• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.2
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• pp.399-415
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• 1999

From bacteria to mammalian cells, one of the most important mediators of intracellular signal transduction mechanisms which regulate a variety of intracellular processes is free calcium. In salivary acinar cells, elevation of intracellular calcium concentration ($[Ca^{2+}]_i$) is essential for the salivary secretion induced by parasympathetic stimulation. However, in addition to $[Ca^{2+}]_i$, gap junctions which couple individual cells electrically and chemically have also been reported to regulate enzyme secretion in pancreatic acinar cells. Since the plasma membrane of salivary acinar cells has a high density of gap junctions, and these cells are electrically and chemically coupled with each other, gap junctions may modulate the secretory function of salivary glands. In this respect, I planned to investigate the role of gap junctions in the modulation of salivary secretion and $[Ca^{2+}]_i$, using mandibular salivary glands of rats. In order to measure the salivary flow rate, fluid was collected from the cannulated duct of the isolated perfused rat mandibular glands at 2 min intervals. $[Ca^{2+}]_i$, was measured from the cells loaded with fura-2 by spectrofluorometry. The results obtained were as follows: 1. CCh-induced salivary secretion was reversibly inhibited by 1 mM octanol, a gap junction blocker. 2. CCh-induced increase in $[Ca^{2+}]_i$, was also reversed by the application of 1 mM octanol. 3. Octanol did not block the initial increase in $[Ca^{2+}]_i$ caused by CCh, which suggested that the reduction of $[Ca^{2+}]_i$, caused by gap junction blockade was not resulted from the inhibition of $Ca^{2+}$ release from intracellular $Ca^{2+}$ stores. 4. Addition of octanol during stimulation with $1{\mu}M$ thapsigargin, a potent microsomal ATPase inhibitor, reduced $[Ca^{2+}]_i$, to the basal level. This suggested that inhibition of gap junction permeability closed plasma membrane $Ca^{2+}$ channels. 5. 2,5-di-tert-butyl-1,4-benzohydroquinone (TBQ) generated $[Ca^{2+}]_i$ oscillations resulting from periodic influx of $Ca^{2+}$ via plasma membrane. The TBQ-induced $[Ca^{2+}]_i$ oscillations were stopped by the application of 1mM octanol which implicated that gap junctions modulate the permeability of plasma membrane $Ca^{2+}$ channels. 6. Glycyrrhetinic acid, another well known gap junction blocker, also inhibited CCh-induced salivary secretion from rat mandibular glands. These results suggested that gap junctions play an important role in the modulation of fluid secretion from the rat mandibular glands and this was probably due to the inhibition of $Ca^{2+}$ influx through the plasma membrane $Ca^{2+}$ channels.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.853-860
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• 1997

Background : Chronic cough, defined as a cough persisting for three weeks or longer, is a common symptom for which outpatient care is sought. The most common etiologies of chronic cough are postnasal drip, asthma, and gastroesophageal reflux. Methacholine challenge is a useful diagnostic study in the evaulation of chronic cough, particularly useful in chronic cough patients with asthmatic symptom. Patients with chronic cough may have dysfunction of bronchial and extrathoracic airways. To evaluate if dysfunction of the bronchial and extrathoracic airways causes chronic cough, we assessed bronchial (BHR) and extrathoracic airway (EAHR) responsiveness to inhaled methacholine in patients with chronic cough. Method : 111 patients with chronic cough were enrolled in our study. Enrolled patients had no recorded diagnosis of asthma, bronchopulmonary disease, hypertension, heart disease or systemic disease and no current treatment with bronchodilator or corticosteroid. Enrolled patients consisted of 46 patients with cough alone, 24 patients with wheeze, 22 patients with dyspnea, 19 patients with wheeze and dyspnea. The inhaled methacholine concentrations causing a 20% fall in forced expiratory volume in 1s($PC_{20}FEV_1$) and 25% fall in maximal mid-inspiratory flow ($PC_{25}MIF_{50}$) were used as bronchial and extra thoracic hyperresponsiveness. Results : There were four response patterns to methacholine challenge study : BHR in 27 patients, EAHR in 16 patients, combined BHR and EAHR in 8 patients, and no hyperresponsiveness in 60 patients. In patients with cough alone, there were BHR in 3 patients, EAHR in 9 patients, and combined BHR and EAHR in 2 patients. In patients with wheeze and/or dyspnea, there were BHR in 24 patients, EAHR in 7 patients, and BHR and EAHR in 6 patients. Compared with patients with wheeze and/or dyspnea, patients with cough alone had more common EAHR than BHR. In patients with wheeze and/or dyspnea, BHR was more common than EAHR. Conclusion : These results show that among patients with hyperresponsiveness to methacholine, those with dyspnea and/or wheezing had mainly bronchial hyperresponsiveness, whereas those with chronic cough alone had mainly extrathoracic airway hyperresponsiveness.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.166-179
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• 2000

Background: The main reason for the failure of anti-cancer chemotherapy is the build up of resistance by cancer cells to apoptosis. The activation of NF-${\kappa}B$ in many cancer cell lines is reported to be underlying mechanism behind the build up of resistance of cancer cells to apoptosis. However, this relationship varied depending on the cells used in the experiments. In this study, the role of NF-${\kappa}B$ activation in the TNF-$\alpha$-induced apoptosis in lung cancer cell line was evaluated. Methods: NCI-H157 cells were used in all experiments. Cells were exposed to a high dose of TNF-$\alpha$(20 ng/ml) for 24 or 48 hours with or without blocking NF-${\kappa}B$ activation. TNF-$\alpha$-induced activation of NF-${\kappa}B$ was inhibited either by overexpression of $I{\kappa}B{\alpha}$-super repressor($I{\kappa}B{\alpha}$-SR) or by pre-treatment with proteasome inhibitor. Cell viability and apoptosis were evaluated with MTT assay and Western blot analysis for PARP fragment, respectively. Results: Cell viability of NCI-H157 cells was not affected by TNF-$\alpha$ treatment alone; however, combined treatment with TNF-$\alpha$ and cycloheximide reduced cell viability significantly, indicating that resistance to TNF-$\alpha$ is mediated by the new proteins synthesized after TNF-$\alpha$ stimulation. To evaluate the role of NF-${\kappa}B$ in the transcription of anti-apoptotic proteins. delete NF-${\kappa}B$ activation was inhibited before TNF-$\alpha$ stimulation. as described above. $AD5I{\kappa}B{\alpha}$-SR-transduction inhibited TNF-$\alpha$-induced nuclear translocation of p65. TNF-$\alpha$-induced cell death and apoptosis increased after inhibition of TNF-$\alpha$-induced activation of NF-${\kappa}$ by methods. Conclusion: These results suggest that TNF-$\alpha$-induced activation of NF-${\kappa}B$ may be closely related to the acquisition of the resistance to TNF-$\alpha$-induced apoptosis in lung cancer cells. Therefore. blocking of NF-${\kappa}B$ pathway can be a useful therapeutic modality in the treatment of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.61 no.4
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• pp.330-338
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• 2006

Background: The main factors associated with weight loss in patients with COPD are not well known. Since chronic inflammation and oxidative stress play a major pathogenic role in COPD, these factors may be responsible for the patients' weight loss. Therefore, this study measured the body mass index (BMI) in COPD patients and evaluated the variables, such as systemic inflammatory marker, oxidative stress and lung function, that correlate with the BMI. Method: The stable COPD patients (M:F=49:4, mean age=$68.25{\pm}6.32$) were divided into the lower (<18.5), normal (18.5-25) and higher (>25) BMI group. The severity of the airway obstruction was evaluated by measuring the $FEV_1$. The serum IL-6 and TNF-$\alpha$ levels were measured to determine the degree of systemic inflammation, and the carbonyl protein and 8-iso-prostaglandin $F_2{\alpha}$ level was measured to determine the level of oxidative stress. Each value in the COPD patients and normal control was compared with the BMI. Results: 1) Serum 8-iso-prostaglandin $F_2{\alpha}$ in COPD patients was significantly higher ($456.08{\pm}574.12pg/ml$) than that in normal control ($264.74{\pm}143.15pg/ml$) (p<0.05). However, there were no significant differences in the serum IL-6, TNF-$\alpha$, carbonyl protein between the COPD patients and normal controls. 2). In the COPD patients, the $FEV_1$ of the lower BMI group was significantly lower ($0.93{\pm}0.25L$) than that of the normal BMI ($1.34{\pm}0.52L$) and higher BMI groups ($1.72{\pm}0.41L$) (p<0.05). The lower $FEV_1$ was significantly associated with a lower BMI in COPD patients (p=0.002, r=0.42). The BMI of very severe COPD patients was significantly lower ($19.8{\pm}2.57$) than that of the patients with moderate COPD ($22.6{\pm}3.14$) (p<0.05). 3). There were no significant differences in the serum IL-6, TNF-$\alpha$, carbonyl protein and 8-iso-prostaglandin $F_2{\alpha}$ according to the BMI in the COPD patients. Conclusion: The severity of the airway obstruction, not the systemic inflammatory markers and oxidative stress, might be associated with the BMI in stable COPD patients. Further study will be needed to determine the factors associated with the decrease in the BMI of COPD patients.

• Childhood Kidney Diseases
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• v.5 no.1
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• pp.51-58
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• 2001

Purpose : Treatment of primary nocturnal enuresis (PNE) includs folk remedies and various treatments based on pathogenesis. We assessed the therapeutic effect of nocturnal water restrict ion as the primary treatment of PNE. Materials and methods : From October 1998 to June 1999, 41 children with PNE (>3 wet nights per week) who visited Ewha Womans University Mokdong hospital and who had good compliances to nocturnal water restriction for 2 months were included. Before and during nocturnal water restriction, daily fluid intake and urine volume were recorded for 2 days every 2 weeks. Responses to nocturnal water restriction were classified according to the decrease of wet nights as complete (>90$\%$), partial (50-90$\%$) and no (<50$\%$) response. Predictors such as age, sex, daytime voiding dysfunction, fluid intake, urine volume, maximum urine volume per void and fasting urine osmolality were evaluated. Results . The response rate to nocturnal water restriction fir 2 month was 82.9$\%$(34/41) [complete response 39.0$\%$(16/41), partial response : 43.9$\%$(18/41)]. The response rate to nocturnal water restriction was significantly higher in monosymptomatic PNE than polysymptomatic PNE and more effective in PNE with or nocturnal fluid intake, nocturnal urine volume, and maximum urine volume than lower nocturnal fluid intake, nocturnal urine volume and maximum urine volume per void (P<0.05). Nocturnal urine volume, maximum urine volume per void and luting urine osmolality after nocturnal water restriction has significantly increased higher in complete response and partial response group than in no response group (P<0.05). Conclusion : The nocturnal water restriction was effective in monosymptomatic PNE with nocturnal polydypsia, nocturnal polyuria and high bladder capacity. (J, Korean Soc Pediatr Nephrol 5 : 51- 8, 2001)

• Journal of Embryo Transfer
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• v.22 no.2
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• pp.121-126
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• 2007

The objective of this study was carried out to examine the selection effects of in vitro matured porcine follicular oocytes with polar body extrusion and early cleavage as non-invasive marker to know the developmental competence in advance. The porcine oocytes matured for 48 h were examined the polar body extrusion. The examined oocytes were matured for additional $16{\sim}18h$ and activated with 7% ethanol and cultured in $5{\mu}g/ml$ cytochalasin B for 5 h for diploid formation. The treated oocytes were cultured and examined the cleavage after 48 h and continued culturing for 5 days. The oocytes of 21.9% were discarded in morphological selection and 32.1% oocytes were discarded by failure of first polar body extrusion. The selected oocytes were matured and activated and then after 48 h the cleavage rates were examined. In morphologically selected oocytes, 15.8% oocytes were not cleaved and 52.6% oocytes were normally cleaved and 31.6% oocytes were hyper-cleaved over 8-cell stage. However in the first polar body extruded oocytes, 7.1% oocytes were not cleaved and 73.1% oocytes were normally cleaved and 19.8% oocytes were hyper-cleaved. The morphologically selected embryos that not cleavage-selected were developed in 16.7% up to blastocyst and the morphologically selected and cleavage-selected embryos were developed in 31.7%. The polar body extruded oocytes that were not carried out cleavage selection were developed in 39.0% and the polar body extruded and cleavage-selected embryos were developed 49.0%. The first cleavage timing was examined with 12 h interval after activation. In $0{\sim}12,\;12{\sim}24,\;24{\sim}36,\;and\;36{\sim}48h$ intervals, 4.1%, 68.6%, 19.1%, and 2.3% oocytes were cleaved and 5.9% oocytes were not cleaved until 48 after activation. The cleaved oocytes in each interval were cultured and developed upto blastocyst with 0, 39.1, 9.5, and 0%, respectively. This results suggests that polar body extruded and cleaved at $12{\sim}36h$ embryo has higher developmental potential than the others.

• The Korean Journal of Nuclear Medicine
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• v.32 no.6
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• pp.516-524
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• 1998

Purpose: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotherapy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. Materials and Methods: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH residue, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. Results: Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were $92.4{\pm}5.9%$ and $84.7{\pm}4.6%$, respectively, In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and $6.59{\times}10^9\;M^{-1}$, respectively, while those of Re-188-CEA79.4 were 41.6% and $4.2{\times}10^9\;M^{-1}$, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. Conclusion: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotheraphy.

• The Journal of the Korean bone and joint tumor society
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• v.12 no.1
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• pp.37-46
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• 2006

Purpose: To evaluate the end results between the surgical treatment with neo-adjuvant chemotherapy in Korea and non-invasive high intensity focused ultrasound (HIFU) technique in China for osteogenic sarcomas. Materials and Methods: The surgical treatment with neoadjuvant chemotherapy for total 67 cases (4 IIA, 58 IIB, and 5 III) in Korea since 1993 and the HIFU therapy for total 71 cases (57 II and 14 III) in China since 1997 was performed. In Korea, neo-adjuvant chemotherapy in 66 cases out of total 67 patients, but the adjuvant chemotherapy in only one case was done. On the contrary, in China, full chemotherapy for more than 9 times for 37 patients with stage II out of total 71 cases, but for less than 8 times of partial chemotherapy for 23 patients (stage II) and 14 patients (stage III) was done. The surgical treatment in total 67 Korean patients was done with wide resection and reconstruction for 56 patients, but wide resection without reconstruction for 5 patients and amputation for 6 patients. In china, total 71 patients was treated with average 1.5 times (1~4 times) of HIFU, and if there are some evidences of residual tumor after HIFU with following MRI, the second HIFU therapy was given 2~4 weeks later. After then, the bony defect was in no touch, keep bracing for long time expecting regeneration. All of them were followed for average 46 Mo (12~150 Mo) in Korea, but followed for average 22 Mo (9 years~8 months) in China. Results: The 5 year survival rate (stage II), was average 92.7% (IIA 100%, IIB 85.5%) in Korea series, and average 78.7% (full chemotherapy 91.8%, part chemotherapy 56.6%) in China series. The 3 year survival rate (stage III) was 20% in Korea and 7.1% in China. So, the final overall survival rate was 65.2% in Korea and 51.8% in China. The overall functional outcome score by ISOLS was 24.3 (81%) in Korea and 19.8 (73%) in China. There are 25.4% (17/67 cases) of complications in Korea and 31% (27 complications in 22 patients out of total 71 cases) in China after each treatment. Conclusions: The end results of Korea series which was treated with neoadjuvant chemo- and surgical methods are better than that of non-invasive thermal ablation in china. But we also believe the HIFU, as one of, was also effective to decrease the local recurrence and symptomatic releaf for stage II or even in III of osteogenic sarcomas.

• Clinical and Experimental Pediatrics
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• v.48 no.8
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• pp.832-838
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• 2005

Purpose : Mycoplasma pneumoniae infection is relatively common in childhood. Its extrapulmonary manifestations have been reported so much, but hepatitis associated with it has been reported rarely in Korea. Methods : A clinical study was performed on 556 patients of M. pneumoniae pneumonia diagnosed serologically at Gil hospital from January 2001 to December 2004. We reviewed 65 cases among these patients, who had elevated level of serum AST and ALT greater than 50 IU/L respectively without evidence of hepatitis A, B, C, Cytomegalovirus and Ebstein-Barr virus infections. Results : Hepatitis occurred in 11.7% of Mycoplasma pneumoniae pneumonia, especially in fall and winter times. Male to female ratio was 1.2 : 1 and the mean age was 4 years and 3 months. Besides hepatitis, cough(95.4%), sputum(52.3%) and dyspnea(12.3%) were common as pulmonary manifestations. And among gastrointestinal manifestations, nausea/vomiting(26.2%) was the most common symptom, followed by poor oral intake(12.3%), diarrhea(12.3%) and abdominal pain(6.2%). In addition to hepatomegaly(4.6%) and splenomegaly(4.6%), coarse breathing sound was the most common physical manifestation, followed by rale(63.1%), pharyngeal injection(26.2%), and rash(10.8%). Anemia was noted in 20.0%, neutrophilia in 10.8%, eosinphilia in 38.5% and thrombocytosis in 6.2%, respectively. Mean level of ESR and CRP was 32.02 mm/hr and 6.69 mg/dL, respectively. Mean level of AST and ALT was 293.80 IU/L and 181.48 IU/L, respectively. Hyperbilirubinemia was noted in 7.7% and hypoalbuminemia was noted in 58.5%. Lobar or lobular pneumonia(78.5%) was the most common finding in chest X-ray and left lower lobe(39.2%) was most commonly affected. Pleural effusion was noted in 26.2%. Mean duration of hospitalization was 9.91 days. Serum AST/ALT level was normalized within 9.94 days and pulmonary consolidation resolved within 14.29 days. Conclusion : The prognosis of M. pneumoniae hepatitis is good. However, liver function should be considerately checked in M. pneumoniae infection because its incidence is not so low.

• The Journal of Korean Society for Radiation Therapy
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• v.27 no.2
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• pp.97-106
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• 2015

Purpose : This study evaluate the thermal changes caused by use of the chemoport for drug administration and blood sampling during radiofrequency hyperthermia. Materials and Methods : 20cm size of the electrode radio frequency hyperthermia (EHY-2000, Oncotherm KFT, Hungary) was used. The materials of the chemoport in our hospital from currently being used therapy are plastics, metal-containing epoxy and titanium that were made of the diameter 20 cm, height 20 cm insertion of the self-made cylindrical Agar phantom to measure the temperature. Thermoscope(TM-100, Oncotherm Kft, Hungary) and Sim4Life (Ver2.0, Zurich, Switzerland) was compared to the actual measured temperature. Each of the electrode measurement position is the central axis and the central axis side 1.5 cm, 0 cm(surface), 0.5 cm, 1.8 cm, 2.8 cm in depth was respectively measured. The measured temperature is $24.5{\sim}25.5^{\circ}C$, humidity is 30% ~ 32%. In five-minute intervals to measure the output power of 100W, 60 min. Results : In the electrode central axis 2.8 cm depth, the maximum temperature of the case with the unused of the chemoport, plastic, epoxy and titanium were respectively $39.51^{\circ}C$, $39.11^{\circ}C$, $38.81^{\circ}C$, $40.64^{\circ}C$, simulated experimental data were $42.20^{\circ}C$, $41.50^{\circ}C$, $40.70^{\circ}C$, $42.50^{\circ}C$. And in the central axis electrode side 1.5 cm depth 2.8 cm, mesured data were $39.37^{\circ}C$, $39.32^{\circ}C$, $39.20^{\circ}C$, $39.46^{\circ}C$, the simulated experimental data were $42.00^{\circ}C$, $41.80^{\circ}C$, $41.20^{\circ}C$, $42.30^{\circ}C$. Conclusion : The thermal variations were caused by radiofrequency electromagnetic field surrounding the chemoport showed lower than in the case of unused in non-conductive plastic material and epoxy material, the titanum chemoport that made of conductor materials showed a slight differences. This is due to the metal contents in the chemoport and the geometry of the chemoport. And because it uses a low radio frequency bandwidth of the used equipment. That is, although use of the chemoport in this study do not significantly affect the surrounding tissue. That is, because the thermal change is insignificant, it is suggested that the hazard of the chemoport used in this study doesn't need to be considered.