• Journal of Genetic Medicine
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• v.4 no.1
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• pp.38-44
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• 2007

Purpose : Menkes disease is an X-linked recessively inherited disorder caused by the mutation of the ATP7A gene encoding copper-transporting P-type AT Pase. The phenotypic features are progressive neurological degeneration, mental retardation, loose skin, and vascular complications. Early diagnosis and treatment are very important for the prognosis of Menkes disease. Here, we describe nov el mutations of the ATP7A gene and prenatal diagnosis by mutation analysis. Methods : Five unrelated Korean Menkes patients were included in this study. They presented with depigmented wool-like hair, progressive neurologic deterioration, and hypotonia in infancy. Serum copper and ceruloplasmin levels w ere decreased. Brain magnetic resonance imaging revealed tortuous intracranial vessels. Mutation analysis has been carried out using cDNA from cultured skin fibroblasts or genomic DNA from peripheral leukocytes. Prenatal diagnosis was performed in two cases using chorionic villi samples or amniocytes. Results : Four novel mutations have been identified from four different families; c.3511+1G>A (p.E1099_N1171delinsMfsX 18), c.4005+5 G>A (p.V1268_R1335del), c.1870_2172del (p.S624_Q724del), and c.3352 G>A (p.G1118S). T he remaining one was previously reported (c.1933 C>T (p.V 1268_R1335del)). On prenatal DNA analysis, one w as diagnosed as normal, while the other turned out to be a female heterozygote with p.S624_Q724del mutation of the ATP7A gene. Conclusion : We identified 4 novel mutations of the ATP7A gene. Prenatal diagnosis in families at risk is critical in order to choose preventiv e options including an early treatment with copper-histidine therapy or therapeutic termination. Most mutations of the ATP7A gene were frame-shift mutations and prenatal diagnosis has been successfully carried out.

• Journal of Life Science
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• v.29 no.8
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• pp.904-915
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• 2019

Prostate cancer (PCa) is one of the most metastatic tumor. Although hormone therapy or surgical castration is mostly conducted to treat PCa, it has a lot of side effects. Recently, many researchers have been exploring the tumor microenvironment to remedy these circumstances. Immune cells, especially macrophages, are an important composition of the tumor microenvironment. Under normal conditions, macrophages exhibit mild tumoricidal activity against tumors. However, once activated by interferon gamma or lipopolysaccharides, macrophages can kill cancer cells directly or indirectly by secreting cytokines and chemokines. In this study, murine macrophage RAW 264.7 cells were treated with Phellinus linteus extract. To analyze their pro-inflammatory phenotype, we were used several assays such as a real-time polymerase chain reaction, an enzyme-linked immunosorbent and nitric oxide assay. Prostate cancer cells were treated with the RAW 264.7-conditioned media, which was identified as a pro-inflammatory nature, for 48 h, and the expression of epithelial-mesenchymal transition (EMT)-related genes was determined. Not only N-cadherin, Snail, Twist, Slug, and Cadherin 11, which are mechenchymal-related proteins, were decrease, but epithelial marker of E-cadherin was increased. In addition, the mRNA level of vimentin, ccl2, and vegfa were decreased, as the EMT is closely related to the migration and invasion of cancer cells. In conclusion, the RAW 264.7-conditioned media stimulated with P. linteus extract inhibited migration and invasion and regulated the EMT pathway in human prostate cancer cells.

• Journal of Chest Surgery
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• v.35 no.6
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• pp.420-429
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• 2002

Moderate hypothermic cardiopulmonary bypass (CPB) has commonly been used in cardiac surgery. Several cardiac centers recently practice normothermic CPB in cardiac surgery, However, the clinical effect and safety of normothermic CPB on cerebral metabolism are not established and not fully understood. This study was prospectively designed to evaluate the clinical influence of normothermic CPB on brain metabolism and to compare it with that of moderate hypothermic CPB. Material and Method: Thirty-six adult patients scheduled for elective cardiac surgery were randomized to receive normothermic (nasopharyngeal temperature ＞34.5 $^{\circ}C$, n=18) or hypothermic (nasopharyngeal temperature 29~3$0^{\circ}C$, n=18) CPB with nonpulsatile pump. Middle cerebral artery blood flow velocity (VMCA), cerebral arteriovenous oxygen content difference (CAVO$_{2}$), cerebral oxygen extraction (COE), modified cerebral metabolic rate for oxygen (MCMRO$_{2}$), cerebral oxygen transport (TEO$_{2}$), cerebral venous desaturation (oxygen saturation in internal jugular bulb blood$\leq$50 %), and arterial and internal jugular bulb blood gas analysis were measured during six phases of the operation： Pre-CPB (control), CPB-10 min, Rewarm-1 (nasopharyngeal temperature 34 $^{\circ}C$ in the hypothermic group), Rewarm-2 (nasopharyngeal temperature 37 $^{\circ}C$ in the both groups), CPB-off and Post-CPB (skin closure after CPB-off). Postoperaitve neuropsychologic complications were observed in all patients. All variables were compared between the two groups. Result： VMCA at Rewarm-2 was higher in the hypothermic group (153.11$\pm$8.98%) than in the normothermic group (131.18$\pm$6.94%) (p＜0.05). CAVO$_{2}$ (3.47$\pm$0.21 vs 4.28$\pm$0.29 mL/dL, p＜0.05), COE (0.30$\pm$0.02 vs 0.39$\pm$0.02, p＜0.05) and MCMRO$_{2}$ (4.71 $\pm$0.42 vs 5.36$\pm$0.45, p<0.05) at CPB-10 min were lower in the hypothermic group than in the normothermic group. The hypothermic group had higher TEO$_{2}$ than the normothermic group at CPB-10 (1,527.60$\pm$25.84 vs 1,368.74$\pm$20.03, p＜0.05), Rewarm-2 (1,757.50$\pm$32.30 vs 1,478.60$\pm$27.41, p＜0.05) and Post-CPB (1,734.37$\pm$41.45 vs 1,597.68$\pm$27.50, p＜0.05). Internal jugular bulb oxygen tension (40.96$\pm$1.16 vs 34.79$\pm$2.18 mmHg, p＜0.05), saturation (72.63$\pm$2.68 vs 64.76$\pm$2.49 %, p＜0.05) and content (8.08$\pm$0.34 vs 6.78$\pm$0.43 mL/dL, p<0.05) at CPB-10 were higher in the hypothermic group than in the normothermic group. The hypothermic group had less incidence of postoperative neurologic complication (delirium) than the normothermic group (2 vs 4 patients, p＜0.05). Lasting periods of postoperative delirium were shorter in the hypothermic group than in the normothermic group (60 vs 160 hrs, p<0.01). Conclusion: These results indicate that normothermic CPB should not be routinely applied in all cardiac surgery, especially advanced age or the clinical situations that require prolonged operative time. Moderate hypothermic CPB may have beneficial influences relatively on brain metabolism and postoperative neuropsychologic outcomes when compared with normothermic CPB.

• Radiation Oncology Journal
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• v.21 no.1
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• pp.54-65
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• 2003

Purpose : To analyze the gene expression Profiles of uterine ceulcal cancer, and its variation after radiation therapy, with or without concurrent chemotherapy, using a CDNA microarray. Materials and Methods :Sixteen patients, 8 with squamous ceil carcinomas of the uterine cervix, who were treated with radiation alone, and the other 8 treated w14h concurrent chemo-radiation, were Included in the study. Before the starling of the treatment, tumor biopsies were carried out, and the second time biopsies were peformed after a radiation dose of 16.2$\~$27 Gy. Three normal cervix tissues were used as a control group. The microarray experiments were peformed with 5 groups of the total RNAs extracted individually and then admixed as control, pre-radiation therapy alone, during-radiation therapy alone, pre-chemoradiation therapy, and during-chemoradlation therapy. The 33P-iabeled CDNAS were synthesized from the total RNAs of each group, by reverse transcription, and then they were hybridized to the CDNA microarray membrane. The gene expression of each microarrays was captured by the intensity of each spot produced by the radioactive isotopes. The pixels per spot were counted with an Arrayguage, and were exported to Microsoft Excel The data were normalized by the Z transformation, and the comparisons were peformed on the Z-ratio values calculated. Results : The expressions of 15 genes, including integrin linked kinase (ILK), CDC28 protein kinase 2, Spry 2, and ERK 3, were increased with the Z-ratio values of over 2.0 for the cervix cancer tissues compared to those for the normal controls. Those genes were involved In cell growth and proliferation, cell cycle control, or signal transduction. The expressions of the other 6 genes, Including G protein coupled receptor kinase 5, were decreased with the Z-ratio values of below -2.0. After the radiation thorapy, most of the genes, with a previously Increase expressions, represented the decreased expression profiles, and the genes, with the Z-ratio values of over 2.0, were cyclic nucleotlde gated channel and 3 Expressed sequence tags (EST). In the concurrent chemo-radiation group, the genes involved in cell growth and proliferation, cell cycle control, and signal transduction were shown to have increased expressions compared to the radiation therapy alone group. The expressions of genes involved in anglogenesis (angiopoietln-2), immune reactions (formyl peptide receptor-iike 1), and DNA repair (CAMP phosphodiesterase) were increased, however, the expression of gene involved In apoptosls (death associated protein kinase) was decreased. Conclusion : The different kinds of genes involved in the development and progression of cervical cancer were identified with the CDNA microarray, and the proposed theory is that the proliferation signal stalls with ILK, and is amplified with Spry 2 and MAPK signaling, and the cellular mitoses are Increased with the increased expression oi Cdc 2 and cell division kinases. After the radiation therapy, the expression profiles demonstrated 4he evidence of the decreased cancer cell proliferation. There was no sigificant difference in the morphological findings of cell death between the radiation therapy aione and the chemo-radiation groups In the second time biopsy specimen, however, the gene expression profiles were markedly different, and the mechanism at the molecular level needs further study.

• Journal of Chest Surgery
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• v.36 no.1
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• pp.1-6
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• 2003

Currently, atrial septal defect repair has been considered low risk operation duo to the development of open heart surgery Not only the operation itself, but also the cosmetic aspect is now focused. Though many methods exist as minimally invasive cardiac surgery in atrial septal defect repair, some surgeons advocate that right anterolateral thoracotomy is better than the others in the cosmetic aspect and we compared right anterolateral thoracotomy with median sternotomy. Material and Method: From January 1999 to August 2002, 43 patient underwent atrial septal defect repair by one operator, including 15 patients through right anterolateral thoracotomy(group A) and 15 patients through median sternotomy(group B) in Hanyang university Hospital. The data were randomized and operation outcomes were analyzed between these two groups. Result: The mean weight of group A was 38.77$\pm$15.57kg and 38.21$\pm$21.82kg in group B. In group A, mean operation (OP) time was 197.6$\pm$61.40min, mean cardiopulmonary bypass(CPB) time was 48.66$\pm$13.02min and mean fibrillation time or aortic cross clamp(ACC) time was 30$\pm$11.64min. In group B, mean OP time was 212.33$\pm$31.95min, mean CPB time was 55$\pm$12.10min, and mean fibrillation or ACC time was 29.33$\pm$9.04min. There was no significant differences in these two groups. In group A, mean mechanical ventilation time was 3.78$\pm$0.78 hours, mean postoperative ICU stay was 1.2$\pm$0.47 days and mean postoperative hospital stay was 10.20 41.08 days. In group B, mean mechanical ventilation time was 5.95$\pm$3.73 hours, mean post operative ICU stay was 1.41$\pm$0.61 days, and mean postoperative hospital stay was 12.20$\pm$3.55 days. There was no any significant difference in two groups. Group A had significantly lower mean thoracic and pleuropericardial drainage than group B (175.33$\pm$90.54cc vs 352.33$\pm$239.43cc, p<0.05). Complication was seen in one case in group B, transient 2nd degree A-V block. Conclusion: Right anterolateral thoracotomy was better than median sternotomy not only in cosmetic aspect but also in postoperative thoracic and pleuropericardial drainage, using the same instrument(p.0.05). But, right anterolateral thoracotomy was more technically difficult due to narrow operative field and we should be careful of aortic cannulation.