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Role of the MDM2 Promoter Polymorphism (-309T>G) in Acute Myeloid Leukemia Development

  • Cingeetham, Anuradha;Vuree, Sugunakar;Jiwatani, Sangeeta;Kagita, Sailaja;Dunna, Nageswara Rao;Meka, Phanni Bhushann;Gorre, Manjula;Annamaneni, Sandhya;Digumarti, Raghunadharao;Sinha, Sudha;Satti, Vishnupriya
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2707-2712
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    • 2015
  • Background: The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML. Materials and Methods: A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy. Results: MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p= 0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036). Conclusions: The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator.

Distribution of Electrically Conductive Sedimentary Layer in Jeju Island Derived from Magnetotelluric Measurements (MT 탐사자료를 이용한 제주도 지역의 전도성 퇴적층 분포 연구)

  • Lee, Choon-Ki;Lee, Heuisoon;Oh, Seokhoon;Chung, Hojoon;Song, Yoonho;Lee, Tae Jong
    • Geophysics and Geophysical Exploration
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    • v.17 no.1
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    • pp.28-33
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    • 2014
  • We investigate the spatial distribution of highly conductive layer using the one-dimensional inversions of the new magnetotelluric (MT) measurements obtained at the mid-mountain (400 ~ 900 m in elevation) western area of Jeju Island and the previous MT data over Jeju Island, Korea. The conductive layer indicates the sedimentary layer comprised of Seoguipo Fomation and U Formation. There is a definite positive correlation between the top of conductive layer and the earth surface in elevation. On the contrary, the bottom of conductive layer has a negative correlation with the surface elevation. In other words, the conductive layer has a shape of convex lens, which is thickest in the central part. The basement beneath the conductive layer could be concave in the central part of Jeju Island. A kriging considering the correlation between the layer boundary and the surface elevation provides a reliable geoelectric structure model of Jeju Island. However, further studies, i.e. three-dimensional modeling and interpretation integrated with other geophysical or logging data, are required to reveal the possible presence of three-dimensional conductive body near the subsurface vent of Mt. Halla and the causes of the bias in the depths of layer estimated from MT and core log data.

THE ANOMALIES OF PERMANENT DENTITION IN CLEIDOCRANIAL DYSPLASIA (쇄골두개 이형성증 환아의 치아발육이상)

  • Shin, Eun-Young;Choi, Byung-Jai;Lee, Jae-Ho;Son, Heung-Kyu
    • Journal of the korean academy of Pediatric Dentistry
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    • v.28 no.1
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    • pp.180-184
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    • 2001
  • Cleidocranial Dysplasia(CCD) is an autosomal dominant human bone disease characterized by abnormal clavicles, patent sutures and fontanelles, and dental anomalies. Among dental anomalies, it is characterized that permanent dentition is severly disturbed due to multiple supernumerary teeth and abnormalities of tooth morphology. A eight-year-old female patient diagnosed as cleidocranial dysplasia visited in our hospital. Upon clinical oral exam, retained deciduous teeth, constriction of dental arch, anterior cross bite, and multiple dental caries were observed. In the dental panoramic radiograph, retained deciduous teeth and multiple supernumerary teeth in the maxilla and the mandible were found. In the cephalometric radiograph, open sutures and wormian bones were seen. In the chest P-A view absence of clavicles was observed. The cleidocranial dysplasia patients have eruption problems in permanent dentition both in regions with and without supernumerary teeth. The severely delayed or arrested eruption of permanent teeth has been ascribed to various factors : 1) The presence of multiple supernumerary teeth, 2) malformed roots with lack of cellular cementum, 3) the jaw bone being too dense, and 4) abnormal resorption of bone and primary teeth. Formation and maturation of primary teeth in cleidocranial dysplasia are normal, whereas the permanent dentition has various anomalies. Therefore, dentists should understand the development of dentition in cleidocranial dysplasia, and treat them in proper time.

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Assessment of Root and Root Canal Morphology of Human Primary Molars using CBCT (CBCT를 이용한 유구치의 치근 및 근관의 형태학적 평가)

  • Choi, Yoomin;Kim, Seonmi;Choi, Namki
    • Journal of the korean academy of Pediatric Dentistry
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    • v.47 no.1
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    • pp.25-35
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    • 2020
  • The purpose of this study is to evaluate the morphological characteristics of the roots and roots canals of primary molar teeth using Cone-Beam Computed Tomography (CBCT). A total of 68 CBCT images of children aged 4 - 5 years was used for this study. A total of 160 molar teeth were analyzed. Various parameters such as the number of roots and canals, length of root and root canal, and the angulation and shape of the roots were analyzed. All maxillary primary molars had 3 roots. The presence of 2 root canals in 1 root was only observed in the mesiobuccal root of maxillary primary second molars. Most mandibular primary molars had 2 roots, and most mesial roots had 2 root canals. Concerning the length of the roots, the palatal root of the maxillary primary molar was found to be longest whereas the distobuccal root was shortest. In mandibular primary molars, the mesial root was longer than the distal root. In maxillary primary molars, the palatal root had the greatest angulation whereas the distal root has the greatest in mandibular molars. The root and root canals of maxillary primary molars were more curved in shape whereas mandibular primary molars were straight.

Entrepreneurship Education in Internet Business;Current Status & Future Direction (인터넷 창업교육 현황과 발전방안에 관한 연구)

  • Jeong, Jin-Su;Yang, Young-Seok
    • 한국벤처창업학회:학술대회논문집
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    • 2007.11a
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    • pp.143-174
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    • 2007
  • The objective of Starts-up education rears leading company that minimize a risk & connect them with successful idea. Internet Starts-up education is serviced in public & civil parts, it is insufficient to reach successful Starts-up support. This study is targeting on review the present condition of the Internet Starts-up education, research which it sees Internet Starts-up education actual condition investigation through investigation student of education satisfactorily and education contents and the plan to grope an Starts-up education progress coat problem and developmental plan it did. The current events point which has become research result escape first, age of the students of education, followed in educational background and, education motive and education experience presence education satisfactory boat song it appeared in these demand different, base grudge the form which is various it fixed and the education was demanded. Second, currently the department of pedagogy joining in establishment leader against the technical element which is advanced swip, the education reinforcement against an enterprise accomplishment ability back human factor, an enterprise propulsion environment and an enterprise item back enterprise environment element was demanded. Time after support and consulting, completion lifestyle community construction, completion lifestyle for item connection support and the trade name net after third, establishing an enterprise we the king, after toe ring back educating which carries on shoulder the importance of the civil official was embossed. The study which it sees led and like this investigation analysis the education progress for the successful support of the Internet Starts-up and time after connection setup construction it led and the plan which it will put out advancement of Starts-up education and it groped.

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Effect of Macmundongtang on Production and Secretion of Respiratory Mucus (맥문동탕이 호흡기 점액의 생성 및 분비에 미치는 영향)

  • Sung, Hyun Kyung;Min, Sang Yeon;Kim, Jang Hyun
    • The Journal of Pediatrics of Korean Medicine
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    • v.27 no.1
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    • pp.69-81
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    • 2013
  • Objectives In this study, effects of Macmundongtang (MMT) on ATP or TNF-${\alpha}$ or PMA or EGF induced MUC5AC mucin production and gene expression from human airway epithelial cells and the increase in airway epithelial mucosubstances of rats were investigated. Materials and Methods Confluent NCI-H292 cells were pretreated for 30min in the presence of MMT and treated with ATP ($200{\mu}M$) or PMA (10 ng/ml) or EGF (25 ng/ml) or TNF-${\alpha}$ (0.2 nM) for 24hrs, to assess the effect of MMT both on ATP- or PMA- or EGF- or TNF-${\alpha}$-induced MUC5AC mucin production using enzyme-linked immunosorbent assay (ELISA) and on gene expression by the same inducers using reverse transcription-polymerase chain reaction (RT-PCR). At the same time, hypersecretion of airway mucus was induced by exposure of rats to SO2 during 3 weeks. Effect of orally-administered MMT during 2 weeks on increase in airway epithelial mucosubstances from tracheal goblet cells of rats was assesed using histopathological analysis after staining the epithelial tissue with PAS-alcian blue. Possible cytotoxicity of MMT was assessed by investigating the potential damage of kidney and liver functions by measuring serum GOT/GPT activities and serum BUN concentration of rats and the body weight gain during experiment, after administering MMT orally. Results (1) MMT did not only inhibit but also increased MUC5AC mucin productions and expression levels of MUC5AC gene from NCI-H292 cells. (2) MMT did not decrease the amount of intraepithelial mucosubstances of trachea of rats. (3) MMT did not show renal and hepatic toxicities and did not affect body weight gain of rats during experiment. Conclusions The result from the present study suggests that MMT might normalize the production and gene expression of airway mucin observed in various respiratory diseases accompanied by yin-deficiency, without in vivo toxicity to liver and kidney functions after oral administration.

Selective Estrogen Receptor Modulation by Larrea nitida on MCF-7 Cell Proliferation and Immature Rat Uterus

  • Ahn, Hye-Na;Jeong, Si-Yeon;Bae, Gyu-Un;Chang, Minsun;Zhang, Dongwei;Liu, Xiyuan;Pei, Yihua;Chin, Young-Won;Lee, Joongku;Oh, Sei-Ryang;Song, Yun Seon
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.347-354
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    • 2014
  • Larrea nitida is a plant that belongs to the Zygophyllaceae family and is widely used in South America to treat inflammatory diseases, tumors and menstrual pain. However, its pharmacological activity remains unclear. In this study we evaluated the property of selective estrogen receptor modulator (SERM) of Larrea nitida extracts (LNE) as a phytoestrogen that can mimic, modulate or disrupt the actions of endogenous estrogens, depending on the tissue and relative amount of other SERMs. To investigate the property of SERM of LNE, we performed MCF-7 cell proliferation assays, estrogen response element (ERE)-luciferase reporter gene assay, human estrogen receptor (hER) binding assays and in vivo uterotrophic assay. To gain insight into the active principles, we performed a bioassay-guided analysis of LNE employing solvents of various polarities and using classical column chromatography, which yielded 16 fractions (LNs). LNE showed high binding affinities for $hER{\alpha}$ and $hER{\beta}$ with $IC_{50}$ values of $1.20{\times}10^{-7}$ g/ml and $1.00{\times}10^{-7}$ g/ml, respectively. LNE induced $17{\beta}$-estradiol (E2)-induced MCF-7 cell proliferation, however, it reduced the proliferation in the presence of E2. Furthermore, LNE had an atrophic effect in the uterus of immature rats through reducing the expression level of progesterone receptor (PR) proteins. LN08 and LN10 had more potent affinities for binding on $hER{\alpha}$ and ${\beta}$ than other fractions. Our results indicate that LNE had higher binding affinities for $hER{\beta}$ than $hER{\alpha}$, and showed SERM properties in MCF-7 breast cancer cells and the rat uterus. LNE may be useful for the treatment of estrogen-related conditions, such as female cancers and menopause.

A high response to controlled ovarian stimulation induces premature luteinization with a negative impact on pregnancy outcomes in a gonadotropin-releasing hormone antagonist cycle

  • Koo, Hwa Seon;Cha, Sun Hwa;Kim, Hye Ok;Song, In Ok;Min, Eung Gi;Yang, Kwang Moon;Park, Chan Woo
    • Clinical and Experimental Reproductive Medicine
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    • v.42 no.4
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    • pp.149-155
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    • 2015
  • Objective: The goal of this study was to investigate the relationship between serum progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration and the pregnancy rate among women undergoing controlled ovarian stimulation for in vitro fertilization (IVF) or intracytoplasmic sperm injection-embryo transfer (ICSI-ET) using a flexible antagonist protocol. Methods: This prospective study included 200 IVF and ICSI-ET cycles in which a flexible antagonist protocol was used. The patients were divided into five distinct groups according to their serum P4 levels at the time of hCG administration (0.80, 0.85, 0.90, 0.95, and 1.00 ng/mL). The clinical pregnancy rate (CPR) was calculated for each P4 interval. Statistically significant differences were observed at a serum P4 level of 0.9 ng/mL. These data suggest that a serum P4 concentration of 0.9 ng/mL may represent the optimal threshold level for defining premature luteinization (PL) based on the presence of a significant negative impact on the CPR. Results: The CPR for each round of ET was significantly lower in the PL group defined using this threshold (25.8% vs. 41.8%; p=0.019), and the number of oocytes retrieved was significantly higher than in the non-PL group ($17.3{\pm}7.2$ vs. $11.0{\pm}7.2$; p=0.001). Elevated serum P4 levels on the day of hCG administration were associated with a reduced CPR, despite the retrieval of many oocytes. Conclusion: Measuring serum P4 values at the time of hCG administration is necessary in order to determine the optimal strategy for embryo transfer.

Seroprevalence of Norwalk-Like Viruses (NLVs) in Seoul: Detection Using Baculovirus-Expressed Norwalk Virus Capsid Antigen (Baculovirus에서 발현된 Norwalk Virus 캡시드 항원에 대한 국내인의 혈청학적 반응도)

  • Kang, Shin-Jai;Nam, Ki-Bum;Cho, Yang-Ja;Kim, Kyung-Hee
    • The Journal of Korean Society of Virology
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    • v.27 no.2
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    • pp.161-168
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    • 1997
  • The present study was designed to estimate the seroprevalence of NLVs among diarrheagenic children and in healthy adults in Seoul and its vicinity with the use of an EIA and an Western blot (WB) based on recombinant Norwalk virus capsid protein (rNV) and crude virus preparations as antigen. Seroconversion was observed in 34 (83%) of 41 tested using the EIA and in 21 (54%) of 39 using the WB, suggesting that the NLVs with epitopes common to rNV are prevalent in Seoul area. Diarrheal children who were known to have been infected with several other strains of the NLVs showed no significant antibody response to the rNV. Infection with rNV occurred earlier in life: primary infections with rNV were common before the age of 6 months and over 91 % of children had evidence of infection by that age by the EIA. Since the amount of the NLV antigens available for seroepidemiologic surveys is limited, we tried to detect NLV antibody by using crude virus preparations as antigen. One crude virus preparation of a child whose stool yielded genetically distinct NLV revealed the presence of the plural number of bands upon SDS-PAGE, but precipitated only one band (62 kDa) after the WB with a serum (collected 10 days after the onset of symptoms) of another diarrheal child. The WB assay we present in this report revealed that the NLVs are prevalent among Korean population and that the sera contained antibody to a single major structural protein, with molecular sizes of 58 to 62 kDa, compatible with the sizes reported for the Norwalk virus and Snow Mountain agent proteins, respectively. When the results of the WB were compared with those obtained by the EIA, the EIA antibody assay was sensitive enough to detect an antibody rise of as much as 4096-fold but not as specific as the WB. The WB assay presented in this paper will provide a powerful tool to elucidate not only antigenic structures of the NL Vs but also seroepidemiology of the NLV infection. The availability of an unlimited source of antigen will enable a large scale serologic studies that will greatly increase our understanding of the role of NLVs in human enteric illness.

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Sequence and Phylogenetic Analysis of Respiratory Syncytial Virus Isolated from Korea (국내에서 유행한 Respiratory Syncytial 바이러스의 염기서열 및 계통분석)

  • Kwon, Soon-Young;Choi, Young-Ju;Kim, So-Youn;Song, Ki-Joon;Lee, Yong-Ju;Choi, Jong-Ouck;Seong, In-Wha
    • The Journal of Korean Society of Virology
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    • v.26 no.1
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    • pp.9-22
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    • 1996
  • Respiratory Syncytial virus (RSV) is an important cause of acute lower respiratory tract infections in human, with infants and young children being particularly susceptible. In the temperate zones, sharp annual outbreaks of RSV occur during the colder months, in both the northern and the southern hemisphere. RSV is unusual in that it can repeatedly reinfect individuals throughout life and infect babies in the presence of maternal antibody. RSV isolates can be divided into two subgroups, A and B, on the basis of their reactions with monoclonal antibodies, and the two subgroups are also distinct at the nucleotide sequence level. The specific diagnosis of RSV infection was best made by isolation of virus in tissue culture, identification of viral antigen, or by specific serologic procedures. Recently, rapid detection of RSV and analysis of RSV strain variation became possible by development of methods of reverse transcription and polymerase chain reaction amplification. In this study, to determine the genetic diversity of RSV found in Korea, 173 bp and 164 bp spanning selected regions of the RSV F and SH genes were enzymatically amplified and sequenced, respectively. Eight for F gene and three for SH gene were detected in 66 nasopharyngeal swap samples tested. Two major antigenic subgroups, A and B were confirmed from Korean samples (seven for subgroup A and one for subgroup B). At the nucleotide level of the F gene region, Korean subgroup A strains showed 95-99% homologies compared to the prototype A2 strain of subgroup A and 93-100% homologies among Korean subgroup A themselves. For the SH gene region, Korean subgroup A strain showed 97.5% homology compared to the prototype A2 strain of subgroup A, and Korean subgroup B strain showed 97% homology compared to the prototype 18537 strain of subgroup B. Most of base changes were transition and occured in codon position 3, which resulted in amino acid conservation. Using the maximum parsimony method, phylogenetic analysis indicated that Korean RSV strains formed a group with other RSV strains isolated from the United States, Canada, the Great Britain and Australia.

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