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Biomedical subjects

Tae Sung Kim

Publications and source records attributed to Tae Sung Kim.

At least 19 recordsLinked to original sources
PubMed2007

OECD validation of the rodent Hershberger assay using three reference chemicals; 17alpha-methyltestosterone, procymidone, and p,p'-DDE.

The rodent Hershberger assay is being validated as an in vivo test method for detecting androgenic or antiandrogenic compounds by the Organization for Economic Cooperation and Development (OECD). As part of the international validation work, we studied 17alpha-methyltestosterone for evaluating androgenic activity, and procymidone and p,p'-DDE for evaluating antiandrogenic activity. Male Sprague-Dawley rats were castrated at postnatal day 42, and only the rats that showed preputial separation were used in this study. Seven days after castration, chemicals were administered daily by gavages to groups of rats for 10 days, as recommended by OECD phase-2 protocol. Administration of 17alpha-methyltestosterone induced increases of weights of accessory sex tissues and glands in a dose-dependent manner. Administration of procymidone and p,p'-DDE produced a dose-dependent decrease of weights of accessory sex tissues and glands in the rats co-treated with testosterone propionate (0.4 mg/kg/day) subcutaneously. Our data strongly suggested that the current protocol of OECD Hershberger assay (phase-2) should be used as a reliable method for the detection of endocrine related toxicity of other chemicals.

Administration, Oral↗
PubMed2007

Enhancement of cell migration by corticotropin-releasing hormone through ERK1/2 pathway in murine melanoma cell line, B16F10.

Melanoma is a malignant skin cancer that displays a high rate of tumor cell migration and metastasis. This study examined how corticotropin-releasing hormone (CRH) affects the migration of melanoma cells in order to further understand the relationship between stress and tumor cell migration. The migration assay data showed that CRH treatment increased the level of B16F10 cell migration in a dose- and time-dependent manner. To determine whether the extracellular signal-regulated protein kinase 1/2 (ERK1/2) signaling pathway is involved in the upregulation of melanoma migration, cells were pretreated with an inhibitor of ERK1/2 (PD098059). The pretreatment of PD098059 blocked the increase in cell migration. Furthermore, CRH induced the phosphorylation of ERK1/2. The maximum activation of ERK1/2 by CRH was observed at 15 min. Taken together, these results suggest that CRH is an important mediator that regulates the migration of melanoma cells in the skin during stress through the ERK1/2 signaling pathway.

Animals↗
PubMed2006

Gestational exposure to nonylphenol causes precocious mammary gland development in female rat offspring.

This study examined whether or not exposure to 4-nonylphenol (NP) during late gestation affects reproductive and mammary development in the offspring of female rats. Time pregnant Long Evans rats were gavaged with NP (10 or 100 mg/kg), atrazine (ATR, 100 mg/kg), or corn oil on gestation days 15-19. The uterus weights of the NP (100 mg/kg/d)-exposed pups were higher than those of the controls but the weights of the other organs were unchanged. Delayed mammary gland (MG) development was detected in the ATR pups on PND 4 and persisted through to PND 66. The high dose NP pups had advanced lobular development of their MG on PND 22, while the glands from the low dose NP pups were no different morphologically from the controls. Immunohistochemical comparisons of the mammary sections from PND 41 demonstrated low levels of estrogen receptor (ER) staining in the control gland stroma and epithelium but higher levels in the tissue of the pups exposed to NP and ATR. ATR also elevated ER in the stroma surrounding the epithelial layer of the terminal end buds. The level of progesterone receptor (PR) staining was markedly lower in the epithelium of the 100 mg/kg NP glands vs. the control glands. However, PR was present at high levels in the epithelium of the 10 mg/kg NP glands and was even more prominent in the ATR-exposed ductal epithelium and fat cell nuclei. The level of prolactin staining was only elevated in glands containing lobule areas (NP-exposed) compared with the control levels. These results suggest that NP and ATR have opposite effects on the development of MG after gestational exposure. Exposure to them during the critical period of epithelial outgrowth altered the receptor levels of mammary progesterone and prolactin and might contribute to the differences in the mammary morphology at PND 41.

Animals↗
PubMed2006

Calbindin-D9k mRNA expression in the rat uterus following exposure to methoxychlor: a comparison of oral and subcutaneous exposure.

Calbindin-D(9k) (CaBP-9k) is a cytosolic calcium-binding protein that is induced by estrogenic compounds possibly through estrogen receptors. We compared CaBP-9k mRNA expression in the uterus with uterotrophic response in immature rats exposed to methoxychlor (MC), an environmental chemical with estrogenic activity. MC was orally or subcutaneously administered to 3-week-old female Sprague-Dawley rats for 3 days. The weights of the uterus and vagina significantly increased in the oral treatment group at a dose of 50, 100 and 200 mg/kg, but those of the subcutaneous (SC) treatment group only increased at 200 mg/kg. Northern blot analysis showed that CaBP-9k mRNA expression was significantly induced in a dose-dependent manner at doses of 50, 100 and 200 mg/kg/day in the oral treatment group. SC administration of MC induced significant expression at only a dose of 200 mg/kg/day; this was similar to the uterotrophic response. MC has an estrogenic effect on the uterus as shown by the increase in weight and induction of CaBP-9k mRNA expression, which were much greater following exposure via oral gavage than via the SC route. The strong correlation between the results of in vivo uterotrophic assay and CaBP-9k mRNA expression suggests that CaBP-9k mRNA expression in the rat uterus may be used as an early gene marker for detection of the estrogenic effects of putative environmental chemicals.

Administration, Oral↗
PubMed2006

Acute pneumonia and empyema caused by Mycobacterium intracellulare.

Nontuberculous mycobacterial infection is rarely accompanied by pleural involvement. We report a very rare case of M. intracellulare pulmonary disease with pleural empyema. A 56-year-old man was admitted to our hospital because of fever, purulent sputum and pleuritic chest pain. A chest radiograph and CT revealed pneumonic consolidation in the left lower lobe and loculated hydropneumothorax. The sputum smear was positive for acid fast bacilli. The aspirated pleural fluid was grossly purulent and the smear of the pleural effusion was also positive for acid fast bacilli. M. intracellulare was identified by culture and PCR from sputum and pleural fluid specimens. The patient improved with percutaneous tube drainage of the purulent effusion and antibiotic treatment including clarithromycin, rifampicin, ethambutol and streptomycin.

Acute Disease↗
PubMed2006

Bronchoalveolar lavage in fibrotic idiopathic interstitial pneumonias.

The purpose of this study was to assess the role of bronchoalveolar lavage (BAL) in differentiating usual interstitial pneumonia (UIP) from non-specific interstitial pneumonia (NSIP) and in predicting the prognosis in fibrotic idiopathic interstitial pneumonia (IIP). A retrospective review of 122 patients (age 58+/-8 years, 70 male) with UIP (n=87) and NSIP (n=35) was carried out. Prior to surgical lung biopsy, all of them underwent BAL and high-resolution-computed tomography (HRCT) of the chest. Neutrophil count in BAL fluid was higher in UIP (7.0%) than NSIP (3.0%) (P=0.027). In contrast, BAL lymphocyte count was significantly higher in NSIP (29.0%) than UIP (5.5%) (P<0.0001). In 62 patients whose HRCT findings were atypical for UIP, BAL lymphocytosis was more frequently observed in NSIP (20/33) than UIP (4/29) (P<0.001) and the absence of BAL lymphocytosis suggested a diagnosis of UIP rather than NSIP (odds ratio 12.7, P<0.001). Pathologic diagnosis of NSIP was the only independent factor predicting a longer survival of our patients (median follow-up 21 months) (hazard ratio (HR) 0.035, P=0.005). When NSIP was not included in the survival analysis, higher BAL lymphocyte count was the only independent predictor of a longer survival (HR 0.909, P=0.029). BAL is an useful non-invasive tool in fibrotic IIP, not only for excluding a variety of specific non-IIP diseases but also for narrowing the differential diagnosis and predicting the prognosis in the absence of the histopathologic diagnosis.

Bronchoalveolar Lavage↗
PubMed2006

Treatment of squamous carcinoma in mice with a vaccine enriched for cells that induce immunity to squamous carcinoma--a new vaccination strategy.

We report a new vaccination strategy for squamous cell carcinoma (SCC). The vaccine was prepared by transfer of unfractionated DNA-fragments (25 kb) from squamous carcinoma cells (KLN205, DBA/2 origin (H-2(d))) into LM mouse fibroblasts (C3H/He origin; H-2(k)), a highly immunogenic cell line. To enhance their nonspecific immunogenic properties, the fibroblasts were modified before DNA transfer to secrete IL-2 and to express additional allogeneic MHC class I determinants. As the transferred DNA integrates into the genome of the recipient cells, and is replicated as the cells divide, sufficient DNA to prepare the vaccine could be obtained from as few as 10(7) squamous carcinoma cells (4 mm tumor). Since only a small proportion of the transfected cell-population was expected to have incorporated genes specifying antigens associated with the squamous carcinoma cells (TAA), we devised a novel approach to enrich the vaccine for cells that induce immunity to the SCC. Aliquots of the transfected population were divided into 10 small pools (initial inoculums = 1 x 10(3)). We reasoned that if the starting inoculums were sufficiently small, then the distribution of highly immunogenic and weakly immunogenic cells in each pool would not be the same. Cells from individual pools were allowed to increase in number. A portion of the expanded cell populations were maintained frozen/viable for later recovery. The remaining portions were used to immunize naïve DBA/2 mice. Pools containing greater numbers of immunogenic cells were identified by 2 independent assays. Frozen aliquots of cells from the pool that stimulated immunity to the squamous carcinoma to the greatest extent were recovered and subdivided for additional rounds of immune selection. Enhanced immunity to squamous carcinoma mediated by CD8+ T cells was induced in tumor-bearing mice treated solely by immunization with the enriched cell-population.

Animals↗
PubMed2006

Enhancing effect of indirubin derivatives on 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced differentiation of HL-60 leukemia cells.

The induction of differentiation represents a new and promising approach to cancer therapy, well illustrated by the treatment of acute promyelocytic leukemia (APL) with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] or all-trans retinoic acid (ATRA). Using combinations of low, nontoxic concentrations of either 1,25-(OH)2D3 or ATRA and differentiation-enhancing chemicals, adverse effects such as hypercalcemic effects have been ameliorated, and long-term survival has been improved. Indirubin has been demonstrated to exert anti-leukemic effects in cases of chronic myelocytic leukemia. Previously, we synthesized a series of indirubin derivatives and evaluated their anti-proliferative properties against cancer cells. In this study, we determined the enhancing activities of these derivatives on 1,25-(OH)2D3- and ATRA-induced differentiation of human promyelocytic leukemia HL-60 cells. Importantly, some of these derivatives were found to synergistically enhance the differentiation of HL-60 cells in a concentration-dependent manner when coupled with low doses of either 1,25-(OH)2D3 or ATRA. The ability of indirubin derivatives to enhance the differentiation potential of 1,25-(OH)2D3 or ATRA may improve the ultimate outcomes of APL therapy.

Antibiotics, Antineoplastic↗
PubMed2006

Light regulation of asexual development in the rice blast fungus, Magnaporthe oryzae.

Light is a major environmental factor that influences many biological processes. We characterized the roles of light in asexual development (including the formation of aerial hyphae and conidiophore) in Magnaporthe oryzae, which is the causal agent of rice blast disease. Our data revealed a complex nature of light regulation in the asexual developments of M. oryzae. Asexual development of M. oryzae is suppressed by blue light in a light/dark cycling environment and asexual spore release is controlled by both blue and red light. We demonstrated that even very dim light, about 10 micromol m(-2), is sufficient to suppress spore-release behavior in M. oryzae. We also generated knockout strains of a blue light receptor, mgwc-1, the M. oryzae homolog of white collar-1 in Neurospora crassa, and demonstrated blue-light-specific regulation in the asexual development and spore release in M. oryzae. Our findings in this agriculturally important pathogen, M. oryzae, broaden our understanding of the roles of light in fungal development.

Blotting, Southern↗
PubMed2006

Combined therapy of an established, highly aggressive breast cancer in mice with paclitaxel and a unique DNA-based cell vaccine.

Here, we describe the enhanced benefits of treating a highly aggressive breast cancer in mice with a combination of paclitaxel and immunization with a unique DNA-based cell vaccine. An adenocarcinoma was isolated from a spontaneous neoplasm that arose in the mammary gland of a C3H/He mouse (H-2(k)) (SB5b cells). The vaccine was prepared by transfer of genomic DNA-fragments (25 kb) from the breast cancer cells into a mouse fibroblast cell line (LM), modified to enhance its immunogenic properties. As the transferred DNA is integrated, and replicated as the recipient cells divide, the vaccine could be prepared from relatively small numbers of cancer cells (10(7) = 4 mm tumor). SB5b cells were injected into the mammary fat pad of naïve C3H/He mice, which are highly susceptible to the growth of the cancer cells. When the tumors reached 3 mm, the mice were injected s.c. with a noncurative dose of paclitaxel. Six days later, when immune competence returned, the mice received the first of 3 weekly s.c. injections of the vaccine. The combined therapy induced robust cellular immunity to the breast cancer, mediated by CD8+ and NK/LAK cells, which resulted in prolonged survival. The immunity was specific, as immunization with a vaccine prepared by transfer of DNA from B16 melanoma cells into the fibroblasts failed to induce immunity to the breast cancer. This type of vaccine raises the possibility that an analogous strategy could be used in the treatment of breast cancer patients at an early stage of the disease.

Animals↗
PubMed2006

Pulmonary fungal infection: imaging findings in immunocompetent and immunocompromised patients.

Histoplasmosis is the most common endemic mycosis in North America, and is followed by coccidioidomycosis and blastomycosis. Although the majority of these infections in immunocompetent persons are self-limited, some patients can develop severe pneumonitis or various forms of chronic pulmonary infection. Cryptococcoci, Aspergillus, Candidas, and Mucorals are ubiquitous organisms, which may affect immunocompromised patients. Specific imaging findings can be expected, depending on the organisms involved, underlying patients' conditions (immune status), and specific situations after immune depleting procedures.

Humans↗
PubMed2006

IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway.

IL-18 is a pleiotropic cytokine that is produced by many cancer cells. A recent report suggested that IL-18 plays a key role in regulating the immune escape of melanoma and gastric cancer cells. Thrombospondin (TSP-1) is known to inhibit angiogenesis in several cancers but some studies have reported that it stimulates angiogenesis in some cancers such as gastric cancer. IL-18 and TSP-1 are related to tumor proliferation and metastasis. This study investigated the relationship between IL-18 and TSP-1 in gastric cancer. RT-PCR and ELISA showed that after the cells had been treated with IL-18, the level of TSP-1 mRNA expression and TSP-1 protein production by IL-18 increased in both a dose- and time-dependent manner. The cells were next treated with specific inhibitors in order to determine the signal pathway involved in IL-18-enhanced TSP-1 production. IL-18-enhanced TSP-1 expression was blocked by SP600125, a c-Jun N-terminal kinase (JNK) specific inhibitor. In addition, Western blot showed that IL-18 enhanced the expression of phosphorylated JNK. Overall, these results suggest that IL-18 plays a key role in TSP-1 expression involving JNK.

Cell Line, Tumor↗
PubMed2006

Chemical modification of santonin into a diacetoxy acetal form confers the ability to induce differentiation of human promyelocytic leukemia cells via the down-regulation of NF-kappaB DNA binding activity.

Many sesquiterpene lactone compounds either induce or enhance the cell differentiation of human leukemia cells. However, we reported in a previous study that santonin, a eudesmanolide sesquiterpene lactone, exerts no effects on the differentiation of leukemia cells. In this report, to evaluate the possibility of chemically modifying santonin into its derivatives with differentiation inducing activity, we synthesized a series of santonin derivatives, and determined their effects on cellular differentiation in the human promyelocytic leukemia HL-60 cell system. A diacetoxy acetal derivative of santonin (DAAS) was found to induce significant HL-60 cell differentiation in a dose-dependent manner, whereas santonin in its original form did not. The HL-60 cells were differentiated into a granulocytic lineage when exposed to DAAS. In addition, the observed induction in cell differentiation closely correlated with the levels of NF-kappaB DNA binding activity inhibited by DAAS. Both Western blot analyses and kinase inhibitor studies determined that protein kinase C, ERK, and phosphatidylinositol 3-kinase were upstream components of the DAAS-mediated inhibition of NF-kappaB binding activity in HL-60 leukemia cells. The results of this study indicate that santonin can, indeed, be chemically modified into a derivative with differentiation inducing abilities, and suggest that DAAS might prove useful in the treatment of neoplastic diseases.

Cell Differentiation↗
PubMed2006

Drug-sensitive tuberculosis, multidrug-resistant tuberculosis, and nontuberculous mycobacterial pulmonary disease in nonAIDS adults: comparisons of thin-section CT findings.

The aim of this work was to compare thin-section CT (TSCT) findings of drug-sensitive (DS) tuberculosis (TB), multidrug-resistant (MDR) TB, and nontuberculous mycobacterial (NTM) pulmonary disease in nonAIDS adults. During 2003, 216 (113 DS TB, 35 MDR TB, and 68 NTM) patients with smear-positive sputum for acid-fast bacilli (AFB), and who were subsequently confirmed to have mycobacterial pulmonary disease, underwent thoracic TSCT. The frequency of lung lesion patterns on TSCT and patients' demographic data were compared. The commonest TSCT findings were tree-in-bud opacities and nodules. On a per-person basis, significant differences were found in the frequency of multiple cavities and bronchiectasis (P < 0.001, chi-square test and multiple logistic regression analysis). Multiple cavities were more frequent in MDR TB than in the other two groups and extensive bronchiectasis in NTM disease (multiple logistic regression analysis). Patients with MDR TB were younger than those with DS TB or NTM disease (P < 0.001, multiple logistic regression analysis). Previous tuberculosis treatment history was significantly more frequent in patients with MDR TB or NTM disease (P < 0.001, chi-square test and multiple logistic regression analysis). In patients with positive sputum AFB, multiple cavities, young age, and previous tuberculosis treatment history imply MDR TB, whereas extensive bronchiectasis, old age, and previous tuberculosis treatment history NTM disease.

Adult↗
PubMed2006

Repeated 28-day oral toxicity study of vinclozolin in rats based on the draft protocol for the "Enhanced OECD Test Guideline No. 407" to detect endocrine effects.

We performed a 28-day repeated-dose toxicity study of vinclozolin, a widely used fungicide, based on the draft protocol of the "Enhanced OECD Test Guideline 407" (Enhanced TG407) to investigate whether vinclozolin has endocrine-mediated properties according to this assay. Seven-week-old SD rats were administered with vinclozolin daily by oral gavage at dose rates of 0, 3.125, 12.5, 50 and 200 mg/kg/day for at least 28 days. The vinclozolin-treated male rats showed a reduction of epididymis and accessory sex organ weights and an alteration of hormonal patterns. A slight prolongation of the estrous cycle and changes in the estrogen/testosterone ratio and luteinizing hormone level were observed in vinclozolin-treated female rats. Thyroxin concentrations were decreased and thyroid-stimulating hormone concentrations were increased in both sexes; however, there were no compound-related microscopic lesions in the thyroid gland or changes in the thyroid weight. The endocrine-related effects of vinclozolin could be detected by the parameters examined in the present study based on the OECD protocol, suggesting the Enhanced TG407 protocol should be a suitable screening test for the detection of endocrine-mediated effects of chemicals.

Administration, Oral↗
PubMed2006

Monitoring the gene expression profiles of doxorubicin-resistant acute myelocytic leukemia cells by DNA microarray analysis.

Acquired drug-resistance phenotype is a key factor in the relapse of patients suffering hematological malignancies. In order to investigate the genes involved in drug resistance, a human leukemia cell line that is resistant to doxorubicin, an anthracycline anticancer agent (AML-2/DX100), was selected and its gene expression profile was analyzed using a cDNA microarray. A number of genes were differentially expressed in the AML-2/DX100 cells, compared with the wild type (AML-2/WT). Pro-apoptotic genes such as TNFSF7 and p21 (Cip1/Waf1) were significantly down-regulated, whereas the IKBKB, PCNA, stathmin 1, MCM5, MMP-2 and MRP1 genes, which are involved in anti-apoptotic or cell cycle progression, were over-expressed. The AML-2/DX100 cells were also resistant to other anticancer drugs, including daunorubicin and camptothecin, and the expression levels of the differentially regulated genes such as STMN1, MMP-2 and CTSG, were constantly maintained. This suggests that the deregulated genes obtained from the DNA microarray analysis in a cell line model of drug resistance might contribute to the acquired drug resistance after chronic exposure.

Antibiotics, Antineoplastic↗
PubMed2006

Inhibition of interleukin-4 production in activated T cells via the downregulation of AP-1/NF-AT activation by N-lauroyl-D-erythro-sphingosine and N-lauroyl-D-erythro-C20-sphingosine.

Allergic diseases are hypersensitivity disorders that are associated with the generation of specific immunoglobulin E (IgE) in response to environmental allergens. Interleukin (IL)-4, which is primarily produced by the CD4(+) T cells, is an important stimulus for the switching of the antibody isotype to IgE in both mice and humans. In a previous study, we demonstrated that ceramide derivatives coupled with a lauroyl group exerted strong inhibitory effects on IL-4 production in T cells. In this study, we attempted to characterize the mechanisms underlying the inhibition of IL-4 production in T cells. Two ceramide derivatives, N-lauroyl-D-erythro-sphingosine and N-lauroyl-D-erythro-C(20)-sphingosine (hereafter abbreviated as LES and LECS, respectively), were shown to significantly inhibit the production of IL-4 in both primary CD4(+) T cells and EL4 T thymoma cells in a dose-dependent manner. LES and LECS also inhibited the activity of the IL-4 gene promoter in EL4 cells transiently transfected with IL-4 gene promoter constructs, but this effect was impaired in EL4 cells that had been transfected with an IL-4 promoter construct deleted of a P4 site harboring the AP-1 and NF-AT binding sites. Furthermore, LES and LECS inhibited the DNA binding activities of both AP-1 and NF-AT transcription factors. In addition, LES and LECS were demonstrated to suppress PMA-stimulated PKC activity, although they exerted no significant effects on the protein levels of the conventional PKCs. These results indicate that the ceramides, LES and LECS, may inhibit the production of IL-4 in the activated T cells, via the downregulation of AP-1/NF-AT activation and PKC activity.

Animals↗