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71.
Chunsun Ryu Kyunghee Lee Han-Jun Hawng Cheon-Kwon Yoo Won-Keun Seong Hee-Bok Oh 《Applied microbiology》2005,71(8):4664-4671
We analyzed the genetic relationships and molecular characteristics of 34 Bacillus anthracis isolates from soil and clinical samples in various regions of Korea and 17 related Bacillus species, using the amplified fragment length polymorphism (AFLP) and multilocus variable-number tandem repeat (MLVA) approaches. Triplicate AFLP profiles of these strains showed high reproducibility and identified 376 polymorphisms. AFLP phylogenetic analysis of B. anthracis isolates showed a high level of similarity, 0.93, and this monomorphic fragment profile proved to be useful to differentiate B. anthracis strains from other Bacillus species. The B. cereus group was separated from other Bacillus species at a level of similarity of 0.68. Among them, some B. cereus strains showed genetic interspersion with B. thuringiensis strains. The evolutionary pattern of nucleotide differences among B. anthracis strains with the eight MLVA markers showed nine MLVA types. Three MLVA types, M1 to M3, were pathogenic B. anthracis isolates and were assigned as new genotypes belonging to the A4 and B3 clusters, compared with 89 genotypes deduced from previous data. This indicates that differences in cluster prevalence and distribution may be influenced more by MLVA markers on two plasmids loci and human activity. Consequently, we suggest that the novel MLVA type may represent significant evidence for historic adaptation to environmental conditions of the Asian continent, particularly Korea. Therefore, MLVA techniques may be available for molecular monitoring on anthrax-release-related bioterrorism and further study is required for the continuous epidemiological study of variable anthrax collections. 相似文献
72.
Molecular chaperone GRP78/BiP interacts with the large surface protein of hepatitis B virus in vitro and in vivo 总被引:5,自引:0,他引:5 下载免费PDF全文
The proper folding and assembly of viral envelope proteins are mediated by host chaperones. In this study, we demonstrated that an endoplasmic reticulum luminal chaperone GRP78/BiP bound specifically to the pre-S1 domain of the L protein in vitro and in vivo where complete viral particles were secreted, suggesting that GRP78/BiP plays an essential role in the proper folding of the L protein and/or assembly of viral envelope proteins. 相似文献
73.
74.
Targeted delivery of a phosphopeptide prodrug inhibits the proliferation of a human glioma cell line
Peptides are ideal candidates for developing therapeutics. Polo-like kinase 1 is an important regulatory protein in the cell cycle and contains a C-terminal polo-box domain, which is the hallmark of this protein family. We developed a peptide inhibitor of polo-like kinase 1 that targets its polo-box domain. This new phosphopeptide, cRGDyK-S-S-CPLHSpT, preferentially penetrates the cancer cell membrane mediated by the integrin receptor, which is expressed at high levels by cancer cells. In the present study, using high performance liquid chromatography and mass spectroscopy, we determined the stability of cRGDyK-S-S-CPLHSpT and its cleavage by glutathione under typical conditions for cell culture. We further assessed the ability of the peptide to inhibit the proliferation of the U87MG glioma cell line. The phosphorylated peptide was stable, and the disulfide bond of cRGDyK-S-S-CPLHSpT was cleaved in 50 mM glutathione. This peptide inhibited the growth of cancer cells and changed their morphology. Therefore, we conclude that the phosphopeptide shows promise as a prodrug and has a high potential to act as an anticancer agent by inhibiting polo-like kinase 1 by binding its polo-box domain. These findings indicate the therapeutic potential of PLHSpT and peptides similarly targeted to surface receptors of cancer cells and to the functional domains of regulatory proteins. 相似文献
75.
76.
Osamu Ichikawa Kazuhiko Okazaki Hiroyuki Nakahira Megumi Maruyama Ryu Nagata Kumiko Tokuda Tomoko Horisawa Kazuto Yamazaki 《Neurochemistry international》2012
Lurasidone is a novel antipsychotic agent with high affinity for dopamine D2, 5-hydroxyltryptamine 5-HT2A, and 5-HT7 receptors. Lurasidone has negligible affinity for histamine H1 and muscarinic M1 receptors, which are thought to contribute to side effects such as weight gain, sedation, and worsening of cognitive deficits. Our interests focus on why lurasidone has such high selectivity for only a part of these aminergic G-protein coupled receptors (GPCRs) and the different binding profile from ziprasidone, which has the same benzisothiazolylpiperazine moiety as lurasidone. In order to address these issues, we constructed structural models of lurasidone–GPCR complexes by homology modeling of receptors, exhaustive docking of ligand, and molecular dynamics simulation-based refinement of complexes. This computational study gave reliable structural models for D2, 5-HT2A, and 5-HT7, which had overall structural complementarities with a salt bridge anchor at the center of the lurasidone molecule, but not for H1 and M1 owing to steric hindrance between the norbornane-2,3-dicarboximide and/or cyclohexane part of lurasidone and both receptors. By comparison with the structural models of olanzapine–GPCRs and ziprasidone–GPCRs constructed using the same computational protocols, it was suggested that the bulkiness of the norbornane-2,3-dicarboximide part and the rigidity and the bulkiness of the cyclohexyl linker gave lurasidone high selectivity for the desired aminergic GPCRs. Finally, this structural insight was validated by a binding experiment of the novel benzisothiazolylpiperazine derivatives. This knowledge on the structural mechanism behind the receptor selectivity should help to design new antipsychotic agents with preferable binding profiles, and the established computational protocols realize virtual screening and structure-based drug design for other central nervous system drugs with desired selectivity for multiple targets. 相似文献
77.
Ryu Sasaki Kazumi Yamasaki Seigo Abiru Atsumasa Komori Shinya Nagaoka Akira Saeki Satoru Hashimoto Shigemune Bekki Yuki Kugiyama Atsushi Kuno Masaaki Korenaga Akira Togayachi Makoto Ocho Masashi Mizokami Hisashi Narimatsu Tatsuki Ichikawa Kazuhiko Nakao Hiroshi Yatsuhashi 《PloS one》2015,10(6)
Measurement of Wisteria floribunda agglutinin-positive human Mac-2 binding protein (WFA+-M2BP) in serum was recently shown to be a noninvasive method to assess liver fibrosis. The aim of this study was to evaluate the utility of serum WFA+-M2BP values to predict the development of hepatocellular carcinoma (HCC) in patients who achieved a sustained virological response (SVR) by interferon treatment. For this purpose, we retrospectively analyzed 238 patients with SVR who were treated with interferon in our department. Serum WFA+-M2BP values were measured at pre-treatment (pre-Tx), post-treatment (24 weeks after completion of interferon; post-Tx), the time of HCC diagnosis, and the last clinical visit. Of 238 patients with SVR, HCC developed in 16 (6.8%) patients. The average follow-up period was 9.1 years. The cumulative incidence of HCC was 3.4% at 5 years and 7.5% at 10 years. The median pre-Tx and post-Tx WFA+-M2BP values were 1.69 (range: 0.28 to 12.04 cutoff index (COI)) and 0.80 (range: 0.17 to 5.29 COI), respectively. The WFA+-M2BP values decreased significantly after SVR (P < 0.001). The median post-Tx WFA+-M2BP value in patients who developed HCC was significantly higher than that in patients who did not (P < 0.01). Multivariate analysis disclosed that age (> 60 years), sex (male), pre-Tx platelet count (< 15.0×103/μL), and post-Tx WFA+-M2BP (> 2.0 COI) were associated with the development of HCC after SVR.
Conclusion
Post-Tx WFA+-M2BP (> 2.0 COI) is associated with the risk for development of HCC among patients with SVR. The WFA+-M2BP values could be a new predictor for HCC after SVR. 相似文献78.
Ryu Tashiro Masahiro Iwamoto Hironobu Morinaga Tomoko Emura Kumi Hidaka Masayuki Endo Hiroshi Sugiyama 《Nucleic acids research》2015,43(14):6692-6700
DNA has recently emerged as a promising material for the construction of nanosized architectures. Chemically modified DNA has been suggested to be an important component of such architectural building blocks. We have designed and synthesized a novel H-shaped DNA oligonucleotide dimer that is cross-linked with a structurally rigid linker composed of phenylene and ethynylene groups. A rotatable DNA unit was constructed through the self-assembly of this H-shaped DNA component and two complementary DNA oligonucleotides. In addition to the rotatable unit, a locked DNA unit containing two H-shaped DNA components was also constructed. As an example of an extended locked structure, a hexagonal DNA origami dimer and oligomer were constructed by using H-shaped DNA as linkers. 相似文献
79.
Hyunsuk Kim Hayne Cho Park Hyunjin Ryu Kiwon Kim Hyo Sang Kim Kook-Hwan Oh Su Jong Yu Jin Wook Chung Jeong Yeon Cho Seung Hyup Kim Hae Il Cheong Kyubeck Lee Jong Hoon Park York Pei Young-Hwan Hwang Curie Ahn 《PloS one》2015,10(12)
Mass effect from polycystic kidney and liver enlargement can result in significant clinical complications and symptoms in autosomal dominant polycystic kidney disease (ADPKD). In this single-center study, we examined the correlation of height-adjusted total liver volume (htTLV) and total kidney volume (htTKV) by CT imaging with hepatic complications (n = 461) and abdominal symptoms (n = 253) in patients with ADPKD. “Mass-effect” complications were assessed by review of medical records and abdominal symptoms, by a standardized research questionnaire. Overall, 91.8% of patients had 4 or more liver cysts on CT scans. Polycystic liver disease (PLD) was classified as none or mild (htTLV < 1,600 mL/m); moderate (1,600 ≤ htTLV <3,200 mL/m); and severe (htTLV ≥ 3,200 mL/m). The prevalence of moderate and severe PLD in our patient cohort was 11.7% (n = 54/461) and 4.8% (n = 22/461), respectively, with a female predominance in both the moderate (61.1%) and severe (95.5%) PLD groups. Pressure-related complications such as leg edema (20.4%), ascites (16.6%), and hernia (3.6%) were common, and patients with moderate to severe PLD exhibited a 6-fold increased risk (compared to no or mild PLD) for these complications in multivariate analysis. Similarly, abdominal symptoms including back pain (58.8%), flank pain (53.1%), abdominal fullness (46.5%), and dyspnea/chest-discomfort (44.3%) were very common, and patients with moderate to severe PLD exhibited a 5-fold increased risk for these symptoms. Moderate to severe PLD is a common and clinically important problem in ~16% of patients with ADPKD who may benefit from referral to specialized centers for further management. 相似文献
80.
Bang Wool Eom Keun Won Ryu Byung-Ho Nam Yunjin Park Hyuk-Joon Lee Min Chan Kim Gyu Seok Cho Chan Young Kim Seung Wan Ryu Dong Woo Shin Woo Jin Hyung Jun Ho Lee 《PloS one》2015,10(2)
BackgroundA small number of nomograms have been previously developed to predict the individual survival of patients who undergo curative resection for gastric cancer. However, all were derived from single high-volume centers. The aim of this study was to develop and validate a nomogram for gastric cancer patients using a multicenter database.MethodsWe reviewed the clinicopathological and survival data of 2012 patients who underwent curative resection for gastric cancer between 2001 and 2006 at eight centers. Among these centers, six institutions were randomly assigned to the development set, and the other two centers were assigned to the validation set. Multivariate analysis using the Cox proportional hazard regression model was performed, and discrimination and calibration were evaluated by external validation.ResultsMultivariate analyses revealed that age, tumor size, lymphovascular invasion, depth of invasion, and metastatic lymph nodes were significant prognostic factors for overall survival. In the external validation, the concordance index was 0.831 (95% confidence interval, 0.784–0.878), and Hosmer-Lemeshow chi-square statistic was 3.92 (P = 0.917).ConclusionsWe developed and validated a nomogram to predict 5-year overall survival after curative resection for gastric cancer based on a multicenter database. This nomogram can be broadly applied even in general hospitals and is useful for counseling patients, and scheduling follow-up. 相似文献