Publications by authors named "Young Ree Kim"

59 Publications

Serotype Distribution and Antimicrobial Resistance of Isolates in Korea between 2016 and 2017.

Ann Lab Med 2022 Mar;42(2):268-273

Department of Laboratory Medicine, Inje University College of Medicine, Busan, Korea.

is one of the major causes of food-borne infections. We investigated the serotype distribution and antimicrobial resistance of isolates collected in Korea between January 2016 and December 2017. In total, 669 isolates were collected from clinical specimens at 19 university hospitals. Serotyping was performed according to the Kauffmann-White scheme, and antimicrobial susceptibility was tested using Sensititre EUVSEC plates or disk diffusion. Among the strains, C (39.8%) and B (36.6%) were the most prevalent serogroups. In total, 51 serotypes were identified, and common serotypes were . enterica serovar I 4,[5],12:i:- (16.7%), . Enteritidis (16.1%), . Bareilly (14.6%), . Typhimurium (9.9%), and . Infantis (6.9%). The resistance rates to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole were 32.6%, 12.1%, and 8.4%, respectively. The resistance rates to cefotaxime and ciprofloxacin were 8.1% and 3.0%, respectively, while 5.4% were multidrug-resistant. serovar I 4,[5],12:i:- and . Enteritidis were highly prevalent, and there was an increase in rare serotypes. Multidrug resistance and ciprofloxacin resistance were highly prevalent. Periodic investigations of serotypes and antimicrobial resistance are needed.
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http://dx.doi.org/10.3343/alm.2022.42.2.268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8548255PMC
March 2022

Human zoonotic infectious disease caused by Streptococcus equi subsp. zooepidemicus.

Zoonoses Public Health 2021 Sep 28. Epub 2021 Sep 28.

Department of Internal Medicine, Jeju National University College of Medicine, Jeju, Korea.

Streptococcus equi subsp. zooepidemicus (SEZ) is a highly contagious infectious organism that causes disease in horses. SEZ is seldom isolated from humans; however, zoonotic infections are occasionally reported in individuals exposed to horses and other livestock. Herein, we report three human cases of SEZ in individuals, one with direct horse contact and two among individuals who had eaten raw horse meat. The phylogenetic tree showed that the genotypes of SEZ isolates from two of the cases on Jeju Island, South Korea, were similar to those of isolates from the United Kingdom and the United States of America.
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http://dx.doi.org/10.1111/zph.12895DOI Listing
September 2021

The first case of abdominal mycotic aneurysm caused by K1 hypervirulent Klebsiella pneumoniae in a healthy adult.

Acute Crit Care 2021 Sep 13. Epub 2021 Sep 13.

Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.

Incidence of hypervirulent Klebsiella pneumoniae (hvKp) infection has been steadily increasing in the Asia-Pacific rim. The characteristic of hvKp infection is its ability to cause multiple site infections and unpredictable metastatic spread in the community. We describe the first case of mycotic aneurysm caused by hvKp serotype K1 in a previously healthy man and review the literature. Of a total of 13 cases, including our case, three cases were related to hvKp. Among patients with hvKp, the level of mycotic aneurysm in most patients was the infrarenal aorta, and they underwent an aortic graft or coil embolization. All strains were susceptible to most antimicrobial agents, except ampicillin. Early detection of hvKp can help to prevent the metastatic spread of pathogens and be useful for optimal patient care and epidemiologic research.
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http://dx.doi.org/10.4266/acc.2021.00010DOI Listing
September 2021

Dynamics and Predictors of Mortality Due to Candidemia Caused by Different Species: Comparison of Intensive Care Unit-Associated Candidemia (ICUAC) and Non-ICUAC.

J Fungi (Basel) 2021 Jul 24;7(8). Epub 2021 Jul 24.

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju 61469, Korea.

We investigated mortality and predictors of mortality due to intensive care unit-associated candidemia (ICUAC) versus non-ICUAC by species. This study included all candidemia cases in 11 hospitals from 2017 to 2018 in South Korea. The all-cause mortality rates in all 370 patients with ICUAC were approximately twofold higher than those in all 437 patients with non-ICUAC at 7 days (2.3-fold, 31.1%/13.3%), 30 days (1.9-fold, 49.5%/25.4%), and 90 days (1.9-fold, 57.8%/30.9%). Significant species-specific associations with 7- and 30-day ICUAC-associated mortality were not observed. Multivariate analysis revealed that ICU admission was an independent predictor of (OR, 2.07-2.48) and -associated mortality (OR, 6.06-11.54). Fluconazole resistance was a predictor of -associated mortality (OR, 2.80-5.14). Lack (less than 3 days) of antifungal therapy was the strongest predictor of 7-day mortality due to ICUAC caused by (OR, 18.33), (OR, 10.52), and (OR, 21.30) compared with 30- and 90-day mortality (OR, 2.72-6.90). ICUAC had a stronger association with lack of antifungal therapy (55.2%) than ICUAC caused by other species (30.6-36.7%, all < 0.05). Most predictors of mortality associated with ICUAC were distinct from those associated with non-ICUAC and were mediated by species.
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http://dx.doi.org/10.3390/jof7080597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397010PMC
July 2021

Antimicrobial Susceptibility Trends of by Age Groups Over Recent 10 Years in a Single Hospital in South Korea.

Yonsei Med J 2021 Apr;62(4):306-314

Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.

Purpose: () causes respiratory tract infections. Its non-vaccine serotypes and multidrug-resistant pneumococcal diseases have increased during the post-pneumococcal vaccination era. Therefore, it is important to understand the regional and age-related antimicrobial susceptibility of to select appropriate empirical antimicrobials.

Materials And Methods: We retrospectively studied trends in the antimicrobial resistance of to commonly prescribed antibiotics in patient groups of various ages at a single teaching hospital in Jeju Island from 2009 to 2018.

Results: In total, 1460 isolates were obtained during the study period. The overall antimicrobial resistance rates of to penicillin, erythromycin, ceftriaxone, levofloxacin, and vancomycin were 16.2%, 84.7%, 25.9%, 3.3%, and 0.0%, respectively, and the MDR rate was 6.7%. Erythromycin and ceftriaxone resistance rates increased by years; however, they were significantly reduced in adult groups. Levofloxacin resistance and MDR rates were also higher in adult groups. Overall, the MDR rate significantly increased during the recent 10 years, as well as in patients with a history of hospitalization within 90 days [odds ratio (OR)=3.58, 95% confidence interval (CI)=1.91-6.71] and sinusitis (OR=4.98, 95% CI=2.07-11.96).

Conclusion: Erythromycin and ceftriaxone resistance rates and the MDR rate of significantly increased during the recent 10 years; the trends in individual antimicrobial resistance rates significantly differed between the age groups. This study indicates the need for caution when using ceftriaxone as an empirical antimicrobial against pneumococcal infections.
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http://dx.doi.org/10.3349/ymj.2021.62.4.306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007430PMC
April 2021

Multilaboratory Evaluation of the MALDI-TOF Mass Spectrometry System, MicroIDSys Elite, for the Identification of Medically Important Filamentous Fungi.

Mycopathologia 2021 Mar 12;186(1):15-26. Epub 2020 Nov 12.

Department of Laboratory Medicine, International St. Mary's Hospital, College of Medicine, Catholic Kwandong University, Incheon, Korea.

With the increasing number of fungal infections and immunocompromised patients, rapid and accurate fungal identification is required in clinical microbiology laboratories. We evaluated the applicability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, MicroIDSys Elite (ASTA Corp., South Korea) for the identification of medically important filamentous fungi. A total of 505 strains comprising 37 genera and 90 species collected from 11 Korean hospitals were sent to the microbiology laboratory of International St. Mary's Hospital. All isolates were tested using MicroIDSys Elite, and data were analyzed using the MoldDB v.1.22 database (ASTA). Correct identification rates were compared with the multigene sequencing results. MicroIDSys Elite correctly identified 86.5% (437/505) and 88.9% (449/505) of all tested isolates at the species and genus level, respectively. About 98.2% of Aspergillus isolates were identified at the species level, including cryptic and rare species of A. calidoustus, A. tamarii, A. lentulus, A. versicolor and A. aculeatus. MicroIDSys Elite identified 75.0% of basidiomycetes, including Schizophyllum commune, and 84.3% of the dermatophytes. It also distinguished Sprothrix globosa at the species level. The mean scores of total isolates corresponding to correct species identification were significantly higher than those obtained for genus-level identification (253.5 ± 50.7 vs. 168.6 ± 30.3, P < 0.001). MicroIDSys Elite showed high accuracy for the identification of filamentous fungi, including cryptic and rare Aspergillus species. It is suitable for use in clinical laboratories as a rapid and efficient tool for clinical mold identification. Further evaluations are recommended for MicroIDSys Elite as a rapid and efficient tool for the identification of medically important filamentous fungi.
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http://dx.doi.org/10.1007/s11046-020-00507-zDOI Listing
March 2021

L-Ascorbic Acid Inhibits Breast Cancer Growth by Inducing IRE/JNK/CHOP-Related Endoplasmic Reticulum Stress-Mediated p62/SQSTM1 Accumulation in the Nucleus.

Nutrients 2020 May 8;12(5). Epub 2020 May 8.

Department of Medicine, School of Medicine, Jeju National University 102 Jejudaehakno, Jeju 63243, Korea.

Anticancer effects of L-ascorbic acid (Vitamin C, L-AA) have been reported in various types of cancers. L-AA intake reduces breast cancer recurrence and mortality; however, the role of L-AA in the treatment of breast cancer remains poorly understood. In this study, we investigated the effect and mechanism action of L-AA on breast cancer growth. L-AA inhibited the growth of breast cancer cells by inducing apoptotic cell death at the evaluated treatment concentrations without affecting normal cells. Moreover, L-AA induces autophagosome formation via regulation of mammalian target of rapamycin (), Beclin1, and autophagy-related genes () and increased autophagic flux. Notably, we observed that L-AA increased p62/SQSTM1 (sequestosome 1) protein levels. Accumulation of p62 protein in cancer cells in response to stress has been reported, but its role in cancer regulation remains controversial. Here, we demonstrated that L-AA-induced p62 accumulation is related to L-AA-induced breast cancer growth inhibition. Furthermore, L-AA induced endoplasmic reticulum (ER) stress via the -- (inositol-requiring endonuclease-c-Jun N-terminal kinase-C/EBP homologous protein) signaling pathways, which increased the nuclear levels of p62/SQSTM1. These findings provide evidence that L-AA-induced ER stress could be crucial for p62 accumulation-dependent cell death, and L-AA can be useful in breast cancer treatment.
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http://dx.doi.org/10.3390/nu12051351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284633PMC
May 2020

Impact of -Positive Enterococcus faecium Exhibiting Diverse Susceptibility Phenotypes to Glycopeptides on 30-Day Mortality of Patients with a Bloodstream Infection.

Antimicrob Agents Chemother 2020 06 23;64(7). Epub 2020 Jun 23.

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea

This study was performed to evaluate the impacts of positivity of exhibiting diverse susceptibility phenotypes to glycopeptides on clinical outcomes in patients with a bloodstream infection (BSI) through a prospective, multicenter, observational study. A total of 509 patients with BSI from eight sentinel hospitals in South Korea during a 2-year period were enrolled in this study. Risk factors of the hosts and causative isolates were assessed to determine associations with the 30-day mortality of BSI patients via multivariable logistic regression analyses. The gene was detected in 35.2% (179/509) of isolates; 131 isolates exhibited typical VanA phenotypes (group -VanA), while the remaining 48 isolates exhibited atypical phenotypes (group -atypical), which included VanD ( = 43) and vancomycin-variable phenotypes ( = 5). A multivariable logistic regression indicated that positivity of causative pathogens was independently associated with the increased 30-day mortality rate in the patients with BSI; however, there was no significant difference in survival rates between the patients of the -VanA and -atypical groups (log rank test, 0.904). A high 30-day mortality rate was observed in patients with -positive BSIs, and positivity of causative isolates was an independent risk factor for early mortality irrespective of the susceptibility phenotypes to glycopeptides; thus, intensified antimicrobial stewardship is needed to improve the clinical outcomes of patients with -positive BSI.
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http://dx.doi.org/10.1128/AAC.02180-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7318022PMC
June 2020

Effects of methionine synthase and methionine synthase reductase polymorphisms on hypertension susceptibility.

Genes Genomics 2020 04 7;42(4):477-483. Epub 2020 Mar 7.

Department of Science Education, Teachers College, Jeju National University, Jeju, 63294, Republic of Korea.

Background: Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are strongly associated with hypertension incidence, although such association is inconsistent among ethnicities studied. However, effects of polymorphisms of other genes related to folate metabolism besides MTHFR on hypertension susceptibility are not well known yet.

Objective: The aim of this study was to elucidate whether methionine synthase (MTR) 2756A>G and methionine synthase reductase (MTRR) 66A>G polymorphisms might be associated with risks of hypertension susceptibility in the Korean population.

Methods: Genotyping of these two polymorphisms was performed for 232 hypertensive patients and 247 unrelated healthy controls using polymerase chain reaction-restriction fragment length polymorphism technique.

Results: In the present study, mutations of MTR 2756A>G and MTRR 66A>G polymorphisms were associated with increased and decreased susceptibility to hypertension, respectively. Allele combinations from these two polymorphisms were also related to hypertension prevalence. When polymorphism data were stratified according to clinical components of hypertension, The G allele of MTR 2756A>G polymorphism was significantly associated with an increased risk of hypertension in subjects with BMI < 26.1 kg/m (P = 0.004), WC < 87.2 in. (P = 0.021), FBG < 95.5 mg/dL (P = 0.011), triglyceride < 133.5 mg/dL (P = 0.034), and HDL-cholesterol < 52.2 mg/dL (P = 0.036). The G allele of MTRR 66A>G polymorphism was significantly associated with a decreased risk of hypertension in subjects with WC ≥ 87.2 in. (P = 0.029), FBG ≥ 95.5 mg/dL (P = 0.032) and triglyceride ≥ 133.5 mg/dL (P = 0.027).

Conclusion: MTR 2756A>G and MTRR 66A>G polymorphisms related to folate metabolism might be genetic markers for risk of hypertension in the Korean population.
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http://dx.doi.org/10.1007/s13258-020-00917-9DOI Listing
April 2020

Phylogenetic Analysis for the Origin of Typhoid Fever Outbreak on Jeju Island, Korea, in 2017.

Infect Chemother 2020 Sep 17;52(3):421-426. Epub 2020 Mar 17.

Division of Infectious Disease, Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

In June 2017, on Jeju Island, six patients were diagnosed with typhoid fever. All six patients were admitted to our hospital with fever, all of them had been working at the same hotel. The and genes of four out of six cases were amplified by polymerase chain reaction. The phylogenetic tree of the genes showed that the isolates from Jeju Island in 2017 had the same genotype and were similar to isolates from the United Kingdom. The origin of the isolates of the outbreak was the same, and the disease strain may have been imported from outside of Korea.
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http://dx.doi.org/10.3947/ic.2020.52.3.421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533213PMC
September 2020

First Report of Tenosynovitis Caused by in Korea.

Ann Lab Med 2020 Mar;40(2):184-186

Department of Internal Medicine, Jeju National University College of Medicine and Graduate School of Medicine, Jeju, Korea.

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http://dx.doi.org/10.3343/alm.2020.40.2.184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6821998PMC
March 2020

Invasive Pneumococcal Disease Caused by Non-Vaccine Type Multidrug-Resistant Transmitted by Close Contact in a Healthy Adult.

Yonsei Med J 2019 Nov;60(11):1103-1107

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

The incidence of vaccine-type carriage and disease have declined in vaccinated children as well as in unvaccinated children and adults. However, diseases caused by non-vaccine type (NVT) are increasing. In this study, we report an invasive pneumococcal disease (IPD) caused by NVT multidrug-resistant (MDR) transmitted from a vaccinated infant to an unvaccinated healthy woman, and the clinical characteristics of this serotype. A 29-year-old previously healthy woman visited our hospital with fever and headache. She had been breastfeeding her baby for 8 months. She was diagnosed with brain abscess and sinusitis caused by . Although the patient had no previous exposure to antibiotics, antibiotic susceptibility test identified the pathogen as MDR. The patient's family members were examined using nasopharyngeal swabs for bacterial culture. The serotype of identified from the blood, abscess, and sputum of the patient was 15B/C. After investing the patient's family members, we found that the serotype from nasopharyngeal specimen of her baby was the same. We described an invasive MDR pneumococcal disease in an immunocompetent young adult in the community. IPD likely spread to the patient by close contact with her baby, who harbored of NVT. The spread of NVT in the post-vaccine era has increased in the community, and resistance pattern for of 15B/C changed compared to the pre-pneumococcal conjugate vaccine era. The spread of MDR pathogens causing IPD among family members should be monitored.
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http://dx.doi.org/10.3349/ymj.2019.60.11.1103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813149PMC
November 2019

Group B streptococcal transmission via a prolonged colonizer in a neonatal intensive care unit.

J Microbiol Immunol Infect 2020 Feb 30;53(1):179-182. Epub 2019 Sep 30.

Department of Pediatrics, Jeju National University School of Medicine, Jeju, Republic of Korea. Electronic address:

This article reports five invasive Group B streptococcal (GBS) infections that occurred in a neonatal intensive care unit for about 3 months. This outbreak might have been associated with a prolonged GBS colonized infant and adjacent environmental contaminations. Infection control interventions prevented the additional spread of GBS infections.
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http://dx.doi.org/10.1016/j.jmii.2019.08.014DOI Listing
February 2020

Antimicrobial resistance in South Korea: A report from the Korean global antimicrobial resistance surveillance system (Kor-GLASS) for 2017.

J Infect Chemother 2019 Nov 13;25(11):845-859. Epub 2019 Jul 13.

Department of Laboratory Medicine, Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea. Electronic address:

At the end of 2015, a global action plan on antimicrobial resistance (AMR) was proposed by the World Health Organization, and the Global AMR Surveillance System (GLASS) was subsequently initiated. The Centers for Disease Control and Prevention of South Korea established a customized AMR surveillance system for South Korea, called Kor-GLASS, in early 2016. A pilot phase of Kor-GLASS was operated from May to December 2016 with six sentinel hospitals, and phase I of Kor-GLASS started in January 2017 with eight sentinel hospitals. Previous surveillance data for overestimated AMR due to duplicate isolation of drug-resistant pathogens were corrected and error-free AMR data were compared with those from other countries. One-half (53.2%, 377/708) of Staphylococcus aureus blood strains exhibited resistance to cefoxitin, indicating methicillin-resistant S. aureus. Resistance to ampicillin in Enterococcus faecalis blood strains was rare (0.6%, 1/175), while the resistance rate to penicillin was 26.3% (46/175). Resistance to vancomycin (34.0%, 98/288) and teicoplanin (18.8%, 98/288) was frequently observed in Enterococcus faecium strains. The resistance rate of Escherichia coli strains to cefotaxime was 32.4% (574/1772), and that of Klebsiella pneumoniae strains was 26.1% (181/693). The resistance rates of Pseudomonas aeruginosa strains to imipenem and meropenem were 19.5% (29/149) and 18.1% (27/149), respectively. And 92.1% (187/203) of Acinetobacter baumannii strains were resistant to both imipenem and meropenem. The high incidence of bacteremia caused by major AMR pathogens among hospitalized patients especially in intensive care units emphasized the importance of hospital infection control and the need to improve the crowded hospitalization system in South Korea. The isolation rate of the Salmonella spp. is decreasing, reflecting the current socio-economic status of South Korea. The proportions of bacterial species in the blood strains were similar to those in other Asian countries with similar lifestyles.
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http://dx.doi.org/10.1016/j.jiac.2019.06.010DOI Listing
November 2019

Serotype Distribution and Antimicrobial Resistance of Invasive and Noninvasive Isolates in Korea between 2014 and 2016.

Ann Lab Med 2019 Nov;39(6):537-544

Department of Laboratory Medicine, Chonnam National University Medical School, Gwangju, Korea.

Background: Several factors contribute to differences in serotype distribution. We investigated the serotype distribution and antimicrobial resistance of isolated between 2014 and 2016 in Korea.

Methods: We collected a total of 1,855 isolates from 44 hospitals between May 2014 and May 2016, and analyzed the serotypes by sequential multiplex PCR. We investigated the distribution of each serotype by patient age, source of the clinical specimen, and antimicrobial resistance pattern.

Results: The most common serotypes were 11A (10.1%), followed by 19A (8.8%), 3 (8.5%), 34 (8.1%), 23A (7.3%), and 35B (6.2%). The major invasive serotypes were 3 (12.6%), 19A (7.8%), 34 (7.8%), 10A (6.8%), and 11A (6.8%). Serotypes 10A, 15B, 19A, and 12F were more common in patients ≤5 years old, while serotype 3 was more common in patients ≥65 years old compared with the other age groups. The coverage rates of pneumococcal conjugate vaccine (PCV)7, PCV10, PCV13, and pneumococcal polysaccharide vaccine 23 were 11.8%, 12.12%, 33.3%, and 53.6%, respectively. Of the 1,855 isolates, 857 (46.2%) were multi-drug resistant (MDR), with serotypes 11A and 19A predominant among the MDR strains. The resistance rates against penicillin, cefotaxime, and levofloxacin were 22.8%, 12.5%, and 9.4%, respectively.

Conclusions: There were significant changes in the major serotypes in the community. Non-PCV13 serotypes increased in patients ≤5 years old following the introduction of national immunization programs with the 10- and 13-polyvalent vaccines.
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http://dx.doi.org/10.3343/alm.2019.39.6.537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660335PMC
November 2019

Associations of MTRR and TSER polymorphisms related to folate metabolism with susceptibility to metabolic syndrome.

Genes Genomics 2019 08 18;41(8):983-991. Epub 2019 Jun 18.

Department of Science Education, Teachers College, Jeju National University, Jeju, 63294, Republic of Korea.

Background: Hyperhomocysteinemia is a potential risk factor for the development of metabolic syndrome (MetS). Among genes involved in homocysteine metabolism, polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene are known to be associated with MetS incidence. However, effects of polymorphisms of other folate metabolism-related genes on MetS susceptibility are not well known yet.

Objective: This study was to determine whether methionine synthase (MTR) 2756A > G, methionine synthase reductase (MTRR) 66A > G, and thymidylate synthase enhancer region (TSER) 2R/3R polymorphisms might be associated with risks of MetS development in the Korean population.

Methods: Genotype analysis of the three polymorphisms was performed for a total of 483 subjects including 236 MetS patients and 247 unrelated healthy controls using polymerase chain reaction-restriction fragment length polymorphism technique.

Results: The present study revealed that MTRR and TSER polymorphisms were associated with susceptibility to MetS. Several genotypes and allele combinations from the three polymorphisms were also related to the MetS prevalence. When polymorphism data were stratified according to the risk components of MetS, MTR polymorphism was significantly associated with an increased risk of MetS in subjects with systolic blood pressure < 132.7 mmHg (AOR 1.842, 95% CI 1.039-3.266, P = 0.037) and fasting blood glucose level < 106.3 mg/dL (AOR 1.772, 95% CI 1.069-2.937, P = 0.027). MTRR polymorphism was significantly associated with a decreased risk of MetS in subjects with triglyceride level < 216.3 mg/dL (AOR 0.616, 95% CI 0.399-0.951, P = 0.029). To the best of our knowledge, this is the first to provide reliable evidence about the association of other folate metabolism-related gene polymorphisms besides MTHFR with MetS susceptibility and its risk factors.

Conclusion: Results of this study suggest that MTRR and TSER polymorphisms might be potential genetic markers for the risk of MetS development in Korean population.
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http://dx.doi.org/10.1007/s13258-019-00840-8DOI Listing
August 2019

Occupational Risk of Severe Fever With Thrombocytopenia Syndrome in Healthcare Workers.

Open Forum Infect Dis 2019 May 6;6(5):ofz210. Epub 2019 May 6.

Department of Internal Medicine, Jeju National University Hospital, Jeju, Republic of Korea.

We identified a healthcare-associated infection of severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV), transmitted through direct blood contact with an index case. Following further epidemiological and clinical investigations, we identified SFTSV seropositivity in 2 healthcare workers and 2 family members, who were positive for anti-SFTSV immunoglobin G. It is important to prevent SFTSV transmission by early diagnosis of SFTS and universal precautions.
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http://dx.doi.org/10.1093/ofid/ofz210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6527088PMC
May 2019

Changes in Serotype of After the Introduction of the 13-Valent Pneumococcal Vaccine in a Homogenous Population on Jeju Island.

Infect Chemother 2019 Mar;51(1):67-72

Department of Microbiology and Immunology, Jeju National University School of Medicine, Jeju, Korea.

We compared the serotypes of between the pre-pneumococcal conjugate vaccine (PCV)13 era and post-PCV13 era among homogenous inhabitants of an isolated South Korean island. A total of 325 strains were isolated. In the pre-PCV13 era, 19A/F, 15A/F, 19B, and 23A serotypes were identified. In the post-PCV13 era, 15 serotypes were identified. The 19F and 23A serotypes showed the highest prevalence in the pre- and post-PCV13 era, respectively. After PCV13 introduction, the PCV 13 serotype coverage rate was decreased (80.0% and 30.5% in the pre- and post-PCV13 eras, respectively), while the proportion of non-PCV 13 serotypes increased.
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http://dx.doi.org/10.3947/ic.2019.51.1.67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6446012PMC
March 2019

Prevalence and Clinical Features of Community-Acquired Pneumonia Caused by Macrolide-Resistant Isolated from Adults in Jeju Island.

Microb Drug Resist 2019 May 28;25(4):577-581. Epub 2018 Nov 28.

2 Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, Republic of Korea.

Although the cases of macrolide-resistant (MRMP) have been increasing substantially among children, there are very few studies that have focused on MRMP in adults. This study aimed to investigate the prevalence and clinical features of community-acquired pneumonia (CAP) caused by MRMP from adults in Jeju Island, Korea. We retrospectively recruited adult patients with CAP in whom infections had been confirmed for a 7-year period. Macrolide resistance was determined by identifying a mutation in the 23S rRNA gene using PCR. In total, 70 subjects were included. Their mean age was 46.1 years and 36 (51.4%) were women. Only two isolates (2.9%) carried macrolide resistance mutations in the 23S rRNA gene, and all the mutations were A2063G transitions. No significant differences were observed in age, comorbidities, symptoms, duration of fever, and length of hospital stay between the MRMP and macrolide-sensitive groups. The number of involved pulmonary lobes was greater in the MRMP group (3.50 vs. 1.44,  = 0.008). The prevalence of CAP caused by MRMP was relatively low in adults in Jeju Island. Patients with MRMP pneumonia tended to have multilobar pneumonic infiltrates.
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http://dx.doi.org/10.1089/mdr.2018.0295DOI Listing
May 2019

Severe Fever with Thrombocytopenia Syndrome Virus Infection, South Korea, 2010.

Emerg Infect Dis 2018 11;24(11):2103-2105

Severe fever with thrombocytopenia syndrome (SFTS) was reported in China in 2009 and in South Korea in 2012. We found retrospective evidence of SFTS virus infection in South Korea in 2010, suggesting that infections in South Korea occurred before previously reported and were more concurrent with those in China.
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http://dx.doi.org/10.3201/eid2411.170756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199997PMC
November 2018

Risk factors for persistent otitis media with effusion in children: a case-control study.

Yeungnam Univ J Med 2018 06 30;35(1):70-75. Epub 2018 Jun 30.

Department of Pediatrics, Jeju National University School of Medicine, Jeju, Korea.

Background: Otitis media with effusion (OME) is defined as middle ear effusion without acute signs of infection. OME usually resolves spontaneously; however, persistent OME may require the insertion of a ventilation tube. This study investigated risk factors for persistent OME in children who undergo ventilation tube insertion.

Methods: Children who were admitted to undergo ventilation tube insertion at Jeju National University Hospital between August 2015 and July 2016 were enrolled as the case group. Healthy children without persistent OME from August 2016 to July 2017 were enrolled as the control group. Baseline characteristics and predisposing factor data were collected using an interview questionnaire. Middle ear fluids were collected from the case group.

Results: A total of 31 patients underwent ventilation tube insertion. The mean age of the case group was 4.53 years, with a male-to-female ratio of 21:10. Twenty-nine (93.5%) children attended a daycare center, and 21 (67.7%) had experience with bottle feeding. Fifteen (48.4%) children in the case group and 3 (9.7%) in the control group first attended a daycare center at <1 year of age (odds ratio=9.96; 95% confidence interval=2.44-39.70; =0.001). No bacteria were found in middle ear fluid collected from the 31 operated children. Nasopharyngeal bacterial colonization was found in 13 (41.9%) and 17 (54.8%) children in the case and control groups, respectively.

Conclusion: Earlier attendance at a daycare center was the only predisposing factor for ventilation tube insertion in our study. The aseptic nature of middle ear fluids found in children with OME highlights the efficacy of antimicrobial use.
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http://dx.doi.org/10.12701/yujm.2018.35.1.70DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784671PMC
June 2018

Ceftaroline Resistance by Clone-Specific Polymorphism in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus.

Antimicrob Agents Chemother 2018 09 27;62(9). Epub 2018 Aug 27.

Department of Laboratory Medicine and Research Institute of Bacterial Resistance, Yonsei University College of Medicine, Seoul, South Korea

A total of 281 nonduplicated blood isolates were collected from January to May 2017 from eight hospitals in South Korea to investigate the epidemiological traits of ceftaroline resistance in methicillin-resistant (MRSA). Cefoxitin-disk diffusion tests and the gene PCR revealed that 56.6% (159/281) of the isolates were MRSA, and most belonged to ST5 (50.3%, 80/281) and ST72 (41.5%, 66/281). Of the MRSA isolates, 44.0% (70/159) were nonsusceptible to ceftaroline (MIC ≥ 2 mg/liter), whereas all of the methicillin-susceptible isolates were susceptible to the drug. Eight amino acid substitutions in penicillin-binding protein 2a (PBP2a), including four (L357I, E447K, I563T, and S649A) in the penicillin-binding domain (PBD) and four (N104K, V117I, N146K, and A228V) in the non-PBD (nPBD) of PBP2a, were associated with ceftaroline resistance. The accumulation of substitutions in PBP2a resulted in the elevation of ceftaroline MICs: one substitution at 1 to 2 mg/liter, two or three substitutions at 2 to 4 mg/liter, and five substitutions at 4 or 16 mg/liter. Ceftaroline resistance in MRSA might be the result of clone-specific PBP2a polymorphism, along with substitutions both in PBD and nPBD, and the elevated ceftaroline MICs were associated with the substitution sites and accumulation of substitutions.
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http://dx.doi.org/10.1128/AAC.00485-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125543PMC
September 2018

Over-activation of AKT signaling leading to 5-Fluorouracil resistance in SNU-C5/5-FU cells.

Oncotarget 2018 Apr 13;9(28):19911-19928. Epub 2018 Apr 13.

Department of Medicine, School of Medicine, Jeju National University, Jeju 63243, Republic of Korea.

Here, we investigated whether over-activation of AKT pathway is important in the resistance to 5-fluorouracil (5-FU) in SNU-C5/5-FU cells, 5-FU-resistant human colon cancer cells. When compared to wild type SNU-C5 cells (WT), SNU-C5/5-FU cells showed over-activation of PI3K/AKT pathway, like increased phosphorylation of AKT, mTOR, and GSK-3β, nuclear localization of β-catenin, and decreased E-cadherin. Moreover, E-cadherin level was down-regulated in recurrent colon cancer tissues compared to primary colon cancer tissues. Gene silencing of AKT1 or treatment of LY294002 (PI3 kinase inhibitor) increased E-cadherin, whereas decreased phospho-GSK-3β. LY294002 also reduced protein level of β-catenin with no influence on mRNA level. PTEN level was higher in SNU-C5/WT than SNU-C5/5-FU cells, whereas the loss of PETN in SNU-C5/WT cells induced characteristics of SNU-C5/5-FU cells. In SNU-C5/5-FU cells, NF-κB signaling was activated, along with the overexpression of COX-2 and stabilization of survivin. However, increased COX-2 contributed to the stabilization of survivin, which directly interacts with cytoplasmic procaspase-3, while the inhibition of AKT reduced this cascade. We finally confirmed that combination treatment with 5-FU and LY294002 or Vioxx could induce apoptosis in SNU-C5/5-FU cells. These data suggest that inhibition of AKT activation may overcome 5-FU-resistance in SNU-C5/5-FU cells. These findings provide evidence that over-activation of AKT is crucial for the acquisition of resistance to anticancer drugs and AKT pathway could be a therapeutic target for cancer treatment.
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http://dx.doi.org/10.18632/oncotarget.24952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5929436PMC
April 2018

Application of therapeutic plasma exchange in patients having severe fever with thrombocytopenia syndrome.

Korean J Intern Med 2019 Jul 10;34(4):902-909. Epub 2017 Nov 10.

Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.

Background/aims: Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever with a high fatality rate. However, effective treatments for SFTS cases not responded to supportive therapy have not been established. Herein, we introduced the therapeutic plasma exchange (TPE) in SFTS patients in a tertiary hospital between 2013 and 2015.

Methods: TPE was performed in patients with rapidly progressing SFTS. Clinical, laboratory, and virological parameters were compared before and after TPE.

Results: Among 27 confirmed SFTS patients, two patients were treated with TPE and ribavirin combination in May 2013, then, 14 patients with rapidly progressing SFTS patients were treated with only TPE from June 2013 to September 2015: their median age was 58 years (interquartile range, 50 to 70) and eight (57.1%) were male. Body temperature, pressure-adjusted heart rate, white blood cell and platelet counts, coagulation profile, serum creatinine, and multiple organ dysfunction score improved immediately after TPE. In addition, the mean cyclic threshold value of real-time reverse transcriptase polymerase chain reaction for SFTS virus after TPE (mean ± standard deviation, 31.3 ± 2.9) was significantly higher than that before TPE (26.5 ± 2.9; p < 0.001), indicating that serum viral loads decreased after TPE. Finally, 13 of 14 TPE-treated patients (92.8%) recovered from rapidly progressing SFTS without sequelae.

Conclusion: SFTS patients treated with TPE showed improvements in clinical, laboratory, and virological parameters. These results suggest that TPE would be a therapeutic modality as rescue therapy in patients with rapidly progressing SFTS.
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http://dx.doi.org/10.3904/kjim.2016.194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610197PMC
July 2019

Clinical Characteristics of Macrolide-Resistant Mycoplasma pneumoniae from Children in Jeju.

J Korean Med Sci 2017 Oct;32(10):1642-1646

Department of Pediatrics, Jeju National University Hospital, Jeju, Korea.

Mycoplasma pneumoniae is the major pathogen of community-acquired pneumonia in children. The prevalence of macrolide-resistant M. pneumoniae (MRMP) is important owing to the limited alternative therapies for children. We analyzed 111 M. pneumoniae obtained from 107 children admitted for lower respiratory tract infection at Jeju National University Hospital between 2010 and 2015. Macrolide resistance of M. pneumoniae was searched for using polymerase chain reaction (PCR) and sequencing. Of 107 clinical M. pneumoniae, 11 (10.3%) carried macrolide resistance mutations in the 23S rRNA gene. All macrolide resistance mutations were A2063G transitions. We found an acquired A2063G mutation of M. pneumoniae from a patient during macrolide treatment. Patients' characteristics and clinical severity did not differ between those with MRMP and macrolide-sensitive M. pneumoniae, with the exception of frequent pleural effusion in the MRMP group. The prevalence of MRMP (10.3%) in Jeju Island was relatively lower than those of surrounding countries in East Asia. Previous antimicrobial usage and timing of diagnostic test should be considered when determining of macrolide resistance of M. pneumoniae.
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http://dx.doi.org/10.3346/jkms.2017.32.10.1642DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5592178PMC
October 2017

Promoter polymorphisms of the vascular endothelial growth factor gene are associated with metabolic syndrome susceptibility in Koreans.

Biomed Rep 2017 May 7;6(5):555-560. Epub 2017 Apr 7.

Department of Science Education, Teachers College, Jeju National University, Jeju 63294, Republic of Korea.

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis. Patients with metabolic syndrome (MetS) have elevated plasma VEGF levels. The aim of the present study was to investigate the association between promoter polymorphisms (the -2578C>A and -1154G>A) of the gene and MetS susceptibility. A total of 640 subjects were enrolled in the study including 320 patients with MetS and 320 healthy controls. Genotyping of the single nucleotide polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism analysis. The CA and AA genotypes of the -2578C>A polymorphism were associated with decreased risk of MetS (P=0.018, P=0.003, respectively). For the -1154G>A polymorphism, although the GA genotype was more significantly frequent in MetS patients (P=0.022), the AA genotype and recessive model (GG+GA vs. AA) were protective against MetS susceptibility (P=0.016, 0.007, respectively). The A-G haplotype frequency composed of the -2578C>A and -1154G>A polymorphisms also differed between the 2 groups (P=0.011). The presented data suggested that the A alleles and A-G haplotype of the -2578C>A and -1154G>A polymorphisms are associated with decreased MetS susceptibility. To the best of the authors' knowledge, the current study is the first to investigate the associations between the -2578C>A and -1154G>A polymorphisms and MetS patients. Further evaluation is necessary to explore the associations between the polymorphisms and MetS patients in larger samples of other ethnic or racial populations.
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http://dx.doi.org/10.3892/br.2017.886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431263PMC
May 2017

Associations of MicroRNA Polymorphisms (miR-146a, miR-196a2, and miR-499) with the Risk of Hypertension in the Korean Population.

Genet Test Mol Biomarkers 2016 Aug 5;20(8):420-6. Epub 2016 Jul 5.

2 Department of Science Education, Teachers College, Jeju National University , Jeju, Republic of Korea.

Aims: Polymorphisms in microRNA (miR) genes are thought to be associated with various cancers and vascular diseases. To date, however, the effects of the miR gene polymorphisms on susceptibility to hypertension have rarely been investigated. In this study, we investigated the associations of three miR gene polymorphisms (miR-146aC>G/rs2910164, miR-196a2T>C/rs11614913, and miR-499A>G/rs3746444) with the risk of hypertension in Korean patients.

Methods: A total of 855 study subjects (340 patients with hypertension and 515 healthy normotensive subjects) were included in this study. Genotyping of the three miR gene polymorphisms was accomplished by polymerase chain reaction-restriction fragment length polymorphism analyses.

Results: Significant differences were observed in the genotype distributions of the miR-146aC>G polymorphism between the hypertensive patients and controls with the GG genotype, in both model-independent analyses, as well as in dominant (CC vs. CG+GG) and recessive (CC+CG vs. GG) models, being highly significantly associated with disease (AOR = 2.293, 95% CI: 1.466-3.586, p = 0.001; AOR = 1.727, 95% CI: 1.182-2.522, p = 0.015; AOR = 1.782, 95% CI: 1.267-2.506, p = 0.001, respectively). Neither the miR-196a2T>C nor the miR-499A>G polymorphisms were distributed significantly differently between hypertensive patients and control subjects. Several allelic combinations of the three miR polymorphisms were also associated with susceptibility to hypertension. Stratified analysis revealed that the miR-146aC>G and miR-499A>G polymorphisms are associated with a greater risk of hypertension.

Conclusion: This study suggests that the variant of miR-146aC>G polymorphism and allelic combinations, at least in Koreans, affect susceptibility to hypertension.
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http://dx.doi.org/10.1089/gtmb.2016.0039DOI Listing
August 2016

Porphyromonas gingivalis causing brain abscess in patient with recurrent periodontitis.

Anaerobe 2016 Jun 13;39:165-7. Epub 2016 Apr 13.

Department of Laboratory Medicine, Jeju National University School of Medicine, Jeju, South Korea. Electronic address:

We report an extremely rare case of Porphyromonas gingivalis causing brain abscess in a patient with recurrent periodontitis. The patient presented with right-sided homonymous hemianopsia and right hemiparesis. Emergent surgical drainage was performed and antibiotics were administered. P. gingivalis was identified from the anaerobic culture of the abscess. The clinical course of the patient improved with full recovery of the neurologic deficit.
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http://dx.doi.org/10.1016/j.anaerobe.2016.04.009DOI Listing
June 2016

Association of Apolipoprotein A5 Gene Polymorphisms with Metabolic Syndrome in the Korean Population.

Genet Test Mol Biomarkers 2016 Mar 13;20(3):130-6. Epub 2016 Jan 13.

2 Department of Science Education, Teachers College, Jeju National University , Jeju, Republic of Korea.

Aims: Functional defects of the ApoA5 protein have been identified as risk factors for hypertriglyceridemia, vascular diseases and susceptibility to metabolic syndrome (MetS). These associations are neither strong nor consistent in all populations studied. In this study, we investigated the association between the ApoA5 -1131T>C and -12,238T>C polymorphic loci in Korean patients with MetS.

Methods: A total of 1074 subjects, including 415 patients with MetS and 659 healthy control subjects, were enrolled to investigate the affect of ApoA5 polymorphisms on risk of MetS. Genotyping of the ApoA5 polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism techniques.

Results: The CC genotype and the dominant (TT vs. TC+CC) and recessive (TT+TC vs. CC) models of the -1131T>C polymorphism were associated with increased MetS susceptibility (p < 0.001, p = 0.018, and p = 0.002, respectively). The association was male-specific when stratified by gender. With regard to the -12,238T>C polymorphism, the TC and CC genotypes and the dominant (TT vs. TC+CC) and recessive (TT+TC vs. CC) models were frequently found in the patient group, compared with the control group (p = 0.001, p < 0.001, p < 0.001, and p = 0.031, respectively). The T-C, C-T, and C-C haplotypes of the ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with an increased risk for MetS (p < 0.001, p = 0.001, and p < 0.001, respectively). The variant of the ApoA5 -1131T>C polymorphism was also associated with increased triglyceride (TG) levels. Dominant models of ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with the risk components of MetS by the stratification analysis.

Conclusion: The -1131C and -12,238C variants and the C-containing haplotypes of ApoA5 -1131T>C and -12,238T>C polymorphisms were associated with higher risk for MetS in the Korean population. The -1131C variant was also associated with the increased level of TG.
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http://dx.doi.org/10.1089/gtmb.2015.0250DOI Listing
March 2016

An Assay of Measuring Platelet Reactivity Using Monoclonal Antibody against Activated Platelet Glycoprotein IIb/IIIa in Patients Taking Clopidogrel.

Korean Circ J 2015 Sep 8;45(5):378-85. Epub 2015 May 8.

Department of Laboratory Medicine, Jeju National University Hospital, Jeju, Korea.

Background And Objectives: Residual platelet reactivity in patients who are taking clopidogrel is commonly measured with VerifyNow assay, which is based on the principle of light transmission aggregometry. However, to evaluate the residual platelet reactivity, it would be more accurate if the reactivity of platelet glycoprotein (GP) IIb/IIIa is directly monitored. In this study, PAC1, a monoclonal antibody against activated platelet GP IIb/IIIa, was used to measure the residual platelet reactivity.

Subjects And Methods: Twenty seven patients with coronary artery disease taking clopidogrel were enrolled. Platelets in whole blood were stained with fluorescein isothiocyanate (FITC)-conjugated PAC1. Mean fluorescence intensity (MFI) and % positive platelets (PP) were measured with flow cytometry, and the binding index (BI; MFI × %PP/100) was calculated. P2Y12 reaction unit (PRU) and % inhibition of VerifyNow assay were also measured in the usual manner.

Results: PRU of VerifyNow assay correlated significantly with MFI, %PP, and BI at 10 µM (r=0.59, 0.73, and 0.60, respectively, all p<0.005) and 20 µM of adenosine diphosphate (ADP; r=0.61, 0.75, and 0.63, respectively, all p<0.005). The % inhibition also correlated significantly with MFI, %PP, and BI at 10 µM (r=-0.60, -0.69, and -0.59, respectively, all p<0.005) and 20 µM of ADP (r=-0.63, -0.71, and -0.62, respectively, all p<0.005).

Conclusion: Direct measurements of the reactivity of platelet GP IIb/IIIa were feasible using PAC1 and flow cytometry in patients taking clopidogrel. Further clinical studies are required to determine the cut-off values which would define high residual platelet reactivity in patients on this treatment protocol.
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http://dx.doi.org/10.4070/kcj.2015.45.5.378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4580696PMC
September 2015
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