• Title/Summary/Keyword: Suppression

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Tuberculin Skin Test and Change of Cytokines in Patients with Allergic Asthma (알레르기성 천식환자에 있어서 투베르쿨린 피부반응 검사와 Cytokine의 변화)

  • Yoon, Hyoung-Kyu;Shin, Yoon;Lee, Sang-Haak;Lee, Sook-Young;Kim, Seok-Chan;Ahn, Joong-Hyun;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Park, Sung-Hak;Song, Jeong-Sup
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.2
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    • pp.175-184
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    • 1999
  • Background: Bronchial asthma is characterized by chronic eosinophilic inflammatory airway disease associated with bronchial hyperresponsiveness and reversible airway obstruction. Bronchial inflammation in asthma may depend in part on the activation of T helper lymphocytes that elaborate proinflammatory cytokines. T helper (Th) lymphocytes can be divided into two categories; Th1 lymphocytes, which secrete IL-2, IL-12 and IFN-$\gamma$, and Th2 lymphocytes, which secrete IL-4, IL-5, IL-6 and IL-10. Th2 lymphocytes appear to induce allergic responses, whereas Th1 lymphocytes induce delayed-type hypersensitivity response. Some infections, such as tuberculosis, cultivate a Th1 immunological environment and inhibit Th2 lymphocytes function. The presence of such infections might inhibit Th2 immune responses and thus protect development of atopic diseases. Method: 15 patients with allergic bronchial asthma, 10 patients with intrinsic bronchial asthma, and 10 healthy volunteers were studied. The serum concentrations of IFN-$\gamma$, IL-12, IL-4, IL-5, and IL-10 were measured by ELISA method and tuberculin skin test was estimated in different groups. Results: The positive response rates of tuberculin test were 46.7% in patients with allergic asthma, 100% in patients with intrinsic asthma and 60% in normal controls. The positive response rates were significantly lower in patients with allergic asthma than those of in patients with intrinsic asthma (p<0.05). Degree of responses to tuberculin test were $12.0{\pm}9.6mm$ in patients with allergic asthma, $18.4{\pm}4.5mm$ in patients with intrinsic asthma and $10.9{\pm}8.8mm$ in normal controls. The degree of responses were significantly reduced in patients with allergic asthma than those of patients with intrinsic asthma (p<0.05). The serum levels of IL-5 in patients with allergic asthma were significantly higher than in patients with intrinsic asthma and normal controls (p<0.05), although it was insignificant. the serum levels of IL-4 and IL-10 in patients with allergic asthma were higher than that of intrinsic asthma and normal controls. The serum levels of IL-12 and IFN-$\gamma$ in patients with allergic asthma and intrinsic asthma were significantly lower than those in normal controls(p<0.05). The serum levels of total immunoglobulin E (IgE) and peripheral blood eosinophile counts in patients with allergic asthma were significantly higher than those in normal controls. Peripheral blood esinophil counts had a significant correlation with the serum levels of total IgE, IL-5 and IL-10 in patients with allergic asthma (p<0.05). Conclusion: These results have showed that Th1 lymphocyte functions were lowered and Th2 lymphocyte functions were elevated in patients with allergic asthma than those in normal controls. Suppression of Th1 lymphocyte functions by activation of Th2 lymphocyte might be one of the important aspects of pathogenesis in allergic bronchial asthma.

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A Clinical Study on Transpulmonary Leukostasis and Prophylactic Effects of Steroid in Cardiac Surgery (심장수술시 백혈구의 폐내정체와 스테로이드의 예방적 효과에 관한 연구)

  • 최석철
    • Biomedical Science Letters
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    • v.2 no.2
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    • pp.133-151
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    • 1996
  • After cardiac surgery, it has been recognized that various complications were associated with injured humoral and cellular immunity by cardiopulmonary bypass(CPB). Especially, in postoperative pulmonary dysfunction, transpulmonary leukostasis followed complement activation and inflammatory responses are major pathogen. Some studies have showed that pretreated-corticosteroids before CPB protected postoperative pulmonary dysfunction. Corticosteroids may inhibit complement and leukocyte activation. On based previous studies, present investigator determined changes of leukocyte counts and transpulmonary leukostasis during cardiac surgery and postoperative periods. For the evaluation of postoperative pulmonary function and edema, $PaO_2$ and chest X-ray were compared between pre-CPB and post-CPB. Fever and other parameters were also observed postoperatively. The aim of this study was to define for the prophylactic effects of corticosteroid(Solu-Medrol: 30mg/kg) on all the researched parameters. This study was prospectively designed with randomized-blind fashion for 50 patients undergoing cardiac surgery. According to the purpose of study, all patients were divided into placebo and steroid group. : Placebo group was 25 patients received normal saline(not corticosteroid), and steroid group was 25patients received corticosteroid(Solu-Medrol: 30mg/kg) before initiation of CPB. The results of study were summarized as follows. 1. Total peripheral leukocyte counts decreased significantly at 5 minutes of CPB in all patients(P<0.01), and began to increase progressively at later periods of CPB with neutrophilia. The significant rise remained at postoperative 7th day(P<0.05). 2. During partial CPB, transpulmonary leukostasis occurred in placebo group(P<0.001), whereas it was prevented in steroid group. 3. In both groups, peripheral lymphocyte counts were stable during CPB, but began to reduce at time of intensive care unit(ICU) and the lymphocytopenia remained until postoperative 3rd day. The lymphocyte counts recovered on postoperative 7th day. 4. In both groups, peripheral counts of monocyte were relatively stable in the early peroid of CPB, and increased gradually in the later periods of CPB. This significant monocytosis remained throughout postoperlative periods(P<0.05). 5. The mean value of postoperative $paO)_2$ was lower than that of pre-CPB in placebo group(P=0.01) but didn't significant in steroid group(P=0.90). In the incidence of pulmonary edema signs and fever, placebo group was higher than steroid group(P=0.001, p=0.01, respectively). However mechanical respiratory supporting and care periods at intensive care unit were not significant difference between two groups(P>.0.05).With the above results, the investigator concluded that leukocyte activation and pulmonary sequestration were caused by cardiac surgery with CPB and demonstrated that high dose corticosteroid will provide prophylactic effect for pulmonary leukostasis and higher neutrophilia. These effects may ameliorate postoperative pulmonary dysfunction and contribute to postoperative less morbidity. However, further study should be performed because postoperative lymphocytopenia continued for 3 days in both groups, which may suspected damage or suppression of cell-mediated immunity with used corticosteroid.

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Utility of Wide Beam Reconstruction in Whole Body Bone Scan (전신 뼈 검사에서 Wide Beam Reconstruction 기법의 유용성)

  • Kim, Jung-Yul;Kang, Chung-Koo;Park, Min-Soo;Park, Hoon-Hee;Lim, Han-Sang;Kim, Jae-Sam;Lee, Chang-Ho
    • The Korean Journal of Nuclear Medicine Technology
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    • v.14 no.1
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    • pp.83-89
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    • 2010
  • Purpose: The Wide Beam Reconstruction (WBR) algorithms that UltraSPECT, Ltd. (U.S) has provides solutions which improved image resolution by eliminating the effect of the line spread function by collimator and suppression of the noise. It controls the resolution and noise level automatically and yields unsurpassed image quality. The aim of this study is WBR of whole body bone scan in usefulness of clinical application. Materials and Methods: The standard line source and single photon emission computed tomography (SPECT) reconstructed spatial resolution measurements were performed on an INFINA (GE, Milwaukee, WI) gamma camera, equipped with low energy high resolution (LEHR) collimators. The total counts of line source measurements with 200 kcps and 300 kcps. The SPECT phantoms analyzed spatial resolution by the changing matrix size. Also a clinical evaluation study was performed with forty three patients, referred for bone scans. First group altered scan speed with 20 and 30 cm/min and dosage of 740 MBq (20 mCi) of $^{99m}Tc$-HDP administered but second group altered dosage of $^{99m}Tc$-HDP with 740 and 1,110 MBq (20 mCi and 30 mCi) in same scan speed. The acquired data was reconstructed using the typical clinical protocol in use and the WBR protocol. The patient's information was removed and a blind reading was done on each reconstruction method. For each reading, a questionnaire was completed in which the reader was asked to evaluate, on a scale of 1-5 point. Results: The result of planar WBR data improved resolution more than 10%. The Full-Width at Half-Maximum (FWHM) of WBR data improved about 16% (Standard: 8.45, WBR: 7.09). SPECT WBR data improved resolution more than about 50% and evaluate FWHM of WBR data (Standard: 3.52, WBR: 1.65). A clinical evaluation study, there was no statistically significant difference between the two method, which includes improvement of the bone to soft tissue ratio and the image resolution (first group p=0.07, second group p=0.458). Conclusion: The WBR method allows to shorten the acquisition time of bone scans while simultaneously providing improved image quality and to reduce the dosage of radiopharmaceuticals reducing radiation dose. Therefore, the WBR method can be applied to a wide range of clinical applications to provide clinical values as well as image quality.

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A Study on Modern People's Consciousness and Wearing Practice of Korean Costumes (우리나라 옷에 대한 현대인(現代人)의 의식(意識)과 춘용실태(春用實態)에 관(關)한 연구(硏究) - 서울 지역(地域)을 중심(中心)으로 -)

  • Hwang, Chun-Sub
    • Journal of the Korean Society of Costume
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    • v.1
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    • pp.119-129
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    • 1977
  • It is significant for developing the future for us to know our present age. In order to preserve our Korean costume as a fola clothes retaining our distinguished independent characterisitics and to help design the tomorrow of our Korean costume playing a role as a racial to develop the world clothing culture, a survey was conducted to investigate modern people's conscious-ness and wearing practumes of Korean costume by questionaire and interviewing methods. The results of the survey were analyzed as follows: (1) At present, Korean costumes were purchased as customtailored(64.0%) and as ready-made(17.8%) and most of them were not made at individual homes. The laundry and ironing of them were carried out at laundry shops(68.8%). Considering our present economic, social and cultural aspects, sowing, laundryand ironing will not be carried out at homes again in the future and ready made costumes seen to be produced in a large scale in the future. Garment makers and laundry shop operators should be trained how to make our Korean costumes retain our traditional beauty in the course of their production and laundry and the makers of ready-made costumes must make research how to efficiently produce ideal ready-made costumes by adopting the synchro system in their wrk odisivion. (2) The age group wearing Korean costumes most frequently was the aged people over 60 (their wearing rate; 45%-50%) and the group wearing them most frequently next io the aged people over 60, was housewives(their wearing rate; 15%-20%). Excludign aged people and housewives, other respondentsdid not wear Korean costumes very frequently. Men's wearing rate was lower their wearing rate was the younger their ages were and the less their monthly incomes were. Korean costumes were used for holiday and festival(60%), wedding and funeral ceremonies (52%), visiting and working(22%), casual wear(12.8%) and home wear(9.2%). The use of Korean costumes as casual and home wears, was lower than the use for holday, festival, visiting and working, Under our present circumstances in which our Korean people use both Western style clothes and Korean costumer, our Korean costume has lostits position as a basic and necessary requiement in Korean people's daily life and become a ceremonical and fancy costume. It is natural that the times and life change everything in our daily life. Our costume has to be made as good ceremonial and fancy clothes satisfying modern sensibility according to its new role. In order for us to get close with our clothes, a keen study must be carried out to cleat the color, material, style, function and harmony of the Korean costume matching the of the times. (3) The 47.8% of the respondents answered that they were proud of our Korean costume as our folk clothes, 47.6% replied that thought them just common and 1.1% responded that they were ashamed of it. Most of them were affirmative in feeling pride with our Korean costume. (4) Considering the functional aspect of Korean costumes, their strong points were symetric beauty, rhythmical beauty, unity feeling, harmonical beauty and detailed decorations. Their common shortcomings were lack of individuality and inadequateness for active life. The shortcomings of woman costumes were suppressing breast, making resperation difficult and in adequnteness in summer time. The main reason not to wear our Korean costumes, was due to the fact that they are incomvenient for active life. As a measure to eliminate such shortcomings, 1) the suspension system of skirt to remove the suppression of breast should be generally adopted. 2) they should be simplified in their structure to make them convenient for active life and adepuate in wearing them in hot weather in an extent to which the traditional beauty of the costume may not be lostand 3) a new technique must be explored for showing individuality by wearing method and new arrangment of colors and decorations. (5) The reasons desiring to wear Korean costumes were classifide as follows: A. Korean costumes are our traditional clothes(43.4%). B. Korean costumes are noble and beautiful(26.8%). C. They are accustomed to wear Korean costumes by habit(19.5%). D. Korean costumes are necessary for attending ceremoneis(9.5%). E. Miscellaneous reasons(0.8%). Classifying these reasons into age groups, the high age group over 40 wore them because they were easy to wear by habit and the low age group of 10-30 never thought that they were east to wear by habit. Considering that even those who were accustomed to wear Korean costumes showed a low wearing rate and that the young generation were accustomed to wear Western style clothes rather than Korean costumes, the wearing rate of Korean costumes will be reduced in the future if such trend continues. It is urgent for us to make our best efforts in order to enhance the interest of young generation in Korean costumes and not to make them lose the strong points of Korean costume in the future. (6) Conicering the plan of the respondents on what kind of clothes they were going to wear in the future, among the age group over 50, those who wanted to wear only Korean costumes were 24.8%(men) and 35.1%(women), those who wanted to wear 49.7%(men) and 47.4(women), those who wanted to wear chiefly Western style clothes were 20.7% (men) and 14.4%(women) and those who wanted to wear only Western style clothes, were 2.4% (men) and 2.1%(women). This shows that the general tendency to wear only or chiefly Korean costumes is more prevalent than that to wear only Western style. Among the age group under 50, the tendency to wear Western style clothes was conspicuous and most of the respondent answered that they would wear chiefly Western style clothes and Korean costumes occasionally. Only 5.4% of the respondent answered that they would wear only Western style clothes and this shows that meny respondents still wonted to wear Korean costumes. Those who wanted their descendants to wear what they desire, were 50.1%(men) and 68.8% (women) and those who wanted their descendants to wear Koran costumes occasionally, were 85.8%(men) and 86.3%(women). This shows that most of respondents wanted their descendants to wear Korean costumes. In order to realize, it is necessory for us to make ourdescendants recognize the preciousness of our traditional culture and modify our Korean costumes according to their taste so that they may like wearing them.

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Comparison of the Result of Radiation Alone and Radiation with Daily Low Dose Cisplatin in Management of Locally Advanced Cervical Cancer (국소적으로 진행된 자궁경부암에서 방사선 단독치료와 방사선 및 저용량 Cisplatin 항암화학요법 병용치료의 비교)

  • Kim Hun Jung;Kim Woo Chul;Lee Mee Jo;Kim Chul Su;Song Eun Seop;Loh John J K.
    • Radiation Oncology Journal
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    • v.22 no.3
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    • pp.200-207
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    • 2004
  • Purpose: An analysis was to compare the results of radiation alone with those of radiation with dally low dose cisplatin as a radiation sensitizer in locally advanced cervical cancer. Materials and Methods: A retrospective analysis of 59 patients diagnosed with locally advanced uterine cervix cancer between December 1996 and March 2001 was peformed. Thirty one patients received radiation alone and 28 patients received dally low dose cisplatin, as a radiation sensitizer, and radiation therapy. The median follow-up period was 34 months, ranging from 2.5 to 73 months. The radiation therapy consisted of 4500 cGy external beam irradiation to the whole pelvis (midline block after 3060 cGy), a 900$\~$l,000 cGy boost to the involved parametrium and high dose-rate intracavitary brachytherapy (a total dose of 3,000$\~$3,500 cGy/500 cGy per fraction to point A, twice per week). In the chemoradiation group, 10 mg of daily intravenous cisplatin was given daily from the 1st day of radiation therapy to the 20th day of radiation therapy. According to the FIGO classification, the patients were subdivided into 51 (86.4$\%$) and 8 (13.6$\%$) stages IIB and stage IIIB, respectively. Results: The overall 5 year survival rate was 65.65$\%$ and according to treatment modality were 56.75$\%$ and 73.42$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.180). The 5 year disease-free survival rates were 49.39$\%$ and 63.34$\%$ in the radiation alone and chemoradiatoin groups, respectively (p=0.053), The 5 year locoregional control rates were 52.34$\%$ and 73.58$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.013). The 5 year distant disease-free survival rates were 59.29$\%$ and 81.46$\%$ in the radiation alone and chemoradiation groups, respectively (p=0.477), Treatment related hematologic toxicity were prominent in the chemoradiation group. Leukopenia $\geq$grade) occurred in 3.2$\%$and 28.5$\%$ of the radiation alone and chemoradiation groups, respectively (p=0.02). There were no statistical differences in the incidences of vesical, rectal and small bowel complications between two groups. Conclusion: Radiation therapy with low dose cisplatin did not improve the rates of survival and response rates, but did improve the rate of disease free survival and locoregional control rates In locally advanced cervical cancer. The incidence of bone marrow suppression was higher in the chemoradiation group.

Depression of Immune Response by Newcastle Disease Virus Infection (Newcastle병(病) 바이러스감염(感染)에 의(依)한 면역반응억제(免疫反應抑制))

  • Kim, Hwan-Jong;Ha, Tai-You
    • The Journal of the Korean Society for Microbiology
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    • v.14 no.1
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    • pp.79-87
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    • 1979
  • The immunosuppressive activity of newcastle disease virus(NDV) and some possible role of interferon(C-IF) in viral suppression of immune response were evaluated by SRBC-induced delayed-type hypersensitivity(DTH), rosette formation in spleen cells, number of lymphocytes in peripheral blood, hemagglutinin and hemolysin response to SRBC in ICR mice sensitized with SRBC. When NDV was inoculated before or after sensitization of mouse with SRBC, virus caused a marked inhibition of DTH, and its depressive effect was dependent on the time of virus inoculation in relation to SRBC sensitization or challenge. Rosette formation of spleen cells was significantly reduced by NDV infection. The degree of the depression of rosette formation was more prominent in mice inoculated before sensitization than after sensitization and could be related to the amount of serum interferon induced by the virus. Humoral response to SRBC of virus infected mouse was significantly depressed when NDV was inoculated 24 or 48 hours before sensitization. However, there was no difference in the response when the virus was inoculated 9 hour before and at the same time of sensitization or even after that. Lymphocytes in peripheral blood of mice were markedly diminished in numbers when NDV was inoculated 48 and 24 hour before sensitization with SRBC, but they were slightly augmented when the virus was inoculated 9 hour before and at the same time of sensitization. When UV-inactivated or heat-inactivated NDV was injected to the mouse at the same time of sensitization with SRBC, DTH and rosette formation of spleen cells were slightly depressed. DTH and rosette formation in mice treated with crude-IF were generally depressed as com pared with those of control mice. These studies suggest that the NDV causes a significant depression of cell-mediated immunity, whereas the humoral immune response is not inhibited markedly, and that the depression of immune response by NDV infection may be caused by interferon produced by NDV and direct viral activity.

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Optimization of Modified Starches on Retrogradation of Korean Rice Cake(Garaeduk) (가래떡의 노화 억제에 관한 변형 전분의 최적화)

  • Park, Hyun-Jeong;Song, Jae-Chul;Shin, Wan-Chul
    • The Korean Journal of Food And Nutrition
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    • v.19 no.3
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    • pp.279-287
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    • 2006
  • This study was carried out to investigate the influences of modified starches on suppression of retrogradation in Korean rice cake for their optimization, Garaeduk. Based upon studying Avrami equation, the Avrami exponent n value of all the experiment samples was found to be 1.03 ${\sim}$ 1.37 in the influence of modified starches on retrogradation of the rice cake. This means that the retrogradation of the Korean rice cake occurred instantly after the crystallization of starch particles in the Korean rice cake formulated by modified starches. The highest Avrami exponent n value was indicated in the control sample. The rate constant k of retrogradation in the Korean rice cake formulated by modified starches showed comparatively low and appeared to be the lowest in the Korean rice cake formulated by SHPP. This tendency was shown well in the time constant(1/k) of retrogradation velocity. According to the DSC analysis, the onset temperature of gelatinization in thermal characteristics showed somewhat high in case of addition of modified starch into the Korean rice cake on storage time and the SHPP was slowly gone up. In peak temperature of gelatinization in thermal characteristics of the DSC analysis, SSOS and ASA were increased a little in comparison with the control. The control was comparatively high increase. Melting enthalphy of all samples added with modified starches (SSOS: 21.1${\rightarrow}$23.7${\rightarrow}$24.1, ASA: 21.1${\rightarrow}$24.8${\rightarrow}$25.4) appeared to be lower than that of the Korean rice cake without modified starches(21.2${\rightarrow}$26.1${\rightarrow}$27.1). The Korean rice cake added with SHPP was shown to be the lowest in the increasing rate of melting enthalpy(20.9${\rightarrow}$21.4${\rightarrow}$22.1). Heat spreadability of all the samples in Martin melting diameter was revealed to be good in order of control, ASA, SSOS, SHPP and especially the Korean rice cake added with SHPP was shown to be the best in heat spreadability. In color, sensory examination and textural characteristic of the Korean rice cake added with modified starches, the L$^*$value was not changed practically with the storage time and seemed to be stable. The a$^*$ value of the samples was followed by control(2.21${\rightarrow}$5.34: 141.6%), ASA (2.01${\rightarrow}$4.22: 110.0%), SSOS (2.78${\rightarrow}$4.87: 75.2%) and SHPP (2.12${\rightarrow}$3.40: 60.4%) in order of color change. Also the b$^*$ value of the samples was followed by control(4.32${\rightarrow}$6.35: 47.0%), ASA (4.66${\rightarrow}$5.73: 23.0%), SSOS (4.90${\rightarrow}$5.89: 20.2%) and SHPP (4.89${\rightarrow}$5.12: 4.7%) and there was the least (or no) color change with the SHPP. Textural characteristics of samples was shown to be the highest in case of modified starch addition and especially SHPP appeared to be the best in texture.

Studies on the Chilling Injury of Rice seedlings. 1. Characterization of Chilling Injury & Recovery Different Leaf Stages (수도의 유초기 냉해에 관한 연구 1. 유묘기 엽령별 냉해발현 및 회복양태)

  • Kwon, Y.W.; Kim, J.H.;Ahn, S.B.
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.24 no.1
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    • pp.11-24
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    • 1979
  • To characterize elastic and plastic chilling injury, rice seedlings grown at 28/$16^{\circ}C$ day/night temp. under 20K lux (13hrs.) in a phytotron were subjected to a 11/$6^{\circ}C$, 20K lux condition for 2, 4, 6 or 8 days at 1, 2, 3, 4 or 5th leaf-stage, respectively, followed by further growth under 28/$16^{\circ}C$condition till 30th day after seeding. Japonica variety Jinheung and Chulwon No.1 survived almost 100% without any significant , discoloration and death of leaves due to chilling even under the chilling of 8 days at all seedling ages tested. Tongil and Yushin, varieties from Indica x Japonica cross, showed increasing discoloration of leaves and death of plants with increase in chilling intensity. The longest chilling duration shown seedling death less than 5% was 4, 6, 1, 4, 8 days for Tongil, and 6, 6, 1, 2, 2, days for Yushin at 1, 2, 3, 5th leaf-stage, respectively. The degree of discoloration and death of leaves or suppression of height growth was not explicitly related to seedling death or the dry weight reduction. The degree of seedling death or dry weight reduction could differentiate chilling tolerance of varieties and seedling ages, but somewhat differently. Reduction in dry weight due to chilling occurred even without any visible injury or seedling death. These suggest that both the degree of seedling death and reduction in dry weight should be considered in the test of varieties for chilling tolerance. Combined evaluation of seedling death and dry weight reduction indicated the most susceptible seedling age to chilling injury to be 1 to 2nd leaf-stage for Jinheung, 2 to 3rd leaf-stage for Chulwon No.1, 3rd leaf- stage for Tongil and Yushin, respectively.

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A Study of Endothelium-dependent Pulmonary Arterial Relaxation and the Role of Nitric oxide on Acute Hypoxic Pulmonary Vasoconstriction in Rats (흰쥐 폐동맥의 내피세포의존성 혈관이완과 급성 저산소성 폐동맥수축에서 산화질소의 역할)

  • In, Kwang-Ho;Lee, Jin-Goo;Cho, Jae-Youn;Shim, Jae-Jung;Kang, Kyung-Ho;Yoo, Se-Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.3
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    • pp.231-238
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    • 1994
  • Backgroud: Since the demonstration of the fact that vascular relaxation by acetylcholine(Ach) results from the release of relaxing factor from the endothelium, the identity and physiology of this endothelium-derived relaxing factor(EDRF) has been the target for many researches. EDRF has been identified as nitric oxide(NO). With the recent evidences that EDRF is an important mediator of vascular tone, there have been increasing interests in defining the role of the EDRF as a potential mediator of hypoxic pulmonary vasoconstriction. But the role of EDRF in modulating the pulmonary circulation is not compeletely clarified. To investigate the endothelium-dependent pulmonary vasodilation and the role of EDRF during hypoxic pulmonary vasoconstriction, we studied the effects of $N^G$-monomethyl-L-arginine(L-NMMA) and L-arginine on the precontracted pulmonary arterial rings of the rat in normoxia and hypoxia. Mothods: The pulmonary arteries of male Sprague Dawley(300~350g) were dissected free of surrounding tissue, and cut into rings. Rings were mounted over fine rigid wires, in organ chambers filled with 20ml of Krebs solution bubbled with 95 percent oxygen and 5 percent carbon dioxide and maintained at $37^{\circ}C$. Changes in isometric tension were recorded with a force transducer(FT.03 Grass, Quincy, USA) Results: 1) Precontraction of rat pulmonry artery with intact endothelium by phenylephrine(PE, $10^{-6}M$) was relaxed completely by acetylcholine(Ach, $10^{-9}-10^{-5}M$) and sodium nitroprusside(SN, $10^{-9}-10^{-5}M$), but relaxing response by Ach in rat pulmonary artery with denuded endothelium was significantly decreased. 2) L-NMMA($10^{-4}M$) pretreatment inhibited Ach($10^{-9}-10^{-5}M$)-induced relaxation, but L-NMMA ($10^{-4}M$) had no effect on relaxation induced by SN($10^{-9}-10^{-5}M$). 3) Pretreatment of the L-arginine($10^{-4}M$) significantly reversed the inhibition of the Ach ($10^{-9}-10^{-5}M$)-induced relaxation caused by L-NMMA($10^{-4}M$) 4) Pulmonary arterial contraction by PE($10^{-6}M$) was stronger in hypoxia than normoxia but relaxing response by Ach($10^{-9}-10^{-5}M$) was decreased, 5) With pretreatment of L-arginine($10^{-4}M$), pulmonary arterial relaxation by Ach($10^{-9}-10^{-5}M$) in hypoxia was reversed to the level of relaxation in normoxia. Conclusion: It is concluded that rat pulmonary arterial relaxation by Ach is dependent on the intact endothelium and is largely mediated by NO. Acute hypoxic pulmonary vasoconstriction is related to the suppression on NO formation in the vascular endothelium.

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Triptolide-induced Transrepression of IL-8 NF-${\kappa}B$ in Lung Epithelial Cells (폐상피세포에서 Triptolide에 의한 NF-${\kappa}B$ 의존성 IL-8 유전자 전사활성 억제기전)

  • Jee, Young-Koo;Kim, Yoon-Seup;Yun, Se-Young;Kim, Yong-Ho;Choi, Eun-Kyoung;Park, Jae-Seuk;Kim, Keu-Youl;Chea, Gi-Nam;Kwak, Sahng-June;Lee, Kye-Young
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.52-66
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    • 2001
  • Background : NF-${\kappa}B$ is the most important transcriptional factor in IL-8 gene expression. Triptolide is a new compound that recently has been shown to inhibit NF-${\kappa}B$ activation. The purpose of this study is to investigate how triptolide inhibits NF-${\kappa}B$-dependent IL-8 gene transcription in lung epithelial cells and to pilot the potential for the clinical application of triptolide in inflammatory lung diseases. Methods : A549 cells were used and triptolide was provided from Pharmagenesis Company (Palo Alto, CA). In order to examine NF-${\kappa}B$-dependent IL-8 transcriptional activity, we established stable A549 IL-8-NF-${\kappa}B$-luc. cells and performed luciferase assays. IL-8 gene expression was measured by RT-PCR and ELISA. A Western blot was done for the study of $I{\kappa}B{\alpha}$ degradation and an electromobility shift assay was done to analyze NF-${\kappa}B$ DNA binding. p65 specific transactivation was analyzed by a cotransfection study using a Gal4-p65 fusion protein expression system. To investigate the involvement of transcriptional coactivators, we perfomed a transfection study with CBP and SRC-1 expression vectors. Results : We observed that triptolide significantly suppresses NF-${\kappa}B$-dependent IL-8 transcriptional activity induced by IL-$1{\beta}$ and PMA. RT-PCR showed that triptolide represses both IL-$1{\beta}$ and PMA-induced IL-8 mRNA expression and ELISA confirmed this triptolide-mediated IL-8 suppression at the protein level. However, triptolide did not affect $I{\kappa}B{\alpha}$ degradation and NF-$_{\kappa}B$ DNA binding. In a p65-specific transactivation study, triptolide significantly suppressed Gal4-p65T Al and Gal4-p65T A2 activity suggesting that triptolide inhibits NF-${\kappa}B$ activation by inhibiting p65 transactivation. However, this triptolide-mediated inhibition of p65 transactivation was not rescued by the overexpression of CBP or SRC-1, thereby excluding the role of transcriptional coactivators. Conclusions : Triptolide is a new compound that inhibits NF-${\kappa}B$-dependent IL-8 transcriptional activation by inhibiting p65 transactivation, but not by an $I{\kappa}B{\alpha}$-dependent mechanism. This suggests that triptolide may have a therapeutic potential for inflammatory lung diseases.

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