• Korean Journal of Clinical Laboratory Science
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• v.50 no.4
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• pp.422-430
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• 2018

The inappropriate and widespread use of quinolones in humans and animals may cause accelerated emergence and spread of antimicrobial-resistant determinants. In this study, we investigated quinolone resistance mechanisms in a total of 65 nalidixic acid-resistant E. coli isolated from swine rectal swabs (N=40) and clinical specimens (N=25). Antimicrobial susceptibilities were determined by the disk diffusion method. PCR and DNA sequencing were performed for investigations of genes and mutations associated with quinolone resistance. In our study, 62 of 65 nalidixic acid-resistant E. coli harbored mutations in gyrA, parC, and/or parE genes; of the 65 isolates, 62 (95.4%) had mutations in the gyrA gene, 35 (53.8%) had mutations in the parC gene, 7 (10.8%) had mutations in the parE gene. The 35 isolates harbored mutations in two genes, gyrA and parC. Plasmid-mediated quinolone resistance (PMQR) determinants were investigated in the 65 isolates. Thirteen of 65 nalidixic acid-resistant E. coli contained the qnrS gene and 10 of those isolates had mutations in the gyrA, parC, and/or parE genes. We confirmed that an important mechanism of quinolone resistance in E. coli isolated from human and swine involves chromosomal mutations in the gyrA, parC, and/or parE genes with increasing use of quinolone for treatment or additives.

• Journal of Microbiology and Biotechnology
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• v.20 no.12
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• pp.1735-1743
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• 2010

The full-length genes gyrB (2,415 bp), parC (2,277 bp), and parE (1,896 bp) in Edwardsiella tarda were cloned by PCR with degenerate primers based on the sequence of the respective quinolone resistance-determining region (QRDR), followed by elongation of 5' and 3' ends using cassette ligation-mediated PCR (CLMP). Analysis of the cloned genes revealed open reading frames (ORFs) encoding proteins of 804 (GyrB), 758 (ParC), and 631 (ParE) amino acids with conserved gyrase/topoisomerase features and motifs important for enzymatic function. The ORFs were preceded by putative promoters, ribosome binding sites, and inverted repeats with the potential to form cruciform structures for binding of DNA-binding proteins. When comparing the deduced amino acid sequences of E. tarda GyrB, ParC, and ParE with those of the corresponding proteins in other bacteria, they were found to be most closely related to Escherichia coli GyrB (87.6% identity), Klebsiella pneumoniae ParC (78.8% identity), and Salmonella Typhimurium ParE (89.5% identity), respectively. The two topoisomerase genes, parC and parE, were found to be contiguous on the E. tarda chromosome. All 18 quinolone-resistant isolates obtained from Korea thus far did not contain subunit alternations apart from a substitution in GyrA (Ser83$\rightarrow$Arg). However, an alteration in the QRDR of ParC (Ser84$\rightarrow$Ile) following an amino acid substitution in GyrA (Asp87$\rightarrow$Gly) was detected in E. tarda mutants selected in vitro at $8{\mu}g/ml$ ciprofloxacin (CIP). A mutant with a GyrB (Ser464$\rightarrow$Leu) and GyrA (Asp87$\rightarrow$Gly) substitution did not show a significant increase in the minimum inhibitory concentration (MIC) of CIP. None of the in vitro mutants exhibited mutations in parE. Thus, gyrA and parC should be considered to be the primary and secondary targets, respectively, of quinolones in E. tarda.

• Journal of Life Science
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• v.20 no.4
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• pp.503-510
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• 2010

Most allergens have protease activities, suggesting that proteases may be a key link between Th2-type immune reactions in allergic responses. Protease activated receptor (PAR) 2 is activated via the proteolytic cleavage of its N-terminal domain by proteinases. To know the role of PAR2 in Aspergillus protease allergen activated Th2 immune responses in airway epithelial cells, we investigated and compared immune cell recruitment and level of chemokines and cytokines between PAR2 knock out (KO) mice and wild type (WT) mice. There were evident immune cell infiltrations into the bronchial alveolar lavage fluid (BALF) of WT mice, but the infiltrations in PAR2 KO mice were significantly lowered than those of WT mice. The IL-25, TSLP, and eotaxin gene expressions were profoundly increased after Aspergillus protease, but their expression was significantly lowered in PAR2 KO mice in this study. Compared to PAR2 KO mice, OVA specific IgE concentrations in serum of WT mice were quite increased; moreover, the IgE level of PAR2 KO mice was lower than in WT mice. The IL-25 expression by Aspergillus protease stimulation was significantly reduced by p38 specific inhibitor treatment. In this study, we determined that Th2 response was initiated with IL-25 and TSLP mRNA up-regulation in lung epithelial cells via PAR2 after Aspergillus protease allergen treatment.

• Journal of the Korea society of information convergence
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• v.6 no.2
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• pp.67-87
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• 2013

La France est un Etat unitaire $r{\acute{e}}agi$ par la Constitution. La $r{\acute{e}}forme$ de la $d{\acute{e}}centralisation$ a $d{\acute{e}}but{\acute{e}}$ par la $d{\acute{e}}claration$ 'des droits et $liber{\acute{e}}s$ des communes, des $d{\acute{e}}partements$ et des $r{\acute{e}}gions'$ qui influence plusieurs domaines de l' administration locale: la suppression du $contr\hat{o}le$ a priori et l' exercice du $contr\hat{o}le$ a posteriori par le commissaire de la Republique et par le Cour des comptes; le transfert des competences de l' Etat vers les communes, les $d{\acute{e}}partements$ et les $r{\acute{e}}gions$ avec la transmission du pouvoir de $d{\acute{e}}cision$; le transfert de moyens financiers pour financer les $d{\acute{e}}penses$ relatives aux $comp{\acute{e}}tences$ acquises; la $r{\acute{e}}forme$ du $syst{\acute{e}}me$ des fonctionnaires territoraux; le paiement des honoraires aux ${\acute{e}}lus$ locaux; la limitation du cumul des mandats.

• Biomedical Science Letters
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• v.10 no.4
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• pp.507-514
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• 2004

The Pseudomonas aeruginosa isolated from the clinical specimens has a mutation on the QRDR (quinolone resistance determining region). There were obvious mutations in both gyrA and parC gene which are major targets of quinolone. Simultaneous mutations were found two sites or more on these genes in all of ten strains. GyrB or parE gene had only silent mutation without converted amino acids. We confirmed that P. aeruginosa from clinical specimens exhibited decreased sensitivity to fluroquiolone due to changed Thr-83→lle and Asp-87→Asn types on gyrA and altered Ser-87→Leu type on parC. This is the first finding that a new Met-93→Thr type on parC as well as mutations on gyrB or parE genes differed from existing patterns. This study showed more mutations of gyrA rather than parC, suggesting that change of Type Ⅳ topoisomerase is more serious than that of type Ⅱ (DNA gyrase).

• Korean Journal of Clinical Laboratory Science
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• v.48 no.2
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• pp.74-81
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• 2016

Ureaplasma species can normally colonize in the bodies of healthy individuals. Their colonization is associated with various diseases including non-gonococcal urethritis, chorioamnionitis, neonatal meningitis, and prematurity. In 2012, the sum of the resistant and intermediate resistant rates of Ureaplasma spp. to ofloxacin and ciprofloxacin was 66.08% and 92.69%, respectively. DNA point mutations in the genes encoding DNA gyrase (topoisomerase II) and topoisomerase IV are commonly responsible for fluoroquinolone resistance. Each enzyme is composed of two subunits encoded by gyrA and gyrB genes for DNA gyrase and parC and parE genes for topoisomerase IV. In the current study, these genes were sequenced in order to determine the role of amino acid substitutions in Ureaplasma spp. clinical isolates. From December 2012 to May 2013, we examined mutation patterns of the quinolone resistance-determining region (QRDR) in Ureaplasma spp. DNA sequences in the QRDR region of Ureaplasma clinical isolates were compared with those of reference strains including U. urealyticum serovar 8 (ATCC 27618) and U. parvum serovar 3 (ATCC 27815). Mutations were detected in all ofloxacin- and ciprofloxacin-resistant isolates, however no mutations were detected in drug-susceptible isolates. Most of the mutations related to fluoroquinolone resistance occurred in the parC gene, causing amino acid substitutions. Newly found amino acid substitutions in this study were Asn481Ser in GyrB; Phe149Leu, Asp150Met, Asp151Ile, and Ser152Val in ParC; and Pro446Ser and Arg448Lys in ParE. Continuous monitoring and accumulation of mutation data in fluoroquinolone-resistant Ureaplasma clinical isolates are essential to determining the tendency and to understanding the mechanisms underlying antimicrobial resistance.

• The Korean Society of Law and Medicine
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• v.15 no.2
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• pp.367-397
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• 2014

Dans le contentieux m$\acute{e}$dical, il est difficile de prouver l'existence d'un lien de causalit$\acute{e}$ entre la faute m$\acute{e}$dicale et les pr$\acute{e}$judices subis par la victime. R$\acute{e}$partir bien de façon raisonnable la charge de la preuve du lien causal est alors une des questions pr$\acute{e}$occup$\acute{e}$es par la doctrine cor$\acute{e}$enne. La Cour supr$\hat{e}$me cor$\acute{e}$enne semble toutefois facilliter l'indemnisation des victimes dans les cas o$\grave{u}$ la responsabilit$\acute{e}$ du m$\acute{e}$decin a ${\acute{e}}t{\acute{e}}$ mise en cause, et cela en admettant des fois une solution op$\acute{e}$rant un renversement de la charge de la preuve du lien causal. Une telle attitude a ${\acute{e}}t{\acute{e}}$ m$\hat{e}$me affirm$\acute{e}$e dans un arr$\hat{e}$t rendu r$\acute{e}$cemment en cas de dommage caus$\acute{e}$ par le fait du produit de sant$\acute{e}$, notamment pour le cas de contamination virale par voie de transfusion. La Cour a $\acute{e}$galement reconnu que l'action se pr$\acute{e}$scrit $\grave{a}$ partir du moment de la consolidation du pr$\acute{e}$judice. Aux termes de cette $\acute{e}$tude, on pourra constater que le juge français reconna$\hat{i}$t aussi l'assouplissement de la charge de la preuve du lien de causalit$\acute{e}$ en mati$\acute{e}$re d'action m$\acute{e}$dicale. Il faudra toutefois souligner que le ph$\acute{e}$nom$\acute{e}$ne ne soit pas g$\acute{e}$n$\acute{e}$ralis$\acute{e}$ en droit français, d'autant plus que la pr$\acute{e}$somption de l'existence de la causalit$\acute{e}$ en la mati$\grave{e}$re a $\acute{e}$t$\acute{e}$ admise de mani$\grave{e}$re restrictive par la l$\acute{e}$gislation sp$\acute{e}$cifique. Tel $\acute{e}$tait notamment le cas pour les accidents de la contamination par le virus du sida ou de l'h$\acute{e}$patite C survenus apr$\grave{e}$s la transfusion. En d$\acute{e}$finitive, on peut dire qu'en droit français, le principe est maintenu en cas de manquement $\grave{a}$ une obligation de r$\acute{e}$sultat n$\acute{e}$e du contrat m$\acute{e}$dical, tandis que la Cour de cassation admet parfois en mati$\grave{e}$re de droit commun de la responsabilit$\acute{e}$ contractuelle la pr$\acute{e}$somption de causalit$\acute{e}$ en cas d'inex$\acute{e}$cution des obligations de r$\acute{e}$sultat. En fait, la pr$\acute{e}$somption de causalit$\acute{e}$ dans le contentieux m$\acute{e}$dical pourra mener les m$\acute{e}$decins $\grave{a}$ se diriger vers les traitements d$\acute{e}$fensifs. Cette situation peut m$\hat{e}$me conduire $\grave{a}$ emp$\hat{e}$cher le d$\acute{e}$veloppement de la science m$\acute{e}$dicale, enfin $\grave{a}$ une situation d$\acute{e}$savantageuse aux patients. Il y a alors lieu de se m$\acute{e}$fier des int$\acute{e}$r$\hat{e}$ts d$\acute{e}$s$\acute{e}$quilibr$\acute{e}$s entre le m$\acute{e}$decin et le patient. De ce point de vue, on peut estimer que le droit français donne des suggestions aux juristes cor$\acute{e}$ens dans la recherche des solutions plus ad$\acute{e}$quates en ce qui concerne la charge de la preuve du lien causal en mati$\acute{e}$re de responsabilit$\acute{e}$ m$\acute{e}$dicale.

• Journal of Digital Convergence
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• v.14 no.4
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• pp.371-378
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• 2016

An aim of current study was to investigate the prevalence and the mechanism of quinolone-resistance in E. coli isolates obtained from chicken cecum in Korea. In addition, multilocus sequence typing (MLST) was also performed for the molecular characterization of E. coli isolates. In an antimicrobial susceptibility test by the disk diffusion method, the 63.5% (54/85) of E. coli isolates showed the resistance to quinolone group of antimicrobial agents. All of the 54 E. coli isolates showing resistant to quinolone group had sense mutations in gyrA gene and point mutations at the $57^{th}$, $80^{th}$, or $84^{th}$ residues in parC gene were detected in 90.7% of the isolates. Interestingly, E. coli ST was closely related to amino acid substitutions in parE gene. Our results indicated that the long-term use of antimicrobial agents in food-producing animals was strongly associated with a prevalence of antimicrobial resistance in commensal Enterobacteriaceae, suggesting the need for continuous surveillance and monitoring of antimicrobial resistant determinants in bacterial isolates from food animals.

• (The) Research of the performance art and culture
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• no.18
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• pp.257-282
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• 2009

Le $th{\acute{e}}{\hat{t}}re$ musical en $Cor{\acute{e}}e$ est devenu aujourd'hui une mode. Beaucoup parlent de musical, mais beaucoup de musicals sont $mont{\acute{e}}s$ sur la $sc{\grave{e}}ne$ sans des recherches $n{\acute{e}}cessaires$ suffisantes. C'est pour cette raison que la plupart des spectacles musicaux qui sont $cr{\acute{e}}es$ en $Cor{\acute{e}}e$ sont $destin{\acute{e}}s$ en faillite $d{\grave{e}}s$ la naissance. D'ailleurs les musicals $liscenci{\acute{e}}s$ par $l^{\prime}Am{\acute{e}}rique$, la France qui sont $mont{\acute{e}}s$ sur la $sc{\grave{e}}ne$ de $Cor{\acute{e}}e$ aujourd'hui sont assez pour nuire le $march{\acute{e}}$ $cor{\acute{e}}en$ $constitu{\acute{e}}$ autour de musical. Quels sont donc les $probl{\grave{e}}mes$ que posent les musicals $liscenci{\acute{e}}s$? $Premi{\grave{e}}rement$ ils encouragent la mime, pas la $cr{\acute{e}}ation$. En d'autre terme, les musicals $liscenci{\acute{e}}s$ que les $Cor{\acute{e}}ens$ montent sur la $sc{\grave{e}}ne$ ne sont pas les $cr{\acute{e}}ations$ propres chez les $Cor{\acute{e}}ens$, par contre, ces derniers sont $demand{\acute{e}}s$ de suivre ${\grave{a}}$ la mot les indications $dict{\acute{e}}es$ par le droit d'auteur. Les $cr{\acute{e}}ateurs$ $cor{\acute{e}}ens$ ne sont pas libres de $cr{\acute{e}}ation$. $Deuxi{\grave{e}}mement$ les musicals ${\grave{a}}$ la mode ont pouvoir de $d{\acute{e}}truire$ la $diversit{\acute{e}}$ de l'homme. L'homme se $caract{\grave{e}}rise$ par la $diversit{\acute{e}}$ et se $diff{\grave{e}}re$ l'un par rapport ${\grave{a}}$ l'autre. C'est l'essence de l'homme. Tous sont $diff{\acute{e}}rents$. Pourtant le musical qui $r{\grave{e}}gne$ sur tous genres de spectacles d'aujourd'hui de $Cor{\acute{e}}e$ ne laisse pas vivre d'autres genres de spectacles, la danse, le $th{\acute{e}}{\hat{a}}tre$, etc. Seul le musical est $compt{\acute{e}}$. $Troisi{\grave{e}}mement$ le musical ne peut pas nier $compl{\grave{e}}tement$ son origine commerciale. En fait le musical est devenu une chose important depuis des investigations immenses par le gouvernement $d^{\prime}Am{\acute{e}}rique$ pour donner des travails aux gens. Donc, $d{\grave{e}}s$ le $d{\acute{e}}but$, il n'y avait pas de $consid{\acute{e}}rations$ artistiques dans et sur le musical. Comme c'est par le commerce que le musical est $r{\acute{e}}pandu$, s'il y aura un $probl{\grave{e}}me$ quelconque, il est $tr{\grave{e}}s$ possible qu'on cherche ${\grave{a}}$ $r{\acute{e}}soudre$ le $probl{\grave{e}}me$ par la vue de commerce. En comprenant les $probl{\grave{e}}mes$ $mentionn{\acute{e}}s$ $l{\grave{a}}$-dessus, il faut $pr{\acute{e}}parer$ le changement de $march{\acute{e}}$ $cor{\acute{e}}enne$ de musical. Le moyen le plus $su{\hat{r}}$ de se $pr{\acute{e}}parer$ est de trouver la $r{\acute{e}}solution$ dans la culture. Pourtant cette $derni{\grave{e}}re$ ne signifie pas la tradition comme $c^{\prime}{\acute{e}}tait$ le cas $jusqu^{\prime}{\grave{a}}$ aujourd'hui, car les $Cor{\acute{e}}ens$ ne sont pas ${\acute{e}}duqu{\acute{e}}s$ par cette $derni{\grave{e}}re$. La $modernit{\acute{e}}$, disons occidentale, traverse la $Cor{\acute{e}}e$. Donc, la signification du mot 'culture' doit ${\hat{e}}tre$ $bas{\acute{e}}e$ sur la tradition et la $modernit{\acute{e}}$ en $m{\hat{e}}me$ temps.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.3
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• pp.217-224
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• 2021

Fluoroquinolone (FQ) resistant gram-negative pathogens have emerged worldwide, and the recent increase in FQ resistant Escherichia coli is of great concern in Korea. This study investigated FQ resistance determinants and the epidemiological relationship of 56 ciprofloxacin-resistant E. coli isolated from a tertiary hospital in Daejeon, South Korea from June to December 2018. Molecular epidemiology was investigated by multilocus sequence typing (MLST). Polymerase chain reaction (PCR) and sequence analysis were performed to identify chromosomal mutations in the quinolone resistance determining regions (QRDR) of gyrA, gyrB, parC, and parE and to describe the occurrence of the following plasmid-mediated quinolone resistance (PMQR) genes: aac(6)-Ib-cr, qepA, qnrA, qnrB, qnrC, qnrD, and qnrS. MLST analysis showed 12 sequence types (STs) and the most prevalent ST was ST131 (31/56, 55.4%), followed by ST1193 (13/56, 23.2%), and ST405 (3/56, 5.4%). In 56 ciprofloxacin-resistant E. coli isolates, Ser83→Leu and Asp87→Asn in gyrA and Ser80→Ile and Glu84→Val in parC (51.8%, 29/56) were the most frequent amino acid substitutions and aac(6)-Ib-cr (33.9%, 19/56) was the most common PMQR gene. These results of FQ resistance determinants were more frequently observed in ST131 compared with other clones. Continuous monitoring of the epidemiological characteristics of ciprofloxacin-resistant E. coli isolates and further investigation of FQ resistance determinants are necessary.