• Journal of Life Science
• /
• v.17 no.4 s.84
• /
• pp.482-492
• /
• 2007

Infection with Shiga-like toxin (SLT)-producing Escherichia coli causes a spectrum of illnesses with high morbidity and mortality. Host mediators play an important role in the pathogenesis of SLT-I toxicity. We here investigated the effect of SLT-I on tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ production, effect of $TNF-{\alpha}$ on glycolipid globotriaosyleramide (Gb3) expression, and relationship between Gb3 level and differential susceptibility of cells to SLT-I. In this study, we observed that detectable levels of $TNF-{\alpha}$ are produced 6 hrs after induction and continued to increase during 48 hrs by SLT-I. It was also found that Vero cells and dendritic cells expressed high levels of Gb3, 83% and 68%, respectively, and that macrophages had a low level of Gb3 (29%) and showed refractory to cytotoxicity against SLT-I. Vero cells and dendritic cells expressing high levels of Gb3 were highly susceptible to SLT-I. furthermore, macrophages showed a resistance to SLT-I cytotoxicity, despite the fact that Gb3 expression was enhanced. These results suggest that the expression of Gb3 is necessary, but not sufficient to confer sensitivity of macrophages to SLT-I and further underpin the important role of SLT-I and its receptor, Gb3, in the pathogenesis of E. coli O157 infection.

• Journal of Life Science
• /
• v.19 no.12
• /
• pp.1690-1697
• /
• 2009

CD11c and costimulatory molecules such as CD80 and CD86 express mainly in dendritic cells (DCs). In this study, we investigated the biologic effects of recombinant Fms-like tyrosine kinase-3 (Flt-3) ligand on the expression of DC surface markers, including CD11c in leukemia cell lines, such as KG-1, HL-60, NB4, and THP-1 cells. The expression of the Flt-3 receptor was found in NB4 and HL-60 cells, as well as KG-1 cells, but not in THP-1 cells. When KG-1 cells were cultured in a medium containing Flt-3 ligand or granulocyte macrophage-colony stimulating factor (GM-CSF) plus tumor necrosis factor (TNF)-$\alpha$, cell proliferation was inhibited and the expression levels of CD11c, major histocompatibility complex (MHC)-I, and MHC-II were increased in the cells. Flt-3 ligand also increased the expression level of CD11c on HL-60 and NB4 cells, but not on THP-1 cells. In comparison with CD11c expression, the expression level of CD11b on KG-1 cells, but not on NB4 and HL-60 cells, was slightly increased by Flt-3 ligand. Flt-3 ligand induced phosphorylation of extracellular signal-regulated kinase-1/2 (ERK-1/2) and p38-mitogen-activated protein kinase (p38-MAPK) in KG-1 cells, and the up-regulation of CD11c expression by Flt-3 ligand in the cells was abrogated by PD98059, an inhibitor of MEK. The results suggest that Flt-3 ligand up-regulates DC surface markers on $CD34^+$ myelomonocytic KG-1 cells, as well as promyelocytic leukemia cells, and that the differentiation of the leukemia cells into DC-like cells by Flt-3 ligand is mediated by ERK-1/2 activity.

• Toxicological Research
• /
• v.8 no.2
• /
• pp.343-357
• /
• 1992

Tumor necrosis factor-${\alpha}$(TNF), a polypeptide hormone secreted primarily by activated macrophages, was originally identified on the basis of its ability to cause hemorrhagic necrosis and tumor regression in vivo. Subsequently, TNF has been shown to be an important component of the host responses to infection and cancer and may mediate the wasting syndrome known as cachexia. These systemic actions of TNF are reflected in its diverse effects on target cells in vitro. TNF initiates its diverse cellular actions by binding to specific cell surface receptors. Although TNF receptors have been identified on most of animal cells, regulation of these receptors and the mechanisms which transduce TNF receptor binding into cellular responses are not well understood. Therefore, in the present study, the mechanisms how TNF receptors are being regulated and how TNF receptor binding is being transduced into cellular responses were investigated in rat liver plasma membranes (PM) and ME-180 human cervical carcinoma cell lines. $^{125}I$-TNF bound to high ($K_d=1.51{\pm}0.35nM$)affinity receptors in rat liver PM. Solubilization of PM with 1% Triton X-100 increased both high affinity (from $0.33{\pm}0.04\;to\;1.67{\pm}0.05$ pmoles/mg protein) and low affinity (from $1.92{\pm}0.16\;to\;7.57{\pm}0.50$ pmoles/mg protein) TNF binding without affecting the affinities for TNF, suggesting the presence of a large latent pool of TNF receptors. Affinity labeling of receptors whether from PM or solubilized PM resulted in cross-linking of $^{125}I$-TNF into $M_r$ 130 kDa, 90 kDa and 66kDa complexes. Thus, the properties of the latent TNF receptors were similar to those initially accessible to TNF. To determine if exposure of latent receptors is regulated by TNF, $^{125}I$-TNF binding to control and TNF-pretreated membranes were assayed. Specific binding was increased by pretreatment with TNF (P<0.05), demonstrating that hepatic PM contains latent TNF receptors whose exposure is promoted by TNF. Homologous up-regulation of TNF receptors may, in part, be responsible for sustained hepatic responsiveness during chronic exposure to TNF. As a next step, the post-receptor events induced by TNF were examined. Although the signal transduction pathways for TNF have not been delineated clearly, the actions of many other hormones are mediated by the reversible phosphorylation of specific enzymes or target proteins. The present study demonstrated that TNF induces phosphorylation of 28 kDa protein (p28). Two dimensional soidum dodecyl sulfate-polyacrylamide gel electrophoresis(SDS-PAGE) resolved the 28kDa phosphoprotein into two isoforms having pIs of 6.2 and 6.1. The pIs and relative molecular weight of p28 were consistent with those of a previously characterized mRNA cap binding protein. mRNA cap binding proteins are a class of translation initiation factors that recognize the 7-methylguanosine cap structure found on the 5' end of eukaryotic mRNAs. In vitro, these proteins are defined by their specific elution from affinity columns composed of 7-methylguanosine 5'-triphosphate($m^7$GTP)-Sepharose. Affinity purification of mRNA cap binding proteins from control and TNF treated ME-180 cells proved that TNF rapidly stimulates phosphorylation of an mRNA cap binding protein. Phosphorylation occurred in several cell types that are important in vitro models of TNF action. The mRNA cap binding protein phosphorylated in response to TNF treatment was purifice, sequenced, and identified as the proto-oncogene product eukaryotic initiation factor-4E(eIF-4E). These data show that phosphorylation of a key component of the cellular translational machinery is a common early event in the diverse cellular actions of TNF.

• Journal of Chest Surgery
• /
• v.30 no.8
• /
• pp.780-785
• /
• 1997

Mediastinal tumor had been fascinated by its location on heart, great vessels, esophagus, and nervous tissue, its convenience of surgical treatment and superiority of its operative result. Between January 1989 and June 1995, eighty-seven patients with mediastinal tumor which were treated surgically in the Department of Thoracic and Cardiovascular Surgery, Asan Medical Center, School of Medicine, University of Ulsan. To provide the appropriate surgical management of mediastinal tumor, the demographic data, diagnostic evaluation, clinical presentation, location, size, operative finding and histopathologic distribution were reviewed and we analyzed relativity between invasiveness in chest computed tomographic finding or invasiveness on operative finding and histopathologic invasiveness. The anterosuperior mediastinum was the most commonly involved site of a mediastinal tumor(57%), followed by the posterior mediastinum(35%) and middle mediastinum(8%). The most frequently encountered tumors were thymic neoplasia(31%), followed by primary cyst(22%), neurogenic tumor(22%) and teratoma(10%) in decreasing order of frequency. Histopathologically invasive tumors were present in 17 patients(20%) and its site included anterosuperior mediastinum(16%) and posterior mediastinum(4%). All patients in this study underwent chest CT. In chest CT's finding, 15 patients(17%) showed invasiveness. A total excision of the tumor was performed 80 patients(92%), subtotal excision 6 patients(7%) and biopsy only 1 patient(2%). In operative finding, 14 patients(16%) were suspected invasiveness. The mean size of the tumor was 6.0$\pm$ 3.2cm. In anterosuperior mediastinum, the mean size was 6.2$\pm$3.1cm, in middle mediastinum, it was 3.9$\pm$1.1cm, in posterior mediastinum, it was 5.8$\pm$2.6cm. In malignant tumors, the mean size was 7.3$\pm$4.6cm, in benign tumor, it was 5.5$\pm$2.6cm(P<0.05). Relativity between histopathological invasiveness(17 patients) and invasiveness in chest CT's finding(15 patients) included sensitivity 35%, specificity 87% and predictability 35%, relativity between histopathological invasiveness(17 patients) and invasiveness on operative finding included sensitivity 52%, specificity 93% and predictability 64%. In conclusion, since it was proved that the compatibility of preoperative chest CT findings or operative findings and histopathological invasiveness is quite low, it is considered that wide excision of the mediastinal tumor except cystic lesion including adjacent tissues would yield better postoperative results.

• Journal of Chest Surgery
• /
• v.36 no.11
• /
• pp.820-827
• /
• 2003

Background: Mitral valve repair rather than replacement for mitral regurgitation (MR) offers a number of well-accepted benefits. However, the surgical results of repair for mitral valve endocarditis remain largely unknown. Material and Method: Fourteen patients who underwent mitral valve repair for MR caused by mitral valve endocarditis from April 1995 through October 2001 were reviewed retrospectively. There were 9 male patients and mean age was 32$\pm$10 years. Four patients had previous embolism and 2 had active infections. The grade of MR were III in 6 patients and IV in 8. Operatively, mitral annuloplasty was performed in 12 patients and various valvuloplasty techniques were applied in all patients. One patient had immediate valve replacement due to residual MR after weaning of cardiopulmonary bypass. Result: There was no early operative death. Early postoperative transthoracic echocardiography revealed no or grade I of MR and no or mild mitral stenosis in 13 patients. After the mean follow-up of 36 months, there was no late death, and no or grade I of MR in 11 patients (84.6%) and no or mild mitral stenosis in 12 patients (92.3%). Reoperation required in one patient (7.1%). The cumulative freedom from recurrent MR and valve-related reoperation at 5 years were 91$\pm$9% and 75$\pm$22%, respectively. Conclusion: This study suggests that mitral valve repair for mitral regurgitation caused by endocarditis offers good early and intermediate survival and functional improvement without reinfection, and it is an attractive alternative to valve replacement in selective patients with bacterial endocariditis.

• Neonatal Medicine
• /
• v.17 no.1
• /
• pp.21-33
• /
• 2010

Purpose : The increased survival of preterm infants in the neonatal intensive care unit recently has resulted in an increased frequency of bronchopulmonary dysplasia (BPD), especially with atypical forms. However, there have been few studies compairing classic and atypical BPD. The aim of this study was to investigate the differences between these two types of BPD. Methods : Infants with a gestational age less than 32 weeks born at the Seoul National University Hospital and Bundang Seoul National University Hospital from May 2004 to April 2007 were included. The data were categorized in 2 groups, classic and atypical BPD. We determined the incidence of BPD, and compared perinatal factors and postnatal managements between two groups. Results : Among 260 study subjects, 141 (54.2%) infants had BPD. Classic BPD infants were 64 and atypical BPD infants were 77. Comparison of differences between 2 groups, classic BPD infants were associated with respiratory distress syndrome, patent ductus arteriosus, intrauterine growth restriction, more high-frequency ventilator (HFV) use, low 1 and 5 minute Apgar scores. Atypical BPD infants were associated with antenatal steroid use, maternal premature rupture of membrane and chorioamnionitis (CAM). In multivariate analysis, more HFV use was associated with classic BPD. Antenatal steroid use, clinical CAM and histological CAM were associated with atypical BPD. Conclusion : The results of this study showed that antenatal factors (antenatal steroid use, clinical CAM, histological CAM) were associated with atypical BPD and postnatal factors (HFV used more) were associated with classic BPD. Further studies are needed for prevention and treatment of BPD.

• Journal of Pharmaceutical Investigation
• /
• v.31 no.4
• /
• pp.289-295
• /
• 2001

Carvedilol is an antihypertensive and antianginal compound that combines nonselective beta-adrenoceptor blocking and vasodilation properties and is devoid of intrinsic sympathomimetic activity. The purpose of the present study was to evaluate the bioequivalence of two carvedilol tablets, $Dilatrend^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Carvelol^{TM}$ (Dae Won Pharmaceutical Co., Ltd.), according to the prior and revised guidelines of Korea Food and Drug Administration (KFDA). The carvedilol release from the two carvedilol tablets in vitro was tested using KP VII Apparatus II method with various different kinds of dissolution media (pH 1.2, 4.0, 6.8 buffer solution, water and blend of PSB80 into water). Eighteen normal male volunteers, $24.22{\pm}1.86$ years in age and $64.81{\pm}4.56\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 25 mg of carvedilol was orally administered, blood was taken at predetermined time intervals and the concentrations of carvedilol in serum were determined using HPLC method with fluorescence detector. The dissolution profiles of two carvedilol tablets were very similar at all dissolution media. Besides, the pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters using non-transformed and logarithmically transformed $AUC_t$ and $C_{max}$. The results showed that the differences in $AUC_t$, $C_{max}$ and $T_{max}$ between two tablets based on the $Dilatrend^{TM}$ were 2.23%, -2.00% and 0.00%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.05$ and $1-{\beta}=0.8$ were less than 20% (e.g., 13.55% and 17.61% for $AUC_t$ and $C_{max}$, respectively). The powers $(l-{\beta})$ at ${\alpha}=0.05$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 98.08% and 88.81%, respectively. The 90% confidence intervals were within ${\pm}20%$ (e.g., $-5.69{\sim}10.16$ and $-12.30{\sim}8.30$ for $AUC_t$ and $C_{max}$, respectively). There were no sequence effect between two tablets in logarithmically transformed $AUC_t$ and $C_{max}$. The 90% confidence intervals using logarithmically transformed were within the acceptance range of log(0.8) to log(1.25) (e.g., $0.95{\sim}1.11$ and $0.89{\sim}1.09$ for $AUC_t$ and $C_{max}$, respectively). Two parameters met the criteria of prior and revised KFDA guideline for bioequivalence, indicating that $Carvelol^{TM}$ tablet is bioequivalent to $Dilatrend^{TM}$ tablet.

• Journal of Hospice and Palliative Care
• /
• v.3 no.1
• /
• pp.39-48
• /
• 2000

Purpose : The purpose of the study is to disclose the spiritual needs of hospice patients. Method : The questionaire survey was carried out on 49 hospice patients and 40 caregivers who were in the 9 hospice institutions from lune to August in 1999. Results : In the patients, mean scores of the spiritual needs were significantly higher in the group with stomach cancer, college education, christians, $8{\sim}14$ days of hospice care and the group thinking that religion was important, and in the caregivers in the group of religions besides christianity and lives under $3{\sim}5$ years of medical treatment. In the total average of the spiritual needs, the patients's average was significantly lower than the caregiver's. Among the different categories, the patient's needs were highest in the area of meaning of life and the hope, the caregiver's needs in the love and the concern. However, both groups were low in the religion area. In the items of the love and the concern, the patient was highly responding to the 'wanting someone to give warm concern in conversation' and the caregiver was highly responding to the 'giving a warm response to questions on the sad and hard time'. And also, the patient was lowly responding to the 'wanting more concerns to him than other patients', and the caregiver was low responding to the 'patients wanting warm response in conversation'. In the categories of religious area both group were highly responding to the 'wanting to be helped to relax out of all'. And they gave lowest response to the 'wanting to introduce a book to know God'. In the area of meaning of life and hope, the both groups gave highest response to the 'wanting to be guided to have the hope' and lowest to the 'wanting to have opportunity to reconcile the person with bad relationship'. Conclusion : Summing up the above results, personal in-depth conversation is necessary to understand more deeply the spiritual needs of hospice patient. Moreover the hospice team needs to have more systematic approach to find out the spiritual needs of hospice patients.

• Journal of Hospice and Palliative Care
• /
• v.7 no.2
• /
• pp.214-220
• /
• 2004

Purpose: As for the malignant bowel obstruction of terminal cancer patient, a prognosis is relatively bad. Physicians consider palliative procedures or surgery for the quality of life, but sometimes it is hard to decide. After diagnosis of a malignant bowel obstruction in terminal cancer patients, we investigated the clinical characteristics, the prognostic factors and the survival of patients with palliative procedures or surgery. Methods: we retrospectively reviewed the medical records in 40 malignant bowel obstruction patients who had been diagnosed as terminal cancer from May in 2002 to May in 2004. Results: There were 21 males (53%) and 19 females (47%), and median age of patients was $64.1{\pm}1.58$ years. The most common cause of malignant bowel obstruction was colorectal cancer (18 patients, 45%), followed by stomach cancer (11, 28%), pancreatic cancer (4, 10%), others (7, 19%). Metastases were carcinomatosis peritonei (14 patients, 35%), liver (13, 33%). During a bowel obstruction, symptoms were vomiting (15 patients, 38%), abdominal pain (10, 25%), constipation (6, 15%), abdominal distension (5, 13%). Performance status (ECOG) was 2 score (16 patients, 40%), 3 score (20, 50%), 4 score (4, 10%). Palliative procedure group were 30 patients, the others 10. Median survival in palliative procedure group was 142 days, that of no palliation group 30. Median survival time of palliative procedure group from palliative procedures or surgery were significantly higher than that of no palliation group from diagnosis of malignant bowel obstruction. Prognostic factors of palliative procedure group were PS, site of obstruction and primary cancer. Median survival in PS 2, lower GI obstruction and colorectal cancer was higher than PS 3, upper GI obstruction and others, respectively. Conclusion: we recommend aggressively palliative procedures or surgery in malignant bowel obstruction patients diagnosed with terminal cancer if palliative procedures or surgery could be performed effectively.

• Tuberculosis and Respiratory Diseases
• /
• v.53 no.3
• /
• pp.265-274
• /
• 2002

Background : Tumor associated antigens, which are produced specifically by tumor cells, are promising targets for the early diagnosis and immunotherapy. Among the tumor associated antigens, MAGE (a melanoma antigen), BAGE, GAGE, PRAME and NY-ESO were named as cancer/testis specific antigens they are detected exclusively in the testis or cancer cells If MAGE is easily detectable in the sputum, it would become a convenient method for diagnosing lung cancer. This study was undertaken to investigate MAGE expression in the induced sputum obtained from lung cancer patients. Materials and Methods : In 14 control patients and 30 lung cancer patients, the induced sputum was collected after inhaling 3% saline(5 cc) delivered by nebulizer for approximately 5 minutes after a mouth rinse and bronchodilator inhalation. The induced sputum was placed in a conservative-mixed solution (guanidinium isothiocyanate, Triton X-100). The total cellular mRNA was extracted from the cells and RT PCR and nested PCR were run in 30 and 35 cycles respectively, with two different types of primers specially designed to detect six subtypes of MAGE DNA simultaneously. Results : MAGE expression was not detected in the 14 controls, but in the 30 cancer patients, MAGE was found in 24 patients (80%, p=0.001). In the cancer patients, there were no differences in the expression level according to the tissue types (squamous cell cancer 13/17, adenocarcinoma 7/9, and small cell cancer 4/4, p-0.56). Among the 24 MAGE-positive patients, the tumor was not visible on a bronchoscopy in 11 patients (45.8%). Conclusion : A study of MAGE in induced sputum appears to be a useful and complementary method in the diagnosis of lung cancer. A further prospective study with more patients is recommended.