• Journal of Life Science
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• v.19 no.9
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• pp.1226-1231
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• 2009

Enzyme substitution with recombinant phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) is currently being explored for treatment of phenylketonuria (PKU), an autosomal recessive genetic disorder with mutations of the gene encoding phenylalanine-4-hydroxylase (EC 1.14.16.1). However, oral administration of PAL is limited because of proteolytic digestion in the gastrointestinal tract. The aim of this study was to determine the biochemical properties of PAL and delinate the susceptibility of wild-type PAL to pancreatic proteolysis by exploring several mutants, and to develop therapeutic drugs with PAL for PKU. The specific activity of PAL was assayed and its optimal pH, temperature stability, and intestinal protease susceptibility were investigated. Its $V_{max}$ values for phenylalanine and tyrosine were 1.77 and $0.47{\mu}mol$/ min/mg protein, respectively, and its $K_m$ values were $4.77{\times}10^{-4}$ and $4.37{\times}10^{-4}\;M$, respectively. PAL showed an optimal pH at 8.5, corresponding to the average pH range of the small intestine. It showed no loss of activity at $-80^{\circ}C$ for 5 months and possessed 93.4% of its activity under $4^{\circ}C$ for 4 wks. PAL was susceptible to chymotrypsin digestion and, to a lesser extent, to trypsin, elastase, carboxypeptidase A, and B. The trypsin and chymotrypsin cleaving sites were mutated to investigate protection from pancreatic digestion and the specific activities of these mutants were evaluated. The six mutants displayed low specific activities compared to the wild-type, suggesting that the primary trypsin and chymotrypsin cleaving sites may be essential for catalytic reaction. The PAL mutants could therefore be applied as a pretreatment modality without susceptibility to proteolytic attack, however, additional modification for enhancing enzymatic activity is needed to reduce the Phe levels effectively.

• Radiation Oncology Journal
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• v.28 no.3
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• pp.117-124
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• 2010

Purpose: To analyze the postoperative radiotherapy results and prognostic factors in patients with WHO grade 3 and 4 gliomas. Materials and Methods: A total of 99 patients with malignant gliomas who underwent postoperative radiotherapy between 1988 and 2007 were enrolled in this study. Total resections, subtotal resections ($\geq$50%), partial resections (<50%), and biopsies were performed in 16, 38, 22, and 23 patients, respectively. In total there were 32, 63 and 4 WHO grade 3, 4, and unspecified high grade gliomas, respectively. The biologically equivalent dose was in the range of 18.6 to $83.3\;Gy_{10}$ (median dose, $72.2\;Gy_{10}$). We retrospectively analyzed survival rate, patterns of failure, prognostic factors, and adverse effects. Results: The median follow-up time was 11 months and there were 54 patients (54.5%) with local failure. The one and 2-year survival rates were 56.6% and 29.3%, respectively, and the median survival duration was 13 months. The one and 2-year progression-free survival rates (PFS) were 31.3% and 18.2%, respectively, and the median PFS was 7 months. The prognostic factors for overall survival were age (p=0.0001), surgical extents (subtotal resection, p=0.023; partial resection, p=0.009; biopsy only, p=0.002), and enhancement of tumor in postoperative imaging study (p=0.049). The factors affecting PFS were age (p=0.036), tumor enhancement of the postoperative imaging study (p=0.006). There were 3 patients with grade 3 and 4 side effects during and after radiotherapy. Conclusions: In addition to age and surgical extents, tumor enhancement of the postoperative imaging study was included in the prognostic factors. The most common relapse patterns were local failures and hence, additional studies are needed to improve local control rates.

• Journal of Chest Surgery
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• v.43 no.2
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• pp.139-143
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• 2010

Background: Thoracic empyema remains a serious problem despite the availability of modern diagnostic methods and appropriate antibiotics. The condition presents in many different forms and stages that require different therapeutic options. Video-assisted thoracic surgery (VATS) has become increasingly popular for use in the treatment of empyema. Material and Method: From January 2005 to May 2009, VATS was performed in 36 patients with pleural empyema and for whom chest-tube drainage and antibiotic therapy had failed or the CT scan showed multiseptate disease. The perioperative clinical factors were analyzed for all the study patients. Result: All the patients underwent VATS, but it was necessary to convert to thoracotomy in one patient. The mean operation time was $90{\pm}38.5\;min$. For the operative evaluation, 11 patients were compatible with ATS stage III. The duration of chesttube insertion was $11.9{\pm}5.8$ (3~24) days. One patient did not improve and therefore this patient underwent additional open drainage. At discharge, costophrenic angle blunting was observed in 22 patients, pleural thickening was noted in 20 patients, both were noted in 17 patients and neither was noted in 11 patients. However, at follow-up, each of these changes was observed in 9, 7, 4 and 24 patients, respectively. All except one patient showed radiographic improvement. Conclusion: VATS is suitable for the treatment of early and fibrinopurulent thoracic empyema, and even in selected patients with stage III disease.

• Clinical and Experimental Pediatrics
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• v.48 no.2
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• pp.186-190
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• 2005

Purpose : The purpose of this study was to evaluate the responses and toxicities of risk-adapted chemotherapy in pediatric intracranial germ cell tumors(IC-GCT). Methods : Fourteen patients who were diagnosed as IC-GCT from October 2002 to December 2003 received chemotherapy as an initial treatment modality. The low risk(LR) group was defined as follows : Pure germinoma and normal AFP level. Beta-hCG level 50 mIU/mL or less. The others belonged to the high risk(HR) group. Chemotherapy was composed of cisplatin, cyclophosphamide, etoposide and vincristine. Double doses of cisplatin and cyclophosphamide was used in HR patients. Results : Pathologic confirmation was done in all but one. Median age at diagnosis was 11.6 yr (1.2-18.7 yr), and nine patients belonged to the HR group. Tumor markers were normalized after chemotherapy in all patients whose tumor markers had been elevated. Four LR patients(80 percent) and seven HR patients(77.8 percent) showed complete response(CR) at the end of chemotherapy. An additional two of the three patients with partial response(PR) achieved CR after radiation therapy (RT), and the remaining one relapsed before RT. Four LR and all HR patients experienced infectious episodes that required hospitalization. Four of the nine HR patients(44.4 percent) suffered from tinnitus, three of whom developed sensorineural hearing loss. All but one are surviving, event-free, with a median follow-up of 13.9 mo(8.1-22.3 mo). Conclusion : Risk-adapted cisplatin-based chemotherapy was effective even in HR patients, but regimen modification seems to be necessary to avoid an unacceptably high toxicity rate.

• Clinical and Experimental Pediatrics
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• v.45 no.11
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• pp.1411-1416
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• 2002

Purpose : Although the use of intravenous gamma-globulin(IVGG) in Kawasaki disease(KD) is effective in reducing clinical symptoms and coronary artery complications, 20-30% of patients have persistent or recrudescent fever and ongoing clinical symptoms. In these patients, the additional infusion of IVGG is considered. The authors studied the characteristics of patients who received IVGG retreatment, and compared them with the patients who did not need IVGG retreatment, for determination of IVGG retreatment. Methods : We reviewed the medical records of 117 KD patients who could be followed up at least six months. We studied the conventional laboratory findings, electrocardiogram(EKG), signal averaged ECG(SAECG) and echocardiogram. Results : Twenty three patients had early cardiac complications during the six months of follow-up. Four patients had late cardiac complications after six months. The early cardiac complication rate was higher in the IVGG retreatment group than the single infusion group(P<0.0001). The late complication rate was also higher in the retreatment group(P<0.0001). The patients who received methyl-prednisolone(m-PD) pulse therapy had much higher rates of early and late cardiac complications than those who received a single IVGG infusion. Among the clinical data and laboratory findings, only CRP increased significantly in patients who have had the cardiac complications. The IVGG retreatment group had increased CRP than the single infusion group. Conclusion : The patients with increased initial CRP may have an increased incidence of complications and an increased possibility of IVGG retreatment. We thought that retreated KD patients might have inflammations severe enough to need high dose IVGG as shown by high CRP levels, and IVGG retreatment could not prevent coronary artery lesions sufficiently.

• The Korean Journal of Nuclear Medicine
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• v.38 no.4
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• pp.282-287
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• 2004

Purpose: Since preoperative staging in esophageal cancer is important in both therapy and prognosis, there had been many efforts to improve its accuracy. Recent studies indicate that whole body FDG-PET has high sensitivity in detection of metastasis in esophageal cancer. Therefore, we added FDG-PET to other conventional methods in staging esophageal cancer to evaluate the usefulness of this method. Materials & Methods: Subjects were 142 esophageal cancer patients (average $62.3{\pm}8.3$ yrs) who received CT and PET just before operation. First, we compared N stage and M stage of the CT or PET with those of the post-operative results. Then we compared the stage according to the EUS (T stage) and CT (N and M stage) or SUS (T stage) and CT & PET (N and M stage) to that according to the post-operative results. Results: Among 142 patients, surgical staging of 69 were N0 and 73 were N1. In M staging, 128 were M0 and 14 were M1. Sensitivity, specificity, and accuracy of N staging were 35.6%, 89.9%, 62.0% with CT and 58.9%, 71.0%, 64.7% with PET, respectively. In M staging, 14.3%, 96.9%, 88.7% with CT and 50.0%, 94.5%, 90.1%, with PET, respectively. The concordances of [EUS+CT] and [EUS+CT+PET] with post-operative results were 41.2% and 54.6%, respectively and there was significant improvement of staging with additional PET scan (p<0.005). Conclusion: The concordance of [EUS+CT+PET] with post-operative result was significantly increased compared to that of [EUS+CT]. Thus, the addition of FDG-PET with other conventional methods may enable more accurate preoperative staging.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.283-292
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• 2000

Purpose :A retrospective review of 72 patients with locally advanced gallbladder carcinoma, between January 1990 and December 1996, was peformed. Survival results and prognostic factors are analyzed for the patients treated with a various modalities. Materials and Methods :We patients were classified by treatment modality: group 1 included to 27 patients treated with palliative surgery alone, and group 2 for 11 patient treated with palliative surgery and radiotherapy; group 3 for 18 patients not treated by any treatment modality, and group 4 for 16 patients treated with radiotherapy alone. Age distribution ranged from 35 to 80 years with mean of 63 years. The stage was classified by TNM and Nevin's staging system; all patients had an advanced stage more than III. Palliative surgery was done in .: patients and adiuvant radiation therapy (RT) was followed in 11. For 34 patients, in whom no resection was tried, definitive RT was done in 16. Radiation delivered to tumor site and draining nodes up to 45~61.2 Gy using 10 MV linear accelerator. Chemotherapy was given to 25 patients with 5-FU based regimens. Results :Modian suwival time was 10.3 months and 3-year survival rates (3-YSR) were 13.0$\%$ in all patients. Survival rates according to the treatment modalities were as followed; in palliative surgery alone, 3-YSR was 2.5$\%$; in palliative surgery and adjuvant RT, 3-YSR was 45.5$\%$, in no treatment group, 3-VSR were 8.3$\%$; and definitive RT was 13.1$\%$. It was better survival in additional RT after palliative surgery group than palliative surgery alone (p=0.0009). It was better survival in definitive RT group than no treatment group (p=0.002). Significant prognostic factors by univariate analysis were treatment moonlities, the type of tumor and TNM stage. Significant prognostic factors by multivariate analysis were treatment modalities, the type of tumor and the presence of jaundice. Conclusion : It is suggested that RT could be potentially of effective as adjuvant treatment modalities after palliative surgery or primary treatment for locally advanced and unresectable gallbladder carcinoma.

• The Journal of Korean Academy of Sensory Integration
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• v.15 no.2
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• pp.46-65
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• 2017

Objective : The purpose of this research is to find clinical effects of application of weighted vest during task-oriented training focused on gross motor performance and balance abilities of children with spastic diplegia. Methods : 34 subjects were divided by simple random sampling into two groups; experimental group (male : 9, female : 8, average age : 8.12) and placebo group (male : 9, female : 9, average age : 7.53). Both two groups underwent to 40 minute intervention, twice a week for 12 weeks. The intervention was task-oriented training focused on facilitating closed kinematic chain and multi-joint functional movement pattern. During the training, the experimental group received loaded-resistance weighted vest and placebo group also received weighted vest but without loaded-resistance. Participants in both groups underwent 8 to 10 reps of the task-oriented training and there were 3 minutes break time between tasks. There were pre-test of gross motor performance and balance abilities, and two times of post-tests were performed upon 6 weeks and 12 weeks after the intervention completed. And in final, an additional follow-up test was performed 12 weeks after the evaluation was finished in order to find any difference between the two groups over time. Results : There was significant difference in Gross Motor Performance Measure (GMPM) between two groups. It is found that average score of the experimental group increased more than the placebo group after 6 weeks and 12 weeks intervention (p<.05). There was significant difference in Pediatric Berg's Balance Scale (PBS) between two groups. It is found that average score of the experimental group increased more than the placebo group after 6 weeks and 12 weeks intervention (p<.05). Conclusion : Based on the results in this study, it is proposed that application of weighted vest into task-oriented training to facilitating closed kinematic chain and multi-joint movement can improve gross motor performance and balance abilities of children with cerebral palsy.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.378-383
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• 1993

Background: In recent reports, it has been reported that increased coagulation and decreased fibrinolytic activity has been responsible for abnormal fibrin turnover in exudative pleural effusion. In the cases of empyema, the fibrinopurulent stage is characterized by the fibrin deposition resulting in formation of limiting membranes in the visceral and parietal pleura. Recently attention has been focused on intrapleural fibrinolytic therapy capable of removing intrapleural fibrin deposits by urokinase (UK) in the treatment of empyema. However, these clinical trials have provided the clinical evidences for resolution of pleural loculation after intrapleural urokinase injection (UK-injection), the profiles of fibrinolytic activity following the treatment were still not investigated. Therefore in order to demonstrate the fibrinolytic evidences behind the clinical efficacy of intracavitary UK-injection, we examined intrapleural plasminogen activator activity (PA-activity) and D-dimer (D-Di) concentrations before and after each repeated UK-injection into the pleura in subjects with loculated empyema cavity. Methods: In a group of 14 patients with multiple loculated empyema cavity, PA-activity and D-Di concentrations were measured before and after repeated UK-injection. One hundred thousand IU of UK was injected at each time and all sujects had at least two times of UK injection accoring to clinical decisions. Nine out of 14 sujects had three times of UK-injection. Results: The mean (${\pm}SE$) PA-activity prior to treatemnt was $10.5{\pm}7.0$ and it was increased to $91.9{\pm}27.0,\;432.3{\pm}177.1,\;170.0{\pm}85.3$ IU tPA/ml after first, second and third time of UK-injection respectively (p<0.01). D-Di concentrations were also increased from $4.16{\pm}1.06{\times}10^5$ to $9.62{\pm}1.54{\times}10^5,\;12.31{\pm}1.89{\times}10^5,\;8.54{\pm}1.56{\times}10^5$ ng/ml in the same order as above (p<0.05). Conclusion: The suppressed fibrinolytic activity in the empyema cavity get removed sinificantly after inrracavitary injection of urokinase by generation of additional intrapleural plasmin.

• Tuberculosis and Respiratory Diseases
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• v.51 no.6
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• pp.530-539
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• 2001

Background : Bronchial asthma is an inflammatory disease of the airways that is associated with airway remodeling. The vascular endothelial growth factor (VEGF) is a potent, multifunctional cytokine that contributes to angiogenesis and inflammation. Matrix metalloproteinase-9 (MMP-9) is a major proteolytic enzyme that in duces bronchial remodeling in asthma. However, there is no data available on the possible role of the VEGF or on the potential relationship between the VEGF and MMP-9 in acute asthma. Therefore, the VEGF was studied to determine whether or not it participates in airway inflammation during acute asthma. An additional aim of this study was to determine whether or not the VEGF levels correlated with the MMP-9 levels in the sputum of acute asthma patients. Methods: Both the VEGF and MMP-9 levels were measured by an enzyme immunoassay and zymographic analysis in the sputum of patients with either stable asthma or with acute asthma. The VEGF and MMP-9 levels were also evaluated during a spontaneous asthma attack. Results : The VEGF levels were significantly higher in the sputum of acute asthmatic patients than in either the stable patients the control subjects. The VEGF levels in the sputum during asthma exacerbation were significantly higher than those on the remission days, and those levels decreased after asthma therapy. In acute asthmatic patients, the VEGF levels in the sputum correlated with the number of neutrophils and eosinophils. In addition, a significant correlation was established between the VEGF and MMP-9 levels in the sputum. Conclusion : These results suggest that VEGF overproduction is associated with airway inflammation during acute asthma and is related to the MMP-9 function.