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Search Results: 1 - 10 of 46122 matches for " Hee-Jin Kim "
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The clinical utility of tuberculin skin test and interferon-γ release assay in the diagnosis of active tuberculosis among young adults: a prospective observational study
Ji Eun Lee, Hee-Jin Kim, Sei Won Lee
BMC Infectious Diseases , 2011, DOI: 10.1186/1471-2334-11-96
Abstract: We prospectively enrolled 166 young participants 20-29 years of age with suspected active TB in a military hospital of South Korea. The TST and QFT-IT were performed for all participants.Of the 143 patients included in the analysis, active TB was diagnosed in 100 (69.9%). There were 141 male patients, none of whom had immunosuppressive disease. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TST were 94% (95% CI, 87-98%), 88% (95% CI, 74-96%), 95% (95% CI, 88-98%), and 86% (95% CI, 72-94%), respectively. The sensitivity, specificity, PPV, and NPV of the QFT-IT were 93% (95% CI, 86-97%), 95% (95% CI, 81-99%), 98% (95% CI, 92-99%), and 84% (95% CI, 69-93%), respectively. No significant differences were found between the TST and QFT-IT in any statistic.Both the TST and QFT-IT showed high sensitivity and specificity in differentiating active TB from other diseases. The diagnostic accuracy of these two tests did not differ significantly when applied to this clinical population of young, immunocompetent adults in whom neonatal BCG vaccination was common, there was no history of previous TB and in whom suspicion of TB was high.ClinicalTrials.gov: NCT00982969Tuberculosis (TB) is an important public health problem worldwide. In 2007, there were 9.27 million cases of TB, and 1.3 million deaths occurred among HIV-negative TB cases [1]. South Korea has an intermediate TB burden; the incidence of new cases is 90 per 100 000 people per year despite an intensive effort for disease control [2]. A prompt and accurate diagnosis is critical for effective control and management of TB, but conventional diagnostic methods have their limitations. Completion of mycobacteria culture takes 3-8 weeks on solid medium and 7-21 days in liquid medium [3,4]. The sensitivity of acid-fast bacilli (AFB) smears is low [3]. The polymerase chain reaction test is often used for rapid microbiological diagnosis of TB, but its sensitivity for smear-negat
Cataloging Coding Sequence Variations in Human Genome Databases
Hong-Hee Won, Hee-Jin Kim, Kyung-A Lee, Jong-Won Kim
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0003575
Abstract: Background With the recent growth of information on sequence variations in the human genome, predictions regarding the functional effects and relevance to disease phenotypes of coding sequence variations are becoming increasingly important. The aims of this study were to catalog protein-coding sequence variations (CVs) occurring in genetic variation databases and to use bioinformatic programs to analyze CVs. In addition, we aim to provide insight into the functionality of the reference databases. Methodology and Findings To catalog CVs on a genome-wide scale with regard to protein function and disease, we investigated three representative databases; the Human Gene Mutation Database (HGMD), the Single Nucleotide Polymorphisms database (dbSNP), and the Haplotype Map (HapMap). Using these three databases, we analyzed CVs at the protein function level with bioinformatic programs. We proposed a combinatorial approach using the Support Vector Machine (SVM) to increase the performance of the prediction programs. By cataloging the coding sequence variations using these databases, we found that 4.36% of CVs from HGMD are concurrently registered in dbSNP (8.11% of CVs from dbSNP are concurrent in HGMD). The pattern of substitutions and functional consequences predicted by three bioinformatic programs was significantly different among concurrent CVs, and CVs occurring solely in HGMD or in dbSNP. The experimental results showed that the proposed SVM combination noticeably outperformed the individual prediction programs. Conclusions This is the first study to compare human sequence variations in HGMD, dbSNP and HapMap at the genome-wide level. We found that a significant proportion of CVs in HGMD and dbSNP overlap, and we emphasize the need to use caution when interpreting the phenotypic relevance of these concurrent CVs. Combining bioinformatic programs can be helpful in predicting the functional consequences of CVs because it improved the performance of functional predictions.
Relationship between Serum Ferritin Levels and Sarcopenia in Korean Females Aged 60 Years and Older Using the Fourth Korea National Health and Nutrition Examination Survey (KNHANES IV-2, 3), 2008–2009
Tae Ho Kim, Hee-Jin Hwang, Sang-Hwan Kim
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090105
Abstract: Context It has been suggested that elevated serum ferritin is associated with several metabolic disorders. However, there is no reported study assessing any association between serum ferritin and sarcopenia despite the close relationship between sarcopenia and metabolic disorders. Objective We investigated whether serum ferritin was associated with sarcopenia in older Koreans. Design and Setting We conducted a cross-sectional study based on data acquired in the second and third years (2008–9) of the fourth Korean National Health and Nutrition Examination Survey. Participants In total, 952 men (mean age 69.0 years) and 1,380 women (mean age 69.3 years) aged 60 years and older completed a body composition study using dual energy X-ray absorptiometry. Measurements Serum ferritin levels were measured. Sarcopenia was defined as an appendicular skeletal mass as a percentage of body weight that was less than two standard deviations below the gender-specific mean for young adults. Results Serum ferritin levels were lower in women than in men. Women with sarcopenia showed a higher level of serum ferritin than women without sarcopenia (men: without sarcopenia 115.7 ng/mL and with sarcopenia 134.4 ng/mL vs. women: without sarcopenia 70.7 ng/mL and with sarcopenia 85.4 ng/mL). The prevalence of sarcopenia increased as the tertile of serum ferritin increased. However, statistical significance was only seen in elderly women (1st tertile 6.3%, 2nd tertile 8.0%, 3rd tertile 12.0%; p = 0.008). Without adjustment, compared with those in the lowest tertile of serum ferritin level, participants in the highest tertile had an odds ratio of 2.02 (95% confidence interval = 1.26–3.23) for sarcopenia in women. After adjusting for known risk factors, the OR for sarcopenia was 1.74 (95% CI = 1.02–2.97) in women. There was no statistically significant association between sarcopenia and serum ferritin tertiles in men. Conclusions Elevated serum ferritin levels were associated with an increased prevalence of sarcopenia in women but not in men from a representative sample of elderly Koreans.
Effects of Methamphetamine on Single Unit Activity in Rat Medial Prefrontal Cortex In Vivo
Jinhwa Jang,Hee-Jin Ha,Yun Bok Kim,Young-Ki Chung,Min Whan Jung
Neural Plasticity , 2007, DOI: 10.1155/2007/29821
Abstract: To investigate how neuronal activity in the prefrontal cortex changes in an animal model of schizophrenia, we recorded single unit activity in the medial prefrontal cortex of urethane-anesthetized and awake rats following methamphetamine (MA) administration. Systemic MA injection (4 mg/kg, IP) induced inconsistent changes, that is, both enhancement and reduction, in unit discharge rate, with a subset of neurons transiently (<30 min) elevating their activities. The direction of firing rate change was poorly predicted by the mean firing rate or the degree of burst firing during the baseline period. Also, simultaneously recorded units showed opposite directions of firing rate change, indicating that recording location is a poor predictor of the direction of firing rate change. These results raise the possibility that systemic MA injection induces random bidirectional changes in prefrontal cortical unit activity, which may underlie some of MA-induced psychotic symptoms.
Hepatic Lipid Accumulation Alters Global Histone H3 Lysine 9 and 4 Trimethylation in the Peroxisome Proliferator-Activated Receptor Alpha Network
Hee-Jin Jun, Jinyoung Kim, Minh-Hien Hoang, Sung-Joon Lee
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044345
Abstract: Recent data suggest that the etiology of several metabolic diseases is closely associated with transcriptome alteration by aberrant histone methylation. We performed DNA microarray and ChIP-on-chip analyses to examine transcriptome profiling and trimethylation alterations to identify the genomic signature of nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease. Transcriptome analysis showed that steatotic livers in high-fat diet-fed apolipoprotein E2 mice significantly altered the expression of approximately 70% of total genes compared with normal diet-fed control livers, suggesting that hepatic lipid accumulation induces dramatic alterations in gene expression in vivo. Also, pathway analysis suggested that genes encoding chromatin-remodeling enzymes, such as jumonji C-domain-containing histone demethylases that regulate histone H3K9 and H3K4 trimethylation (H3K9me3, H3K4me3), were significantly altered in steatotic livers. Thus, we further investigated the global H3K9me3 and H3K4me3 status in lipid-accumulated mouse primary hepatocytes by ChIP-on-chip analysis. Results showed that hepatic lipid accumulation induced aberrant H3K9me3 and H3K4me3 status in peroxisome proliferator-activated receptor alpha and hepatic lipid catabolism network genes, reducing their mRNA expression compared with non-treated control hepatocytes. This study provides the first evidence that epigenetic regulation by H3K9me3 and H3K4me3 in hepatocytes may be involved in hepatic steatosis and the pathogenesis of NAFLD. Thus, control of H3K9me3 and H3K4me3 represents a potential novel NAFLD prevention and treatment strategy.
NTRK1 Fusion in Glioblastoma Multiforme
Jinkuk Kim, Yeri Lee, Hee-Jin Cho, Young-Eun Lee, Jaeyeol An, Gye-Hyun Cho, Young-Hyeh Ko, Kyeung Min Joo, Do-Hyun Nam
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0091940
Abstract: Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, yet with no targeted therapy with substantial survival benefit. Recent studies on solid tumors showed that fusion genes often play driver roles and are promising targets for pharmaceutical intervention. To survey potential fusion genes in GBMs, we analysed RNA-Seq data from 162 GBM patients available through The Cancer Genome Atlas (TCGA), and found that 3′ exons of neurotrophic tyrosine kinase receptor type 1 (NTRK1, encoding TrkA) are fused to 5′ exons of the genes that are highly expressed in neuronal tissues, neurofascin (NFASC) and brevican (BCAN). The fusions preserved both the transmembrane and kinase domains of NTRK1 in frame. NTRK1 is a mediator of the pro-survival signaling of nerve growth factor (NGF) and is a known oncogene, found commonly altered in human cancer. While GBMs largely lacked NTRK1 expression, the fusion-positive GBMs expressed fusion transcripts in high abundance, and showed elevated NTRK1-pathway activity. Lentiviral transduction of the NFASC-NTRK1 fusion gene in NIH 3T3 cells increased proliferation in vitro, colony formation in soft agar, and tumor formation in mice, suggesting the possibility that the fusion contributed to the initiation or maintenance of the fusion-positive GBMs, and therefore may be a rational drug target.
Comparison of the Tuberculin Skin Test and Interferon Gamma Release Assay for the Screening of Tuberculosis in Adolescents in Close Contact with Tuberculosis TB Patients
Seung-Eun Song, JiYeon Yang, Kil Soo Lee, Hyungjun Kim, Young Mi Kim, Seonghan Kim, Mi-Sun Park, Su Yeon Oh, Jin Bum Lee, EunPyo Lee, Sang-Hee Park, Hee-Jin Kim
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0100267
Abstract: Background The tuberculin skin test (TST) frequently yields false positive results among BCG-vaccinated persons thereby limiting its diagnostic value particularly in settings with high BCG vaccination rate. We determined the agreement between IGRA and TST using 2 cutoff values and identified possible relationships between the results of these tests and the development of active tuberculosis. Methodology Adolescents aged 11–19 years in close contact with smear-positive tuberculosis cases and with normal chest radiographs were recruited from middle and high schools in South Korea. The TST was conducted by trained nurses, and blood was drawn for the QuantiFERON-TB Gold In-Tube (QFT-GIT). Participants were followed up for 2 years to check for incidence tuberculosis. Results A total of 2,982 subjects were included in the study, the average age was 15.1 years (SD 1.3), 61% had BCG vaccination scars. The agreement of QFT-GIT and the TST was low (κ = 0.38, 95% CI 0.32 to 0.42) using 10 mm cutoff; however, when the 15 mm cutoff was used, the agreement was intermediate (κ = 0.56, 95% CI 0.50 to 0.61). The odds ratio (OR) for the development of active tuberculosis was 7.9 (95% CI 3.46 to 18.06) for QFT-GIT positive patients, 7.96 (95% CI 3.14-20.22) for TST/QFT-GIT+ and the OR 4.62 (95% CI 2.02 to 10.58) and 16.35 (95% CI 7.09 to 37.71) for TST 10 mm and 15 mm cutoff respectively. Conclusions The results of this study suggest that the TST cutoff point for patients aged 11–17 years would be 15 mm in other study. The OR of QFT-GIT for the development of active tuberculosis and its intermediate agreement with TST using 15 mm cutoff demonstrates its role as an adjunct diagnostic tool to current clinical practice. Positive responders to both TST and QFT-GIT at the outset may benefit from chemoprophylaxis.
Copy number variations (CNVs) identified in Korean individuals
Tae-Wook Kang, Yeo-Jin Jeon, Eunsu Jang, Hee-Jin Kim, Jeong-Hwan Kim, Jong-Lyul Park, Siwoo Lee, Yong Kim, Jong Kim, Seon-Young Kim
BMC Genomics , 2008, DOI: 10.1186/1471-2164-9-492
Abstract: We identified 65 copy number variation regions (CNVRs) in 116 normal Korean individuals by analyzing Affymetrix 250 K Nsp whole-genome SNP data. Ten of these CNVRs were novel and not present in the Database of Genomic Variants (DGV). To increase the specificity of CNV detection, three algorithms, CNAG, dChip and GEMCA, were applied to the data set, and only those regions recognized at least by two algorithms were identified as CNVs. Most CNVRs identified in the Korean population were rare (<1%), occurring just once among the 116 individuals. When CNVs from the Korean population were compared with CNVs from the three HapMap ethnic groups, African, European, and Asian; our Korean population showed the highest degree of overlap with the Asian population, as expected. However, the overlap was less than 40%, implying that more CNVs remain to be discovered from the Asian population as well as from other populations. Genes in the novel CNVRs from the Korean population were enriched for genes involved in regulation and development processes.CNVs are recently-recognized structural variations among individuals, and more CNVs need to be identified from diverse populations. Until now, CNVs from Asian populations have been studied less than those from European or American populations. In this regard, our study of CNVs from the Korean population will contribute to the full cataloguing of structural variation among diverse human populations.Understanding variations in the human genome is the key to unraveling the phenotypic diversity among individuals and understanding various human diseases. Genomic variations exist at various levels, from differences in single nucleotides to microscopic chromosome-level variation [1]. Copy number variations (CNVs), a new type of genomic variation that has recently received considerable attention, are deletions, insertions, duplications, and more complex variations ranging from 1 kb to submicroscopic sizes [1-4]. Recent advances in array technolo
SNP Linkage Analysis and Whole Exome Sequencing Identify a Novel POU4F3 Mutation in Autosomal Dominant Late-Onset Nonsyndromic Hearing Loss (DFNA15)
Hee-Jin Kim, Hong-Hee Won, Kyoung-Jin Park, Sung Hwa Hong, Chang-Seok Ki, Sang Sun Cho, Hanka Venselaar, Gert Vriend, Jong-Won Kim
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079063
Abstract: Autosomal dominant non-syndromic hearing loss (AD-NSHL) is one of the most common genetic diseases in human and is well-known for the considerable genetic heterogeneity. In this study, we utilized whole exome sequencing (WES) and linkage analysis for direct genetic diagnosis in AD-NSHL. The Korean family had typical AD-NSHL running over 6 generations. Linkage analysis was performed by using genome-wide single nucleotide polymorphism (SNP) chip and pinpointed a genomic region on 5q31 with a significant linkage signal. Sequential filtering of variants obtained from WES, application of the linkage region, bioinformatic analyses, and Sanger sequencing validation identified a novel missense mutation Arg326Lys (c.977G>A) in the POU homeodomain of the POU4F3 gene as the candidate disease-causing mutation in the family. POU4F3 is a known disease gene causing AD-HSLH (DFNA15) described in 5 unrelated families until now each with a unique mutation. Arg326Lys was the first missense mutation affecting the 3rd alpha helix of the POU homeodomain harboring a bipartite nuclear localization signal sequence. The phenotype findings in our family further supported previously noted intrafamilial and interfamilial variability of DFNA15. This study demonstrated that WES in combination with linkage analysis utilizing bi-allelic SNP markers successfully identified the disease locus and causative mutation in AD-NSHL.
Spectrum of Cognitive Impairment in Korean ALS Patients without Known Genetic Mutations
Seong-il Oh, Aram Park, Hee-Jin Kim, Ki-Wook Oh, Hojin Choi, Min-Jung Kwon, Chang-Seok Ki, Hee-Tae Kim, Seung Hyun Kim
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0087163
Abstract: Background Cognitive impairment is associated with a negative prognosis in amyotrophic lateral sclerosis (ALS), as well as with clinical specificity. We investigate neuropsychological function in ALS patients without known genetic mutations in a Korean tertiary clinic. Methods Three hundred and eighteen patients were enrolled in a prospective longitudinal cohort from September 2008 to February 2012. At the time of diagnosis of sporadic ALS, we carried out genetic and comprehensive neuropsychological tests on all patients, and collected demographic and clinical characteristics. Six cognitive domains, namely executive function, attention, language, calculation, visuospatial function and memory were evaluated. ANOVA and t-tests were used to assess differences in clinical characteristics and neuropsychological parameters between sporadic ALS patients. The Kaplan-Meier method and Cox proportional hazard model were used for survival analysis. Results One hundred and sixty-six patients were categorized into five subtypes: normal cognition (ALS pure), cognitive impairment (ALSci), behavioral impairment (ALSbi), frontotemporal dementia (ALS-FTD), and other types of dementia. Seventy patients (70/166, 42.2%) were cognitively or behaviorally impaired. Among the impaired patients, eight (8/166, 4.8%) had FTD-type dementia and one (1/166, 0.6%) was Alzheimer's disease-type. The ALS patients with cognitive impairment (ALSci) and with FTD (ALS-FTD) were more severely impaired in executive function, attention, language and memory than the cognitively intact ALS patients (ALS pure). In a survival analysis, ALSci (β = 1.925, p = 0.025) and ALS-FTD groups (β = 4.150, p = 0.019) tended to have shorter survival than the ALS pure group. Conclusions About half of ALS patients without known genetic variation have cognitive or behavioral impairment. ALS patients with cognitive abnormalities, especially FTD, have a poorer prognosis than those without cognitive impairment. In neuropsychological profiling, executive tasks were effective in identifying cognitive impairment in the ALS patients. It would be useful for clinicians to classify ALS according to neuropsychological profiles, and screen for subtle cognitive impairment.
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