Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa

This research was originally published in Journal of Biological Chemistry. Hiroyuki Akama, Takanori Matsuura, Sachiko Kashiwagi, Hiroshi Yoneyama, Shin-ichiro Narita, Tomitake Tsukihara, Atsushi Nakagawa and Taiji Nakae. Crystal structure of the membrane fusion protein, MexA, of the multidrug transporter in Pseudomonas aeruginosa. Journal of Biological Chemistry. 2004; 279, 25939-25942. © the American Society for Biochemistry and Molecular Biology

Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end

This research was originally published in Journal of Biological Chemistry. Hiroyuki Akama, Misa Kanemaki, Masato Yoshimura, Tomitake Tsukihara, Tomoe Kashiwagi, Hiroshi Yoneyama, Shin-ichiro Narita, Atsushi Nakagawa and Taiji Nakae. Crystal structure of the drug discharge outer membrane protein, OprM, of Pseudomonas aeruginosa : Dual modes of membrane anchoring and occluded cavity end. Journal of Biological Chemistry. 2004; 279, 52816-52819. © the American Society for Biochemistry and Molecular Biology

PKCα mediates TGFβ-induced growth inhibition of human keratinocytes via phosphorylation of S100C/A11

Growth regulation of epithelial cells is of major concern because most human cancers arise from them. We demonstrated previously a novel signal pathway involving S100C/A11 for high Ca2+-induced growth inhibition of normal human keratinocytes (Sakaguchi, M., M. Miyazaki, M. Takaishi, Y. Sakaguchi, E. Makino, N. Kataoka, H. Yamada, M. Namba, and N.H. Huh. 2003. J. Cell Biol. 163:825–835). This paper addresses a question whether transforming growth factor β (TGFβ) shares the pathway with high Ca2+. On exposure of the cells to TGFβ1, S100C/A11 was phosphorylated, bound to nucleolin, and transferred to the nucleus, resulting in induction of p21WAF1/CIP1 and p15INK4B through activation of Sp1. Protein kinase C α (PKCα) was shown to phosphorylate 10Thr of S100C/A11, which is a critical event for the signal transduction. The TGFβ1-induced growth inhibition was almost completely mitigated when PKCα activity was blocked or when S100C/A11 was functionally sequestered. These results indicate that, in addition to the well-characterized Smad-mediated pathway, the PKCα–S100C/A11-mediated pathway is involved in and essential for the growth inhibition of normal human keratinocytes cells by TGFβ1

シュヨウナイ シュッケツ ニヨリ ゾウダイ シタ イ GIST ノ 1レイ

Although there are a lot of case-reports of GIST （Gastrointestinal stromal tumor） with bleeding into the alimentary tract, cases of bleeding inside of the GIST are rare. We report a case in which a GIST increased its size associated with bleeding inside and was resected successfully. An ８２-year-old man was diagnosed as GIST （１．０×２．０ cm in size） and followed for ３ years. Its size increased to １１×８ cm in size, therefore, we performed an operation. During laparotomy, the tumor was elastic hard and located on the upper body and posterior wall of the stomach. The tumor size was approximately the head of child. A total gastrectomy with splenectomy was done. A case of sudden increasing of the tumor was histologically thought to bleed inside of it. The increased size of tumors revealed a malignant potential and/or hemorrage, the tumor should be resected as soon as possible

Experimental Investigation of the Cs Behavior in the Cesiated H- Ion Source During High Power Long Beam Operation

The behavior of the Cesium (Cs) in the Cs-seeded negative ion sources has been investigated experimentally under the beam accelerations of up to 0.5 MeV. The pulse length was extended to 100 s to catch the precise variations of the Cs D2 emission, discharge power, negative ion current and temperatures in the ion source. The variations of the negative ions were estimated by the beam current and the heat loads in the accelerator. This experiment shows that the buildup of temperature in the chamber walls lead to the evaporation of deposited Cs to enter the plasma region and influence the H- ion production. The H- ion beams were sustained stably by reducing the temperature rise of the chamber wall below 50 ℃. A stable long pulse beam could be achieved through the temperature control of the surfaces inside the source chamber walls

Sigma-2 receptor ligands potentiate conventional chemotherapies and improve survival in models of pancreatic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>We have previously reported that the sigma-2 receptor is highly expressed in pancreas cancer. Furthermore, we have demonstrated that sigma-2 receptor specific ligands induce apoptosis in a dose-dependent fashion. Here, we examined whether sigma-2 receptor ligands potentiate conventional chemotherapies such as gemcitabine and paclitaxel.</p> <p>Methods</p> <p>Mouse (Panc-02) and human (CFPAC-1, Panc-1, AsPC-1) pancreas cancer cell lines were used in this study. Apoptosis was determined by FACS or immunohistochemical analysis after TUNEL and Caspase-3 staining. Combination therapy with the sigma-2 ligand SV119 and the conventional chemotherapies gemcitabine and paclitaxel was evaluated in an allogenic animal model of pancreas cancer.</p> <p>Results</p> <p>SV119, gemcitabine, and paclitaxel induced apoptosis in a dose-dependent fashion in all pancreas cancer cell lines tested. Combinations demonstrated increases in apoptosis. Mice were treated with SV119 (1 mg/day) which was administered in combination with paclitaxel (300 μg/day) over 7 days to mice with established tumors. A survival benefit was observed with combination therapy (p = 0.0002). Every other day treatment of SV119 (1 mg/day) in combination with weekly treatment of gemcitabine (1.5 mg/week) for 2 weeks also showed a survival benefit (p = 0.046). Animals tolerated the combination therapy and no gross toxicity was noted in serum biochemistry data or on necropsy.</p> <p>Conclusion</p> <p>SV119 augments tumoricidal activity of paclitaxel and gemcitabine without major side effects. These results highlight the potential utility of the sigma-2 ligand as an adjuvant treatment in pancreas cancer.</p

Chiral azabicyclo-N-oxyls mediated enantioselective electrooxidation of sec-alcohols

Enantiomerically pure azabicyclo-N-oxyls were prepared from l-hydroxyproline. They mediated enantioselective electrooxidation of racemic sec-alcohols to afford optically active sec-alcohols with moderate to high s value (up to 21)