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RISS 인기검색어
- 검색키워드
- 저자 : Toshiyuki Kohno (검색결과 4 건)
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Tumor necrosis factor-α converting enzyme is a key mediator of abdominal aortic aneurysm development
Kaneko, Hidehiro,Anzai, Toshihisa,Horiuchi, Keisuke,Kohno, Takashi,Nagai, Toshiyuki,Anzai, Atsushi,Takahashi, Toshiyuki,Sasaki, Aya,Shimoda, Masayuki,Maekawa, Yuichiro,Shimizu, Hideyuki,Yoshikawa, Tsu Elsevier 2011 Atherosclerosis Vol.218 No.2
<P><B>Abstract</B></P><P><B>Objective</B></P><P>Tumor necrosis factor (TNF)-α is known to be elevated in plasma and the aorta in abdominal aortic aneurysm (AAA) patients. We sought to clarify the role of TNF-α converting enzyme (Tace), which cleaves the transmembrane precursor of TNF-α, in AAA development.</P><P><B>Methods</B></P><P>We obtained aortic sample of AAA during surgical operation to assess the histological features and protein expression of human AAA. AAA was induced in mice with temporal systemic deletion of Tace by the inducible Mx-1 Cre transgene (TaceMx1) and in wild-type littermates (CON) by periaortic application of CaCl<SUB>2</SUB> (AAA/TaceMx1, AAA/CON).</P><P><B>Results</B></P><P>Tace expression was increased in human AAA samples as compared with normal aorta. Six weeks postoperatively, aortic diameter in AAA/TaceMx1 was decreased than in AAA/CON in association with attenuated TNF-α expression and extracellular matrix disruption. Increased activities of matrix metalloproteinase (MMP)-9 and MMP-2, numbers of Mac-2-positive macrophages, CD3-positive T lymphocytes and CD31-positive vessels in periaortic tissues, mRNA expression of CD68, monocyte chemotactic protein-1, TNF-α, vascular endothelial growth factor-A, p47 and glutathione peroxidases, and protein expression of phospho-c-Jun N-terminal kinase in AAA were all attenuated by Tace deletion. Protein expression of transforming growth factor (TGF)-β1 was upregulated by Tace deletion in sham-operated mice. TGF-β1 expression was further increased in AAA/TaceMx1.</P><P><B>Conclusions</B></P><P>Tace was overexpressed in the aortic wall in human and experimental AAA. Temporal systemic deletion of Tace prevented AAA development in association with attenuating inflammation, oxidative stress, neoangiogenesis and extracellular matrix disruption, suggesting a crucial role of Tace in AAA development.</P>
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Neutron and Proton Measurements of Cylindrical Radially Convergent Beam Fusion
sonoe Oura,Akitoshi Okino,Eiki Hotta,Kunihito Yamauchi,Masato Watanabe,Morimasa Yuura,Toshiyuki Kohno 한국물리학회 2006 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.49 No.III
Radially convergent beam fusion (RCBF) has been studied for practical use as a portable neutron/ proton source for various applications such as landmine detection and medical positron emission tomography. However, some problems remain for practical use, and the most critical one is the insufficiency of absolute neutron/proton yields. In this study, a new RCBF device was designed and tested to obtain higher neutron/proton yields. The key features of the new device are the cylindrical electrode configuration in consideration of better electrostatic confinement of ions and extraction of protons, and an integrated ion source. From the experiments using deuterium gas, it was confirmed that the ion source works effectively. At the same discharge condition of voltage and current, the obtained neutron production rate was about one order of magnitude higher than that of the conventional spherical RCBF device. A maximum neutron production rate of 6.8 × 109 n/s was obtained at a pulsed discharge of .70 kV, 10 A. For application as a proton source, proton yield in the RCBF device should be investigated, but the RCBF device also produces X-rays and electrons. To count protons by Solid-State Detector (SSD), it is necessary to eliminate these X-rays and electrons. Therefore, a new proton-counting system that has been designed has three magnetic deflectors. The SSD position was determined by a calculation of the proton trajectory.bt
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Lee, Chul Won,Bae, Chanhyung,Lee, Jaeho,Ryu, Jae Ha,Kim, Ha Hyung,Kohno, Toshiyuki,Swartz, Kenton J.,Kim, Jae Il American Chemical Society 2012 Biochemistry Vol.51 No.9
<P/><P>Kurtoxin is a 63-amino acid polypeptide isolated from the venom of the South African scorpion <I>Parabuthus transvaalicus</I>. It is the first and only peptide ligand known to interact with Cav3 (T-type) voltage-gated Ca<SUP>2+</SUP> channels with high affinity and to modify the voltage-dependent gating of these channels. Here we describe the nuclear magnetic resonance (NMR) solution structure of kurtoxin determined using two- and three-dimensional NMR spectroscopy with dynamical simulated annealing calculations. The molecular structure of the toxin was highly similar to those of scorpion α-toxins and contained an α-helix, three β-strands, and several turns stabilized by four disulfide bonds. This so-called “cysteine-stabilized α-helix and β-sheet (CSαβ)” motif is found in a number of functionally varied small proteins. A detailed comparison of the backbone structure of kurtoxin with those of the scorpion α-toxins revealed that three regions [first long loop (Asp<SUP>8</SUP>–Ile<SUP>15</SUP>), β-hairpin loop (Gly<SUP>39</SUP>–Leu<SUP>42</SUP>), and C-terminal segment (Arg<SUP>57</SUP>–Ala<SUP>63</SUP>)] in kurtoxin significantly differ from the corresponding regions in scorpion α-toxins, suggesting that these regions may be important for interacting with Cav3 (T-type) Ca<SUP>2+</SUP> channels. In addition, the surface profile of kurtoxin shows a larger and more focused electropositive patch along with a larger hydrophobic surface compared to those seen on scorpion α-toxins. These distinct surface properties of kurtoxin could explain its binding to Cav3 (T-type) voltage-gated Ca<SUP>2+</SUP> channels.</P>
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