• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.5
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• pp.383-393
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• 2008

Purpose: Cancer specific killing can be achieved by therapeutic gene activated by cancer specific promotor. Expression of sodium iodide symporter (NIS) gene causes transportation and concentration of iodide into the cell, therefore radioiodine treatment after NIS gene transfer to cancer cell could be a form of radionuclide gene therapy. luciferase (Luc) gene transfected cancer cell can be monitored by in vivo optical imaging after D-luciferin injection. Aims of the study are to make vector with both therapeutic NIS gene driven by AFP promoter and reporter Luc gene driven by CMV promoter, to perform hepatocellular carcinoma specific radiodiodine gene therapy by the vector, and assessment of the therapy effect by optical imaging using luciferase expression. Materials and Methods: A Vector with AFP promoter driven NIS gene and CMV promoter driven Luc gene (AFP-NIS-CMV-Luc) was constructed. Liver cancer cell (HepG2, Huh-7) and non liver cancer cell (HCT-15) were transfected with the vector using liposome. Expression of the NIS gene at mRNA level was elucidated by RT-PCR. Radioiodide uptake, perchlorate blockade, and washout tests were performed and bioluminescence also measured by luminometer in these cells. In vitro clonogenic assay with 1-131 was performed. In vivo nuclear imaging was obtained with gamma camera after 1-131 intraperitoneal injection. Results: A Vector with AFP-NIS-CMV-Luc was constructed and successfully transfected into HepG2, Huh-7 and HCT-15 cells. HepG2 and Huh-7 cells with AFP-NIS-CMV-Luc gene showed higher iodide uptake than non transfected cells and the higher iodide uptake was totally blocked by addition of perchlorate. HCT-15 cell did not showed any change of iodide uptake by the gene transfection. Transfected cells had higher light output than control cells. In vitro clonogenic assay, transfected HepG2 and Huh-7 cells showed lower colony count than non transfected HepG2 and Huh-7 cells, but transfected HCT-15 cell did not showed any difference than non transfected HCT-15 cell. Number of Huh-7 cells with AFP-NIS-CMV-Luc gene transfection was positively correlated with radioidine accumulation and luciferase activity. In vivo nuclear imaging with 1-131 was successful in AFP-NIS-CMV-Luc gene transfected Huh-7 cell xenograft on nude mouse. Conclusion: A Vector with AFP promoter driven NIS and CMV promoter driven Luc gene was constructed. Transfection of the vector showed liver cancer cell specific enhancement of 1-131 cytotoxicity by AFP promoter, and the effect of the radioiodine therapy can be successfully assessed by non-invasive luminescence measurement.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.291-298
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• 2007

Purpose: To investigate the feasibility of TI-201 SPECT with intra coronary injection (lC-I) in the detection of viable myocardium, we have performed SPECT imaging after direct intracoronary injection of TI-201 and images were compared with those of stress-reinjection (Re-I) SPECT. Methods: Fourteen coronary artery disease patients (male 11, mean age 54 years) who had myocardial infarction or demonstrated left ventricular wall motion abnormality on echocardiography were enrolled. Three mCi of TI-201 was injected into both coronary arteries during angiography and images were acquired between 6- and 24-hour after injection. Reinjection imaging with 1 mCi of TI-201 was performed at 4-hour after adenosine stress imaging with 3 mCi of TI-201. Images were interpreted according to 4-grade visual scoring system (grade 0-3). Segments with mild to moderated uptake (${\leq}$grade 1), and upgraded more than one score with reinjection, and were defined as viable myocardium. Results: Image quality was poor in two cases with IC-I. Numbers of non-viable segments were 60 (23.8%) with IC-I, and 38 (15.1%) with Re-I, respectively. Overall agreement for perfusion grade per myocardial segment in each IC-I and Re-I was 76.5%. Overall agreement for viable segment between IC-I and Re-I was 90.5%. Only one out of 38 segments interpreted as non-viable with Re-I were interpretated as viable with IC-I. And 23 out of 214 segments interpreted as viable with Re-I were interpreted as non-viable with IC-I. Conclusion: Intracoronary TI-201 SPECT seemed to be not advantageous over stress-rest reinjection imaging in the assessment of myocardial viability, mainly due to low count statistics at 6-hour or 24-hour delayed time points. The feasibility of intracoronary TI- 201 SPECT is considered to be limited.

• Tuberculosis and Respiratory Diseases
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• v.46 no.6
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• pp.817-825
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• 1999

Background : Forceps biopsy, bronchial brushing, and bronchial washing are used in conjunction with bronchoscopy to provide specimens for histologic and cytologic analysis in patients with suspected lung cancer. This study was performed to evaluate how many times brushing should be done and how much fluid should be used during bronchial washing for increasing diagnostic yield, and to evaluate which combination of these procedures gives the highest diagnostic yield. Methods : Forty patients, with suspected lung cancer, who had bronchoscopically visible lesions were enrolled in this prospective study. During one bronchoscopic examination four forceps biopsies, four bronchial brushings, and bronchial washing were done in all patients. The patients were divided into four groups by the amount of normal saline used for bronchial washing; group I, 10 ml ; group II, 20ml ; group III 30ml, and group IV, 40ml. We analyzed the results in 36 patients confirmed as lung cancer. Results : The diagnostic sensitivity of bronchial washing before and after forceps biopsy and bronchial brushing were 36% and 28%, respectively. The cumulative diagnostic sensitivity of bronchial washing was 47% and significantly higher than that of bronchial washing before or after forceps biopsy and bronchial brushing (p<0.05). The diagnostic sensitivity of bronchial washing with saline of 30ml was significantly higher than that of bronchial washing with saline of 10ml or 20ml (p<0.05). The diagnostic sensitivity of the first brushing was 75%, the second brushing 78%, the third brushing 83%, and the fourth brushing 67%. With repeated brushing up to three times, the diagnostic sensitivity increased to 92% (p<0.05). However, inclusion of the fourth brushing did not give a further increase of the diagnostic sensitivity. The diagnostic sensitivity of forceps biopsy was 86%. The diagnostic sensitivities of forceps biopsy by the type of bronchial lesion were as follows: tumor, 88%; infiltration, 67%; infiltration with nodularity, 80%; and collapse, 100%. The combination of forceps biopsy and bronchial washing gave a diagnostic sensitivity of 89%. The diagnostic sensitivity of combining forceps biopsy with bronchial brushing was 97%. Addition of bronchial washing did not increase the diagnostic yield over forceps biopsy and bronchial brushing. Conclusion : In patients with central lung cancer, forceps biopsies and repeated brushings up to three times should be done for maximal diagnostic yield.

• Korean Journal of Cleft Lip And Palate
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• v.9 no.2
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• pp.85-92
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• 2006

Korean Cleft Lip and Palate Association (KCLPA) was founded in 1996. The first overseas charity operation was in Karachi, Pakistan, 2002 and our association has visited fourteen times in six countries for the free cleft surgery: Pakistan, Egypt, Kenya, Morocco, Jordan and Vietnam. The cumulated number of operated patients reaches to 280. Before our association, many Korean oral and maxillofacial surgeons have performed charity operations individually since 1964. It was started from Vietnam but the activity is now carried on in Africa, middle-east Asia, south-east Asia, China, and Korea as an official team. LG electronics, a Korean company helped to propagate our team's activity to middle-east Asia to Africa. This paper is a report concerning about the results of our association's charity activities especially in Kenya, east Africa. We provided free cleft surgery for 30 patients in 2004 and 27 patients in 2005, in Nairobi. As the blood test for HIV of the cleft patients was not allowed before and during surgery, our surgeons and nurses were cautious about every movement during the surgeries. Thus the operation time for each patient was longer than any other time. The attitude of the local hospital and the doctors seemed to be accustomed to this situation. They helped us in case of needle injuries. Safety of medical staff and patients is more important than the number of the patients operated in charity operation. This belief should be approached being parallel and multidisciplinary as an international cooperation, focusing on international funding for medical support and continuous education for local doctors who are willing to devote to their people.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.33 no.4
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• pp.339-347
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• 2000

An algicidal bacterium, Micrococcus sp. LG-5 against the harmful dinoflagellate, Cochlodinium polykrikoides was isolated. The optimal conditions for the highest algicidal activity of bacterial culture filtrate showed in the range of $20{\~}30^{\circ}C$, at pH 7.0 and $3.0{\%}$ of NaCl concentration. In addition, $IC_(50)(mean of 50{\%} inhibitory concentration)$ of the culture filtrate against C. polykrikoides after incubation of 5 days was $0.482{\%}$. To investigate heat and pH stability of the culture filtrate of Micrococcus sp. LG-5, the culture filtrate ($pore size, 0.1 {\mu}m$) was heated to $121^{\circ}C for 15 min$ and adjusted pH from 2.0 to 10.0. There were no significant changes in algicidal activity by heat treatment and the pH change between pH from 5.0 to 10.0. The algicidal substances produced from Micrococcus sp. LG-5 were mainly detected in the fraction of $10,000{\~}1,000$ MWCO (molecular weight cut-off). The culture filtrate of Micrococous sp. LG-5 showed antimicrobial activity against Enterococcus faecalis, Escheiichia coli, Uebsiella pneunioniae and Vibrio altinolyticus, but did not show against Pseudomonas aeminosa, P. Buorescens, Salmonella typhi, Staphylococcus aureus, V. cholerae and V parahaemolyicus. The culture filtrate of Micrococcus sp. LG-5 was examined against 16 phytoplankton species and showed the algicidal activity against Ajexandzium tuarense, Eutreptiella Drnnastin, Gymnodinium catenatum, G. mikimotoi, G. sanguineum, eyodinium impuaicum, Heterocapsa triquetra, Heterosipa akashiwo, Prorocentrum micans and Pyraminonas sp.. However no algicidal effects of Micrococcus sp. LG-5 were observed against Chlamydomonas sp., Cylindrotheoa closterium, P. mininum, P. triestimum, Pseudonieschia sp. and Sczipuiella trochoidea. On the other hand, algicidal activity on the tested marinelivefood was not detected except for Isochrysis galbana. In addition, physiological responses of cultured olive flounder (Paralichthys oliraceus) exposed to $1 and 10{\%}$ of the culture filtrate of Micrococcus sp. LG-5 were measured. There were no clear changes in AST, GGT, creatinine, urea, total cholesterol, total protein, albumine, $Mg^(+2), Ca^(+2), Na^+, K^+, and Cl^-$. These results indicate that olive flounders were not affected when they were exposed to the culture filtrate of Micrococcus sp. LG-5.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.57-67
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• 1998

Purpose : This study was undertaken to determine the preoperative predictors of mortality and morbidity after lung cancer resection. Method: During the period from October 1, 1995 to August 31, 1996, a prospective study was conducted in 92 lung resection candidates diagnosed as lung cancer. For preoperative predictors of nonpulmonary factors, we considered age, sex, weight loss, hematocrit, serum albumin, EKG and concomitant illness, and for those of pulmonary factors, smoking history, presence of pneumonia, dyspnea scale(1 to 4), arterial blood gas analysis with room air breathing, routine pulmonary function test. And predicted postoperative(ppo) pulmonary factors such as PPO-$FEV_1$, ppo-diffusing capacity(DLco), predicted postoperative product(PPP) of ppo-$FEV_1%{\times}ppo$-DLco% and ppo-maximal $O_2$ uptake($VO_2$max) were also considered. Results: There were 78 men and 14 women with a median age of 62 years(range 42 to 82) and a mean $FEV_1$ of $2.37\pm0.06L$. Twenty nine patients had a decreased $FEV_1$ less than 2.0L. Pneumonectomy was performed in 26 patients, bilobectomy in 12, lobectomy in 54. Pulmonary complications developed in 10 patients, cardiac complications in 9, other complications(empyema, air leak, bleeding) in 11, and 16 patients were managed in intensive care unit for more than 48hours. Three patients died within 30 days after operation. The ppo-$VO_2$max was less than 10ml/kg/min in these three patients, but its statistical significance could not be determined due to small number of patients. In multivariate analysis, the predictor related to postoperative death was weight loss(p<0.05), and as for pulmonary complications, weight loss, dyspnea scale, ppo-DLco and extent of resection(p<0.05). Conclusions: Based on this study, preoperative nonpulmonary factors such as weight loss and dyspnea scale are more important than the pulmonary factors in the prediction of postoperative mortality and/or morbodity in lung resection candidates, but exercise pulmonary fuction test may be useful Our study suggests that ppo-$VO_2$max value less than 10ml/kg/min is associated with death after lung cancer resection but further studies are needed to validate this result.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.322-332
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• 1998

Background: Accurate staging is important to determine treatment modalities and to predict prognosis for the patients with lung cancer. The simple two-stage system of the Veteran's Administration Lung Cancer study Group has been used for staging of small cell lung cancer(SCLC) because treatment usually consists of chemotherapy with or without radiotherapy. However, this system does not accurately reflect segregation of patients into homogenous prognostic groups. Therefore, a variety of new staging system have been proposed as more intensive treatments including either intensive radiotherapy or surgery enter clinical trials. We evaluate the prognostic importance of TNM staging, which has the advantage of providing a uniform detailed classification of tumor spread, in patients with SCLC. Methods: The medical records of 166 patients diagnosed with SCLC between January 1989 and December 1996 were reviewed retrospectively. The influence of TNM stage on survival was analyzed in 147 patients, among 166 patients, who had complete TNM staging data. Results: Three patients were classified in stage I / II, 15 in stage III a, 78 in stage IIIb and 48 in stage IV. Survival rate at 1 and 2 years for these patients were as follows: stage I / II, 75% and 37.5% ; stage IIIa, 46.7% and 25.0% ; stage III b, 34.3% and 11.3% ; and stage IV, 2.6% and 0%. The 2-year survival rates for 84 patients who received chemotherapy(more than 2 cycles) with or without radiotherapy were as follows: stage I / II, 37.5% ; stage rna, 31.3% ; stage IIIb 13.5% ; and stage IV 0%. Overall outcome according to TNM staging was significantly different whether or not received treatment. However, there was no significant difference between stage IIIa and stage IIIb though median survival and 2-year survival rate were higher in stage IIIa than stage IIIb. Conclusion: These results suggest that the TNM staging system may be helpful for predicting the prognosis of patients with SCLC.

• Tuberculosis and Respiratory Diseases
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• v.63 no.1
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• pp.17-23
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• 2007

Background: Many diagnostic approaches for defining the definitive cause of pleurisy should be included due to the large variety of diseases resulting in pleural effusion. Although ADA is a useful diagnostic tool for making a differential diagnosis of pleural effusion, particularly for tuberculous pleural effusion, a definitive diagnostic cut-off value remains problematic in Korea. It was hypothesized that ADA multiplied by the Lymphocyte/Neutrophil ratio(L/N ratio) might be more powerful for making a differential diagnosis of pleural effusion. Methods: One hundred and ninety patients, who underwent thoracentesis and treatment in Chung-Ang University Hospital from January, 2005 through to February 2006, were evaluated. The clinical characteristics, radiologic data and the examination of the pleural effusion were analyzed retrospectively. Results: 1. Among the 190 patients, 59 patients (31.1%) were diagnosed with tuberculous pleurisy, 45 patients(23.7%) with parapneumonic effusion, 42 patients(22.1%) with malignant effusions, 36 patients(18.9%) with transudate, and 8 patients(4.2%) with empyema. One hundred and twenty one patients were found to have an ADA activity of 1 to 39 IU/L(63.7%). Twenty-nine were found to have an ADA activity of 40 to 75 IU/L(15.3%) and 40 were found to have an ADA activity of 75 IU/L or greater(21.0%). 2. Among the patients with tuberculous pleurisy, 5(8%), 18(30%) and 36 patients(60%) had an ADA activity ranging from 1 to 39 IU/L, 40 to 75 IU/L, and 75 IU/L or greater, respectively. In those with an ADA activitiy 40 to 75 IU/L, 18 patients(62%) had tuberculous pleurisy, 9(31%) had parapneumonic effusion and empyema, and 1(3.4%) had a malignant effusion. 3. In those with an ADA activity of 40 to 75 IU/L, there was no significant difference between tuberculous pleurisy and non-tuberculous pleural effusion(tuberculous pleurisy : 61.3 ${\pm}$ 9.2 IU/L, non-tuberculous pleural effusion : 53.3${\pm}$10.5 IU/L). 4. The mean L/N ratio of those with tuberculous pleurisy was 39.1 ${\pm}$ 44.6, which was significantly higher than nontuberculous pleural effusion patients (p<0.05). The mean ADA x L/N ratio of the tuberculous pleurisy patients was 2,445.7 ${\pm}$ 2,818.5, which was significantly higher than the non-tuberculous pleural effusion patients (level p<0.05). 5. ROC analysis showed that the ADA x L/N ratio had a higher diagnostic value than the ADA alone in the group with an ADA between 40-75 IU/L. Conclusion: The ADA multiplied by the lymphocyte-to-neutrophil ratio might provide a more definitive diagnosis of tuberculous pleurisy.

• The Korean Journal of Nuclear Medicine
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• v.38 no.6
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• pp.516-521
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• 2004

Background: Radioactive iodine (RAI) therapy and whole-body scanning are the fundamentals of treatment and follow-up of patients with differentiated thyroid cancer. It is generally accepted that a Thyroid-Stimulating Hormone (TSH) level of at least 30 ${\mu}U/ml$ is a prerequisite for the effective use of RAI, and that it requires 4-6 weeks of off-thyroxine to attain these levels. Because thyroxine withdrawal and the consequent hypothyroidism are often poorly tolerated, and occasionally might be hazardous, it is important to be certain that these assumptions are correct. We have measured serial changes in serum TSH after total thyroidectomy or withdrawl of thyroxine in patients with thyroid cancer. Subjects and Methods: Serum TSH levels were measured weekly after thyroidectomy in 10 patients (group A) and after the discontinuation of thyroxine in 12 patients (group B). Symptoms and signs of hypothyroidism were also evaluated weekly by modified Billewicz diagnostic index. Results: By the second week, 78% of group A patients and 17% of group B patients had serum TSH levels ${\geq}30{\mu}U/ml$. By the third week, 89% of group A patients and 90% of group B patients had serum TSH levels ${\geq}30{\mu}U/ml$. By the fourth week, all patients in two groups achieved target TSH levels and there were no overt hypothyroidism. Conclusion: in all patients, serum TSH elevated to the target concentration (${\geq}30{\mu}U/ml$) within 4 weeks without significant manifestation of hypothyroidism. The schedule of RAI administration could be adjusted to fit the needs and circumstances of individual patients with a shorter preparation period than the conventional.