Distribution and Potential Toxicological Effects of 2,2',4,4'-tetrabromodiphenyl Ether (BDE-47) as a Endocrine Disrupting Chemical in Human and Animals

Jung, Eui-Man,Yang, Hyun,An, Beum-Soo,Lee, Geun-Shik,Hyun, Sang-Hwan,Choi, Kyung-Chul,Jeung, Eui-Bae 韓國受精卵移植學會 2011 한국동물생명공학회지 Vol.26 No.4

Polybrominated diphenyl ethers (PBDEs) are a class of "brominated" (bromine containing) man-made chemicals used as flame retardant additives in plastics, foams, and textiles. PBDEs are found in various environmental contaminants in air, soil, sediment, and water, and 209 individual forms (congeners) of PBDE exist. Among these, 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) is the dominant congener found in the environment. Exposure to BDE-47 is now worldwide, and levels of BDE-47 have been detected in the blood of animals, including humans. BDE-47 can adversely affect the developmental system in both humans and animals. BDEs have structural similarities to polychlorinated biphenyls and thyroid hormones. However, recent studies have shown that BDEs may act as hormonal disrupting chemicals with detrimental effects. Therefore, a reliable assessment of BDE-47 toxicological action is required to understand the detrimental impacts of BDE-47 on human health. In this review, we overview recent studies on the distribution and potential toxicological effects of BDE-47 in humans and animals.

초등학교 체육교육과정 변천

박정화,김만의 대구교육대학교 1996 論文集 Vol.31 No.-

7개 대학 병원에서 조사한 지역사회 폐렴의 원인균

정문현,김성민,강문원,최희정,정희진,이경원,한성우,송재훈,신형식,김의종,최강원,김민자,박승철,배현주,정윤섭,김준명,백경란,신완식,이규만,김양리 대한감염학회 1997 감염 Vol.29 No.5

목 적 : 폐렴은 많이 발생하면서 사망률이 크게 줄지 않는 질환이며, 이를 적절히 치료하기 위해서는 원인균의 상대적 빈도, 기저 질환에 따른 변화, 항균제 내성률, 사망에 관련된 인자들을 알아야 한다. 원인균의 빈도는 지역마다 차이가 있고 국내에서는 항균제 내성률이 높아 지역사회에서 발생한 폐렴을 치료하기 위한 경험적 항균제 선택에 도움이 되기 위해 서울 소재 6개 대학 병원과 천안의 1개 대학 병원이 참여하여 위의 사항들에 대해 조사를 하였다. 방 법 : 1995년에 내과에 입원했던 16세 이상 환자를 대상으로 했다. 퇴원 진단명이 폐렴 또는 폐결핵인 병록지을 찾았고, 이중에서 병원 감염을 제외하였다. 특이도를 높이기 위해, 이들 중에서 호흡기 증상이 있고 발열이나 저체온이 있으면서 흉부 X-선에서 이상 음영이 있는 환자만을 대상으로 했다. 폐결핵은 위의 기준에 입원 초기에 항균제 치료를 하고 입원 7일 이후에야 항결핵제가 투여된 경우만을 폐렴의 원인균으로 하였다. 혈액 배양에서 양성, 객담에서 항상균이나 M. tuberculosis가 증명된 경우, 혈청학적으로 항체가가 4배 이상 증가된 경우, 조직에서 원인균이 진단된 경우는 확정(definitive) 원인균으로 하였고, 객담에서 배양된 균이 그람 도말과 일치할때, 항결액제에 대한 반응으로 진단한 폐결핵, 단일 항체가 양성이고 이에 대해 항균제를 사용했을 때는 가능(probable) 원인균으로 정의하였다. 다세균 감염균은 각각 다 른 원인균으로 처리하였다. 임상 조사와 함께 임상병리과에서 S. pneumoniae, H. influenzae, M. catarrhalis, mycoplasma, 항상균에 대해 검사 의뢰 건수, 배양 양성수, 항균제 감수성 결과를 조사하였다. 결 과 : 폐렴의 증례 정의에 부합하지 않은 135명과 폐결핵의 정의에 해당하지 않는 230명을 제외하고 남은 246명의 평균 나이는 58.2세이고 남성이 142명(58.2%) 이었고, 71%의 환자에서 기저 질환이 있었다. 진단 방법의 시행 횟수는 혈액 배양 77.6%, 혈청 검사 18.3%, 기관지경 검사는 4.1%였고, 세균의 항원 검사를 한 예는 없었다. 원인균이 밝혀진 예는 77명(31.3%)이었다. 다세균 감염이 4명에서 있었고, 원인균의 상대적 빈도는 결핵 20명(확정 17, 가능 3: 6개 병원 자료), 폐렴구균 18(확정8 가능 10)명과 폐렴구균이 아닌 Streptococcus 3명 (모두 확정), H. influenzae 11명(모두 가능), 그람음성간균 11명(확정 7, 가능 4) (K. pneumoniae 8건), Mycoplasma 5명(확정 1, 가능 4), S. aureus 4명(확정 2, 가능 2), mucormycosis 1명(확정)이었다. 평균 입원 기간은 19일이고, 중환자실 입원률과 인공 호흡기 사용율은 각각 18%와 9.3%였다. 사망률은 13.8%였고 사망까지 평균 기간은 14.6일 이었다. 다변량 분석에서 사망을 예측할 수 있는 인자는 저체온과 빈호흡이었다. 임상병리과에서 배양되었던 모든 폐렴구균의 Penicillin 내성률은 서울 3개 병원에서 82-88%, 천안에서 72%였다. 폐렴 환자의 혈액에서 배양된 7주는 모두 Penicillin에 감수성이 있었다. K. pneumoniae 8주 모두 cefotaxime과 gentamicin에 감수성을 보였다. 결 론 : 후향적 조사이고 병원마다 원인균 진단에 차이가 있지만, 원인이 밝혀진 경우에는 결핵과 폐렴균이 흔하였고, 무균 부위에서 배양된 폐렴구균의 항균제 내성률은 낮았다. 원인이 밝혀지지 않은 경우가 많고, 혈청검사로 진단되는 원인균이 드물며, 분리균주가 적어 항균제 내성 정도를 추정하기 어려워, 이를 밝히기 위한 전향적 조사가 필요하다. Background : Community-acquired pneumonia (CAP) is one of the leading causes of mortality and morbidity, but its management is still challenging. The limitation of diagnostic methods to identify etiologic agents rapidly make it necessary to use empiric antibiotics in almost all patients, and furthermore the discovery of new respiratory pathogens and the emergence of antibiotic-resistant organisms pose difficulties to the selection of an empiric regimen. To clarify the factors necessary for the optimal choice of empirical antibiotics, such as the frequency of etiologic agents, the attributable rates to death and antimicrobial resistance rates in the community, six university hospitals in Seoul and one university hospital in Cheonan were participating in this study. Methods : medical records of adults (>15 years of age) hospitalized for CAP or pulmonary tuberculosis between April 1995 and March 1996, were reviewed. Patients who satisfied all of the following criteria were included in the study: (1) fever or hypothermia; (2) respiratory symptoms; and (3) pulmonary infiltrates on chest roentgenogram. To exclude cases of pulmonary tuberculosis whose roentgenographic features were so typical that it could be easily differentiated from conventional pneumonia, two additional criteria were required for inclusion: antibiotic treatment during the first week of hospital admission and initiation of anti-tuberculosis medications thereafter. Organisms isolated from sterile body sites, acid-fast bacilli or Mycobacterium tuberculosis isolated from sputum, pathogens diagnosed by a 4-fold rising titer of antibodies to “atypical”pathogens, or pathogens revealed by histopathology were defined as definitive cause of pneumonia; isolates from sputum withcompatible Gram stain, pathogens diagnosed by a single diagnostic titer plus use of a specific antimicrobial agent, or tuberculosis diagnosed by clinucal response to anti- tuberculosis medications were considered probable cause of pneumonia. The records of the clinical microbiology were reviewed for isolates of S. pneumoniae, H. influenzae, M. catarrhalis, Mycobacterium or acid-fast bacilli, and Mycoplasma. Then the frequency of these agents, antimicrobial resistance rates of resiratory pathogens from all body sites, and their clinical significance were evaluated. Results: After excluding 365 patients (230 with pulmonary tuberculosis and 135 with CAP) who were screened for inclusion but did not meet the inclusion criteria,246 persons were enrolled in this study. Their mean age was 58.2 years old with slight male predominance (58.2%), and 171(71%) patients had underlying illnesses. Blood cultures were performed on 191 (77.6%) patients and serologic tests on 44(18.3%) patients. The etiologic agents were identified in 31.3%, and the list of individual agents, in decreasing order, was pulmonary tuberculosis (17 definite and 3 probable: data of six hospitals), S. pneumoniae (8 definite and 10 probable), non-pneumococci (3 definite), aerobic gram-negative bacilli (7 definite and 4 probable), Haemophilus spp. (11 probable), mycoplasma (1 definite and 4 probable), polymicrobial infections (2 definite and 2 probable: E. coli and S. agalactiae, M. tuberculosis and S. aureus, S. pneumoniae and H. influenzae and A. baumannii and K. pneumonias), S. aureus (2 definite and 2 probable) , and mucormycosis (1 definite). Among gram-negative bacilli, K. pneumoniae was the most common agent (8isolates). therates of admission to the intensive care unitand of using assisted ventilation were 18% and 9.3%, respectively. The mortality was 13.8% and logistic regression analysis showed that hypothermia and tachypnea were associated with death. Hospital stay averaged 19 days. Susceptible rates of S. pneumoniae isolated from all body sites to penicillin ranged from 8% to 28% but seven isolated from blood of patients with pneumonia were susceptible to penicillin. Also all 8 isolated of k> pneumoniae from patients with pneumonia were susceptible to cefotaxime and gentamicin. Conclusion: In Korea, in addition to S. pneumoniae, M. tuberculosis is an important agent causing community-acquired pneumonia. The low incidence of etiologic diagnosis is probably related to infrequent requesting of test "atypical" pathogens and does not represent the true incidence of infections by "atypical" pathogens, which well be answered by a prospective study. The antimicrobial resistance rates of major respiratory pathogens from sterile body sites are low, however, because of a small number of the isolates this result needs confirmation by a nationwide surveillance of antimicrobial resistance.

Apoptosis‐ and endoplasmic reticulum stress‐related genes were regulated by estrogen and progesterone in the uteri of calbindin‐D_9k and ‐D_28k knockout mice

Jung, Eui‐,Man,An, Beum‐,Soo,Choi, Kyung‐,Chul,Jeung, Eui‐,Bae Wiley Subscription Services, Inc., A Wiley Company 2012 Journal of cellular biochemistry Vol.113 No.1

<P><B>Abstract</B></P><P>Calcium (Ca<SUP>2+</SUP>) is an important regulator of apoptotic signaling. Calbindin‐D<SUB>9k</SUB> (CaBP‐9k) and ‐D<SUB>28k</SUB> (CaBP‐28k) have a high affinity for Ca<SUP>2+</SUP> ions. Uterine calbindins appear to be involved in the regulation of myometrial activity by intracellular Ca<SUP>2+</SUP>. In addition, uterine calbindins are expressed in the mouse endometrium and are regulated by steroid hormones during implantation and development. The aim of the present study was to evaluate the regulation of apoptosis in the uteri of CaBP‐9k, CaBP‐28k, and CaBP‐9k/28k knockout (KO) mice. Our findings indicated that Bax protein was enhanced in the uteri of CaBP‐28k and CaBP‐9k/28k KO mice compared to wild‐type (WT) and CaBP‐9k KO mice, but no difference was observed in Bcl‐2 protein expression. The expressions of caspase 3, 6, and 7 proteins were higher in both CaBP‐28k and CaBP‐9k/28k KO mice than in WT and CaBP‐9k KO mice. These results suggest that the absence of CaBP‐28k increases apoptotic signaling. We also investigated the expression of endoplasmic reticulum (ER) stress genes by Western blot analysis in calbindin KO mice. C/EBP homologous protein and immunoglobulin heavy chain‐binding protein protein levels were elevated in CaBP‐28k KO mice compared to WT mice. When immature mice were treated with 17β‐estradiol (E2) or progesterone (P4) for 3 days, we found that the expressions of Bax and caspase 3 protein were increased by E2 treatment in WT and CaBP‐9k KO mice, and by P4 treatment in CaBP‐28k KO mice. These results indicate that CaBP‐28k blocks the up‐regulation of apoptosis‐related genes and ER stress genes, implying that CaBP‐28k may decrease the expression of genes involved in apoptosis and ER stress in murine uterine tissue. J. Cell. Biochem. 113: 194–203, 2012. © 2011 Wiley Periodicals, Inc.</P>

Embryonic Stem Cell Test: Human Embryonic Stem Cell Use in Predicting Developmental Toxicity

Eui-Man Jung,Yeo-ul Choi,Hong-Seok Kang,Eui-Bae Jeung 한국동물생명공학회(구 한국동물번식학회) 2012 발생공학 국제심포지엄 및 학술대회 Vol.2012 No.1

Poster Session 1 : oral Presentation ; Gene Structure and Regulation : Characterization and regulation of a third gene encoding thioredoxin from Schizosaccharomyces pombe

( Eui Man Jung ),( Sung Min Hong ),( Hye Won Lim ),( Chang Jin Lim ) 한국생화학분자생물학회 (구 한국생화학회) 2005 62회 KSBMB Annual Meeting in 2005 Vol.- No.-

Functional role of a novel form of 60 kDa Mg-dependent neutral sphingom yelinase

KIM dae kyong,AHN kyong hoon,JUNG sang mi,JUNG sung yun,CHANG dong hoon,JEONG hyun chul,CHIN mi reyong,JEONG eui man,JO dong hwan,JUNG kwang mook,JEON hyung jun 大韓藥學會 2005 大韓藥學會 總會 및 學術大會 Vol.2005 No.2

Cytotoxicity evaluation and mechanism of endocrine-disrupting chemicals by the embryoid body test

Jung Eui-Man,Yoo Yeong-Min,Lee Jae-Hwan,Jeung Eui-Bae 한국독성학회 2022 Toxicological Research Vol.38 No.4

Endocrine-disrupting chemicals (EDCs) are a structurally diverse class of synthetic and natural compounds. EDCs can cause non-communicable diseases such as obesity, type 2 diabetes, thyroid disorders, neurodevelopmental disease, hormonedependent cancers, and reproductive disorders. The embryoid body test (EBT) is a developmental toxicity test method that determines the size of embryoid bodies (EBs) and the viability of mouse embryonic stem cells (mESCs) and fibroblasts (3T3 cells). The present study used the EBT to perform cytotoxicity evaluations of 10 EDCs and assessed the mechanistic relationship between endoplasmic reticulum (ER) stress and cytotoxicity. According to the statistical analysis and prediction model results, methylparaben, butylparaben, propylparaben, ethylparaben, triclosan, octylphenol, methoxychlor, bisphenol A, and diethylstilbestrol were classified as cytotoxic, but trichloroacetic acid was non-toxic. Classification accuracy was 90%. The mechanistic study showed that the cytotoxicities of butylparaben, propylparaben, octylphenol, and triclosan were induced by ER stress. The mRNA expressions of BiP, CHOP, and ATF4 were significantly higher following treatments with four EDCs compared to those after the control treatment. Compared to the control treatment, the mRNA levels of XBP1u and XBP1s increased significantly after butylparaben and propylparaben treatments, but did not increase with octylphenol and triclosan treatments. These results indicate that the EBT can be applied as an alternative toxicity test when evaluating the cytotoxicity of EDCs.

Establishment of transgenic fibroblasts for producing recombinant human interferon-α and erythropoietin in bovine milk.

Jung, Eui-Man,An, Beum-Soo,Kim, Yu-Kyung,Hwang, Inho,Lee, Jong-Yun,Shin, Tae-Young,Hyun, Sang-Hwan,Hwang, Woo-Suk,Jeung, Eui-Bae D. A. Spandidos 2013 MOLECULAR MEDICINE REPORTS Vol.7 No.2

<P>Human interferon α (IFN-α) and erythropoietin (EPO) have been used for a variety of purposes in clinical medicine. Human IFN-α has been used to treat several types of viral infection and cancer, as well as renal anemia, via stimulation of erythrocyte formation in the bone marrow. Transgenic cattle are excellent candidates for pharmaceutical production for humans due to their ability to produce recombinant proteins in milk. The purpose of the present study was to generate bovine transgenic fibroblasts capable of producing recombinant human IFN-α and EPO proteins in transgenic cattle milk. First, we analyzed the promoter activities of various bovine milk protein genes in HC11 mouse mammary epithelial cells. The bovine milk protein gene promoters were cloned into the Luc gene in a promoter-less pGL3-Basic vector. Presence of the αS1-casein promoter (-175 to +796 nt) resulted in an up to 16-fold increase in luciferase activity compared with that of the promoter-less construct. In addition, the human IFN-α and EPO genes were identified as significantly overexpressed in HC11 cells compared with the promoter-less construct. Together, the present results demonstrate that the construct with the αS1-casein promoter may induce secretion of recombinant human IFN-α and EPO into bovine milk. Furthermore, we generated transgenic fibroblasts expressing human IFN-α and EPO cDNA controlled by the αS1-casein promoter and two screening markers, enhanced green fluorescent protein and neomycin resistance. These transgenic fibroblasts may be a source of somatic cells for generating transgenic cattle that produce recombinant human IFN-α and EPO proteins during lactation.</P>

Establishment of inducible cAMP early repressor transgenic fibroblasts in a porcine model of human type 1 diabetes mellitus.

Jung, Eui-Man,Kim, Yu-Kyung,Lee, Geun-Shik,Hyun, Sang-Hwan,Hwang, Woo-Suk,Jeung, Eui-Bae D. A. Spandidos 2012 MOLECULAR MEDICINE REPORTS Vol.6 No.1

<P>Diabetes mellitus is a metabolic disease caused by impaired insulin secretion from the pancreatic β cells and increased insulin resistance in peripheral tissues. Recently, the overexpression of inducible cyclic AMP (cAMP) early repressor (ICER) Iγ in rodent pancreatic β cells was found to induce insulin deficiency and glucagon overproduction similar to that found in human diabetes mellitus. ICER Iγ with only a DNA binding domain interrupts the transcriptional regulation of the cAMP responsive element-binding protein (CREB) target genes. Based on this information, we hypothesized that the overexpression of ICER Iγ, the most powerful competitor to CREB, could be useful for generating a pig model of diabetes. First, we evaluated the promoter activities of the human insulin gene for the β cell-specific overexpression of ICER Iγ in the pig pancreas. The maximum promoter activity region [-1,431 nucleotides (nt) to +1 nt, +1 = the transcriptional start site] of the insulin gene presented an activity level 3-fold higher than a promoterless construct. Second, ICER Iγ overexpression controlled by this promoter region significantly blocked the glucose-mediated insulin transcription, such as that regulated by the viral promoter in the pancreatic β?cell line, MIN6. This suggests that the human insulin promoter may facilitate the overexpression of ICER?Iγ in porcine pancreatic β cells. In addition, the overexpression of ICER?Iγ in porcine β cells may induce human-like type 1 diabetes mellitus in pigs. In the present study, we generated transgenic fibroblasts containing ICER Iγ cDNA controlled by the human insulin promoter, as well as two screening markers, the green fluorescence protein and the neomycin resistance gene. These fibroblasts may provide a source for somatic cell nuclear transfer to generate a pig model that mimics human diabetes mellitus.</P>