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An International Collaborative Program To Discover New Drugs from Tropical Biodiversity of Vietnam and Laos

  • Soejarto, Djaja D.;Pezzuto, John M.;Fong, Harry H.S.;Tan, Ghee Teng;Zhang, Hong Jie;Tamez, Pamela;Aydogmus, Zeynep;Chien, Nguyen Quyet;Franzblau, Scott G.;Gyllenhaal, Charlotte;Regalado, Jacinto C.;Hung, Nguyen Van;Hoang, Vu Dinh;Hiep, Nguyen Tien;Xuan, Le Thi;Hai, Nong Van;Cuong, Nguyen Manh;Bich, Truong Quang;Loc, Phan Ke;Vu, Bui Minh;Southavong, Boun Hoong
    • Natural Product Sciences
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    • v.8 no.1
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    • pp.1-15
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    • 2002
  • An International Cooperative Biodiversity Group (ICBG) program based at the University of Illinois at Chicago initiated its activities in 1998, with the following specific objectives: (a) inventory and conservation of of plants of Cuc Phuong National Park in Vietnam and of medicinal plants of Laos; (b) drug discovery (and development) based on plants of Vietnam and Laos; and (c) economic development of communities participating in the ICBG project both in Vietnam and Laos. Member-institutions and an industrial partner of this ICBG are bound by a Memorandum of Agreement that recognizes property and intellectual property rights, prior informed consent for access to genetic resources and to indigenous knowledge, the sharing of benefits that may arise from the drug discovery effort, and the provision of short-term and long-term benefits to host country institutions and communities. The drug discovery effort is targeted to the search for agents for therapies against malaria (antimalarial assay of plant extracts, using Plasmodium falciparum clones), AIDS (anti-HIV-l activity using HOG.R5 reporter cell line (through transactivation of the green fluorescent protein/GFP gene), cancer (screening of plant extracts in 6 human tumor cell lines - KB, Col-2, LU-l, LNCaP, HUVEC, hTert-RPEl), tuberculosis (screening of extracts in the microplate Alamar Blue assay against Mycobacterium tuberculosis $H_{37}Ra\;and\;H_{37}Rv),$ all performed at UIC, and CNS-related diseases (with special focus on Alzheimer's disease, pain and rheumatoid arthritis, and asthma), peformed at Glaxo Smith Kline (UK). Source plants were selected based on two approaches: biodiversity-based (plants of Cuc Phuong National Park) and ethnobotany-based (medicinal plants of Cuc Phuong National Park in Vietnam and medicinal plants of Laos). At mc, as of July, 2001, active leads had been identified in the anti-HIV, anticancer, antimalarial, and anti- TB assay, after the screening of more than 800 extracts. At least 25 biologically active compounds have been isolated, 13 of which are new with anti-HIV activity, and 3 also new with antimalarial activity. At GSK of 21 plant samples with a history of use to treat CNS-related diseases tested to date, a number showed activity against one or more of the CNS assay targets used, but no new compounds have been isolated. The results of the drug discovery effort to date indicate that tropical plant diversity of Vietnam and Laos unquestionably harbors biologically active chemical entities, which, through further research, may eventually yield candidates for drug development. Although the substantial monetary benefit of the drug discovery process (royalties) is a long way off, the UIC ICBG program provides direct and real-term benefits to host country institutions and communities.

Biological Functions of N- and O-linked Oligosaccharides of Equine Chorionic Gonadotropin and Lutropin/Chorionic Gonadotropin Receptor

  • Min, K.S.
    • Korean Journal of Animal Reproduction
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    • v.24 no.4
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    • pp.357-364
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    • 2000
  • Members of the glycoprotein family, which includes CG, LH, FSH and TSH, comprise two noncovalently linked $\alpha$- and $\beta$-subunits. Equine chorionic gonadotropin (eCG), known as PMSG, has a number of interesting and unique characteristics since it appears to be a single molecule that possesses both LH- and FSH-like activities in other species than the horse. This dual activity of eCG in heterologous species is of fundamental interest to the study of the structure-function relationships of gonadotropins and their receptors. CG and LH $\beta$ genes are different in primates. In horse, however, a single gene encodes both eCG and eLH $\beta$ -subunits. The subunit mRNA levels seem to be independently regulated and their imbalance may account for differences in the quantities of $\alpha$ - and $\beta$-subunits in the placenta and pituitary. The dual activities of eCG could be separated by removal of the N-linked oligosaccharide on the $\alpha$-subunit Asn 56 or CTP-associated O-linked oligosaccharides. The tethered-eCG was efficiently secreted and showed similar LH-like activity to the dimeric eCG. Interestingly, the FSH-like activity of the tethered-eCG was increased markedly in comparison with the native and wild type eCG. These results also suggest that this molecular can implay particular models of FSH-like activity not LH-like activity in the eCG/indicate that the constructs of tethered molecule will be useful in the study of mutants that affect subunit association and/or secretion. A single-chain analog can also be constructed to include additional hormone-specific bioactive generating potentially efficacious compounds that have only FSH-like activity. The LH/CG receptor (LH/CGR), a membrane glycoprotein that is present on testicular Leydig cells and ovarian theca, granulosa, luteal, and interstitial cells, plays a pivotal role in the regulation of gonadal development and function in males as well as in nonpregnant and pregnant females. The LH/CGR is a member of the family of G protein-coupled receptors and its structure is predicted to of a large extracellular domain connected to a bundle of seven membrane-spanning a-helices. The LH/CGR phosphorylation can be induced with a phorbol ester, but not with a calcium ionophore. The truncated form of LHR also was down-regulated normally in response to hCG stimulation. In contrast, the cell lines expressing LHR-t631 or LHR-628, the two phosphorylation-negative receptor mutant, showed a delay in the early phase of hCG-induced desensitization, a complete loss of PMA-induced desensitization, and an increase in the rate of hCG-induced receptor down-regulation. These results clearly show that residues 632~653 in the C-terminal tail of the LHR are involved in PMA-induced desensitization, hCG-induced desensitization, and hCG-induced down-regulation. Recently, constitutively activating mutations of the receptor have been identified that are associated with familial male-precocious puberty. Cells expressing LHR-D556Y bind hCG with normal affinity, exhibit a 25-fold increase in basal cAMP and respond to hCG with a normal increase in cAMP accumulation. This mutation enhances the internalization of the free and agoinst-occupied receptors ~2- and ~17- fold, respectively. We conclude that the state of activation of the LHR can modulate its basal and/or agonist-stimulated internalization. Since the internalization of hCG is involved in the termination of hCG actions, we suggest that the lack of responsiveness detected in cells expressing LHR-L435R is due to the fast rate of internalization of the bound hCG. This statement is supported by the finding that hCG responsiveness is restored when the cells are lysed and signal transduction is measured in a subcellular fraction (membranes) that cannot internalize the bound hormone.

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Effects of Heat-stress on Rumen Bacterial Diversity and Composition of Holstein Cows (고온 스트레스 영향에 따른 홀스타인종 젖소의 반추위내 미생물 균총 변화)

  • Kim, Dong Hyeon;Kim, Myung Hoo;Kim, Sang Bum;Ha, Seung Min;Son, Jun Kyu;Lee, Ji Hwan;Hur, Tai Young;Lee, Jae Yeong;Park, Ji Hoo;Choi, Hee Chul;Lee, Hyun Jeong;Park, Beom Young;Ki, Kwang Seok;Kim, Eun Tae
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.39 no.4
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    • pp.227-234
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    • 2019
  • This study was performed to investigate the effect of heat-stressed environment on rumen microbial diversity in Holstein cows. Rectal temperature and respiration rate were measured and rumen fluid was collected under normal environment (NE; Temperature humidity index (THI)=64.6) and heat-stressed environment (HE; THI=87.2) from 10 Holstein cows (60±17.7 months, 717±64.4 kg) fed on the basis of dairy feeding management in National Institute of Animal Science. The rumen bacteria diversity was analyzed by using the Illumina HiSeqTM 4000 platform. The rectal temperature and respiratory rate were increased by 1.5℃ and 53 breaths/min in HE compared to that in NE, respectively. In this study, HE exposure induced significant changes of ruminal microbe. At phylum level, Fibrobacteres were increased in HE. At genus level, Ruminococcaceae bacterium P7 and YAD3003, Butyrivibrio sp. AE2032, Erysipelotrichaceae bacterium NK3D112, Bifidobacterium pseudolongum, Lachnospiraceae bacterium FE2018, XBB2008, and AC2029, Eubacterium celulosolvens, Clostridium hathewayi, and Butyrivibrio hungatei were decreased in HE, while Choristoneura murinana nucleopolyhedrovirus, Calothrix parasitica, Nostoc sp. KVJ20, Anabaena sp. ATCC 33047, Fibrobacter sp. UWB13 and sp. UWB5, Lachnospiraceae bacterium G41, and Xanthomonas arboricola were increased in HE. In conclusion, HE might have an effect to change the rumen microbial community in Holstein cows.

Investigations on Conditions Required for Decomposition and Disinfection of infected Poultry under Different Fermentation Systems (발효방법에 의한 감염가금의 분해 및 발효소독 특성에 관한 연구)

  • Hong, J.T.;Yu, B.K.;Kim, H.J.;Lee, S.H.;Park, K.S.;Oh, K.Y.;Kim, D.G.;Lee, J.J.
    • Journal of Animal Environmental Science
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    • v.16 no.2
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    • pp.153-160
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    • 2010
  • Recently, the treatment of dead poultry has become more important issue because, the infected poultry, which was buried under the ground, causes environmental contaminations such as steep water and reek occurrence, etc. Therefore, in this study, we investigated the type of treatment and the composting methods influencing to the characteristics on decomposition and fermentative disinfection of dead poultry with poultry manure and sawdust. The results of the port tests showed that amputated poultry treated by the cut-sterilization were not only more decomposed, with less smell compared to the non-treated poultry carcass. When we treated thermophilic microorganism such as bacillus in this amputated poultry, the temperature of treated poultry increased much fester, the fermentation temperature didn't rise and not maintained constantly for long time due to the small size of the fermentation port. On the other hand, we did fermentation test by the layered disposal method with more poultry. In this experiment, the temperature of fermented poultry rose to $54^{\circ}C$ in a day and maintained around $55^{\circ}C$ during four weeks period. With less odor outside the experiment room. further. Also, we inoculated AI virus, ND virus in the excrement for studying the effect of fermentative disinfection. The result of the test revealed that AI virus was destructed within 60 minutes and ND virus was destructed within 30 minutes at the temperature of $56^{\circ}C$. Therefore, the investigations revealed scope of composting method for steam sterilized infected poultry in the originated area mixed with poultry manure, sawdust by thermophilic microorganism could increase the effectiveness of fermentative disinfection and decrease the environmental contamination.

A Study of a Teaching Plan for Gifted Students in Elementary School Mathematics Classes (일반학급에서의 초등 수학 영재아 지도 방안 연구)

  • Kim, Myeong-Ja;Shin, Hang-Kyun
    • Journal of Elementary Mathematics Education in Korea
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    • v.13 no.2
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    • pp.163-192
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    • 2009
  • Currently, our country operates gifted education only as a special curriculum, which results in many problems, e.g., there are few beneficiaries of gifted education, considerable time and effort are required to gifted students, and gifted students' educational needs are ignored during the operation of regular curriculum. In order to solve these problems, the present study formulates the following research questions, finding it advisable to conduct gifted education in elementary regular classrooms within the scope of the regular curriculum. A. To devise a teaching plan for the gifted students on mathematics in the elementary school regular classroom. B. To develop a learning program for the gifted students in the elementary school regular classroom. C. To apply an in-depth learning program to gifted students in mathematics and analyze the effectiveness of the program. In order to answer these questions, a teaching plan was provided for the gifted students in mathematics using a differentiating instruction type. This type was developed by researching literature reviews. Primarily, those on characteristics of gifted students in mathematics and teaching-learning models for gifted education. In order to instruct the gifted students on mathematics in the regular classrooms, an in-depth learning program was developed. The gifted students were selected through teachers' recommendation and an advanced placement test. Furthermore, the effectiveness of the gifted education in mathematics and the possibility of the differentiating teaching type in the regular classrooms were determined. The analysis was applied through an in-depth learning program of selected gifted students in mathematics. To this end, an in-depth learning program developed in the present study was applied to 6 gifted students in mathematics in one first grade class of D Elementary School located in Nowon-gu, Seoul through a 10-period instruction. Thereafter, learning outputs, math diaries, teacher's checklist, interviews, video tape recordings the instruction were collected and analyzed. Based on instruction research and data analysis stated above, the following results were obtained. First, it was possible to implement the gifted education in mathematics using a differentiating instruction type in the regular classrooms, without incurring any significant difficulty to the teachers, the gifted students, and the non-gifted students. Specifically, this instruction was effective for the gifted students in mathematics. Since the gifted students have self-directed learning capability, the teacher can teach lessons to the gifted students individually or in a group, while teaching lessons to the non-gifted students. The teacher can take time to check the learning state of the gifted students and advise them, while the non-gifted students are solving their problems. Second, an in-depth learning program connected with the regular curriculum, was developed for the gifted students, and greatly effective to their development of mathematical thinking skills and creativity. The in-depth learning program held the interest of the gifted students and stimulated their mathematical thinking. It led to the creative learning results, and positively changed their attitude toward mathematics. Third, the gifted students with the most favorable results who took both teacher's recommendation and advanced placement test were more self-directed capable and task committed. They also showed favorable results of the in-depth learning program. Based on the foregoing study results, the conclusions are as follows: First, gifted education using a differentiating instruction type can be conducted for gifted students on mathematics in the elementary regular classrooms. This type of instruction conforms to the characteristics of the gifted students in mathematics and is greatly effective. Since the gifted students in mathematics have self-directed learning capabilities and task-commitment, their mathematical thinking skills and creativity were enhanced during individual exploration and learning through an in-depth learning program in a differentiating instruction. Second, when a differentiating instruction type is implemented, beneficiaries of gifted education will be enhanced. Gifted students and their parents' satisfaction with what their children are learning at school will increase. Teachers will have a better understanding of gifted education. Third, an in-depth learning program for gifted students on mathematics in the regular classrooms, should conform with an instructing and learning model for gifted education. This program should include various and creative contents by deepening the regular curriculum. Fourth, if an in-depth learning program is applied to the gifted students on mathematics in the regular classrooms, it can enhance their gifted abilities, change their attitude toward mathematics positively, and increase their creativity.

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Effects of Weed Removal Time on Growth and Yield of Maize (잡초제거(雜草除去) 시기(時期)가 옥수수의 생육(生育) 및 수량(收量)에 미치는 영향(影響))

  • Kang, Y.K.;Park, K.Y.;Jong, S.K.;Park, S.U.;Moon, H.G.
    • Korean Journal of Weed Science
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    • v.5 no.1
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    • pp.50-55
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    • 1985
  • Effects of weed removal time on maize growth and yield were evaluated in the fields dominated with Poligonum spp., Chenopodium album, Echinochloa crusgalli and Digitaria adsendens from 1982 to 1983 in Suweon. Weed removal treatments were as follows: (a) kept weedfree all season, (b) weeded at 10 day intervals after maize emergence but stopped weeding at 3,5,7,9 leaf stages, (c) weeds initially removed at 3,5,7 and 9 leaf stages and the plots then kept weed free, (d) weeds left all season. Maize kept weed free from maize emergence to 7 leaf stages showed no grain yield reduction due to competition from weeds emerging later, but weeding from emergence to 3 and 5 leaf stages reduced grain yield 46 and 44%, respectively, in 1982 and 29 and 18%, respectively, in 1983. Weeding at 3 leaf stage and thereafter did not influence grain yield but initial weedings at 5, 7 and 9 leaf stages reduced grain yield 10, 36, and 67%, respectively, in 1982 and 14,18, and 21%, respectively, in 1983. Responses of maize to weeding time in the dry matter yields were same as in the grain yields.

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Performance assessment of an urban stormwater infiltration trench considering facility maintenance (침투도랑 유지관리를 통한 도시 강우유출수 처리 성능 평가)

  • Reyes, N.J. D.G.;Geronimo, F.K.F.;Choi, H.S.;Kim, L.H.
    • Journal of Wetlands Research
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    • v.20 no.4
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    • pp.424-431
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    • 2018
  • Stormwater runoff containing considerable amounts of pollutants such as particulates, organics, nutrients, and heavy metals contaminate natural bodies of water. At present, best management practices (BMP) intended to reduce the volume and treat pollutants from stormwater runoff were devised to serve as cost-effective measures of stormwater management. However, improper design and lack of proper maintenance can lead to degradation of the facility, making it unable to perform its intended function. This study evaluated an infiltration trench (IT) that went through a series of maintenance operations. 41 monitored rainfall events from 2009 to 2016 were used to evaluate the pollutant removal capabilities of the IT. Assessment of the water quality and hydrological data revealed that the inflow volume was the most relative factor affecting the unit pollutant loads (UPL) entering the facility. Seasonal variations also affected the pollutant removal capabilities of the IT. During the summer season, the increased rainfall depths and runoff volumes diminished the pollutant removal efficiency (RE) of the facility due to increased volumes that washed off larger pollutant loads and caused the IT to overflow. Moreover, the system also exhibited reduced pollutant RE for the winter season due to frozen media layers and chemical-related mechanisms impacted by the low winter temperature. Maintenance operations also posed considerable effects of the performance of the IT. During the first two years of operation, the IT exhibited a decrease in pollutant RE due to aging and lack of proper maintenance. However, some events also showed reduced pollutant RE succeeding the maintenance as a result of disturbed sediments that were not removed from the geotextile. Ultimately, the presented effects of maintenance operations in relation to the pollutant RE of the system may lead to the optimization of maintenance schedules and procedures for BMP of same structure.

Development of cordycepin fortified meat production in Hanwoo steers I. Determination of the chemical composition and safety of Cordyceps militaris from grain or pupae and Paecilomyces tenuipes (Cordycepin 강화 한우고기 생산에 관한 연구 I. 곡립기주 동충하초 균사체의 화학적 성분 및 안전성 조사)

  • Kim, W.Y.;Lee, S.H.;Kim, D.H.;Lee, J.H.;Nho, W.G.;Hwang, J.H.;Yeo, J.M.
    • Journal of Practical Agriculture & Fisheries Research
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    • v.11 no.1
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    • pp.35-51
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    • 2009
  • Three different Cordyceps militaris(Paecilomyces tenuipes and Cordyceps militaris from grain or pupae) were analysed for their chemical composition, fatty acids composition and the concentration of amino acids, cordycepin and heavy metal to obtain basic information on them as feed supplements for livestock. The crude protein content of C. militaris from grain and pupae was 76.16 and 75.45%, respectively, being higher than that of P. tenuipes(57.21%). The concentration of linoleic acid was much higher but that of linolenic acid was much lower for C. militaris from grain than for the others. The cordycepin content was significantly higher for C. militaris from grain than for that from pupae (1.64% vs 0.68% on a DM basis). But cordycepin was not detected in P. tenuipes. Heavy metal contents(Cr, Pb, Cd, Hg) for all C. militaris were below the allowance levels recommended by Ministry of Agriculture and Forestry in Republic of Korea.

Do some patients receive unnecessary parenteral nutrition after pancreatoduodenectomy? Results from an international multicentre study

  • Thomas B. Russell;Peter L. Labib;Paula Murphy;Fabio Ausania;Elizabeth Pando;Keith J. Roberts;Ambareen Kausar;Vasileios K. Mavroeidis;Gabriele Marangoni;Sarah C. Thomasset;Adam E. Frampton;Pavlos Lykoudis;Manuel Maglione;Nassir Alhaboob;Hassaan Bari;Andrew M. Smith;Duncan Spalding;Parthi Srinivasan;Brian R. Davidson;Ricky H. Bhogal;Daniel Croagh;Ismael Dominguez;Rohan Thakkar;Dhanny Gomez;Michael A. Silva;Pierfrancesco Lapolla;Andrea Mingoli;Alberto Porcu;Nehal S. Shah;Zaed Z. R. Hamady;Bilal Al-Sarrieh;Alejandro Serrablo;Somaiah Aroori
    • Annals of Hepato-Biliary-Pancreatic Surgery
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    • v.28 no.1
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    • pp.70-79
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    • 2024
  • Backgrounds/Aims: After pancreatoduodenectomy (PD), an early oral diet is recommended; however, the postoperative nutritional management of PD patients is known to be highly variable, with some centers still routinely providing parenteral nutrition (PN). Some patients who receive PN experience clinically significant complications, underscoring its judicious use. Using a large cohort, this study aimed to determine the proportion of PD patients who received postoperative nutritional support (NS), describe the nature of this support, and investigate whether receiving PN correlated with adverse perioperative outcomes. Methods: Data were extracted from the Recurrence After Whipple's study, a retrospective multicenter study of PD outcomes. Results: In total, 1,323 patients (89%) had data on their postoperative NS status available. Of these, 45% received postoperative NS, which was "enteral only," "parenteral only," and "enteral and parenteral" in 44%, 35%, and 21% of cases, respectively. Body mass index < 18.5 kg/m2 (p = 0.03), absence of preoperative biliary stenting (p = 0.009), and serum albumin < 36 g/L (p = 0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication, i.e., those who had a relatively uneventful recovery, 20% received PN. Conclusions: A considerable number of patients who had an uneventful recovery received PN. PN is not without risk, and should be reserved for those who are unable to take an oral diet. PD patients should undergo pre- and postoperative assessment by nutrition professionals to ensure they are managed appropriately, and to optimize perioperative outcomes.

The Difference in Chemokine Expression in Airway Epithelial Cells According to the Virulence of Tubercle Bacilli (결핵균 독성 여부에 따른 기도 상피세포의 Chemokine 발현에 관한 연구)

  • Kwon, O-Jung;Kim, Ho-Joong;Kim, Jung-Hee;Kim, Ho-Cheol;Suh, Gee-Young;Park, Jeong-Woong;Park, Sang-Joon;Chung, Man-Pyo;Choi, Dong-Chull;Rhee, Chong-H.
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.729-741
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    • 1997
  • Background : We have recently reported that airway epithelial cells can produce RANTES and IL-8 in response to the stimulation of tubercle bacilli suggesting a certain role of airway epithelial cells in the pathogenesis of pulmonary tuberculosis. The pathogenesis of tuberculosis is determined by several factors including phagocytosis, immunological response of host, and virulence of tubercle bacilli. Interestingly, there have been reports suggesting that difference in immunological response of host according to the virulence of tubercle bacilli may be related with the pathogenesis of tuberculosis. We, therefore, studied the expressions and productions of RANTES and IL-8 in airway epithelial cells in response to tubercle bacilli(H37Rv, virulent strain and H37Ra, avirulent strain), in order to elucidate the possible pathophysiology of pulmonary tuberculosis. Methods : Peripheral blood monocytes were isolated from normal volunteers. Peripheral blood monocytes (PBM) were stimulated with LPS($10{\mu}g/ml$), H37Rv, or H37Ra($5{\times}10^5$ bacilli/well) along with normal control for 24 hours. A549 cells were stimulated with supernatants of cultured PBM for 24 hours. ELISA kit was used for the measurement of $TNF{\alpha}$ and IL-$1{\beta}$ production in supernatants of cultured PBM and for the measurement of RANTES and IL-8 in supernatants of cultured A549 cells. Northern blot analysis was used for the measurement of RANTES and IL-8 mRNA expression in cultured A549 cells. Results : $TNF{\alpha}$ and IL-$1{\beta}$ productions were increased in cultured PBM stimulated with LPS or tubercle bacilli(H37Rv or H37Ra) compared with the control. There was, however, no difference in $TNF{\alpha}$ and IL-$1{\beta}$ production between cultured PBM stimulated with H37Rv and H37Ra. RANTES and IL-8 expressions and productions were also increased in cultured A549 cells stimulated with LPS or tubercle bacilli compared with the control. RANTES and IL-8 mRNA expressions were significantly increased in cultured A549 cells stimulated with H37Ra-conditioned media(CM) compared with A549 cells stimulated with H37Rv-CM (p<0.05). However, there was no difference in RANTES and IL-8 productions between A549 cells stimulated with H37Rv-CM and H37Ra-CM. Conclusion : Airway epithelial cells can produce the potent chemokines such as RANTES and IL-8, in response to the stimulation of tubercle bacilli. These results suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis. However, the role of airway epithelial cells in the pathogenesis of tuberculosis according to the virulence of tubercle bacilli was not clear in this study.

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