• Development and Reproduction
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• v.10 no.1
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• pp.1-7
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• 2006

Ovarian follicular atresia in mammals is finely regulated by gonadotropins and sex steroid hormones. It is well known that granulosa cell pyknosis is a common cytological feature of atretic follicles in the ovary. The present study hypothesized that granulosa cell pyknosis during follicular atresia might be related to apoptotic process and associated with caspase-3 activation. Healthy (normal) and atretic follicles were isolated from porcine ovaries based on macro-morphological criteria. Isolated follicles were either processed for histological observation or used for collection of granulosa cells by aspiration. Hoechst 33258 staining of the cells showed a significantly higher number of fragmented nuclei, a typical morphological feature of apoptotic cell, in granulosa cells from atretic follicles than those from healthy follicles. In addition, the rate of cell death was significantly higher in granulosa cells from atretic follicles than healthy follicles, as measured by flow-cytometric cell cycle analysis. In situ detection of apoptotic cells by TUNEL revealed that apoptosis was mostly restricted to granulosa cells in follicles. Theca cells were TUNEL-negative. Finally, it has been shown by caspase-3 activity assay that granulosa cells from atretic follicles retain a higher caspase-3 activity compared to healthy follicles. Taken together, it is suggested that granulosa cell degeneration during folliclar atresia occurs by caspase-3-dependent apoptotic fashion.

• Development and Reproduction
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• v.15 no.4
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• pp.373-383
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• 2011

Tributyltin (TBT) is one of endocrine disrupters which are known as having similar function to sex steroid hormone inducing apoptosis in various tissues of rodents. Recently, it has been reported that TBT induces apoptosis in thymus causing the decreased thymic function, but little is known about the mechanism. To elucidate the mechanism, three-week-old SD female rats were orally administrated with TBT 1, 10, and 25 mg per body weight (kg) and sesame oil as a control for 7 days. On day 8, the thymi were obtained and weighed, and then the number of thymocytes was counted. We also performed H&E staining, TUNEL assay, and Annexin V flow cytometric analysis to examine the apoptosis rates and the structure in the thymus. Next, we investigated the adipogenesis and apoptosis-related mRNA expression levels in the thymi by real-time PCR. The thymic weight and the number of thymocytes were decreased by TBT in a dose-dependent manner. As a result of the H&E staining, the boundary between cortical and medullary area was blurred in the thymi of TBT treated rats compared to those of controls. In the results of TUNEL assay and Annexin V flow cytometric analysis, apoptosis rates in the thymus were increased after TBT treatment. The expression levels of thymic epithelial cell marker genes such as EVA, KGF, AIRE, and IL-7 were significantly decreased in the thymi of TBT treated rats, but $PPAR{\gamma}$, aP2, PEPCK, and CD36 were significantly increased. The expression of $TNF{\alpha}$ and TNFR1 as apoptosis-related genes also was significantly increased after TBT treatment. The present study demonstrates that TBT can increase the expression of adipogenesis and apoptosis-related genes leading to apoptosis in the thymus. These results suggest that the increased adipogenesis of thymus by TBT exposure might induce apoptosis in the thymus resulting in a loss in thymic immune function.

• Korean Journal of Poultry Science
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• v.41 no.4
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• pp.287-296
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• 2014

Chicken eggs undergo various physiological changes during egg maturation. To study genes associated with the egg maturation in pre-ovulation (immature) and post-ovulation (mature), we compared gene expression patterns between in the immature egg and mature egg using RNA sequencing data. Mature and immature eggs were obtained from a Heuksaek Jaerae-jong of Korean native chicken. Total RNAs obtained from the eggs were sequenced by Illumina HiSeq 2000 platform, and the generated sequence reads were mapped to Galgal4 reference sequence assembly using Tuxedo Protocol. From the comparison of the RNA sequencing data, 315 genes were differentially expressed between mature and immature eggs, and 46 genes were only detected in immature egg. Further gene ontology (GO) analysis was performed for the differentially expressed genes using DAVID, showing that 29 and 28 GO terms were independently clustered from mature and immature, respectively. From those clustered GO terms, genes related to germ cell development, sex differentiation and defense response to bacterium were mainly expressed in the immature egg, while genes related to regulation of apoptosis, steroid metabolic process and lipid homeostasis were mainly detected in the mature egg. Our results could contribute to understand egg maturation before and after ovulation, and develop genetic markers for improving egg quality and productivity.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.144-151
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• 1994

Background: Miliary tuberculosis almost always results from the discharge of infected caseous material into the blood stream, usually from a well hidden lymph node in the presentation of this disease in the past four decades, and although it is seen less frequent1y today than previously, its presentation and manifestation may require greater suspicion and diligence by the physician. We investigated the clinical characteristics, predisposing factors and accompanying diseases of miliary tuberculosis and tried to acquire the early diagnosis and treatment of this disease. Methods: A retrospective clinical study was done on 40 cases of miliary tuberculosis admitted to Hanyang University Hospital from Mar. 1989 to Dec.1992. The study investigated age and sex distribution, seasonal distribution, duration of symptoms before admission, pre-disposing factors, clinical symptoms, biochemical findings, chest X-ray findings, extrapulmonary tuberculosis associated with miliary tuberculosis, prognosis and mortality rate. Results: 1) The patients were most common in the age group between 20 and 29(23%) and the ratio of male to female was 1.4:1(male 23 : female 17). 2) Sputum smears for tubercle bacilli were positive in 5 cases(13%). 3) The most common clinical symptoms were fever with chilling(47.5%), coughing(47.5%), second most common symptom was dyspnea(32.5%), and the physical findings on admission were tachycardia(30%), weight loss(27.5%), meningeal signs(17.5%) in order. 4) The predisposing factors were heavy alcohol drinking(6 cases), steroid use(3 cases), pregnancy(2 cases) etc. 5) The chest X-ray findings on admission were miliary shadow only(40%), in addition pneumonic infiltration, pleurisy, and calcification in order. 6) The extrapulmonary tuberculosis associated with miliary tuberculosis were tuberculous meningitis(30%), bone and joint tuberculosis(17.5%), intestinal tuberculosis(15%) in order. 7) Biochemical findings were increased SGOT/SGPT(32.5%), increased alkaline phosphatase(32.5%), hypoalbuminemia(15%), hyponatremia(15%) etc. 8) About 4-6 weeks later after treatment(INH, RFP, PZA, EMB), 26 cases(65%) were improved on clinical symptoms or chest X-ray, 12 cases(30%) were stationary or aggravated, and 2 cases(5%) were died. Conclusion: For the early diagnosis and treatment of miliary tuberculosis, we must see its presentation and manifestation with greater interest and suspicion and investigate its predisposing factors and accompanying diseases.

• Clinical and Experimental Pediatrics
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• v.50 no.7
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• pp.636-642
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• 2007

Purpose : Fluconazole prophylaxis for very low birth weight (VLBW) infants has been shown to reduce invasive fungal infection and its mortality. This study aims to evaluate the effect of fluconazole prophylaxis in VLBW infants on the incidence and mortality of fungal infection. Methods : VLBW infants with endotracheal intubation and central vascular access admitted to the Neonatal Intensive Care Unit (NICU) at Chonnam University Hospital were enrolled. Twenty eight infants of 7-month baseline period from January to July 2005 ('non-fluconazole group') were compared with 29 infants of a 7-month fluconazole period from January to July 2006 ('fluconazole group'). Results : Gestational age, birth weight, sex, mode of delivery, frequency of twin pregnancy, chorioamnionitis, antenatal steroid and rupture of membranes were similar between the fluconazole and non-fluconazole groups. The rate of extremely low birth weight (ELBW) infants, frequency and duration of prophylactic antibiotics, total parenteral nutrition and umbilical catheters, duration of intralipid, mechanical ventilation and nasal continuous positive airway pressure (CPAP) were also not significant. However, frequency of percutaneous central venous catheterization (PCVC) and intralipid administration, and duration of PCVC were significant between the two groups. The overall incidence and mortality of fungal infection were not different between the two groups. Although the Malassezia infection was increased in the fluconazole group (P<0.05), candida was significantly decreased compared to the non-fluconazole group (P<0.05). Conclusion : Fluconazole prophylaxis in high risk VLBW infants decreased the candida infection significantly. Antifungal prophylaxis is recommended in terms of cost effectiveness, but further study is needed to clarify the reason for the increase of Malassezia infection.

• Journal of Chest Surgery
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• v.32 no.3
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• pp.281-286
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• 1999

Background: The purpose of this study is to analyze the types of complications, the incidences of complications, and preoperative and postoperative risk factors affecting the incidence of the complication. Material and Method: Between August 1990 and August 1997 in Asan Medical Center, 42 patients(24 men and 18 women) underwent surgical resection for pulmonary aspergilloma. The mean age was 46.6${\pm}$11.5 years(range 29 to 69 years). Hemoptysis(90%) was the most common presentation. Pulmonary tuberculosis was the most common predisposing cause(81%). The associated diseases were bronchiectasis(n=11), active puolmonary tuberculosis(n=9), diabetes mellitus(n=8), lung carcinoid(n=1), and acute myeloblastic leukemia(n=1). Lobectomy was done in 32 cases(76%), segmentectomy or wedge resection in 4, pneumonectomy in 2, and lobectomy combined with segmentectomy in 4. Result: Operative mortality was 2%. The most common postoperative complication was persistent air leakage(n=6). The variables such as age, sex, pulmonary function test, amount and duration of hemoptysis, associated diseases(diabetes mellitus, active pulmonary tuberculosis), mode of preoperative management(steroid, antifungal agent, bronchial arterial embolization), and modes of operative procedures were statistically insignificant. The radiologic extent of infiltration to normal lung parenchyme was statistically significant(p=0.04). Conclusion: We conclude that the extent of the infiltration to normal lung parenchyme in preoperative radiologic studies should be carefully evaluated to reduce the postoperative complications in surgery for pulmonary aspergilloma.

• Childhood Kidney Diseases
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• v.7 no.2
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• pp.133-141
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• 2003

Purpose : Idiopathic Membranous Nephropathy(IMN) is a rare renal disease in children. To help better understanding of its clinical course and treatment strategies, we reviewed the clinical manifestations and pathological findings of children with IMN. Methods : Among 58 cases with MN, from 1977 to 2003, 42(72.4%) were hepatitis B virus (HBV) associated and 16(27.6%), 6 males and 10 females, were idiopathic. All cases diagnosed aster 2000 were IMN. Several clinicopathological findings(sex, onset age, proteinuria, serum albumin, cholesterol, creatinine clearance, tubulointerstitial changes, glomerular sclerosis, hypertension, renal vein thrombosis, the use of ACE inhibitor, and immunosuppressive therapy) were compared between the remission and the non-remission group of the patients with IMN. Results : The median onset age was 13.4 years. Clinical manifestations were nephrotic syn-drome(7 cases, 43.8%), gross hematuria(5 cases, 31.3%) and microscopic hematuria with proteinuria(3 cases, 18.8%). Hypertension, hypocalcemic tetany and renal vein thrombosis were accompanied in 2, 1 and 2 cases, respectively. In addition to the typical findings of MN, the kidney biopsies showed segmental sclerosis(5 cases, 31.3%) or global sclerosis(6 cases, 37.5 %), diffuse crescents(1 case), and mild(11 cases, 68.7%) or moderate tubulointerstitial changes(3 cases, 18.8%). Thirteen cases(86.7%) received oral steroid. Among them 2 cases received cyclophophamide and 1 received cyclosporin as well. Ten cases(62.5%) received ACE inhibitors. In the patients followed up, 7 cases(46.7%) became free from proteinuria (remission group) while 8(53.3%) presented continous proteinuria (non-remission group), two (13.3%) of which progressed to renal failure. Clinicopathological findings showed no significant differences between the two groups. Conclusion : With HBV vaccination, HBV associated MN decreased markedly and IMN has taken up most of MN in children. For better understanding of this rare disease, a prospective multicenter study of the clinical course and treatment strategies should be done.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.535-547
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• 1995

Background: Intensive care units(ICUs) probably represent the single largest identifiable source of infection within the hospital. Although there are several studies on ICU infections in respect to their bacteriology or mortality rate for individual types of ICU, few studies have compared ICU infections between different types of ICU. The aim of this study was to identify clinical differences in bacteremia between medical ICU(MICU) and surgical ICU(SICU) patients. Methods: 256 patients with bacteremia were retrospectively evaluated. Medical records were reviewed to obtain the clinical and bacteriologic informations. Results: 1) The mean age of the patients with bacteremia of MICU($58.6{\pm}17.2\;yr$) was greater than that of all MICU patients($54.3{\pm}17.1\;yr$)(p<0.01), but there was no significant difference in SICU patients(patients with bacteremia of SICU: $56.3{\pm}18.6\;yr$, all SICU patients: $62.0{\pm}16.8$)(p>0.05). ICU stay was longer(MICU patients: $23.4{\pm}40.8$ day, SICU patients: $30.3{\pm}26.8$ day) than the mean stay of all patients($6.8{\pm}15.5$ day)(p<0.05, respectively). Bacteremia of both ICU patients developed past the average day of ICU stay(all MICU patients: 7.9 day, all SICU patients: 6.0 day, MICU bacteremia: 19th day, SICU bacteremia: 17th day of ICU stay)(p<0.05, respectively). 2) There were no significant differences in mean age, sex, and length of stay of both ICU patients with bacteremia. 3) Use of antibiotics or steroid, use of percutaneous devices and invasive procedures before development of bacteremia were more frequent in SICU patients than in MICU patients(prior antibiotics use: MICU 45%, SICU 63%, p<0.05; steroid use: MICU 14%, SICU 36%, p<0.01; use of percutaneous devices: MICU 19%, SICU 39%, p<0.01; invasive procedures: MICU 19%, SICU 61 %, p<0.01). 4) The prevalence of community acquired infections was significantly higher in MICU patients than in SICU patients(MICU 42%, SICU 9%)(p<0.01), whereas SICU patients showed higher prevalence of ICU-acquired infection than MICU patients(MICU 48%, SICU 78%)(p<0.01). 5) There were no differences in causative organisms, primary sites of infection and time interval to bacteremia between both ICUs. 6) There were no significant differences in outcome according to pathogenic organisms or primary sites of infection. 7) The mortality rate was higher in patients with bacteremia than without bacteremia(MICU mortality rate: patients with bacteremia 72.5%, patients without bacteremia 36.0%, p<0.01; SICU mortality rate: patients with bacteremia 40.3%, patients without bacteremia 8.5%, p<0.05), and the mortality rate of MICU bacteremia was significantly higher compared with that of SICU bacteremia(MICU 72.5%, SICU 40.3%)(p<0.01). Conclusion: ICU patients with bacteremia stayed longer before the development of bacteremia, and showed higher mortality than the overall ICU population. The incidence of bacteremia was higher in MICU patients than SICU patients. MICU patients with bacteremia showed higher prevalence of liver diseases and acute respiratory failure, community-acquired bacteremia and greater mortality rate than SICU patients with bacteremia. SICU patients with bacteremia, on the other hand, showed higher prevalence of trauma, prior use of immunosuppressive agents, invasive procedures, and ICU-acquired bacteremia, and lower mortality rate than MICU patients with bacteremia.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.130-144
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• 1999

Purpose : Long-term use of Cyclosporine(CsA) reduce renal blood flow by afferent arteriolar vasoconstriction and lead to chronic pathologic changes of CsA nephrotoxicity - 1) interstitial nephritis(IN); tubular atrophy (TA) and/or interstitial fibrosis(IF),2) arteriolopathy(AP). The Object of this study is to estimate the incidence of chronic pathologic CsA nephrotoxicity by duration of treatment and type of renal disease, relationship between histologic and clinical nephrotoxicity, and optimal duration of CsA therapy. Methods : 102 children with steroid resistant or dependent nephrotic syndrome confirmed by renal biopsy and treated with CsA from 1986 to 1997 were enrolled in this study(58 MCNS, 10 FSGS, 10 MGN, 15 $Henoch-Sch\"{o}nlein$ purpura nephritis with nephrotic syndrome (HSPN) and 9 IgA nephropathy with nephrotic syndrome(IgAN)). CsA was administered for 1yr, 1.5yr, 2yr in 24, 12, 22 MCNS patients and 2, 2, 6 FSGS patients respectively, 1yr, 2yr in MGN and 1yr in HSPN and IgAN. Sequential biopsies were done in all 102 patients after CsA treatment for evaluation of pathologic nephrotoxicity. Results : Complete remission rate was 92.2% (100% in MCNS and MGN, 80% in FSGS, 86.6% in HSPN and 55.5% in IgAN). Incidence of relapse during 6months after CsA treatment was significantly decreased compaed with relapsing spisodes during 6months before CsA treatment in MCNS(P<0.0001) and FSGS(P<0.0001). According to pathologic changes, 71 patients(69.6%) showed no pathological change, 24 patients(23.5%) showed IN and 7 patients(6.8%) showed AP. IN was 16.6%, 33.3%, 27.2% in 1, 1.5, 2 year of CsA treatment group in MCNS. AP was 0%, 16.6%, 9% in 1, 1.5, 2 year of CsA treatment group in MCNS. 14 out of 58 MCNS(24.1%) showed IN and 4 out of 58 MCNS(6.8%) showed AP. Incidence of pathologic change was significantly lower in CsA therapy of <1yr than >1yr(P=0.03). There were no significant difference of incidence of pathologic change in original renal disease, age and sex. Conclusion : Duration of CsA treatment was significant risk factor for nephrotoxicity and optimal duration seemed to be 1 year. Pathologic change due to nephrotoxicity did not correlate with deterioration of renal function and only detectable by renal biopsy.