Purpose : It has been recognized that interaction of the Fas : Fas ligand plays an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas mutation in radiation-induced apoptosis in vivo. Materials and Method : Mice with mutations in Fas, $MRL/Mpj-Fas^{Ipr}$, and its normal control, MRL/Mpj, were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed and their spleens were collected at different time intervals. Tissue samples were stained with hematoxylin-eosin and the numbers of apoptotic cells were scored. Regulating molecules of apoptosis including p53, Bcl-2, Bax, $Bcl-X_L,\;and\;Bcl-X_S$ were also analyzed by Western blotting. Results : At 25 Gy irradiation, the level of apoptosis reached the peak value at 8 hr after radiation and recovered to the normal value at 24 hr after radiation in MRL/Mpj mice. In contrast, the peak apoptosis level appeared at 4 hr after radiation in $MRL/Mpj-Fas^{Ipr}$. At 8 hr after radiation, the levels of apoptosis in MRL/Mpj mice and $MRL/Mpj-Fas^{Ipr}$ mice were $52.3{\pm}7.8\%\;and\;8.0{\pm}8.6\%$, respectively (p<0.05). The expression of apoptosis regulating molecules, p53, $Bcl-X_L\;and\;Bcl-X_S$, increased in MRL/Mpj mice in response to radiation; p53 with a peak level of 3-fold at 8 h, $Bcl-X_L$ with a peak level of 3.3-fold at 12 h, and $Bcl-X_S$ with a peak level of 3-fold at 12 h after 25 Gy radiation. Bcl-2 and Bax did not show significant change in MRL/Mpj mice. However in $MRL/Mpj-Fas^{Ipr}$ mice, the expression levels of p53, Bcl-2, Bax, $BCl-X_L\;and\;BCl-X_S$ showed no significant change. Conclusion : The level of radiation-induced apoptosis was lower in Fas mutated mice, Ipr, than in control mice. This seemed to be related to the lack of radiation-induced p53 activation in the Ipr mice. This result suggests that Fas plays an important role in radiation-induced apoptosis in vivo.
Kim, Yeon-Joo;Lee, Seung-Hee;Wu, Hong-Gyun;Go, Heoun-Jeong;Jeon, Yoon-Kyung
Radiation Oncology Journal
/
v.28
no.2
/
pp.57-63
/
2010
Purpose: We performed an immunohistochemical study with pre-treatment biopsy specimens to evaluate the prognostic significance of four biomolecular markers which can be used as a predictive assay for radiotherapy (RT) treatment of nasopharyngeal carcinoma (NPC). Materials and Methods: From January 1998 through December 2006, 68 patients were histologically diagnosed as non-metastatic NPC and treated by RT. Only 38 patients had the paraffin block for the immunohistochemical study. Thirty-one patients had undifferentiated carcinoma and 7 patients had squamous cell carcinoma. Thirtytwo patients (84%) had advanced stage NPC (2002 AJCC Stage III~IV). Immunohistochemical staining was performed for Met, COX-2, nm23-H1, and epidermal growth factor receptor (EGFR) expression using routine methods. Results: The median follow-up time was 30 months (range, 11 to 83 months) for all patients, and 39 months (range, 19 to 83 months) for surviving patients. The 5-year overall survival (OS) rate of the patients with high Met extent (${\geq}50%$) was significantly lower than that of the patients with low Met extent (48% vs. 84%, p=0.02). In addition, Met extent was also a significant prognostic factor in multivariate analysis (p=0.01). No correlation was observed between Met extent and T stage, N stage, stage group, gender, age, and the response to chemotherapy or RT. Met extent showed moderate correlation with COX-2 expression (Pearson coefficient 0.496, p<0.01), but COX-2 expression did not affect OS. Neither nm23-H1 or EGFR expression was a prognostic factor for OS in this study. Conclusion: High Met extent (${\geq}50%$) might be an independent prognostic factor that predicts poor OS in NPC treated with RT.
Purpose : Three-dimensional radiation dosimetry using magnetic resonance imaging of polymer gel was recently introduced. This dosimetry system is based on radiation induced chain polymerization of acrylic monomers in a muscle equivalent gel and provide accurate 3 dimensional dose distribution. We planned this study to evaluate the clinical value of this 3-dimensional dosimetry. Materials and Methods: The polymer gel poured into a cylindrical glass flask and a spherical glass flask. The cylindrical test tubes were for dose response evaluation and the spherical flasks, which is comparable to the human head, were for isodose curves. T2 maps from MR images were calculated using software, IDL. Dose distributions have been displayed for dosimetry. The same spherical flask of gel and the same irradiation technique was used for film and TLD dosimetry and compared with each other. Results : The R2 of the gel respond linearly with radiation doses in the range of 2 to 15 Gy. The repeated dosimetry of spherical gel showed the same isodose curves. These isodose curves were identical to dose distributions from treatment planning system especially high dose range. In addition, the gel dosimetry system showed comparable or superior results with the film and TLD dosimetry. Conclusion : The 3-dimensional dosimetry for conformal radiation therapy using MRI of polymer gal showed stable and accurate results. Although more studies are needed for convenient clinical application, it appears to be a useful tool for conformal radiation therapy.
Paik, Ji Yeun;Choi, Jae Hong;Cho, Eun Young;Oh, Chi Eun;Lee, Jina;Choi, Eun Hwa;Lee, Hoan Jong
Pediatric Infection and Vaccine
/
v.18
no.2
/
pp.109-116
/
2011
Purpose : Pneumococcus is one of the most important causes of invasive infection through the childhood period. In January 2008, the Clinical and Laboratory Standards Institute (CLSI) published revised penicillin breakpoints for Streptococcus pneumoniae and penicillin susceptibility rates of S. pneumoniae increased in Korea. This study was performed to determine the probability of oral amoxicillin for the empirical treatment achieving bactericidal exposure against pneumococcus using pharmacodynamics model. Methods : Twenty-three isolates of pneumococci were subjected to determine minimum inhibitory concentration (MIC) for ${\beta}$-lactams and macrolide. For the ${\beta}$-lactams, exposure of fT >MIC (time that free drug concentrations remain above the MIC) for 50% of the administration interval have determined the probability of target attainment (PTA), and regimens that had a PTA >90% were considered optimal. An analysis was performed by applying MIC of 23 isolates to a 5000-patient Monte Carlo simulation model. Results : Among 23 isolates from healthy children, 7 (30.4%) isolates were MIC ${\leq}$1.0 ${\mu}g$/mL and 19 (82.6%) were MIC ${\leq}$2 ${\mu}g$/mL for amoxicillin. Amoxicillin 40 mg/kg/day achieved PTA >90% at MIC ${\leq}$1.0 ${\mu}g$/mL but PTA decreased to 52% at MIC 2 ${\mu}g$/mL, whereas amoxicillin 90 mg/kg/day can predict 97% of PTA at MIC 2 ${\mu}g$/mL. Overall, oral amoxicillin 90 mg/ kg/day for the empirical treatment against pneumococcus can expect more successful response in Korean children. Conclusion : Considering the resistantce pattern of pneumococci in Korean children, we estimate that oral amoxicillin 90 mg/kg/day will provide a pharmacodynamic advantage for the empirical treatment against pneumococcus. And low dose amoxicillin or macrolide are expected to have higher chance of treatment failure than high dose oral amoxicillin.
Industrial glues, known as 'Bonds' in Korea, contain many kinds of organic solvents, and glue sniffing of youths became one of the social problems in Korea. Mixed exposures to solvents by glue sniffing may induce chronic toxicities different from those by exposures to solvents of single component. To test effects of the glue sniffing on weight gain or central nervous system, two groups of 20 male Sprague-Dawley rats were exposed to air(control group) or vapors of the glues to narcotic status(exposed group), and weight check, tail flick test, hot plate test, rotarod treadmill test were done on the 14th,24th, 36th, 45th, 53rd, 86th, 102nd, 117th, 134th and 151st days after the first exposure. On the 188th day, their brains were excised and examined by a pathologist. Weight gain, controlled against time change, showed significant difference between the groups, but response times in tail flick test, hot plate tests, and rotarod treadmill test didn't. In pathological examination with blind method, no macroscopic or microscopic differences were found between the two groups. These results suggests that organic lesion in central nervous system may not ensue glue sniffing, but, before firm conclusion, more studies in various exposure conditions should be followed.
Migration and differentiation of mesenchymal stem cells are crucial for tissue regeneration in response to injury. Sphingosine-1-phosphate (S1P) is a bioactive lipid that regulates a variety of biological processes, including proliferation, survival, differentiation and motility. In the present study, we determined the role of S1P in migration and differentiation of human bone marrow-derived mesenchymal stem cells (BMSCs). S1P stimulated migration of BMSCs in a dose- and time-dependent manner, and pre-incubation of the cells with pertussis toxin completely abrogated S1P-induced migration, suggesting involvement of Gi-coupled receptors in S1P-induced cell migration. S1P elicited elevation of intracellular concentration of $Ca^{2+}$ ($[Ca^{2+}]_i$) and pretreatment with VPC23019, an antagonist of $S1P_1/S1P_3$, blocked S1P-induced migration and increase of $[Ca^{2+}]_i$. Small interfering RNA-mediated knockdown of endogenous $S1P_1$ attenuated S1P-induced migration of BMSCs. Furthermore, S1P treatment induced expression of $\alpha$-smooth muscle actin ($\alpha$-SMA), a smooth muscle marker, and pretreatment with VPC23019 abrogated S1P-induced $\alpha$-SMA expression. S1P induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), and pretreatment of cells with SB202190, an inhibitor of p38 MAPK, or adenoviral overexpression of a dominant-negative mutant of the p38 MAPK blocked S1P-induced cell migration and $\alpha$-SMA expression. Taken together, these results suggest that S1P stimulates migration and smooth muscle differentiation of BMSCs through an $S1P_1$-p38 MAPK-dependent mechanism.
The objective of this study was to determine the effects of residual nitrite contents, chitosan with different molecular weight and nitrite addition on emulsified sausage during cold storage. Six types of sausages were evaluated: control, 0.5% 50 kDa chitosan (T1), 0.5% 200 kDa chitosan (T2), 150 ppm nitrite (T3), 0.5% 50 kDa chitosan+150 ppm nitrite (T4), and 0.5% 200 kDa chitosan+150 ppm nitrite (T5). Each type of sausage was tested in triplicate and assigned to one of four storage periods: 0, 10, 20 and 30 days. As the storage time increased, the presence of chitosan and nitrite resulted in decreased residual nitrite value and increased pH (in control and T2), TBARS (thiobarbituric acid reactive substance) values, and total plate counts (TPC). Values for pH, TBARS, residual nitrite and total plate counts decreased significantly in response to the addition of chitosan and nitrite relative to the control (p<0.05). T5 was redder than the control (higher CIE$a^*$) at 30 d; however, no difference in the CIE $L^*$ and $b^*$ values was observed. T5 was significantly (p<0.05) more effective at delaying lipid oxidation when compared to the other treatment groups. T5 presented TPC that was significantly lower (p<0.05) than the other groups after three days of storage. In addition, the use of chitosan and nitrite in combination had much better antioxidant and antimicrobial effectiveness than other treatment groups. In conclusion, this study demonstrates that the addition of 0.5% 200 kDa chitosan and 150 ppm nitrite in combination with emulsified sausages tended to improve antioxidative and antimicrobial effects during storage when compared to other treatment groups.
This study was performed to establish a simple and accurate method for the determination of oxygen that is a processing aid in various beverage. The quantitative determination of dissolved oxygen (DO) contents in 30 cases of samples were performed by traditional titration method and polarography. As a result of the study, the analysis of DO contents in fruit-extract beverages containing oxygen by titration method was time consuming and large sample volumes were needed. Besides, serious interferences with compounds such as hydroxylamine and nitric oxide were observed, leading to false response. Although the polarography is easily affected by $H_2S$, proteins, and various organic compounds, it is a simple and practical method that provides inexpensive and relatively rapid analysis. The polarography is best suited to the routine determination of DO in a large number of samples and it is expected that the polarography can directly be applied to the quality control of the beverages containing added oxygen. The analysis results of DO contents in various fruit-extract beverages with oxygen and without oxygen were as follows: 23.10 ppm to 32.60 ppm for various frutis extract beverages with oxygen, 0.70 pp to 2.54 ppm for mixed beverages without oxygen, 7.63 ppm to 8.28 ppm for drinking water.
Since database management systems(DBMSS) have limited lock resources, transactions requesting locks beyond the limit mutt be aborted. In the worst carte, if such transactions are aborted repeatedly, the DBMS can become paralyzed, i.e., transaction execute but cannot commit. Lock escalation is considered a solution to this problem. However, existing lock escalation methods do not provide a complete solution. In this paper, we prognose a new lock escalation method, adaptive lock escalation, that selves most of the problems. First, we propose a general model for lock escalation and present the concept of the unescalatable look, which is the major cause making the transactions to abort. Second, we propose the notions of semi lock escalation, lock blocking, and selective relief as the mechanisms to control the number of unescalatable locks. We then propose the adaptive lock escalation method using these notions. Adaptive lock escalation reduces needless aborts and guarantees that the DBMS is not paralyzed under excessive lock requests. It also allows graceful degradation of performance under those circumstances. Third, through extensive simulation, we show that adaptive lock escalation outperforms existing lock escalation methods. The results show that, compared to the existing methods, adaptive lock escalation reduces the number of aborts and the average response time, and increases the throughput to a great extent. Especially, it is shown that the number of concurrent transactions can be increased more than 16 ~256 fold. The contribution of this paper is significant in that it has formally analysed the role of lock escalation in lock resource management and identified the detailed underlying mechanisms. Existing lock escalation methods rely on users or system administrator to handle the problems of excessive lock requests. In contrast, adaptive lock escalation releases the users of this responsibility by providing graceful degradation and preventing system paralysis through automatic control of unescalatable locks Thus adaptive lock escalation can contribute to developing self-tuning: DBMSS that draw a lot of attention these days.
Background: Korean ginseng (KG) has been used as a general tonic, and for voiding dysfunction for a long time in oriental society. However, scientific basic studies on the use of KG, have been rare, especially for voiding and erectile dysfunction. This study was performed to investigate the effects of KG on voiding and erectile function by examining the effects of total saponin (TS) on the bladder, urethral and penile cavernosal smooth muscle. Materials and methods: To examine the effects of TS, NewZeland white rabbits were used to obtain tissue strips from the smooth muscle of the bladder, proximal urethra and corpus cavernosum. Adult Sprague Dawley rats were used to examine the changes in urodynamic findings and penile erection after administration of TS. Results: In proximal urethral strips, the rate of relaxation of the proximal urethra was increased from $9.0{\pm}2.9$ to $33.7{\pm}4.8%$ in a dose-dependent manner when the concentration of TS was added accumulatively from 0.25 mg/ml to 4.0 mg/ml (p<0.05). However, no significant response was observed in the bladder strips within these concentration ranges. For the corpus cavernosal strips, the rate of relaxation ranged from $5.8{\pm}2.1$ to $36.7{\pm}5.8%$, increasing in a dose-dependent manner when TS was increased from 1.0 mg/ml to 4.0 mg/ml (p<0.05). After administration of 0.1 ml of TS (32 mg/ml) in the rat, the bladder pressure was $37.5{\pm}8.5$ mmHg at $52.1{\pm}7.0$ sec. during isovolumetric bladder contraction, showing no significant differences from $35.7{\pm}7.8mmHg$ and $50.7{\pm}7.2$ sec, respectively, before treatment. However, when 0.1 ml of TS (32 mg/ml) was administered, the relative reduction of urethral pressure was $6.9{\pm}0.5mmHg$ at $62{\pm}7.5$ sec, which was significantly higher compared to $4.6{\pm}1.1mmHg$ at $45{\pm}10$ sec before treatment (p<0.05). For the cavernosal injection study, the change in intracavernosal pressure (${\Delta}ICP$) was examined after administering 0.1 ml of TS. The cumulative additions of TS at concentrations from 0.5 mg/ml to 32 mg/ml increased ${\Delta}ICP$ from $1.3{\pm}0.5$ to $21.3{\pm}7.8mmHg$ in a dose-dependent manner (p<0.05). The duration of tumescence was from $0.3{\pm}0.1$ to $5.2{\pm}0.2$ min, showing dose-dependent increase (p<0.05). Furthermore, the cumulative addition of TS at concentrations from 0.5 mg/ml upto 32 mg/ml did not cause any significant change in systemic blood pressure. Conclusion: These results suggest that ginseng improves voiding functions, which is mainly achieved by TS relaxing the proximal urethra, the most important part of the bladder outlet function. In addition, ginseng safely induced a penile erection hemodynamically by relaxing the corpus cavernosum.
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