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The Value of Interleukin-12 as an Activity Marker of Pulmonary Sarcoidosis (폐유육종증의 활동성 지표로서 IL-12의 효용성에 관한 연구)

  • Kim, Tae-Hyung;Jeon, Yong-Gam;Shim, Tae-Sun;Lim, Chae-Man;Koh, Yun-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.2
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    • pp.215-228
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    • 1999
  • Background: Sarcoidosis is a chronic granulomatous inflammatory disease of unknown etiology often involving the lungs and intrathoracic lymph nodes. The natural course of sarcoidosis is variable from spontaneous remission to significant morbidity or death. But, the mechanisms causing the variable clinical outcomes or any single parameter to predict the prognosis was not known. In sarcoidosis, the number and the activity of CD4 + lymphocytes are significantly increased at the loci of disease and their oligoclonality suggests that the CD4 + lymphocytes hyperreactivity may be caused by persistent antigenic stimulus. Recently, it has been known that CD4+ lymphocytes can be subdivided into 2 distinct population(Th1 and Th2) defined by the spectrum of cytokines produced by these cells. Th1 cells promote cellular immunity associated with delayed type hypersensitivity reactions by generating IL-2 and IFN-$\gamma$. Th2 cells playa role in allergic responses and immediate hypersensitivity reactions by secreting IL-4, IL-5, and IL-10. CD4+ lymphocytes in pulmonary sarcoidosis were reported to be mainly Th1 cells. IL-12 has been known to play an important role in differentiation of undifferentiated naive T cells to Th1 cells. And, Moller et al. observed increased IL-12 in bronchoalveolar lavage fluid(BALF) in patients with sarcoidosis. So it is possible that the elevated level of IL-12 is necessary for the continuous progression of the disease in active sarcoidosis. This study was performed to test the assumption that IL-12 can be a marker of active pulmonary sarcoidosis. Methods: We measured the concentration of IL-12 in BALF and in conditioned medium of alveolar macrophage(AM) using ELISA(enzyme-linked immunosorbent assay) method in 26 patients with pulmonary sarcoidosis(10 males, 16 females, mean age: $39.8{\pm}2.1$ years) and 11 normal control. Clinically, 14 patients had active sarcoidosis and 12 patients had inactive. Results: Total cells counts, percentage and number of lymhocytes, number of AM and CD4/CD8 lymphocyte ratio in BALF were significantly higher in patients with sarcoidosis than in control group. But none of these parameters could differentiate active sarcoidosis from inactive disease. The concentration of IL-12 in BALF was significantly increased in sarcoidosis patients ($49.3{\pm}9.2$ pg/ml) than in normal control ($2.5{\pm}0.4$ pg/ml) (p<0.001). Moreover it was significantly higher in patients with active sarcoidosis ($70.3{\pm}14.8$ pg/ml) than in inactive disease ($24.8{\pm}3.l$ pg/ml) (p=0.001). Also, the concentration of IL-12 in BALF showed significant correlation with the percentage of AM(p<0.001), percentage(p<0.001) and number of lymphocyte(p<0.001) in BALF, suggesting the close relationship between the level of IL-12 in BALF and the inflammatory cell infiltration in the lungs. Furthermore, we found a significant correlation between the level of IL-12 and the concentration of soluble ICAM-1 : in serum(p<0.001) and BALF (p=0.001), and also between IL-12 level and ICAM-1 expression of AM(p<0.001). The AM from patients with pulmonary sarcoidosis secreted significantly larger amount of IL-12 ($206.2{\pm}61.9$ pg/ml) than those of control ($68.3{\pm}43.7$ pg/ml) (p<0.008), but, there was no difference between inactive and active disease group. Conclusion : Our data suggest that the BALF IL-12 level can be used as a marker of the activity of pulmonary sarcoidosis.

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Localization of Sensory Neurons Innervating the Rat Intestine Using the Cholera Toxin B Subunit(CTB) and Wheat Germ Agglutinin-Horseradish Peroxidase(WGA-HRP) (표지방식을 이용한 흰 쥐 복강 내장을 지배하는 감각신경세포체와 신경섬유의 표지부위)

  • Lee, Dong-Hyup;Lee, Chang-Hyun;Lee, Moo-Sam
    • Journal of Yeungnam Medical Science
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    • v.15 no.1
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    • pp.75-96
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    • 1998
  • The local arrangement of sensory nerve cell bodies and nerve fibers in the brain stem, spinal ganglia and nodose ganglia were observed following injection of cholera toxin B subunit(CTB) and wheat germ agglutinin-horseradish peroxidase(WGA-HRP) into the rat intestine. The tracers were injected in the stomach(anterior and posterior portion), duodenum, jejunum, ileum, cecum, ascending colon or descending colon. After survival times of 48-96 hours, the rats were perfused and their brain, spinal and nodose ganglia were frozen sectioned ($40{\mu}m$). These sectiones were stained by CTB immunohistochemical and HRP histochemical staining methods and observed by dark and light microscopy. The results were as follows: 1. WGA-HRP labeled afferent terminal fields in the brain stem were seen in the stomach and cecum, and CTB labeled afferent terminal fields in the brain stem were seen in all parts of the intestine. 2. Afferent terminal fields innervating the intestine were heavily labeled bilaterally gelalinous part of nucleus of tractus solitarius(gelNTS), dorsomedial part of gelNTS, commissural part of NTS(comNTS), medial part of NTS(medNTS), wall of the fourth ventricle, ventral border of area postrema and comNTS in midline dorsal to the central canal. 3. WGA-HRP labeled sensory neurons were observed bilaterally within the spinal ganglia, and labeled sensory neurons innervating the stomach were observed in spinal ganglia $T_2-L_1$ and the most numerous in spinal ganglia $T_{8-9}$. 4. Labeled sensory neurons innervating the duodenum were observed in spinal ganglia $T_6-L_2$ and labeled cell number were fewer than the other parts of the intestines. 5. Labeled sensory neurons innervating the jejunum were observed in spinal ganglia $T_6-L_2$ and the most numerous area in the spinal ganglia were $T_{12}$ in left and $T_{13}$ in right. 6. Labeled sensory neurons innervating the ileum were observed in spinal ganglia $T_6-L_2$ and the most numerous area in the spinal ganglia were $T_{11}$ in left and $L_1$ in right. 7. Labeled sensory neurons innervating the cecum were observed in spinal ganglia $T_7-L_2$ and the most numerous area in the spinal ganglia were $T_{11}$ in left and $T_{11-12}$ in right. 8. Labeled sensory neurons innervating the ascending colon were observed in spinal ganglia $T_7-L_2$ in left, and $T_9-L_4$ in right. The most numerous area in the spinal ganglia were $T_9$ in left and $T_{11}$ in right. 9. Labeled sensory neurons innervating the descending colon were observed in spinal ganglia $T_9-L_2$ in left, and $T_6-L_2$ in right. The most numerous area in the spinal ganglia were $T_{13}$ in left and $L_1$ in right. 10. WGA-HRP labeled sensory neurons were observed bilaterally within the nodose ganglia, and the most numerous labeled sensory neurons innervating the abdominal organs were observed in the stomach. 11. The number of labeled sensory neurons within the nodose ganglia innervating small and large intestines were fewer than that of labeled sensory neurons innervating stomach These results indicated that area of sensory neurons innervated all parts of intestines were bilaterally gelatinous part of nucleus tractus solitarius(gelNTS), dorsomedial part of gelNTS, commissural part of NTS (comNTS), medial part of NTS, wall of the fourth ventricle, ventral border of area postrema and com NTS in midline dorsal to the central canal within brain stem, spinal ganglia $T_2-L_4$ and nodose ganglia. Labeled sensory neurons innervating the intestines except the stomach were observed in spinal ganglia $T_6-L_4$. The most labeled sensory neurons from the small intestine to large intestine came from middle thoracic spinal ganglia to upper lumbar spinal ganglia.

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Radioimmunoassay Reagent Survey and Evaluation (검사별 radioimmunoassay시약 조사 및 비교실험)

  • Kim, Ji-Na;An, Jae-seok;Jeon, Young-woo;Yoon, Sang-hyuk;Kim, Yoon-cheol
    • The Korean Journal of Nuclear Medicine Technology
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    • v.25 no.1
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    • pp.34-40
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    • 2021
  • Purpose If a new test is introduced or reagents are changed in the laboratory of a medical institution, the characteristics of the test should be analyzed according to the procedure and the assessment of reagents should be made. However, several necessary conditions must be met to perform all required comparative evaluations, first enough samples should be prepared for each test, and secondly, various reagents applicable to the comparative evaluations must be supplied. Even if enough comparative evaluations have been done, there is a limit to the fact that the data variation for the new reagent represents the overall patient data variation, The fact puts a burden on the laboratory to the change the reagent. Due to these various difficulties, reagent changes in the laboratory are limited. In order to introduce a competitive bid, the institute conducted a full investigation of Radioimmunoassay(RIA) reagents for each test and established the range of reagents available in the laboratory through comparative evaluations. We wanted to share this process. Materials and Methods There are 20 items of tests conducted in our laboratory except for consignment tests. For each test, RIA reagents that can be used were fully investigated with the reference to external quality control report. and the manuals for each reagent were obtained. Each reagent was checked for the manual to check the test method, Incubation time, sample volume needed for the test. After that, the primary selection was made according to whether it was available in this laboratory. The primary selected reagents were supplied with 2kits based on 100tests, and the data correlation test, sensitivity measurement, recovery rate measurement, and dilution test were conducted. The secondary selection was performed according to the results of the comparative evaluation. The reagents that passed the primary and secondary selections were submitted to the competitive bidding list. In the case of reagent is designated as a singular, we submitted a explanatory statement with the data obtained during the primary and secondary selection processes. Results Excluded from the primary selection was the case where TAT was expected to be delayed at the moment, and it was impossible to apply to our equipment due to the large volume of reagents used during the test. In the primary selection, there were five items which only one reagent was available.(squamous cell carcinoma Ag(SCC Ag), β-human chorionic gonadotropin(β-HCG), vitamin B12, folate, free testosterone), two reagents were available(CA19-9, CA125, CA72-4, ferritin, thyroglobulin antibody(TG Ab), microsomal antibody(Mic Ab), thyroid stimulating hormone-receptor-antibody(TSH-R-Ab), calcitonin), three reagents were available (triiodothyronine(T3), Tree T3, Free T4, TSH, intact parathyroid hormone(intact PTH)) and four reagents were available are carcinoembryonic antigen(CEA), TG. In the secondary selection, there were eight items which only one reagent was available.(ferritin, TG, CA19-9, SCC, β-HCG, vitaminB12, folate, free testosterone), two reagents were available(TG Ab, Mic Ab, TSH-R-Ab, CA125, CA72-4, intact PTH, calcitonin), three reagents were available(T3, Tree T3, Free T4, TSH, CEA). Reasons excluded from the secondary selection were the lack of reagent supply for comparative evaluations, the problems with data reproducibility, and the inability to accept data variations. The most problematic part of comparative evaluations was sample collection. It didn't matter if the number of samples requested was large and the capacity needed for the test was small. It was difficult to collect various concentration samples in the case of a small number of tests(100 cases per month or less), and it was difficult to conduct a recovery rate test in the case of a relatively large volume of samples required for a single test(more than 100 uL). In addition, the lack of dilution solution or standard zero material for sensitivity measurement or dilution tests was one of the problems. Conclusion Comparative evaluation for changing test reagents require appropriate preparation time to collect diverse and sufficient samples. In addition, setting the total sample volume and reagent volume range required for comparative evaluations, depending on the sample volume and reagent volume required for one test, will reduce the burden of sample collection and planning for each comparative evaluation.

The Effect of Platelets on Endothelin Production in Bovine Pulmonary Artery Endothelial Cells (혈소판이 소 폐동백 내피세포의 Endothelin 생산에 미치는 효과)

  • Lee, Sang-Do;Shim, Tae-Sun;Kwon, Seog-Woon;Ryu, Jin-Sook;Lee, Jae-Dam;Lim, Chae-Man;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.5
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    • pp.1114-1124
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    • 1997
  • Background : Endothelin(ET) is a very potent vasoconstrictive peptide produced by endothelial cells of pulmonary artery. The endothelin level was increased in plasma of primary pulmonary hypertension and acute pulmonary thromboembolism and it was suggested that the endothelin might do a critical role in the cardiopulmonary dysfunction in these two conditions. But the exact mechanism of increase of ET has not been known. In these two conditions, platelet activation and thrombosis are the main pathophysiologic findings. So there is a possibility that the platelet might stimulate endothelin secretion from endothelial cells. Therefore, we performed this study to evaluate the role of platelet and its mediators on endothelin production in bovine pulmonary artery endothelial(BPAE) cells. Method : Bovine pulmonary artery endothelial cells, ATCC certified cell line 209, were cultured and treated with human platelets($10^6{\sim}10^8/ml$), thrombin (0.1~10u/ml), TGF-${\beta}1$(1~100uM), serotonin(1~100uM), and endotoxin(1ug/ml) in a final volume of 500ul for 18 hours. Levels of ir(immunoreactive)-ET in each conditioned medium were measured by a radioimmunoassay specific for ET. Result : The increase of ir-ET levels was platelet number and time dependent over 18 hours. When washed human platelets were added($10^8/ml$), the ir-ET levels were significantly higher than that of control(p<0.05) at 8 and 18 hours after culture. Subthreshold concentration of platelets($10^7/ml$) coincubated with endotoxin(1ug/ml) or subthreshold dose of thrombin(0.1u/ml) stimulated ir-ET secretion from BPAE cells significantly(p<0.05) compared with control. Thrombin(1ug/ml, 10ug/ml) and TGF-${\beta}1$(100pM, 1000pM) significantly increased ir-ET secretion from BP AE cells(p<0.05) compared with control, but serotoin(1~100uM) and endotoxin(1ug/ml) did not stimulate the ir-ET secretion. Conclusions : Platelets stimulate endothelin secretion from bovine pulmonary artery endothelial cells. The mechanism of increase of endothelin secretion seems to be a stimulation by platelet itself or by mediators, such as TGF-${\beta}1$, secreted from activated platelets. And, in this study, the priming effect of platelets on endothelin secretion from BPAE cells could be another possibility.

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Retrograde Autologous Priming: Is It Really Effective in Reducing Red Blood Cell Transfusions during Extracorporeal Circulation? (역행성 자가혈액 충전법: 체외순환 중 동종적혈구 수혈량을 줄일 수 있는가?)

  • Lim, Cheong;Son, Kuk-Hui;Park, Kay-Hyun;Jheon, Sang-Hoon;Sung, Sook-Whan
    • Journal of Chest Surgery
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    • v.42 no.4
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    • pp.473-479
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    • 2009
  • Background: Retrograde autologous priming (RAP) is known to be useful in decreasing the need of transfusions in cardiac surgery because it prevents excessive hemodilution due to the crystalloid priming of cardiopulmonary bypass circuit. However, there are also negative side effects in terms of blood conservation. We analyzed the intraoperative blood-conserving effect of RAP and also investigated the efficacy of autotransfusion and ultrafiltration as a supplemental method for RAP. Material and Method: From January 2005 to December 2007, 117 patients who underwent isolated coronary artery bypass operations using cardiopulmonary bypass (CPB) were enrolled. Mean age was 63.9$\pm$9.1 years (range 36$\sim$83 years) and 34 patients were female. There were 62 patients in the RAP group and 55 patients in he control group. Intraoperative autotransfusion was performed via the arterial line. RAP was done just before initiating CPB using retrograde drainage of the crystalloid priming solution. Both conventional (CUF) and modified (MUF) ultrafiltrations were done during and after CPB, respectively. The transfusion threshold was less than 20% in hematocrit. Result: Autotransfusions were done in 79 patients (67.5%) and the average amount was 142.5$\pm$65.4 mL (range 30$\sim$320 mL). Homologous red blood cell (RBC) transfusion was done in 47 patients (40.2%) and mean amount of transfused RBC was 404.3$\pm$222.6 mL. Risk factors for transfusions were body surface area (OR 0.01, 95% CI 0.00 $\sim$ 0.63, p=0.030) and cardiopulmonary bypass time (OR 1.04, 95% CI 1.01 $\sim$ 1.08, p=0.019). RAP was not effective in terms of the rate of transfusion (34.5% vs 45.2%, p=0.24). However, the amount of transfused RBC was significantly decreased (526.3$\pm$242.3ml vs 321.4$\pm$166.3 mL, p=0.001). Autotransfusion and ultrafiltration revealed additive and cumulative effects decreasing transfusion amount (one; 600.0$\pm$231.0 mL, two; 533.3$\pm$264.6 mL, three; 346.7$\pm$176.7 mL, four; 300.0$\pm$146.1 mL, p=0.002). Conclusion: Even though RAP did not appear to be effective in terms of the number of patients receiving intraoperative RBC transfusions, it could conserve blood in terms of the amount transfused and with the additive effects of autotransfusion and ultrafiltration. If we want to maximize the blood conserving effect of RAP, more aggressive control will be necessary - such as high threshold of transfusion trigger or strict regulation of crystalloid infusion, and so forth.

A Study on an Effective Decellularization Technique for a Xenograft Cardiac Valve: the Effect of Osmotic Treatment with Hypotonic Solution (이종 심장 판막 이식편에서 효과적인 탈세포화 방법에 관한 연구; 저장성 용액(hypotonic solution)의 삼투압 처치법 효과)

  • Sung, Si-Chan;Kim, Yong-Jin;Choi, Sun-Young;Park, Ji-Eun;Kim, Kyung-Hwan;Kim, Woong-Han
    • Journal of Chest Surgery
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    • v.41 no.6
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    • pp.679-686
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    • 2008
  • Background: Cellular remnants in the bioprosthetic heart valve are known to be related to a host's immunologic response and they can form the nidus for calcification. The extracellular matrix of the decellularized valve tissue can also be used as a biological scaffold for cell attachment, endothelialization and tissue reconstitution. Thus, decellularization is the most important part in making a bioprosthetic valve and biological caffold. Many protocols and agents have been suggested for decellularization, yet there ave been few reports about the effect of a treatment with hypotonic solution prior to chemical or enzymatic treatment. This study investigated the effect of a treatment with hypotonic solution and the appropriate environments such as temperature, the treatment duration and the concentration of sodium dodecylsulfate (SDS) for achieving proper decellularization. Material and Method: Porcine aortic valves were decellularized with odium dodecylsulfate at various concentrations (0.25%, 0.5%), time durations (6, 12, 24 hours) and temperatures ($4^{\circ}C$, $20^{\circ}C$)(Group B). Same the number of porcine aortic valves (group A) was treated with hypotonic solution prior to SDS treatment at the same conditions. The duration of exposure to the hypotonic solution was 4, 7 and 14 hours and he temperature was $4^{\circ}C$ and $20^{\circ}C$, respectively. The degree of decellularization was analyzed by performing hematoxylin and eosin staining. Result: There were no differences in the degree of decellularization between the two concentrations (0.25% 0.5%) of SDS. Twenty four hours treatment with SDS revealed the best decellularization effect for both roups A and B at the temperature of $4^{\circ}C$, but there was no differences between the roups at $20^{\circ}C$. Treatment with hypotonic solution (group A) showed a better ecellularization effect at all the matched conditions. Fourteen hours treatment at $4^{\circ}C$ ith ypotonic solution prior to 80S treatment revealed the best decellularization effect. The treatment with hypotonic solution at $20^{\circ}C$ revealed a good decellularization effect, but his showed significant extracellular matrix destruction. Conclusion: The exposure of porcine heart valves to hypotonic solution prior to SDS treatment is highly effective for achieving decellularization. Osmotic treatment with hypotonic solution should be considered or achieving decellularization of porcine aortic valves. Further study should be carried out to see whether the treatment with hypotonic solution could reduce the exposure duration and concentration of chemical detergents, and also to evaluate how the structure of the extracellular matrix of the porcine valve is affected by the exposure to hypotonic solution.

A Therapeutic Effect of Ozonated Oil on Bovine Mastitis (젖소 유방염에 대한 Ozonated oil의 치료효과)

  • Jo Sung-Nam;Liu Jianzhu;Lee Sang-Eun;Hong Min-Sung;Kim Duck-Hwan;Kim Myung-Cheol;Cho Sung-Whan;Jun Moo-Hyung
    • Journal of Veterinary Clinics
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    • v.22 no.4
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    • pp.318-321
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    • 2005
  • Forty- nine quarters from 24 lactating cows with chronic mastitis were selected. The cows were raised on dairy farms in Gongju, Jochiwon and Yeongi in Chungnam province, and Iksan in Jeonbuk province, Korea. The 49 quarters with bovine mastitis were divided into control (7 quarters) and experimental (42 quarters) groups. The experimental quarters were assigned to experimental group A (10 quarters, somatic cell count: $50-100\times10^4/ml)$, experimental group B (14 quarters, somatic cells count: $100-300{\times}10^4/ml)$, and experimental group C (18 quarters, somatic cells count: $>300\times10^4/ml$), according to the number of the somatic cells in their milk. The quarters of control group were treated with norfloxacin ointment (10 g/tube) based on the result of sensitivity, twice a day for 3 days. The quarters or experimental groups were infused 10ml or ozonated oils twice a day for 3 days. After treatment, the milk of the control group contained non-significantly lower numbers of somatic cells and bacteria on day 7, compared with pretreatment levels. Experimental groups A, B and C had lower somatic and bacterial cells in their milk on day 7, compared with pretreatment levels. Experimental group B and C had significantly lower numbers of somatic cells in their milk ell day 7 than before treatment (p<0.01). However, no significant difference in somatic cell numbers was detected between the control alld experimental groups. It was concluded that ozone therapy with ozonated oil applied on bovine mastitis might be effective.

Combined Chemoradiotherapy vs Radiotherapy Alone for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (국소적으로 진행된 두경부 편평상피세포종양의 방사선- 항암화학 병용요법과 방사선단독치료의 비교)

  • Jeong, Hyeon-Ju;Suh, Hyun-Suk;Kim, Chul-Soo;Kim, Re-Hwe;Kim, Sung-Rok
    • Radiation Oncology Journal
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    • v.14 no.1
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    • pp.9-15
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    • 1996
  • Purpose: The traditional approach with surgery and/or radiotherapy(RT) for advanced head and neck cancer Provides anticipated cure rates of $10-65\%$ depending on stages and sites. Recently, combined modality with chemotherapy have been extensively investigated in attempts to improve survival and local control. We retrospectively analysed our experience of 31 patients with advanced head and neck cancer. Materials and Methods : November 1983 to October 1994. 31 Patients with Stage III and IV squamous cell head and neck cancer were treated with RT. Sixteen patients were treated with RT alone, and IS patients were treated with combined RT plus chemotherapy. All patients were treated with 4-MV LINAC and radiation dose ranged from 5000 cGy to 7760 cGy (median 7010 cGy). In combined group, 7 patients were treated with cisplatin plus 5-FU 2 patients were treated with methotrexate plus leucovorin plus 5-FU plus cisplatin or carboplatin, and 6 patients were treated with cisplatin as a radiosensitizer. Results : Median follow up period was 16 months (range 4-134 months). The major responses (CR+PR) were noted in 10 patient ($66.6\%$) of the RT alone group and 14 patient ($93.3\%$) of the chemoradiation group. There was no statistical difference in CR rate between the two groups The overall survival rates at 5 years were $23.4\%$ in the radiation alone group, $23.5\%$ in the chemoradiation group Disease-free survival rates at 3 years were $44.5\%$ in the radiation alone group, $40\%$ in the chemoradiation group. There was no statistical differences in overall survival rates and disease-free survival rates between the two groups. Local recurrences occurred in $71.5\%$ of the radiation alone group, $72.7\%$ of the chemoradiation group and distant metastasis occurred in $14.4\%$ of radiation alone group, $9.1\%$ of the chemoradiation group. The frequencies of complications were comparable in both groups except hematologic toxicity Conclusion : Total response rates in the combined chemotherapy and radiotherapy was relatively higher than radiotherapy alone. But our result failed to show any survival benefit of the combined chemotherapy and radiotherapy. The accrual of large number of patients and long term follow-un may be necessary to confirm the present result of combined chemotherapy and radiotherapy.

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Comparative Analysis of Patterns of Care Study of Radiotherapy for Esophageal Cancer among Three Countries: South Korea, Japan and the United States (한국, 미국, 일본의 식도암 방사선 치료에 대한 PCS($1998{\sim}1999$) 결과의 비교 분석)

  • Hur, Won-Joo;Choi, Young-Min;Kim, Jeung-Kee;Lee, Hyung-Sik;Choi, Seok-Reyol;Kim, Il-Han
    • Radiation Oncology Journal
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    • v.26 no.2
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    • pp.83-90
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    • 2008
  • Purpose: For the first time, a nationwide survey of the Patterns of Care Study(PCS) for the various radiotherapy treatments of esophageal cancer was carried out in South Korea. In order to observe the different parameters, as well as offer a solid cooperative system, we compared the Korean results with those observed in the United States(US) and Japan. Materials and Methods: Two hundreds forty-six esophageal cancer patients from 21 institutions were enrolled in the South Korean study. The patients received radiation theraphy(RT) from 1998 to 1999. In order to compare these results with those from the United States, a published study by Suntharalingam, which included 414 patients[treated by Radiotherapy(RT)] from 59 institutions between 1996 and 1999 was chosen. In order to compare the South Korean with the Japanese data, we choose two different studies. The results published by Gomi were selected as the surgery group, in which 220 esophageal cancer patients were analyzed from 76 facilities. The patients underwent surgery and received RT with or without chemotherapy between 1998 and 2001. The non-surgery group originated from a study by Murakami, in which 385 patients were treated either by RT alone or RT with chemotherapy, but no surgery, between 1999 and 2001. Results: The median age of enrolled patients was highest in the Japanese non-surgery group(71 years old). The gender ratio was approximately 9:1(male:female) in both the Korean and Japanese studies, whereas females made up 23.1% of the study population in the US study. Adenocarcinoma outnumbered squamous cell carcinoma in the US study, whereas squamous cell carcinoma was more prevalent both the Korean and Japanese studies(Korea 96.3%, Japan 98%). An esophagogram, endoscopy, and chest CT scan were the main modalities of diagnostic evaluation used in all three countries. The US and Japan used the abdominal CT scan more frequently than the abdominal ultrasonography. Radiotherapy alone treatment was most rarely used in the US study(9.5%), compared to the Korean(23.2%) and Japanese(39%) studies. The combination of the three modalities(Surgery+RT+Chemotherapy) was performed least often in Korea(11.8%) compared to the Japanese(49.5%) and US(32.8%) studies. Chemotherapy(89%) and chemotherapy with concurrent chemoradiotherapy(97%) was most frequently used in the US study. Fluorouracil(5-FU) and Cisplatin were the most preferred drug treatments used in all three countries. The median radiation dose was 50.4 Gy in the US study, as compared to 55.8 Gy in the Korean study regardless of whether an operation was performed. However, in Japan, different median doses were delivered for the surgery(48 Gy) and non-surgery groups(60 Gy). Conclusion: Although some aspects of the evaluation of esophageal cancer and its various treatment modalities were heterogeneous among the three countries surveyed, we found no remarkable differences in the RT dose or technique, which includes the number of portals and energy beams.

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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