Biomedical subjects

Eun-Joo Kim

Publications and source records attributed to Eun-Joo Kim.

33 records · Page 2Linked to original sources

PubMed2004

Safety pharmacology of DW-224a, a novel fluoroquinolone antibiotic agent.

To investigate the safety pharmacology of a novel fluoroquinolone antibiotic agent, DW-224a, on the vital functions, we studied its effects on the central nervous system, cardiovascular system and respiratory system. To determine the effects on the central nervous system, we used a modified Irwin's test at each time point after oral administration of DW-224a to mice. In this test, we found that the treatment of test article had no effects on motor activity, behavioral changes, coordination, and sensory/motor reflex responses. The effects of DW-224a on the cardiovascular system were evaluated by the use of a telemetry system in beagle dogs. At 360 min post-DW-224a (100 mg/kg) administration, QT interval prolongation was observed. However, there were no changes in heart rate, blood pressure, and electrocardiogram at all doses and each time points with the exception of QT-interval prolongation as compared to the vehicle treated group. In experiments designed to determine the changes of respiratory function in rats, we found no changes at all doses and time points. We investigated the effects of DW-224a on the human ether-a-go-go-related gene (hERG) mediated potassium currents to evaluate its potential to induce QT interval prolongation. When whole cell patch-clamp electrophysiology was used, DW-224a inhibited hERG currents with IC50 of 218.12 +/- 39.51 microM though its effect was less potent than that of E-4031, a positive control drug. Our data suggested that DW-224a showed no adverse effects on the central nervous system, cardiovascular system, and respiratory system, with the exception of the effect on the QT interval prolongation.

Animals↗

PubMed2004

Pseudoneglect in solid-line versus character-line bisection tasks: a test for attention dominance theory.

OBJECTIVE: Normal subjects tend to bisect lines slightly to the left of the true midpoint, a phenomenon termed pseudoneglect. To test whether pseudoneglect relates to the right hemisphere's dominance for spatial attention or to the hemispheric difference in processing global-local stimulus properties, we administered conventional solid-line (SBT) and novel character-line (CBT) bisection tasks to normal subjects of different ages. METHODS: Normal subjects, consisting of 40 young and 40 older individuals, received 3 experimental tasks, a standard SBT and 2 types of CBT. Each subject completed 10 consecutive trials of each task presented in counterbalanced order between subjects. RESULTS: Across age groups, deviations on CBT were further to the right than those of SBT, and the leftward bias (pseudoneglect) was significant only in SBT. CONCLUSION: These results indicate that the bisection errors in normal subjects depend on the characteristics demanded by the specific task. Thus, our findings argue against the attention dominance theory and support a "task specificity" theory for pseudoneglect.

Adult↗

PubMed2004

General pharmacology of DW-286a, a new fluoronaphthyridone antibiotic: effects on central nervous, cardiovascular, and respiratory systems.

DW-286a is a new class of fluoronaphthyridone antibiotic. Its effect on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied. The doses given were 30, 50, 100, 150, 300, and 1000 mg/kg and drugs were administered orally. DW-286a did not show any effects on general behavior, motor coordination, analgesic action, seizure and mortality, blood pressure and heart rate, contractile response of isolated guinea pig ileums, and renal function. On the other hand, DW-286a decreased spontaneous locomotor activity from 120 to 240 min after administration at the doses of 300 and 1000 mg/kg and the respiration rate from 30 to 240 min after the administration of doses up to 100 mg/kg. The sleeping time and body temperature were increased significantly in mice at the dose of 1000 mg/kg. DW-286a increased the charcoal transport significantly at doses of 300 and 1000 mg/kg. DW-286a inhibited gastric acid secretion, reduced the volume of the gastric juice and total acidity, and increased the pH dose dependently. Based on the above results, it was concluded that DW-286a affects spontaneous locomotor activity, respiration and body temperature, gastrointestinal transport, gastric secretory action, and hexobarbital sleeping time at high doses.

Animals↗

PubMed2004

[A study of the relationship between the child-rearing attitudes and the maternal role strain in mothers with infants].

PURPOSE: The main purpose of this study was to identify the correlation between the child rearing attitudes and the maternal role strain of mother with infants. METHOD: This study is designed as a descriptive research study and the data was collected from 82 mothers and infants by means of an interview and questionnaire in a period from July 2002 to December 2002, when they came to screen their infant's growth and developmental state at a public health center. RESULT: The results of this study were as follows: There was a significant positive correlation between the child rearing attitudes and maternal role strain(r.=.53, p=.000). There was a significant difference between the father's employment state and child rearing attitude of mothers(t.=5.22, p<.000). There was a significant difference between male infant and female infants in maternal role strain(t.=3.8, p=0.04). CONCLUSION: When the child rearing attitude was positive, the subject's maternal role strain was high. Also further research is needed on social support or other factors in the subjects in child-rearing attitudes and maternal role strain.

Adult↗

PubMed2003

Identification of Daxx interacting with p73, one of the p53 family, and its regulation of p53 activity by competitive interaction with PML.

We performed a yeast two-hybrid screen using p73alpha, which is a member of the p53 family, as bait. We found that the p53 family members were functionally associated with Daxx, which was described originally as a cytoplasmic mediator of Fas signaling, but has been identified recently as a nuclear protein that co-localizes with the promyelocytic leukemia (PML) protein and regulates transcription. Extensive yeast two-hybrid assays indicated a physical interaction between a region including the oligomerization domain (OD) of p73alpha (amino acids 345-380) or p53 (amino acids 319-360) and amino acids 161-311 and 667-740 (C-terminal S/P/T-rich domain) of hDaxx, which is the common binding region of Fas, ASK1 and PML. This interaction was further confirmed by in vitro GST pull-down and in vivo immunoprecipitation assays. Both Daxx and p73/p53 co-localized in nuclear dot-like structures, which are probably nuclear PML oncogenic domains (PODs) or the nuclear domain NB10. Transient co-expression of Daxx resulted in strong inhibition of p73- and p53-mediated transcriptional activation of the synthetic p53-responsive and p21WAF1 promoters. Consequently, Gal4-Daxx repressed basal transcription in a dose-dependent manner. Treatment with trichostatin A, which is an inhibitor of histone deacetylase, or PML over-expression relieved Daxx-mediated transcriptional repression of p53. The mechanism underlying PML-mediated derepression appears to be competitive binding between Daxx, p53 and PML. Taken together, these findings delineate a transcriptional regulatory network that is modulated by differential Daxx-p53-PML interactions in the nuclear PODs. Therefore, Daxx is implicated in the regulation of the cell cycle and apoptosis through transcriptional regulation of p53 and possibly its family members.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Functional dissection of the transactivation domain of interferon regulatory factor-1.

Interferon regulatory factor-1 (IRF-1), a putative tumor suppressor protein, is a transcriptional mediator of interferon-responsive signaling pathways that are involved in antiviral defense, apoptosis, immune response, and cell growth regulation. To delineate the IRF-1 domain responsible for transactivation, we performed a detailed deletion analysis of IRF-1. We found that the amino acid segment 217-260 was necessary and sufficient for transactivation. The structure of this region was predicted to be loop-helix-loop-sheet using the program PHD. Further studies indicated that casein kinase II and protein kinase C sites on each of the two loops are not important for transactivation, and a region containing amino acids 233-255 comprises the core activation domain. To verify the physiological role of segment 233-255, we constructed an IRF-1 deletion mutant lacking these amino acids and examined it using IRF-1 transactivation assay, fluorescence-activated cell sorting, and in situ beta-galactosidase staining techniques. From the results of these studies, we conclude that the amino acid segment 233-255 of IRF-1 comprises the core activation domain required for the physiological functions of IRF-1.

3T3 Cells↗

PubMed2003

cDNA microarray gene expression profiling of hydroxyurea, paclitaxel, and p-anisidine, genotoxic compounds with differing tumorigenicity results.

The potential application of toxicogenomics to predictive toxicology has been discussed widely, but the utility of the approach remains largely unproven. Using cDNA microarrays, we compared the gene expression profiles produced in mouse lymphoma cells by three genotoxic compounds, hydroxyurea (a carcinogen), p-anisidine (a noncarcinogen), and paclitaxel (carcinogenicity unknown). To minimize the effect of biological variability and technological limitations, quadruplicate observations were made for each compound and a subset of genes yielding reproducible induction/repression was selected for comparison. A method was applied to attach normalized expression data to genes with a low false-discovery rate (<0.1) to yield more confidence regarding differential expression. This analysis identified genotoxicity-specific gene expression. Seven genes were consistently upregulated and 12 downregulated more than 2-fold by the three genotoxic compounds. Using additional genes, the expression pattern induced by the genotoxic noncarcinogen, p-anisidine, was readily distinguished from that associated with the genotoxic carcinogen, hydroxyurea. Comparison of paclitaxel-induced expression data to data for p-anisidine and hydroxyurea suggested that paclitaxel's profile is more similar to the genotoxic noncarcinogen. With further supporting evidence it may be possible to perform large-scale monitoring of gene expression during drug and chemical development that can provide an early warning of potential toxicological responses.

Aniline Compounds↗

PubMed2003

Potent cytotoxic effects of novel retinamide derivatives in ovarian cancer cells.

4-(N-Hydroxyphenyl)retinamide (also known as 4-HPR or fenretinide), a synthetic amide of all-trans retinoic acid (RA), has been implicated as a promising anticancer agent associated with reducing the toxicity related to RA. However, the low plasma levels of 4-HPR in patients limited clinical trials, leading to a search for derivatives with better efficacy. In this study, we synthesized a series of 4-HPR derivatives in good yields by introducing acetate (compound 1). propionate (2). pyruvate (3). butyrate (4). or stearate (5). to the 4-hydroxylphenyl moiety of 4-HPR. In our initial proliferation assays, we identified compound 3 as the most cytotoxic of the series against four ovarian cancer cell lines (OVCAR-3, PA-1, 2774, and SKOV-3). Dose-response curves yielded IC(50) values of 3.75-7.75 microM for AtRA, 2.80-5.50 microM for 9-cis RA, 0.65-4.05 microM for 4-HPR, and 0.25-0.75 microM for compound 3, depending on the cell type treated. Nuclear staining with 4',6-diamidino-2-phenylindole (DAPI) and DNA fragmentation assays clearly indicated that the antiproliferative effect of compound 3 was mediated by apoptosis. In contrast to natural retinoids, both 4-HPR and compound 3 activated two (RARbeta and RARgamma) of the three retinoic acid receptor (RAR) subtypes tested, but did not activate any of the three retinoid X receptors (RXRs), as determined by transcription assays in OVCAR-3 cells. However, like natural retinoids, 4-HPR and compound 3 actively suppressed c-Jun transcriptional activity. Thus, compound 3 not only showed more potent antiproliferative activity than any other retinoid derivatives tested, but also effectively inhibited the c-Jun activity that has been implicated in tumor promotion and invasion. These results, together with compound 3's selectivity for RAR subtypes, suggest that compound 3 could be an effective anticancer drug for ovarian cancer, with less toxicity than RA.

Cell Count↗

PubMed2003

[Factors influencing care dependency in patients with dementia].

PURPOSE: The purpose of this study was to explore factors that influence care dependency of institutionalized patients with dementia. METHOD: This study utilized descriptive correlational design. The convenience sample was composed of 110 residents with dementia of two long-term care facilities in Korea. Stepwise multiple regression was used to identify significant factors influencing care dependency in patients with dementia. Care dependency was measured using the Care Dependency Scale, Korean version(CDS-K). Cognition was measured by the MMSE-K. Functional disability was measured by the PULSES Profile. Behavioral dysfunction was measured by the modified E-BEHAVE AD. RESULT: Care dependency was significantly influenced by cognition, functional disability, behavioral dysfunction, and duration of dementia. This regression model explained 61% of the variances in care dependency. Cognition explained 37% of the variances, and functional disability explained 21% of the variances. CONCLUSION: Results of this study suggest that professional caregivers intervene more effectively in caring for their patients with dementia by recognizing the patients cognitive, functional, behavioral disability, and its periodic change. Individually, remaining abilities-focused intervention should be applied to enhance patient to be dependent and to prevent unnecessary independency.

English Abstract↗

PubMed2002

Down-regulation of human papillomavirus E6/E7 oncogene by arsenic trioxide in cervical carcinoma cells.

Arsenic trioxide (As2O3) has been implicated as a promising anticancer agent for treatment of many cancers including acute promylocytic leukemia. However, the molecular mechanisms are not yet fully defined in solid tumor cells, especially cervical cancer cells carrying human papillomavirus (HPV) genome. To analyze detailed mechanisms in vitro, we treated As2O3 to transformed HeLa cells, a well-studied cervical cancer cell line carrying HPV-18 sequence, and investigated its antiproliferative, antiviral and antimetastatic effects. As2O3 reduced survival and growth of HeLa cells in a dose- and time-dependent manner. Several indicatives of apoptosis were demonstrated by DNA fragmentation assay, DAPI nuclear staining and FACS analysis, respectively. Protein levels of p53 and cleavage of poly(ADP)-ribose polymerase were increased in a dose-dependent manner following treatment of As2O3. In parallel, semi-quantitative reverse transcription-polymerase chain reaction showed that the treatment inhibited HPV-18 E6/E7 viral gene expression in HeLa cells. Using transient transfection and CAT ELISA, we also found that AP-1 sites, located proximal to HPV-18 upstream regulatory region (URR) promoter, could be the major target sites for As2O3. Furthermore, As2O3-treated HeLa cells showed lesser capacity of invasion than those of untreated cells by in vitro invasion assay. Taken together, we proposed that antiviral effect, i.e. down-regulation of HPV E6/E7 oncogenes through targeting for AP-1 sites located in HPV URR might be associated with antiproliferative effect, i.e. induction of apoptosis as be resulted from the accumulation of p53, and that antimetastatic effect could be due to the targeted inactivation of AP-1, a transcription factor required for the expression of MMP-1 and -3. Therefore, our finding may provide a logical basis for the development of a new agent treating HPV-associated cervical neoplasia.

Apoptosis↗

PubMed2002

Abrogation of IRF-1 response by high-risk HPV E7 protein in vivo.

We have previously reported that human papillomavirus (HPV) E7 interacts with IRF-1, a key regulator of cellular immune response, and abrogates its transactivation function at the molecular level in vitro. To confirm our previous data, we investigated in vivo the E7-mediated down-regulation of IRF-1 using HPV E7-inducible cells and transgenic mice expressing HPV-18 E6/E7. When E7 was induced in the absence of tetracycline, the expression of target genes of IRF-1 (TAP-1, IFN-beta, MCP-1 that are important for cellular immunity) was clearly reduced as determined by RT-PCR. In addition, the IRF-1 activity was down-regulated in E7-expressing cells into which IFN-beta-CAT reporter plasmid was transfected. To further investigate the E7-mediated immune regulation in vivo, we constructed transgenic mice expressing E6 and E7 genes of HPV-18 under the control of HPV-18 promoter (URR). From several rounds of breeding, we obtained from a transgenic line that developed a cervical dysplasia and expressed E6/E7 as determined by histological examination and RT-PCR, respectively. Subsequent RT-PCR analysis indicated that TAP-1, IFN-beta, and MCP-1 genes were less expressed in a cervical tissue derived from transgenic mouse, when compared with a cervix derived from normal mouse. From these results, we conclude that the E7 transgene expression inactivates the transactivation function of IRF-1 in vivo, which might be important for the elucidation of the E7-mediated immune evading mechanism that is frequently found in cervical cancer.

3T3 Cells↗

PubMed2002

Identification and characterization of HIPK2 interacting with p73 and modulating functions of the p53 family in vivo.

To study the biological role of p73 alpha, a member of the p53 tumor suppressor family, we performed a yeast two-hybrid screen of a human cDNA library. Using a p73 alpha fragment consisting of amino acids 49-636 as bait, we found that p73 alpha is functionally associated with the human homologue of mouse and hamster homeodomain-interacting protein kinase 2 (HIPK2). The hamster homologue, also known as haHIPK2 or PKM, was used for further characterization of interactions between HIPK2 and members of the p53 protein family. Systematic yeast two-hybrid assays indicated a physical interaction between the oligomerization domains of p73 alpha and p53 (amino acid regions 345-380 and 319-360, respectively) and amino acid region 812-907 of haHIPK2. This region of haHIPK2 includes a PEST sequence, an Ubc9-binding domain, and a partial speckle retention sequence and is identical to amino acid residues 846-941 of human HIPK2 (hHIPK2). The interaction was confirmed by glutathione S-transferase pull-down assays in vitro and immunoprecipitation assays in vivo. HIPK2 colocalized with p73 and p53 in nuclear bodies, as shown by confocal microscopy. Overexpression of HIPK2 stabilized the p53 protein and greatly increased the p73- and p53-induced transcriptional repression of multidrug-resistant and collagenase promoters in Saos2 cells but had little effect on the p73- or p53-mediated transcriptional activation of synthetic p53-responsive and p21WAF1 promoters. Stable expression of HIPK2 in U2OS cells enhanced the cisplatin response of sub-G(1) and G(2)/M populations, and it also increased the apoptotic response to cisplatin and adriamycin as demonstrated by fluorescence-activated cell sorter and 4',6-diamidino-2-phenylindole-staining analyses. HIPK2 potentiated the inhibition of colony formation by p73 and p53. These results suggest that physical interactions between HIPK2 and members of the p53 family may determine the roles of these proteins in cell cycle regulation and apoptosis.

Carrier Proteins↗

PubMed2002

Interferon regulatory factor-1 mediates interferon-gamma-induced apoptosis in ovarian carcinoma cells.

Interferon-gamma (IFN-gamma), as one of interferon family that regulates antiviral, antiproliferative, and immunomodulatory responses, has been implicated for the growth regulation of ovarian cancer cells. However, the molecular mechanisms are not yet fully defined. To analyze detailed mechanisms, the ovarian cancer cell lines (2774, PA-1, OVCAR-3, and SKOV-3) were treated with IFN-gamma. The growth of 2774 was most effectively suppressed than that of other cells in both time-course and dose-dependent experiments. The order of sensitivity in other cells was PA-1 >> OVCAR-3 > SKOV-3 (not responded at all). The DNA fragmentation and DAPI staining assays suggested that the IFN-gamma-mediated cytotoxicity could be triggered by apoptosis. The treatment induced IFN regulatory factor-1 (IRF-1) in two IFN-gamma-sensitive cells (2774, PA-1), whereas IRF-1 was not induced in two IFN-gamma-resistant cells (OVCAR-3, SKOV-3). The levels of p53 and p21WAF1 were not strikingly changed in all four cells. Interestingly, the expression of interleukin-converting enzyme (ICE, or caspase-1) was increased by the treatment in a kinetically consistent manner to the induction of IRF-1. However, CD95 (Fas/APO-1) was not changed. Apoptosis was greatly induced, when IRF-1 was transiently expressed in PA-1 without the treatment of IFN-gamma. However, it was repressed when IRF-1 together with IRF-2, an antagonist of IRF-1, were coexpressed. In addition, the effect of IFN-gamma was reduced in the 2774 and PA-1 cells stably expressing either IRF-1 antisense or IRF-2 sense, as shown by the cytotoxicity and FACS analysis. Furthermore, the IFN-gamma-induced apoptosis was greatly reduced, when inhibitors of ICE were treated into PA-1 cells. Taken together, these results suggest that IRF-1 directly mediates the IFN-gamma-induced apoptosis via the activation of caspase-1 gene expression in IFN-gamma-sensitive ovarian cancer cells.

Apoptosis↗

PubMed2002

Inhibition of oocyte development in Japanese medaka (Oryzias latipes) exposed to di-2-ethylhexyl phthalate.

Di-2-ethylhexyl phthalate (DEHP) is a widely used plasticizer known to be a suspected endocrine disrupter, but its precise effects on aquatic organisms are not yet known. When Japanese medaka (Oryzias latipes) were exposed from the time of hatching to 3 months of age to an aqueous DEHP solution at nominal concentrations of 1, 10, and 50 microg/l, DEHP-treated female fish showed distinct reproductive effects as follows. First, blood vitellogenin levels in all treated test subjects markedly decreased. Second, Gonado Somatic Index (GSI) decreased to 33% and 38% of the control GSI in 10 microg/l and 50 microg/l treated female fish, respectively. Third, 54% of female fish in the control treatment had completely matured oocytes in their ovaries, but only 37%, 0% and 22% of female fish matured to the last stage in the 1, 10 and 50 microg/l treated test subjects, respectively. Unlike female fish, no change or adverse effects were observed in the male fish. In summary, DEHP hinders the development of reproductive organs in the female Japanese medaka. In this work, the possibility o f anti-estrogenic activity of DEHP is proposed as the cause.

Animals↗

PubMed2002

A Korean family with Arg1448Cys mutation of SCN4A channel causing paramyotonia congenita: electrophysiologic, histopathologic, and molecular genetic studies.

A family with paramyotonia congenita (PC) is presented. At least 10 family members were affected in an autosomal dominant inheritance pattern. The proband had cold-sensitive muscle stiffness, paradoxical myotonia, and intermittent muscle weakness since childhood. The serum level of creatine kinase was mildly elevated and short exercise test with cooling revealed a drastic reduction of compound muscle action potentials with repetitive discharges. Muscle biopsy revealed marked variation in the fiber size and increased internal nuclei. The molecular biological study revealed a common missense mutation (Arg1448Cys) at the voltage-gated sodium channel gene (SCN4A). The repetitive CMAP discharges during short exercise test with cooling observed in the proband has not been reported previously. This observation needs to be confirmed among PC patients with different mutations. This is the first report on a PC family confirmed by the molecular biological technique in Korea.

Adult↗