Tae-Eun Kim

Dysplastic nodules of the liver: imaging findings

AbstractBackground: To verify characteristic features of hepatic dysplastic nodules at different imaging modalities. Methods: Twenty-eight patients with 37 dysplastic nodules of the liver (0.8–3.0 cm) underwent sonography (28 patients), computed tomography (CT; 24 patients), magnetic resonance (MR; 11 patients), and angiography (12 patients). Each nodule was analyzed for echogenicity, attenuation, signal intensity, and vascularity. Results: Echogenicity of nodules was high in 16 (43%), homogeneous in two (6%), and low in 19 (51%) of 37 nodules. Attenuation of nodules was high in one (7%), homogeneous in four (26%), and low in 10 (67%) of 15 nodules on the arterial-phase CT images; homogeneous in five (33%) and low in 10 (67%) of 15 nodules on the portal-phase CT images; and high in four (17%), homogeneous in six (26%), and low in 13 (57%) of 23 nodules on the delayed-phase CT images. Signal intensity of nodules was high in 15 (94%) and homogeneous in one (6%) of 16 nodules on T1-weighted MR images and was homogeneous in seven (44%) and low in nine (56%) of 16 nodules on T2-weighted MR images. Vascularity of nodules was avascular in 14 (88%) and slightly vascular in two (12%) of 16 nodules. Conclusions: Hepatic dysplastic nodules show diverse imaging characteristics with different imaging techniques; however, common imaging findings of hepatic dysplastic nodules are low echo, low attenuation, and high, low, or homogeneous intensity on T1- and T2-weighted MR, and avascularity.

FOXL2 mutation in granulosa-cell tumours of the ovary.

following mutation of components of the mitochondrial oxidative phosphorylation complex. Complex 1 mutations have been described in oncocytoma, and RCCs have been found in patients with fumarate hydratase deficiency. These several data support the hypothesis that alteration of mitochondrial oxidative phosphorylation predisposes to renal tumours of several types. Recent data suggest that accumulation of succinate inhibits hypoxia-inducible factor-1 (HIF1) prolyl hydroxylase, stabilizing HIF-1 and leading to its accumulation, causing up-regulation of tumorigenic hypoxia-inducible factors. Interestingly, in the present case there are morphological abnormalities of mitochondria in association with mutation and wildtype allelic loss of a nuclear encoded mitochondrial gene.

Pharmacokinetic interaction of fimasartan, a new angiotensin II receptor antagonist, with amlodipine in healthy volunteers.

Aim: Fimasartan (BR-A-657) is a new angiotensin II receptor antagonist used as antihypertensive agent. The objective of this study was to investigate the effect of the coadministration of fimasartan and amlodipine on the steady-state pharmacokinetics of each drug. Methods: This study comprised 2 separate parts, A and B; each was a multiple-dose, open-label, 2-period crossover study in healthy male volunteers. In part A, 20 subjects were administered 120 mg of fimasartan alone in period I and fimasartan with 10 mg of amlodipine in period II. In part B, 14 subjects were administered amlodipine alone, followed by coadministration with fimasartan. Blood samples for pharmacokinetics were collected up to 24 hours after the last dosing. The pharmacokinetics of the coadministration of fimasartan and amlodipine were compared with that of each drug alone. Results: The geometric mean ratio and 90% confidence intervals for Cmax,ss and area under the plasma concentration-time curve (AUC)τ,ss of fimasartan (with/without amlodipine) were 1.096 (0.746-1.610) and 1.163 (1.001-1.351), respectively. The geometric mean ratios (90% confidence interval) for Cmax,ss and AUCτ,ss of amlodipine (with/without fimasartan) after coadministration with fimasartan were 1.037 (0.969-1.110) and 0.975 (0.920-1.033), respectively. Conclusions: Coadministration of fimasartan and amlodipine did not result in clinically relevant changes in the systemic exposure of fimasartan or amlodipine.

Groundwater flow system inferred from hydraulic stresses and heads at an underground LPG storage cavern site

Underground Liquefied Petroleum Gas (LPG) storage caverns were constructed below the groundwater table to contain pressurized gas by groundwater pressure. Continuous and regular groundwater monitoring data were used to analyze whether the gas containment condition was satisfied or not. The monitoring data included time series analysis of hydraulic heads, gas and groundwater pressures, and groundwater chemistry. Through cross-correlation analyses of the time series data, the major factors causing hydraulic head fluctuation were found to be groundwater recharge from precipitation and cavern gas pressures. Hydraulic head and hydrochemical data indicate that a fault zone acts as the groundwater recharge zone and water curtain tunnels reduce head fluctuations.

Chronological Study of Antibiotic Resistances and Their Relevant Genes in Korean Avian Pathogenic Escherichia coli Isolates

ABSTRACT Antibiograms and relevant genotypes of Korean avian pathogenic Escherichia coli (APEC) isolates (n = 101) recovered between 1985 and 2005 were assessed via disc diffusion test, PCR, restriction enzyme analysis, and sequencing. These isolates were highly resistant to tetracycline (84.2%), streptomycin (84.2%), enrofloxacin (71.3%), and ampicillin (67.3%), and most of the tetracycline, streptomycin, enrofloxacin, and ampicillin resistances were associated with tetA and/or tetB, aadA and/or strA-strB, mutations in gyrA and/or parC, and TEM, respectively. Class 1 integrons were detected in 40 isolates (39.6%), and a variety of gene cassettes conferring streptomycin (aadA), gentamicin (aadB), and trimethoprim (dfr) resistances were identified: aadA1a (27.5%), dfrV-orfD (2.5%), aadB-aadA1a (2.5%), dfrI-aadA1a (47.5%), dfrXVII-aadA5 (12.5%), and dfrXII-orfF-aadA2 (7.5%). In addition, several types of common promoters (Pant) of the gene cassettes (hybrid P1, weak P1, or weak P1 plus P2) and single-nucleotide polymorphisms in aadA1a were identified. The results of a chronological analysis demonstrated significant and continuous increases in the frequencies of resistances to several antibiotics (tetracycline, streptomycin, enrofloxacin, ampicillin, and trimethoprim-sulfamethoxazole) and of the relevant resistance genes (tetA, strA-strB, and TEM), mutations in gyrA and parC, and multidrug-resistant APEC strains during the period 2000 to 2005.

Variation of a Newcastle Disease Virus Hemagglutinin-Neuraminidase Linear Epitope

ABSTRACT Fifty-six Newcastle disease virus strains collected from 2000 to 2006 could be grouped into subgenotype VIId. However, they displayed cumulative mutations in and around the linear epitope of hemagglutinin-neuraminidase (residues 345 to 353) with time. The antigenicities of the variants that became predominant in Korea differ from each other and from the wild type.

Reduced valproic acid serum concentrations due to drug interactions with carbapenem antibiotics: overview of 6 cases.

Background: The plasma concentrations of valproic acid (VPA) are known to decrease during the concomitant administration of carbapenem antibiotics, such as meropenem, imipenem, and ertapenem. This study summarizes 6 cases of drug–drug interactions between VPA and carbapenem antibiotics. Methods: To investigate the onset and severity of the reductions in the concentration of VPA in patients with or without the coadministration of carbapenem antibiotics, the authors performed a retrospective evaluation of therapeutic drug monitoring (TDM) reports that described a decrease in the serum concentrations of VPA during the concomitant use of carbapenem antibiotics from January 2008 to December 2010 in the Seoul National University Hospital. The evaluated TDM reports included 6 cases. The decrement ratio of the VPA serum concentration was calculated from the TDM reports, and the change in the half-life of the VPA was also estimated. Results: Six cases presented with changes in the VPA serum concentration before and after the administration of carbapenem antibiotics. (Three cases were treated with meropenem, 2 were treated with ertapenem, and 1 was treated with imipenem.) The VPA concentrations reduced by (mean ± SD) 88.7 ± 5.3% (3 cases of meropenem), 74.0 ± 9.8% (2 cases of ertapenem), and 73.3% (1 case of imipenem), respectively, and the half-life of VPA reduced by 80.1 ± 9.0%, 64.4 ± 24.2%, and 50.6%, respectively. Conclusion: The interaction between VPA and carbapenem antibiotics caused decreases in the VPA serum concentrations; the extent of this decrease was greater in the meropenem-treated patients than in the imipenem-treated or ertapenem-treated cases. Because the therapeutic effect of VPA depends on its serum concentration, it should be recognized that there may be a loss of seizure control in patients using VPA with carbapenem antibiotics.

Comparative Pharmacokinetics and Tolerability of Branded Etanercept (25 mg) and Its Biosimilar (25 mg): A Randomized, Open-Label, Single-Dose, Two-Sequence, Crossover Study in Healthy Korean Male Volunteers

BACKGROUND The biosimilar is a recombinant dimeric tumor necrosis factor receptor (TNFR) under development for the treatment of rheumatoid arthritis. OBJECTIVE The aim of this study was to compare the pharmacokinetics and/or tolerability of branded etanercept and its biosimilar in healthy Korean men before investigating the clinical efficacy of the biosimilar in subjects. METHODS Etanercept (reference, 25 mg) or its biosimilar (test, 25 mg) was subcutaneously injected to the periumbilical area of healthy volunteers in a randomized, open-label, single-dose, active-controlled, two-sequence, crossover study. Plasma concentrations of TNFR in serial blood samples for 480 hours after dosing were measured by ELISA. The primary outcome, pharmacokinetic characteristics, was assessed via geometric mean ratios (GMRs) of the log-transformed pharmacokinetic parameters. The second outcome, tolerability, was evaluated using physical examinations, electrocardiograms, clinical laboratory tests, vital sign measurements, and adverse events (AEs) by unmasked investigators. RESULTS Twenty-three men of mean age (%CV) 25.8 years (17.1%) and weight 70.5 kg (12.8%) were administered study medication. Four subjects dropped out after the first period; their data were included in the analysis. Both test and reference drugs were absorbed with a median T(max) of 72 (range, 36-144) hours and eliminated with mean (%CV) t(½) of 92.7 (20.9%) and 87.4 (16.6%) hours, respectively. The GMRs (90% CIs) of the test to reference drug for C(max), AUC(0-t), and AUC(0-∞) were 0.99 (0.83-1.17), 0.95 (0.79-1.13), and 0.95 (0.80-1.13), respectively. Eleven of 21 (52.4%) and 8 of 21 (38.1%) subjects administered the test and reference drugs reported 22 and 21 AEs, respectively. Common AEs were headache (14.3%), throat irritation (8.5%), and epistaxis (9.5%). Three serious AEs related to a traffic accident (back, neck, and musculoskeletal pain) were reported in a test drug-treated subject. CONCLUSIONS In this select group of Korean healthy male volunteers, the reference drug and the test biosimilar met the standard criteria for assuming bioequivalence as defined by Korean regulatory authorities. Because the reference drug is a biological product, further trials for assessment of its efficacy are still required by Korean authorities. World Health Organization International Clinical Trials Registry Platform identifier: KCT0000118.

Characterization of a T7-like lytic bacteriophage (φSG-JL2) of Salmonella enterica serovar gallinarum biovar gallinarum

ABSTRACT φSG-JL2 is a newly discovered lytic bacteriophage infecting Salmonella enterica serovar Gallinarum biovar Gallinarum but is nonlytic to a rough vaccine strain of serovar Gallinarum biovar Gallinarum (SG-9R), S. enterica serovar Enteritidis, S. enterica serovar Typhimurium, and S. enterica serovar Gallinarum biovar Pullorum. The φSG-JL2 genome is 38,815 bp in length (GC content, 50.9%; 230-bp-long direct terminal repeats), and 55 putative genes may be transcribed from the same strand. Functions were assigned to 30 genes based on high amino acid similarity to known proteins. Most of the expected proteins except tail fiber (31.9%) and the overall organization of the genomes were similar to those of yersiniophage φYeO3-12. φSG-JL2 could be classified as a new T7-like virus and represents the first serovar Gallinarum biovar Gallinarum phage genome to be sequenced. On the basis of intraspecific ratios of nonsynonymous to synonymous nucleotide changes (Pi[a]/Pi[s]), gene 2 encoding the host RNA polymerase inhibitor displayed Darwinian positive selection. Pretreatment of chickens with φSG-JL2 before intratracheal challenge with wild-type serovar Gallinarum biovar Gallinarum protected most birds from fowl typhoid. Therefore, φSG-JL2 may be useful for the differentiation of serovar Gallinarum biovar Gallinarum from other Salmonella serotypes, prophylactic application in fowl typhoid control, and understanding of the vertical evolution of T7-like viruses.

Characterization of a Recombinant Newcastle Disease Virus Vaccine Strain

ABSTRACT A recombinant La Sota strain (KBNP-C4152R2L) in which fusion (F) and hemagglutinin-neuraminidase (HN) genes were replaced with those of a contemporary genotype VIId virus, KBNP-4152, has been developed. To attenuate the virulence of the recombinant strain, the F cleavage motif was mutated from 112RRQKR116 to 112GRQAR116, and to reduce pathogenic instability, a codon which does not allow changes to basic amino acids by single point mutation was inserted at codon 115. In addition a six-nucleotide sequence was inserted into the intergenic region between matrix protein and F genes for attenuation without breaking the “rule-of-six.” The HN protein length was increased from 571 to 577 as a marker. Serological tests revealed that the antigenicity of KBNP-C4152R2L was similar to that of KBNP-4152 but distinct from that of the La Sota strain. KBNP-C4152R2L was avirulent (intracerebral pathogenicity index, 0.0; mean death time, >168 h) and stable in pathogenicity through in vivo passages. The killed oil emulsion of and live KBNP-C4152R2L were completely protective against mortality and egg drop caused by virulent strains, and KBNP-C4152R2L was applicable to in ovo vaccination. Therefore, KBNP-C4152R2L is a promising vaccine strain and viral vector in terms of antigenicity, productivity, safety, and pathogenic stability.