• Clinical and Experimental Pediatrics
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• v.45 no.8
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• pp.1000-1006
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• 2002

Purpose : In the course of treatment, patients with hematological or oncological disorders often develop pulmonary complication. The patients who develop a severe pulmonary complication have a poor outlook. The causes of pulmonary complication are either infectious or non-infectious in origin. We have analyzed the etiology and outcome of these patients admitted to the pediatric intensive care unit of Asan Medical Center. Methods : Medical records of 95 patients on Pediatric oncology service who were admitted to pediatric intensive care unit(PICU) of Asan Medical Center from Jan 1997 to May 2000 were retrospectively reviewed. Results : The mean age of the patients was 8.5 years(2 months-18 years). The underlying malignancies of these 95 patients were as following; acute lymphoblastic leukemia(31 cases), lymphoma (11 cases), acute myeloid leukemia(nine cases), brain tumor(eight cases) and other solid tumors(25 cases). Pulmonary complications included pneumonia, acute respiratory failure, pneumothorax and pleural effusion. The most common cause of pulmonary complication was infection(88%) in etiology. The overall mortality rate was 56.8%. Pulmonary complications in these patients carried high rates of mortality regardless of whether they were immune compromised(76%) or not(69%). Even without pulmonary complications, the hematological or oncological patients admitted to PICU had high mortality rates of 43%. Conclusion : Pulmonary complications are frequent finding in the hematological or oncological patients admitted to Intensive Care Unit. The main etiology of these pulmonary complications was infection, which carried a high mortality rate regardless of their immune status at the time when they were admitted to PICU.

• Tuberculosis and Respiratory Diseases
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• v.43 no.5
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• pp.728-735
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• 1996

Background : Recognition and ingestion of opsonized microorganisms by neutrophils induces the burst of oxidative metabolic activity. Products of the respiratory burst activity provide powerful oxygen dependent killing mechanism. Measurement of respiratory burst activity has been a major indicator of the functional capacity of neutrophils. We determined the respiratory burst activity of neutrophils in patients with pneumonia and observed the changes during the clinical course of pneumonia. Methods: The EDTA blood was drawn from 24 normal controls and same numbers of pneumonia patients. The respiratory burst activity(with the production of $H_2O_2$ which changes nonfluorescent DCF-DA to green fluorescent DCF) in the non-stimulated state and the stimulated state with fMLP and PMA of neutrophils was measured by flowcytometry at day 1, 3, 5, 7 and 9 of admission. Results: The respiratory burst activity of neutrophils was mildly increased by stimulation with fMLP. But there was no statistical significance between normal control and patients with pneumonia. The respiratory burst activity of neutrophils was markedly increased by stimulation with PMA in both groups. There was a significant difference in response to PMA between normal control and patients with pneumonia. The production of hydrogen peroxide from neutrophils was decreased during early course of pneumonia and it was recuperated gradually to normal level in 9 days. Conclusion : Hydrogen peroxide production from neutrophils was suppressed during early course of pneumonia and restored after treatment. It is suggested that the production of oxygen radical in response to PMA stimulation from each neutrophils is decreased rather than increased during the early course of pneumonia.

• Tuberculosis and Respiratory Diseases
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• v.46 no.3
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• pp.338-349
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• 1999

Polymorphonuclear leukocytes(PMN) are the predominant inflammatory cells recruited in acute lung injury such as adult respiratory distress syndrome, pneumonia and also chronic lung disease such as idiopathic pulmonary fibrosis and pulmonary emphysema. Interleukin-8(IL-8) is an 8,000 D protein produced by many cells and has potent neutrophil chemoattractant and activating properties. The GRO, also called melanoma growth-stimulatory activity(MGSA), referring to a peptide of 73 amino acids, was reported to be mitogenic for cultured human melanoma cells. Mature GRO/MGSA has marked sequence similarity to IL-8. In view of the structural similarities to IL-8, it was of particular interest to test GRO for neutrophil activating and chemotactic properties. We found a significant release of IL-8 and GRO/MGSA from the cultured human umbilical vein endothelial cell(HUVEC) which was stimulated either with TNF$\alpha$ or IL-1$\beta$ and also found the expression of IL-8 and GRO/MGSA mRNA. Neutrophil chemotactic activity was enhanced in accordance with the increased IL-8 and GRO/MGSA. Our study also suggest that the IL-8 is more important in the increased neutrophil chemotactic activity than GRO/MGSA when endothelial cell is stimulated with TNF$\alpha$ or IL-1$\beta$ in vitro.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.249-249
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• 1994

PAF (Platelet-activating factor: 혈소판 활성화인자)는 1972년 Benveniste등에 의해 토끼의 호중구 배양 상청액중에서 발견되어 1979년 그 구조가 1-alkyl-2-acethyl-sn glycero-3-phosphocholine의 구조를 갖는 에테르형 인 지질임이 밝혀졌다. 그후 혈소판 이외 과립구, 단구나 macrophage, 혈관내피세포등 조직의 염증담당세포가 다양한 자극에 응하여 PAF를 생성됨이 보고되었다. PAF가 나타내는 대표적 활성으로는 혈소판, 호중구, 단구들의 활성화, 호중구의 유주 활성, 혈관투과성 항진, 혈압강하작용. 기관지 수축 등이 알려졌으며. 또한 염증, 알러지, 천식 endotoxin shock 등 여러질병에 직·간접적으로 관여함이 알려졌다. 이와같은 여러 생리 현상은 PAF의 특이적수용체를 개재하여 일어난다는 것이 밝혀졌다. 따라서 PAF의 다양한 질병의 관여가 밝혀짐으로서, PAF길항제의 개발이 활발히 진행되어왔다. 지금까지 PAF길항제의 개발은 PAF 구조 유사체. benzodiazepam유도체, thiazole유도체 등과 같은 합성품과 ginkolide, kadsurenone과 같은 천연물 유리의 것이 알려져 in vivo model에서도 그 효능이 확인되었다. 본 연구는 이와 같은 배경에서 20여 종의 생약에서 PAF 길항제를 검색하던 중 5종류의 생약에서 PAF 길항작용을 갖는 분획을 찾았기에 이에 보고한다.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.379-390
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• 1997

Background : It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pulmonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutropenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. Method : The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cells was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. Results : The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA : More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells : In the ETX-group, the number of total cells (p < 0.01) and of macrophage and neutrophil (p < 0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC-group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and it took part in less than 0.1% of total BAL cells (p < 0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF : In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p < 0.05 and < 0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p < 0.05 vs NC-group), but the value was statistically not different from that of ETX-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p < 0.05), but showed still a higher value compared to that of NC-group (p < 0.05). A change of cytokine concentration in the BALF : TNF -alpha and IL-6 were elevated in the ETX - and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells : There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p < 0.0008 vs NC-group), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion : Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveolar macrophages.

• Tuberculosis and Respiratory Diseases
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• v.43 no.4
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• pp.579-589
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• 1996

Background : Activation of neutrophil is critical for the clearance of microorganisms and toxic host mediators during sepsis. Unfortunately the activated neutrophil and its toxic byproducts can produce tissue injury and organ dysfunction. The leucocyte CD11/18 adhesion complex regulates neutrophil-endothelial cell adhesion, the first step in neutrophil migration to sites of injection and inflammation. To investigate the potential of neutrophil inhibition as a treatment strategy for sepsis, we evaluated the effects of monoclonal antibody against CD11b (MAb 1B6) in rats intrabronchial challenged with Escherichia coli. Methods : Animals were randomly assigned to receive monoclonal antibody against CD11b (1 mg/kg, sc) and bovine serum albumin(BSA, 1 mg/kg, sc) 6 hr before, at 0 and 6 hr after intrabronchial challenge of $20x10^9$ CFU/kg E. coli 0111. Animals were randomized to treat either 24, 60 or 90% oxygen after bacterial challenge and begining 4 hr after inoculation, all animals were received 100 mg/kg ceftriaxone qd for 3 days. Peripheral and alveolar neutrophil(by bronchoalveolar lavage) counts and lung injury parameters such as alveolar-arte rial $PO_2$ difference, wet to dry lung weight ratio and protein concentration of alveolar fluid were measured in survived rats at 12 hr and 96 hr. Results : Monoclonal antibody against CD11b decreased circulating and alveolar neutrophil especially more in 12 hr than in 96 hr The lung injury parameters of antibody-treated animals were not different from those of BSA-treated animals. but It was meaningless due to small number of survived animals. The early(6 hr) mortality rate was significantly increased in antibody-treated group(51%) compared to BSA-treated group(31%) (P=0.02) but late(from 12 hr to 72 hr) mortality rate was not different in antibody-treated group(44%) from BSA-treated group(36%) (P =0.089). Conclusion : Leucocyte CD11b/18 adhesion molecule is known to regulate neutrophil migration to the site of infection and inflammation. The monoclonal antibody against CD11b decreased alveolar neutrophil in rats with pulmonary sepsis and increased early mortality rate. Therefore, we can speculate that monoclonal antibody against CD11b blocks of alveolar recruitment of neutrophils, impairs host defense mechanism and increases early mortality rate of pulmonary sepsis in rat.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.417-424
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• 1996

The present study was done to examine the involvement of protein kinase C and protein tyrosine kinase in intracellular $Ca^{2+}$ mobilization in C5a-stimulated neutrophils. Although protein kinase C inhibitors, staurosporine and H-7 inhibited intracellular $Ca^{2+}$ release in C5a-stimulated neutrophils, they did not affect $Ca^{2+}$ influx across the plasma membrane and elevation of $[Ca^{2+}]_i$ C5a-induced intracellular $Ca^{2+}$ release and $Ca^{2+}$ influx were inhibited by protein tyrosine kinase inhibitors, genistein and methyl-2,5-dihydroxycinnamate. ADP-evoked elevation of $[Ca^{2+}]_i$ was inhibited by genistein and methyl-2,5-dihydroxycinnamate but was not affectd by staurosporine and H-7. Genistein and methyl-2,5-dihydroxycinnamate reduced the store-regulated $Ca^{2+}$ influx in thapsigargin-treated neutrophils, while the effect of staurosporine and H-7 was not detected. When neutrophils were preincubated wih phorbol 12-myristate 13-acetate, the stimulatory effect of C5a on the elevation of $[Ca^{2+}]_i$ was reduced. These results suggest that protein tyrosine kinase may be involved in control of intracellular $Ca^{2+}$ release and $Ca^{2+}$ influx across the plasma membrane in C5a-activated neutrophils.

• Clinical and Experimental Pediatrics
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• v.49 no.11
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• pp.1167-1173
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• 2006

Purpose : To evaluate various sepsis screening tests, individually and in combination, to formulate a guideline for the diagnosis of neonatal sepsis. Methods : The study was a retrospective cohort study. It took place at the neonatal intensive care unit of the Paediatric Department, Il Sin Christian Hospital, Busan, Korea, over a period of 68 months from 1st, April, 2001 to 31st, December, 2005. This study evaluated 100 neonates having clinical features of sepsis and 100 normal asymptomatic neonates and used screening tests including C-reactive protein (CRP), total leukocyte count (TLC), absolute neutrophil count (ANC), immature neutrophils to total neutrophil count ratio (I/T ratio), thrombocytopenia, degenerative changes in the neutrophils and gastric aspirate cytology (GAC) for the diagnosis of neontal sepsis. Results : The sensitivity of CRP and ANC was high. CRP had 86 percent sensitivity for group-A (proven sepsis) and 74 percent sensitivity for group-B (probable sepsis) and 94 percent specificity for group-A, B. ANC had sensitivity of 72 percent for group-A and 62 percent for group-B and 86 percent specificity for group-A, B. For group-A, sensitivity, specificity of GAC for polymorphs was 74 percent and 94 percent respectively. As for sensitivity, specificity of platelet count for group-A was 64 percent and 89 percent respecively. The sensitivity, specificity and predictive values (PV) of the individual tests and different test combinations were also calculated for group-A and B. Conclusion : For the detection of culture negative cases in neonatal sepsis, screening tests including CRP, TLC, ANC, thrombocytopenia, cytoplasmic vacuolization in the neutrophils and GAC for polymorphs have high sensitivity. A combination of three tests has higher sensitivity.

• 대한위암학회:학술대회논문집
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• 2002.04a
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• pp.9-17
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• 2002

위의 parietal cell 혹은 대식세포와 유사한 세포 내부에서 H. pylori가 발견된다는 보고가 있기는 하나 일반적으로 H. pylori는 Shigella와 같은 침습성 세균은 아닌 것으로 알려져 있다. 그럼에도 불구하고 H. pylori에 감염된 위점막에는 많은 수의 호중구를 위시한 염증세포의 침윤이 관찰되는데 H. pylori가 위상피세포에 부착 할 경우 위상피세포를 자극하여 interleukin-8을 위시한 cytokine 을 발현케하고 이에 의하여 호중구 등의 염증세포가 몰려들게 된다. 한편 고유층에 몰려든 호중구에서는 다시 interleukin-8을 위시한 일련의 호중구 활성화 chemokine을 분비하여 염증반응을 증폭해 나갈 것이다. 호중구에서 발현되는 myeloperoxidase나 활성 산소 등도 위점막의 조직 손상에 기여할 것이다. 위상피세포를 덮고 있는 점액층은 위상피세포를 보호한다고 알려져 있으나 H. pylori 감염의 경우 점액층에 의하여 H. pylori의 운동성이 증가하고 이것이 위상피세포로부터의 cytokine 발현을 자극하여 염증반응을 증폭하는데 관여할 가능성도 있다. H. pylori는 위상피세포에 대하여 apoptosis를 유도함과 동시에 고유층에 몰려든 호중구에 대하여는 apoptosis를 억제케하여 궁극적으로 염증반응을 증폭 및 지속시켜 나가는 쪽으로 작용한다. 한편 H. pylori는 위상피세포로부터 COX-2의 발현을 증가시키는데 이는 위상피세포의 apoptosis를 억제하는 방향으로 작용한다. 이외에 H. pylori의 urease에 의하여 발생한 암모니아나 H. pylori 자신이 분비하는 세포독소가 세포 손상을 유발할 가능성도 있다. 상술한 여러 독성 인자들 중 어느 하나가 단독으로 작용하기보다는 여러 인자가 같이 동시에 또는 시차를 두고 작용할 가능성이 많다고 생각된다.(\gamma-FeOOH)$, 침철광$(\alpha-FeOOH)$, 적금광$(\beta-FeOOH)$, 그리고 자철광$(Fe_3O_4)$이다. 인위적 부식에서는 전부 인철광의 부식물이 생성되었고 자연적 부식에서는 모두 침철광의 부식물이 생성되었다. 특히 철제 표면에 자연적으로 생성된 공식 녹을 XRD 분석한 결과 적금광으로 동정되었다. 이런 모든 시편들을 각 탈염방법에 따라 탈염처리한 후 XRD와 SEM-EDS으로 분석한 결과 인철광과 침철광은 어떠한 변화도 보이지 않았고, 다만 적금광으로 동정된 시편만이 잔존하지 않았다. 철기 제작별 $Cl^-$ 이온 추출량과 탈염효과에 대한 비교 실험은 이온 크로마토그래피 분석 결과와 마찬가지로 단조 철제유물이 주조 철제보다 $Cl^-$ 이온을 많이 가지고 있었으며, 탈염 처리 후에는 $Cl^-$ 이온은 전혀 발견되지 않았다. 이상의 결과 $K_2CO_3$와 Sodium 용액은 탈염처리에서 가장 적합한 탈염처리 용액으로 알수가 있었으며 특히 어떠한 탈염 용액으로 유물을 처리한다 해도 철제유물에 생성된 부식물은 제거되지 않는다는 것을 알게 되었다. 따라서 보존처리자는 유물 표면의 부식 상태만을 보고 처리하기 보다는 철기제작물로 고려하여 처리하는 것이 필요하다. 또한 금속에 부식을 야기시키는 $Cl^-$ 이온과 부식물을 완전하게 제거하여 탈염처리를 하는 것이 유물 부식을 최대한 지연시킬 수 있는 것이라 생각된다.TEX>$88\%$)였다.(P=0.063). 결론: 본 연구에서는 MTHFR C/T & T/T 유전자 다형성이 위암의 발생과 그 위치에 대해 관련이 있는 것으로 여겨지고, 흡연력, 음주력과는 관련이 없는 것으로 여겨진다.험이

• Parasites, Hosts and Diseases
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• v.35 no.2
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• pp.79-86
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• 1997

Toxoplasmn gonnii, an intracellular protozoan infecting many kinds of eukaryotic cells, has been used to experimentally infect macrophages, epithelial cells, fibroblasts, and various cancer cells, but rarely T and B Iymphocytes or granulocytes. The present study was performed to determine the susceptibility of murine (BALB/c or CBA) splenic T and B llrnphocytes, and granulocytes to infection trio T. gondii RH tachyzoites. The ultrastructure of the infected host cells was observed by TEM, and the degree of intracellular parasite proliferation was quantified using 3H-uracil uptake assay. At 24 hrs post-culture, the host cell cytoplasm was found to contain 1 or 2, or a maximum of 7-8 tachyzoites. Infected T Iymphocytes demonstrated a peripherally displaced nucleus, a parasitophorous vacuole enveloping the parasite, and an increased number of mitochondria. In B Iymphocytes infected with tachyzoites, RER was not well developed compared to uninfected B Iymphocytes. Uninfected granulocytes contained many electron dense granules, but T. gondii-infected granulocytes demonstrated a decreased number of granules. Based on the 3H-uracil uptake assay. the susceptibility of T and B Iymphocytes, and granulocytes, to infection with T. gonnii tachyzoites was fairly high irrespective of cell type and strain of mouse. This strongly suggests deterioration in the functioning of infected host immune cells.