• Journal of Chest Surgery
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• v.30 no.10
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• pp.949-960
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• 1997

Background. Limited ischemic tolerance of the lung has remained one of the factors that limits the expansion of pulmonary transplantation as a treatment for end-stage pulmonary disease. Numerous studies on safe long term preservation for lung transplantation has been performed for the purpose of developing ideal preservation solution with extracellular type or intracellular type solutions. In this. study, we examined the efficacy of L DG solution in lung preservation longer than 20 hours by comparison with modified Euro-Collins solution. Iwethods. Thirty-(our adult mongrel dogs were divided into two groups. Donor lungs were flushed with LPDG solution(n=9) or modified Euro-Collins(MEC) solution(n=8) and stored for 24 hours at 1$0^{\circ}C$. All donor lungs were perfused through the pulmonary arteries with solutions containing prostaglandin El and verapamil. Left canine lung allotransplantations wereperformed. Assessment(hemodynamic indices and arterial blood gas analysis) of left implanted lung was made by occluding the right pulmonary artery for ten minutes using pulmonary artery Cuff. Assessment was repeated at the interval of 30 minutes, one hour, and two hours later after reperfusion and then chest X-ray, computed tomogram and lung perfusion scan were obtained. In survival dogs follow-up studies were done with assessment with chest X-ray, computed tomogram of the chest and lung perfusion scan on 7th day postoperatively. After preservation above 20 hours, pathological examinations for ultrastructural findings on right lung were performed in each group. Results. With respect to arterial oxygen tension, LPDG group was superior to MEC but there was no statistical significance for 2 hours after reperfusion. Mean pulmonary artery pressure was less increased(p < 0.05) and cardiac output higher(p <0.05) than MEC group until 2 hours after reperfusion. After 2 hours of reperfusion, both groups showed transplanted lung function deteriorated gradually. Perfusion scan of the transplanted lung in LPDG group showed better perfusion rate in immediate post-reperfusion, 3 days and 7 days later respectively but there was no statistical significance and corelation with PaO2 and computed tomoRravhic views. In scanning electron microscopy of pulmonary artery after preservation, LPDG group relatively shows less irregular protrusion of the inner surface of endothelial cell of poulmonary artery than MEC group. Conclusions, e concluded that LPDG solution can offer safe lung preservation above 20 hours with adequate immunosuppressive therapy and prevention of the infection.

• Journal of Life Science
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• v.34 no.5
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• pp.339-355
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• 2024

The pulmonary system is a highly complex system that can only be understood by integrating its functional and structural aspects. Hence, in vivo animal models are generally used for pathological studies of pulmonary diseases and the evaluation of inhalation toxicity. However, to reduce the number of animals used in experimentation and with the consideration of animal welfare, alternative methods have been extensively developed. Notably, the Organization for Economic Co-operation and Development (OECD) and the United States Environmental Protection Agency (USEPA) have agreed to prohibit animal testing after 2030. Therefore, the latest advances in biotechnology are revolutionizing the approach to developing in vitro inhalation models. For example, lung organ-on-a-chip (OoC) and organoid models have been intensively studied alongside advancements in three-dimensional (3D) bioprinting and microfluidic systems. These modeling systems can more precisely imitate the complex biological environment compared to traditional in vivo animal experiments. This review paper addresses multiple aspects of the recent in vitro modeling systems of lung OoC and organoids. It includes discussions on the use of endothelial cells, epithelial cells, and fibroblasts composed of lung alveoli generated from pluripotent stem cells or cancer cells. Moreover, it covers lung air-liquid interface (ALI) systems, transwell membrane materials, and in silico models using artificial intelligence (AI) for the establishment and evaluation of in vitro pulmonary systems.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1167-1177
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• 1998

Background : Pulmonary tuberculosis is one of the diseases characterized granuloma formation which was controlled by cellular immune reactions. In the process of granulomatous changes, activated alveolar macrophages and T lymphocytes secrete many cytokines including interleukin-1 (IL-1), tumor necrosis factor-alpha(TNF-$\alpha$), interferon-gamma(IFN-$\gamma$) which mediate inflammatory reactions. Intercelluar adhesion molecule-1(ICAM-1) also known to major role player in inflammatory processes, and increased cellular expressions when endothelial cell was stimulated by IL-1, TNF and IFN. Method : To evaluate relationships among cellular immune reactions and clinical stages, pulmonary tuberculosis patients were classified into three groups according to their clinical stages including minimal, moderate and far advanced tuberculosis. TNF-$\alpha$ IFN-$\gamma$, sICAM-1 (soluble form of ICAM-1) were measured at the time of diagnosis and after 6-months anti-tuberculosis medications by radioimmuno assay or enzyme linked immunosolvent assay. Result : TNF-$\alpha$, IFN-$\gamma$, sICAM-1 were significantly increased in moderate and far advanced pulmonary tuberculosis patients but no meaningful changes in minimal staged patients. 6-months anti-tuberculosis medications reduced serum sICAM-1 levels significantly, related to clinical improvement but no significant changes were found in the serum levels of TNF-$\alpha$ and IFN-$\gamma$. In the point of correlations. positive ones revealed between TNF-$\alpha$ and sICAM-1, also between IFN-$\gamma$ and sICAM-1 but no correlation between TNF-$\alpha$ and IFN-$\gamma$. Conclusion : Measurement of serum sICAM-1 could be useful parameter to evaluate the severity of pulmonary tuberculosis and to monitor disease activities during anti-tuberculosis medications.

• Tuberculosis and Respiratory Diseases
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• v.47 no.2
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• pp.239-246
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• 1999

Hyperhomocysteinemia is an independent risk factor for cardiovascular, cerebrovascular and peripheral vascular diseases complicated with atherosclerosis and thromboembolism. Increased plasma homocystein level develops from genetic defect of enzyme for homocystein metabolism or vitamine deficiency, has direct toxic effect for vascular endothelium and makes damages to antithrombotic action of vascular endothelial cell. Most of hyperhomocysteinemia is asymptomatic, but rarely develops cardiopulmonary or cerebrovascular accidents. In case of thromboembolism with unknown cause, the hyperhomocysteinemia should be considered as one of the many etiologies. The authors, first in korea, report a case of multiple thromboembolisms of deep vein of lower extremity, pulmonary vessels, superior sagittal and transverse sinus of brain in a patient with the hyperhomocysteinemia with a review of literature.

• BMB Reports
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• v.49 no.4
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• pp.214-219
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• 2016

A nucleosomal protein, high mobility group box 1 (HMGB1) is known to be a late mediator of sepsis. Dabrafenib is a B-Raf inhibitor and initially used for the treatment of metastatic melanoma therapy. Inhibition of HMGB1 and renewal of vascular integrity is appearing as an engaging therapeutic strategy in the administration of severe sepsis or septic shock. Here, we examined the effects of dabrafenib (DAB) on the modulation of HMGB1-mediated septic responses. DAB inhibited the release of HMGB1 and downregulated HMGB1-dependent inflammatory responses by enhancing the expressions of cell adhesion molecules (CAMs) in human endothelial cells. In addition, treatment with DAB inhibited the HMGB1 secretion by CLP and sepsis-related mortality and pulmonary injury. This study demonstrated that DAB could be alternative therapeutic options for sepsis or septic shock via the inhibition of the HMGB1 signaling pathway.

• Tuberculosis and Respiratory Diseases
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• v.41 no.1
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• pp.36-41
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• 1994

Angiosarcoma is a very rare malignant tumor of endothelial cell origin. We experienced a case of angiosarcoma presented with massive pleural effusion, which was considered as a metastasis from right kidney. A 44-year-old male patient was admitted due to dyspnea for one month. He had a history of transient hematuria 3 months before admission, which disappeared spontaneously. Chest roentgenography showed total haziness in left hemithorax with multiple nodular shadows in right lung. Abdominal ultrasonogram showed a single heterogeneous hyperechoic mass, measuring about $7.3{\times}7.1{\times}6.5cm$ in size in the upper and mid-pole of the right kidney, involving renal sinus. Computed tomography of the chest revealed highly enhanced multiple pulmonary and subpleural nodules with loculated pleurisy. In bronchoscopic finding, a fungating, hypervascular tumor mass was noticed at the orifice of anterior basal segment of left lower lung after removal of tenaceous mucus. Pleural and bronchoscopic biopsies showed findings of angiosarcoma confirmed by immunochemical stains with factor VIII related antigen(+), laminin(+) and vimentin(+), and by characteristic electronmicroscopic findings. Massive pleural effusion was controlled with several times of pleurodesis in both pleural spaces.

• Tuberculosis and Respiratory Diseases
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• v.40 no.2
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• pp.104-111
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• 1993

Background: Gram-negative bacterial endotoxin induced septicemia is known to be a leading cause in the development of adult respiratory distress syndrome(ARDS). The mechanism of endotoxin induced lung injury is mainly due to the activated neutrophils which injure the capillary endothelial cells by releasing oxidant radical and resulted in pulmonary edema. We studied the change of antioxidant enzyme in the case of large or small, intermittant dose of endotoxin infused rat lungs. Methods: Endotoxin was given to the rat through the peritoneal cavity in the dose of 7 mg/kg body weight in the large dose group and 1 mg/kg for 10 days in the small dose group. Bronchoalveolar lavage (BAL) was done and rats were killed at 6, 12, 24 hours after single endotoxin injection in the large dose group and 3, 7, 10 days after daily endotoxin injection for 10 days in the small dose group. The lungs were perfused with normal saline through the pulmonary artery to remove the blood and were homogenized in 5 volume of 50 mM potassium phosphate buffer containing 0.1 mM EDTA. After centrifuging at 100,000 g for 60 minute, the supernatent was removed and stored at $-70^{\circ}C$ until measuring for superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and protein. Results: We observed the following results. 1) The lung wet/dry weight ratio and albumin concentration in the BAL fluids were increased to peak at 12 hours and neutrophil number in the BAL fluids were peak at 6 hours after endotoxin injection in the large dose group. 2) Cu, Zn SOD (IU/mg protein) was significantly decreased after 6, 12 hours after endotoxin injection in the large dose group. 3) There were no singnificant change in the level of Mn SOD, catalase, GSH-Px after endotoxin injection in both groups. Conclusion: Endotoxin in the large dose group produced the acute pulmonary edema and decreased the Cu, Zn SOD in the lung tissue after injecting endotoxin at 6 and 12 hours. These phenomenon may be due to the cell membrane damage by endotoxin. Further research would be necessary whther giving SOD by intratracheal route or method to increase the synthesis of SOD may lessen the acute lung injury by endotoxin.

• Journal of Korean Physical Therapy Science
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• v.8 no.1
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• pp.745-758
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• 2001

The purpose of study to phenomenological examine and the mechanism regarding the gene(DNA, RNA, Protein) and sports to studied, analyzed. and evaluated. This review considers the evidence for genetic effects in several determinants of endurance performance and resistance performance, namely: body measurements and physique, body fat pulmonary functions, cardiac and circulatory functions, muscle characteristics. substrate utilization, maximal aerobic power and other. Moreover, the response to aerobic training of indicators aerobic work metabolism and endurance performance is reviewed, with emphasis on the specificity of the response and the individual differences observed in training ability. This study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. and think that occurred with exercise influence on skeletal muscle into cell have to Myosin Heavy Chain (MHC) changed was after exercise performance, which accompanied into skeletal muscle that were exercise-induces gene-modulation that is, take gene mutations. This study known that existed hormone(epinephrine)-immune system with interaction. Exercise were altered insulin binding and MAP Kinase signaling increased into immune cells. This review suggested that the high rate of glutamine utilization by cells of the immune system serves to maintain a high intra cellular concentration of the intermediates of biosynthetic pathways such that optimal rates of DNA, RNA and protein synthesis can be maintained. In the absence of glutamine, lymphocytes do not proliferate in vitro: proliferation increase greatly as the glutamine concentration increase. Glutamine is synthesized in skeletal muscle. Skeletal muscle and plasma glutamine levels are lowered by sepsis, injury, bums, surgery and endurance exercise and in the overtrained athlete. The study of result show that production of ET-1 is markedly increased tissue specifically in the heart by exercise without appreciable changes in endothelin-converting enzyme and endothelial receptor expressions, suggest that myocardial ET-1 may participate in modulation of cardiac function during exercise. Conclusionally, this study indicate that improvement of 'Enhancer Action' in RNA genes changed by exercise or sports. Moreover exercise was effect on Central Dogma with DNA makes RNA makes Protein. This study is expected to contribute the area of sports science, medicine, hereafter more effort is required to establish the relation between gene alters and exercise amount.

• Korean Journal of Radiology
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• v.24 no.7
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• pp.647-659
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• 2023

Objective: The study was conducted to investigate the effect of correct occlusion of the left atrial appendage (LAA) on intracardiac blood flow and thrombus formation in patients with atrial fibrillation (AF) using four-dimensional (4D) flow magnetic resonance imaging (MRI) and three-dimensional (3D)-printed phantoms. Materials and Methods: Three life-sized 3D-printed left atrium (LA) phantoms, including a pre-occlusion (i.e., before the occlusion procedure) model and correctly and incorrectly occluded post-procedural models, were constructed based on cardiac computed tomography images from an 86-year-old male with long-standing persistent AF. A custom-made closed-loop flow circuit was set up, and pulsatile simulated pulmonary venous flow was delivered by a pump. 4D flow MRI was performed using a 3T scanner, and the images were analyzed using MATLAB-based software (R2020b; Mathworks). Flow metrics associated with blood stasis and thrombogenicity, such as the volume of stasis defined by the velocity threshold ($\left|\vec{V}\right|$ < 3 cm/s), surface-and-time-averaged wall shear stress (WSS), and endothelial cell activation potential (ECAP), were analyzed and compared among the three LA phantom models. Results: Different spatial distributions, orientations, and magnitudes of LA flow were directly visualized within the three LA phantoms using 4D flow MRI. The time-averaged volume and its ratio to the corresponding entire volume of LA flow stasis were consistently reduced in the correctly occluded model (70.82 mL and 39.0%, respectively), followed by the incorrectly occluded (73.17 mL and 39.0%, respectively) and pre-occlusion (79.11 mL and 39.7%, respectively) models. The surfaceand-time-averaged WSS and ECAP were also lowest in the correctly occluded model (0.048 Pa and 4.004 Pa^-1, respectively), followed by the incorrectly occluded (0.059 Pa and 4.792 Pa^-1, respectively) and pre-occlusion (0.072 Pa and 5.861 Pa^-1, respectively) models. Conclusion: These findings suggest that a correctly occluded LAA leads to the greatest reduction in LA flow stasis and thrombogenicity, presenting a tentative procedural goal to maximize clinical benefits in patients with AF.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.55-66
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• 1998

Pathophysiological mechanism of hemorrhagic fever with renal syndrome (HFRS) is not fully understood. Major clinical findings of HFRS patients are widespread hemorrhage, acute renal failure and shock. Basic lesion is vascular injury with microvascular hemorrhage and relatively little inflammation. According to autopsy findings, renal medulla shows focal hemorrhage, tubular necrosis and interstitial mononuclear infiltrates. The predominant cell type in the renal and pulmonary interstitium is a fibroblast and it participates in the healing process at the injury site by secreting a large amount of extracellular matrix proteins. Cultured human lung fibroblasts and Mongolian gerbil fibroblasts were known to be good host cells for the hantaan virus. It is possible that not only the endothelial cell but also the fibroblast is a target of Hantaan virus and the fibroblast might be involved in the pathogenesis and the healing process in HFRS. Integrins are adhesion molecules, and act as receptors for many extracellular matrix proteins. Recently, there are many reports that cell surface integrins influence on some viral infections or reversely viruses influence on the expression of integrins. The ${\alpha}_5{\beta}_1$ integrin is a major receptor for the fibronectin which is an important extracellular matrix protein secreted by fibroblasts. In this study, the role of ${\alpha}_5{\beta}_1$ integrin in the infection of Hantaan virus was examined by using anti-${\alpha}_5{\beta}_1$, integrin, anti-${\alpha}_5$ integrin and anti-${\beta}_1$, integrin antibodies in chicken embryo fibroblasts (CEF) and Mongolian gerbil fibroblasts(MGF). The treatment of anti-${\alpha}_5{\beta}_1$, integrin antibody in CEF reduced the virion titers 26.8% and the amount of nucleocapsid N protein 32.6% when compared with control CEF. When MGF were treated with anti-${\alpha}_5$, anti-${\beta}_1$ and anti-${\alpha}_5{\beta}_1$ integrin antibodies, virion titers were reduced by 26.5%, 29.4% and 28.7% and the amount of nucleocapsid N protein were reduced by 65.2%, 59.7% and 72.6%. These results suggested that ${\alpha}_5{\beta}_1$ integrin might act as a receptor for the Hantaan virus or blocking of ${\alpha}_5{\beta}_1$ integrin influences on the viral replication in CEF and MGF. It is also possible that the blocking of only one subunit of integrin represents similar results in that of whole molecule.