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41.
Previously, we found brevetoxins PbTx-3, BTX-B5 and BTX-B1 in cockle, Austrovenus (A.) stutchburyi, PbTx-2, PbTx-3 and BTX-B1 in Pacific oyster, Crassostrea (C.) gigas and PbTx-3 and BTX-B1 in greenshell mussel, Perna (P.) canaliculus following outbreak of neurotoxic shellfish poisoning (NSP) in New Zealand by isolation and/or liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). In this study, procedures for quantitative determination of PbTx-2 and BTX-B5 were developed and those for PbTx-3 and BTX-B1 were further examined by LC-MS/MS. In mass spectrometry with an electrospray ionization interface operating in the positive or negative ion mode, the protonated ions [M+H]+ of PbTx-2 (m/z 895), [M+H]+ of PbTx-3 (m/z 897), [M-H]- of BTX-B5 (m/z 909), and [M-Na]- of BTX-B1 (m/z 1016) were generated abundantly, when 0.1% formic acid-acetonitrile was used as the mobile phase for column chromatography. The product ions of m/z 877, 725, 111 and 80 from PbTx-2, PbTx-3, BTX-B5 and BTX-B1 were identified, respectively, allowing unambiguous confirmation of these toxins by selective reaction monitoring LC-MS/MS analysis. High levels of PbTx-3 and BTX-B5 were detected in C. gigas, of PbTx-3, BTX-B1 and BTX-B5 in A. stutchburyi, and of PbTx-2, PbTx-3 and BTX-B5 in P. canaliculus by this LC-MS/MS method. 相似文献
42.
Shiozawa T Tada A Nukaya H Watanabe T Takahashi Y Asanoma M Ohe T Sawanishi H Katsuhara T Sugimura T Wakabayashi K Terao Y 《Chemical research in toxicology》2000,13(7):535-540
We have previously determined the chemical structures of two 2-phenylbenzotriazole mutagens (PBTA-1 and PBTA-2) in blue cotton-adsorbed material from the Nishitakase River in Kyoto, Japan. In the present study, further analysis of mutagenic substances in the Nikko River, which flows through Aichi Prefecture in Japan, allowed the isolation of a new mutagen. Material (2.2 g) adsorbed on blue cotton (3 kg) at a site below the sewage plant on the Nikko River was purified by various column chromatographies, and a mutagen (120 microg) accounting for 11% of the total mutagenicity was isolated. On the basis of data from UV, mass, and (1)H NMR spectra of the mutagen, the compound was deduced to be a PBTA-1 analogue. As with PBTA-1, the mutagen was able to be synthesized from the azo dye 2-[(2-bromo-4, 6-dinitrophenyl)azo]-4-methoxy-5-[(2-hydroxyethyl)amino]acetanilide by reduction and chlorination. Since all spectra of the mutagen isolated from the river water were the same as those of the synthesized form, the structure was concluded to be 2-[2-(acetylamino)-4-[(2-hydroxyethyl)amino]-5-methoxyphenyl]-5-amino -7-bromo-4-chloro-2H-benzotriazole (PBTA-3). PBTA-3 is a potent mutagen, inducing 81 000 and 3 000 000 revertants per microgram of Salmonella typhimurium TA 98 and YG1024 respectively, in the presence of an S9 mix. In addition to its detection in the water of the Nikko River, PBTA-3 was detected in water samples from three other rivers flowing through regions where dyeing industries have been developed. Like PBTA-1 and PBTA-2, PBTA-3 might have also been produced from azo dyes during industrial processes in dyeing factories and/or through treatment at sewage plants. 相似文献
43.
Screening of HLA-A24-restricted epitope peptides from prostate-specific membrane antigen that induce specific antitumor cytotoxic T lymphocytes. 总被引:2,自引:0,他引:2
Yutaka Horiguchi Ikuei Nukaya Kazuhide Okazawa Ichiro Kawashima John Fikes Allesandro Sette Masaaki Tachibana Kazutoh Takesako Masaru Murai 《Clinical cancer research》2002,8(12):3885-3892
PURPOSE: Prostate-specific membrane antigen (PSMA), which is a transmembrane glycoprotein predominantly expressed in prostate cancer, is an attractive target for tumor-specific immunotherapy. To identify human leukocyte antigen (HLA)-A24-restricted epitope peptides from PSMA for further application of the dendritic cell (DC)-based immunotherapy targeting prostate cancer, we have screened several PSMA-encoded HLA-A24-binding peptides for their capabilities to elicit specific antitumor CTL response in vitro. EXPERIMENTAL DESIGN: The amino acid sequence of PSMA was screened for peptides consisting of 9 or 10 amino acids, which possess the known HLA-A24-binding motif. Nine candidate peptides were screened for binding to HLA-A24 molecules. Then, each of these nine peptides was studied to determine whether CTL responses could be induced by primary in vitro immunization of CD8(+) T cells using peptide-pulsed autologous DCs derived from peripheral blood mononuclear cells of HLA-A24(+) healthy donor as antigen-presenting cells. The antigen specificity of the CTL lines was confirmed using several tumor cell lines as target cells, which were genetically modified to express both HLA-A24 and PSMA. RESULTS: Two peptides, LYSDPADYF and NYARTEDFF, were demonstrated to elicit CTL lines that lyse peptide-pulsed, HLA-A24(+) B-lymphoblastoid cells. Each of the CTL lines recognized their specific PSMA-expressing target cells in a HLA-A24-restricted manner. The capability to release IFN-gamma by the CTL lines was specifically inhibited by anti-MHC class I and anti-CD8 monoclonal antibodies but not by anti-MHC class II and anti-CD4 monoclonal antibodies. CONCLUSION: Two novel HLA-A24-restricted PSMA-derived epitopes were identified in this study. These epitopes can be used to further evaluate the clinical utility of DC-based immunotherapeutic strategies for treatment of hormone-refractory prostate cancers. 相似文献
44.
Makoto Sumitomo Kiyoshi Takahara Kenji Zennami Tomomi Nagakawa Yasuhiro Maeda Kazuya Shiogama Yasuko Yamamoto Yoshinari Muto Takuhisa Nukaya Masashi Takenaka Kosuke Fukaya Manabu Ichino Hitomi Sasaki Kuniaki Saito Ryoichi Shiroki 《Cancer science》2021,112(3):1038-1047
Indoleamine 2,3-dioxygenase 1 (IDO1) is a key enzyme associated with immunomodulation through its regulation of the tryptophan-kynurenine (Kyn) pathway in advanced cancers, including metastatic renal cell carcinoma (mRCC). However, the failure of IDO1 inhibitors when used in combination with immune checkpoint inhibitors (ICIs), as observed in clinical trials, raises a number of questions. This study aimed to investigate the association of tryptophan 2,3-dioxygenase (TDO) and IDO1 with cancer development and resistance to immunotherapy in patients with RCC. In our analysis of RCC tissue samples, tissue Kyn levels were elevated in advanced-stage RCC and correlated well with TDO expression levels in RCC tumor cells. In patients with mRCC, TDO rather than IDO1 was expressed in RCC tumor cells, showing a strong association with Kyn expression. Furthermore, immunohistochemical staining of TDO was strongly associated with the staining intensity of forkhead box P3, as well as ICI therapy response and survival in patients with mRCC. Our study is the first to show that TDO expression in tumor tissues is associated with progression and survival, confirming its potential as a predictive biomarker of primary resistance to immunotherapy in patients with mRCC. Our findings suggest that strategies aimed at inhibiting TDO, rather than IDO1, in combination with ICI therapy may aid in the control of mRCC progression. 相似文献
45.
Koichiro Wada Teruhiko Yokoyama Satoshi Uno Motoo Araki Takuya Sadahira Yuki Maruyama Herik Acosta Hirochika Nakajima Yoshiki Hiyama Yasuharu Kunishima Yoshikazu Togo Takuhisa Nukaya Hiroki Yamada Katsumi Shigemura Shin Ito Masanobu Tanimura Kanao Kobayashi Hiroyuki Kitano Shingo Yamamoto 《Journal of infection and chemotherapy》2021,27(8):1169-1180
IntroductionThe aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data.MethodsWe enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum β-lactamase (ESBL) detection method.ResultsA total of 847 eligible cases were collected. Escherichia coli (E. coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E. coli (QREC) and ESBL-producing E. coli isolates at 15.6% and 9.5% of all E. coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S. saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E. coli, isolates from Eastern Japan had significantly higher susceptibility to cefazolin, cefotiam and cefpodoxime and lower susceptibility to levofloxacin in postmenopausal women. ESBL-producing E. coli isolates had a high susceptibility to tazobactam-piperacillin, cefmetazole, carbapenems, aminoglycosides, and fosfomycin. In S. saprophyticus, the susceptibility to β-lactams including carbapenems was 40–60%.ConclusionsThe proportions of QREC and ESBL-producing E. coli were increasing trends and lower susceptibility to LVFX in postmenopausal women was observed. Such surveillance, consisting of the collecting only clinical data, could be conducted easily and inexpensively. It is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains. 相似文献
46.
Preferential gene expression and epigenetic memory of induced pluripotent stem cells derived from mouse pancreas 下载免费PDF全文
Daiki Nukaya Kohtaro Minami Ritsuko Hoshikawa Norihide Yokoi Susumu Seino 《Genes to cells : devoted to molecular & cellular mechanisms》2015,20(5):367-381
Induced pluripotent stem cells (iPSCs) have been established from various somatic cell types. Accumulating evidence suggests that iPSCs from different cell sources have distinct molecular and functional properties. Here, we establish iPSC derived from mouse pancreas (Panc‐iPSC) and compared their properties with those of iPSC derived from tail‐tip fibroblast (TTF‐iPSC). The metabolic profile differs between Panc‐iPSC and TTF‐iPSC, indicating distinct cell properties in these iPSCs. Expression of Pdx1, a marker of pancreas differentiation, is increased through formation of embryoid body (EB) in Panc‐iPSC, but the level is similar to that in TTF‐iPSC. In contrast, EBs derived from Panc‐iPSC express liver‐specific albumin (Alb) and alpha‐fetoprotein (Afp) genes much more strongly than those from TTF‐iPSC. Epigenetic analysis shows a different histone modification pattern between Panc‐iPSC and TTF‐iPSC. Promoter regions of Alb and Afp genes in Panc‐iPSC are suggested to have a more open chromatin structure than those in TTF‐iPSC, which also is seen in primary cultured pancreatic cells. Our data suggest that Panc‐iPSC possesses distinct differentiation capacity from that of TTF‐PSC, which may be influenced by epigenetic memory. 相似文献
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48.
Tada Akihiro; Ochiai Masako; Wakabayashi Keiji; Nukaya Haruo; Sugimura Takashi; Nagao Minako 《Carcinogenesis》1994,15(6):1275-1278
The N-hydroxylamine of a carcinogenic heterocyclic amine, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline(MeIQ), was reacted with four 2'-deoxynucleoside 3'-monophosphatesafter O-acetylation. 32P-Postlabeing analysis demonstrated thatthe adduct was formed with only the guanine nucleotide, andthe structure of the compound in the obtained adduct spot wasdetermined to be N-(deoxyguanosin-8-yl)-MeIQ 3',5'-diphosphate(3',5'-pdGp-C8-MeIQ). DNA samples from livers of mice fed MelQwere also 32P labeled under standard conditions and additionallytreated with nuclease P1 and phosphodiesterase I. A single adductspot was obtained and the structure of the adduct was identifiedas 5'-pdG-C8-MeIQ. Thus, MelQ binds at the C-8 position of guaninein vitro and in vivo, like other heterocyclic amines. 相似文献
49.
Akiyama Y Tanosaki R Inoue N Shimada M Hotate Y Yamamoto A Yamazaki N Kawashima I Nukaya I Takesako K Maruyama K Takaue Y Yamaguchi K 《Journal of translational medicine》2005,3(1):4-10
BACKGROUND: Metastatic, chemotherapy-resistant melanoma is an intractable cancer with a very poor prognosis. As to immunotherapy targeting metastatic melanoma, HLA-A2+ patients were mainly enrolled in the study in Western countries. However, HLA-A24+ melanoma patients-oriented immunotherapy has not been fully investigated. In the present study, we investigated the effect of dendritic cell (DC)-based immunotherapy on metastatic melanoma patients with HLA-A2 or A24 genotype. METHODS: Nine cases of metastatic melanoma were enrolled into a phase I study of monocyte-derived dendritic cell (DC)-based immunotherapy. HLA-genotype analysis revealed 4 cases of HLA-A*0201, 1 of A*0206 and 4 of A*2402. Enriched monocytes were obtained using OptiPreptrade mark from leukapheresis products, and then incubated with GM-CSF and IL-4 in a closed serum-free system. After pulsing with a cocktail of 5 melanoma-associated synthetic peptides (gp100, tyrosinase, MAGE-2, MAGE-3 and MART-1 or MAGE-1) restricted to HLA-A2 or A24 and KLH, cells were cryopreserved until used. Finally, thawed DCs were washed and injected subcutaneously (s.c.) into the inguinal region in a dose-escalation manner. RESULTS: The mean percentage of DCs rated as lin-HLA-DR+ in melanoma patients was 46.4 +/- 15.6 %. Most of DCs expressed high level of co-stimulatory molecules and type1 phenotype (CD11c+HLA-DR+), while a moderate number of mature DCs with CD83 and CCR7 positive were contained in DC products. DC injections were well tolerated except for transient liver dysfunction (elevation of transaminases, Grade I-II). All 6 evaluable cases except for early PD showed positive immunological responses to more than 2 melanoma peptides in an ELISPOT assay. Two representative responders demonstrated strong HLA-class I protein expression in the tumor and very high scores of ELISPOT that might correlate to the regression of metastatic tumors. Clinical response through DC injections was as follows : 1CR, 1 PR, 1SD and 6 PD. All 59 DC injections in the phase I study were tolerable in terms of safety, however, the maximal tolerable dose of DCs was not determined. CONCLUSIONS: These results suggested that peptide cocktail-treated DC-based immunotherapy had the potential for utilizing as one of therapeutic tools against metastatic melanoma in Japan. 相似文献
50.
Koda H Yokoo Y Matsumoto N Suwa Y Fukazawa H Ishida H Tsuji K Nukaya H Kuriyama K 《Japanese journal of pharmacology》1999,81(3):313-315
We examined the effect of N-methyltyramine (NMT) on alpha2-adrenoceptor. NMT (10(-8)-10(-3) M) inhibited the binding of [3H]p-aminoclonidine to alpha2-adrenoceptor dose-dependently. However, the IC50 value for NMT (5.53 x 10(-6) M) was higher than that for RX821002, an alpha2-adrenoceptor antagonist (1.07 x 10(-8) M). RX821002 (5 mg/kg, i.p.) inhibited hypermotility induced by scopolamine (8 mg/kg, s.c.) in male ddY mice. NMT (20 or 100 mg/kg, i.p.) was found to have a dose-dependent inhibitory effect similar to that of RX821002. These findings indicate that NMT has the properties of an alpha2-adrenoceptor antagonist. However, the affinity of NMT for alpha2-adrenoceptor is weaker than that of RX821002. 相似文献