• Childhood Kidney Diseases
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• v.7 no.2
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• pp.166-173
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• 2003

Purpose : The cause and pathogenesis of $Henoch-Sch\"{o}nlein$ purpura has been studied for many years but the results are disappointing. Recently the hypothesis that abnormalities involving the glycosylation of the hinge region of immunoglobulin Al(IgAl) may have an important role in the pathogenesis of $Henoch-Sch\"{o}nlein$ purpura is being approved. $Henoch-Sch\"{o}nlein$ purpura is the most common vasculitis Ihat affects children and the prognosis is good. But if kidney invovement occurs, the course may be chronic and troublesome. So we evaluated children with $Henoch-Sch\"{o}nlein$ purpura especially from the point of epidemiology and clinical manifestations. Methods : Investigation of 124 children who were diagnosed with $Henoch-Sch\"{o}nlein$ purpura at Inje University Ilsan Paik Hospital from December 1999 to July 2003 was performed retrospectively through chart review. Efforts were made to get informations about the profile, epidemiology, clinical manifestations, progress of the disease and recurrence rate of patients. Results : The patients were 69 boys and 55 girls, with a mean age of $6.1{\pm}2.7$ years at the time of data collection. The male to female ratio was 1.25 : 1. The occurrence rate was much higher in autumn(from September to November, 31.5%) and winter(from December to February, 28.2%) than in spring and summer, with a peak in November. Joint involvement was shown in 66.9% of patients mostly on the foot/ankle(75.9%), knee(39.8%). Seventy(56.5%) out of 124 patients had abdominal pain and 10 patients(8.1%) showed bloody stools. Renal involvement was observed in 24 patients(19.4%) after 21.1 days on the average. IgA was elevated in 10 of 21 patients(47.6%). $C_3$ and $C_4$ levels were normal in 40 of 49 patients (81.7%) and 47 of 48 patients(97.9%), respectively Antistreptolysin-O(ASO) titer was elevated over 250 Todd units in 29 of 62 Patients(46.8%). Mycoplasma antibody titer was elevated in 21 of 49 patients(42.9%) equal or greater than 1:80. Radiologic studies were peformed in 23 patients. Seven patients(30.4%) showed bowel wall thickening and one of them received intestinal resection and anastomosis operation due to terminal ileum necrosis. Eighty four patients took steroid 1.4 mg/kg/day in average. Recurrence rate was 2.5 in 37 patients(29.8%). Conclusion : $Henoch-Sch\"{o}nlein$ purpura in childhood appears most in about 6 years of age. The occurrence rate is much higher in autumn and winter relatively. Diagnosis can be made through the perspective history taking and the inspection of clinical manifestations, but the laboratory findings are not of great help. A small portion of the patients might show abdominal pain or arthritis before purpura develops, therfore various diagnosis can be made. Radiologic evaluation should be performed to avoid surgical complications in cases accompanying abdominal pain, and long term follow up should be needed especially in patients suffering from kidney involvement. In about 30% of the patients $Henoch-Sch\"{o}nlein$ purpura would recur. Steroid can be used safely without side effects.

• Journal of Hospice and Palliative Care
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• v.6 no.1
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• pp.51-57
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• 2003

Purpose : Anorexia-cachexia syndrome is one of the most common symptoms and main cause of death in terminal cancer patients. This symptom is due to the enlarged cancer mass as well as tumor released cytokines. Some doctors have suggested that vitamin C was preferentially toxic to tumor cells in vitro and in vivo, and improved clinical symptoms in terminal cancer patients. Therefore, we measured cytokines in serum of terminal cancer patients to determine whether vitamin C treatment improved the anorexia-cachexia syndrome. Methods : We investigated that 49 terminal cancer patients admitted to the department of family medicine, National Health Insurance Corporation Ilsan hospital from March 1, 2002 to August 31, 2002. The study was done on 22 patients who were given 10 g/day of vitamin C infusions during 1 week and 27 patients who were not infused. We measured the cytokines levels ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$) before and after 1 week between terminal cancer patients treated vitamin C and without vitamin C. Results : Out of 49 patients, patents treated with vitamin C infusions were 22 (12 male, 10 female), and these without vitamin C were 27 (18 male, 9 female). In patients treated with vitamin C, $IL-1{\beta}\;were\;6.19{\pm}5.17$ before day and $8.76{\pm}5.72$ after 1 week, IL-6 were $3.07{\pm}8.09$ before day and $1.31{\pm}2.36$ after 1 week, and $TNF-{\alpha}\;were\;2.74{\pm}14.24$ before day and $0.50{\pm}2.00$ after 1 week. In patients treated without vitamin C, $IL-1{\beta}\;were\;2.50{\pm}3.58$ before day and $6.49{\pm}12.01$ after 1 week, IL-6 were $1.00{\pm}2.19$ before day and $17.16{\pm}81.55$ after 1 week, and $TNF-{\alpha}\;were\;1.19{\pm}2.98$ before day and $1.27{\pm}1.52$ after 1 week. The level of cytokines in patients treated with vitamin C decreased more than those without vitamin C. However, this represented no statistical value (P=0.0598 in $IL-1{\beta}$, P=0.1664 in IL-6, and P=0.5395 in $TNF-{\alpha}$). Conclusion : In terminal cancer, even if there was no statistical difference in the cytokines levels between patients treated with vitamin C and those not treated, those who were treated had a decrease all cytokines levels. Vitamin C is very safe with almost no side effects. Therefore, vitamin C treatment in terminal cancer patients can be seen as beneficial and helpful for clinical symptoms.

• The Korean Nurse
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• v.20 no.4 s.112
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• pp.50-59
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• 1981

간호학생들이 당연하고 있는 문제점 미래의 간호학생들이 교육문제를 논하기 위하여는 간호학생들이 가지고 있는 문제점을 파악하고 또 이해하는 것이 우선순위가 될 것이다. 간호학생들이 문제점에 대한 연구는 한국에서 뿐아니라 미국에서도 꽤 많이 시행되어져 왔으며 특히 간호학과정에서 중간 탈락되는 중퇴자들에 대한 연구들 중에 이러한 문제점에 대해서 언급한 것이 많다. 고등학교를 졸업하고 곧 대학과정에 진학한 학생들을 대상으로 조사 보고될 Munro의 자료에 의하면 전문대학과정에서 27$\%$, 대학과정에서는 41$\%$의 간호학생들이 간호학과정에서 중간 탈락하고 있음이 보고되고 있다. 이들이 중간탈락하는 데에는 여러 가지 이유가 있으나 그 중 ''간호학에 흥미를 잃어서''가 가장 큰 이유로 보고되고 있다. 이곳 한국사회에서도 역시 비슷한 현상을 보이고 있다. 그러나 대학입시경쟁과 대학내에서의 전과가 거의 허용되지 않는 특수여건이기 때문에 학교를 중간 탈락하는 율은 미국이 보고만큼 높지는 않으나 역시 ''간호학에 흥미를 잃는다''는 것이 간호학생들의 가장 큰 문제점으로 대두되고 있다. 최근 한국에서 시행된 간호학생들에 관한 연구(표 1 참조)에 의하면 간호학생들의 학문에 대한 만족도는 조사자의 35$\~$50$\%$정도에 불과하였고 더우기 이 비율은 고학년에 올라갈수록 더욱 감소되고 있는 경향을 보이고 있다. 한국에서 시행된 어느 연구보고에 의하면 간호학에 실망했다고 생각하는 학생이 전체의 67$\%$였으며, 다른 학교로 전과를 희망한 경험이 있다는 학생이 71$\%$나 되는 것으로 보고되고 있다. 그러나 왜 흥미를 잃게 되는지 그 이유에 대하여 설명해 주는 연구는 많지 않았다. 미국의 한 저자는 간호학생들이 간호학에 흥미를 잃게 되는 원인을 간호원의 역할에 대한 이해가 정확하지 못한 것과 졸업 후 진로기회에 대한 인식부족 때문이라고 추측하고 있다. 간호학에 흥미를 잃게 되는 이유는 크게 다음의 세 가지로 분류 요약될 수 있다. 첫째, 간호학을 전공으로 택한 동기이다. 간호학의 특수성으로 인하여 학생들이 간호학을 전공으로 택한 동기도 다른 전공분야보다는 훨씬 다른 여러 종류를 보이고 있다. 즉, 종교적 이유, 다른 사람들에게 봉사할 수 있는 직업이기 때문에, 쉽게 취업을 할 수 있어서, 결혼 후에도 직업을 가질 수 있기 때문에, 외국으로 쉽게 취업할 수 있어서 등이 간호학을 선택한 이유로 보고되고 있다. 흥미나 적성에 맞다고 생각하기 때문에 간호학을 택한 학생의 수는 다른 과에 비하여 훨씬 적다. 이러한 흥미나 적성 때문이 아닌 여러 가지 다른 이유들로 인하여 간호학을 택한 경우에 특히 간호학에 쉽게 흥미를 잃어버리는 것을 볼 수 있다. 간호학에 현실적인 개념을 가지고 있는 학생들일수록 추상적이고 현실적인 개념을 가지고 있는 학생들보다 더 간호학에 지속적인 흥미를 가지며 중간에 탈락하는 율이 훨씬 적다는 것이 많은 연구에서 보고되었다. 또한 흥미나 적성 때문에 간호학을 택하였다는 학생들이 다른 과로 전과를 희망하는 율이 낮다는 것도 보고되었다. 둘째, 교과내용자체나 실습에 대한 불만족이다. 간호학에 대한 체계적인 교과내용의 결여, 과중한 과제물, 임상실습에서의 욕구불만, 실습으로 인한 부담, 지식과 실습의 차이점에 대한 갈등 등이 주요 이유로 보고되고 있다. 대부분의 연구들이 이 교과목이나 실습에 대한 불만족, 특히 실습경험에서의 갈등을 학생들이 흥미를 잃는 가장 중요한 요인이 되는 것으로 보고하고 있다. 어느 한 연구에서는 응답자의 90$\%$가 임상실습에 만족하지 못한다고 응답하였으며 그들 중의 88$\%$가 실습감독에 문제가 있다고 생각한다고 보고하였다. 셋째, 교수들에 대한 불만족이다. 대부분의 연구들이 학년이 올라가면 갈수록 교수에 대한 신뢰도가 낮아지며 또한 그에 비례하여 간호학에 대한 만족도가 낮아진다고 보고하고 있다. 교육내용에 대한 전문지식의 결여, 학생들과의 인간적인 관계의 결여, 교수법에 대한 불만족 등이 교수에 대한 불만의 주요내용으로 보고되었다. 미래의 간호에 부응할 학생교육 계속적인 사회적 변동과 더불어 급격하게 변화하고 있는 일반인들의 건강에 대한 요구도와 앞에서 기술한 문제점 등을 감안할 때 학생들에게 동기를 부여하고 간호학에 확신감을 가질 수 있도록 준비시키므로써 간호환경에서 실망하기보다는 오히려 그것을 받아들여 변화하는 사회요구에 책임감을 느낄 수 있도록 교육시키는 것이 미래의 간호학생을 준비시키는데 가장 중요한 요인이라고 할 수 있겠다. 이러한 교육을 위하여 다음의 두가지 안을 제시한다. 1. 교수와 학생간의 관계-서로의 좋은 동반자 : 교수들이 학생에게 미치는 영향, 특히 학생들의 성취도에 대한 영향에 대하여는 이미 많은 연구가 시행되었다. Tetreault(1976)가 간호학생들의 전문의식에 영향을 미치는 요인에 대하여 연구한 바에 의하면 다른 어느 것보다도 교수의 전문의식여부가 학생들의 전문의식 조성에 가장 큰 영향을 미친다고 하였다. 또한 학생들이 교수에게 신뢰감을 가지고 있을때, 교수들이 전문가로서의 행동을 하는 것을 보았을때 비로서 배움이 증가된다고 하였다. Banduras는 엄격하고 무서운 교수보다는 따뜻하고 인간적인 교수에게 학생들이 더 Role Model로서 모방하려는 경향을 나타낸다고 보고 하였다. 그러면 어떻게 학생에게 신뢰받는 교수가 될 수 있겠는가? apos;학생들의 요구에 부응할 때apos;라고 한마디로 표현할 수 있을 것이다. Lussier(1972)가 언급한 것처럼 학생들의 요구에 부응하지 못하는 교육은 Piaget이 언급한 교육의 기본 목표, 즉 개인에게 선배들이 한 것을 그대로 반복하여 시행하도록 하는 것이 아니라 새로운 것을 시도할 수 있는 능력을 가지게 하는 목표에는 도달할 수 없으며 이러한 목표는 간호학에도 가장 기본이 되어야 할 기본목표이기 때문이다. 학생들이 현재 어떤 요구를 가지고 있으며 또 어떤 생각을 하고 있는지 계속 파악하고 있는 것이 학생요구에 부응하는 교육을 할 수 있는 기본조건이 될 것이다. 의외로 많은 교수들이 학생들을 이해하고 있다고 생각하고 있으나 잘못 이해하고 있는 경우가 많다. 표 2는 현 간호학생들이 생각하고 있는 가치관과 문제점을 파악하고 또 교수가 그 가치관과 문제점을 어느 정도 파악하고 있는지 알아보기 위하여 일개 4년제 대학 200여명의 학생과 그 대학에 근무하는 18명의 교수진을 대상으로 질문한 결과를 간략하게 보고한 것이다. 또한 여기에서 학생이 보고하는 가치관, 문제점, 교수에게 바라는 점이 교수가 이해하고 있는 것과 차이가 있다는 것도 보여주고 있다. 우리가 학생들의 요구를 파악할 수 있도록 귀를 기울이고 이해하며, 그 요구에 부응하려고 노력할때 진정한 교수와 학생간의 관계가 이루어질 수 있을 것이며 이때 비로서 우리는 apos;partnershipapos;을 이룰 수 있을 것이다. 이때 간호학에 대한 실망은 줄어들 수 있을 것이며 우리도 학생들에게 전문가적인 태도를 함양시켜줄 수 있는 기회를 부여할 수 있을 것이다. 이렇게 될때 앞으로 기다리고 있는 미지의 의무에 효과적으로 또 적극적으로 대처할 수 있는 자질을 형성한 학생들을 준비해 낼 수 있을 것이다. 2. 간호모델에 의한 교과과정의 확립과 임상실습에의 적용 : 교과과정이 학생들의 모양을 만들어주는 하나의 기본틀이라고 말할 수 있다면 미래의 요구에 부응하는 학생들을 준비시키기 위하여 지금까지와는 다른 새로운 방향의 교과과정이 필요하다는 것은 재론할 필요가 없을 것이다. 이미 진취적인 간호대학에서는 guided design systems approach 또는 integrated curriculum 등의 새로운 교과과정을 시도하고 있음은 알려진 사실이다. 물론 간호모델에 준한 교과과정을 발전시키는데 대한 장점과 이에 수반되는 여러가지 새로운 문제점에 대하여 많은 논란이 있으나 모든 교과과정이 처음 시도될 때부터 완전한 것이 있을 수 없으며 시간이 지남에 따라 성숙되는 것임을 감안해 볼 때 이러한 새로운 교과과정에의 시도는 미래의 새로운 간호방향에 필수적인 사업이라고 하겠다. 이러한 교과과정을 개발하는데 몇가지 게안점을 첨부하려 한다. (1) 새로운 교과과정의 개발은 처음부터 끝까지 모든 교수진의 협력과 참여로 이루어져야 한다. (2) 비록 처음에는 어렵고 혼란이 있더라도 교과과정은 의학모델이 아닌 간호모델을 중심으로 이루어져야 한다. (3) 간호모델에서 다루어지는 개념들은 모두 직접 간호업무에 적용될 수 있는 것으로 선택되어야 한다. (4) 교과과정의 결과로 배출되는 학생들의 준비정도는 그 지역사회에 적합하여야 한다. (5) 그 지역사회의 고유한 문화적 요소가 포함되어야 한다. 아직 우리는 간호분야 내부의 갈등을 해결하지 못하고 있는 시기에 있다. 우리 내부의 문제점을 잘 해결할 수 있을때 외부와의 갈등에 잘 대처할 수 있을 것이다. 내부의 갈등을 잘 해결하기 위한 힘을 모으기 위하여는 동반자, 즉 교수와 학생, 간호교육자와 임상간호원 등이 서로 진정한 의미의 동반자 될때 가장 중요한 해결의 실마리가 될 것이다.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.729-741
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• 1997

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

• Tuberculosis and Respiratory Diseases
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• v.41 no.5
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• pp.452-461
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• 1994

Background: Tumor necrosis factor(TNF)-$\alpha$ and Interleukin(lL)-$1{\beta}$ are thought to play a major role in the pathogenesis of the septic syndrome, which is frequently associated with adult respiratory distress syndrome(ARDS). In spite of many reports for the role of TNF-$\alpha$ in the pathogenesis of ARDS, including human studies, it has been reported that TNF-$\alpha$ is not sensitive and specific marker for impending ARDS. But there is a possibility that the results were affected by the diversity of pathogenetic mechanisms leading to the ARDS because of various underlying disorders of the study group in the previous reports. The purpose of the present study was to evaluate the roles of TNF-$\alpha$ and IL-$1{\beta}$ as a predictable marker for development of ARDS in the patients with septic syndrome, in which the pathogenesis is believed to be mainly cytokine-mediated. Methods: Thirty-six patients of the septic syndrome hospitalized in the intensive care units of the Asan Medical Center were studied. Sixteens suffered from ARDS, whereas the remaining 20 were at the risk of developing ARDS(acute hypoxemic respiratory failure, AHRF). In all patients venous blood samples were collected in heparin-coated tubes at the time of enrollment, at 24 and 72 h thereafter. TNF-$\alpha$ and IL-$1{\beta}$ was measured by an enzyme-linked immunosorbent assay (ELISA). All data are expressed as median with interquartile range. Results: 1) Plama TNF-$\alpha$ levels: Plasma TNF-$\beta$ levels were less than 10pg/mL, which is lowest detection value of the kit used in this study within the range of the $mean{\pm}2SD$, in all of the normal controls, 8 of 16 subjects of ARDS and in 8 in 20 subjects of AHRF. Plasma TNF-$\alpha$ levels from patients with ARDS were 10.26pg/mL(median; <10-16.99pg/mL, interquartile range) and not different from those of patients at AHRF(10.82, <10-20.38pg/mL). There was also no significant difference between pre-ARDS(<10, <10-15.32pg/mL) and ARDS(<10, <10-10.22pg/mL). TNF-$\alpha$ levels were significantly greater in the patients with shock than the patients without shock(12.53pg/mL vs. <10pg/mL) (p<0.01). There was no statistical significance between survivors(<10, <10-12.92pg/mL) and nonsurvivors(11.80, <10-20.8pg/mL) (P=0.28) in the plasma TNF-$\alpha$ levels. 2) Plasma IL-$1{\beta}$ levels: Plasma IL-$1{\beta}$ levels were less than 0.3ng/mL, which is the lowest detection value of the kit used in this study, in one of each patients group. There was no significant difference in IL-$1{\beta}$ levels of the ARDS(2.22, 1.37-8.01ng/mL) and of the AHRF(2.13, 0.83-5.29ng/mL). There was also no significant difference between pre-ARDS(2.53, <0.3-8.34ngfmL) and ARDS(5.35, 0.66-11.51ng/mL), and between patients with septic shock and patients without shock (2.51, 1.28-8.34 vs 1.46, 0.15-2.13ng/mL). Plasma IL-$1{\beta}$ levels were significantly different between survivors(1.37, 0.4-2.36ng/mL) and nonsurvivors(2.84, 1.46-8.34ng/mL). Conclusion: Plasma TNF-$\alpha$ and IL-$1{\beta}$ level are not a predictable marker for development of ARDS. But TNF-$\alpha$ is a marker for shock in septic syndrome. These result could not exclude a possibility of pathophysiologic roles of TNF-$\alpha$ and IL-$1{\beta}$ in acute lung injury because these cytokine could be locally produced and exert its effects within the lungs.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.43 no.3
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• pp.308-322
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• 1996

Background : Neutrophils are considered to play critical roles in the development of acute respiratory distress syndrome. Histamine, which is distributed abundantly in lung tissue, increases the rolling of neutrophills via increase of P-selectin expression on the surface of endothelial cells and is known to have some interrelationships with IL-1, IL-8 and TNF-$\alpha$. We studied to investigate the effect of the histamine on the acute lung injury of the rats induced by intratracheal insufflation of TNF-$\alpha$ which has less potency to cause lung injury compared to IL-1 in rats. Methods : We intratracheally instilled saline or TNF(R&D, 500ng), IL-1(R&D, 50ng)or histamine of varius dose(1.1, 11 and $55\;{\mu}g/kg$) with and without TNF separately in Sprague-Dawley rats weighing 270-370 grams. We also intratracheally treated IL-1(50ng) along with histamine($55\;{\mu}g/kg$). In cases, there were synergistic effects induced by histamine on the parameters of TNF-induced acute lung injury, antihistamines(Sigma, mepyramine as a $H_1$ receptor blockade and ranitidine as a $H_2$ receptor blockade, 10 mg/kg in each)were co-administered intravenously to the rats treated TNF along with histamine($1.1\;{\mu}g/kg$) intratraeheally. Then after 5 h we measured lung lavage neutrophil numbers, lavage cytokine-induced neutrophil chemoattractants(CINC), lung myeloperoxidase activity(MPO) and lung leak. We also intratracheally insufflated TNF with/without histamine($11\;{\mu}g/kg$), then after 24 h measured lung leak in rats. Statistical analyses were done by Kruskal-Wallis nonparametric ANOVA test with Dunn's multiple comparison test or by Mann-Whitney U test. Results : We found that rats given TNF, histamine alone(11 and $55\;{\mu}g/kg$), and TNF with histamine(l.1, 11, and $55\;{\mu}g/kg$) intratracheally had increased (p<0.05) lung MPO activity compared with saline-treated control rats. TNF with histamine $11\;{\mu}g/kg$ had increased MPO activity (P=0.0251) compared with TNF-treated rats. TNF and TNF with histamine(1.1, 11, and $55\;{\mu}g/kg$) intratracheally had all increased (p<0.05) lung leak, lavage neutophil numbers and lavage CINC activities compared with saline. TNF with histamine $1.1\;{\mu}g/kg$ had increased (p=0.0367) lavage neutrophil numbers compared with TNF treated rats. But there were no additive effect of histamine with TNF compared with TNF alone in acute lung leak on 5 h and 24 h in rats. Treatment of rats with the $H_1$ and $H_2$ antagonists resulted in inhibitions of lavage neutrophil accumulations and lavage CINC activity elevations elicited by co-treated histamine in TNF-induced acute lung injury intratracheally in rats. We also found that rats given IL-1 along with histamine intratracheally did not have increase in lung leak compared with IL-1 treated rats. Conclusion : Histamine administered intratracheally did not have synergistic effects on TNF-induced acute lung leak inspite of additive effects on increase in MPO activity and lavage neutrophil numbers in rats. These observations suggest that instilling histamine intratracheally would not play synergistic roles in neutrophil-mediated acute lung injury in rats.

• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.51-66
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• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.4 no.1
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• pp.37-53
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• 1998

The sprig of Jinryungtang Gagambang has been used for curing as a traditional medicine without any experimental evidence to support the rational basis for their clinical use. This experiment was carried out to evaluate the possible therapeutic or antitumoral effects of Jinryungtang Gagambang extract against cancer, and to study some mechanisms responsible for its effect. The cytotoxic and antitumor effects were evaluated on human cell liens (A549, hep3B, Caki-1, Sarcoma 180) after exposure to Jinryungtang Gagambang extract using in ILS, colony forming efficency and SRB assay which were regarded as a valuable method for cytotoxic and antitumor effects of unknown compound on tumor cell lines. The results obtained in this studies were as follows. 1. As a result of exposure to Jinryungtang Gagambang extract, the proliferation of A549, hep3B, Caki-1, good correlations were shown from the results of SRB assay and those of clogenetic assay. 2. The oral administration of Jinryungtang Gagambang extract showed significant effects of increase of MST(mean survival time) and ILS(increased life span) depending on the increasing concentration. 3. Against squamous cell carcinoma induced by MCA, Jinryungtang Gagambang decreased not only the frequency of tumor production but also the number and weight of tumors per tumor bearing mice(TBM). Jinryungtang Gagambang also significantly suppressed the development of 3LL cell-implanted tumors by frequency and their size, and some developed tumors were regressed by the continuous treatment of Jinryungtang Gagambang extract into TBM. 4. Jinryungtang Gagambang extract also increased NK cell activities. According to the above results, it could be suggested that Jinryungtang Gagambang extract has prominent antiutmor effect.