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Biomedical subjects

Soo-Young Kim

Publications and source records attributed to Soo-Young Kim.

At least 19 recordsLinked to original sources

Prevalence and mechanisms of decreased susceptibility to carbapenems in Klebsiella pneumoniae isolates.

In this study, we examined the prevalence of and mechanisms of decreased susceptibility to either imipenem or meropenem in Klebsiella pneumoniae isolates. A total of 230 clinical isolates of K. pneumoniae were collected from 13 clinical laboratories from a nationwide distribution. The MICs of imipenem and meropenem were determined by the agar dilution method. To characterize the isolates with decreased susceptibility to carbapenems (MICs of >2 microg/mL), we performed polymerase chain reaction amplification of a variety of beta-lactamase genes, isoelectric focusing, and outer membrane profile analysis using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass spectrometry. Three isolates (BD6, BD8, and KN16) exhibited decreased susceptibility to carbapenems with imipenem MICs of 1, 4, and 8 microg/mL and meropenem MICs of 4, 8, and 4, respectively. Isolate BD6 produced bla(TEM-1), bla(SHV-12), and bla(OXA-17); isolate BD8 produced bla(GES-3), bla(SHV-12), and bla(OXA-17); and isolate KN16 produced bla(TEM-11), bla(SHV-12), and bla(DHA-1). In all the 3 isolates, OmpK35 porin was not expressed, and in 1 isolate (KN16), OmpK36 was not expressed either. The prevalence of decreased susceptibility to carbapenems was low (1.3%), and none of them showed overt resistance to carbapenems. Decreased susceptibility to carbapenems can occur in K. pneumoniae when bla(GES-3), bla(TEM-11), bla(SHV-12), bla(OXA-17), and/or bla(DHA-1) are produced in combination with porin loss. In addition, to our knowledge, this is the 1st report of bla(OXA-17) in Enterobacteriaceae.

Amino Acid Sequence↗

X-gal inhibits the swarming of Vibrio species.

The expressional levels of genes in swarmer cells can be determined by a simple method using X-gal-containing semisolid agars and lacZ-fusion transcription reporter strains of the genes concerned. However, X-gal alone inhibited the swarming of Vibrio, regardless of their ability to digest X-gal. Moreover, X-gal inhibited the growth of V. vulnificus containing functional lacZ. These effects of X-gal itself should be carefully considered when trying to determine the expression levels of genes in swarming cells using X-gal-containing semisolid agar.

Chromogenic Compounds↗

Evaluation of the CombiChip Mycobacteria Drug-Resistance detection DNA chip for identifying mutations associated with resistance to isoniazid and rifampin in Mycobacterium tuberculosis.

The CombiChip Mycobacteriatrade mark Drug-Resistance Detection DNA chip, recently developed by GeneIn (Pusan, South Korea), is an oligonucleotide microchip coupled with polymerase chain reaction for the detection of mutations associated with resistance to isoniazid (INH) and rifampin (RIF). This oligonucleotide chip was compared with DNA sequencing and phenotypic drug susceptibility testing with 69 INH- and/or RIF-resistant and 27 all tested drug-susceptible Mycobacterium tuberculosis isolates. Two selected codons (the katG codon 315 and inhA15) allowed identification of 84.1% of INH-resistant isolates and 100% of RIF resistance were detected by screening for 7 codons: rpoB511, rpoB513, rpoB516, rpoB522, rpoB526, rpoB531, and rpoB533. The overall specificity of this oligonucleotide chip for detecting INH and RIF resistance were 100 and 95.3%, respectively. This level of sensitivity and specificity is concordant with that from the determination of M. tuberculosis drug resistance by DNA sequencing. This oligonucleotide chip is a rapid and reliable genotypic method capable of detecting multiple mutations associated with INH and RIF resistance simultaneously in a single microchip slide.

Antitubercular Agents↗

Urinary concentrations of bisphenol A in relation to biomarkers of sensitivity and effect and endocrine-related health effects.

The impact of endocrine-disrupting chemicals (EDCs) on human health is not yet clear because of difficulties in ascertaining their biological effects. In the present study, we evaluated exposure to the EDC, bisphenol A (BPA), in 172 Koreans in relation to biomarkers of susceptibility and effect. The subjects completed questionnaires, which documented occupation, education, lifestyle factors, potential sources of BPA-exposure, and the occurrence of self-diagnosed endocrine disorders. None of the subjects were occupationally exposed to BPA; however, urinary levels of conjugated BPA, determined by HPLC/FD, ranged from 0.03-62.4 microg/l (median, 7.86). The frequencies of potential susceptibility biomarkers, the UGT1A6-Arg184Ser and the SULT1A1-Arg213His polymorphisms, were not associated with urinary BPA levels, either as single genes or in combination. Indirect effects of BPA exposure on the susceptibility to mutagens were evaluated by comparing urinary BPA concentrations with MNNG-induced sister-chromatid exchange (SCE) in lymphocytes cultured from the subjects. BPA exposure showed marginal or significant associations with theSCEs induced by the low doses of MNNG (0-0.4 mM). However, there was no overall association between urinary BPA levels and MNNG-induced frequency at doses ranging from 0.2-0.6 mM. Finally, we did not detect an association between urinary BPA concentration and endocrine-related disorders. Even though we were unable to find a strong association between BPA exposure and a biological response, possibly because of the limited number of subjects, we observed that most of the subjects were exposed to BPA. Therefore, continuous biological monitoring of BPA is a prudent measure to prevent possible BPA-related health risks.

Adult↗

Suppression and inactivation of Vibrio vulnificus hemolysin in cirrhotic ascites, a human ex vivo experimental system.

To elucidate the mechanisms underlying the in vivo suppression and inactivation of Vibrio vulnificus hemolysin (VvhA), we used cirrhotic ascites fluid as a human ex vivo experimental system. VvhA expression was suppressed in proportion to the amount of cirrhotic ascites. The expression of vvhA in undiluted cirrhotic ascites could be suppressed further by the addition of glucose, a constituent of cirrhotic ascites. VvhA was readily inactivated in the presence of cirrhotic ascites by a cholesterol-mediated oligomerization and interaction with an undefined constituent(s) of cirrhotic ascites. These results indicate that the expression of vvhA can be suppressed and that any VvhA produced is inactivated by the constituents of cirrhotic ascites. Our results suggest that only a very small portion of the VvhA that is produced in human body fluids may actually contribute to the pathogenesis of V. vulnificus septicemia. It is suggested that cirrhotic ascites could be used as a human ex vivo experimental system for the studies on the in vivo expression and the significance of V. vulnificus virulence factors.

Ascites↗

Vibrio vulnificus vulnibactin, but not metalloprotease VvpE, is essentially required for iron-uptake from human holotransferrin.

The roles of metalloprotease (VvpE) and catechol-siderophore (vulnibactin) in the uptake of iron from human transferrins by Vibrio vulnificus have been determined using different experimental conditions and methods. Therefore, in this study, we attempted to elucidate the roles of VvpE and vulnibactin using the same methods and experimental conditions, in an in vitro and a human ex vivo system, and in accordance with the molecular version of Koch's postulates. Neither vvpE mutation nor in trans vvpE complementation affected vulnibactin production, iron-assimilation from human holotransferrin (HT), and bacterial growth in a HT-containing deferrated Heart-Infusion medium (HT-DF-HI) or a HT-containing cirrhotic ascites (HT-CA). In contrast, the mutation of fur gene encoding Fur, a repressor regulating expression of the vulnibactin-mediated iron-uptake system, derepressed vulnibactin production, and facilitated iron-assimilation from HT and bacterial growth in HT-DF-HI or HT-CA. The mutation of vis gene encoding isochorismate synthase required for vulnibactin synthesis abolished vulnibactin production, iron-assimilation from HT and bacterial growth in HT-DF-HI or HT-CA. These results demonstrate that vulnibactin is essentially required for iron-assimilation from transferrin, and that VvpE has no direct effect on facilitating vulnibactin-mediated iron-assimilation from transferrin in vitro or in a human ex vivo system.

Amides↗

Swarming differentiation of vibrio vulnificus downregulates the expression of the vvhBA hemolysin gene via the LuxS quorum-sensing system.

Swarming has proven to be a good in vitro model for bacterial surface adherence and colonization, and the swarming differentiation of a bacterium has been shown to be coupled with changes in the expression of virulence factors associated with its invasiveness, particularly in the early stages of infection. In this study, we attempted to determine whether the expression of vvhA, which encodes for hemolysin/cytolysin (VvhA), is either upregulated or downregulated during the swarming differentiation of V. vulnificus. The insertional inactivation of vvhA itself exerted no detectable effect on the expression of V. vulnificus swarming motility. However, in our lacZ-fused vvhA transcriptional reporter assay, vvhA expression decreased in swarming V. vulnificus as compared to non-swarming or planktonic V. vulnificus. The reduced expression of vvhA in swarming V. vulnificus increased as a result of the deletional inactivation of luxS, a gene associated with quorum sensing. These results show that vvhA expression in swarming V. vulnificus is downregulated via the activity of the LuxS quorum-sensing system, suggesting that VvhA performs no essential role in the invasiveness of V. vulnificus via the adherence to and colonization on the body surfaces required in the early stages of the infection. However, VvhA may play a significant role in the pathophysiological deterioration occurring after swarming V. vulnificus is differentiated into planktonic V. vulnificus.

Bacterial Adhesion↗

Vibrio vulnificus metalloprotease VvpE has no direct effect on the iron-assimilation from human holotransferrin.

In order to elucidate the role of Vibrio vulnificus metalloprotease VvpE in the uptake of iron from human transferrin, we constructed a VvpE-deficient mutant and a merozygotic vvpE-transcriptional reporter from the wild type strain MO6-24/O. All three strains were able to grow only in deferrated Heart Infusion broth (DF-HI) with human holotransferrin (HT), but not in DF-HI containing partially iron-saturated transferrin or apotransferrin, without noticeable differences among the strains. All strains consumed most iron in the early growth phase. Both the transcription and extracellular production of VvpE proceeded at undetectable levels when bacterial growth was severely retarded in the DF-HI. When HT or FeCl(3) was added to the DF-HI, the retarded bacterial growth was restored and vvpE transcription dramatically increased in the late growth phase, but the extracellular VvpE production was negligible as compared to its transcription. All strains were unable to degrade HT even in normal HI broth containing HT, in which extracellular VvpE activity was remarkably high. The uptake of iron from HT in all strains was consistent with the production of catechol-siderophore rather than hydroxamate-siderophore. Similar results were also observed when clinical isolates from septicemic patients were used. In conclusion, we determined that VvpE was not directly involved in the siderophore-mediated iron-uptake from human transferrin. In addition, the discrepancy between the transcription and extracellular production of VvpE suggests that additional posttranscriptional events are involved in the extracellular production of VvpE.

Culture Media↗

Novel molecular drug carrier: encapsulation of oxaliplatin in cucurbit[7]uril and its effects on stability and reactivity of the drug.

Oxaliplatin forms a stable 1:1 inclusion complex with cucurbit[7]uril as indicated by NMR, mass spectrometry, isothermal titration calorimetry and X-ray crystallography. The encapsulation of the drug results in a large enhancement in stability, a moderate decrease in reactivity toward guanosine but a much larger decrease in reactivity toward L-methionine, which suggests the encapsulation not only increases the stability of the drug but also may reduce unwanted side effects caused by protein binding of the platinum drug. A preliminary in vitro assay using various tumor cell lines reveals that the encapsulation results in a decrease in the antitumor activity of oxaliplatin.

Antineoplastic Agents↗

Tid-1 interacts with the von Hippel-Lindau protein and modulates angiogenesis by destabilization of HIF-1alpha.

The von Hippel-Lindau protein (pVHL) is a major tumor suppressor protein and also associated with the inhibition of angiogenesis via HIF-1alpha ubiquitination and proteasomal degradation. To further elucidate the biological activity of pVHL in angiogenesis, pVHL-interacting proteins were screened using the yeast two-hybrid system. We found that a mouse homologue of the long form of Drosophila tumor suppressor l(2)tid, Tid-1(L), directly interacts with pVHL in vitro and in vivo. Furthermore, Tid-1(L) protein; enhanced the interaction between HIF-1alpha and pVHL, leading to the destabilization of HIF-1alpha protein; therefore, Tid-1(L) protein decreased vascular endothelial growth factor expression and inhibited angiogenesis in vivo and in vitro. These findings propose that Tid-1(L) may play a critical role in pVHL-mediated tumor suppression by modulating the pVHL-dependent HIF-1alpha stability.

Chorioallantoic Membrane↗

Uranium accumulation of crop plants enhanced by citric acid.

Citric acid was applied to soil to enhance U accumulation in four crop plants. While the highest enhanced U accumulation of aboveground tissues (a.c. 2000 mg kg(-1) dry weight) occurred in the leaves of Indian mustard (Brassica juncea), the highest enhanced U accumulation of roots (a.c. 3500 mg kg(-1) dry weight) occurred in canola (Brassica napus var. napus). Uranium translocation among tissues of test plants is in the relation of roots>shoots congruent with leaves. The flowers of sunflower (Helianthus annuus) contained similar or higher U concentrations than those found in shoots, but concentrations in seeds are close to zero. In conclusion, Indian mustard is recommended as a potential species for phytoextraction for U-contaminated soil due to its high U accumulation of aboveground biomass (a.c. 2200 microg per plant). There is no evidence that two types of soils cause a significant difference of the enhanced U accumulation (p<0.05). Results, however, indicate that additional citric acid may result in downward U migration that may contaminate groundwater. Speciation of U that is taken up by plants is also discussed in the end.

Citric Acid↗

Inactivation of Vibrio vulnificus hemolysin by oligomerization but not proteolysis.

Vibrio vulnificus extracellular protease (VvpE) is believed to destroy its hemolysin (VvhA) in the late growth phase, without obvious experimental evidence. So, we attempted to elucidate the mechanism. The hemolytic activity steeply increased with the expression of the VvhA in the early growth phase, and then abruptly declined with the expression of VvpE in the late growth phase. However, the VvhA activity also abruptly declined in a VvpE-deficient mutant. In Western blot, the degradation of VvhA was not observed; instead, the oligomerization of VvhA increased with the concomitant loss of hemolytic activity. These results evidently indicate that the inactivation of VvhA is due to the novel oligomerization of VvhA by unknown mechanism, but not to the destruction of VvhA by VvpE, so that the routine functional assay measuring hemolytic activity cannot reflect the actual production of VvhA.

Biopolymers↗

Comparison of the BDProbeTec ET system with the roche COBAS AMPLICOR System for detection of Mycobacterium tuberculosis complex in the respiratory and pleural fluid specimens.

The new BDProbeTec ET System (BDET; BD Biosciences, Sparks, MD) was compared with the Roche COBAS AMPLICOR System (CAS) and culture for Mycobacterium tuberculosis (MTB). A total of 253 specimens (152 respiratory and 101 pleural fluid specimens) collected from 240 patients were tested in parallel with the 3 assays. After resolving the discrepancies, the sensitivity, specificity, and positive and negative predictive values of the BDET for detecting MTB was 76.9%, 93.7%, 71.4%, and 95.2% for the respiratory specimens and 88.9%, 92.4%, 53.3%, and 98.8% for the pleural fluid specimens, respectively. The corresponding values of the CAS were 69.2%, 100%, 100%, and 94% for the respiratory specimens and 33.3%, 100%, 100%, and 93.9% for the pleural fluid specimens, respectively. No significant differences in sensitivities were observed between the results of both assays for the respiratory specimens. However, statistically significant differences in sensitivities were found between the BDET and CAS for the pleural fluid specimens (P =.02). Although the BDET was less specific than the CAS (P =.007), the BDET has an excellent sensitivity for detecting MTB in the pleural fluid specimens. Considering the low sensitivity of other available tests, the BDET can be a useful diagnostic tool for excluding MTB, particularly in the pleural fluid specimens.

Bacteriological Techniques↗

Antimicrobial susceptibilities and epidemiological analysis of Salmonella enteritidis isolates in Korea by phage typing and pulsed-field gel electrophoresis.

A total of 81 isolates of Salmonella Enteritidis were analyzed by antibiotic susceptibility, phage typing, and pulsed-field gel electrophoresis (PFGE). Thirty-two isolates came from broiler carcasses and pig feces, and 49 isolates were from humans in Seoul and suburbs of Seoul, Korea. Antibiotic resistance was most prevalent among human isolates. Of human isolates, 89.8% were resistant to more than two antibiotics, while 64.7% of poultry isolates and 13.3% of pig isolates showed multiple resistance to more than two antibiotics. The most common phage type (PT) was PT1, followed by PT30 or 33, PT21 and PT20a. The isolates showed six PFGE patterns with XbaI or SpeI digestion, and five PFGE patterns with NotI digestion. But a single pattern, PFGE X1, S1, or N1, was predominant and the rest of the PFGE patterns differed by only one or two bands. Results indicated the spread of a genetically related clone of Salmonella Enteritidis in foods and humans in Korea and that phage typing as well as PFGE may offer an improved level of discrimination for the epidemiological investigation of Salmonella Enteritidis.

Animals↗

Coordinated interaction of the vascular and nervous systems: from molecule- to cell-based approaches.

Endothelial cells (ECs) build blood vessels and regulate their plasticity in coordination with neurons. Likewise, neurons construct nerves and regulate their circuits in coordination with ECs. Blood vessel/nerve interactions, ultimately, play essential roles for the neurovascular network and brain function. With conventional molecular approaches, such coordinated interaction is likely due to complex interplay of neuroangiogenic factors and receptors. Aside from molecular regulation of neuroangiogenic factors, currently, cell-based approaches to investigate how blood vessels (or nerves) respond to nerves (or blood vessels) appropriately in the pathophysiological situation are gradually emerging. In order to define responsiveness and flexibility of the neurovascular network in response to the local need, the intercellular communication and coordinated interaction between the vascular and nervous systems need to be thought as a working unit. Based on the scale of the working unit which is in the millimeter range with respect to the physical distance of the neurovascular network, we propose to use a rather conceptual term "Millibiology". The millibiological approach for the coordinated interaction might bring us new paradigm to define neurovascular functions in the pathophysiological state.

Adaptation, Physiological↗

Facile synthesis of cucurbit[n]uril derivatives via direct functionalization: expanding utilization of cucurbit[n]uril.

A long-standing problem in cucurbituril chemistry is answered through the first direct functionalization of cucurbit[n]uril (CB[n]; n = 5-8)) leading to perhydroxyCB[n] which can be further modified to provide tailored CB[n] derivatives with desired functional groups and good solubility. Anchoring a CB[6] derivative on the surface and its potential application as a sensor are demonstrated. A CB[6] derivative forms nanospheres with possible use in protein and peptide drug delivery.

Journal Article↗

Biological monitoring of bisphenol a in a Korean population.

To conduct proper biological monitoring of environmental exposure to bisphenol A (BPA), the variation in host susceptibility need to be investigated. For this purpose, we studied effects of genetic polymorphism in sulfotransferase (SULT) 1A1 on urinary BPA, a biomarker for BPA exposure, in 73 Koreans (male, 34; female, 39; age, 48.9 +/- 11.9 yrs). We used reverse phase-HPLC/FD for analysis of urinary BPA and obtained information from each subject on lifestyle, environment, and potential exposure to BPA via food. The HPLC/FD method showed good reproducibility (CVs < 0.1) and a relatively sensitive detection limit of 0.012 microg/L. These methods yielded a geometric mean of urinary BPA as 9.54 microg/L (8.91 microg/g creatinine), with a geometric standard deviation of 8.32 microg/L. Among potential routes for BPA exposure, only "vinyl wrapping of microwave heating" indicated a borderline positive association with urinary BPA level (p = 0.1). After PCR-RFLP, we found the allele frequencies of SULT1A1*1 and SULT1A1*2 were 0.89 and 0.11, respectively within the subjects. As the SULT1A1*1 allele of SULT1A1 is known to be a rapid sulfonylation-allele, the presence of SULT1A1*1 is suspected to rapidly dispose of environmental BPA. However resultant, urinary BPA levels were not significantly different between the SULT1A1*1/*1 identified subjects and the SULT1A1*1/*2 subjects. Therefore, to clarify host variability in urinary BPA level, different genetic polymorphisms in BPA metabolic enzymes other than SULT1A1 should be further studied.

Arylsulfotransferase↗