• Progress in Medical Physics
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• v.17 no.3
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• pp.136-143
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• 2006

The respiratory gating radiation therapy which Irradiates only in the stable respiratory period with analyzing the periodic motion of a reflective marker on the patient's abdomen has been applied to the precise radiation treatment in order to minimize the effect of organ motion induced by the respiration. This respiratory gating system establishes irradiation region using the amplitude-based or phase-based method. Although phase-based method Is preferred because of the stability in the real treatment conditions, it has some limits to explain the exact correlation between the marker motion and organ motion. Even when the variation of amplitude which can introduce target motion considered as an error is produced, the phase-based method has the possibility to irradiate including the error positions. In this study, the error analysis program was developed for the verification of the tumor position's variation correlated with the variation of marker's amplitude which can be occurred during a phase-based respiratory sating treatment. The analysis program was tested with a virtual treatment record file and with a record file using moving phantom which were modified considering the irregular amplitude's variation simulating the real clinical situations. In both cases, accurate discrimination of error points and error calculation were produced. When the treatment record files of a real patient were analyzed with the program, the accurate recognition and calculation of the error points were also verified. The analysis program developed in this study will be applied as a useful tool for the analysis of errors due to the irregular variation of patients' respiration during the phase-base respiratory gating radiation treatment.

• Radiation Oncology Journal
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• v.20 no.2
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• pp.130-138
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• 2002

Purpose : This study analyzed the prognostic factors affecting the survival rate and evaluated the role of radiation therapy in muscle-invading bladder cancer. Materials and Methods : Twenty eight patients with bladder cancer who completed planned definitive radiotherapy in the Departments of Therapeutic Radiology and Urology, Chonnam National University Hospital between Jan. 1986 to Dec. 1998 were retrospectively analyzed. The reviews were peformed based on the patients' medical records. There were 21 males and 7 females in this study. The median of age was 72 years old ranging from 49 to 84 years. All patients were confirmed as having transitional cell carcinoma with histological grade 1 in one patient, grade 2 in 15, grade 3 in 9, and uninformed in 3. Radiation therapy was peformed using a linear accelerator with 6 or 10 MV X-rays. Radiation was delivered daily with a 1.8 or 2.0 Gy fraction size by 4 ports (anterior-posterior, both lateral, alternatively) or 3 ports (Anterior and both lateral). The median radiation dose delivered to the isocenter of the target volume was 61.24 Gy ranging from 59 to 66.6 Gy. The survival rate was calculated by the Kaplan-Meier method. Multivariate analysis was peformed on the prognostic factors affecting the survival rate. Results : The survival rate was $76\%,\;46\%,\;33\%,\;33\%$ at 1, 2, 3, 5 years, respectively, with 19 months of median survival. The potential factors of age (less than 70 years vs above 70), sex, diabetes mellitus, hypertension, hydronephrosis, 1-stage (T3a vs T3b), TUR, chemotherapy, total duration of radiotherapy, radiation dose (less than 60 Gy vs above 60 Gy), and the treatment response were investigated with uniand multivariate analysis. Un univariate analysis, the T-stage (p=0.078) and radiation dose (p=0.051) were marginally significant, and the treatment response (p=0.011) was a statistically significant factor on the survival rate. Multivariate analysis showed there were no significant prognostic factors affecting the survival rate. Conclusion : The treatment response and radiation dose are suggested as th은 statistically significant factors affecting the survival rate of muscle invasive bladder cancer. A Further prospective randomized study is needed to confirm these prognostic factors.

• Radiation Oncology Journal
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• v.22 no.1
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• pp.25-32
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• 2004

Purpose : Evaluate the efficacies and toxicities of concurrent chemoradiotherapy (CCRT), with or without intraluminal brachytherapy (ILB), using a retrospective analysis in esophageal carcinomas with respect to survival. Materials and Methods : From April 1995 to July 2001, a total of 65 patients, diagnosed with an esophageal carcinoma, were treated by CCRT, with 21 also treated by ILB after CCRT. External radiotherapy was peformed using 6 or 10 MV X-rays, with a dose range of $46.8~\69.6$ Gy (median; 59.4). The ILB was peformed using high-dose-rate brachytherapy with Ir-192. The fractionation of ILB was 3 Gy by 4, or 5 Gy by 2 fractions. Cisplatin $(75\;mg/m^2)$ was given on each first day of weeks 1, 5, 9 and 13, and 5-FU $(1,000\;mg/m^2)$ as a continuous infusion for the first 4 days of each course. Results : The median survival time of all patients was 15 months, and the 1, 2 and 3-year survival rates were 55.4, 29.2 and $20.7\%$, respectively. The 2-year survival rates of the patients with and without ILB were 33.3 and $27.3\%$, respectively (p=0.80). The 2-year survival rates of the patients with a complete, partial and no response were 44.1, 13.8 and $0\%$, respectively (p=0.02). The response to treatment was the only significant factor affecting the overall survival from a multivariate analysis. Conclusion : This study has shown that the survival outcomes of CCRT were much better than previous results with radiotherapy alone. However, the addition of ILB after CCRT showed no advantage over that of CCRT alone.

• Journal of Dairy Science and Biotechnology
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• v.33 no.2
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• pp.111-118
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• 2015

Probiotic, prebiotic, and synbiotic substances as well as microorganisms were added to infant formula in an attempt to influence the intestinal microflora with an aim to stimulate the growth of lactic acid bacteria, especially bifidobacteria and lactobacilli. Over the last 10 years, new synbiotic infant formulas containing probiotics and prebiotics have been proposed in order to simulate the effect of breast-feeding on the intestinal microflora. Owing to their synergistic effect, the new synbiotics are expected to be more helpful than using probiotics and prebiotics individually. Maintenance of the viability of the probiotics during food processing and the passage through the gastrointestinal tract should be the most important consideration, since a sufficient number of bacteria ($10^8cfu/g$) should reach the intended location to have a positive effect on the host. Storage conditions and the processing technology used for the manufacture of products such as infant formula adversely affect the viability of the probiotics. When an appropriate and cost-effective microencapsulation methodology using the generally recognized as safe (GRAS) status and substances with high biological value are developed, the quality of infant formulas would improve. The effect of probiotics may be called a double-effect, where one is an immunomodulatory effect, induced by live probiotics that advantageously alter the gastrointestinal microflora, and the other comprises anti-inflammatory responses elicited by dead cells. At present, a new terminology is required to define the dead microorganisms or crude microbial fractions that positively affect health. The term "paraprobiotics" (or ghost probiotics) has been proposed to define dead microbial cells (not damaged or broken) or crude cell extracts (i.e., cell extracts with complex chemical composition) that are beneficial to humans and animals when a sufficient amount is orally or topically administered. The fecal microflora of bottle-fed infants is altered when the milk-based infant formula is supplemented with probiotics or prebiotics. Thus, by increasing the proportion of beneficial bacteria such as bifidobacteria and lactobacilli, prebiotics modify the fecal microbial composition and accordingly regulate the activity of the immune system. Therefore, considerable attention has been focused on the improvement of infant formula quality such that its beneficial effects are comparable to those of human milk, using prebiotics such as inulin and oligosaccharides and potential specific probiotics such as bifidobacteria, which selectively stimulate the proliferation of beneficial bacteria in the microflora and the indigenous intestinal metabolic activity of the microflora.

• Journal of Life Science
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• v.30 no.3
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• pp.285-290
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• 2020

Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. FMDV causes various clinical symptoms, including severe inflammation in infected tissue. Genome RNA of FMDV shows a positive single-strand chain approximately 8.3 kb long and encodes a single long open reading frame (ORF). The ORF is translated into structural and non-structural proteins by viral proteases. The FMDV 2C protein is one of the non-structural proteins encoded by FMDV and plays a critical role in FMD pathogenesis, including inflammation, apoptosis, and viral replication. In this study, we examined whether FMDV 2C induces intracellular expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). FMDV 2C expression in pig IBRS-2 cells increased mRNA and protein expression of TNFα at the transcriptional level via activation of TNFα promoter. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress reducer, decreased TNFα expression induced by FMDV 2C. Activating transcription factor 4 (ATF4), a transcription factor mediating ER stress response, induced transactivation of TNFα promoter and expression of mRNA and protein of TNFα. However, the dominant negative mutant of ATF4 did not induce FMDV 2C-mediated TNFα expression. The results indicate that FMDV 2C protein increases clinical inflammation via ATF4-mediated TNFα expression and is associated with ER stress induction.

• The korean journal of orthodontics
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• v.33 no.6 s.101
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• pp.485-497
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• 2003

The form and function of the craniofacial structure critically depend on genetic information. With recent advances in the molecular technology, genes that are important for normal growth and morphogenesis of the craniofacial skeleton are being rapidly uncovered, shaping up modem craniofacial biology. One of them is fibroblast growth factor receptor 2 (FGFR2). Specific point mutations in the. FGFR2 gene have been linked to Apert syndrome, which is characterized by premature closure of cranial sutures and craniofacial anomalies as well as limb deformities. To study pathogenic mechanisms underlying craniosynostosis phenotype of Apert syndrome, we used a transgenic approach; an FGFR2 minigene construct containing an Apert mutation (a point mutation that substitute proline at the position 253 to arginine; P253R) was introduced into fertilized mouse germ cells by DNA microinjection. The injected cells were then allowed to develop into transgenic mice. We used a bone-specific promoter (a DNA fragment from the type I collagen gene) to confine the expression of mutant FGFR2 gene to the bone tissue, and asked whether expression of mutant FGFR2 in bone is sufficient to cause the craniosynostosis phenotype in mice. Initial characterization of these mice shows prematurely closed cranial sutures with facial deformities expected from Apert patients. We also demonstrate that the transgene produces mutant FGFR2 protein with increased functional activities. Having this useful mouse model, we now can ask questions regarding the role of FGFR2 in normal and abnormal development of cranial bones and sutures.

• Radiation Oncology Journal
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• v.13 no.1
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• pp.9-18
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• 1995

Purpose : A retrospective analysis was performed to investigate the proper management of maxillary sinus carcinoma. Materials and Methods : Authors analysed 33 patients of squamous cell carcinoma of maxillary sinus treated at Chonnam University Hospital from January 1986 to December 1992. There were 24 men and 9 women with median age of 55 years. According to AJCC TNM system of 1988, a patient of T2, 10 patients of T3 and 22 patients of T4 were availalbe, respectively. Cervical lymph node metastases was observed in 5 patients(N 1;4/33, N2b; 1/33). Patients were classified as 3 groups according to management method. The first group, named as 'FAR' (16 patients), was consisted or preoperative intra-arterial chemotherapy with 5-fluorouracil(5-FU;mean of total dosage;3078mg) through the superficial temporal artery with concurrent radiation(mean dose delivered:3433cGy, daily 180-200cGy) and vitamin A(50,000 IU daily), and followed by total maxillectomy and postoperative radiation therapy(mean dose;2351cGy). The second group, named as 'SR'(7 patients), was consisted of total maxillectomy followed by postoperative radiation therapy(mean dose 5920 cGy). The third group, named as 'R'(6 patients), was treated with radiation alone(mean dose;7164cGy). Kaplan-Meier product limit method was used for survival analysis and Mantel-Cox test was performed for significance of survival difference between two groups. Results : Local recurrence free survival rate in the end of 2 year was $100\%$, $50\%$ and $0\%$ in FAR, SR and R group, respectively. Disease free survival rate in 2 years was $88.9\%$, $28.0\%$ and $0\%$ in FAR, SR and R group, respectively. Overall survival rate in 2 years was $88.9\%$, $40\%$ and $50\%$ in FAR, SR and R group, respectively. There were statistically significant difference between FAR and SR or FAR and R group in their local recurrence free, disease free and overall survial rates. But difference of each survival rate between SR and R group was not significant. Conclusion : In this study FAR group revealed better results than SR or R group. In the future prospective randomized study is in need.

• Molecules and Cells
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• v.21 no.1
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• pp.52-62
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• 2006

In previous reports we demonstrated that ginsenosides, active ingredients of Panax ginseng, affect some subsets of voltage-dependent $Ca^{2+}$ channels in neuronal cells expressed in Xenopus laevis oocytes. However, the major component(s) of ginseng that affect cloned $Ca^{2+}$ channel subtypes such as ${\alpha}_{1C}$(L)-, ${\alpha}_{1B}$(N)-, ${\alpha}_{1A}$(P/Q)-, ${\alpha}_{1E}$(R)- and ${\alpha}_{1G}$(T) have not been identified. Here, we used the two-microelectrode voltage clamp technique to characterize the effects of ginsenosides and ginsenoside metabolites on $Ba^{2+}$ currents ($I_{Ba}$) in Xenopus oocytes expressing five different $Ca^{2+}$ channel subtypes. Exposure to ginseng total saponins (GTS) induced voltage-dependent, dose-dependent and reversible inhibition of the five channel subtypes, with particularly strong inhibition of the ${\alpha}_{1G}$-type. Of the various ginsenosides, $Rb_1$, Rc, Re, Rf, $Rg_1$, $Rg_3$, and $Rh_2$, ginsenoside $Rg_3$ also inhibited all five channel subtypes and ginsenoside $Rh_2$ had most effect on the ${\alpha}_{1C}$- and ${\alpha}_{1E}$-type $Ca^{2+}$ channels. Compound K (CK), a protopanaxadiol ginsenoside metabolite, strongly inhibited only the ${\alpha}_{1G}$-type of $Ca^{2+}$ channel, whereas M4, a protopanaxatriol ginsenoside metabolite, had almost no effect on any of the channels. $Rg_3$, $Rh_2$, and CK shifted the steady-state activation curves but not the inactivation curves in the depolarizing direction in the ${\alpha}_{1B}$- and ${\alpha}_{1A}$-types. These results reveal that $Rg_3$, $Rh_2$ and CK are the major inhibitors of $Ca^{2+}$ channels in Panax ginseng, and that they show some $Ca^{2+}$ channel selectivity.

• Molecules and Cells
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• v.27 no.5
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• pp.591-599
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• 2009

Nicotinic acetylcholine receptors (nAChRs) play important roles in nervous system functions and are involved in a variety of diseases. We previously demonstrated that ginsenosides, the active ingredients of Panax ginseng, inhibit subsets of nAChR channel currents, but not ${\alpha}7$, expressed in Xenopus laevis oocytes. Mutation of the highly conserved Leu247 to Thr247 in the transmembrane domain 2 (TM2) channel pore region of ${\alpha}7$ nAChR induces alterations in channel gating properties and converts ${\alpha}7$ nAChR antagonists into agonists. In the present study, we assessed how point mutations in the Leu247 residue leading to various amino acids affect 20(S)-ginsenoside $Rg_3$ ($Rg_3$) activity against the ${\alpha}7$ nAChR. Mutation of L247 to L247A, L247D, L247E, L247I, L247S, and L247T, but not L247K, rendered mutant receptors sensitive to $Rg_3$. We further characterized $Rg_3$ regulation of L247T receptors. We found that $Rg_3$ inhibition of mutant ${\alpha}7$ nAChR channel currents was reversible and concentration-dependent. $Rg_3$ inhibition was strongly voltage-dependent and noncompetitive manner. These results indicate that the interaction between $Rg_3$ and mutant receptors might differ from its interaction with the wild-type receptor. To identify differences in $Rg_3$ interactions between wild-type and L247T receptors, we utilized docked modeling. This modeling revealed that $Rg_3$ forms hydrogen bonds with amino acids, such as Ser240 of subunit I and Thr244 of subunit II and V at the channel pore, whereas $Rg_3$ localizes at the interface of the two wild-type receptor subunits. These results indicate that mutation of Leu247 to Thr247 induces conformational changes in the wild-type receptor and provides a binding pocket for $Rg_3$ at the channel pore.

• The korean journal of orthodontics
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• v.36 no.4
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• pp.284-294
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• 2006

Objective: Activating mutations in the fibroblast growth factor receptor-2 (FGFR2) have been shown to cause syndromic craniosynostosis such as Apert and Crouzon syndromes. The purpose of this pilot study was to investigate the resultant phenotypes induced by the two distinctive bone-targeted gene constructs of FGFR2, Pro253Arg and Cys278Phe, corresponding to human Apert and Crouzon syndromes respectively. Methods: Wild type and a transgenic mouse model with normal FGFR2 were used as controls to examine the validity of the microinjection. Micro-CT and morphometric analysis on the skull revealed the following results. Results: Both Apert and Crouzon mutants of FGFR2 induced fusion of calvarial sutures and anteroposteriorly constricted facial dimension, with anterior crossbite present only in Apert mice. Apert mice differed from Crouzon mice and transgenic mice with normal FGFR2 in the anterior cranial base flexure and calvarial flexure angle which implies a possible difference in the pathogenesis of the two mutations. In contrast, the transgenic mice with normal FGFR2 displayed normal craniofacial phenotype. Conclusion: Apert and Crouzon mutations appear to lead to genotype-specific phenotypes, possibly causing the distinctive sites and sequence of synostosis in the calvaria and cranial base. The exact function of the altered FGFR2 at each suture needs further investigation.