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Role of Growth Factors and Cytokines on Bleomycin Induced Pulmonary Fibrosis (Bleomycin 유도 폐 섬유화에 있어서 성장인자 및 Cytokine의 역할)

  • Lee, Yong-Hee;Jung, Soon-Hee;Ahn, Chul-Min;Kim, Sung-Kyu;Cho, Sang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.871-888
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    • 1997
  • Background : It is now thought that the earliest manifestation of idiopathic pulmonary fibrosis is alveolitis, that is, an accumulation of inflammatory and immune effector cells within alveolar walls and spaces. Inflammatory cells including alveolar macrophages and resident normal pulmonary tissue cells participate through the release of many variable mediators such as inflammatory growth factors and cytokines, which contribute to tissue damage and finally cause chronic pulmonary inflammation and fibrosis. This study was performed to investigate the source and distribution pattern of transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), platelet derived growth factor(PDGF), basic fibroblast growth factor(bFGF), interleukin 1(IL-1), interleukin 6(IL-6), tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and the role of these mediators on bleomycin(BLM)-induced pulmonary injury and fibrosis in rats. Method : Wistar rats were divided into three groups(control group, BLM treated group, BLM and vitamine E treated group). Animals were sacrificed periodically at 1, 2, 3, 4, 5, 7, 14, 21, 28 days after saline or BLM administration. The effects were compared to the results of bronchoalveolar lavage fluid analysis, light microscopic findings, immunohistochemical stains for six different mediators(TGF-${\beta}_1$, PDGF, bFGF, IL-1, IL-6 and TNF-$\alpha$) and mRNA in situ hybridization for TGF-${\beta}_1$. Results : IL-1 and IL-6 are maximally expressed at postbleomycin 1~7th day which are mainly produced by neutrophils and bronchiolar epithelium. It is thought that they induce recruitment of inflammatory cells at the injury site. The expression of IL-1 and IL-6 at the bronchiolar epithelium within 7th day is an indirect evidence of contribution of bronchiolar epithelial cells to promote and maintain the inflammatory and immune responses adjacent to the airways. TNF-$\alpha$ is mainly produced by neutrophils and bronchiolar epithelial cells during 1~5th day, alveolar macrophages during 7~28th day. At the earlier period, TNF-$\alpha$ causes recruitment of inflammatory cells at the injury site and later stimulates pulmonary fibrosis. The main secreting cells of TGF-${\beta}_1$ are alveolar macrophages and bronchiolar epithelium and the target is pulmonary fibroblasts and extracellular matrix. TGF-${\beta}_1$ and PDGF stimulate proliferation of pulmonary fibroblasts and TGF-${\beta}_1$ and bFGF incite the fibroblasts to produce extracellular matrix. The vitamine E and BLM treated group shows few positive cells(p<0.05). Conclusion : After endothelial and epithelial injury, the neutrophils and bronchiolar epithelium secrete IL-1, IL-6, TNF-$\alpha$ which induce infiltration of many neutrophils. It is thought that variable enzymes and $O_2$ radicals released by these neutrophils cause destruction of normal lung architecture and progression of pulmonary fibrosis. At the 7~28th day, TGF-${\beta}_1$, PDGF, bFGF, TNF-$\alpha$ secreted by alveolar macrophages sting pulmonary fibroblasts into proliferating with increased production of extracellular matrix and finally, they make progression of pulmonary fibrosis. TNF-$\alpha$ compares quite important with TGF-${\beta}_1$ to cause pulmonary fibrosis. Vitamine E seems to decrease the extent of BLM induced pulmonary fibrosis.

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A Study of Microsatellite Instability in Primary Small Cell Lung Cancers by Microsatellite Analysis (원발성 소세포폐암에서 Microsatellite 분석을 이용한 Microsatellite 불안정화에 대한 연구)

  • Cho, Eun-Song;Chang, Joon;Park, Jae-Min;Shin, Dong-Hwan;Kim, Se-Hoon;Kim, Young-Sam;Chang, Yoon-Soo;Cho, Chul-Ho;Kwak, Seung-Min;Lee, Jun-Gu;Chung, Kyung-Young;Kim, Sung-Kyu;Lee, Won-Young;Kim, Se-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.2
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    • pp.180-190
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    • 2000
  • Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

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The detection of collapsible airways contributing to airflow limitation (기류 제한에 영향을 미치는 허탈성 기도의 분석)

  • Kim, Yun Seong;Park, Byung Gyu;Lee, Kyong In;Son, Seok Man;Lee, Hyo Jin;Lee, Min Ki;Son, Choon Hee;Park, Soon Kew
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.4
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    • pp.558-570
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    • 1996
  • Background : The detection of Collapsible airways has important therapeutic implications in chronic airway disease and bronchial asthma. The distinction of a purely collapsible airways disease from that of asthma is important because the treatment of the dormer may include the use of pursed lip breathing or nasal positive pressure ventilation whereas in the latter, pharmacologic approaches are used. One form of irreversible airflow limitation is collapsible airways, which has been shown to be a Component of asthma or to emphysema, it can be assessed by the volume difference between what exits the lung as determined by a spirometer and the volume compressed as measured by the plethysmography. Method : To investigate whether volume difference between slow and forced vital Capacity(SVC-FVC) by spirometry may be used as a surrogate index of airway collapse, we examined pulmonary function parameters before and after bronchodilator agent inhalation by spirometry and body plethysmography in 20 cases of patients with evidence of airflow limitation(chronic obstructive pulmonary disease 12 cases, stable bronchial asthma 7 cases, combined chronic obstructive pulmonary disease with asthma 1 case) and 20 cases of normal subjects without evidence of airflow limitation referred to the Pusan National University Hospital pulmonary function laboratory from January 1995 to July 1995 prospectively. Results : 1) Average and standard deviation of age, height, weight of patients with airflow limitation was $58.3{\pm}7.24$(yr), $166{\pm}8.0$(cm), $59.0{\pm}9.9$(kg) and those of normal subjects was $56.3{\pm}12.47$(yr), $165.9{\pm}6.9$(cm), $64.4{\pm}10.4$(kg), respectively. The differences of physical characteristics of both group were not significant statistically and male to female ratio was 14:6 in both groups. 2) The difference between slow vital capacity and forced vital capacity was $395{\pm}317ml$ in patients group and $154{\pm}176ml$ in normal group and there was statistically significance between two groups(p<0.05). Sensitivity and specificity were most higher when the cut-off value was 208ml. 3) After bronchodilator inhalation, reversible airway obstructions were shown in 16 cases of patients group, 7 cases of control group(p<0.05) by spirometry or body plethysmography d the differences of slow vital capacity and forced vital capacity in bronchodilator response group and nonresponse group were $300.4{\pm}306ml$, $144.7{\pm}180ml$ and this difference was statistically significant. 4) The difference between slow vital capacity and forced vital capacity before bronchodilator inhalation was correlated with airway resistance before bronchodilator(r=0.307 p=0.05), and the difference between slow vital capacity and forced vital capacity after bronchodilator was correlated with difference between slow vital capacity and forced vital capacity(r=0.559 p=0.0002), thoracic gas volume(r=0.488 p=0.002) before bronchodilator and airway resistance(r=0.583 p=0.0001), thoracic gas volume(r=0.375 p=0.0170) after bronchodilator, respectively. 5) The difference between slow vital capacity and forced vital capacity in smokers and nonsmokers was $257.5{\pm}303ml$, $277.5{\pm}276ml$, respectively and this difference did not reach statistical significance(p>0.05). Conclusion : The difference between slow vital capacity and forced vital capacity by spirometry may be useful for the detection of collapsible airway and may help decision making of therapeutic plans.

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The Effect of a Bypass Operation for Atherosclerotic Arterial Obstructive Disease at the Lower Extremity (동맥경화성 하지 동맥 폐색증에 대한 우회로 수술의 효과)

  • Choi, Won-Suk;Park, Jae-Min;Lee, Yang-Haeng;Han, Il-Yong;Jun, Hee-Jae;Yoon, Young-Chul;Hwang, Youn-Ho;Cho, Kwang-Hyun
    • Journal of Chest Surgery
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    • v.41 no.5
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    • pp.610-618
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    • 2008
  • Background: There are various treatment modalities for atherosclerotic arterial obstructive disease at the lower limbs, for example, conservative physical therapy, medication, operation etc. Yet it has been established that an arterial bypass operation is the most effective treatment. The aim of this study is to evaluate the effect of arterial bypass operation within our experience and to determine the indicators of treatment. Material and Method: Ninety six patients received arterial bypass operation for atherosclerotic arterial obstructive disease from June 2002 to April 2006. We evaluated the feasibility of arterial bypass operation based on the improvement of symptoms and the ankle-brachial index (ABI) and the surgical outcomes, as based on the complications, the amputation rates and the patency rates. We also assessed the possible risk factors such as gender, age, a smoking history, co-morbidities, the anastomotic sites, the graft size and the graft type. We retrospectively reviewed the medical records of the patients. The total mean follow-up period was $29.4{\pm}13.1$ months. Result: The mean age was $65.95{\pm}9.61$ and there were 88 male patients. The most common clinical manifestation was ischemic resting pain in the lower extremities. The underlying combined diseases were hypertension (61%), diabetes (43%), cardiac problems (35%) and smoking (91.7%). The most frequent site of arterial obstruction was the superficial femoral artery (44 cases, 40%). A femoropopliteal artery bypass operation with a Polytetrafluoroethylene(PTFE) synthetic graft was done in 44 cases (40%) and the great saphenous vein graft was used in 11 cases. The postoperative ABI increased significantly from $0.30{\pm}0.11$ preoperatively to $0.63{\pm}0.11$ (p<0.001) postoperatively. In 8 cases, amputations above the ankle level were necessary. The graft patency rates were 86.4% and 68.0% after 1 and 3 years, respectively. There were 29 cases (30.21%) of patency failure; the male gender, smokers and hypertension were significantly more frequent in the failure group. Of these, hypertension was the most powerful risk factor (p=0.042). Conclusion: The arterial bypass operation is an effective treatment modality for controlling the symptoms such as pain and claudication, and for preventing major amputations for the patients with atherosclerotic arterial obstructive disease. This study suggests quitting smoking, strict blood pressure control, selection of an appropriate graft, regular outpatient follow up and proper medication would offer higher patency rates and more favorable outcomes.

The Effect of Surfactant on Neutrophil Apoptosis in Lipopolysaccharide Induced Acute Lung Injury in Rat (기관내 내독소 투여로 유도한 백서의 급성 폐손상 모델에서 surfactant가 호중구의 아포토시스에 미치는 영향)

  • Yoo, Ji-Hoon;Lee, Byoung-Jun;Jeong, Do-Young;Lee, Sang-Hoon;Shin, Jong-Wook;Kim, Jae-Yeol;Park, In-Won;Choi, Byoung-Whui
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.4
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    • pp.409-419
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    • 2002
  • Background : The therapeutic effects of surfactant on acute lung injury derive not only from its recruiting action on collapsed alveoli but also from its anti-inflammatory effects. Pro-apoptotic action on alveolar neutrophils represents one of the important anti-inflammatory mechanisms of surfactant. In the present study, we evaluated the effects of sufactant on the apoptosis of human peripheral and rat alveolar neutrophils. Methods : In the (Ed- the article is not definitely needed but it helps to separate the two prepositions 'in') in vitro study, human neutrophils were collected from healthy volunteers. An equal number of neutrophils ($1{\times}10^6$) (Ed-confirm) was treated with LPS (10, 100, 1000ng/ml), surfactant (10, 100, $1000{\mu}g/ml$), or a combination of LPS (1000ng/ml) and surfactant (10, 100, $1000{\mu}g/ml$). After incubation for 24 hours, the apoptosis of neutrophils was evaluated by Annexin V method. In the in vivo study, induction of acute lung injury in SD rats by intra-tracheal instillation of LPS (5mg/kg) was followed by intra-tracheal administration of either surfactant (30mg/kg) or normal saline (5ml/kg). Tenty-four hours after LPS instillation, alveolar neutrophils were collected and the apoptotic rate was evaluated by Annexin V method. In addition, changes of the respiratory mechanics of rats (respiratory rate, tidal volume, and airway resistance) were evaluated with one chamber body plethysmography before, and 23 hours after, LPS instillation. Results : in the in vitro study, LPS treatment decreased the apoptosis of human peripheral blood neutrophils (control: $47.4{\pm}5.0%$, LPS 10ng/ml; $30.6{\pm}10.8%$, LPS 100ng/ml; $27.5{\pm}9.5%$, LPS 1000ng/ml; $24.4{\pm}7.7%$). The combination of low to moderate doses of surfactant with LPS promoted apoptosis (LPS 1000ng/ml + Surf $10{\mu}g/ml$; $36.6{\pm}11.3%$, LPS 1000ng/ml +Surf $100{\mu}g/ml$; $41.3{\pm}11.2%$). The high dose of surfactant ($1000{\mu}g/ml$) decreased apoptosis ($24.4{\pm}7.7%$) and augmented the anti-apoptotic effect of LPS (LPS 1000ng/ml + Surf $1000P{\mu}g/ml$; $19.8{\pm}5.4%$). In the in vivo study, the apoptotic rate of alveolar neutrophils of surfactant-treated rats was higher than that of normal saline-treated rats ($6.03{\pm}3.36%$ vs. $2.95{\pm}0.58%$). The airway resistance (represented by Penh) of surfactant-treated rats was lower than that of normal saline-treated rats at 23 hours after LPS injury ($2.64{\pm}0.69$ vs. $4.51{\pm}2.24$, p<0.05). Conclusion : Surfactant promotes the apoptosis of human peripheral blood and rat alveolar neutrophils. Pro-apoptotic action on neutrophils represents one of the important anti-inflammatory mechanisms of surfactant.

The Usefulness of B-type Natriuretic Peptide test in Critically Ill, Noncardiac Patients (심질환 병력이 없었던 중환자에서 B-type Natriuretic Peptide 검사의 유용성)

  • Kim, Kang Ho;Park, Hong-Hoon;Kim, Esther;Cheon, Seok-Cheol;Lee, Ji Hyun;Lee, Stephen YongGu;Lee, Ji-Hyun;Kim, In Jai;Cha, Dong-Hoon;Kim, Sehyun;Choi, Jeongeun;Hong, Sang-Bum
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.3
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    • pp.311-319
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    • 2003
  • Background : Previous studies have suggested that a B-type natriuretic peptide(BNP) test can provide important information on diagnosis, as well as predicting the severity and prognosis of heart failure. Myocardial dysfunction is often observed in critically ill noncardiac patients admitted to the Intensive Care Unit, and the prognosis of the myocardial dysfunction needs to be determined. This study evaluated the predictability of BNP on the prognosis of critically ill noncardiac patients. Methods : 32 ICU patients, who were hospitalized from June to October 2002 and in whom the BNP test was evaluated, were enrolled in this study. The exclusion criteria included the conditions that could increase the BNP levels irrespective of the severity, such as congestive heart failure, atrial fibrillation, ischemic heart disease, and renal insufficiencies. A triage B-Type Natriuretic Peptide test with a RIA-kit was used for the fluorescence immunoassay of BNP test. In addition, the acute physiology and the chronic health evaluation (APACHE) II score and mortality were recorded. Results : There were 16 males and 16 females enrolled in this study. The mean age was 59 years old. The mean BNP levels between the ICU patients and control were significantly different ($186.7{\pm}274.1$ pg/mL vs. $19.9{\pm}21.3$ pg/mL, p=0.033). Among the ICU patients, there were 14(44----) patients with BNP levels above 100 pg/mL. The APACHE II score was $16.5{\pm}7.6$. In addition, there were 11 mortalities reported. The correlation between the BNP and APACHE II score, between the BNP and mortality were significant (r=0.443, p=0.011 & r=0.530, p=0.002). The mean BNP levels between the dead and alive groups were significantly different ($384.1{\pm}401.7$ pg/mL vs. $83.2{\pm}55.8$ pg/mL p=0.033). However, the $PaO_2/FiO_2$ did not significantly correlate with the BNP level. Conclusion : This study evaluated the BNP level was elevated in critically ill, noncardiac patients. The BNP level could be a useful, noninvasive tool for predicting the prognosis of the critically ill, noncardiac patients.

Expression of Phospholipase C Isozymes in Human Lung Cancer Tissues (인체 폐암조직에서 Phospholipase C 동위효소의 발현양상)

  • Hwang, Sung-Chul;Mah, Kyung-Ae;Choi, So-Yeon;Oh, Yoon-Jung;Choi, Young-In;Kim, Deog-Ki;Lee, Hyung-Noh;Choi, Young-Hwa;Park, Kwang-Ju;Lee, Yi-Hyeong;Lee, Kyi-Beom;Ha, Mahn-Joon;Bae, Yoon-Su
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.3
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    • pp.310-322
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    • 2000
  • Background : Phospholipase C(PLC) plays an important role in cellular signal transduction and is thought to be critical in cellular growth, differentiation and transformation of certain malignancies. Two second messengers produced from the enzymatic action of PLC are diacylglycerol (DAG) and inositol 1, 4, 5-trisphosphate (IP3). These two second messengers are important in down stream signal activation of protein kinase C and intracellular calcium elevation. In addition, functional domains of the PLC isozymes, such as Src homology 2 (SH2) domain, Src homology 3 (SH3) domain, and pleckstrin homology (PH) domain play crucial roles in protein translocation, lipid membrane modificailon and intracellular memrane trafficking which occur during various mitogenic processes. We have previously reported the presence of PLC-${\gamma}1$, ${\gamma}2$, ${\beta}1$, ${\beta}3$, and ${\delta}1$ isozymes in normal human lung tissue and tyrosine-kinase-independent activation of phospholipase C-${\gamma}$ isozymes by tau protein and AHNAK. We had also found that the expression of AHNAK protein was markedly increased in various mstologic types of lung can∞r tissues as compared to the normallungs. However, the report concerning expression of various PLC isozymes in lung canærs and other lung diseases is lacking. Therefore, in this study we examined the expression of PLC isozymes in the paired surgical specimens taken from lung cancer patients. Methods : Surgically resected lung cancer tissue samples taken from thirty seven patients and their paired normal control lungs from the same patients, The expression of various PLC isozymes were studied. Western blot analysis of the tissue extracts for the PLC isozymes and immunohistochemistry was performed on typical samples for localization of the isozyme. Results : In 16 of 18 squamous cell carcinomas, the expression of PLC-${\gamma}1$ was increased. PLC-${\gamma}1$ was also found to be increased in all of 15 adenocarcinoma patients. In most of the non-small cell lung cancer tissues we had examined, expression of PLC-${\delta}1$ was decreased. However, the expression of PLC-${\delta}1$ was markedly increased in 3 adenocarcinomas and 3 squamous carcinomas. Although the numbers were small, in all 4 cases of small cell lung cancer tissues, the expression of PLC-${\delta}1$ was nearly absent. Conclusion : We found increased expression of PLC-${\gamma}1$ isozyme in lung cancer tissues. Results of this study, taken together with our earlier findings of AHNAK protein-a putative PLD-${\gamma}$, activator-over-expression, and the changes observed in PLC-${\delta}1$ in primary human lung cancers may provide a possible insight into the derranged calcium-inositol signaling pathways leading to the lung malignancies.

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Multimodality Treatement in Patients with Clinical Stage IIIA NSCLC (임상적 IIIA병기 비소세포폐암의 다각적 치료의 효과)

  • Lee, Yun Seun;Jang, Pil Soon;kang, Hyun Mo;Lee, Jeung Eyun;Kwon, Sun Jung;An, Jin Yong;Jung, Sung Soo;Kim, Ju Ock;Kim, Sun Young
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.6
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    • pp.557-566
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    • 2004
  • Background : To find out effectiveness of multimodality treatments based on induction chemotherapy(CTx) in patients with clinical stage IIIA NSCLC Methods : From 1997 to 2002, 74 patients with clinical stage IIIA NSCLC underwent induction CTx at the hospital of Chungnam National University. Induction CTx included above two cycles of cisplatin-based regimens(ectoposide, gemcitabine, vinorelbine, or taxol) followed by tumor evaluation. In 30 complete resection group, additional 4500-5000cGy radiotherapy(RTx) was delivered in 15 patients with pathologic nodal metastasis. 29 out of 44 patients who were unresectable disease, refusal of operation, and incomplete resection were followed by 60-70Gy RTx in local treatment. Additional 1-3 cycle CTx were done in case of induction CTx responders in both local treatment groups. Results : Induction CTx response rate were 44.6%(complete remission 1.4% & partial response 43.2%) and there was no difference of response rate by regimens(p=0.506). After induction chemotherapy, only 33 out of resectable 55 ones(including initial resectable 37 patients) were performed by surgical treatment because of 13 refusal of surgery by themselves and 9 poor predicted reserve lung function. There were 30(40.5%) patients with complete resection, 2(2.6%) persons with incomplete resection, and 1(1.3%) person with open & closure. Response rate in 27 ones with chest RTx out of non-operation group was 4.8% CR and 11.9% PR. In complete resection group, relapse free interval was 13.6 months and 2 year recur rate was 52%. In non-complete resection(incomplete resection or non-operation) group, disease progression free interval was 11.2 months and 2 year disease progression rate was 66.7%. Median survival time of induction CTx 74 patients with IIIA NSCLC was 25.1months. When compared complete resection group with non-complete resection group, the median survival time was 31.7 and 23.4months(p=0.024) and the 2-year overall survival rate was 80% and 41%. In the complete resection group, adjuvant postoperative RTx subgroup significantly improved the 2-year local control rate(0% vs. 40%, p= 0.007) but did not significantly improve overall survival(32.2months vs. 34.9months, p=0.48). Conculusion : Induction CTx is a possible method in the multimodality treatments, especially followed by complete resection, but overall survival by any local treatment(surgical resection or RTx) was low. Additional studies should be needed to analysis data for appropriate patient selection, new chemotherapy regimens and the time when should RTx be initiated.

Essay on Form and Function Design (디자인의 형태와 기능에 관한 연구)

  • 이재국
    • Archives of design research
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    • v.2 no.1
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    • pp.63-97
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    • 1989
  • There is nothing more important than the form and function in design, because every design product can be done on the basis of them. Form and Function are already existed before the word of design has been appeared and all the natural and man-made things' basic organization is based on their organic relations. The organic relations is the source of vitality which identifies the subsistance of all the objects and the evolution of living creatures has been changed their appearances by the natural law and order. Design is no exception. Design is a man-made organic thing which is developed its own way according to the purposed aim and given situations. If so, what is the ultimate goal of design. It is without saying that the goal is to make every effort to contribute to the -human beings most desirable life by the designer who is devoting himself to their convenience and well-being. Therefore, the designer can be called the man of rich life practitioner. This word implies a lot of meanings since the essence of design is improving the guality of life by the man-made things which are created by the designer. Also, the things are existed through the relations between form and function, and the things can keep their value when they are answered to the right purpose. In design, thus, it is to be a main concern how to create valuable things and to use them in the right way, and the subject of study is focused on the designer's outlook of value and uk relations between form and function. Christopher Alexander mentioned the importance of form as follows. The ultimate object of design is form. Every design problem begins with an effort to achieve fittness between the form and its context. The form is the solution to the problem: the context defmes the problem. In other words, when we speak of design, the real object of discussion is not form alone, but the ensemble comprising the form and its context. Good fit is a desirable property of this ensemble which relates to some particular division of the ensemble into form and context. Max Bill mainatined how important form is in design. Form represents a self-contained concept, and its embodiment in an object results in that object becoming a work of art. Futhermore, this explains why we use form so freguently in a comparative sense for determining whether one thing is less or more beautiful than another, and why the ideal of absolute beauty is always the standard by which we appraise form, and through form, art itself. Hence form has became synonymous with beauty. On the other hand, Laszlo Moholy-Nagy stated the importance of function as follows. Function means the task an object is designed to fulfill the task instrument is shaping the form. Unfortunately, this principle was not appreciated at the same time but through the endeavors of Frank Lloyd Wright and of the Bauhaus group and its many collegues in Europe, the idea of functionalism became the keynote of the twenites. Functionalism soon became a cheap slogan, however, and its original meaning blurred. It is neccessary to reexamine it in the light of present circumstances. Charles William Eliot expressed his idea on the relations between function and beauty. Beauty often results chiefly from fittness: indeed it is easy to manitain that nothing is fair except what is fit its uses or functions. If the function of the product of a machine be useful and valuable, an the machine be eminently fit for its function, it conspicuously has the beauty of fittness. A locomotive or a steamship has the same sort of beauty, derived from the supreme fittness for its function. As functions vary, so will those beauty..vary. However, it is impossible to study form and function in separate beings. Function can't be existed without form, and without function, form is nothing. In other words, form is a function's container, and function is content in form. It can be said that, therefore, the form and function are indispensable and commensal individuals which have coetemal relations. From the different point of view, sometimes, one is more emphasized than the other, but in this case, the logic is only accepted on the assumption of recognizing the importance of the other's entity. The fact can be proved what Frank Hoyd wright said that form and function are one. In spite of that, the form and function should be considered as independent indivisuals, because they are too important to be treated just as the simple single one. Form and function have flexible properties to the context. In other words, the context plays a role as the barometer to define the form and function, also which implies every meaning of surroun'||'&'||'not;dings. Thus, design is formed under the influence of situations. Situations are dynamic, like the design process itself, in which fixed focus can be cripping. Moreover, situations control over making the good design. Judging from the respect, I defined the good design in my thesis An Analytic Research on Desigh Ethic, "good design is to solve the problem by the most proper way in the situations." Situations are changeable, and so is design. There is no progress without change, but change is not neccessarily progress. It is highly desirable that there changes be beneficial to mankind. Our main problem is to be able to discriminate between that which should be discarded and that which should be kept, built upon, and improved. Form and Function are no exception. The practical function gives birth to the inevitable form and the $$\mu$ti-classified function is delivered to the varieties of form. All of these are depended upon changeable situations. That is precisely the situations of "situation de'||'&'||'not;sign", the concept of moving from the design of things to the design of the circumstances in which things are used. From this point of view, the core of form and function is depended upon how the designer can manage it efficiently in given situations. That is to say that the creativity designer plays an important role to fulfill the purpose. Generally speaking, creativity is the organization of a concept in response to a human need-a solution that is both satisfying and innovative. In order to meet human needs, creative design activities require a special intuitive insight which is set into motion by purposeful imagination. Therefore, creativity is the most essential quality of every designer. In addition, designers share with other creative people a compulsive ingenuity and a passion for imaginative solutions which will meet their criteria for excellence. Ultimately, it is said that the form and function is the matter which belongs to the desire of creative designers who constantly try to bring new thing into being to create new things. In accordance with that the main puppose of this thesis is to catch every meaning of the form and function and to close analyze their relations for the promotion of understanding and devising practical application to gradual progression in design. The thesis is composed of four parts: Introduction, Form, Function and Conclusion. Introduction, the purpose and background of the research are presented. In Chapter I, orgin of form, perception of form, and classification of form are studied. In Chapter II, generation of function, development of function, and diversification of function are considered. Conclusion, some concluding words are mentioned.ioned.

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An Appreciation of Functional Role of Macrophage in the Acute Lung Injury in the Neutropenic Rat. (호중구 감소증을 보이는 백서의 급성폐손상에서 대식세포의 기능적 역할)

  • Kim, Yong-Hoon;Ki, Sin-Young;Im, Keon-Il;Moon, Seung-Hyug;Cheong, Seung-Whan;Kim, Hyeon-Tae;Uh, Soo-Taek;Park, Choon-Sik;Jin, Byung-Won
    • 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.

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