• Radiation Oncology Journal
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• v.27 no.4
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• pp.210-217
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• 2009

Purpose: To assess the influence of cyclooxygenase-2 (COX-2) expression on the survival of patients with a combination of rectal cancer and lymph node metastasis. Materials and Methods: The study included rectal cancer patients treated by radical surgery and postoperative radiotherapy at the Dong-A university hospital from 1998 to 2004. A retrospective analysis was performed on a subset of patients that also had lymph node metastasis. After excluding eight of 86 patients, due to missing tissue samples in three, malignant melanoma in one, treatment of gastric cancer around one year before diagnosis in one, detection of lung cancer after one year of diagnosis in one, liver metastasis in one, and refusal of radiotherapy after 720 cGy in one, 78 patients were analyzed. The immunohistochemistry for COX-2 was conducted with an autostainer (BenchMark; Ventana, Tucson, AZ, USA). An image analyzer (TissueMine; Bioimagene, Cupertino, CA, USA) was used for analysis after scanning (ScanScope; Aperio, Vista, CA, USA). A survival analysis was performed using the Kaplan Meier method and significance was evaluated using the log rank test. Results: COX-2 was stained positively in 62 patients (79.5%) and negatively in 16 (20.5%). A total of 6 (7.7%), 15 (19.2%), and 41 (52.6%) patients were of grades 1, 2, and 3, respectively for COX-2 expression. No correlation was found between being positive of COX-2 patient characteristics, which include age (<60-year old vs. $\geq$60), sex, operation methods (abdominoperineal resection vs. lower anterior resection), degrees of differentiation, tumor size (<5 cm vs. $\geq$5 cm), T stages, N stages, and stages (IIIa, IIIb, IIIc). The 5-year overall and 5-year disease free survival rates for the entire patient population were 57.0% and 51.6%, respectively. The 5-year overall survival rates for the COX-2 positive and negative patients were 53.0% and 72.9%, respectively (p=0.146). Further, the 5-year disease free survival rates for the COX-2 positive and negative patients were 46.3% and 72.7%, respectively (p=0.118). The 5-year overall survival rates were significantly different (p<0.05) for the degree of differentiation, N stage, and stage, whereas the 5-year disease free survival rates were significant for N stage and stage. Conclusion: Being positive for and the degree of COX-2 expression did not have a significant influence on the survival of rectal cancer patients with lymph node metastasis. However, N stage and stage did significantly influence the rateof survival. Further analysis of a greater sample size is necessary for the verification of the effect of COX-2 expression on the survival of rectal cancer patients with lymph node involvement.

• Childhood Kidney Diseases
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• v.4 no.2
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• pp.120-126
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• 2000

Purpose : This retrospective study has been undertaken to find out the clinical outcome of children with HS nephntis and its relationship with initial clinical presentation and/or renal pathologic finding. Patients and methods : Study population consisted of 59 children with HS nephritis who have been admitted to the Pediatric department of Kyungpook University Hospital from 1987 to 1999, and biopsy was done with indications of heavy proteinuria (> 1 g/m2/day) lasting over 1 month, nephrotic syndrome, and persistent hematuria and/or proteinuria over 1 year. Patients were divided clinically into 3 groups ; isolated hematuria, hematuria with proteinuria and heavy proteinuria (including nephrotic syndrome). Biopsy findings ore graded from I-V according to International Study of Kidney Disease in Children (ISKDC). Results : Mean age of presentation was $8.1{\pm}3.0$ years and slight male preponderance m noted (33 boys md 26 girls). Histopathologic grading showed Grade I ; 2, Grade II ; 44, and Grade III ; 13 cases. Clinical outcome at the follow-up period of 1-2 year (49 cases) and 3-4 years (30 cases) shooed normal urinalysis in 75 (30.6$\%$) and 18 cases (60.0$\%$), persistent isolated hematuria in 20 (40.8$\%$) and 2 cases (6.7$\%$), hematuria with proteinuria in 11 (22.5$\%$) and 8 cases (26.6$\%$), and persistent heavy proteinuria in 3 (6.1$\%$) and 2 cases (6.7$\%$) respectively. Clinical outcome according to histopathologic grading showed the frequency of normalization of urinalysis being lower in Grade III compared to grade I or II. Clinical outcome according to initial clinical presentation showed no relationship to the normalization or urinalysis at follow-up periods. However, 15-20$\%$ of children with initial heavy proteinuria showed persistent heavy proteinuria (3 out of 20 cases at 1-2 years, and 2 out of 10 case at 3-4 years of follow-up periods). Conclusion : The majority of children with HS nephritis (histopathologic grade I, II, III) improved within 3-4 years and persistent heavy proteinuria was seen only in a kw of children with initial clinical presentation of heavy proteinuria.

• Journal of Preventive Medicine and Public Health
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• v.22 no.1 s.25
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• pp.29-44
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• 1989

A household survey was conducted to determine the utilization rate of medical facilities and to identify the factors related with the utilization in the South District of Taegu from July 3 to July 15, 1988. Study population included 1,723 family members of 431 households which were selected by one-stage simple cluster random sampling. Well trained medical college students interviewed mainly housewives with a structurized questionnaire. Morbidity rate of acute illness during the 2-week period was 101 per 1,000 persons and it was highest in the age group of 9 years below. The rate for chronic illness was 77 per 1,000 persons, increasing with age, low income and medicaid benefit. During the 2-week period, 689 of 1,000 persons utilized the medical facilities. Of the facilities, most number, 294, used hospital and clinic, and the order ran as pharmacy, health center, and herb medical clinic. The utilization rate was higher in the female, 70-year and older group, medicaid group, the lowest income class and self-employed group than other groups. The average number of visits among users of medical facilities during the 2-week period was 3.25. those who visited medical facilities most frequently were females, the 70-year and older group, the lowest income class and blue collar worker group. During one-year period, admission rate of 1,000 persons was 27.6 and that of female was 38.9, higher than that of male. the eldest group had the highest admission rate. Admission rate of medical insurance beneficiaries was twice or higher than non-beneficiaries. The higher the family monthly income, the more frequently they admitted. During one-year period, average admission days of the persons hospitalized were 22.5 days and males were hospitalized longer than females. The groups which were hospitalized longest were those between the ages of 40 and 49, medical insurance beneficiaries, the lowest income group and unemployed group. During one-year period, average admission days of 1,000 persons were 560 days and those of female were 661 days, more than those of male. The guoups which had the longest admission days were those above 70 years of age, the lowest income and unemployed groups. The medical insurance beneficiaries were three times or longer than non-beneficiaries. In logistic regression analysis of utilization of physician significant independent variables were the 9-year and younger group(+), the 70-year and older group(+), acute illness episode(+), chronic illness episode(+), medical insurance beneficiary(+) and white collar workers(-). Acute and chronic illness episode(+), and medical insurance for government employees and private school teacher(-) were significant variables in analysis of utilization of pharmacy. In multiple regression analysis of the number of physician visits, siginificant variables were acute illnes episode(+), chronic illness episode(+), industrial, occupational and regional medical insurance beneficiary(+), white collar workers(-). Acute and chronic illness episode(+), and medical insurance beneficiary(-) were significant variables in analysis of the number of pharmacy visits. In logistic regression analysis of admission event, significant independent variables were the 9-year and younger group(+), the 70-year and older group(+) , chronic illness episode(+), and medical insurance beneficiary(+).

• Journal of radiological science and technology
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• v.33 no.1
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• pp.37-44
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• 2010

We sought to confirm an independent factor about in-stent restenosis (ISR) in the patients who underwent drug-eluting stent (DES) and know a possibility as a predictor of measured coronary artery calcium score by MDCT. A total of 178 patients (159 men, $61.7{\pm}10.0$ years of age) with 190 coronary artery lesions were included in this study out of 1,131 patients who underwent percutaneous coronary intervention (PCI) with DES implantation for significant stenosis on MDCT at Chonnam National University Hospital between May 2006 and May 2009. All lesions were divided into two groups with the presence of ISR : group I (re ISR, N = 57) and group II (no ISR, N = 133). Compared to group II, group I was more likely to be older ($65.8{\pm}9.0$ vs. $60.2{\pm}9.9$ years, p = 0.0001), diabetic (21.8% vs. 52.6%, p = 0.0001), have old myocardial infarction (8.8% vs. 2.3%, p = 0.040), left main stem disease (5.3% vs. 0.8%, p = 0.047), and smaller stent size ($3.1{\pm}0.3\;mm$ vs. $3.3{\pm}0.4\;mm$, p = 0.004). Group II was more likely to be smokers (19.3% vs. 42.1%, p = 0.003), have dyslipidemia (8.8% vs. 23.3%, p = 0.019). Left ventricular ejection fraction, lesion complexity, and stent length were not different between the two groups. Total CAC score was $389.3{\pm}458.3$ in group I and $371.2{\pm}500.8$ in group II (p = 0.185). No statistical difference was observed between the groups in CAC score in the culprit vessel, left main stem, left anterior descending artery, left circumflex artery, and right coronary artery. On multivariate logistic regression analysis, left main stem disease (OR = 168.0, 95% CI = 7.83-3,604.3, p = 0.001), male sex (OR = 36.5, 95% CI = 5.89-2,226.9, p = 0.0001), and the presence of diabetes (OR = 2.62, 95% CI = 1.071-6.450, p = 0.035) were independent predictors of ISR after DES implantation. In patients who underwent DES implantation for significant coronary stenosis on MDCT, ISR was associated with left main stem disease, male sex, and the presence of diabetes. However, CAC score by MDCT was not a predictor of ISR in this study population.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.77-82
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• 2008

Purpose: We evaluated the failure pattern of the celiac axis, gastric lymph node, and treatment outcome in the upper and mid-esophageal region of cancer patients treated by definitive radiotherapy, except when treating the celiac axis and gastric lymph node for treatment volume, retrospectively. Materials and Methods: The study constituted the evaluation 108 patients with locally advanced esophageal cancer receiving radiotherapy or a combination of radiotherapy and chemotherapy at Chonbuk National University Hospital from January 1986 to December 2006. In total, 82 patients treated by planned radiotherapy, except when treating the celiac axis and gastric lymph node for treatment volume, were analysed retrospectively. The study population consisted of 78 men and 2 women(mean age of 63.2 years). In addition, 51 patients received radiotherapy alone, whereas 31 patients received a combination of radiation therapy and chemotherapy. The primary cancer sites were located in the upper portion(17 patients), and mid portion(65 patients), respectively. Further, the patients were in various clinical stages including T1N0-1M0(7 patients), T2N0-1M0(18 patients), T3N0-1M0(44 patients) and T4N0-1M0(13 patients). The mean follow up period was 15 months. Results: The various treatment outcomes included complete response(48 patients), partial response(31 patients) and no response(3 patients). The failure patterns of the lymph node were comprised of the regional lymph node(23 patients) and the distance lymph node which included celiac axis and gastric lymph node(13 patients). However, metastasis was not observed in the regional and distant lymph node in 10 patients, whereas 36 patients were not evaluated. Furthermore, of the 13 patients who developed celiac axis and gastric lymph node metastases, 3 were in stage T1N0-1M0 and 10 were in stage T2-4N0-1M0. A complete response appeared in 12 patients, whereas a partial response appeared in 1 patient. The mean survival time of the patients who appeared for regional and distant lymph node metastasis was 14.4 and 7.0 months, respectively. Conclusion: In locally advanced esophageal cancer patients, who were treated by definitive radiotherapy without celiac axis and gastric lymph node irradiation, the distant lymph node metastasis rate was high and the overall survival rate was lower compared to the regional lymph node metastasis. The incidence of regional and distant lymph node metastasis was high in patients who appeared beyond clinical stage T2 and received radiotherapy alone.

• 한국유가공학회:학술대회논문집
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• 2007.09a
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• pp.49-58
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• 2007

Inflammatory process leads to the well-known mucosal damage and therefore a further disturbance of the epithelial barrier function, resulting abnormal intestinal wall function, even further accelerating the inflammatory process[1]. Despite of the records, etiology and pathogenesis of IBD remain rather unclear. There are many studies over the past couple of years have led to great advanced in understanding the inflammatory bowel disease(IBD) and their underlying pathophysiologic mechanisms. From the current understanding, it is likely that chronic inflammation in IBD is due to aggressive cellular immune responses including increased serum concentrations of different cytokines. Therefore, targeted molecules can be specifically eliminated in their expression directly on the transcriptional level. Interesting therapeutic trials are expected against adhesion molecules and pro-inflammatory cytokines such as TNF-${\alpha}$. The future development of immune therapies in IBD therefore holds great promises for better treatment modalities of IBD but will also open important new insights into a further understanding of inflammation pathophysiology. Treatment of cytokine inhibitors such as Immunex(Enbrel) and J&J/Centocor(Remicade) which are mouse-derived monoclonal antibodies have been shown in several studies to modulate the symptoms of patients, however, theses TNF inhibitors also have an adverse effect immune-related problems and also are costly and must be administered by injection. Because of the eventual development of unwanted side effects, these two products are used in only a select patient population. The present study was performed to elucidate the ability of TNF-${\alpha}$ antibodies produced in sheep colostrums to neutralize TNF-${\alpha}$ action in a cell-based bioassay and in a small animal model of intestinal inflammation. In vitro study, inhibitory effect of anti-TNF-${\alpha}$ antibody from the sheep was determined by cell bioassay. The antibody from the sheep at 1 in 10,000 dilution was able to completely inhibit TNF-${\alpha}$ activity in the cell bioassay. The antibodies from the same sheep, but different milkings, exhibited some variability in inhibition of TNF-${\alpha}$ activity, but were all greater than the control sample. In vivo study, the degree of inflammation was severe to experiment, despite of the initial pilot trial, main trial 1 was unable to figure out of any effect of antibody to reduce the impact of PAF and LPS. Main rat trial 2 resulted no significant symptoms like characteristic acute diarrhea and weight loss of colitis. This study suggested that colostrums from sheep immunized against TNF-${\alpha}$ significantly inhibited TNF-${\alpha}$ bioactivity in the cell based assay. And the higher than anticipated variability in the two animal models precluded assessment of the ability of antibody to prevent TNF-${\alpha}$ induced intestinal damage in the intact animal. Further study will require to find out an alternative animal model, which is more acceptable to test anti-TNF-${\alpha}$ IgA therapy for reducing the impact of inflammation on gut dysfunction. And subsequent pre-clinical and clinical testing also need generation of more antibody as current supplies are low.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.426-436
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• 2001

Background : Chronic obstructive pulmonary disease(COPD) is one of the major contributors to morbidity and mortality among the adult population. Cigarette smoking(CS) is undoubtedly the single most important factor in the pathogenesis of COPD. However, its mechanism is unclear. The current hypothesis regarding the pathogenesis of COPD postulates that an imbalance between proteases and antiproteases leads to the destructive changes in the lung parenchyma. This study had two aims. First, to evaluate the effect of CS exposure on histologic changes of the lung parenchyme, and second, to evaluate the effect of CS exposure on the expression of the gelatinolytic enzymes in BAL fluid cells in guinea pigs. Methods : Two groups of five guinea pigs were exposed to the whole smoke of 20 commercial cigarettes per day, 5 hours/day, 5 days/week, for 6weeks, and 12 weeks, respectively, using a smoking apparatus. Five age-matched guinea pigs exposed to room air were used as controls. Five or more sections were microscopically extamined(${\times}400$) and the number of cellular infiltration of the alveolar wall was measured in order to evaluate the effect of CS exposure on the histologic changes of lung parenchyme. The statistical significance was analyzed by a linear regression method. To evaluate the expression of the gelatinolytic enzymes in intraalveolar cells, BAL fluid was obtained and the intraalveolar cells were separated by centrifugation (500 g for 10 min at $4^{\circ}C$). Two sets of culture plates were loaded with $1{\times}10^6$ intraalveolar cells. One plate, contained O.1mM EDTA, a inhibitor of matrix metalloproteases(MMPs), and the other plate had no EDTA. Both plates were incubated for 48 hours at $37^{\circ}C$. After incubation, gelatinolytic protease expression in the supernatants was analyzed by gelatin zymography. Results : At the end of CS exposure, the level of blood carboxy Hb had increased significantly(4.1g/dl in control group, 24g/dl immediately after CS exposure, 18g/dl 30 min after CS exposure, 15g/dl 1 hour after CS exposure). Alveolar inflammatory cells were identified in the CS exposed guinea pigs. The number of alveolar cellular cells observed in a microscopic field ($400{\times}$) was $121.4{\pm}7.2$, $158.0{\pm}20.2$, $196.8{\pm}32.8$, in the control, the 6 weeks, and the 12 weeks group, respectively. The increased extent of inflammatory cellular infiltration of the lung parenchema showed a statistically significant linear relationship with the duration of CS exposure(p=0.001, $r^2=0.675$). Several types of gelatinolytic enzymes in the intraalveolar cells of CS exposed guinea pigs were expressed, of which some were inhibited by EDT A. However, the gelatinolytic enzymes were not expressed in the control groups. Conclusion : CS exposure increases inflammatory cellular infiltration of the alveolar wall and the expression of gelatinolytic proteases in guinea pigs. EDTA inhibits some of the gelatinolytic proteases. These findings suggest a possibility that CS exposure may increase MMP expression in the lungs of guinea pigs.

• Tuberculosis and Respiratory Diseases
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• v.50 no.4
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• pp.450-461
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• 2001

Background : The underlying pathogenesis of radiation-induced lung fibrosis (RTLF) has not been very well defined. However, the role of TGF-$\beta$ in the generation of RTLF has been a major focus because there is an increase in the expression of both the TGF-${\beta}m$-RNA and its protein preceding RTLF lesions. The down stream signal after a TGF-$\beta$ stimulated lung fibrosis includes the activation of many mediators such as Smad and c-Jun N-terminal kinase (JNK) through TAK1. It is we hypothesized that JNK activation may play a pivotal role in RTLF pathogenesis through increased transcription of the fibrogenic cytokines. The present study evaluates JNK activity in alveolar macrophages after irradiation and the relationship between JNK activity and the amount of collagen in the lung tissues. Methods : C57BL/6 mice(20-25 gr, males) received chlorotetracycline(2g/L) in their drinking water 1 week prior to irradiation and continuously there after. The mice were irradiated once with 1400 cGy of $60CO{\gamma}$-ray over the whole chest. The cellular composition of the whole lung bronchoalveoalr lavage fluids(BALF), elastin expression in the lung tissues, the level of hydroxyproline in lung tissues, and an in vitro JNK assay was measured before irradiation and one, four, and eight weeks after irradiation (RT). Results : The volumes of BALF retrieved from instilled 4 mL of saline with 2% heparin were 3.7-3.8 mL for each group. The cell numbers were similar before($4.1{\times}10^4{\pm}0.5{\times}10^4/mL$) and 1 week($3.1{\times}10^4{\pm}0.5{\times}10^4/mL$) after RT. At four and eight weeks after RT, the cell number reached to $14.0{\times}10^4{\pm}1.5{\times}10^4mL$ and $10.0{\times}10^4{\pm}1.3{\times}10^4/mL$, respectively. There we no changes in the lymphocytes and neutrophils population observed in the BALF after RT. The H-E stain of the lung tissues did not show any structural and fibrotic change in the lung tissues at 4 and 8 weeks after RT. In addition, the amount of elastin and collagen were not different on Verhoeff staining of the lung tissues before RT to eight weeks after RT. The hydroxyproine content was measured with the left lung dissected from the left main bronchus. The lung were homogenized and hydrolyzed with 6 N Hel for 12 hours at $110^{\circ}C$ then measured as previously described. The content of hydroxyproline, standardized with a lung protein concentration, reached a peak 4 weeks after RT, and thereafter showed a plateau. AnIn vitro JNK assay using c-$Jun_{1-79}$-GST sepharose beads were performed with the alveolar macrophages obtained from the BAL. JNK activity was not detected prior to RT, However, the JNK activity increased from one week after RT and reached a peak four weeks after RT. Conclusion : JNK may be involved in the pathogenesis because the JNK activity showed similar pattern observed with the hydroxyproine content. However, it is necessary to clarify that the JNK increases the transcription of fibrogenic cyiokines through the transcription factor.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.478-486
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• 2000

Background : In acute lung injury, alveolar macrophages play a pivotal role in the inflammatory process during the initiation phase and in the reconstruction and fibrosis process during the later phase. Recently, it has been proven that alveolar macrophages are constituted by morphologically, biochemically and immunologically heterogenous cell subpopulations. The possibility of alterations to these characteristics of the alveolar macrophage population during lung disease has been raised. To investigate such a possibility a hyperoxic rat lung model was made to check the distributional and morphological changes of rat alveolar macrophage subpopulation in acute hyperoxic lung injury. Method : Alveolar macrophage were lavaged from normal and hyperoxic lung injury rats and separated by discontinuous gradients of percoll. After cell counts of each density fraction were accessed, the morphomeric analysis of alveolar macrophages was performed on cytocentrifuged preparations by transmission electron micrograph. Result : 1. The total alveolar macrophage cell count significantly increased up to 24 hours after hyperoxic challenge (normal control group $171.6{\pm}24.1{\times}10^5$, 12 hour group $194.8{\pm}17.9{\times}10^5$, 24 hour group $207.6{\pm}27.1{\times}10^5$, p<0.05). oHoHH However the 48 hour group ($200.0{\pm}77.8{\times}10^5$) did not show a significant difference. 2. Alveolar septal thickness significantly increased up to 24 hours after hyperoxic challenge(normal control group $0.7{\pm}0.2{\mu}m$, 12 hour group $1.5{\pm}0.4{\mu}m$, 24 hour group $2.3{\pm}0.4{\mu}m$, p<0.05). However the 48 hour group did not show further change ($2.5{\pm}0.4{\mu}m$). Number of interstitial macrophage markedly increased at 24 hour group. 3. Hypodense fraction(fraction 1 and fraction 2) of alveolar macrophage showed a significant increase following hyperoxic challenge ($\beta=0.379$.$\beta=0.694$. p<0.05) ; however, fraction 3 was rather decreased following the hyperoxic challenge($\beta=0.815$. p<0.05), and fraction 4 showed an irregular pattern. 4. Electron microscopic observation of alveolar macrophage from each fraction revealed considerable morphologic heterogeneity. Cells of the most dense subfraction(fraction 4) were small, round, and typically highly ruffled with small membrane pseudopods. Cells of the least dense fraction (fraction 1) were large and showed irregular eccentric nucleus and high number of heterogenous inclusions. Conclusion : In conclusion, these results suggest that specific hypodense alveolar macrophage subpopulation may play a an important role in an acute hyperoxic lung injury model But further study, including biochemical and immunological function of these subpopulations, is needed.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.4
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• pp.361-368
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• 2010

Objective: The aim of this study was to evaluate the influences of uterine septum and their elimination on the reproductive outcomes in women who have history of recurrent spontaneous abortion (RSA) and/or infertility. Methods: The medical records of reproductive outcomes in patients who have had history of RSA and infertility who were diagnosed with uterine septum only by hysterosalpingogram (HSG) between January 2008 and December 2009 were retrospectively analyzed. The subjects who have had severe male factor, tubal factors, other uterine factors, endocrine abnormalities, peritoneal factors, and abnormal karyotyping among both partners were excluded. In 27 patients, confirmation of diagnosis by laparoscopy and elimination of uterine septum by trans-vaginal hysteroscopy was done. Seventeen patients were strongly suspected to uterine septum on HSG but tried to get pregnancy without any other procedure for evaluation and management of uterine anomaly. Age matched 42 patients who have history of RSA and/or infertility and diagnosed to normal HSG finding at same period were randomly selected as control. The medical records of reproductive outcomes were analyzed and compared between groups. Results: The mean time of observation after diagnosis was 21.8 months (10 to 32). 55.6% (15/27) of patients in patients who received trans-vaginal hysteroscopic uterine septotomy were success to get pregnancies and was significantly higher than that of 17 patients who did not receive proper management (23.5%, 4/17, p<0.05). In control population, 40.5% (17/42) were success to pregnancies and the differences were not statistically significant compared to both two study groups. The live birth rate which was excluded pregnancy loss by abnormal fetal karyotyping and congenital anomaly were 75% (9/12) in treated septated uterus group and 84.6% (11/13) in control group each which have no statistically significant different. In patients with septated uterus who did not receive proper management showed lower delivery rate (50%, 2/4) than that of other groups but was not statistically significant. Conclusion: According to present data, women with a uterine septum have an increased chance of successful pregnancy with improved obstetric outcome after proper management of the uterine cavity. And these results were showed in patients with no regard to their reproductive history. But, in case of failed to receive proper management, uterine septum can affect not only pregnancy ongoing but successful pregnancy too.