• Journal of Gastric Cancer
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• v.6 no.1
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• pp.36-42
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• 2006

Purpose: The $p21^{Waf1/Cip1}$ protein Inhibits the cell cycle by Inhibiting the phosphorylation at the $G1{\rightarrow}S$ check point, and the $p27^{kip1}$ protein similarly performs the suppressor function by controlling the p27-mediated G1 arrest. In this study, we analysed the clinical status and survival rates in correlations with p21 and p27 expression patterns in gastric cancer. Materials and Methods: Between 1993 and 1997, 192 patients who underwent surgeries in Catholic Medical Center were analysed retrospectively in this study. Immunohistochemical staining was performed and if the nuclei of the tumor cells were stained, we assumed those as positive results. Statistical analysis was based on clinicopathological findings and differences in survival rates. Results: The expression rate of p27 was 28.1% and 15.6% in p21 each. The ratio of T1-2(80.0%) was significantly high in p21 (+), but the ratio of T3-4 (50.6%) was slightly high in p21 (-). There was no statistical significance regarding other factors. The results in p27 was not much different from expression rate of p21 in T-stage. In addition, p27 expression in diffuse type (91.3%) was higher than in intestinal type (62.7%) by Lauren's classification (P<0.05). Also, there was no statistical significance in other factors. In the correlation of p21 and p27, p27 was positive when p21 was positive (53.5%). Conversely, p27 was negative when p21 was negative (76.5%, p<0.05). In the p21 and p27 combination test, there was higher rate of T1-2 (87.5%) in p21 (+)/p27 (+), and higher rate of T3-4 (58.1%) in p21 (-)/p27 (-) (P<0.05). Results showed higher rate of intestinal type (100%) in p21 (+)/p27 (+), and diffuse type (87.0%) was dominant in p21 (-)/p27 (-) (P<0.05) by Lauren's classification. Moreover, there was no statistical significance in the 5-year survival rate in the expression of p21 and p27, and the 5-year survival rate was highest in the case of p21 (+)/p27 (+) without statistical significance. Conclusion: In our study, $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ expressed similar patterns. The expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ affected the degree of invasiveness of the tumor, and. Combined examination result revealed the correlation of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ with Lauren's classification and depth of invasion of the tumor. However, we assumed that little difference between the survival rates depending on expression of $p21^{Waf1/Cip1}\;and\;p27^{kip1}$ has limited their value as predictable prognostic indicators.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.861-869
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• 1998

Backgrounds: The injury of a tissue results in the infalmmation, and the imflammed tissue is replaced by the normal parenchymal cells during the process of repair. But, constitutional or repetitive damage of a tissue causes the deposition of collagen resulting in the loss of its function. These lesions are found in the lung of patients with idiopathic pulmonary fibrosis, complicated fibrosis after diffuse alveolar damage (DAD) and inorganic dust-induced lung fibrosis. The tissue from lungs of patients undergoing episodes of active and/or end-stage pulmonary fibrosis shows the accumulation of inflammatory cells, such as mononuclear cells, neutrophils, mast cells and eosinophils, and fibroblast hyperplasia. In this regard, it appears that the inflammation triggers fibroblast activation and proliferation with enhanced matrix synthesis, stimulated by inflammatory mediators such as interleukin-1 (IL-1) and/or tumor necrosis factor (TNF). It has been well known that TGF-$\beta$ enhance the proliferation of fibroblasts and the production of collagen and fibronectin, and inhibit the degradation of collagen. In this regard, It is likely that TGF-$\beta$ undergoes important roles in the pathogenesis of pulmonary fibrosis. Nevertheless, this single cytokine is not the sole regulator of the pulmonary fibrotic response. It is likely that the balance of many cytokines including TGF-$\beta$, IL-1, IL-6 and TNF-$\alpha$ regulates the pathogenesis of pulmonary fibrosis. In this study, we investigate the interaction of TGF-$\beta$, IL-1$\beta$, IL-6 and TNF-$\alpha$ and their effect on the proliferation of fibroblasts. Methods: We used a human fibroblast cell line, MRC-5 (ATCC). The culture of MRC-5 was confirmed by immunofluorecent staining. First, we determined the concentration of serum in cuture medium, in which the proliferation of MRC-5 is supressed but the survival of MRC-5 is retained. Second, we measured optical density after staining the cytokine-stimulated cells with 0.5% naphthol blue black in order to detect the effect of cytokines on the proliferation of MRC-5. Result: In the medium containing 0.5% fetal calf serum, the proliferation of MRC-5 increased by 50%, and it was maintained for 6 days. IL-1$\beta$, TNF-$\alpha$ and IL-6 induced the proliferation of MRC-5 by 45%, 160% and 120%, respectively. IL-1$\beta$ and TNF-$\alpha$ enhanced TGF-$\beta$-induced proliferation of MRC-5 by 64% and 159%, but IL-6 did not affect the TGF-$\beta$-induced proliferation. And lNF-$\alpha$-induced proliferation of MRC-5 was reduced by IL-1$\beta$ in 50%. TGF-$\beta$, TNF-$\alpha$ and both induced the proliferation of MRC-5 to 89%, 135% and 222%, respectively. Conclusions: TNF-$\alpha$, TGF-$\beta$ and IL-1$\beta$, in the order of the effectiveness, showed the induction of MRC-5 proliferation of MRC-5. TNF-$\alpha$ and IL-1$\beta$ enhance the TGF-$\beta$-induced proliferation of MRC-5, but IL-6 did not have any effect TNF-$\alpha$-induced proliferation of MRC-5 is diminished by IL-1, and TNF-$\alpha$ and TGF-$\beta$ showed a additive effect.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.5-19
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• 1998

Introduction: Direct histologic and bacteriologic examination of a representative specimen of lung tissue is the only certain method of providing an accurate diagnosis in various pulmonary diseases including diffuse pulmonary diseases. The purpose of national survey was to define the indication, incidence, effectiveness, safety and complication of open and thoracoscopic lung biopsy in korea. Methods: A multicenter registry of 37 university or general hospitals equipped more than 400 patient's bed were retrospectively collected and analyzed for 3 years from the January 1994 to December 1996 using the same registry protocol. Results: 1) There were 511 cases from the 37 hospitals during 3 years. The mean age was 50.2 years(${\pm}15.1$ years) and men was more prevalent than women(54.9% vs 45.9%). 2) The open lung biopsy was performed in 313 cases(62%) and thoracoscopic lung biopsy was performed in 192 cases(38%). The incidence of lung biopsy was more higher in diffuse lung disease(305 cases, 59.7%) than in localized lung disease(206 cases, 40.3%) 3) The duration after abnormalities was found in chest X-ray until lung biopsy was 82.4 days(open lung biopsy: 72.8 days, thoracoscopic lung biopsy: 99.4 days). The bronchoscopy was performed in 272 cases(53.2%), bronchoalveolar lavage was performed in 123 cases(24.1%) and percutaneous lung biopsy was performed in 72 cases(14.1%) before open or thoracoscopic lung biopsy. 4) There were 230 cases(45.0%) of interstitial lung disease, 133 cases(26.0%) of thoracic malignancies, 118 cases(23.1%) of infectious lung disease including tuberculosis and 30 cases (5.9 %) of other lung diseases including congenital anomalies. No significant differences were noted in diagnostic rate and disease characteristics between open lung biopsy and thoracoscopic lung biopsy. 5) The final diagnosis through an open or thoracoscopic lung biopsy was as same as the presumptive diagnosis before the biopsy in 302 cases(59.2%). The identical diagnostic rate was 66.5% in interstitial lung diseases, 58.7% in thoracic malignancies, 32.7% in lung infections, 55.1 % in pulmonary tuberculosis, 62.5% in other lung diseases including congenital anomalies. 6) One days after lung biopsy, $PaCO_2$ was increased from the prebiopsy level of $38.9{\pm}5.8mmHg$ to the $40.2{\pm}7.1mmHg$(P<0.05) and $PaO_2/FiO_2$ was decreased from the prebiopsy level of $380.3{\pm}109.3mmHg$ to the $339.2{\pm}138.2mmHg$(P=0.01). 7) There was a 10.1 % of complication after lung biopsy. The complication rate in open lung biopsy was much higher than in thoracoscopic lung biopsy(12.4% vs 5.8%, P<0.05). The incidence of complication was pneumothorax(23 cases, 4.6%), hemothorax(7 cases, 1.4%), death(6 cases, 1.2%) and others(15 cases, 2.9%). 8) The 5 cases of death due to lung biopsy were associated with open lung biopsy and one fatal case did not describe the method of lung biopsy. The underlying disease was 3 cases of thoracic malignancies(2 cases of bronchoalveolar cell cancer and one malignant mesothelioma), 2 cases of metastatic lung cancer, and one interstitial lung disease. The duration between open lung biopsy and death was $15.5{\pm}9.9$ days. 9) Despite the lung biopsy, 19 cases (3.7%) could not diagnosed. These findings were caused by biopsy was taken other than target lesion(5 cases), too small size to interpretate(3 cases), pathologic inability(11 cases). 10) The contribution of open or thoracoscopic lung biopsy to the final diagnosis was defininitely helpful(334 cases, 66.5%), moderately helpful(140 cases, 27.9%), not helpful or impossible to judge(28 cases, 5.6%). Overall, open or thoracoscopic lung biopsy were helpful to diagnose the lung lesion in 94.4 % of total cases. Conclusions: The open or thoracoscopic lung biopsy were relatively safe and reliable diagnostic method of lung lesion which could not diagnosed by other diagnostic approaches such as bronchoscopy. We recommend the thoracoscopic lung biopsy when the patients were in critical condition because the thoracoscopic biopsy was more safe and have equal diagnostic results compared with the open lung biopsy.

• Tuberculosis and Respiratory Diseases
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• v.45 no.6
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• pp.1265-1276
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• 1998

Background : Nitric oxide(NO) is an endogenously produced free radical that plays an important role in regulating vascular tone, inhibition of platelet aggregation and white blood cell adhesion to endothelial cells, and host defense against infection. The highly reactive nature of NO with oxygen radicals suggests that it may either promote or reduce oxidant-induced cell injury in several biological pathways. Oxidant injury and interactions between pulmonary vascular endothelium and leukocytes are important in the pathogenesis of acute lung injury, including acute respiratory distress syndrome(ARDS). In ARDS, therapeutic administration of NO is a clinical condition providing exogenous NO in oxidant-induced endothelial injury. The role of exogenous NO from NO donor or the suppression of endogenous NO production was evaluated in oxidant-induced endothelial injury. Method : The oxidant injury in cultured rat lung microvascular endothelial cells(RLMVC) was induced by hydrogen peroxide generated from glucose oxidase(GO). Cell injury was evaluated by $^{51}$chromium($^{51}Cr$) release technique. NO donor, such as S-nitroso-N-acetylpenicillamine(SNAP) or sodium nitroprusside(SNP), was added to the endothelial cells as a source of exogenous NO. Endogenous production of NO was suppressed with N-monomethyl-L-arginine(L-NMMA) which is an NO synthase inhibitor. L-NMMA was also used in increased endogenous NO production induced by combined stimulation with interferon-$\gamma$(INF-$\gamma$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), and lipopolysaccharide(LPS). NO generation from NO donor or from the endothelial cells was evaluated by measuring nitrite concentration. Result : $^{51}Cr$ release was $8.7{\pm}0.5%$ in GO 5 mU/ml, $14.4{\pm}2.9%$ in GO 10 mU/ml, $32.3{\pm}2.9%$ in GO 15 mU/ml, $55.5{\pm}0.3%$ in GO 20 mU/ml and $67.8{\pm}0.9%$ in GO 30 mU/ml ; it was significantly increased in GO 15 mU/ml or higher concentrations when compared with $9.6{\pm}0.7%$ in control(p < 0.05; n=6). L-NMMA(0.5 mM) did not affect the $^{51}Cr$ release by GO. Nitrite concentration was increased to $3.9{\pm}0.3\;{\mu}M$ in culture media of RLMVC treated with INF-$\gamma$ (500 U/ml), TNF-$\alpha$(150 U/ml) and LPS($1\;{\mu}g/ml$) for 24 hours ; it was significantly suppressed by the addition of L-NMMA. The presence of L-NMMA did not affect $^{51}Cr$ release induced by GO in RLMVC pretreated with INF-$\gamma$, TNF-$\alpha$ and LPS. The increase of $^{51}Cr$ release with GO(20 mU/ml) was prevented completely by adding 100 ${\mu}M$ SNAP. But the add of SNP, potassium ferrocyanate or potassium ferricyanate did not protect the oxidant injury. Nitrite accumulation was $23{\pm}1.0\;{\mu}M$ from 100 ${\mu}M$ SNAP at 4 hours in phenol red free Hanks' balanced salt solution. But nitrite was not detectable from SNP upto 1 mM The presence of SNAP did not affect the time dependent generation of hydrogen peroxide by GO in phenol red free Hanks' balanced salt solution. Conclusion : Hydrogen peroxide generated by GO causes oxidant injury in RLMVC. Exogenous NO from NO donor prevents oxidant injury, and the protective effect may be related to the ability to release NO. These results suggest that the exogenous NO may be protective on oxidant injury to the endothelium.

• Tuberculosis and Respiratory Diseases
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• v.45 no.1
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• pp.140-152
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• 1998

Background: Prone position improves oxygenation in patients with ARDS probably by reducing shunt Reduction of shunt in prone position is thought to be effected by lowering of the critical opening pressure (COP) of the dorsal lung because the pleural pressure becomes less positive in prone position compared to supine position. It can then be assumed that prone position would bring about greater improvement in oxygenation when PEEP applied in supine position is just beneath COP than when PEEP is above COP. Hemodynamically, prone position is expected to attenuate the lifting of cardiac fossa induced by PEEP. Based on these backgrounds, we investigated whether the effect of prone position on oxygenation differs in magnitude according to the level of PEEP applied in supine position, and whether impaired cardiac output in supine position by PEEP can be restored in prone position. Methods: In seven mongrel dogs, $PaO_2/F_1O_2$(P/F) was measured in supine position and at prone position 30 min. Cardiac output (CO), stroke volume (SV), pulse rate (PR), and pulmonary artery occlusion pressure (PAOP) were measured in supine position, at prone position 5 min, and at prone position 30 min. After ARDS was established with warmed saline lavage(P/F ratio $134{\pm}72$ mm Hg), inflection point was measured by constant flow method($6.6{\pm}1.4cm$ $H_2O$), and the above variables were measured in supine and prone positions under the application of Low PEEP($5.0{\pm}1.2cm$ $H_2O$), and Optimal PEEP($9.0{\pm}1.2cm$ $H_2O$)(2 cm $H_2O$ below and above the inflection point, respectively) consecutively. Results : P/F ratio in supine position was $195{\pm}112$ mm Hg at Low PEEP and $466{\pm}63$ mm Hg at Optimal PEEP(p=0.003). Net increase of P/F ratio at prone position 30 min, however, was far greater at Low PEEP($205{\pm}90$ mm Hg) than at Optimal PEEP($33{\pm}33$ mm Hg)(p=0.009). Compared to CO in supine position at Optimal PEEP($2.4{\pm}0.5$ L/min), CO in prone improved to $3.4{\pm}0.6$ L/min at prone position 5 min (p=0.0180) and $3.6{\pm}0.7$ L/min at prone position 30 min (p=0.0180). Improvement in CO was attributable to the increase in SV: $14{\pm}2$ ml in supine position, $20{\pm}2$ ml at prone position 5 min (p=0.0180), and $21{\pm}2$ ml at prone position 30 min (p=0.0180), but not to change in PR or PAOP. When the dogs were turned to supine position again, MAP ($92{\pm}23$ mm Hg, p=0.009), CO ($2.4{\pm}0.5$ L/min, p=0.0277) and SV ($14{\pm}1$ ml, p=0.0277) were all decreased compared to prone position 30 min. Conclusion: Prone position in a dog with saline-lavaged acute lung injury appeared to augment the effect of relatively low PEEP on oxygenation, and also attenuate the adverse hemodynamic effect of relatively high PEEP. These findings suggest that a PEEP lower than Optimal PEEP can be adopted in prone position to achieve the goal of alveolar recruitment in ARDS avoiding the hemodynamic complications of a higher PEEP at the same time.

• Journal of agricultural medicine and community health
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• v.30 no.1
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• pp.1-14
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• 2005

Objectives: This study attempts to analyze the length of hospital stay and expenses of frequent disease admitted in a Vaterans Hospital. Methods: Data was collected from January 1, 2001 to December 31, 2003 from the Claim records of 9,640 patients in a Vaterans Hospital. Results: The results were as follows: 1. In age & sex distribution, there was male 70.9%, female 29.1%, and 35.8% of them is 70 age group. Frequency by insurance program was Health insurance 78.1%, Medical aid 14.2%, no insurance 4.1%, others 3.6%. Distribution of each department was internal medicine 28.3%, orthopedic surgery 21.3%, surgery 16.6%, neurosurgey 7.1%, pediatrics 5.9%. Also, in the veterans group, male to female patient ratio was 99.3% male to 0.7% female, them over 70 years old was 51.6%, and them which live in daejeon was 43.5%. 2. In frequency of disease, there was gastroenteritis 4.8%, pneumonia 3.8%, cartaract 3.7%, cerebral infarct 3.2%, hyperplasia of prostate 3.0%. In frequency of korean standard classification of diseases, there was injury and poisoning and certain other consequences of external causes 17.1%, diseases of digestive system 16.1%, diseases of musculoskeletal system and connective tissue 13.9%, diseases of respiratory system 9.4%, diseases of genitourinary system 8.6%. Also, in veterans group, frequency of them was diseases of musculoskeletal system and connective tissue 19.4%, diseases of digestive system 16.8%, injury and poisoning and certain other consequences of external causes 15.7%, diseases of genitourinary system 9.7%, diseases of circuatory system 8.2%. 3. Average length of hospital stay was 29.0 days for total patients, 51.8 days for the veterans group, 15.7 days for the non-veterans one. Average total expenses was 3,669,579 won, the veterans group 7,263,877 won, the non-veterans one 1,560,333 won. The ratio of insurer to insuree was 55.2 : 44.8, the ratio of amount paid by patient in the veterans group 61.7%, in the non-veterans one 33.0%. 4. In items of medical expenses, fee for hospital accommodation was 34.7%, fee for medication 13.2%(injection 7.8%, drug 5.4%), fee for service 48.6%(physical therapy 26.3%, operation 9.7%, laboratory examination 5.2%, radiological examination 3.1%, etc), others 3.4%. In them for the veterans group, fee for physical therapy was 35.3%, fee for hospital accommodation 35.2%, fee for injection 6.2%, fee for operation 5.9%, for the non-veterans one, fee for hospital accommodation 35.7%, fee for operation 16.4%, fee for injection 11.4%, fee for laboratory examination 8.3%. 5. In the comparison of the frequency by Korean standard classification of diseases and distance between the hospital and home, the region under 21.5Km was more frequent in symptoms, signs an abnormal clinical and laboratory findings 56.0%, injury and poisoning and certain other consequences of external causes 55.6%, diseases of the eye and adnexa 52.9%, the one over 21.5Km was more frequent in neoplasms 57.4%, diseases of musculoskeletal system and connective tissue 55.9%, diseases of genitourinary system 53.5%.

• The Korean Journal of Nuclear Medicine
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• v.4 no.1
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• pp.19-26
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• 1970

1. Sixteen normal healthy subjects free from occult blood in the stool were selected and administered with their $^{51}Cr$ labeled own blood via duodenal tube and the recovery rate of radioactivity in feces and urine was measured. The average fecal recovery rate was 90.7 per cent ($85.7{\sim}97.7%$) of the administered radioactivity, and the average urinary excretion rate was 0.8 per cent ($0.5{\sim}1.5%$) 2. There was a close correlation between the amount of blood administered and the recovery rate from the feces; the more the blood administered, the higher the recovery rate was. It was also found that the administration of the tagged blood in the amount exceeding 15ml was suitable for measuring the radioactivity in the stools. 3. In five normal healthy subjects whose circulating erythrocytes had been tagged with $^{51}Cr$, there was little fecal excretion of radioactivity (average 0.9 ml of blood per day). This excretion is not related to hemorrhage and the main route of excretion of such an negligible radioactivity was postulated as gastric juice and bile. 4. A comparison of the radioactivity in the blood and feces of the patients with $^{51}Cr$ labeled erythrocytes seems to be a valid way of estimating intestinal blood loss.