
SHIROZU, Takahiro,IWANO, Hiroki,OGISO, Takatoshi,SUZUKI, Toshiyuki,BALBOULA, Ahmed Z.,BAI, Hanako,KAWAHARA, Manabu,KIMURA, Koji,TAKAHASHI, Hitomi,RULAN, Bai,KIM, Sung-Woo,YANAGAWA, Yojiro,NAGANO, Masa 家畜繁殖硏究所 2017 Journal of Reproduction and Development Vol.63 No.3
<P> Interferon tau (IFN-τ) is a ruminant-specific type I IFN secreted by a conceptus before its attachment to the uterus. IFN-τ induces the expression of IFN-stimulated genes (ISGs) via the type I IFN receptor (IFNAR), which is composed of IFNAR1 and IFNAR2 subunits in the endometrium. However, expression patterns of IFNARs during the estrous cycle have not been reported. We hypothesized that the response to a type I IFN changes along with IFNARs and the IFN-regulatory factors (IRFs) driving transcription of IFN signal-related genes and modulating a type I IFN signal during the estrous cycle. We investigated the estrous cycle stage-dependent type I IFN induction of ISGs and expression patterns of IFN signal-related genes in bovine endometrial tissues. Endometrial tissue pieces collected from bovine uteri at each estrous stage (early, mid, and late) were cultured with or without recombinant bovine IFN-α or concentrated pregnant uterine flushing (PUF) on day 18 after confirming the presence of a conceptus. IFN-α and PUF each significantly increased the expression of ISGs in endometrial tissues. The induction levels of the typical ISGs (<I>MX1-a</I> and <I>ISG15</I>) were significantly higher at the mid stage and correlated with high expression of <I>IRFs</I> at the mid stage. The immunostaining of IFNARs showed strong fluorescence intensities in luminal and glandular epithelia at the early and mid stages. Collectively, these results suggest that the endometrium exhibits estrous cycle stage-dependent responsiveness to type I IFN that may be associated with the expression of IFNARs and IRFs for pregnancy recognition.</P>
Numerical Study of Slow-wave Instabilities in an Oversized Coaxial Slow-wave Structure
Kazuo Ogura,Shingo Abe,Hiroki Kimura,Kazumasa Yamamoto,Kiyoyuki Yambe,Ruhul Amin 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.59 No.61
In this paper, slow-wave instabilities in oversized coaxial SWSs are numerically analyzed. An infinitesimally thin annular beam with transverse perturbations and guided by a finite axial magnetic field is considered as the energy source for creating the instabilities. The coaxial SWSs consist of an outer oversized hollow waveguide and a central conductor and have sinusoidal corrugations. An electromagnetic slow-wave is generated by the inner corrugation and is called inner surface wave (ISW). The ISW is a cylindrical surface wave and can exist even if the outer conductor is removed. The higher-order modes are produced by the outer waveguide. The annular beam interacts with the ISW and higher-order modes. Slow cyclotron instability occurs due to the transversely modulated beam boundary, in addition to the conventional Cherenkov instability. The slow-wave instabilities are able to be controlled by the beam radius and the relative position of inner and outer corrugations.
Bin, Bum-Ho,Hojyo, Shintaro,Hosaka, Toshiaki,Bhin, Jinhyuk,Kano, Hiroki,Miyai, Tomohiro,Ikeda, Mariko,Kimura-Someya, Tomomi,Shirouzu, Mikako,Cho, Eun-Gyung,Fukue, Kazuhisa,Kambe, Taiho,Ohashi, Wakana BlackWell Publishing Ltd 2014 EMBO molecular medicine Vol.6 No.8
<P>The zinc transporter protein ZIP13 plays critical roles in bone, tooth, and connective tissue development, and its dysfunction is responsible for the spondylocheirodysplastic form of Ehlers-Danlos syndrome (SCD-EDS, OMIM 612350). Here, we report the molecular pathogenic mechanism of SCD-EDS caused by two different mutant ZIP13 proteins found in human patients: ZIP13<SUP>G64D</SUP>, in which Gly at amino acid position 64 is replaced by Asp, and ZIP13<SUP>ΔFLA</SUP>, which contains a deletion of Phe-Leu-Ala. We demonstrated that both the ZIP13<SUP>G64D</SUP> and ZIP13<SUP>ΔFLA</SUP> protein levels are decreased by degradation via the valosin-containing protein (VCP)-linked ubiquitin proteasome pathway. The inhibition of degradation pathways rescued the protein expression levels, resulting in improved intracellular Zn homeostasis. Our findings uncover the pathogenic mechanisms elicited by mutant ZIP13 proteins. Further elucidation of these degradation processes may lead to novel therapeutic targets for SCD-EDS.</P>
Thermoelectric Power in Single-crystalline CeRhSi3
Hidekazu A. Tanaka,Naofumi Aso,Masato Hedo,Takao Nakama,Yoshinao Takaesu,Hiroki Iida,Noriaki Kimura,Haruyoshi Aoki 한국물리학회 2013 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.62 No.12
The thermoelectric power S of a heavy-fermion superconductor CeRhSi3 has been measured attemperatures from 2.0 K to 300 K under hydrostatic pressures up to 2.7 GPa in order to clarify theKondo effect in CeRhSi3. S exhibits a large value of up to 60 µV/K, which is characteristic of heavyfermionsystems. S shows a maximum in its temperature dependence mainly due to the Kondoeffect, and its maximum temperature TSmax gradually increases from 96 K at ambient pressure to127 K at 2.7 GPa when a pressure is applied.
SUZUKI, Toshiyuki,SAKUMOTO, Ryosuke,HAYASHI, Ken-Go,OGISO, Takatoshi,KUNII, Hiroki,SHIROZU, Takahiro,KIM, Sung-Woo,BAI, Hanako,KAWAHARA, Manabu,KIMURA, Koji,TAKAHASHI, Masashi 家畜繁殖硏究所 2018 Journal of Reproduction and Development Vol.64 No.6
<P>Interferon-tau (IFNT), a type I interferon (IFN), is known as pregnancy recognition signaling molecule secreted from the ruminant conceptus during the preimplantation period. Type I IFNs, such as IFN-alpha and IFN-beta, are known to activate cell-death pathways as well as induce apoptosis. In cows, induction of apoptosis with DNA fragmentation is induced by IFNT in cultured bovine endometrial epithelial cells. However, the status of cell-death pathways in the bovine endometrium during the preimplantation period still remains unclear. In the present study, we investigated the different cell-death pathways, including apoptosis, pyroptosis, and autophagy, in uterine tissue obtained from pregnant cows and <I>in vitro</I> cultured endometrial epithelial cells with IFNT stimulation. The expression of <I>CASP7</I>, <I>8,</I> and <I>FADD</I> (apoptosis-related genes) was significantly higher in pregnant day 18 uterine tissue in comparison to non-pregnant day 18 tissue. The expression of <I>CASP4</I>, <I>11,</I> and <I>NLRP3</I> (pyroptosis-related genes) was significantly higher in the pregnant uterus in comparison to non-pregnant uterus. In contrast, autophagy-related genes were not affected by pregnancy. We also investigated the effect of IFNT on the expression of cell-death pathway-related genes, as well as DNA fragmentation in cultured endometrial epithelial cells. Similar to its effects in pregnant uterine tissue, IFNT affected the increase of apoptosis-related (<I>CASP8</I>) and pyroptosis-related genes (<I>CASP11</I>), but did not affect autophagy-related gene expression. IFNT also increased γH2AX-positive cells, which is a marker of DNA fragmentation. These results suggest that apoptosis- and pyroptosis-related genes are induced by IFNT in the pregnant bovine endometrial epithelial cells.</P>
Khaled Mohamed El-Dakhly,El-Shaymaa El-Nahass,Kosei Inui,Junpei KIMURA,Hiroki Sakai,Tokuma Yanai 대한수의학회 2013 Journal of Veterinary Science Vol.14 No.4
An adult male rufous turtle dove, Streptopelia (S.) orientalis (Aves: Columbiformes), was found dead in Yorii-machi Town, Osato District 369-1217, Saitama Prefecture, Japan,and subjected to necropsy. A large number of immobile hypopi (deutonymphs) of the hypoderatid mite, Hypodectes (H.) propus (Acarina: Hypoderatidae), were found individually encapsulated subcutaneously primarily in the adipose tissue. The mites were 1.43 mm in length and 0.44 mm in width on average, and had provoked mild inflammatory reactions that predominantly manifested as foamy macrophages and lymphoplasmocytes. PCR analysis using ribosomal DNA extracted from paraffin-blocked tissues produced a 240 bp band specific for hypoderatids. Based on the morphological features (distinct coxal apodemes,especially in the anterior portion) and PCR-based findings,the hypopi were identified as H. propus. To the best of our knowledge, this is the first case describing the subcutaneous mite H. propus in a rufous turtle dove, S. orientalis, in Japan. This study also highlights the use of paraffin blocks as a source of tissue DNA for molecular evaluation.
Naoki Okano,Yoshinori Igarashi,Ken Ito,Saori Mizutani,Hiroki Nakagawa,Kouji Watanabe,Yuuto Yamada,Kensuke Yoshimoto,Yuusuke Kimura,Susumu Iwasaki,Kensuke Takuma,Seiichi Hara,Yuui Kishimoto 대한소화기내시경학회 2021 Clinical Endoscopy Vol.54 No.5
Background/Aims: Bleeding is a complication of endoscopic snare papillectomy for ampullary tumors. This study aimed toinvestigate the clinical efficacy of hypertonic saline-epinephrine (HSE) local injection before endoscopic papillectomy for preventionof bleeding. Methods: We retrospectively reviewed the data of 107 consecutive patients with ampullary tumors who underwent endoscopicpapillectomy. The rates of en bloc resection, pathological resection margins, and prevention of immediate or delayed bleeding in thesimple snaring resection group (Group A) and the HSE injection group (Group B) were compared. Results: A total of 44 and 63 patients were enrolled in Groups A and B, respectively. The total complete resection rate was 89.7%(96/107); the clinical complete resection rates in Group A and Group B were 86.3% (38/44) and 92.1% (58/63), respectively (p=0.354). Post-papillectomy bleeding occurred in 22 patients. In Groups A and B, the immediate bleeding rates were 20.5% (9/44) and 4.8%(3/63), respectively (p=0.0255), while the delayed bleeding rates were 7% (3/44) and 11% (7/63), respectively (p=0.52). The rates ofpositive horizontal and vertical pathological margin in both groups were 27% and 16%, respectively. Conclusions: HSE local injection was effective in preventing immediate bleeding and was useful for safely performing endoscopicpapillectomy for ampullary tumors.
Yui Kishimoto,Naoki Okano,Ken Ito,Kensuke Takuma,Seiichi Hara,Susumu Iwasaki,Kensuke Yoshimoto,Yuto Yamada,Koji Watanabe,Yusuke Kimura,Hiroki Nakagawa,Yoshinori Igarashi 대한소화기내시경학회 2022 Clinical Endoscopy Vol.55 No.2
Background/Aims: Endoscopic evaluation of intraductal papillary mucinous neoplasms (IPMNs) is useful in determining whetherthe lesions are benign or malignant. This study aimed to examine the usefulness of peroral pancreatoscopy (POPS) in determiningthe prognosis of IPMNs. Methods: POPS with videoscopy was performed using the mother–baby scope technique. After surgery, computed tomography/magnetic resonance cholangiopancreatography or ultrasonography and blood tests were performed every 6 months during thefollow-up. Results: A total of 39 patients with main pancreatic duct (MPD)–type IPMNs underwent POPS using a videoscope, and theprotrusions in the MPD were observed in 36 patients. The sensitivity and specificity of cytology/biopsy performed at the time ofPOPS were 85% and 87.5%, respectively. Of 19 patients who underwent surgery, 18 (95%) patients had negative surgical margins and1 (5%) patient had a positive margin. Conclusions: In IPMNs with dilatation of the MPD, POPS is considered effective if the lesions can be directly observed. Thediagnosis of benign and malignant lesions is possible depending on the degree of lesion elevation. However, in some cases, slightlyelevated lesions may increase in size during the follow-up or multiple lesions may be simultaneously present; therefore, carefulfollow-up is necessary.