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1.
Yasuhiro Sano Shigeharu Yamashiro Asuka Komano Hisashi Maruko Hiroshi Sekiguchi Yasuo Takayama Ryoji Sekioka Kouichiro Tsuge Isaac Ohsawa Mieko Kanamori-Kataoka Yasuo Seto Akiyoshi Satoh 《Forensic Toxicology》2007,25(2):76-79
We previously reported that the Guardian Bio-Threat Alert (BTA) system could detect (detection limit: about 0.1 μg/ml) staphylococcal
enterotoxin B (SEB), botulinum toxins (BTX) A and B, and ricin, with no interference by white-powdered materials or colored
matrices. In this study, the capability of the BTA system was further assessed. With 10 min of preheating at 60°C, all toxins
could be detected, but with preheating at 80°C, BTX A and B and ricin became undetectable. About 20% SEB could be detected
after heating at 80°C, but this detection ability was completely removed after heating at 100°C. The effects of chemicals
usually used for decontamination, such as sodium hypochlorite, hydrogen peroxide, formaldehyde, and sodium nitrite, on the
detectability of SEB, BTX A, or ricin in the BTA system were also tested. The concentrations giving 50% line intensity for
SEB, BTX A, and ricin were 3.1, 11, and 15 μM for sodium hypochlorite and 88, 210, and 60 mM for formaldehyde, respectively.
The addition of hydrogen peroxide or sodium nitrite did not decrease the detectability even when used at high concentrations. 相似文献
2.
Norihiro Ishida Koji Hayashi Asuka Hattori Keiichiro Yogo Toru Kimura Tatsuo Takeya 《Journal of bone and mineral research》2006,21(1):48-57
We found that a chemokine receptor gene, CCR1, acts downstream of NFAT2 in RANKL-stimulated RAW264 and bone marrow cells. The upstream regulatory region of CCR1 showed RANKL-dependent and CsA-suppressible promoter activity. Downregulation of the expression and function of CCR1 suppressed cell migration. INTRODUCTION: We previously reported that the expression of NFAT2 induced by RANKL is a key process for progression to multinucleated cells in an in vitro osteoclastogenesis system. Identifying the target genes of NFAT2 would thus be informative about the differentiation process. We focused here on chemokine and chemokine receptor genes that act downstream of NFAT2 in RAW264 cells as well as osteoclast precursors prepared from bone marrow cells. MATERIALS AND METHODS: RAW264 mouse monocyte/macrophage line cells were cultured with or without cyclosporin A (CsA) in the presence of RANKL or glutathione S-transferase (GST). Osteoclast precursors were prepared from bone marrow cells. RANKL-inducible and CsA-suppressible genes were searched for by microarray analysis, and expression was confirmed by quantitative RT-PCR. Promoter activity was measured by luciferase gene reporter assay. Short interfering (si)RNA for CCR1 was introduced in RAW264 cells. Cell migration activity was examined using a Boyden chamber assay. RESULTS AND CONCLUSIONS: We identified the chemokine receptor gene CCR1 as a gene showing significant differential expression profiles in osteoclastogenesis in the presence versus the absence of CsA, an inhibitor of NFAT. This property was unique to CCR1 among the chemokine and chemokine receptor genes examined in both RAW264 and bone marrow cells. The upstream regulatory region was isolated from CCR1, and its RANKL-dependent and CsA-suppressible promoter activity was confirmed. The functional significance of CCR1 was assessed by monitoring the migration of cells in a transwell migration assay, and this activity was abolished when either CsA- or CCR1 siRNA-treated cells were used. Moreover, treatment with a Galpha inhibitor pertussis toxin (PTX) or methiolynated-regulated on activation, normal T cells expressed and secreted (Met-RANTES), an antagonist of CCR1, suppressed multinucleated cell formation in the bone marrow cell system. Together, these results suggest that the CCR1 signaling cascade is under the control of NFAT2 and seems to enhance the migration of differentiating osteoclasts. 相似文献
3.
Traf6 is essential for murine tooth cusp morphogenesis. 总被引:5,自引:0,他引:5
Atsushi Ohazama Jo-Maree Courtney Abigail S Tucker Asuka Naito Sakae Tanaka Jun-Ichiro Inoue Paul T Sharpe 《Developmental dynamics》2004,229(1):131-135
Ectodermal appendages such as skin, hair, teeth, and sweat glands are affected in patients with hypohidrotic (anhydrotic) ectodermal dysplasia (HED). It has been established that mutations in the tumor necrosis factor (TNF) superfamily of molecules, i.e., ectodysplasin (EDA), EDA receptor (EDAR), and EDAR-associated death domain (EDARADD; the intracellular adaptor for EDAR), are responsible for several forms of HED in humans and mice. We show here by in situ hybridisation that another TNF family (orphan) receptor, TROY (also known TAJ, TAJ-alpha, TRADE, and TNFRSF19), is strongly coexpressed with Edar in the epithelial enamel knot signalling centres that are believe to regulate cuspal morphogenesis during murine tooth development. Traf6 is known to function as an intracellular adaptor protein for Troy and examination of Traf6 mutant mice revealed abnormalities in molar teeth that are similar but more severe than those produced by mutations in Eda signalling molecules. This finding suggests that, in additional to ectodysplasin, another TNF pathway involving Troy/Traf6 is involved in molar tooth cusp formation and identifies an essential role for a Traf in tooth development. Developmental Dynamics 229:131-135, 2004. 相似文献
4.
5.
Keiji Inoue Takashi Karashima Satoshi Fukata Asuka Nomura Chiaki Kawada Atsushi Kurabayashi Mutsuo Furihata Yuji Ohtsuki Taro Shuin 《Clinical cancer research》2005,11(18):6669-6677
PURPOSE: Transitional cell carcinoma (TCC) of the urinary tract is a chemosensitive tumor. Most deaths from TCC of the urinary tract are caused by metastasis, which is resistant to conventional chemotherapy. Frequent sites of metastases from TCC of the urinary tract are regional lymph nodes, liver, lung, and bone. Of these distant metastases, bone metastasis is consistently resistant to cisplatin-based conventional chemotherapy. Therefore, in this study, we investigated whether or not a newly developed minodronate, YM529, could prevent osteolytic bone metastasis of human TCC and also enhance the effect of docetaxel in a bone tumor model of athymic nude mice. EXPERIMENTAL DESIGN: In the present study, we evaluated the effect of in vitro treatment with minodronate and/or docetaxel on the proliferation by cell count, the induction of apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, and the biological activity of osteoclast by pit formation assay in human bladder cancer cell line, UMUC-14, and mouse osteoclast cells. In vivo, we examined the effect of minodronate in a bone tumor model of athymic nude mice, in which the percutaneous intraosseal injection in the tibia of UMUC-14, leads to osteolytic bone tumor, as a bone metastasis model. To examine whether or not minodronate could inhibit tumorigenicity and enhance the effect of the chemotherapeutic agent, docetaxel, we gave minodronate i.p. and/or docetaxel i.p. to nude mice 3 days after an intraosseal tumor implantation. Moreover, proliferation and the induction of apoptosis of cancer cells and osteoclasts in bone tumors were determined by immunohistochemistry and the TUNEL assay. RESULTS: In vitro: In vitro treatment with docetaxel inhibited proliferation and resorption pit-forming activity and induced apoptosis of mouse osteoclast cells and UMUC-14 cells. In vitro treatment with minodronate inhibited proliferation and activity and induced apoptosis of mouse osteoclast cells but not UMUC-14 cells. The treatment with minodronate enhanced the inhibition of proliferation and activity by docetaxel in osteoclasts. In vivo: In vivo combination therapy with docetaxel and minodronate significantly reduced the tumor incidence compared with the control (P < 0.05) and also growth of intraossal TCC in athymic nude mice compared with the control (P < 0.001), single therapy with docetaxel (P < 0.01), and minodronate (P < 0.05). Drug-induced body weight loss was not significantly different in any treatment group. Therapy with minodronate significantly enhanced inhibition of proliferation by docetaxel in osteoclasts of bone tumors compared with the control (P < 0.01), single therapy with docetaxel (P < 0.01), and minodronate (P < 0.05). CONCLUSIONS: These studies indicate that combination therapy with minodronate and docetaxel may be beneficial in patients with bone metastasis of human TCC in the urinary tract. 相似文献
6.
Kosuke Okuya Junki Mine Kaori Tokorozaki Isshu Kojima Mana Esaki Kohtaro Miyazawa Ryota Tsunekuni Saki Sakuma Asuka Kumagai Yoshihiro Takadate Yuto Kikutani Tsutomu Matsui Yuko Uchida Makoto Ozawa 《Emerging infectious diseases》2022,28(7):1451
Genetic analyses of highly pathogenic avian influenza H5 subtype viruses isolated from the Izumi Plain, Japan, revealed cocirculation of 2 genetic groups of clade 2.3.4.4b viruses among migratory waterfowl. Our findings demonstrate that both continuous surveillance and timely information sharing of avian influenza viruses are valuable for rapid risk assessment. 相似文献
7.
Hirotomo Dochi Satoru Kondo Takayuki Murata Masaki Fukuyo Asuka Nanbo Kousho Wakae WenPing Jiang Toshihide HamabeHoriike Mariko Tanaka Takumi Nishiuchi Harue Mizokami Makiko MoriyamaKita Eiji Kobayashi Nobuyuki Hirai Takeshi Komori Takayoshi Ueno Yosuke Nakanishi Miyako Hatano Kazuhira Endo Hisashi Sugimoto Naohiro Wakisaka ShinHun Juang Masamichi Muramatsu Atsushi Kaneda Tomokazu Yoshizaki 《Cancer science》2022,113(8):2862
8.
Asuka Watanabe Misa Togi Terutsugu Koya Makoto Taniguchi Takuya Sakamoto Kuniyoshi Iwabuchi Tomohisa Kato Jr. Shigetaka Shimodaira 《Genes to cells : devoted to molecular & cellular mechanisms》2021,26(5):313-327
As the sentinels of innate and adaptive immune system, dendritic cells (DCs) have been considered to hold a great promise for medical application. Among the diverse types of DCs, monocyte-derived DCs (mo-DCs) generated in vitro have been most commonly employed. We have been improving the culture protocol and devised a protocol to produce mature interferon-α-induced DCs (IFN-DCs), hereinafter called (mat)IFN-DCs. While exploring the relationship between the expression of CD56 and the cytotoxic activity of (mat)IFN-DCs, we unexpectedly found that sorting of (mat)IFN-DCs with CD56 antibody-coated microbeads (MB) resulted in fractionating cells with tumoricidal activity into the flow-through (FT) but not MB-bound fraction. We uncovered that the FT fraction contains cells expressing low but substantial level of CD56. Moreover, those cells express granzyme B (GrB), perforin (PFN), and serpin B9 at high levels. By employing a specific inhibitor of PFN, we confirmed that direct tumoricidal activity relies on the GrB/PFN pathway. We designated subpopulation in FT fraction as CD56dim and that in CD56 positively sorted fraction as CD56bright, respectively. This is the first time, to our knowledge, to identify subpopulations of CD56-positive IFN-DCs with distinct tumoricidal activity which is ascribed to high expression of the components of GrB/PFN pathway. 相似文献
9.
Role of Dok-1 and Dok-2 in myeloid homeostasis and suppression of leukemia 总被引:5,自引:0,他引:5 下载免费PDF全文
Yasuda T Shirakata M Iwama A Ishii A Ebihara Y Osawa M Honda K Shinohara H Sudo K Tsuji K Nakauchi H Iwakura Y Hirai H Oda H Yamamoto T Yamanashi Y 《The Journal of experimental medicine》2004,200(12):1681-1687
Dok-1 and Dok-2 are closely related rasGAP-associated docking proteins expressed preferentially in hematopoietic cells. Although they are phosphorylated upon activation of many protein tyrosine kinases (PTKs), including those coupled with cytokine receptors and oncogenic PTKs like Bcr-Abl, their physiological roles are largely unidentified. Here, we generated mice lacking Dok-1 and/or Dok-2, which included the double-deficient mice succumbed to myeloproliferative disease resembling human chronic myelogenous leukemia (CML) and chronic myelomonocytic leukemia. The double-deficient mice displayed medullary and extramedullary hyperplasia of granulocyte/macrophage progenitors with leukemic potential, and their myeloid cells showed hyperproliferation and hypo-apoptosis upon treatment and deprivation of cytokines, respectively. Consistently, the mutant myeloid cells showed enhanced Erk and Akt activation upon cytokine stimulation. Moreover, loss of Dok-1 and/or Dok-2 induced blastic transformation of chronic phase CML-like disease in mice carrying the bcr-abl gene, a cause of CML. These findings demonstrate that Dok-1 and Dok-2 are key negative regulators of cytokine responses and are essential for myeloid homeostasis and suppression of leukemia. 相似文献
10.
The echoic memory trace (EMT) refers to neuronal activity associated with the short-term retention of stimulus-related information, especially within the primary and association auditory cortex. Using magnetoencephalography it is possible to determine quantitatively the lifetime of the EMT. Previous studies assumed that each new stimulus drives the EMT to its full strength, which then passively decays. In this study we show the limitations of this assumption using trains of auditory stimuli designed specifically for computing the EMT lifetime and its contextual sensitivity. We estimated a time-dependent EMT using a data-driven approach, which allows contributions from a relatively wide area around the auditory cortex in our quantitative measures. We identified: (1) internally generated cortical activations during the silent period between stimuli well separated in time from each other, which had influence on the morphology of the neuromagnetic response to the next external stimulus; and (2) EMTs with different lifetimes that modulate the amplitude of the evoked responses at different latencies, suggesting the existence of multiple neural delay lines. Long EMT lifetimes were observed on the descending part of the M100 complex, which showed handedness and gender-dependent interhemispheric asymmetry. Specifically, all subjects showed longer EMT lifetimes on the left hemisphere, except left-handed males. Distributed source analysis of the data for one left- and one right-handed male subject identified a secondary generator in the right-handed subject, which was located posterior to the early primary generator and dominated the auditory response at late latencies, where EMT lifetime asymmetry was high. The identified multiple neural delay lines and their laterality may provide a link between macroneuronal activity and left hemisphere specialization for processing linguistic material. 相似文献