• Journal of Life Science
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• v.23 no.10
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• pp.1230-1238
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• 2013

The regulatory effect of the tumor-suppressor protein p53 on the apoptogenic activity of $17{\alpha}$-estradiol ($17{\alpha}-E_2$) was compared between HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$) cells. When the HCT116 ($p53^{+/+}$) and HCT116 ($p53^{-/-}$) cells were treated with $2.5{\sim}10{\mu}M$ $17{\alpha}-E_2$ for 48 h or with $10{\mu}M$for various time periods, cytotoxicity and an apoptotic sub-$G_1$ peak were induced in the HCT116 ($p53^{+/+}$) cells in a dose- and time-dependent manner. However, the HCT116 ($p53^{-/-}$) cells were much less sensitive to the apoptotic effect of $17{\alpha}-E_2$. Although $17{\alpha}-E_2$ induced aberrant mitotic spindle organization and incomplete chromosome congregation at the equatorial plate, $G_2/M$ arrest was induced to a similar extent in both cell types. In addition, $17{\alpha}-E_2$-induced activation of Bak and Bax, ${\Delta}{\Psi}m$ loss, and PARP degradation were more dominant in the HCT116 ($p53^{+/+}$) than in the HCT116 ($p53^{-/-}$) cells. In accordance with enhancement of p53 phosphorylation (Ser-15) and p53 levels, p21 and Bax levels were elevated in the HCT116 ($p53^{+/+}$) cells treated with $17{\alpha}-E_2$. The HCT116 ($p53^{-/-}$) cells exhibited barely or undetectable levels of p21 and Bax, regardless of $17{\alpha}-E_2$ treatment. On the other hand, although the level of Bcl-2 was slightly lower in the HCT116 ($p53^{+/+}$) than in the HCT116 ($p53^{-/-}$) cells, it remained relatively constant after the $17{\alpha}-E_2$ treatment. Together, these results show that among the components of the $17{\alpha}-E_2$-induced apoptotic-signaling pathway, which proceeds through mitotic spindle defects causing mitotic arrest, subsequent activation of Bak and Bax and the mitochondria-dependent caspase cascade, leading to PARP degradation, $17{\alpha}-E_2$-induced activation of Bak and Bax is the upstream target of proapoptotic action of p53.

• Journal of Yeungnam Medical Science
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• v.10 no.2
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• pp.451-474
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• 1993

Lidocaline if frequently administered as a component of an anesthetic : for local or regional nerve blocks, to mitigate the autonomic response to laryngoscopy and tracheal intubation, to suppress the cough reflex, and for antiarrythmic therapy. Diazepam dectease the potential central nervous system (CNS) toxicity of local anesthetic agents but may modify the sitmulant action of lidocaine in addition to their own cardiovascular depressant. The potential cardiovascular toxicity of local anesthetics may be enhanced by the concomitant administration of diazepam. This study was designed to investigate the effects of lidocaine dose and pretreated diazepam to cardiovascular system and plasma concentration of lidocaine. Lidocaine in 100 mcg/kg/min, 200 mcg/kg/min, and 300 mcg/kg/min was given by sequential infusion to dogs anesthetized with halothane-nitrous oxide (Group I). And in group II, after diazepam pretreatment, lidocaine was infused by same way when lidocaine was administered in 100 mcg/kg/min, the low plasma levels ($3.97{\pm}0.22-4.48{\pm}0.36$ mcg/ml) caused a little reduction in cardiovascular hemodynamics. As administered in 200 mcg/kg/min, 300 mcg/kg/min, the higher plasma levels ($7.50{\pm}0.66-11.83{\pm}0.59$ mcg/ml) reduced mean arterial pressure (MAP), cardiac index (CI), stroke index (SI), left ventricular stroke work index (LVSWI), and right ventricular stroke work index (PVSWI) and increased pulmonary artery wedge pressure (PAWP), central venous pressure (CVP), systemic vascular resistance index (SVRI), but was associated with little changes of heart rate (HR), mean pulmonary artery pressure (MPAP), and pulmonary vascular resistance index (PVRI). When lidocaine with pretreated diazepam was administered in 100 mcg/kg/min, the low plasma level, the lower level than when only lidocaine administered, reduced MAP, but was not changed other cardiovascular hemodynamics. While lidocaine was infused in 200 mcg/kg/min, 300 mcg/kg/min in dogs pretreated diazepam, the higher plasma level ($7.64{\pm}0.79-13.79{\pm}0.82$ mcg/ml) was maintained and was associated with reduced CI, SI, LVSWI and incresed PAWP, CVP, SVRI but was a little changes of HR, MPAP, PVRI. After $CaCl_2$ administeration, CI, SI, SVRI, LVSWI was recovered but PAWP, CVP was rather increased than recovered. The foregoing results demonstrate that pretreated diazepam imposes no additional burden on cardiovascular system when a infusion of large dose of lidocaine is given to dogs anesthetized with halothanenitrous oxide. But caution may be advised if the addition of lidocaine is indicated in subjects who have impared autonomic nervous system and who are in hypercarbic, hypoxic, or acidotic states.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.485-496
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• 2002

Background : The NF-${\kappa}B$ transcription factors control various biological processes including the immune response, acute phase reaction and cell cycle regulation. NF-${\kappa}B$ complexes are retained in the cytoplasm in the basal state and various stimuli cause a translocation of the NF-${\kappa}B$ complexes into the nucleus where they bind to the ${\kappa}B$ elements and regulate the transcription of the target genes. Recent reports also suggest that NF-${\kappa}B$ proteins are involved in oncogenesis, tumor growth and metastasis. High expression of NF-${\kappa}B$ expression was reported in many cancer cell lines and tissues. The constitutive activation of NF-${\kappa}B$ was also reported in several cancer cell lines supporting its role in cancer development and survival. The anti-apoptotic action of NF-${\kappa}B$ is important for cancer survival. NF-${\kappa}B$ also controls the expression of several proteins that are important for cellular adhesion (ICAM-1, VCAM-1) suggesting a role in cancer metastasis. In lung cancer, high expression levels of the NF-${\kappa}B$ subunit p50 and c-Rel were reported. In fact, high expression does not mean a high activity, and the activation pattern of NF-${\kappa}B$ in lung cancer has not been reported. Materials and Methods : In this study, the NF-${\kappa}B$ nuclear binding activity in the basal and TNF-${\alpha}$ stimulated states were exmined in various lung cancer cell lines and compared with the normal bronchial epithelial cell line. Twelve lung cancer cell lines including the non-small cell and small cell lung cancer cell lines (A549, NCI-H358, NCI-H441, NCI-H552, NCI-H2009, NCI-H460, NCI-H1229, NCI-H1703, NCI-H157, NCI-H187, NCI-H417, NCI-H526) and BEAS-2B bronchial epithelial cell line were used. To evaluate the NF-${\kappa}B$ expression and DNA binding activity, western blot analysis and an electrophoretic mobility shift assay with the nuclear protein extracts. Results : The basal expressions of the p65 and p50 subunits were observed in the BEAS-2B cell line and all lung cancer cell lines except for NCI-H358 and NCI-H460. The expression levels of p65 and p50 were increased 30 minutes after stimulation with TNF-${\alpha}$ in BEAS-2B and in 10 lung cancer cell lines. In the NCI-H358 and NCI-H460 cell lines, p65 expression was not observed in the basal and stimulated states and the two p50 related protein levels were higher after stimulation with TNF-${\alpha}$ These new proteins were smaller than p50 and are thought to be variants of p50. In the basal state, NF-${\kappa}B$ was nearly activated in the BEAS-2B and all lung cancer cell lines. The DNA binding activity of the NF-${\kappa}B$ complexes was markedly higher after stimulation with TNF-${\alpha}$ In the BEAS-2B and all lung cancer cell line except for NCI-H358 and NCI-H460, the activated NF-${\kappa}B$ complex was a p65/p50 heterodimer. In the NCI-H358 and NCI-H460 lung cancer cell lines, the NF-${\kappa}B$ complex was variant of a p50/p50 homodimer. Conclusion : The NF-${\kappa}B$ activation pattern in the lung cancer cell lines and the normal bronchial epithelial cell lines was similar except for the activation of a variant of the p50/p50 homodimer in some lung cancer cell linse.

• Clinical and Experimental Pediatrics
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• v.50 no.6
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• pp.565-569
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• 2007

Purpose : With a duration of action of approximately 24 hours and peakless levels, Lantus is a more physiologic basal insulin analogue compared with NPH. The aim of this study was to compare the glycemic control of Lantus plus Humalog with that of premixed insulin in children and adolescents with type 1 diabetes mellitus. Methods : The subjects consisted of 25 patients with type 1 diabetes mellitus, aged 12-19 years, who changed their insulin regimen from premixed insulin to Lantus plus Humalog. Daily insulin doses, frequency of hypoglycemia, fasting blood glucose, C-peptide concentration and HbA1c before and 6 months after Lantus treatment were compared. 24 hour blood glucose of 11 patients among Lantus treatment group (n=25) and premixed insulin treatment group (n=10) were self-monitored and compared. Results : 6 months after Lantus treatment, the episodes of hypoglycemia were reduced by 50%(15.1 vs. 7.6 events/month), especially nocturnal hypoglycemia by 67%(6.7 vs. 2.5 events/month). HbA1c was reduced from 9.3% to 8.7% after Lantus treatment. Self-monitored blood glucose of Lantus treatment group at postbreakfast 30, 60, 90 and 120 minutes were 171.1, 169.5, 171.0 and 154.1 mg/dL respectively and lower than those of premixed insulin treatment group (259.7, 282.7, 280.0 and 250.9 mg/dL respectively). Conclusion : Compared with premixed insulin, Lantus plus Humalog is more effective in glycemic control and reduction in nocturnal hypoglycemia in children and adolescents with type 1 diabetes mellitus.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.5
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• pp.669-676
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• 2010

This study was performed to investigate the effect of Brassica rapa (BR) sprouts on weight reduction and cholesterol-lowering action in rats fed high fat diet for 4 weeks. Weight-matched male Sprague-Dawley rats were assigned to four groups according to dietary fat levels (10% or 20% of diet wt.). Experimental groups were normal diet group (N), high fat diet group (HF), high fat diet with 5% BR sprouts powder group (HF-BRL), and high fat diet with 10% BR sprouts powder group (HF-BRH). The body weight gain was increased in HF group, but gradually decreased to the corresponding level of the N group fed BR sprouts powder. The concentrations of serum LDL-cholesterol, atherogenic index and cardiac risk factor tended to decrease in the BR sprouts powder fed groups compared with the HF group. However, HDL-cholesterol concentration in serum decreased in the HF group and markedly increased in the BR sprouts powder fed groups. Concentrations of triglyceride and total cholesterol in liver were also markedly decreased in the BR sprouts powder fed groups. Triglyceride concentrations of epididymal and mesenteric adipose tissues in the BR sprouts powder fed groups were also decreased compared with the HF group. These results indicate that BR sprouts powder may reduce fat accumulation and body weight, and have cholesterol-lowering effect.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.484-491
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• 2016

The present study investigated the effect of Sinetrol-XPur (polyphenolic Citrus spp. and Paullinia cupana Kunth dry extract) and defined the action mode for cyclic adenosine monophosphate (cAMP)-dependent uncoupling protein (UCP)-2 activation. Leptin-deficient obese mice were treated with two different doses, 100 mg/kg body weight (BW) and 300 mg/kg BW of each AIN93G supplement, for 7 weeks. Treatment of obese mice with both low and high doses of Sinetrol-XPur significantly reduced body weight gain compared to control obese mice. White adipose tissue weight of mice was reduced by 30.96% in high dose-supplemented groups. Serum total cholesterol and triglyceride were reduced by a high dose of Sinetrol-XPur by 20.02% and 30.96%, respectively. Serum level of high density lipoprotein (HDL) was significantly increased by treatment with both doses, as the ratio of HDL to low density lipoprotein increased by 138.78% and 171.49%, respectively. Regarding expression of biochemical factors related to lipid metabolism, fatty acid synthase significantly decreased and UCP-2 increased upon treatment with a high dose of Sinetrol-XPur, but there was no significant difference in lipoprotein lipase and hormone-sensitive lipase. To define cellular mechanism, intracellular cAMP levels in 3T3-L1 adipocytes significantly increased in a dose-dependent manner over the range of $50{\sim}250{\mu}m/mL$. The phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine clearly blocked cAMP, suggesting that Sinetrol-XPur promotes lipolysis of adipocytes through inhibition of cAMP-dependent PDE, resulting in induction of cAMP response element binding protein and UCP-2. These results suggest that Sinetrol-XPur supplementation is a viable option for reducing body weight and fat by improving serum lipid profiles and genetic expression of lipid metabolic factors, especially activation of cAMP-dependent UCP-2.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.11
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• pp.1648-1657
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• 2014

In this study, the hepatic lipid-lowering effects and related mechanism of action of sujeonggwa were examined in hypercholesterolemia-induced apoprotein E knockout (apo E ko) mice. Sujeonggwa drink was prepared with cinnamon, ginger, and sugar by modifying the traditional recipe of sujeonggwa. Sugar was partially substituted with either stevia or short chain fructooligosaccharide (scFOS) in order to reduce the calorie content of sujeonggwa, which was measured by descriptive analysis. Apo E ko mice (n=42) were induced to have hypercholesterolemia (plasma total cholesterol concentration >1,000 mg/dL) by administration of a high cholesterol diet for 4 weeks, followed by division into six groups. Experimental groups were orally administered water as a vehicle (normal group), sugar solution (control group), commercially available 'V' sujeonggwa drink (positive control group), or three different types of sujeonggwa drinks (S-sugar, S-stevia, and S-scFOS group) for 6 weeks while high cholesterol diet was provided to all animals. Compared to the control group, concentrations of hepatic triglycerides, total cholesterol, thiobarbituric acid reactive substances, and reactive oxygen species in S-sugar, S-stevia, S-scFOS were significantly reduced (P<0.05), indicating that sujeonggwa had inhibitory effects on hepatic lipid accumulation. Protein expression levels of fatty acid synthase (FAS) and its transcription factor, sterol regulatory element-binding protein (SREBP)-1 responsible for triglyceride synthesis, as well as 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) and its transcription factor, SREBP-2 responsible for cholesterol synthesis, were also reduced in S-sugar, S-stevia, and S-scFOS groups (P<0.05). These benefits of sujeonggwa were even greater in S-stevia and S-scFOS compared to S-sugar. The beneficial effects of S-stevia on regulation of hepatic lipid metabolism were slightly greater than those of S-scFOS although the differences were not significant. In conclusion, sujeonggwa drinks, especially functional sujeonggwa drinks in which sugar was partially substituted with stevia or scFOS, inhibited hepatic lipid accumulation via suppressing FAS and HMGCR protein expression through down-regulation of SREBP-1 and 2.

• Korean Journal of Food Science and Technology
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• v.38 no.6
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• pp.730-737
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• 2006

High performance liquid chromatographic methods for the simultaneous determination of 12 biogenic amines were developed and contents of biogenic amines in 23 varieties of Korean commercial fermented food were analyzed. Dansyl derivatives of biogenic amine were very stable and had good peak resolution. Except agmatine, the recovery of biogenic amines from soybean paste with extraction of 0.1 N HC1 added biogenic amines to soybean paste was greater 85%. The calibration curve showed good linearity over a concentration range up to 50 ${\mu}g/mL$. In the determination of biogenic amine level in Korean commercial fermented foods, doenjang and chungkukjang (fermented soybean pastes), soy sauce, anchovy and pacific sand lance liquid jeotkal (fermented fish sauce products), and cabbage kimchi had high level biogenic amines. Especially, traditional doenjang had a histamine (HIS) level of 952.0 mg/kg, a tyramine (TYR) level of 1,430.7 mg/kg. Most cheese had low level of biogenic amines, but one Gouda cheese had a tyramine (TYR) level of 97.5 mg/kg. A low level of biogenic amines was detected in wines, beer, yoghurt, and sausage. Putrescine (PUT), cadaverine (CAD), tryptamine (TRY), histamine (HIS), tyramine (TYR), and 2-phenylethylamine (PHE) were mainly formed in fermented foods by the action of microorganism, so their levels were high with a range. On the other hand, spermidine (SPD), spermine(SPM), serotonin (SER), noradrenaline (NOR), and dopamine (DOP) were formed originally via biosynthesis with consequent low level.

• Journal of the Korean Society for Library and Information Science
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• v.4
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• pp.43-71
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• 1975

Operations research has developed rapidly since its origins in World War II. Practitioners of O. R. have contributed to almost every aspect of government and business. More recently, a number of operations researchers have turned their attention to library and information systems, and the author believes that significant research has resulted. It is the purpose of this essay to introduce the library audience to some of these accomplishments, to present some of the author's hypotheses on the subject of library management to which he belives O. R. has great potential, and to suggest some future research directions. Some problem areas in librianship where O. R. may play a part have been discussed and are summarized below. (1) Library location. It is usually necessary to make balance between accessibility and cost In location problems. Many mathematical methods are available for identifying the optimal locations once the balance between these two criteria has been decided. The major difficulties lie in relating cost to size and in taking future change into account when discriminating possible solutions. (2) Planning new facilities. Standard approaches to using mathematical models for simple investment decisions are well established. If the problem is one of choosing the most economical way of achieving a certain objective, one may compare th althenatives by using one of the discounted cash flow techniques. In other situations it may be necessary to use of cost-benefit approach. (3) Allocating library resources. In order to allocate the resources to best advantage the librarian needs to know how the effectiveness of the services he offers depends on the way he puts his resources. The O. R. approach to the problems is to construct a model representing effectiveness as a mathematical function of levels of different inputs(e.g., numbers of people in different jobs, acquisitions of different types, physical resources). (4) Long term planning. Resource allocation problems are generally concerned with up to one and a half years ahead. The longer term certainly offers both greater freedom of action and greater uncertainty. Thus it is difficult to generalize about long term planning problems. In other fields, however, O. R. has made a significant contribution to long range planning and it is likely to have one to make in librarianship as well. (5) Public relations. It is generally accepted that actual and potential users are too ignorant both of the range of library services provided and of how to make use of them. How should services be brought to the attention of potential users? The answer seems to lie in obtaining empirical evidence by controlled experiments in which a group of libraries participated. (6) Acquisition policy. In comparing alternative policies for acquisition of materials one needs to know the implications of each service which depends on the stock. Second is the relative importance to be ascribed to each service for each class of user. By reducing the level of the first, formal models will allow the librarian to concentrate his attention upon the value judgements which will be necessary for the second. (7) Loan policy. The approach to choosing between loan policies is much the same as the previous approach. (8) Manpower planning. For large library systems one should consider constructing models which will permit the skills necessary in the future with predictions of the skills that will be available, so as to allow informed decisions. (9) Management information system for libraries. A great deal of data can be available in libraries as a by-product of all recording activities. It is particularly tempting when procedures are computerized to make summary statistics available as a management information system. The values of information to particular decisions that may have to be taken future is best assessed in terms of a model of the relevant problem. (10) Management gaming. One of the most common uses of a management game is as a means of developing staff's to take decisions. The value of such exercises depends upon the validity of the computerized model. If the model were sufficiently simple to take the form of a mathematical equation, decision-makers would probably able to learn adequately from a graph. More complex situations require simulation models. (11) Diagnostics tools. Libraries are sufficiently complex systems that it would be useful to have available simple means of telling whether performance could be regarded as satisfactory which, if it could not, would also provide pointers to what was wrong. (12) Data banks. It would appear to be worth considering establishing a bank for certain types of data. It certain items on questionnaires were to take a standard form, a greater pool of data would de available for various analysis. (13) Effectiveness measures. The meaning of a library performance measure is not readily interpreted. Each measure must itself be assessed in relation to the corresponding measures for earlier periods of time and a standard measure that may be a corresponding measure in another library, the 'norm', the 'best practice', or user expectations.

• The Korean Journal of Pharmacology
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• v.30 no.1
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• pp.137-143
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• 1994

Enhancement or diminution of leukocyte migration to the specific site might be important factors for the development of inflammatory diseases. To investigate the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on chemotaxis of neutrophil, we obtained neutrophils by Hypaque-Ficoll step gradient centrifugation and tested the effects of seven drugs on the n-formyl-leucyl-phenylalanine (FMLP)-induced migration of neutrophil using a 48-well micro chemotaxis assembly. Oxyphenbutazone, phenylbutazone, sulindac, zomepirac, and ibuprofen suppressed the migration of neutrophil at the therapeutic concentrations, however, indomethacin showed stimulation effect. IC50s for inhibition of neutrophil migration by these drugs are less than 100uM. When drugs were preincubated with FMLP, no inhibition on migration of neutrophil was observed. These results indicated that inhibitory effects of these drugs on migration of neutrophil might be related to the receptor sites of neutrophil rather than molecular inactivation of chemoattractant (FMLP). In conclusion, we suggested that the property of inhibition effects on neutrophil migration of several NSAIDs might be another mode of pharmacological action for anti-iflammatory effect, which showed significant effects at concentrations below therapeutic levels, in addition to cyclooxygenase inhibition.