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Biomedical subjects

Eun Young Song

Publications and source records attributed to Eun Young Song.

At least 19 recordsLinked to original sources

Up-regulation of Mac-2 binding protein by hTERT in gastric cancer.

Mac-2 binding protein (Mac-2BP) is a secreted tumor antigen that is elevated in many cancers and implicated in tumor metastasis, as well as cell adhesion and immune functions. We focused on the human telomerase reverse transcriptase (hTERT) induced Mac-2BP expression and the relationship between Mac-2BP expression and the progression of gastric cancer. A cDNA expression array analysis was performed on the telomerase-negative cell line, SW13, which was engineered to overexpress hTERT when compared with the parental SW13 cell. hTERT-induced Mac-2BP expression was confirmed via RT-PCR and Northern blotting. ELISA and flow cytometric analyses revealed that Mac-2BP protein was increased by 2- to 4-fold in hTERT-overexpressing cells compared with the mock control. Mac-2BP expression was significantly reduced when the overexpressed hTERT was neutralized by the introduction of hTERT-specific siRNA. These results suggest that Mac-2BP expression is modulated by hTERT. Mac-2BP levels in both gastric cancer cells and tumor tissues were determined via Northern blot analysis and immunohistochemistry. Mac-2BP protein was highly expressed in most gastric cancer cell lines, and gastric tumor tissues were stained more densely than normal tissues. The intracellular and secreted Mac-2BP levels were also evaluated via ELISA, indicating that Mac-2BP was expressed and secreted more abundantly in gastric cancer patients than in healthy donors. The elevated serum Mac-2BP level in gastric tumor patients was also significantly associated with distant metastasis (p = 0.05) and higher tumor stage (p = 0.04). Our findings suggest that Mac-2BP is induced by hTERT, and that it may prove to be a useful prognostic marker for the detection of malignant progression of metastatic stomach cancers.

Adult↗

Apoptosis-inducing factor (AIF) inhibits protein synthesis by interacting with the eukaryotic translation initiation factor 3 subunit p44 (eIF3g).

Apoptosis-inducing factor (AIF) is a ubiquitous FAD-binding flavoprotein comprised of 613 amino acids and plays an important role in caspase-independent apoptosis. During apoptotic induction, AIF is translocated from the mitochondrial intermembrane space to the nucleus, where it interacts with DNA and activates a nuclear endonuclease. By performing a yeast two-hybrid screen with mature AIF, we have isolated the eukaryotic translation initiation factor 3 subunit p44 (eIF3g). Our deletion mutant analysis revealed that the eIF3g N-terminus interacts with the C-terminal region of AIF. The direct interaction between AIF and eIF3g was confirmed in a GST pull-down assay and also verified by the results of co-immunoprecipitation and confocal microscopy studies. Using an in vitro TNT coupled transcription-translation system, we found that mature AIF could inhibit newly-translated protein synthesis and this inhibition was significantly blocked by eIF3g competitively. These results were also confirmed in cells. In addition, mature AIF overexpression specifically resulted in the activation of caspase-7, thereby amplifying the inhibition of protein synthesis including eIF3g cleavage. Our data suggest that eIF3g is one of the cytosolic targets that interacts with mature AIF, and provide insight into the AIF's cellular functions of the inhibition of protein synthesis during apoptosis.

Active Transport, Cell Nucleus↗

A computer vision-based automated Figure-8 maze for working memory test in rodents.

The benchmark test for prefrontal cortex (PFC)-mediated working memory in rodents is a delayed alternation task utilizing variations of T-maze or Figure-8 maze, which requires the animals to make specific arm entry responses for reward. In this task, however, manual procedures involved in shaping target behavior, imposing delays between trials and delivering rewards can potentially influence the animal's performance on the maze. Here, we report an automated Figure-8 maze which does not necessitate experimenter-subject interaction during shaping, training or testing. This system incorporates a computer vision system for tracking, motorized gates to impose delays, and automated reward delivery. The maze is controlled by custom software that records the animal's location and activates the gates according to the animal's behavior and a control algorithm. The program performs calculations of task accuracy, tracks movement sequence through the maze, and provides other dependent variables (such as running speed, time spent in different maze locations, activity level during delay). Testing in rats indicates that the performance accuracy is inversely proportional to the delay interval, decreases with PFC lesions, and that animals anticipate timing during long delays. Thus, our automated Figure-8 maze is effective at assessing working memory and provides novel behavioral measures in rodents.

Algorithms↗

Diagnostic accuracy of serum asialo-alpha1-acid glycoprotein concentration for the differential diagnosis of liver cirrhosis and hepatocellular carcinoma.

BACKGROUND: Serum asialoglycoproteins concentration are increased in patients with hepatic disease. We developed an antibody-lectin sandwich assay that is sensitive and specific to measure asialo-alpha(1)-acid glycoprotein (AsAGP) concentration in human serum and evaluated it as a biochemical marker for hepatic disease. METHODS: Serum AsAGP concentration was measured by antibody-lectin sandwich assay with 610 serum specimens of patients with hepatic disease. Serum from 41 healthy donors and 155 patients with non-hepatic disease served as negative controls. The AsAGP values were analyzed by receiver operator characteristics (ROC) curve analysis. The diagnostic accuracy of AsAGP value was compared with those of the conventional biochemical markers in the liver function test. RESULTS: Serum AsAGP concentration in 83% of patients with liver cirrhosis (LC) and 89% of patients with hepatocellular carcinoma (HCC) was increased over the cutoff value (1.33 microg/ml), indicating that an increase of serum AsAGP concentration is restricted to LC or HCC cases. The area under curve (AUC) in the ROC curve was 0.919 for LC and 0.946 for HCC. CONCLUSIONS: Serum AsAGP concentration exhibited good diagnostic accuracy as a biochemical marker for LC and HCC. The addition of AsAGP to conventional liver function tests may significantly improve the diagnosis and prognosis.

Adolescent↗

Measurement of CGRP in dried blood spots using a modified sandwich enzyme immunoassay.

Calcitonin gene-related peptide (CGRP) has roles as a neurotransmitter, neuromodulator and trophic factor. CGRP has been reported to be elevated in neonatal blood of children with autism or mental retardation as compared with normal subjects by recycling immuno-affinity chromatography (RIC). While CGRP detection in neonatal blood is thus important, it is not easy to detect CGRP in dried blood spots because of the limitations of sample volume and the specificity and the sensitivity of available assay systems. In the present study, we modified a "Sandwich Enzyme Immunoassay" for the purpose of detecting CGRP in blood spot eluate. We have prepared blood spots from blood collected from normal human subjects and measured CGRP level in eluates from these blood spots. Instead of a purification step, we have introduced a pre-incubation step and used washed erythrocytes as a dilution solution. The modified assay has good recovery and specificity and appropriate dilution curves. We have compared the eluate levels with levels in serum and plasma from the same individuals and find that CGRP levels in blood spot eluate were similar to those of serum and plasma. Thus, the newly modified EIA may be a useful method for the detection of CGRP in blood spot eluate.

Antibody Specificity↗

Stress effects in the hippocampus: synaptic plasticity and memory.

It is now well-documented that exposures to uncontrollable (inescapable and unpredictable) stress in adulthood can have profound effects on brain and behavior. Converging lines of evidence from human and animal studies indicate that stress interferes with subsequent performances on a variety of hippocampal-dependent memory tasks. Animal studies further revealed that stress impedes ensuing induction of long-term potentiation (LTP) in the hippocampus. Because the hippocampus is important for key aspects of memory formation and because LTP has qualities congruent to an information storage mechanism, it is hypothesized that stress-induced modifications in hippocampal plasticity contribute to memory impairments associated with stress. Recent studies provide evidence that the amygdala, a structure important in stress- and emotion-related behaviors, plays a necessary role in the emergence of stress-associated changes in hippocampal LTP and memory. Early life stress also alters hippocampal plasticity and memory in a manner largely consistent with effects of adult stress exposure. This review focuses on endocrine-system-level mechanisms of stress effects in the hippocampus, and how stress, by altering the property of hippocampal plasticity, can subsequently influence hippocampal memory.

Amygdala↗

Development of a rapid, immunochromatographic strip test for serum asialo alpha1-acid glycoprotein in patients with hepatic disease.

Serum asialoglycoprotein (desialylated glycoproteins) concentrations have been reported to be elevated in patients with hepatic disease as compared with that of normal subjects. We recently developed a solid-phase sandwich assay for asialo alpha1-acid glycoprotein (AsAGP) as a representative of the serum asialoglycoproteins and evaluated the utility of this AsAGP as a diagnostic marker for liver cirrhosis (LC) and/or hepatocellular carcinoma (HCC). In this study, we developed a rapid, one-step immunochromatographic strip capable of specifically detecting AsAGP in serum specimens. We have produced a monoclonal antibody (mAb) to AGP, and based on ELISA and Western blot analysis, we have selected four hybridoma clones which generated mAbs to recognize AsAGP. In the immunochromatographic strip test, one mAb was used for conjugation with colloidal gold microparticles. Ricinus communis agglutinin (RCA) was immobilized onto a nitrocellulose membrane strip to form a result line in the path of chromatographic migration. Likewise, a control line was created above the result line by the immobilization of anti-mouse IgG. A serum specimen was then applied to the sample pad. The AsAGP in the sample specifically bound to the microparticles via mAb (As16.89) and co-migrated upward until the AsAGP was sandwiched with the immobilized lectin (RCA), revealing a visible result line. The colloidal gold microparticles without bound AsAGP continued to migrate, forming a visible control line. Thus, an AsAGP-positive specimen (>1.5 microg/mL) yielded a result line and a control line, whereas an AsAGP-negative specimen (<1.5 microg/mL) produced only a single control line. The entire test procedure was completed in less than 5 min. In order to examine the reliability of the testing procedures, we carried out the immunochromatographic strip test with 102 serum samples and compared the results of these tests with those obtained by ELISA. The two methods showed excellent correlation, with 83-100% above/below the cut-off value (1.5 microg/mL). Therefore, we concluded that the results of the immunochromatographic test are in excellent accordance with those of the sandwich ELISA.

Animals↗

Selected neurotrophins, neuropeptides, and cytokines: developmental trajectory and concentrations in neonatal blood of children with autism or Down syndrome.

Using a double-antibody immunoaffinity assay (Luminex) and ELISA technology, we measured concentrations of certain neurotrophins, neuropeptides, and cytokines in pooled samples (one to three subjects per sample) eluted from archived neonatal blood of children with later-diagnosed autism, Down syndrome, very preterm birth, or term control infants. We also measured analytes in blood from healthy adult controls. Case or control status for infant subjects was ascertained by retrospective review of service agency medical records. We observed inhibitory substances in eluates from archived bloodspots, especially marked for measurement of BDNF. Concentrations in control subjects differed by age: BDNF rose markedly with age, while NT-3 and NT-4/5 concentrations were lower in adults than in newborn infants. IL-8 concentrations were higher in newborn infants, preterm and term, than in adults. Considered by diagnostic group, total protein was higher in Down syndrome than in either autism or control subjects. In infants with Down syndrome, concentrations of IL-8 levels were higher than in controls, whether or not corrected for total protein; NT-3 and CGRP were lower and VIP higher. In samples from autistic subjects, NT-3 levels were significantly lower than controls and an increase in VIP approached statistical significance. Concentrations of NT-4/5 and CGRP were correlated in infants with autism but not in Down syndrome or controls. Some of these results differ from earlier findings using a single-antibody recycling immunoaffinity chromatography (RIC) system. We discuss interrelationships of VIP, NT-3 and IL-8 and their potential relevance to features of the neuropathology of autism or Down syndrome.

Adult↗

Association of HLA-DR and HLA-DQ genes with susceptibility to pulmonary tuberculosis in Koreans: preliminary evidence of associations with drug resistance, disease severity, and disease recurrence.

Only 10% of persons infected with Mycobacterium tuberculosis develop clinical tuberculosis (TB), indicating the existence of host genetic factors regulating disease expression. We investigated the association of human leukocyte antigen (HLA) class II genes with the susceptibility to pulmonary TB in Koreans, with special emphasis on their association with drug resistance, disease severity, and disease recurrence. Human leukocyte antigens (HLA)-DRB1 and -DQB1 gene polymorphisms were analyzed in 160 Korean patients with pulmonary TB and 200 ethnically matched healthy controls. HLA-DRB1*0803 (25.0% vs. 14.5% in controls, OR = 1.97, p = 0.012, corrected p (p(c)) > 0.05) and DQB1*0601 (27.5% vs. 15.5% in controls, OR = 2.07, p = 0.005, p(c) > 0.05) were weakly associated with general susceptibility to TB. DRB1*0803 was significantly associated with drug resistance (30.9% vs. 14.5%, OR = 2.63, p(c) = 0.047) and more advanced lung lesion (29.8% vs. 14.5%, OR = 2.50, p(c) = 0.022). DRB1*0803 showed the strongest association with disease recurrence, especially after curative treatment for the earlier infection (47.4% vs. 14.5%, OR = 5.31, p(c) = 0.00009). DQB1*0601, which is strongly linked to DRB1*0803 in this population showed similar changes in the patients as those of DRB1*0803. It is suggested that DRB1*0803 and DQB1*0601 alleles are associated with disease progression of TB in Koreans, exerting influence on the development of drug resistance, severe disease, and recurrent disease.

Adult↗

Upregulation of Bcl-2 is associated with cisplatin-resistance via inhibition of Bax translocation in human bladder cancer cells.

The efficacy of cisplatin in cancer chemotherapy is limited by the development of resistance. To elucidate the molecular basis of resistance to cisplatin, we compared cisplatin-induced apoptotic responses of the parental human bladder cancer cell line, T24 and its resistant subclone, T24R2. In T24 cells, cisplatin induce apoptosis and the activation of caspase-8, -9 and -3 and poly(ADP-ribose) polymerase cleavage. The expression levels of Fas, FasL, and FADD were not changed by the treatment with cisplatin. Furthermore, neither Fas-neutralizing antibody nor dominant negative mutant of FADD affected cisplatin-induced apoptosis. Western blot analysis of subcellular fractions showed that cisplatin induced redistribution of Bax and cytochrome c. Thus, cisplatin causes apoptosis in a death receptor-independent and mitochondria-dependent fashion in T24 cells. In contrast, overexpressed Bcl-2 protein inhibited cisplatin-induced Bax translocation and its downstream events in T24R2. Downregulation of Bcl-2 by RNAi potentiated the redistribution of Bax and cytochrome c and reversed cisplatin-resistance. Our results indicate that upregulation of Bcl-2 contributes to the development of cisplatin-resistance and usage of siRNA which targets the Bcl-2 gene may offer a potential tool to reverse the resistance to cisplatin in bladder cancer.

Antineoplastic Agents↗

Measurement of vasoactive intestinal peptide using a competitive fluorescent microsphere immunoassay or ELISA in human blood samples.

The concentration of Vasoactive Intestinal Peptide (VIP) as measured by recycling immunoaffinity chromatography (RIC) has been reported to be elevated in the blood of patients with autism as compared with normal subjects. In this study, we have developed a "Competitive Fluorescent Microsphere Immunoassay" (cFMI) in which VIP competes with biotinylated VIP in binding to polyclonal antibodies on microspheres. The results were obtained using the Luminex100 system. We measured VIP in serum, plasma, and material eluted from dried blood spots on filter paper with both the cFMI and an ELISA procedure. We found that a purification procedure was necessary for obtaining useful results from plasma and serum, however, a preincubation step was required with the blood eluates. This newly developed cFMI was more sensitive (2.5 vs. 20.0 pg/ml), and more reproducible than the ELISA. To get accurate measurements of VIP in eluted material high sensitivity is especially important. Thus, the cFMI using the Luminex system has definite advantages over a conventional ELISA including the possibility that samples can be assayed at higher dilutions. We have determined that the VIP concentrations of serum, plasma, and dried blood spot eluate specimens as measured with the cFMI assay system were similar to those measured with ELISA. Thus, the new cFMI using Luminex system may be useful for detection of VIP in human blood samples.

Adult↗

Role of active movement in place-specific firing of hippocampal neurons.

The extent of external and internal factors contributing to location-specific firing of hippocampal place cells is currently unclear. We investigated the role of active movement in location-specific firing by comparing spatial firing patterns of hippocampal neurons, while rats either ran freely or rode a motorized cart on the same circular track. Most neurons changed their spatial firing patterns across the two navigation conditions ("remapping"), and they were stably maintained across repeated active or passive navigation sessions. These results show that active movement is a critical factor in determining place-specific firing of hippocampal neurons. This could explain why passive displacement is not an effective way of acquiring spatial knowledge for subsequent active navigation in an unfamiliar environment.

Action Potentials↗

Inhibition of hepatitis B virus by an aqueous extract of Agrimonia eupatoria L.

Inhibition of HBsAg release against hepatitis B virus (HBV) was investigated in an aqueous extract prepared from the aerial parts (stems and leaves) of Agrimonia eupatoria. The inhibitory effect on HBsAg secretion was footed using aqueous extracts of Agrimonia eupatoria at four different temperatures (37 degrees C 45 degrees C, 55 degrees C and 60 degrees C), and the extract prepared at 60 degrees C was found to have the greatest effect. The inhibitory activity of Agrimonia eupatoria extracts on HBsAg secretion varied over the growing season and was the highest at mid-July. This inhibitory activity was also shown with the aqueous extracts of two other species of the genus Agrimonia: A. pilosa and A. coreana pilosella. These results suggest that some plants of the genus Agrimonia contain potential antiviral activity against HBV.

Agrimonia↗

Association of HLA-DR and -DQ genes with Graves disease in Koreans.

Graves disease (GD) is an autoimmune thyroid disease and is associated with human leukocyte antigen (HLA)-DR3 and DQA1*0501 in Caucasians. However, the association of HLA with GD is less clear-cut in East Asian populations. We analyzed HLA-DRB1 and -DQB1 associations with GD in 198 Korean patients compared with 200 healthy controls. HLA-DRB1*0803 (27.8% vs. 14.5% in controls, OR = 2.27, corrected p [p(c)] = 0.03) and *1602 (5.1% vs. 0%, OR = 22.34, p(c) = 0.03) alleles and closely linked haplotypes, DRB1*0803-DQB1*0601 and DRB1*1602-DQB1*0502, conferred susceptibility to GD in Koreans. Weak association of DRB1*0301 with GD susceptibility was observed in male patients only (12.5% vs. 3.5%, OR = 3.57, p < 0.05). HLA-DRB1*0101, *0701, *1202, and *1302 alleles were weakly associated with resistance to the disease (OR < 0.5, p < 0.05). Some HLA alleles were weakly associated with clinical characteristics in GD patients. Patients with DRB1*1301-DQB1*0603 developed their diseases in younger ages and were more frequently associated with larger goiter (p < 0.05). Although HLA class II alleles associated with GD in Koreans were different from those in Caucasians, some associations are shared, such as association of DRB1*0301 in male patients and protective effect of DRB1*0701 to GD susceptibility.

Adolescent↗

Buccal DNA samples for DNA typing: new collection and processing methods.

With the recent expansion of DNA database laws in many states, there is a critical need for the rapid and simple collection of DNA samples and streamlined processing for downstream applications. The Buccal DNA Collector was developed to address the need for a reliable, practical alternative to blood collection that is compatible with high-throughput operations. The collection area consists of filter paper that is placed against the inside of the cheek, and the sample is taken by swiping the cheek several times while pulling the device out of the mouth. Using this method, DNA profiles have been obtained from samples stored for 2 years at room temperature. Cells are collected on all regions of the filter paper with the maximum DNA recovery from the tip. The processing of DNA for DNA typing is accomplished with BodeElute, a new product that prepares DNA for amplification in a single 30-min heating step. Extracted DNA samples were successfully amplified with four commonly used multiplex short tandem repeat (STR) amplification kits. These products provide simplified approaches for collecting and processing buccal cell samples.

DNA↗

Tree-based model for breast cancer prognostication.

PURPOSE: To define prognostic groups for recurrence-free survival in breast cancer, assess relative effects of prognostic factors, and examine the influence of treatment variations on recurrence-free survival in patients with similar prognostic-factor profiles. PATIENTS AND METHODS: We analyzed 1,055 patients diagnosed with stage I-III breast cancer between 1990 and 1996. Variables studied included socioeconomic factors, tumor characteristics, concurrent medical conditions, and treatment. The primary end point was recurrence-free survival (RFS). Multivariable analyses were performed using recursive partitioning and Cox proportional hazards regression. RESULTS: The most significant difference in prognosis was between patients with fewer than four and those with at least four positive nodes (P <.0001). Four distinct prognostic groups (5-year RFS, 97%, 78%, 58%, and 27%) were developed, defined by the number of positive nodes, tumor size, progesterone receptor (PR) status, differentiation, race, and marital status. Patients with fewer than four positive nodes and tumor < or = 2 cm, PR positive, and well or moderately differentiated had the best prognosis. RFS in this group was unaffected by type of adjuvant therapy (P =.38). Patients with at least four positive nodes and PR-negative tumors had the worst prognosis, and those treated with tamoxifen plus chemotherapy had the best outcome in this group (P =.0001). Among patients in the two intermediate-risk groups, those treated with tamoxifen or a combination of tamoxifen and chemotherapy had the best outcome. CONCLUSION: Lymph node status, PR status, tumor size, differentiation, race, and marital status are valuable for prognostication in breast cancer. The prognostic groups derived can provide guidance for clinical trial design, patient management, and future treatment policy.

Adult↗

HLA-DRB1 and -DRB3 allele frequencies and haplotypic associations in Koreans.

We have investigated the frequencies of human leukocyte antigen-DRB1 (HLA-DRB1) and -DRB3 alleles and DRB1-DRB3 haplotypic associations in 800 Koreans. DRB1 genotyping was done using polymerase chain reaction-sequence-specific oligonucleotide (PCR-SSO) and PCR-single strand conformation polymorphism (SSCP) methods. DRB3 genotyping was done on 447 samples carrying DRB3-associated DRB1 alleles (DRB1*03, *11, *12, *13, and *14) using PCR-SSCP method. The allele frequencies of DRB3*0101, DRB3*0202, and DRB3*0301 were 0.073, 0.136, and 0.120, respectively, and we found one case of a probable new allele (DRB3*01new, 0.001). DRB1-DRB3 haplotypes with frequency (HF) > 0.005 exhibited strong associations between DRB3*0101 and DRB1*1201, *1301, and *1403; between DRB3*0301 and DRB1*1202 and *1302; between DRB3*0202 and DRB1*0301, *1101, *1401, *1405, and *1406 alleles. Most of the DRB1 alleles with frequency > 0.005 were exclusively associated with particular DRB3 alleles with relative linkage disequilibrium values of 1.0, except for DRB1*1201, *1202 and *1301; the rare presence (HF < 0.005) of DRB3*0202 associations were observed for these DRB1 alleles. We also investigated and presented rare DRB1-DRB3 associations in additional 6000 Koreans. Comparison with other ethnic groups revealed that DRB1*0301 and *1301 related DRB1-DRB3 haplotypes vary among different populations, in that Koreans and other Asian populations show less diversity compared with Caucasoids or African Americans.

Gene Frequency↗

Current status of therapeutic plasma exchange in Korea.

A nationwide survey on the status of plasma exchange in Korea was performed during the 2 year period 2001-02. Data from 496 patients were collected from 15 major hospitals. The most common indication was myasthenia gravis (15.3%), followed by thrombotic thrombocytopenic purpura (14.5%) and hemolytic uremic syndrome (9.7%). Clinical improvement was noted in 70.1% of the 415 cases. Plasma exchange by centrifugation alone accounted for 92.4%. Postcentrifugal filtration was carried out in 5.6% and double filtration in 2.0% of treatments. The most common instruments for the centrifugation were Cobe Spectra (71.3%) and Fenwal CS3000 (15.8%). Filtration was performed by either Kuraray KM8300 or Kuraray KM8800. The overall frequency of complications was 11.1% (293/2647 cases), of which symptomatic hypocalcemia was the most common (2.3%).

Health Care Surveys↗