• Biomedical Science Letters
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• v.6 no.4
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• pp.281-288
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• 2000

Leukocyte activation with cardiac surgery procedures produces various iuflammatory substances and involves in postoperative pathophysiology. The present study was carried out to elucidate changes in leukocyte myeloperoxidase level and effect on the heart and lung during cardiac operation. Total leukocyte and differential counts in peripheral blood, myeloperoxidase (MPO) and troponin-T concentratiens (TnT) in coronary sinus blood, and pulmonary vascular resistance (PVR) were measured at preoperative and postoperative period. The parameters were compared between sampling periods, and relationship was investigated between MPO and each variable. At the end of operation, there were leukocytosis with neutrophilia (p＜0.01), and increases of MPO and TnT concentrations (p＜0.05), but decrease in PVR (p＜0.05). MPO had a positive correlation to TnT, total leukocyte, neutrophil, or operative times (p＜0.05), whereas PVR had a negative relationship to total leukocyte or neutrophil counts (p＜0.05). These results indicate that cardiac surgery leads to elevated liberations of myeloperoxidase from neutrophils and may harmfully affect myocardium.

• Pediatric Infection and Vaccine
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• v.12 no.1
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• pp.75-85
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• 2005

Purpose : Fungal infection is one of the important causes of morbidity and mortality in patients with hematologic malignancies. Amphotericin B(ABV) and itraconazole(ITZA) have been used as the standard empirical antifungal therapy in neutropenic patients with acute leukemia who have persistent fever that does not respond to antibiotic therapy. ABV is an antifungal drug associated with side effects such as fever and chills, symptoms which may be mediated by pro-inflammatory cytokines such as interleukin-$1{\beta}$(IL-$1{\beta}$) and tumor necrosis factor-${\alpha}$(TNF-${\alpha}$). We assessed modulation of these pro-inflammatory cytokines as well as the anti-inflammatory cytokines(IL-4, IL-1Ra) by ABV and ITZA. Methods : From March 2004 to February 2005, a total of 30 episodes from acute leukemia patients with febrile neutropenia were analyzed for this study. They were randomly allocated to receive intravenous ABV or ITZA for 14 days. Clinical responses were evaluated at the completion of therapy, and cytokine IL-$1{\beta}$, TNF-${\alpha}$, IL-4, and IL-1Ra were measured for determination to know the correlation between two antifungal agents and inflammatory cytokines. Results : Empirical antifungal agents were given to 37 patients(ABV 20, ITZA 17), and 30 patients(ABV 15, ITZA 15) were evaluable for efficacy. White blood cell and absolute neutrophil count in the group treated with ITZA increased early days of treatment, so the duration of neutropenia in ITZA group is shorter. Serum creatinine level is lower in ITZA group than in ABV group but this is not statistically significant. There was no significant difference in response rate between two groups. The IL-$1{\beta}$ was increased in ABV treatment group and the ratio of IL-1Ra/IL-$1{\beta}$ is markedly decreased in ABV treatment group while increased in ITZA group. Conclusion : ITZA and ABV have at least equivalent efficacy as empirical antifungal therapy in neutropenic children with acute leukemia. However ITZA is associated with significantly less toxicity in clinical and molecular aspects.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.4 no.1
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• pp.18-27
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• 2001

Purpose: The aims of this study are to investigate the effect of the eradication of H. pylori on histological change of gastric mucosa in children with H. pylori gastritis and to determine whether the histological grading by the Sydney system is valuable in predicting the effect of treatment. Methods: 1) Histological scores by the Sydney system and the endoscopic characteristics were assessed before and at least four weeks after anti-H. pylori therapy in 42 children with H. pylori gastritis. 2) In 32 children treated with omeprazole, amoxicillin and clarithromycin (OAC), pretreatment histological scores and endoscopic findings were compared between the eradicated and the noneradicated to evaluate their predictive value for the successful eradication. Results: 1) In the eradicated (27 cases), nodular gastritis significantly decreased from 89% to 63% (p<0.05). There was an significant improvement in the mean activity score from 2.06 before treatment to 0.24 after treatment (p<0.01). The mean inflammatory score also improved from 2.61 before treatment to 1.89 after treatment (p<0.05). Lymphoid follicles significantly decreased from 48% to 15% (p<0.05). Epithelial damage improved in all 4 cases. But in the noneradicated (15 cases), there was no significant change in the frequency of nodular gastritis, the mean activity score, the mean inflammatory score and the frequency of the lymphoid follicles. 2) In 32 children treated with OAC, there was a tendency that the higher was the pretreatment score of the bacterial density, the lower was the eradication rate of H. pylori (p=0.072). Conclusion: The loss of the polymorphonuclear cell infiltration is the most prominent histological change after successful eradication. There may be negative correlation of the grade of the bacterial density with the success rate of the anti-H. pylori therapy.

• 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 Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.1
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• pp.115-122
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• 2006

기관지 천식은 가역적 기도 폐색, 호산구에 의한 만성기관지 염증 및 기관지 수축 물질에 대한 기관지 평활근의 과민반응 등 3가지 주 증상을 갖는 만성 염증성 호흡기 질환의 일종으로서 천식은 항원에 대한 노출이 과민반응으로 이어져 기도 내 염증 유발로 이어지면 조직 내 백혈구 침윤이 일어나게 되어 기도 상피세포의 손상 및 기도 폐색이 일어나게 된다. 이 때 백혈구를 혈액에서 조직으로 끌어오는 것이 chemotactic cytokine, 즉 chemokine이다. 본 실험은 사람의 폐 상피세포를 이용하여 염증유발 매개물질인 $TNF-{\alpha}$와 IL-4를 단독 혹은 병용 투여하여, 폐 상피세포에서 chemokine 중 호중구의 화학주성에 관여하는 TARC, eotaxin, RANTES의 생성을 유도하였고, 이러한 chemokine의 생성과정에서 청열소독음(淸熱消毒飮)이 미치는 영향에 대하여 연구하였다. 본 연구를 통하여 청열소독음(淸熱消毒飮)이 사람의 폐 상피세포에서 $TNF-{\alpha}$와 IL-4로 유발시킨 TARC, exotain, RANTES의 생성을 농도 의존적으로 억제하는 효과를 볼 수 있었다. 따라서 청열소독음(淸熱消毒飮)은 TARC, eotaxin, RANTES와 같은 chemokine 생성을 억제함으로써 천식을 포함한 알레르기 질환 치료 전반에 유의적인 효과를 보일 것으로 사려 된다.

• Journal of Life Science
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• v.21 no.1
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• pp.22-30
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• 2011

Apolipoprotein A-I (apoA-I) has anti-inflammatory and anti-oxidative properties. This study was designed to investigate whether apoA-I affects apoptosis and cytokine production of human blood neutrophils in an in vitro culture system. Spontaneous apoptosis of neutrophils was significantly delayed by apoA-I. In addition, high density lipoprotein containing apoA-I also delayed apoptosis of neutrophils. Apoptosis of neutrophils was inhibited by anti-scavenger receptor type B-I antibodies. The amounts of interleukin-8, interferon (IFN)-inducible protein 10 (IP-10), and tumor necrosis factor-$\alpha$ (TNF-$\alpha$) in the supernatants of cultured neutrophils treated with apoA-I were significantly increased. Combined treatment of neutrophils with IFN-$\gamma$ and apoA-I produced higher amounts of IP-10 and TNF-$\alpha$ than did treatment with IFN-$\gamma$ or apoA-I alone. The present study reveals that apoA-I activates neutrophils to produce cytokines and delays spontaneous apoptosis of neutrophils. These findings suggest that apoA-I, although a well-known negative acute-phase protein, has a pro-inflammatory effect in neutrophils.

• 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.

• Journal of Yeungnam Medical Science
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• v.19 no.1
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• pp.55-62
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• 2002

Background: Interleukin-1(IL-1) and neutrophil appear to contribute to the pathogenesis of acute respiratory distress syndrome(ARDS). Elastase, as well as reactive oxygen species released from activated neutrophil, are thought to play pivotal roles in the experimental models of acute lung leak. This study investigated whether ICI 200,355, a synthetic elastase inhibitor, can attenuate acute lung injury induced by IL-1 in rats. Materials and Methods: We intratracheally instilled either saline or IL-1 with and without treatment of ICI 200,355 in rats. Lung lavage neutrophils, lung lavage cytokine-induced neutrophil chemoattractant(CINC) concentration, lung lavage protein concentration, lung myeloperoxidase(MPO) activity and lung leak index were measured at 5 hours of intratracheal treatment. Results: In rats given IL-1 intratracheally, lung lavage neutrophils, lung lavage CINC concentration, lung lavage protein concentration, lung MPO activity and lung leak index were higher. Intratracheal ICI 200,355 administration decreased lung lavage neutrophils, lung MFO activity and lung leak index, respectively, but did not decrease lung lavage CINC concentration. Conclusion: These results suggest that ICI 200,355 decreases lung inflammation and leak without decreasing lung lavage CINC concentration in rats given IL-1 intratracheally.

• Tuberculosis and Respiratory Diseases
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• v.54 no.1
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• pp.80-90
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• 2003

Background : Goblet cell hyperplasia is a critical pathological feature in hypersecretory diseases of the airways. A bacterial infection of the lung is also known to induce inflammatory responses, which can lead to the overproduction of mucus. Recently, mucin synthesis in the airways has been reported to be regulated by neutrophilic inflammation-induced epidermal growth factor receptor (EGFR) expression and activation. In addition, it was reported that migration of the activated neutrophils is dependent on the matrix metalloproteinases (MMPs), especially MMP-9. In this study, bacterial lipopolysaccharide (LPS)-induced goblet cell hyperplasia and mucus hypersecretion by EGFR cascade, resulting from the MMPs-dependent neutrophilic inflammation were investigated in the rat airways. Methods : Pathogen-free Sprague-Dawley rats were studied in vivo. Various concentrations of LPS were instilled into the trachea in $300{\mu}{\ell}$ PBS (LPS group). Sterile PBS ($300{\mu}{\ell}$) was instilled into the trachea of the control animals (control group). The airways were examined on different days after instilling LPS. For an examination of the relationship between the LPS-induced goblet cell hyperplasia and MMPs, the animals were pretreated 3 days prior to the LPS instillation and daily thereafter with the matrix metalloproteinase inhibitor (MMPI; 20 mg/Kg/day of CMT-3; Collagenex Pharmaceuticals, USA). The neutrophilic infiltration was quantified as a number in five high power fields (HPF). The alcian blue/periodic acid-Schiff (AB/PAS) stain were performed for the mucus glycoconjugates and the immunohistochemical stains were performed for MUC5AC, EGFR and MMP-9. Their expressions were quantified by an image analysis program and were expressed by the percentage of the total bronchial epithelial area. Results : The instillation of LPS induced AB/PAS and MUC5AC staining in the airway epithelium in a time- and dose-dependent manner. Treatment with the MMPI prevented the LPS-induced goblet cell hyperplasia significantly. The instillation of LPS into the trachea induced also EGFR expression in the airway epithelium. The control airway epithelium contained few leukocytes, but the intratracheal instillation of LPS resulted in a neutrophilic recruitment. A pretreatment with MMPI prevented neutrophilic recruitment, EGFR expression, and goblet cell hyperplasia in the LPS-instilled airway epithelium. Conclusion : Matrix metalloproteinase is involved in LPS-induced mucus hypersecretion, resulting from a neutrophilic inflammation and EGFR cascade. These results suggest a potential therapeutic role of MMPI in the treatment of mucus hypersecretion that were associated with a bacterial infection of the airways.

• 한국체육학회지인문사회과학편
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• v.54 no.5
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• pp.769-780
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• 2015

This study investigated the changes in inflammatory mediators, immunocompetent cells and bone merrow progenitor cells by the magnitude of muscle damage and type of the muscle contraction in the elderly. Twenty older adults who had not been involved in a resistance-training program at least 6 months prior to the present study were assigned to eccentric exercise group (ECC, n=10) and concentric exercise group (CON, n=10). All subjects performed 10 sets of 6 maximal isokinetic eccentric (ECC 1) or concentric (CON) contractions with the non-dominant arm in a randomized, with 4 wk between bouts (ECC 2). Skeletal muscle damage index (ROM, VAS, Plasma CK), inflammation mediators (TNF-α, IL-1, IL-6), immunocomperent cells (CD3+, CD4+, CD8+, CD19+), bone merrow progenitor cell (CD34+) and leukocytes were measured before, immediately after, 2, 24, 48, 72, and 96 h after exercise. Changes in ROM and VAS were greater (P<.05) after ECC 1 than CON and ECC 2. Increases in TNF-α and IL-6 were greater (P<.05) 24, 48 and 72 h after ECC 1 than CON and ECC 2. Increases in neutrophils were greater (P<.05) 2 h after ECC 1 than CON and ECC 2. It was confirmed that muscle damage was greater following eccentric than concentric contractions as well as first bout than second bout in the elderly, and suggested that TNF-α, IL-6 and neutrophils should closely correlate with magnitude of muscle damage.