Alterations in regulatory regions of erm(B) genes from clinical isolates of enterococci resistant to telithromycin.

We determined rates of resistance to the ketolide telithromycin in 56 Enterococcus faecalis isolates and 44 Enterococcus faecium isolates collected from hospitals in Korea between 2005 and 2006. Twenty nine (51.8%) isolates of E.

In-depth identification of pathways related to cisplatin-induced hepatotoxicity through an integrative method based on an informatics-assisted label-free protein quantitation and microarray gene expression approach.

Cisplatin is used widely for treatment of a variety of cancer diseases. Recently, however, the use of cisplatin is restricted because of its adverse effects such as hepatotoxicity. There is no study with current proteomics technology to evaluate cisplatin-induced hepatotoxicity, even if some studies have reported on the hepatotoxicity.

Antioxidant mechanism of isoflavone metabolites in hydrogen peroxide-stimulated rat primary astrocytes: critical role of hemeoxygenase-1 and NQO1 expression.

The brain is highly vulnerable to oxidative stress, thus controlling oxidative stress is considered to be an important therapeutic target for neurodegenerative diseases. In this study, we found that two isoflavone metabolites (tectorigenin and glycitein) inhibited hydrogen peroxide-induced reactive oxygen species (ROS) generation and subsequent cell death in rat primary astrocytes. The isoflavone metabolites increased the expression of phase II antioxidant enzymes, such as hemeoxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), and pre-treatment of cells with their specific inhibitors or small interfering RNA (siRNA) reversed the antioxidant and cytoprotective effects of isoflavones.

Downregulation of lamin A by tumor suppressor AIMP3/p18 leads to a progeroid phenotype in mice.

Although AIMP3/p18 is normally associated with the macromolecular tRNA synthetase complex, recent reports have revealed a new role of AIMP3 in tumor suppression. In this study, we generated a transgenic mouse that overexpresses AIMP3 and characterized the associated phenotype in vivo and in vitro. Surprisingly, the AIMP3 transgenic mouse exhibited a progeroid phenotype, and the cells that overexpressed AIMP3 showed accelerated senescence and defects in nuclear morphology.

Metallopharmaceuticals based on silver(I) and silver(II) polydiguanide complexes: activity against burn wound pathogens.

Objectives: The in vitro pharmacodynamics of silver(I) and silver(II) complexes of a polydiguanide ligand, chlorhexidine, were assayed to examine the value of the bactericidal endpoint as an alternative means of evaluating their antibacterial activities against burn wound pathogens.

Methods: Synthesis of silver(I) chlorhexidine [Ag(I)CHX] was accomplished by in situ precipitation of the complex from a feebly acidic or neutral aqueous solution of AgNO(3) and chlorhexidine, whereas silver(II) chlorhexidine [Ag(II)CHX] was synthesized by oxidation of Ag(I), followed by complexation of the oxidized metal with chlorhexidine. Their antibacterial potencies were assessed in vitro by determining the MICs and MBCs for four Gram-positive and four Gram-negative bacteria.

Extended spectrum of quinolone resistance, even to a potential latter third-generation agent, as a result of a minimum of two GrlA and two GyrA alterations in quinolone-resistant Staphylococcus aureus.

Background: This study was performed to determine the extended spectrum of quinolone resistance caused by increased mutations within the target enzymes of quinolones.

Methods: The minimum inhibitory concentrations (MICs) for ciprofloxacin, sparfloxacin, trovafloxacin and DW286 were determined against 98 ciprofloxacin-resistant Staphylococcus aureus strains. Also, PCR-amplified grlA, grlB, gyrA and gyrB DNA fragments were sequenced and amino acid changes were analyzed.

Aminoacyl-tRNA synthetase-interacting multifunctional proteins (AIMPs): a triad for cellular homeostasis.

Aminoacyl-tRNA synthetases (ARSs) are highly conserved for efficient and precise translation of genetic codes. In higher eukaryotic systems, several different ARSs including glutamyl-prolyl-, isoelucyl-, leucyl-, methionyl-, glutaminyl-, lysyl-, arginyl-, and aspartyl-tRNA synthetase form a macromolecular protein complex with three nonenzymatic cofactors (AIMP1/p43, AIMP2/p38, and AIMP3/p18). Although the structure and functional implications for this complex formation are not completely understood, rapidly accumulating evidences suggest that this complex would work as a molecular hub linked to the multiple signaling pathways that involve the components of enzymes and cofactors.

Development of TaqMan probe-based real-time PCR method for erm(A),erm(B), and erm(C), rapid detection of macrolide-lincosamide-streptogramin B resistance genes, from clinical isolates.

To achieve more accurate and rapid detection of macrolidelincosamide- streptogramin B resistance genes, erm(A), erm(B), and erm(C), we developed a TaqMan probe-based real-time PCR (Q-PCR) method and compared it with conventional PCR (C-PCR), which is the most widely using erm gene identification method. The detection limit of Q-PCR was 5 fg of genomic DNA or 5-8 CFU of bacterial cells of Staphylococcus aureus. The utilization of Q-PCR might shorten the time to erm detection from 3-4 h to about 50 min.

Synthesis of highly antibacterial nanocrystalline trivalent silver polydiguanide.

Highly monodispersed nanoparticles of a trivalent silver polydiguanide complex are synthesized by oxidation of the monovalent silver, followed by stabilization of the oxidized higher-valent metal through complexation with a polydiguanide ligand in a reverse microemulsion at room temperature. The synthesized nanoparticles have excellent photostability and displayed superior antibacterial activity toward Gram-positive and Gram-negative prokaryotes of clinical interest in vitro compared to silver sulfadiazine. These nanoparticles may serve as a new generation antibacterial metallopharmaceutical in wound care.

AIMP2 promotes TNFalpha-dependent apoptosis via ubiquitin-mediated degradation of TRAF2.

AIMP2 (aminoacyl-tRNA synthetase interacting multifunctional protein 2; also known as JTV-1) was first identified as p38 in a macromolecular protein complex that consisted of nine different aminoacyl-tRNA synthetases and two other auxiliary factors. AIMP2 also plays pivotal roles in the regulation of cell proliferation and death. Although AIMP2 was previously shown to augment TNFalpha-induced cell death, its working mechanism in this signal pathway was not understood.

[Study on the history of exchange in pharmaceutical science between Japan and Korea after the Modern period: focus on Korean students sent to Japan with expenses funded by the Japanese government].

According to an old historical text, Nihonshoki [Chinese and Korean characters: see text]), there are records of medical doctors ([Chinese and Korean characters: see text]) and herbal pharmacists ([Chinese and Korean characters: see text]) being dispatched to Japan as early as 554 A.D. ([Chinese and Korean characters: see text]).

Molecular analysis of constitutive mutations in ermB and ermA selected in vitro from inducibly MLSB-resistant enterococci.

Frequencies of spontaneous mutation from inducible resistance to constitutive resistance were determined for the four clinical isolates of erythromycin-resistant enterococci, including one isolate with ermB gene and three clinical isolates with ermA gene. The rate of ermB mutation was higher than that of ermA mutation by more than 10 fold. Sequence analysis of the regulatory regions of erm genes revealed that mutation type of ermB was just point mutation, by contraries the mutation type of ermA was either deletion or tandem duplication.

Determination of three-dimensional structure and residues of the novel tumor suppressor AIMP3/p18 required for the interaction with ATM.

Although AIMP3/p18 is normally associated with the multi-tRNA synthetase complex via its specific interaction with methionyl-tRNA synthetase, it also works as a tumor suppressor by interacting with ATM, the upstream kinase of p53. To understand the molecular interactions of AIMP3 and the mechanisms involved, we determined the crystal structure of AIMP3 at 2.0-angstroms resolution and identified its potential sites of interaction with ATM.

Translational attenuation and mRNA stabilization as mechanisms of erm(B) induction by erythromycin.

Translational attenuation has been proposed to be the mechanism by which the erm(B) gene is induced. Here, we report genetic and biochemical evidence, obtained by using erythromycin as the inducing antibiotic, that supports this hypothesis. We also show that erythromycin increases the level of the erm(B) transcript by stalling the ribosome on the leader mRNA and thereby facilitating the stabilization and processing of the mRNA.

Foggy D-shaped zone of inhibition in Staphylococcus aureus owing to a dual character of both inducible and constitutive resistance to macrolide-lincosamide-streptogramin B.

Objectives: We identified Staphylococcus aureus strains having blunt inhibitory zones around the clindamycin or josamycin discs proximal to the erythromycin disc filled with slight bacterial growth. This ambiguous phenotype was termed as 'macrolide-lincosamide-streptogramin B antimicrobial (MLS(B)) resistance having a foggy D-shaped inhibitory zone' (fMLS(B)), and we tried to analyse its molecular mechanisms.

Methods: Forty-one clinically isolated strains of fMLS(B) S.

Activities of clindamycin, synercid, telithromycin, linezolid, and mupirocin against Gram-positive coccal strains resistant to erythromycin in Korea.

The antibacterial activities of clindamycin, synercid, telithromycin, linezolid and mupirocin were evaluated against erythromycin-resistant Gram-positive coccal clinical isolates collected in Korean hospitals. In Staphylococcus aureus, synercid, linezolid and mupirocin were the most active agents. Against coagulase-negative staphylococci (CNS), synercid, linezolid and mupirocin were also active.

Identification, biological activity, and mechanism of the anti-ischemic quinolone analog.

The quinolone analog SQ-4004 has been identified as a potentially excellent anti-ischemic agent, which exhibited highly potent efficacy in reducing infarct volume size in vivo rat MCAO model (32.1% at 0.01mg/kg) and potent cardioprotective effect at myocardial infarction in vivo model (26.

Comparison of antibiotic effect and corneal epithelial toxicity of levofloxacin and moxifloxacin in vitro.

Purpose: To compare the bacterial susceptibility and corneal epithelial toxicity of levofloxacin and moxifloxacin in the human corneal epithelial cells (HCECs).

Methods: We used 2 types of strains, ie, American Type Culture Collection strains and resistant strains. The former included Staphylococcus aureus, coagulase-negative staphylococci, Pseudomonas aeruginosa, and Serratia marcescens, The latter were methicillin-resistant Staphylococcus aureus; methicillin-resistant, coagulase-negative Staphylococcus sp.

ErmK leader peptide : amino acid sequence critical for induction by erythromycin.

The ermK gene from Bacillus lichenformis encodes an inducible rRNA methylase that confers resistance to the macrolide-lincosamide-streptogramin B antibiotics. The ermK mRNA leader sequence has a total length of 357 nucleotides and encodes a 14-amino acid leader peptide together with its ribosome binding site. The secondary structure of ermK leader mRNA and a leader peptide sequence have been reported as the elements that control expression.

Hierarchical network between the components of the multi-tRNA synthetase complex: implications for complex formation.

The macromolecular tRNA synthetase complex consists of nine different enzymes and three non-enzymatic factors. This complex was recently shown to be a novel signalosome, since many of its components are involved in signaling pathways in addition to their catalytic roles in protein synthesis. The structural organization and dynamic relationships of the components of the complex are not well understood.

In vitro and in vivo activities of DW-224a, a novel fluoroquinolone antibiotic agent.

Objectives: The objective of the present study was to assess the in vitro and in vivo activities of DW-224a in order to eventually use it as an antibiotic.

Methods: DW-224a was compared with DW286, ciprofloxacin and trovafloxacin. MICs of DW-224a, DW286, ciprofloxacin and trovafloxacin were determined against several groups of clinical isolates.

Design and synthesis of quinolinones as methionyl-tRNA synthetase inhibitors.

Five new structural analogues of substituted-1H-quinolinones (19, 20, 23, 24, and 26) have been synthesized and evaluated for Staphylococcus aureus methionyl-tRNA synthetase enzyme inhibitory activity. These compounds were also tested against pathogens of six S. aureus, two Enterococcus faecalis, and one Enterococcus faecium.

Extracellular potassium deprivation reversibly dephosphorylates cofilin.

Cofilin is essential for actin filament remodeling in various cell types. We previously reported that ouabain leads to dephosphorylation of cofilin, resulting in cytoskeletal reorganization and cell volume change. We report here that the extracellular [K(+)](e) deprivation causes dephosphorylation of cofilin with disruption of cytoskeletal structures and cell shrinkage.

In vitro and in vivo antibacterial activities of DW-224a, a new fluoronaphthyridone.

DW-224a showed the most potent in vitro activity among the quinolone compounds tested against clinical isolates of gram-positive bacteria. Against gram-negative bacteria, DW-224a was slightly less active than the other fluoroquinolones. The in vivo activities of DW-224a against gram-positive bacteria were more potent than those of other quinolones.