記述言語：英語   掲載種別：研究論文（学術雑誌）  

The bacterium Vibrio alginolyticus, an opportunistic pathogen in humans, has a type III secretion system (T3SS) that is responsible for its cytotoxicity toward eukaryotic cells. The effector of T3SS that is responsible for the cytotoxicity had not been identified. Here we demonstrate that VepA, a homolog of the T3SS effector in V. parahaemolyticus, is required for cytotoxicity in V. alginolyticus. VepA induces lysosomal membrane permeabilization, and it allows the leakage of only small molecules into the cytosol. Our findings revealed that VepA induces cathepsin-independent cell death in mammalian cells. The ferrous ion, one of the small molecules in the lysosome contents, appears to be involved in the cell death caused by V. alginolyticus VepA.

DOI： 10.18926/AMO/56068

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s00232-017-9991-9

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その他リンク： http://link.springer.com/content/pdf/10.1007/s00232-017-9991-9.pdf

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.neulet.2016.11.043

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掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI AG  

DOI： 10.3390/toxins7082906

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.resmic.2014.07.016

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記述言語：英語   出版者・発行元：Okayama University Medical School  

Clostridium botulinum type C and D strains recently have been found to produce PLC on egg yolk agar plates. To characterize the gene, enzymatic and biological activities of C. botulinum PLCs (Cb-PLCs), the cb-plc genes from 8 strains were sequenced, and 1 representative gene was cloned and expressed as a recombinant protein. The enzymatic and hemolytic activities of the recombinant Cb-PLC were measured and compared with those of the Clostridium perfringens alpha-toxin. Each of the eight cb-plc genes encoded a 399 amino acid residue protein preceded by a 27 residue signal peptide. The protein consists of 2 domains, the N- and C-domains, and the overall amino acid sequence identity between Cb-PLC and alpha-toxin was greater than 50%, suggesting that Cb-PLC is homologous to the alpha-toxin. The key residues in the N-domain were conserved, whereas those in the C-domain which are important in membrane interaction were different than in the alpha-toxin. As expected, Cb-PLC could hydrolyze egg yolk phospholipid, p-nitrophenylphosphorylcholine, and sphingomyelin, and also exhibited hemolytic activity;however, its activities were about 4- to over 200-fold lower than those of alpha-toxin. Although Cb-PLC showed weak enzymatic and biological activities, it is speculated that Cb-PLC might play a role in the pathogenicity of botulism or for bacterial survival.

DOI： 10.18926/AMO/49252

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その他リンク： http://search.jamas.or.jp/link/ui/2013249132

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Okayama University Medical School  

Several studies have demonstrated the efficacy of intraprostatic injection of botulinum neurotoxin type A (BoNT/A) against symptomatic benign prostatic hyperplasia (BPH). The most commonly used BoNT/A product, Botox®, forms large complexes and composed of neurotoxin (NTX) as well as non-toxic components. We purified NTX lacking non-toxic components. We investigated the efficacy of this newly purified NTX for men with BPH. Ten male patients (mean age, 70.0 years) with BPH received 100 units (prostate volume [PV] ＜30ml) or 200 units (PV ｧ30ml) of NTX injected into the prostate via a minimally invasive outpatient technique. Evaluation included uroflowmetry, postvoid residual urine volume (PVR), PV, and International Prostate Symptom Score (IPSS) measured at baseline and 1, 3, 6, and 12 months post-treatment. The status of 7 of the 10 patients examined was found to have improved within 1 month of treatment. The mean IPSS decreased from 23.8±7.0 to 16.3±10.3 (p＝0.0093) at 1 month, to 14.9±8.2 (p＝0.0074) at 3 months, and to 16.9±7.3 (p＝0.018) at 12 months. The mean PV decreased from 47.8±21.2 to 39.2±19.5ml (p＝0.0076) at 3 months. The PVR improved at 3 and 6 months post-treatment. Intraprostatic NTX injection induces prostate shrinkage and is effective in men with BPH.

DOI： 10.18926/AMO/48668

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その他リンク： http://search.jamas.or.jp/link/ui/2013306579

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Okayama University Medical School  

Cultured Clostridium botulinum strains produce progenitor toxins designated as 12S, 16S, and 19S toxins. The 12S toxin consists of a neurotoxin (NTX, 7S) and a non-toxic non-hemagglutinin (NTNH). The 16S and 19S toxins are formed by conjugation of the 12S toxin with hemagglutinin (HA), and the 19S toxin is a dimer of the 16S toxin. Type A cultures produce all 3 of these progenitor toxins, while type E produces only the 12S toxin. The 7S toxin is cleaved into heavy (H) and light (L) chains by a protease(s) in some strains, and the H chain has 2 domains, the N-terminus (Hn) and C-terminus (Hc). It has been reported that type A toxins bind to the intestinal cells or cultured cells via either HA or Hc. In this study, we investigated the binding of type A and E toxins to Caco-2 cells using Western blot analysis. Both the type E 7S and 12S toxins bound to the cells, with the 7S toxin binding more strongly, whereas, in the type A strain, only the 16S/19S toxins showed obvious binding. Pre-incubation of the type E 7S toxin with IgG against recombinant type E Hc significantly inhibited the 7S toxin binding, indicating that Hc might be a main binding domain of the type E toxin.

DOI： 10.18926/AMO/48565

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その他リンク： http://search.jamas.or.jp/link/ui/2013156720

掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/j.1365-2842.2011.02236.x

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Hindawi Limited  

Type A neurotoxin (NTX) of<italic>Clostridium botulinum</italic>was purified by a simple procedure using a lactose gel column. The toxicity of this purified toxin preparation was retained for at least 1 year at −30°C by supplementation with either 0.1% albumin or 0.05% albumin plus 1% trehalose. When purified NTX was used to treat 49 patients with urinary incontinence caused by either refractory idiopathic or neurogenic detrusor overactivity, 36 patients showed significant improvement in symptoms. These beneficial effects were also observed in cases of prostatic hyperplasia. The results obtained with NTX were similar to that of Botox. The effects of NTX on trigeminal neuralgia induced by infraorbital nerve constriction (IoNC) in rats were also studied. Trigeminal ganglion neurons from ipsilateral to IoNC exhibited significantly faster onset of FM4-64 release than sham-operated contralateral neurons. Intradermal injection of NTX in the area of IoNC alleviated IoNC-induced pain behavior and reduced the exaggerated FM4-64 release in trigeminal ganglion neurons.

DOI： 10.1155/2012/648384

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その他リンク： http://downloads.hindawi.com/journals/jt/2012/648384.xml

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.urology.2009.01.047

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.bbabio.2009.03.004

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Microbiology  

<title>ABSTRACT</title>

<italic>Clostridium botulinum</italic>
cultures are classified into seven types, types A to G, based on the antigenicity of the neurotoxins produced. Of these seven types, only types C and D produce C2 toxin in addition to the neurotoxin. The C2 toxin consists of two components designated C2I and C2II. The genes encoding the C2 toxin components have been cloned, and it has been stated that they might be on the cell chromosome. The present study confirmed by using pulsed-field gel electrophoresis and subsequent Southern hybridization that these genes are on a large plasmid. The complete nucleotide sequence of this plasmid was determined by using a combination of inverse PCR and primer walking. The sequence was 106,981 bp long and contained 123 potential open reading frames, including the
<italic>c2I</italic>
and
<italic>c2II</italic>
genes. The 57 products of these open reading frames had sequences similar to those of well-known proteins. It was speculated that 9 these 57 gene products were related to DNA replication, 2 were responsible for the two-component regulatory system, and 3 were σ factors. In addition, a total of 20 genes encoding proteins related to diverse processes in purine catabolism were found in two regions. In these regions, there were 9 and 11 genes rarely found in plasmids, indicating that this plasmid plays an important role in purine catabolism, as well as in C2 toxin production.

DOI： 10.1128/jb.01797-08

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.neuroscience.2009.01.066

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：HINDAWI PUBLISHING CORPORATION  

Helicobacter pylori (H. pylori) infection is a definite causative factor for gastric ulcers (GUs). In the present study we detected a specific antigen of gastric epithelial cells (HGC-27) using cell ELISA, which was recognized by the sera of GU patients (n = 20) but not in patients with chronic gastritis (CG; n = 20) or in healthy volunteers (HC; n = 10). This antigen was over-expressed by a stressful (heat-stressed) environment, and was identified as elongation factor 2 kinase (EF-2K) by western blotting. The GU patients&apos; lymphocytes stimulated by H. pylori specifically disrupted heat-stressed HGC-27 cells in a cytotoxic assay. In flow cytometry, the effector cells (lymphocytes) from GU patients were significantly differentiated to T helper type 1 lymphocyte (Th1) and cytotoxic T lymphocyte (CTL) as opposed to those from CG patients. The target cells (HGC-27) expressed EF-2K and MHC-class I together with costimulatory molecules from heat stress. This antigen specific immune mechanism could have a prominent role in the pathogenesis of GU. Copyright (C) 2009 Kiyoshi Ayada et al.

DOI： 10.1155/2009/850623

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.micpath.2008.04.007

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記述言語：英語  

DOI： 10.1016/j.toxicon.2008.04.019

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

DOI： 10.1007/978-1-4020-6709-9_136

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

DOI： 10.1111/j.1574-695x.2007.00301.x

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

DOI： 10.1111/j.1574-6968.2007.00653.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Center for Academic Pub. Japan  

DOI： 10.1111/j.1348-0421.2007.tb03919.x

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Microbiology Society  

Previous reports have indicated that <italic>Helicobacter pylori</italic> heat-shock protein 60 (<italic>H. pylori</italic>-HSP60), as an immunodominant antigen, induces interleukin (IL)-8 production in human monocytes. The exact mechanism by which <italic>H. pylori</italic>-HSP60 induces IL-8 production in monocytes has not been fully elucidated. In the present study, the downstream pathway by which <italic>H. pylori</italic>-HSP60 induces IL-8 secretion in human monocytic cell lines was investigated. Intact <italic>H. pylori</italic>, heat-killed <italic>H. pylori</italic> and <italic>H. pylori</italic> recombinant HSP60 (rHpHSP60) all induced the secretion of IL-8 and the activation of mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK) and p38, but not c-Jun N-terminal kinase (JNK), up to 24 h in NOMO1 cells. The specific inhibitors PD98059 and U0126 (for ERK1/2 signalling) and SB203580 (for p38 MAPK signalling) down-regulated IL-8 secretion from rHpHSP60-treated NOMO1 cells. An anti-Toll-like receptor (TLR)2 antibody or TLR2 small interfering RNA (siRNA) partially inhibited the secretion of IL-8, and anti-TLR2 antibody also suppressed activation of ERK and p38 MAPK in rHpHSP60-treated NOMO1 cells. These reactions were associated with nuclear factor-<italic>κ</italic>B (NF-<italic>κ</italic>B)-mediated transcriptional activation, since U0126, SB203580 and the anti-TLR2 antibody decreased NF-<italic>κ</italic>B activation. Taken together, the results suggest that ERK and p38 MAPK signalling linked to the TLR2 recognition receptor in human monocytes may be an important pathway in <italic>H. pylori</italic>-HSP60-induced IL-8 secretion.

DOI： 10.1099/jmm.0.46882-0

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

<title>Abstract</title>
PsbP and PsbQ proteins are extrinsic subunits of photosystem II (PSII) and participate in the normal function of photosynthetic water oxidation. Both proteins exist in a broad range of the oxygenic photosynthetic organisms; however, their physiological roles in vivo have not been well defined in higher plants. In this study, we established and analyzed transgenic tobacco (Nicotiana tabacum) plants in which the levels of PsbP or PsbQ were severely down-regulated by the RNA interference technique. A plant that lacked PsbQ showed no specific phenotype compared to a wild-type plant. This suggests that PsbQ in higher plants is dispensable under the normal growth condition. On the other hand, a plant that lacked PsbP showed prominent phenotypes: drastic retardation of growth, pale-green-colored leaves, and a marked decrease in the quantum yield of PSII evaluated by chlorophyll fluorescence. In PsbP-deficient plant, most PSII core subunits were accumulated in thylakoids, whereas PsbQ, which requires PsbP to bind PSII in vitro, was dramatically decreased. PSII without PsbP was hypersensitive to light and rapidly inactivated when the repair process of the damaged PSII was inhibited by chloramphenicol. Furthermore, thermoluminescence studies showed that the catalytic manganese cluster in PsbP-deficient leaves was markedly unstable and readily disassembled in the dark. The present results demonstrated that PsbP, but not PsbQ, is indispensable for the normal PSII function in higher plants in vivo.

DOI： 10.1104/pp.105.068643

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s00425-005-0011-4

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その他リンク： http://link.springer.com/article/10.1007/s00425-005-0011-4/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s11120-004-7160-3

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その他リンク： http://link.springer.com/article/10.1007/s11120-004-7160-3/fulltext.html

記述言語：英語   出版者・発行元：Japanese Society of Plant Physiologists  

DOI： 10.1093/pcp/pci207

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その他リンク： http://orcid.org/0000-0001-9497-4452

記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：Kluwer Academic Publishers  

DOI： 10.14841/jspp.2005.0.012.0

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s00425-004-1328-0

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その他リンク： http://link.springer.com/article/10.1007/s00425-004-1328-0/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

DOI： 10.1271/bbb.67.107

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1016/s0014-5793(01)03180-5

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1074/jbc.m008877200

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1016/s0014-5793(98)00671-1

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記述言語：英語   掲載種別：研究論文（国際会議プロシーディングス）   出版者・発行元：SPRINGER  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Japanese Society of Plant Physiologists  

The D1 protein (D1) of photosystem II (PSII) reaction center is synthesized as a precursor (pD1) and then processed at its carboxyl terminus to establish the function of water cleavage. The amino acid sequence of the carboxyl terminal extension excised by this process is poorly con-served except for a residue after the cleavage site at position of 345. We have constructed a vector for site-directed mutagenesis of the chloroplast psbA gene encoding D1 of the green alga, Chlamydomonas reinhardtii. The vector enables one to transform the chloroplasts of a psbA deletion mutant (Fud7) and directly select transformants for resistance to spectinomycin. Using this transforming vector, we have substituted Ser345 to Gly, Cys, Val and Phe in order to investigate effects of the amino acid side chain at this position on the processing rate. All of the resulting transformants exhibited the PSII activity as wild type and grew normally under photoautotrophic conditions even under strong light where rapid turnover of D1 protein is expected to occur. Western blotting analysis demonstrated that mature D1 accumulates in these transformants at wild type level. Pulse and chase labeling of chloroplast-encoded proteins using [^<35>S]sulfate revealed that the processing of D1 precursor protein occurs in all four transformants as efficiently as in wild type, at least under the experimental conditions examined. The results suggest that either the amino acid side chain at position of 345 (+1 position) is not crucial to the enzymatic cleavage of pD1 in vivo or the apparent rate of processing in vivo is not limited by the enzymatic cleavage.

DOI： 10.1093/oxfordjournals.pcp.a028927

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/bf00017801

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その他リンク： http://link.springer.com/article/10.1007/BF00017801/fulltext.html

掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1074/jbc.270.18.10711

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1016/0014-5793(93)81796-3

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：英語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：日本細菌学会  

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記述言語：日本語   出版者・発行元：(公社)日本歯科医師会  

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記述言語：英語   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/j.neuroscience.2009.04.067

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記述言語：日本語   出版者・発行元：日本歯科医学会  

高齢者に多発する三叉神経痛の病態解明は現時点では十分とは言えず、根本的な治癒が得られずに激痛に苛まれている患者も少なくない。治療には抗てんかん薬や抗うつ薬などが用いられるが、それらの薬物が有するめまいやふらつきなどの中枢性副作用のため継続服用が不可能となることがある。我々は三叉神経痛などの慢性難治性疼痛に対する中枢性副作用の少ない治療法開発のため、研究を継続している。現在、毒素成分のみを精製した改良型ボツリヌス毒素(BoNT)を投与することにより、三叉神経節細胞における神経伝達物質の遊離が抑制されるのか、BoNTの末梢への注射により、三叉神経痛モデル動物の疼痛を抑制することができるのかを検討している。三叉神経痛モデルラットでは、三叉神経節細胞において神経伝達物質の遊離が増加していた。また、三叉神経痛モデルラットでは、疼痛閾値が低下しており、このラットモデルが疼痛を有していることが理解できた。このモデルラットの顔面部皮膚にBoNTを注射することにより、疼痛閾値が上昇し、疼痛が減弱することが確認できた。以上より、三叉神経痛患者治療において中枢性副作用を誘発しない、新しい治療法の開発に新たな展開が見られた。(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本口腔顔面痛学会  

J-GLOBAL

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/j.toxicon.2008.04.122

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：PERGAMON-ELSEVIER SCIENCE LTD  

DOI： 10.1016/j.toxicon.2008.04.020

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記述言語：英語   出版者・発行元：BLACKWELL PUBLISHING  

DOI： 10.1111/j.1574-695X.2007.00351.x

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：SPRINGER  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）   出版者・発行元：OXFORD UNIV PRESS  

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記述言語：英語   出版者・発行元：Japanese Society of Plant Physiologists  

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記述言語：日本語  

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記述言語：日本語  

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