• Title/Summary/Keyword: 인자 중요도

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Interleukin 1 Receptor Antagonist(IL-1ra) Gene Polymorphism in Children with Henoch-$Sch{\ddot{o}}nlein$ Purpura Nephritis (Henoch-$Sch{\ddot{o}}nlein$ Purpura 신염에서 Interleukin 1 Receptor Antagonist(IL-1ra) 유전자 다형성)

  • Hwang, Phil-Kyung;Lee, Jeong-Nye;Chung, Woo-Yeong
    • Childhood Kidney Diseases
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    • v.9 no.2
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    • pp.175-182
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    • 2005
  • Purpose : Interleukin 1 receptor antagonist(IL-1ra) is an endogenous antiinflammatory agent that binds to IL-1 receptor and thus competitively inhibits the binding of IL-1$\alpha$ and IL-1$\beta$. Allele 2 in association with various autoimmune diseases has been reported. In order to evaluate the influence of IL-1ra gene VNTR polymorphism on the susceptibility to HSP and its possible association with disease severity, manifested by severe renal involvement and renal sequelae, we studied the incidence of carriage rate and allele frequency of the 2 repeats of IL-1ra allele 2($IL1RN^{*}2$) of the IL-1ra gene in children with HSP with and without renal involvement. Methods : The IL-1ra gene polymorphisms were determined in children with HSP with(n=40) or without nephritis(n=34) who had been diagnosed at Busan Paik Hospital and the control groups(n=163). Gene polymorphism was identified by PCR amplification of the genomic DNA. Results : The allelic frequency and carriage rate of $IL1RN^{*}1$ were found most frequently in patients with HSP and in controls. The allelic frequency of $IL1RN^{*}2$ was higher in patients with HSP compared to that of controls($4.7\%\;vs.\;2.5\%$, P=0.794). The carriage rate of $IL1RN^{*}2$ was higher In patients with HSP compared to that of controls($8.1\%\;vs.\;6.8\%$, P=0.916). The allelic frequency of $IL1RN^{*}2$ was higher in patients with HSP nephritis compared to that of HSP($5.3\%\;vs.\;2.9\%$, P=0.356). The carriage rate of $IL1RN^{*}2$ was higher in Patients with HSP nephritis compared to that of HSP($10.0\%\;vs.\;5.9\%$, P=0.523). Among 13 patients with heavy proteinuria(>1.0 g), 11 had $IL1RN^{*}1$, 1 had $IL1RN^{*}2$ and the others had $IL1RN^{*}4$. At the time of last follow up 4 patients had sustained proteinuria and their genotype was $IL1RN^{*}1$. Conclusion : The allelic frequency and carriage rate of $IL1RN^{*}1$ were found most frequently in patients with HSP and in controls. Our study suggests that the carriage rate and allele frequency of the 2-repeats of IL-1lra allele 2($IL1RN^{*}2$) of the IL-1ra gene may not be associated with susceptibility and severity of renal involvement in children with HSP (J Korean Soc Pediatr Nephrol 2005;9:175-182)

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Effects of Concurrent Chemotherapy and Postoperative Prophylactic Paraaortic Irradiation for Cervical Cancer with Common Iliac Node Involvement (자궁경부암의 근치적 절제술 후 총장골동맥림프절 침범 시 동시항암화학치료와 예방적 대동맥주위림프절 방사선조사의 효과)

  • Han, Tae-Jin;Wu, Hong-Gyun;Kim, Hak-Jae;Ha, Sung-Whan;Kang, Soon-Beom;Song, Yong-Sang;Park, Noh-Hyun
    • Radiation Oncology Journal
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    • v.28 no.3
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    • pp.125-132
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    • 2010
  • Purpose: To retrospectively assess the advantages and side effects of prophylactic Paraaortic irradiation in cervical cancer patients with common iliac nodal involvement, the results for survival, patterns of failure, and treatment-related toxicity. Materials and Methods: From May 1985 to October 2004, 909 patients with cervical carcinoma received postoperative radiotherapy at the Seoul National University Hospital. Among them, 54 patients with positive common iliac nodes on pathology and negative Paraaortic node were included in the study. In addition, 44 patients received standard pelvic irradiation delivered 50.4 Gy per 28 fractions (standard irradiation group), and chemotherapy was combined in 16 of them. The other 10 patients received pelvic irradiation at a dose of 50.4 Gy per 28 fractions in addition to Paraaortic irradiation at 45 Gy per 25 fractions (extended irradiation group). In addition, all of them received chemotherapy in combination with radiation. Follow-up times for pelvic and Paraaortic irradiation ranged from 6 to 201 months (median follow-up time, 58 months) and 21 to 58 months (median follow-up time, 47 months), respectively. Results: The 4-year overall survival, disease free survival, and distant metastasis free survival in the standard irradiation group and extended irradiation group were 67.2% vs. 90.0% (p=0.291), 59.0% vs. 70.0% (p=0.568) and 67.5% vs. 90.0% (p=0.196), respectively. The most common site of first failure for the standard irradiation group was the paraaortic lymph node, while no paraaortic failure was observed in the extended irradiation group. Relatively, hematologic toxicity grade 3 or greater was common in the extended irradiation group (2/10 extended vs. 2/44 standard), while gastrointestinal toxicity of grade 3 or greater was lower (2/10 extended vs. 6/44 standard), and urologic toxicity of grade 3 or greater was observed in the standard irradition group only (0/10 vs. 3/44). Conclusion: Concurrent chemotherapy and prophylactic Paraaortic irradiation in patients with common iliac nodal involvement showed slightly improved clinical outcomes aside from increased hematologic toxicity, which was statistically insignificant. Considering the relatively small number of patients and short follow-up times, additional studies are needed to obtain more conclusive outcomes.

Nocturnal Arterial Oxygen Saturation Monitoring in Patients with Respiratory Disease (호흡기 질환 환자들에서 야간 동맥혈 산소포화도 감시 성적)

  • Choi, In-Seon;Yang, Jae-Beom;Kim, Young-Chul;Chung, Ik-Joo;Kang, Yu-Ho;Koh, Yeoung-Il;Park, Sang-Seon;Lee, Min-Su;Park, Kyung-Ok
    • Tuberculosis and Respiratory Diseases
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    • v.41 no.2
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    • pp.103-110
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    • 1994
  • To find out the predictors of nocturnal arterial oxygen desaturation in patients with respiratory diseases, transcutaneous oxygen saturation($StcO_2$) monitoring studies using a pulse oximeter were performed during sleep in 20 patients. $StcO_2$ was decreased more than 4% from the baseline value in 18 patients(90%) and more than 10%("Desaturator") in 8(40%). Five of the seven patients(71.4%) with awake $PaO_2$<60mmHg and three of the thirteen patients(23.1%) with awake $PaO_2{\geq}60mmHg$ were "desaturators". The awake $PaO_2/FIO_2$ and $PaO_2/PAO_2$ could distinguish "desaturator" from "nondesaturator", and $PaO_2,\;SaO_2$ or $StcO_2$ could not. These results suggest that the nocturnal oxygen desaturation depends on the severity of the underlying disease rather than the baseline $PaO_2$. Anthropomorphic and lung function factors could not separate between "desaturator" and "non-desaturator", and about a quater of patients with a wake $PaO_2{\geq}60mmHg$ developed significant desaturation. Therefore, it is necessary to monitor the nocturnal arterial oxygen saturation in patients with respiratory diseases regardless of their severity of airflow obstruction or awake $PaO_2$.

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The Irradiated Lung Volume in Tangential Fields for the Treatment of a Breast (유방암의 접선 조사시 피폭 폐용적)

  • Oh Young Taek;Kim Juree;Kang Haejin;Sohn Jeong Hye;Kang Seung Hee;Chun Mison
    • Radiation Oncology Journal
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    • v.15 no.2
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    • pp.137-143
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    • 1997
  • Purpose : Radiation pneumonitis is one of the complications caused by radiation therapy that includes a Portion of the lung tissue. The severity of radiation induced pulmonary dysfunction depends on the irradiated lung volume, total dose, dose rate and underlying Pulmonary function. It also depends on whether chemotherapy is done or not. The irradiated lung volume is the most important factor to predict the pulmonary dysfunction in breast cancer Patients following radiation therapy. There are some data that show the irradiated lung volume measured from CT scans as a part of treatment Planning with the tangential beams. But such data have not been reported in Korea. We planned to evaluate the irradiated lung volume quantitatively using CT scans for the breast tangential field and search for useful factors that could Predict the irradiated lung volume Materials and Methods : The lung volume was measured for 25 patients with breast cancer irradiated with tangential field from Jan.1995 to Aug.1996. Parameters that can predict the irradiated lung volume included; (1) the peruendicular distance from the Posterior tangential edge to the posterior part of the anterior chest wall at the center of the field (CLD) ; (2) the maximum perpendicular distance from the posterior tangential field edge to the posterior Part of the anterior chest wall (MLD) ; (3) the greatest perpendicular distance from the Posterior tangential edge to the posterior part of anterior chest wall on CT image at the center of the longitudinal field (GPD) ; (4) the length of the longitudinal field (L). The irradiated lung volume(RV), the entire both lung volume(EV) and the ipsilateral lung volume(IV) were measured using dose volume histogram. The relationship between the irradiated lung volume and predictors was evaluated by regression analysis. Results :The RV is 61-279cc (mean 170cc), the RV/EV is $2.9-13.0\%\;(mean\;5.8\%)$ and the RV/IV is $4.9-29.0\%\;(mean\;12.2\%)$. The CLD, the MLD and the GPD ave 1.9-3.3cm, 1.9-3.3cm and 1.4-3.1cm respectively. The significant relations between the irradiated lung volume such as RV. RV/EV, RV/IV and parameters such as CLD, MLD, GPO, L. $CLD\timesL,\;MLD\timesL\;and\;GPD\timesL$ are not found with little variances in parameters. The RV/IV of the left breast irradiation is significantly larger than that of the right but the RV/EVS do not show the differences. There is no symptomatic radiation pneumonitis at least during 6 months follow up. Conclusion : The significant relationship between the irradiated lung volume and predictors is not found with little variation on parameters. The irradiated lung volume in the tangential held is liss than $10\%$ of entire lung volume when CLO is less than 3cm. The RV/IV of the left tangential field is larger than that of the right but there was no significant differences in RV/EVS. Symptomatic radiation pneumonitis has not occurred during minimum 6 months follow up.

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Prospective Study of the Immunologic Factors Affecting the Prognosis of Severe Community-Acquired Pneumonia (중증 지역사회획득 폐렴환자의 예후에 영향을 미치는 면역지표에 대한 연구)

  • Hwang, Jae-Kyung;Lee, Ho-Moeng;Song, Kwang-Sik;Park, Gye-Young;Park, Jeong-Woong;Park, Jae-Kyung;Jeong, Seong-Hwan;Ahn, Jeong-Yeal;Seo, Yiel-Hea;Nam, Gui-Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.4
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    • pp.437-449
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    • 2001
  • Background : In the severe community-acquired pneumonia, it has been known that the immune status is occasionally suppressed. This study was performed to identify the immunologic markers related with the prognostic factors in severe community-acquired pneumonia. Methods : 23 patients with severe community-acquired pneumonia were involved in this study, and divided into survivor (16) and nonsurvivor (7) groups. In this study, the medical history, laboratory tests(complete blood counts, routine chemistry profile, immunoglobulins, complements, lymphocyte subsets, cytokines, sputum and blood culture, urine analysis), and chest radiographs were scrutinized. Results : 1) Both groups had lymphopenia(total lymphocyte count $995.6{\pm}505.7/mm^3$ in the survivor and $624.0{\pm}287.6/mm^3$ in the nonsurvivor group). 2) The T-lymphocyte count of the nonsurvivor group($295.9{\pm}203.0/mm^3$) was lower than the survivor group($723.6{\pm}406.5/mm^3$) (p<0.05). 3) The total serum protein(albumin) was $6.0{\pm}1.0(2.7{\pm}0.7)\;g/d{\ell}$ in the survivor and $5.2{\pm}1.5(2.3{\pm}0.8)g/d{\ell}$ in the nonsurvivor group. The BUN of the nonsurvivor group($41.7{\pm}30.0mg/d{\ell}$) was higher than that of the survivor group($18.9{\pm}9.8mg/d{\ell}$)(p<0.05). The creatinine concentration was higher in the nonsurvivor group($1.8{\pm}1.0mg/d{\ell}$) than that in the survivor group($1.0{\pm}0.3mg/d{\ell}$)(p<0.05). 4) The immunoglobulin G level was higher in the survivor group($1433.0{\pm}729.5mg/d{\ell}$) than in the nonsurvivor group($849.1{\pm}373.1mg/d{\ell}$) (p<0.05). 5) The complement $C_3$ level was $108.0{\pm}37.9mg/d{\ell}$ in the survivor group and $88.0{\pm}32.1mg/d{\ell}$ in the nonsurvivor group. 6) A cytokine study showed an insignificant difference in both groups. 7) Chronic liver disease, DM, and COPD were major underlying diseases in both groups. Conclusion : These results suggest that decreased a T-lymphocyte count and immunoglobulin G level, and an increased BUN and creatinine level may be associated with the poor prognosis of severe community-acquired pneumonia.

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Factors Related with the Compliance and Treatment in Patients with Pulmonary Tuberculosis in Urban and Suburb Area (도시와 농촌지역의 폐결핵 환자 순응도 및 치료에 관련된 요인)

  • Kim, Sang-Soon;Kim, Yoon-Ock
    • Research in Community and Public Health Nursing
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    • v.7 no.1
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    • pp.69-79
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    • 1996
  • To investigate the factors related with the compliance and the treatment of the patients with pulmonary tuberculosis in urban and suburb area, we followed up all the 755 registered patients(at urban Public Health Office 544, at suburb 210) as follow from January 1,1992 to December 31, 1993. We describe the general characteristics and the characteristics related with the disease of the patients according to the area as follow. 150 patients(27.5%) were at their age of 20 to 29 years in the urban area, whereas 45 patients (21.4%) were 60 to 69 years and another 45 patients(21.4%) were 70 to 79 years in the suburb area. According to the first chest X -ray examination, 54.5% of all cases were proved to be mild in the urban area. But in the suburb area, moderate cases (44.3%) were more than mild cases(p<0.01). Follow-up X-ray's were performed more properly(p<0.05) in the urban area(94.3%) than in the suburb area(90.0%). Most cases were found in the chest X -ray examination performed by Public Health Office (p<0.01) : payable chest X-ray in the urban area (56.7%) and free chest X-ray in the suburb area(35.2%). More patients were cured in the urban area(90.8%) than in the suburb area(87.1%). The presence of supporting family member were significantly higher(p<0.05) in the urban area(79.1%) than in the suburb area(88.1%). In the analysis of the treatment efficacy, more cure ate were found in the patients cytologically confirmed to be culture (+). In the urban area, 201 culture (+) patients (93.5%) 294 culture (-) patients (89.1%) were cured. In the suburb area, 99 culture (+) patients(91.7%) and 84 culture (-) patients(82.4%) were cured. Age, the presence of supporting family member, and the socioeconomic status of the patient had significant association with the prescription compliance related with the general characteristics of the patients. Whereas, X-ray finding and AFB culture finding were the significant factors associated with the prescription compliance related with pulmonary tuberculosis (p<0.05). The cumulative compliance in the survival analysis was 92.5% in the urban area and 88.1% in suburb area, at sixth month of follow-up. Failure rate for regular drug receipt was highest at second month in the urban area(3.75%) and at fourth month in the suburb area(4.15%). In logistic regression of the factors related with the tratment result, first X-ray examination and prescription compliance were significantly associated in the urban area(p<0.05). However, there is no factor significantly associated with the treatment result in the suburb area. It could be explained by too small size of the sample. In logistic regression of the factors related with the prescription compliance, first chest X-ray, sputum culture outcome and the presence of supporting family member were significant variables in the urban area(p<0.05). Most patients with family member were proved to be compliant with the prescription. This shows that it is important for the patients with long-lasting ilnesses to have supporting family member. Therefore, to improve prescription compliance we should strengthen the health education before the initiation of treatment and take special interest in the patients without supporting family member.

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Acute Respiratory Distress Syndrome in Respiratory Intensive Care Unit (호흡기계 중환자실에서 치료 관리된 급성호흡곤란증후군의 임상특성)

  • Moon, Seung-Hyug;Song, Sang-Hoon;Jung, Ho-Seuk;Yeun, Dong-Jin;Uh, Su-Tack;Kim, Yong-Hoon;Park, Choon-Sik
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.6
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    • pp.1252-1264
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    • 1998
  • Background : Patients with established ARDS have a mortality rate that exceeds 50 percent despite of intensive care including artificial ventilation modality, Mortality has been associated with sepsis and organ failure preceding or following ARDS ; APACHE II score ; old age and predisposing factors. Revised ventilator strategy over last 10 years especially at ARDS appeared to improve the mortality of it. We retrospectively investigated 40 ARDS patients of respiratory-care unit to examine how these factors influence outcome. Methods : A retrospective investigation of 40 ARDS patients in respiratory-care unit with ventilator management over 46 months was performed. We investigated the clinical characteristics such as a risk factor, cause of death and mortality, and also parameters such as APACHE II score, number of organ dysfunction, and hypoxia score (HS, $PaO_2/FIO_2$) at day 1, 3, 7 of severe acute lung injury, and simultaneously the PEEP level and tidal volume. Results : Clinical conditions associated with ARDS were sepsis 50%, pneumonia 30%, aspiration pneumonia 20%, and mortality rate based on the etiology of ARDS was sepsis 50%, pneumonia 67%(p<0.01 vs sepsis), aspiration pneumonia 38%. Overall mortality rate was 60%. In 28 day-nonsurvivors, leading cause of death was severe sepsis(42.9%) followed by MOF(28.6%), respiratory failure(19.1 %), and others(9.5%). There were no differences in variables of age, sex, APACHE II score, HS, and numbers of organ dysfunction at day 1 of ARDS between 28-days survivor and nonsurvivors. In view of categorized variables of age(>70), APACHE II score(>26), HS(<150) at day 1 of ARDS, there were significant differences between 28-days survivor and nonsurvivors(p<0.05). After day 1 of ARDS, the survivors have improved their APACHE II score, HS, numbers of organ dysfunction over the first 3d to 7d, but nonsurvivors did not improve over a seven-day course. There were significant differences in APACHE II score and numbers of organ dysfunction of day 3, 7 of ARDS, and HS of day 7 of ARDS between survivors and nonsurvivors(p<0.05). Fatality rate of ARDS has been declined from 68% to less than 40% between 1995 and 1998. There were no differences in APACHE II score, HS, numbers of organ dysfunction, old age at presentation of ARDS. In last years, mean PEEP level was significantly higher and mean tidal volume was significantly lower than previous years during seven days of ARDS(p<0.01). Conclusions : Improvement of HS, APACHE II score, organ dysfunction over the first 3d to 7d is associated with increased survival Decline in ARDS fatality rates between 1995 and 1998 seems that this trend must be attributed to improved supportive therapy including at least high PEEP instead of conventional-least PEEP approach in ventilator management of acute respiratory distress syndrome.

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Proliferative Properties and Cytokine Secretion of Lung Fibroblast Cell Lines of the Patients with Idiopathic Pulmonary Fibrosis (정상인 및 간질성 폐섬유증 환자들의 폐 병변내 섬유모세포주의 증식양상 및 Cytokine분비능에 관한 연구)

  • Kim, Dong-Soon;Paik, Sang-Hoon;Kong, Kyung-Yup;Kim, Dong-Kwan;Park, Seong-Il;Shim, Tae-Sun;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.1
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    • pp.128-139
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    • 1998
  • Background: It is well known that various cytokines and growth factors secreted mainly from alveolar macrophages do the key role in the pathogenesis of IPF. But recently it has been known that structural cells like fibroblast can also release cytokines. So the phenotypic changes in fibroblasts of IPF may do a role in continuous progression of fibrosis. The aim of this study is to find out whether there is a change in the biologic properties of the lung fibroblasts of IPF. Subjects and Method: The study was done on 13 patients with IPF diagnosed by open or thoracoscopic lung biopsy and 7 control patients who underwent resectional surgery for lung cancer. Lung fibroblast cell lines (FB) were established by explant culture technique from the biopsy or resected specimen Result: Basal proliferation of the fibroblast of IPF(IFB) measured by BrdU uptake tended to be highter than control fibroblast(NFB) (0.212 0.107 vs $0.319{\pm}0.143$, p=0.0922), also there was no significant difference in proliferation after the stimulation with PDGF or 10% serum. On the contrary, the degree of inhibition in proliferation by PGE2 was significantly lower($33.0{\pm}13.1%$) in IFB than control($46.7{\pm}10.0%$, p=0.0429). The IFB secreted significantly higher amount of MCP-l($l574{\pm}1283$ pg/ml) spontaneously than NFB($243{\pm}100$ pg/ml) and also after the stimulation with TGF-$\beta$($3.23{\pm}1.31$ ng/ml vs $0.552{\pm}0.236$ ng/ml, p=0.0012). Similarly IL-8 and IL-6 seretion of IFB was significantly higher than NFB at basal state and with TGF-$beta$ stimulation. But after the maximal stimulation with IL-1,8, no significant difference in cytokine secretion was found between IFB and NFB. Conclusion : Above data suggest that the fibroblasts of IPF were phenotypically changed and these change may do a role in the pathogenesis of IPF.

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Role of Oxygen Free Radical in the Expression of Interleukin-8 and Interleukin-$1{\beta}$ Gene in Mononuclear Phagocytic Cells (내독소에 의한 말초혈액 단핵구의 IL-8 및 IL-$1{\beta}$ 유전자 발현에서 산소기 역할에 관한 연구)

  • Kang, Min-Jong;Kim, Jae-Yeol;Park, Jae-Seok;Lee, Seung-Joon;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.42 no.6
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    • pp.862-870
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    • 1995
  • Background: Oxygen free radicals have generally been considered as cytotoxic agents. On the other hand, recent results suggest that small nontoxic amounts of these radicals may act a role in intracellular signal transduction pathway and many efforts to reveal the role of these radicals as secondary messengers have been made. It is evident that the oxygen radicals are released by various cell types in response to extracellular stimuli including LPS, TNF, IL-1 and phorbol esters, all of which translocate the transcription factor $NF{\kappa}B$ from cytoplasm to nucleus by releasing an inhibitory protein subunit, $I{\kappa}B$. Activation of $NF{\kappa}B$ is mimicked by exposure to mild oxidant stress, and inhibited by agents that remove oxygen radicals. It means the cytoplasmic form of the inducible tanscription factor $NF{\kappa}B$ might provide a physiologically important target for oxygen radicals. At the same time, it is well known that LPS induces the release of oxygen radicals in neutrophil with the activation of $NF{\kappa}B$. From above facts, we can assume the expression of IL-8 and IL-$1{\beta}$ gene by LPS stimulation may occur through the activation of $NF{\kappa}B$, which is mediated through the release of $I{\kappa}B$ by increasing amounts of oxygen radicals. But definitive evidence is lacking about the role of oxygen free radicals in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. We conducted a study to determine whether oxygen radicals act a role in the expression of IL-8 and IL-$1{\beta}$ gene in mononuclear phagocytic cells. Method: Human peripheral blood monocytes were isolated from healthy volunteers. Time and dose relationship of $H_2O_2$-induced IL-8 and IL-$1{\beta}$ mRNA expression was observed by Northern blot analysis. To evaluate the role of oxygen radicals in the expression of IL-8 and IL-$1{\beta}$ mRNA by LPS stimulation, pretreatment of various antioxiants including PDTC, TMTU, NAC, ME, Desferrioxamine were done and Northern blot analysis for IL-8 and IL-$1{\beta}$ mRNA was performed. Results: In PBMC, dose and time dependent expression of IL-8 and IL-$1{\beta}$ mRNA by exogenous $H_2O_2$ was not observed. But various antioxidants suppressed the expression of LPS-induced IL-8 and IL-$1{\beta}$ mRNA expression of PBMC and the suppressive activity was most prominant when the pretreatment was done with TMTU. Conclusion: Oxygen free radical may have some role in the expression of IL-8 and IL-$1{\beta}$ mRNA of PBMC but that radical might not be $H_2O_2$.

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Evaluation of the Radioimmunotherapy Using I-131 labeled Vascular Endothelial Growth Factor Receptor2 Antibody in Melanoma Xenograft Murine Model (흑색종에서의 I-131표지 혈관내피세포성장인자 수용체2항체를 이용한 방사면역치료 평가)

  • Kim, Eun-Mi;Jeong, Hwan-Jeong;Park, Eun-Hye;Cheong, Su-Jin;Lee, Chang-Moon;Jang, Kyu-Yun;Kim, Dong-Wook;Lim, Seok-Tae;Sohn, Myung-Hee
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.4
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    • pp.307-313
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    • 2008
  • Purpose: Vascular endothelial growth factor (VEGF) and its receptor, fetal liver kinase 1 (Flk-1), play an important role in vascular permeability and tumor angiogenesis. The aim of this study is to evaluate the therapeutic efficacy of $^{131}I$ labeled anti-Flk-1 monoclonal antibody (DC101) on the growth of melanoma tumor, which is known to be very aggressive in vivo. Materials and Methods: Balb/c nude mice were injected subcutaneously with melanoma cells in the right flank. Tumors were allowed to grow up to $200-250\;mm^3$ in volume. Gamma camera imaging and biodistribution studies were performed to identify an uptake of $^{131}I$-DC101 in various organs. Mice with tumor were randomly divided into five groups (10 mice per group) and injected intravenously; control PBS (group 1), $^{131}I$-DC101 $50\;{\mu}g/mouse$ (group 2), non-labeled DC101 $50\;{\mu}g/mouse$ (group 3), $^{131}I$-DC101 $30\;{\mu}g/mouse$ (group 4) and $15\;{\mu}g/mouse$ (group 5) every 3 or 4 days for 20 days. Tumor volume was measured with caliper twice a week. Results: In gamma camera images, the uptake of $^{131}I$-DC101 into tumor and thyroid was increased with time. Biodistribution results showed that the radioactivity of blood and other major organ was gradually decreased with time whereas tumor uptake was increased up to 48 hr and then decreased. After 4th injection of $^{131}I$-DC101, tumor volume of group 2 and 4 was significantly smaller than that group 1. After 5th injection, the tumor volume of group 5 also significantly reduced. Conclusion: These results indicated that delivery of $^{131}I$ to tumor using FlK-1 antibody, DC101, effectively blocks tumor growth in aggressive melanoma xenograft model.