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DNA Structural Perturbation Induced by the CPI-Derived DNA Interstrand Cross-linker : Molecular Mechanisms for the Sequence Specific Recognition

  • Park, Hyun-Ju
    • Archives of Pharmacal Research
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    • v.24 no.5
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    • pp.455-465
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    • 2001
  • The highly potent cytotoxic DNA-DNA cross-linker consists of two cyclopropa[c]pyrrolo[3,4-3]indol-4(5H)-ones insoles [(+)-CPI-I] joined by a bisamido pyrrole (abbreviated to "Pyrrole"). The Pyrrole is a synthetic analog of Bizelesin, which is currently in phase II clinical trials due to its excellent in vivo antitumor activity. The Pyrrole has 10 times more potent cytotoxicity than Bizelesin and mostly form DNA-DNA interstrand cross-links through the N3 of adenines spaced 7 bp apart. The Pyrrole requires a centrally positioned GC base pair for high cross-linking reactivity (i.e., $5^1$-T$AT_2$A*-$3^1$), while Bizelesin prefers purely AT-rich sequences (i.e., $5^1$-T$AT_4$A*-$3^1$, where /(equation omitted) represents the cross-strand adenine alkylation and A* represents an adenine alkylation) (Park et al., 1996). In this study, the high-field $^1$H-NMR and rMD studies are conducted on the 1 1-mer DNA duplex adduct of the Pyrrole where the 5′(equation omitted)TAGTTA*-3′sequence is cross-linked by the drug. A severe structural perturbation is observed in the intervening sequences of cross-linking site, while a normal B-DNA structure is maintained in the region next to the drug-modified adenines. Based upon these observations, we propose that the interplay between the bisamido pyrrole unit of the drug and central C/C base pair (hydrogen-bonding interactions) is involved in the process of cross-linking reaction, and sequence specificity is the outcome of those interactions. This study suggests a mechanism for the sequence specific cross-linking reaction of the Pyrrole, and provides a further insight to develop new DNA sequence selective and distortive cross-linking agents.

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New Whitening agent: Kojyl-APPA

  • Hwang, Jae-Sung;Kim, Duck-Hee;Soomi Anh;Baek, Heung-Soo;Park, Hyunjung -Jin;Lee, Jin-Young;Lee, Byeong-Gon;Ihseop Chang;Kang, Hak-Kee
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.27 no.1
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    • pp.119-131
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    • 2001
  • Exposure of the human skin to UV-light can cause sun-tanning, photoaging and even photo-carcinogenesis. Melanin is important in protecting the skin against UV damage, but excessive or uneven melanin production can lead to the formation of freckles and aged spot. Control of hyperpigmentation is becoming even more important as aged population continues to grow. These needs led us to develop effective and safe depigmenting-agent, kojyl 3-aminopropyl phosphate (kojyl-APPA), called Whitegen. The development of whitegen was based on the fact that phosphate group of 3-aminopropyl phosphate can make kojic acid more compatible to the skin membrane and more stable. Instability of kojic acid has been a problem in cosmetic use. The insertion of phosphoester group has been recognized as a powerful tool to improve such physical properties as solubility and stability, because the phosphodiester residue is well characterized as a non-toxic moiety, having a high affinity for cell membranes. Kojyl-APPA showed no tyrosinase inhibition effect compared to kojic acid in vitro, but showed tyrosinase inhibition effect in situ. It means that kojyl-APPA is converted to kojic acid enzymatically in cells. Kojyl-APPA showed the inhibitory activity on melanin synthesis in mouse melanoma and normal humal melnaocytes and also showed long-lasting stability in comparison with its original form (kojic acid). Kojyl-APPA showed depigmenting effects when applied to UVB-induced hyperpigmentated region of guinea pig skin. Based on these results, kojyl 3-aminopropyl phosphate can be used as a safe and effective ingredient for the brightness and cleanness of skin.

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A Numerical Study of Ventilation System Operation for Smoke Control in a Subway Station when a Train under Fire is Approaching (화재열차가 진입하여 정차하는 지하철 역사에서 제연을 위한 환기장치 운전에 대한 수치해석 연구)

  • Lee, Seung-Ho;Hur, Nahm-Keon;Cha, Chul-Hyun;Ryou, Hong-Sun;Kim, Dong-Hyeon;Jang, Yong-Jun
    • Proceedings of the SAREK Conference
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    • 2009.06a
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    • pp.136-141
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    • 2009
  • The platform screen door(PSD) is installed in the station of the Seoul Metro 9th line for passengers' safety and comfortable environment of the station. The track way exhaust system(TES) is also operated with PSD to exhaust heat released from train. TES can also be used for the purpose of the heat and smoke control in an emergency case of the carriage fire. When the fire is occurred, operation of TES is switched to the smoke exhaust mode form its normal ventilation mode. In the present study, a subway station of Seoul Metro 9th line is modeled, and a 3-D CFD simulation is performed to investigate effectiveness of designed TES in case of fire. A scenario that a train under fire is arriving the station is simulated for several possible operation modes of the TES using moving mesh technique. As a result, temperature and CO concentration distribution in the station is obtained for each operation modes of TES. The effectiveness of TES operation in case of fire is also discussed.

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Fine Needle Aspiration Cytology of Peripheral T Cell Lymphoma of the Lung - A Case Report - (폐에 발생한 말초 T 세포 림프종의 세침흡인 세포학적 소견 - 1예 보고 -)

  • Shin, Ok-Ran;Lee, Youn-Soo;Kang, Chang-Suk;Kim, Byung-Kee;Shim, Sang-In;Jung, Eun-Sun
    • The Korean Journal of Cytopathology
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    • v.10 no.2
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    • pp.157-162
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    • 1999
  • Primary non-Hodgkin's lymphoma of the lung is rare among extranodal lymphomas. The most common form is low grade B-cell type originated from the mucosa-associated lymphoid tissue (MALT) of the lung and primary peripheral T cell lymphoma of the lung is extremely rare. We recently experienced a case of fine needle aspiration cytology of primary peripheral T cell lymphoma of the lung in a 39-year-old male patient. The cytologic smears revealed some sheets of reactive epithelial cells, epithelioid histiocytes, and numerous polymorphous population of lymphoid cells composed of small and intermediate sized lymphoid cells and mature lymphocytes. Lymphoid cells were slightly larger than normal mature lymphocytes and showed significant irregularity of nuclear membrane. The internal nuclear structure was marked by chromatin clumping, clear parachromatin areas, and inconspicuous nucleoli. Histopathologically, atypical small lymphocytes infiltrated in the interstitium and alveolar sac. By the immunohistochemical study and molecular biologic study of gene rearrangement, the T cell clonality of atypical lymphoid cells was confirmed.

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Types of Shared Medical Decision Making for Terminally Ill Patients (말기 환자의 공유 의료적 의사결정에 관한 의료인의 인식 유형)

  • Jo, Kae Hwa;Kim, Gyun Moo
    • Journal of Hospice and Palliative Care
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    • v.17 no.4
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    • pp.278-288
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    • 2014
  • Purpose: The purpose of this study is to analyze types of shared medical decision making by health professionals in a decision making position. Methods: The Q-methodology was used. Q sample was constructed with a total of 35 Q-statements that were offered with a 9-point rating scale. The statements were structured to generate answers that would form a shape of a normal distribution. Answers to Q sample were analyzed using a QUANL PC program. Results: Four types of shared medical decision making were identified. Type I is patient-centered decision making, Type II is physician-centered, Type III is health professional-centered and Type IV is patient-family-centered. Conclusion: Study results indicate that it is recommended to develop an education program based on the four types of shared medical decision making so that health professionals can be provided with different approaches according to their decision making style.

Molecular Mechanism of Male Germ Cell Apoptosis after Busulfan Treatment

  • Kim, Jin-Hoi
    • Proceedings of the Korean Society of Embryo Transfer Conference
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    • 2002.11a
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    • pp.63-65
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    • 2002
  • Identification of spermatogonial stem cell-specific surface molecules is important in understanding the molecular mechanisms underlying the maintenance and differentiation of these cells. We have found that spermatogonia from busulfan treated mice expressed an autoantigen that distinguishes between undifferentiated and differentiated spermatogonia. Four to six weeks after busulfan treatment, germ cells located in the basal compartment of seminiferous epithelium show isotype-specific IgG deposits that form due to autoimmunity. Before busulfan treatment, the level of testicular IgG was very low but IgG levels began to increase after week 4 and peaked at week 6. When cells from the busulfan treated testis were analyzed using laser scanning cytomeoy (LSC), the frequency of cells positive for IgG deposits, 6-integrin, and 1-integrin were 16.5${\pm}$3.8%, 11.8${\pm}$2.6%, and 9.0${\pm}$ 1.4%, respectively. Immunofluorescent staining suggested that most, if not all of the cells with IgG-deposits isolated from a laminin-coated dish, were also positive for a spermatogonial stem cell marker \ulcorner6-integrins as well as for a germ cell-specific marker TRA 98. We determined serum and intratesticular IgG levels and the soundness of seminiferous tubule basement membrane from busulfan treated mice using electron microscopy, in order to study the mechanism responsible for IgG deposits in spermatogonia. We found that the basement membranes of seminiferous tubules from busulfan treated mice were severely impaired when compared to those of normal adult, neonates and w/wv mice. Furthermore, new blood cells were observed in the surface of the damaged basement membrane along the seminiferous tubules. These results suggest that the IgG in spermatogonial stem cells accumulates from circulating blood through the impaired basement membranes induced by busulfan treatment. Taken together, our study suggests that IgG can be used as a new marker for undifferentiated spermatogonia cells.

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Breast augmentation surgery using an inframammary fold incision in Southeast Asian women: Patient-reported outcomes

  • Randquist, Charles;Por, Yong Chen;Yeow, Vincent;Maglambayan, Joy;Simonyi, Susan
    • Archives of Plastic Surgery
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    • v.45 no.4
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    • pp.367-374
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    • 2018
  • Background This analysis presents patient-reported outcomes of breast augmentation procedures performed in Singapore using an inframammary fold incision and the "5 Ps" best practice principles for breast augmentation. These data are the first of their kind in Southeast Asian patients. Methods Through a retrospective chart review, patients who underwent primary breast augmentation with anatomical form-stable silicone gel breast implants using an inframammary fold incision were followed for ${\geq}6$ months postoperatively. The BREAST-Q Augmentation Module (scores standardized to 0 [worst] - 100 [best]) and Patient and Observer Scar Assessment Scale (POSAS; 1 [normal skin] to 10 [worst scar imaginable]) were administered. Responses were summarized using descriptive statistics. Patient-reported events were collected. Results Twenty-two Southeast Asian patients (mean age, 35.1 years) completed ${\geq}1$ postoperative BREAST-Q and POSAS assessment and were assessed 11 months to 5.5 years postoperatively. The mean postoperative BREAST-Q satisfaction with breasts and psychosocial well-being scores were 69.2 and 84.0, respectively. The mean POSAS score for their overall opinion of the scar was 4.2; the mean scores for all scar characteristics ranged from 1.2 to 4.2. Over 90% of patients (20/22) said that they would recommend the procedure. Patient complaints following surgery included anisomastia (possibly pre-existing; n=2), sensory loss at the nipple (n=2) or around the nipple (n=3), scarring (n=4), and slight capsular contracture (n=1). No patients required reoperation. Conclusions Southeast Asian patients reported high long-term satisfaction scores on the BREAST-Q scale and with their scar characteristics following breast augmentation using an inframammary fold incision, and nearly all said they would recommend this procedure. No reoperations were necessary in patients assessed for up to 5.5 years postoperatively.

Is Pneumocystis carinii vertically transmitted to neonatal rats?

  • Hong, Sung-Tae;Park, Yun-Kyu;Kim, Jin;Kim, Dug-Ha;Yun, Chong-Ku
    • Parasites, Hosts and Diseases
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    • v.37 no.3
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    • pp.149-156
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    • 1999
  • Pneumocystis carinii is pulmonary pathogen of immunocompromised humans or other mammals. Its infection results from activation of organism involves in latent infection or form new infection through the air. Almost all children are known to be infected within 2 to 4 years of birth, though prenatal transplacental transmission has not yet been demonstrated. In this study we observed experimental P.carinii infection in neonatal rats, thus investigating the possibility of transplacental vertical transmission by Diff-Quik staining of the lung impression smears and in-sity hybridization for lung sections. The postive rate of P.carinii infection in immunosuppressed maternal rats was 100%, but that in normal maternal rats was 0%. Cystic forms of P.carinii were observed in three of six 1-week old neonatal rats born of heavily infected mothers, but none of them was positive by in-situ hybridization. Five weeks after birth, cystic forms were detected in four neonatal rats. In the lobes of the lungs, no predilection site of P.carinii was recognized. Counts of cystic forms on smears and the reactivity of in-situ hbridization in the lungs of neonatal rats 0 were signficantly lower than in maternal rats. The present findings suggest that P.carinii is rarely transmitted through the placenta and proliferates less successfully in the lungs of neonatal rats than in mothers.

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Antitumor Components of the Cultured Mycelia of Lepiota procera (갓버섯의 항균 분석)

  • 김병각;심미자;김옥남;김하원;최응칠
    • Journal of Food Hygiene and Safety
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    • v.4 no.2
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    • pp.109-118
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    • 1989
  • To find antitumor components in the cultured mycelia of Lepiota procera, the proteinpolysaccharide obtained from the mycelia was subjected to DEAE - Sephadex A-50 column chromatography and Sepharose-4B gel filtration. Of the fractions, the purified Fraction C1 was named lepiotan and examined for antitumor activity against the solid form of sarcoma 180 in ICR mice. The inhibition ratio of lepiotan was 64% at the dose of 10 mg/kg/day for 10days. The chemical analysis of lepiotan showed 60% polysaccharide and 21 % protein. The polysaccharide moiety was found to be a heteromannoglucan which consisted of 46.3% glucose, 40.2% mannose and 11.0% fucose. When the antitumor component, Fraction A, was examined for immunopotentiation activity, it was found to increase the number of plaques in hemolytic plaque assay and to restore the immunity in the tumor-bearing mice up to 89.7% of the normal level. Also the antitumor acitivity was suppressed by the treatment with carrageenan, an antimacrophage agent. These results indicate that the antitumor activity was exerted through immunopotentiation, but not through direct cytotoxicity against the tumor.

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Development of An User-Friendly Integrated Program and Teaching System for Automatic Polishing Robot System (자동 연마 시스템의 사용자 지향형 통합 프로그램 및 자동 교시 시스템 개발)

  • Go, Seok-Jo;Lee, Min-Cheol;Lee, Man-Hyeong;An, Jung-Hwan;Jeon, Cha-Su;Lee, Don-Jin
    • Journal of Institute of Control, Robotics and Systems
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    • v.7 no.4
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    • pp.334-343
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    • 2001
  • Polishing a die that has free-form surfaces is a time-consuming and tedious job, and requires a considerable amount of high-precision skill. Some workers tend to gradually avoid the polishing work because of the poor environment caused by dust and noise. In order to reduce the polishing time and cope with the shortage of skilled workers, a user-friendly automatic polishing system was developed in this research. The polishing system with five degrees of freedom is able to keep the polishing tool normal to the die surface. The polishing system is controlled by a PC-NC controller. To easily operate the developed polishing robot system, this study developed an integrated program in the Windows environment. This program consists of four modules: the polishing module, the graphic simulator, the polishing data generation module, and the teaching module. Also, the automatic teaching system was developed to easily obtain teaching data and it consists of a three dimensional joystick and a proximity sensor. The joystick is used to simultaneously drive the polishing system to an arbitrary orientation and the proximity sensor is used to obtain teaching points precisely. Also, to evaluate the stability of the driving program and the teaching system, polishing experiments of a die of saddle shape were carried out.

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