• Title/Summary/Keyword: Lymphocytes

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CD45RA+ Depleted Lymphocyte Infusion for Treatment of Refractory Cytomegalovirus Disease in Complete DiGeorge Syndrome: A Case Report

  • HyungJin Chin;Young Hye Ryu;Da Yun Kang;Hyun Jin Park;Kyung Taek Hong ;Jung Yoon Choi;Ki Wook Yun;Bongjin Lee;Hyoung Jin Kang;Eun Hwa Choi
    • Pediatric Infection and Vaccine
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    • v.30 no.3
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    • pp.173-179
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    • 2023
  • Complete DiGeorge syndrome (cDGS) refers to DGS with profound T cell deficiency. Herein, we present the case of an infant with cDGS suffering from refractory cytomegalovirus (CMV) infection and who was treated with CD45RA+ depleted lymphocyte infusion. The patient was diagnosed with cDGS by fluorescence in situ hybridization which verified 22q11.2 deletion and as well as by the observed profound T cell deficiency (CD3+ T cells 69/μL, CD4+ T cells 7/μL). On the 45th day of age, CMV viremia was first detected with a plasma viral load (VL) of 120,000 IU/mL. Ganciclovir treatment effectively reduced VL post 56 days of treatment; however, VL subsequently rebounded. A CMV UL97 phosphotransferase M460V mutation conferring ganciclovir resistance emerged and foscarnet was incorporated. Despite this, high titers of CMV viremia (VL 2,820,000 IU/mL) and CMV retinitis were complicated. To restore T cell immunity and treat refractory CMV infection, CD45RA+ depleted CMV-specific lymphocytes from the patient's father were infused twice on the 196th and 207th days after birth. After receiving the second infusion, a decline in CMV VL was observed, with a decrease to 87,100 IU/mL by the tenth day following infusion, despite the failure in maintaining T cell increase. The patient died of Pneumocystis jirovecii pneumonia and Elizabethkingia meningoseptica sepsis on the 222nd day after birth. CD45RA+ depleted lymphocyte infusion may be a therapeutic option for refractory CMV disease in cDGS patients.

Measuring Intracellular Mycobacterial Killing Using a Human Whole Blood Assay (인체 전혈 모델을 이용한 세포내 결핵균 살균력에 관한 연구)

  • Cheon, Seon-Hee;Song, Ho-Yeon;Lee, Eun-Hee;Oh, Hee-Jung;Kang, In-Sook;Cho, Ji-Yoon;Hong, Young-Sun
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.5
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    • pp.497-509
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    • 2002
  • Background : The mechanisms through which cellular activation results in intracellular mycobacterial killing is only partially understood. However, in vitro studies of human immunity to Mycobacterium tuberculosis have been largely modeled on the work reported by Crowle, which is complicated by several factors. The whole blood culture is simple and allows the simultaneous analysis of the relationship between bacterial killing and the effect of effector cells and humoral factors. In this study, we attempted to determine the extent to which M. tuberculosis is killed in a human whole blood culture and to explore the role of the host and microbial factor in this process. Methods : The PPD positive subject were compared to the umbilical cord blood and patients with tuberculosis, diabetes and lung cancer. The culture is performed using heparinized whole blood diluted with a culture medium and infected with a low number of M. avium or M. tuberculosis $H_{37}Ra$ for 4 days by rotating the culture in a $37^{\circ}C$, 5% $CO_2$ incubator. In some experiments, methlprednisolone- or pentoxifyline were used to inhibit the immune response. To assess the role of the T-cell subsets, CD4+, CD8+ T-cells or both were removed from the blood using magnetic beads. The ${\Delta}$ log killing ratio was defined using a CFU assay as the difference in the log number of viable organisms in the completed culture compared to the inoculum. Results : 1. A trend was noted toward the improved killing of mycobacteria in PPD+ subjects comparing to the umbilical cord blood but there was no specific difference in the patients with tuberculosis, diabetes and lung cancer. 2. Methylprednisolone and pentoxifyline adversely affected the killing in the PPD+ subjects umbilical cord blood and patients with tuberculosis. 3. The deletion of CD4+ or CD8+ T-lymphocytes adversely affected the killing of M. avium and M. tuberculosis $H_{37}Ra$ by PPD+ subjects. Deletion of both cell types had an additive effect, particularly in M. tuberculosis $H_{37}Ra$. 4. A significantly improved mycobacterial killing was noted after chemotherapy in patients with tuberculosis and the ${\Delta}$ logKR continuously decreased in a 3 and 4 days of whole blood culture. Conclusion : The in vitro bactericidal assay by human whole blood culture model was settled using a CFU assay. However, the host immunity to M. tuberculosis was not apparent in the human whole blood culture bactericidal assay, and patients with tuberculosis showed markedly improved bacterial killing after anti-tuberculous chemotherapy compared to before. The simplicity of a whole blood culture facilitates its inclusion in a clinical trial and it may have a potential role as a surrogate marker in a TB vaccine trial.

Effects of Supplementary Multiple Probiotics or Single Probiotics on the Performance, Intestinal Microflora, Immune Response of Laying Hens and Broilers (혼합 또는 단일 생균제가 산란계와 육계의 생산성, 소장내 미생물 균총 및 면역 체계에 미치는 영향)

  • Kim, Chan-Ho;Woo, Kyung-Chun;Kim, Geun-Bae;Park, Yong-Ha;Paik, In-Kee
    • Korean Journal of Poultry Science
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    • v.37 no.1
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    • pp.51-62
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    • 2010
  • This study was conducted to investigate the effects of dietary supplementation of multiple probiotics on the performance, small intestinal microflora and immune response in laying hens and broilers. In Exp.1, a total of 800, 82 wk old Hy-line Brown$^{(R)}$ laying hens were assigned to one of the following five dietary treatment; Control, Antibiotics (avilamycin 6 ppm), Probiotics; PB-M (Micro-ferm$^{(R)}$ 0.2%), PB-L (Lacto-sacc$^{(R)}$ 0.1%), PB-Y (Y University probiotics 0.2%). Each treatment was replicated eight times with 20 birds in each replicate and two birds were housed in each cage. Twenty birds units were arranged according to completely randomized block design. Feeding trial lasted 6 wk under 16 h lighting regimen. The Exp. 2, was conducted with a total of 1,000 broilers chicks (Ross$^{(R)}$). They were divided into five treatments, same as those of Exp. 1. Birds were fed starter (0~3 wk) and grower (4~5 wk) diets. Each treatment was replicated four times with 50 birds per pen comprising of deep litter. In Exp. 1, egg production parameters, such as hen-day and hen-house egg production, egg weight, broken and soft shell egg production, feed intake and feed conversion were not significantly different among treatments. However, strength and thickness of eggshell were significantly (P<0.05) different. Among the probiotics, PB-Y showed the highest strength and thickness of eggshell. Eggshell color, egg yolk color and Haugh unit were not significantly influenced. In Exp. 2, overall weight gain (0~5 wk) and mortality were not significantly different among treatments. However, weight gain of birds from PB-Y treatment during starter (0~3 wk) was significantly lower than the birds from Control and Antibiotic treatment. During the whole period (0~5 wk), birds from Antibiotics treatment had higher feed intake and Production Index (PI) and lower feed conversion than birds from Control treatment. Probiotics treatments were not significantly different from the Control on feed intake and feed conversion. In Exp.1, there were significant (P<0.05) differences in leukocytes parameters, such as white blood cell (WBC), hetrophil (HE), lymphocytes (LY), monocyte (MO), eosinophil (EO) and stress index (SI; HE/LY) in the blood of layers. Birds from Antibiotics and probiotics treatments tended to increase these parameters. In Exp. 2, however, only SI was significantly (P<0.05) decreased in Antibiotics treatments. Concentration of serum immunoglobulin (IgG) were higher (P<0.05) in PB-M and PB-Y treatments when compared with Control treatment in Exp. 1. The population of E. coli significantly (P<0.05) decreased in birds from Antibiotics, PB-L and PB-Y treatments when compared with birds from Control treatment in Exp. 1. Metalbolizability of crude fat decreased significantly (P<0.05) in birds from probiotic treatments in Exp. 2. It was concluded that the response of probiotics on the productivity of layers and broilers were different. Probiotics increased strength and thickness of eggshell in layers, and decreased feed conversion and increased PI in broilers. Leukocytes and IgG tended to increase by supplementation of antibiotics and probiotics in layers. Intestinal E. coli tended to decrease in layers. Digestibility of crude fat of diet decreased in probiotics treatments broilers. Parameters of blood and microbial were more sensitive in layers than broilers.

The Mechanism of Interferon-$\gamma$ Induced Cytotoxicity on the Lung Cancer Cell Line, A549 (인터페론감마에 의한 A549 폐암세포주 세포독성의 기전)

  • Oh, Yeon-Mok;Yoo, Chul-Gyu;Chung, Hee-Soon;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.1
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    • pp.63-68
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    • 1996
  • Background: Interferon-$\gamma$ has various biologic effects, including antiviral effect, antitumor proliferative effect, activation of macrophage and B lymphocyte, and increased expression of major histocompatibility complex. Especially, antitumor proliferative effect of interferon-$\gamma$ has already been proved to be important in vivo as well as in vitro. And, clinical studies of interferon-$\gamma$ have been tried in lung cancer patients. However, the mechanism of antitumor effect of interferon-$\gamma$ has not yet been established despite of many hypotheses. "Necrosis" is a type of cell death which is well known to occur in the circumstances of severe stresses. In contrast, "apoptosis" is another type of cell death which occurs in such biological circumstances as embryonic development, regression of organs, and self-tolerance of lymphocytes. And, apoptosis is an active process of cell death in which cells are dying with fragmentations of their cytoplasms and nuclei. And, in the process of apoptosis the DNAs of cells are cleaved between nucleosomes by unidentified endonuclease and therefore DNAs of apoptotic cells result in a typical electrophoresis pattern known as DNA ladder pattern. Recently it has been suggested that cytotoxic effect of interferon-$\gamma$ occurs via apoptosis. To elucidate the mechanism of antitumor cytotoxic effect of interferon-$\gamma$, we microscopically observed a lung cancer cell line, A549 which was treated with interferon-$\gamma$. We observed A545 treated with interferon-$\gamma$ was dying fragmented. And so, we performed this study to find out that the mechanism of antitumor cytotoxic effect of interferon-$\gamma$ be apoptosis. Method: We treated A549, human lung cancer cell line with various concentration of interferon-$\gamma$ and quantified its cytotoxic effect of various periods, 24 hours, 72 hours and, 120 hours by MTT(dimethylthiazolyl diphenyltetrazolium bromide) bioassay. Also, after we treated A549 with 100 units/mi of interferon-$\gamma$ for 120 hours, we observed the pattern of cell death with inverted microscope and we extracted DNAs from the dead A549 cells and observed the pattern of 1.5% agarose gel electrophoresis with ethidium bromide staining. Result: 1) Cytotoxic effect of interferon-$\gamma$ on A549: For the first 24 hours, threre was little cytotoxic effect and for between 24 hours and 72 hours, there was the beginning of cytotoxic effect and for 120 hours there was increased cytotoxic effect. 2) Pattern of A549 cell death by interferon-$\gamma$: We observed with inverted microscope that A549 cells were dying fragmented. 3) DNA ladder pattern of gel electrophoresis: We observed DNA ladder pattern of gel electrophoresis of extracted DNAs from dead A549 cells. Conclusion: We concluded that the mechanism of interferon-$\gamma$induced cytotoxicity on lung cancer cell line, A549 be via apoptosis.

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The Expression of Adhesion Molecules on BAL Cells and Serum Soluble ICAM-1 Level after the Radiotherapy for the Lung Cancer and Its Relationship to the Development of of Radiation Pneumonitis and Fibrosis (방사선 치료후 기관지-폐포세척액내 폐포대식세포 및 임파구의 접착분자발현 변화와 방사선에 의한 폐렴 및 폐섬유증발생의 예측인자로서의 의의)

  • Kim, Dong-Soon;Paik, Sang-Hoon;Choi, Eun-Kyung;Chang, Hye-Sook;Choi, Jung-Eun;Lim, Chae-Man;Koh, Yun-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.1
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    • pp.75-87
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    • 1996
  • Background: Lung cancer is the second most frequent malignancy in man in Korea. Surgery is the best treatment modality for non-small cell lung cancer, but most patients were presented in far advanced stage. So radiation therapy(RT) with or without chemotherapy is the next choice and radiation-induced pneumonitis and pulmonary fibrosis is the major limiting factor for the curative RT. Radiation pneumonitis is manifested with fever, cough and dyspnea, 2~3 months after the termination of radiotherpy. Chest X ray shows infiltration, typically limited to the radiation field, but occasionally bilateral infiltration was reported. Also Gibson et al reported that BAL lymphocytosis was found in both lungs, even though the radiation was confined to one lung. The aim of this study is to investigate the change of adhesion molecules expression on BAL cells and serum soluble ICAM-1(sICAM-1) level after the RT and its relationship to the development of radiation pneumonitis. The second aim is to confirm the bilaterality of change of BAL cell pattern and adhesion molecule expression. Subjects: BAL and the measurement of sICAM level in serum and BALF were done on 29 patients with lung cancer who received RT with curative intention. The BAL was done before the RT in 16 patients and 1~2 month after RT in 18 patients. 5 patients performed BAL before and after RT. Result: Clinically significant radiation pneumonitis developed in 7 patients. After RT, total cell count in BAL was significantly increased from $(20.2{\pm}10.2){\times}10^6\;cells/ml$ to $(35.3{\pm}21.6){\times}10^6\;cells/ml$ (p=0.0344) and %lymphocyte was also increased from $5.3{\pm}4.2%$ to $39.6{\pm}23.4%$ (p=0.0001) in all patient group. There was no difference between ipsilateral and contraleteral side to RT, and between the patients with and without radiation-pneumonitis. In whole patient group, the level of sICAM-1 showed no significant change after RT(in serum: $378{\pm}148$, $411{\pm}150\;ng/ml$, BALF: $20.2{\pm}12.2$, $45.1{\pm}34.8\;ng/ml$, respectively), but there was a significant difference between the patients with pneumonitis and without pneumonitis (serum: $505{\pm}164$ vs $345{\pm}102\;ng/ml$, p=0.0253, BALF: $67.9{\pm}36.3$ vs $25.2{\pm}17.9\;ng/ml$, p=0.0112). The expression of ICAM-1 on alveolar macrophages (AM) tends to increase after RT (RMFI: from $1.28{\pm}0.479$ to $1.63{\pm}0.539$, p=0.0605), but it was significantly high in patients with pneumonitis ($2.10{\pm}0.390$) compared to the patients without pneumonitis ($1.28{\pm}0.31$, p=0.0002). ICAM-1 expression on lymphocytes and CD 18 (${\beta}2$-integrin) expression tended to be high in the patients with pneumonitis but the difference was statiastically not significant. Conclusion: Subclinical alveolitis on the basis of BAL finding developed bilaterally in all patients after RT. But clinically significant pneumonitis occurred in much smaller fraction and the ICAM-1 expression on AM and the sICAM-1 level in serum were good indicator of it.

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Development and Assessment Individual Maximum Permissible Dose Method of I-131 Therapy in High Risk Patients with Differentiated Papillary Thyroid Cancer (물리학 선량법을 이용한 갑상선암의 개인별 최대안전용량 I-131 치료법 개발과 유용성 평가)

  • Kim, Jeong-Chul;Yoon, Jung-Han;Bom, Hee-Seung;JaeGal, Young-Jong;Song, Ho-Chun;Min, Jung-Joon;Jeong, Heong;Kim, Seong-Min;Heo, Young-Jun;Li, Ming-Hao;Park, Young-Kyu;Chung, June-Key
    • The Korean Journal of Nuclear Medicine
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    • v.37 no.2
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    • pp.110-119
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    • 2003
  • Purpose: Radioiodine (I-131) therapy is an effective modality to reduce both recurrence and mortality rates in differentiated thyroid cancer. Whether higher doses shows higher therapeutic responses was still debatable. The purpose of this study was to validate curve-fitting (CF) method measuring maximum permissible dose (MPD) by a biological dosimetry using metaphase analysis of peripheral blood lymphocytes. Materials and Methods: Therapeutic effects of MPD was evaluated in 58 patients (49 females and 9 males, mean age $50{\pm}11$ years) of papillary thyroid cancer. Among them 43 patients were treated with ${\Leq}7.4GBq$, while 15 patients with ${\geq}9.25GBq$. The former was defined as low-dose group, and the latter high-dose group. Therapeutic response was defined as complete response when complete disappearance of lesions on follow-up I-131 scan and undetectable serum thyroglobulin levels were found. Statistical comparison between groups were done using chi-square test. P value less than 0.05 was regarded as statistically significant. Results: MPD measured by CF method using tracer and therapeutic doses were $13.3{\pm}1.9\;and\;13.8{\pm}2.1GBq$, respectively (p=0.20). They showed a significant correlation (r=0.8, p<0.0001). Exposed doses to blood measured by CF and biological methods were $1.54{\pm}0.03\;and\;1.78{\pm}0.03Gy$ (p=0.01). They also showed a significant correlation (r=0.86, p=0.01). High-dose group showed a significantly higher rate of complete response (12/15, 80%) as compared to the low-dose group (22/43, 51.2%) (p=0.05). While occurrence of side effects was not different between two groups (40% vs. 30.2%, p=0.46). Conclusion: Measurement of MPD using CF method is reliable, and the high-dose I-131 therapy using MPD gains significantly higher therapeutic effects as compared with low-dose therapy.

Granulocytic Sarcoma(Chloroma) in Leukemic Patients (백혈병 환자의 과립구 육종(녹색종양))

  • Rhee, Seung-Koo;Kang, Yong-Ku;Bahk, Won-Jong;Jung, Yang-Kuk;Lee, Sang-Wook;Jeong, Ji-Ho
    • The Journal of the Korean bone and joint tumor society
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    • v.11 no.1
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    • pp.54-61
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    • 2005
  • Purpose: The granulocytic sarcoma which developed in leukemic patients are quite rare and it will have bad prognosis, but it's tumor pathogenesis and also their treatment are not yet established. Through this study we have tried to know their clinical course, prognosis and their end result of recent treatment. Material and Methods: Total 20 patients of granulocytic sarcoma which were developed in total 2,197 leukemic patients from April, 1998 to September, 2004 were treated at the leukemic center and the orthopaedic department of St. Mary's hospital, Catholic University of Korea, and followed them for 1~78 months(average 18 months). Results: Total 20 cases of granulocytic sarcoma was found in 14 cases of total 1,331 acute myelocytic leukemic patients(AML), 4 cases of total 744 of chronic myelocytic leukemic patients(CML), and only one case in total 122 of acute biphenotype of leukemia. And so their occurrence rate in leukmic patients are actually 0.91%, total 20 cases of granulocytic sarcoma in total 2,197 leukemic patients at same period. Their ages are average 28.3 years(4~52 years), and male are predominant(13 cases) than female(7 cases). Single involvement was found in 11 cases but multiple lesions are in 9 cases, and spine, brain, extremities, chest, and pelvic bone are involved in frequency. The granulocytic sarcoma was developed in various stages of the leukemia, ie, 8 cases in complete remission of leukemia, and 12 cases in the treatment process of AML. The pathohistologic evaluation of granulocytic sarcoma was done in 6 cases which was developed in their extremities, and confirmed numerous immature myeloblasts and lymphocytes mixed. The treatment of these granulocytic sarcoma was mainly limited for the treatment of leukemia by Glivac and massive steroid therapy(19cases) and also combined with the bone marrow transplantation(13 cases), but radiation therapy with average 3,500 rads in 15 cases out of total 20 sarcomas was also done, and followed them for average 17.5 months after development of granulocytic sarcomas. Finally their prognosis was so bad that 12 patients(60%) out of total 20 granulocytic sarcoma were dead in 6.5 months after sarcoma developed and we found the granulocytic sarcoma was more fatal if they are developed during the process of CML(mortality: 100%(4/4cases). Conclusion: The prognosis of granulocytic sarcomas in leukemic patients are quite fatal, and much more studies for their pathogenesis and ways of treatment should be performed continuously.

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Clinical Features and Treatment Response in 18 Cases with Idiopathic Nonspecific Interstitial Pneumonia (특발성 비특이성 간질성 폐렴 18례의 임상상 및 치료반응)

  • Kang, Eun-Hae;Chung, Man-Pyo;Kang, Soo-Jung;An, Chang-Hyeok;Ahn, Jong-Woon;Han, Joung-Ho;Lee, Kyung-Soo;Lim, Si-Young;Suh, Gee-Young;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.4
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    • pp.530-542
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    • 2000
  • Background : Nonspecific interstitial pneumonia (NSIP) has been reported recently to have shown much better response to medical treatment and better prognosis compared with idiopathic UIP. However, clinical characteristics of idiopathic NSIP discriminating it from UIP have not been clearly defined. Method : Among 120 patients with biopsy-proven diffuse interstitial lung diseases admitted to the Samsung Medical Center between July 1996 and March 2000, 18 patients with idiopathic NSIP were included in this study. Retrospective chart review and radiographic analysis were performed. Results : 1) At diagnosis, 17 patients were female and the average age was $55.2{\pm}8.4$ years (44~73 years). The average duration from development of respiratory symptom to surgical lung biopsy was $9.9{\pm}17.1$ months. Increase in bronchoalveolar lavage fluid lymphocytes ($23.0{\pm}13.1%$) was noted. On HRCT, ground glass and irregular linear opacity were observed, but honeycombing was absent in all patients. 2) Corticosteroids were initially given to 13 patients, but the medication was stopped in 3 patients due to severe side effects. Further medical therapy was not possible in 1 patient who experienced streroid-induced psychosis. Herpes zoster (n=3), tuberculosis (n=1), avascular necrosis of the hip (n=1), cataract (n=2) and diabetes mellitus (n=1) developed during prolonged corticosteroid administration. Of the 7 patients receiving oral cyclophosphamide therapy, hemorrhagic cystitis hindered one patient from continuing with the medication. 3) After medical treatment, 14 of 17 patients improved, and 3 patients remained stable (mean follow-up ; $24.1{\pm}11.2$ months). FVC increased by $20.2{\pm}11.2%$ of predicted value and the extent of ground glass opacity on HRCT decreased significantly ($15.7{\pm}14.7%$). 4) Of the 14 patients who had stopped medication, 5 showed recurrence of NSIP and 2 became aggravated during steroid tapering. All patients with recurrence showed deterioration within one year after completion of initial treatment. Conclusion : Since idiopathic NSIP has unique clinical profiles and shows good prognosis, diagnosis different from UIP, and aggressive medical treatment are needed.

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The Role of c-Jun N-terminal Kinase in the Radiation-Induced Lung Fibrosis (방사선에 의한 폐 섬유화증에서 c-Jun N-terminal Kinase(JNK)의 역할)

  • Uh, Soo-Taek;Hong, Ki-Young;Lee, Young-Mok;Kim, Ki-Up;Kim, Do-Jin;Moon, Seung-Hyuk;Kim, Yong-Hoon;Park, Choon-Sik;Yeom, Uk;Kim, Eun-Suk;Choi, Doo-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.4
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    • pp.450-461
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    • 2001
  • Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

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Soluble IL-2R, IFN-$\gamma$ and Neopterin as Immunologic Markers in Patients with Tuberculosis (결핵 환자에서 면역학적 지표로서의 sIL-2R, IFN-$\gamma$, Neopterin에 관한 연구)

  • Ryu, Yon-Ju;Ryu, Kum-Hei;Kim, Su-Hyun;Lee, Jong-Soo;Cheon, Seon-Hee;Seoh, Ju-Young
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.294-308
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    • 2002
  • Background : The cell-mediated immune response plays an important role in tuberculosis. After being activated by mycobacterial antigens, T lymphocytes express a high affinity receptor (IL-2R) for interleukin-2 (IL-2) on their own surface and release a soluble fraction of the IL-2 receptor (sIL-2R) from the cell membrane into the circulation. Neopterin is a metabolite of guanosine-triphosphate, which is produced by stimulated macrophages under the influence of IFN-$\gamma$ with a T lymphocyte origin. Therefore, the utility of sIL-2R, IFN-$\gamma$ and the neopterin levels as immunologic indices of the cell-mediated immune response and severity of disease in patients with pulmonary tuberculosis was assessed. Methods : The serum sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 39 patients with pulmonary tuberculosis, 6 patients with tuberculous lymphadenitis prior to treatment and 10 healthy subjects. The serum and pleural sIL-2R, neopterin and ADA levels were measured in 22 patients with tuberculous pleurisy. The patients with pulmonary tuberculosis were divided into a mild, moderate and severe group according to the severity by ATS guidelines. To compare the results from these patients with those of the pretreatment levels, the sIL-2R, IFN-$\gamma$ and neopterin levels were measured in 36 of the 39 patients(1 patient, expired; 2 patients were referred to a sanitarium) with pulmonary tuberculosis after 2 months of treatment. Results : 1) the serum sIL-2R and IFN-$\gamma$ levels were elevated in patients with tuberculosis when compared to those of healthy subjects (p>0.05). The neopterin concentration in the serum was significantly lower in patients with pulmonary tuberculosis($2967{\pm}2132.8$ pg/ml) than in healthy controls($4949{\pm}1242.1$ pg/ml)(p<0.05). 2) In the pulmonary tuberculosis group, the serum sIL-2R and IFN-$\gamma$ levels were higher in patients with severe disease than those in patients with mild and moderate disease. However, the neopterin levels declined as the pulmonary tuberculosis became more severe (p<0.01). 3) The mean serum sIL-2R and IFN-$\gamma$ levels declined from $1071{\pm}1139.4$ U/ml to $1023{\pm}1920.9$ U/ml(p>0.05), $41{\pm}52.8$ pg/ml to $22{\pm}23.9$ gm/ml(p<0.05), respectively, after 2 month of treatment. The mean serum neopterin levels increased from $3158{\pm}2272.6$ pg/ml to $3737{\pm}2307.5$ pg/ml(p>0.05) after a 2 month of treatment. These findings were remarkable in the severe group of pulmonary tuberculosis with a clinical correlation. 4) In the patients with tuberculous pleurisy, the serum sIL-2R and ADA were significantly higher than those in the pleural fluid, However, the neopterin levels in the sera and pleural effusion were similar. Conclusion : On the basis of this study, sIL-2R, IFN-$\gamma$ and neopterin measurements may not only provide an insight into the present state of the cell-mediated immune response, but also serve as parameters monitoring of the prognosis of the disease, particularly in patients with severe pulmonary tuberculosis. In addition, an assay of the pleural sIL-2R levels might signal a stimulated local immunity including T cell activation in the tuberculous pleural effusion.