• Journal of Food Hygiene and Safety
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• v.6 no.1
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• pp.1-12
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• 1991

Fischer 344 rats aged six weeks were diYided into four groups and group 1, 2, and 3 of rats were given an intraperitoneal injection of diethylnitrosamine at 200 mg/kg body weight and group 4 was given saline alone. Two weeks after beginning of the experiment, group 1 and 2 of rats were begun to feed on diets containing 0.02% 2-acetylaminofluorene as a promoter for four weeks. Three weeks after beginning of the experiment, all groups were performed partial hepatectomy. During the last two weeks, group 1 and 3 of rats were received subcutaneously 3 consecutive weekly doses of iron dextran at 0.125 ml/100 g body weight. Subcutaneous injection of iron dextran resulted in hepatic siderosis in group 1 and 3 of rats. Pre neoplastic nodules were identified histopathologically by two markers, resistance to exogenous iron accumulation and glutathione S-transeferase placental form (GST-P) activity, while early carcinogen induced foci were hardly resistant to iron accumulation and though a few lesions were identified, it could hardly be distincted from normal hepatocytes of surroundings. However, GST-P positive nodules as well as foci were clearly distincted from normal hepatic cells of surroundings. In the quantitative analysis of carcinogen-induced nodules and foci, more lesions were detected by immunohistochemical method for GST-P than by prussian blue staining for resistant to iron accumulation. It is concluded that immunohistochemical marker for GST-P is more sensitive and reliable than iron-resistance marker, and that iron-resistance is not useful marker for early detection of carcinogen-induced hepatic lesions.

• Tuberculosis and Respiratory Diseases
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• v.56 no.5
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• pp.505-513
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• 2004

Background : In lung cancer patients, the presence of metastatic neck nodes is a crucial indicator of inoperabilty. So thorough physical examination of neck is always mandatory, but sometimes those are hardly palpable even by the skillful hand. Ultrasonography is a useful diagnostic method in detection of small impalpable lymph nodes and in guidance of fine needle aspiration biopsy. In this study we evaluated the clinical usefulness of ultrasonography(USG) and ultrasound-guided fine needle aspiration cytology(US-FNA) in lung cancer patients without palpable neck nodes. Methods and Materials : From Sep 2002 to Sep 2003, 36 non-small cell lung cancer patients (20 adenocarcinoma, 16 squamous cell cancer) and 10 small cell lung cancer patients without palpable neck nodes on physical examiation were enrolled. patients who had contralateral mediastinal nodal enlargement(>1cm) on chest CT were excluded. After the routine check of USG on the neck, US-FNA was done in cases with enlarged neck nodes (${\geq}5mm$ in the short axis). The presence of enlarged lymph node on USG, and of malignant cells on cytology were evaluated by the histological type and the patients' clinical stage of lung cancer. Results : Among 36 non-small lung cell cancer patients, 14 (38.8%) had enlarged neck nodes on USG, and 5 of 10 small cell lung carcinoma patients. The mean diameter of the neck nodes was 9.8 mm (range, 7-12 mm). US-FNA of 14 non-small cell lung cancer patients revealed tumor cells in eight patients (57.1%). In 5 small cell lung cancer pateints, tumor cells were found in all cases. By the result of US-FNA, the clinical stage of 8 out of 36 (22.2%) non-small cell lung cancer patients had changed, including two cases of shift from the operable IIIa to the inoperable IIIb. In small cell lung cancer patients their clinical stage was not changed after US-FNA, but their pathological diagnosis was easily done in two cases, in whom endobronchial lesions were not found on bronchoscopy. Conclusions : USG and US-FNA of neck node seem to be safe, sensitive and cost-effective diagnostic tools in the evaluation of lung cancer patients without palpable neck nodes.

• Development and Reproduction
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• v.13 no.2
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• pp.105-114
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• 2009

Ethane 1,2-dimethane sulfonate (EDS) is a well-known alkylating agent used as selective Leydig cell (LC) toxicant to create a testicular dysfunction model. Previous studies including our own clearly demonstrated the dramatic weight loss of the androgen dependent accessory sex organs such as epididymis, seminal vesicle and prostate gland in this 'LC knock-out' rats. The present study was performed to evaluate the effect of EDS administration on histological changes of the epididymis, seminal vesicle and prostate in adult rats. Adult male Sprague-Dawley rats (350$\sim$400 g B.W.) were injected with a single dose of EDS (75 mg/kg, i.p.) and sacrificed on weeks 0, 1, 2, 3, 4, 5, 6 and 7. Tissue weights (testis, epididymis, seminal vesicle and prostate gland) were measured. The histological changes of tissue were observed by a light microscopy using hematoxylin & eosin staining. Weights of the reproductive and accessory organs progressively declined after the EDS treatments (weeks 1, 2 and 3). After this, the decrease was stopped, then gradually returned to the normal levels. There was a partial (about 60%) recovery of the epididymis weight during weeks $6{\sim}7$. The cross section of epididymis revealed an increase in thickness of the epithelium during weeks $1{\sim}3$. In contrast, considerable reduction of epithelial thickness in seminal vesicle was observed during same period. Similarly, a reduction in thickness of prostate epithelial layer was found during weeks $1{\sim}3$, then it was back to normal thickness after week 4. Taken together, the present study demonstrated that the temporally induced androgen-deficiency by EDS treatment could result the prominent alterations in histology of the accessory sex organs. Further studies on the physiological and molecular regulation of these androgen-sensitive organs using EDS model will be helpful to understand the normal and pathological development and differentiation mechanism of these organs.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.323-334
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• 1996

Male Mongolian gerbils $(60{\sim}80g)$ were given DL-difluoromethylornithine (DFMO; 250mg/kg, ip) and methylglyoxal bis(guanylhydrazone) (MGBG; 50 mg/k, ip), respectively, 1 h prior to transient (7 min) occlusion of bilateral common carotid arteries (OBC7) and a daily dose of one of them for 6 days after recirculation, and the polyamine contents, activities of ornithine and S-adenosylmethionine decarboxylases (ODC and SAM-DC), and light microscopic findings of the hippocampus were evaluated. The hippocampal putrescine (PT) levels of the control gerbils treated with saline (STGr), markedly increased after OBC7, showing a peak level at 24 h after recirculation. The peak PT level was reduced in DFMO treated gerbils (DTCr) and in MGBG treated gerbils (MTGr). And 7 days after recirculation, the PT level of DTGr was decreased to about 75% of the PT level in the sham operated group (nonTGr) and to about 55% of the STGr level, respectively. The hippocampal spermidine (SD) level of STGr tended to decline, showing the lowest value at 8 h after recirculation. But the spermidine (SD) level of DTGr was somewhat higher at 8 h after OBC7 than those of STGr and MTGr The hippocampal spermine (SM) levels of all the experimental groups were little changed for 7 days after OBC. OBC7 markedly increased the hippocampal ODC activity. reaching a maximum (about 3 times higher than preischemic level) at 8 h and rapidly recovered to the control value by 24 h in STGr gerbils, and the OBC7-induced increase of ODC activity was significantly attenuated by DFMO or MGBG treatment. Whereas OBC7 induced a rapid decrease of the hippocampal SAMDC activity follwed by gradual recovery to the preischemic level, and the decrease of the SAMDC activity was slightly attenuated by DFMO or MGBG treatment. 7 Days after OBC7 the histological finding of the hippocampal complex stained with cresyl violet showed an extensive delayed neuronal damage in the CA1 region and to a lesser extent, in the dentate gyrus, sparing the CA3 region. And the neuronal death was aggevated by DFMO but significantly attenuated by MGBG. The immunochemical reactivity of hippocampus to anti-GFAP antibody was significantly increased in the CA1 region and to a lesser extent, in the dentate gyrus 7 days after OBC7, but was little changed in the CA3. And the increase of the anti-GFAP immunoreactivity was moderately enhanced by DFMO and significantly suppressed by MGBG. These results suggest that the polyamine metabolism may play a modulatory role in the ischemic brain damage.

• Development and Reproduction
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• v.14 no.4
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• pp.287-295
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• 2010

It was recently reported that nesfatin-1/NUCB2, which is secreted from the brain, controls appetite and energy metabolism. The purpose of this research was to confirm whether or not the protein and its binding site should have been expressed in the mouse reproductive organs and to know the possible effects of nesfatin-1 on the reproductive function. Using the ICR female mouse ovary and uterus, the expression of NUCB2 mRNA was confirmed with the conventional PCR and the relative amount of NUCB2 mRNA in the tissues was analyzed with real-time PCR. Immunohistochemical staining was performed using the nesfatin-1 antibody to investigate the nesfatin-1 protein expression and the biotin conjugated nesfatin-1 to confirm the binding site for nesfatin-1 in the ovary. Furthermore, in order to examine if the expression of NUCB2 mRNA in the ovary and uterus is affected by gonadotropin, its mRNA expression was analyzed after PMSG administration into mice. As a result, the expression level of NUCB2 mRNA in the ovary and the uterus was as much as the expression level in hypothalamus. As a result of the immunohistochemical staining, nesfatin-1 proteins were localized at the theca cells, the interstitial cells, and some of the luteal cells. However, the granulosa cells in the follicles did not stain. Interestingly, the oocytes in the some follicles were stained with nesfatin-1. On the other hand, nesfatin-1 protein binding sites were displayed at the theca cells and the interstitial cells near the tunica albuginea. After PMSG administration the expression level of NUCB2 mRNA was increased in the ovary and the uterus. These results demonstrate that for the first time the nesfatin-1 and its binding site were expressed in the ovary and NUCB2 mRNA expression was controlled by gonadotropin, suggesting an important role in the reproductive organs as a local regulator. Therefore, further study is needed to elucidate the functions of nesfatin-1 on the reproductive organs.

• Development and Reproduction
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• v.14 no.4
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• pp.281-286
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• 2010

Recent evidence has revealed that the intratesticular injection of hypertonic saline(20%) resulted in a chemically castrated state such as nadir testosterone levels in rats. To confirm the efficacy of this simple saline-injection method further, we investigated the changes in the gross and microscopic anatomy of testis. Our study comprised three groups; intact(control) group, orchidectomy group and saline-injection (experimental) group. Single dose of hypertonic saline (sterilized, $750{\mu}{\ell}/testis$) were directly administered into both testis of adult rats (about 300 g BW). Bilateral orchidectomy was performed at the same day of saline injection. Following 30 days post-injection, reproductive tissues were surgically removed, weighed and fixed for histological examination. The body weights were not changed in both orchidectomy group and saline-injection group when compared to those in intact group. The wet weights of testis were significantly decreased in saline-injection group when compared to those in intact group. The wet weights of epididymis and seminal vesicle and prostate were significantly decreased in orchidectomy group and saline-injection group when compared to those in intact group. Macroscopically, the testes exerted slight atrophy and the tunica albuginea seemed to be intact in saline injection group. Histologically, however, larger parts of testicular tissue underwent necrosis and were barely recognizable after hematoxylin-eosin staining. In the same section, only the opposite part of the injection site was stained showing abnormal state of cell layers mostly fibrosis and infiltrated leukocytes. Sloughing of immature germ cells from the basement membrane along with shedding cells in the intraluminal space was notable in most seminiferous tubules from the saline injected testis. The present study confirmed that the direct injection of hypertonic saline into testis can induce a castration-like, testosterone-depriving effects on accessory sex organs. Our findings suggest that the efficacy of this less expensive and minimally invasive method seems to be almost even with that of conventional orchidectomy and chemical castration, though more in-depth evaluation should be supported.

• Radiation Oncology Journal
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• v.25 no.4
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• pp.193-200
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• 2007

Purpose: This study evaluated the pretreatment expression patterns of MDM2, p53, and pRb proteins to determine if the expression patterns could predict the outcome of concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma and aid in the decisions for the selection of treatment modalities. Materials and Methods: Fifty-one patients that were treated with definitive chemoradiotherapy for stage $I{\sim}IVa$ esophageal squamous cell carcinoma were selected for this study. Radiotherapy was administered with daily $1.8{\sim}2\;Gy$ fractions up to a median dose of 54 Gy for primary tumors, and with four cycles of cisplatin/5-fluorouracil chemotherapy that was administered every 4 weeks, the first two cycles of which were administered concurrently with radiotherapy. Expression of MDM2, p53, and pRb was investigated by immunohistochemical analysis using pretreatment biopsy specimens. Results: MDM2, p53, and pRb were detected with high immunoreactivity in 19.6%, 27.5%, and 66.7% of the patients, respectively. However, there was no significant correlation between expression of these factors and clinical outcome. By the use of multivariate analysis with nine covariates-age, tumor location, tumor length, stage, pathological response, clinical response, MDM2 expression, p53 expression, and pRb expression, only pathological response and stage were significant factors for cause-specific survival. Conclusion: Expression of MDM2, p53, and pRb was not found to be clinically significant for predicting outcomes after CCRT in this study. Further studies with a larger patient population and longer follow-up periods are needed to re-evaluate the expression pattern and to identify new predictors for CCRT response.

• Journal of Gastric Cancer
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• v.5 no.3 s.19
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• pp.200-205
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• 2005

Purpose: KLF4, a member of the KLF family, is a zinc finger tumor suppressor protein that is critical for gastric epithelial homeostasis. Our aim was to determine whether the altered expression of KLF4 might be associated with gastric cancer development and, if so, to determine to which pathologic parameter it is linked. Materials and Methods: For the construction of the gastric cancer tissue microarray, 84 paraffin-embedded tissues containing gastric cancer areas were cored 3 times and transferred to the recipient master block. The expression pattern of KLF4 was examined on tissue microarray slides by using immunohistochemistry and was compared with pathologic parameters, including histologic type, depth of invasion, lymph node metastasis, and peritoneal dissemination. Results: The KLF4 protein was expressed in cytoplasm and nucleus of superficial and foveolar epithelial cells in the normal gastric mucosa. We found markedly reduced or loss of KLF4 expression in 43 (51.2%) of the 84 gastric cancer tissues. There was no significant correlation between KLF4 expression and pathologic parameters, including histologic type, depth of invasion, lymph node metastasis and peritoneal dissemination. Conclusion: Our findings suggest that altered expression of KLF4 may contribute to abnormal regulation of gastrointestinal epithelial cell growth and differentiation and to the development of Korean gastric cancer, as an early event.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.607-614
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• 2001

Background : Residual pleural thickening is frequently seen following treatment for tuberculous pleurisy, and pleural decortication is performed occasionally in patients with severe residual pleural thickening. However, predictive factors for the development of residual pleural thickening are uncertain at the initial diagnosis of the tuberculous pleurisy. Therefore, the purpose of this study was to identify the associated factors for residual pleural thickening at initial diagnosis. Methods : We separated 63 patients diagnosed as tuberculous pleurisy into two groups; group 1 consisted of patients without residual pleural thickening and group 2 comprised patients with residual pleural thickening at the end of tuberculous pleurisy treatment. We analyzed the clinical characteristics, radiological findings, pleural biopsy and characteristics of pleural fluid between group 1 and group 2. Results : The study population and clinical symptoms of the two groups were not significantly different and the duration of symptoms before treatment and the peripheral WBC were similar between the two groups. The presence of pulmonary tuberculosis, pleural fluid loculation or the amount of pleural effusion sid not differ significantly between the two groups. The incidence of positive AFB staining(group 1 : 8%, group 2 : 38%) and granuloma(group 1 : 30%, group 2: 62%)on pleural biopsy specimens was significantly higher in group 2 than in group 1. Pleural fluid WBC and differential count, adenosine deaminase level, pH, protein level or glucose level did not differ between the two groups. However, group 2 had higher LDH levels ($1370{\pm}208mg/dL$) than group 1 ($860{\pm}71mg/dL$, p<0.05). Conclusion : In tuberculous pleurisy, patients with residual pleural thickening following treatment demonstrated a higher incidence of positive AFB staining and granuloma on the pleural biopsy specimens or higher LDH level in the pleural fluid than patients without residual pleural thickening From these results, we speculate that the amount of tuberculous bacilli and granuloma are probably correlated with residual pleural thickening in the tuberculous pleurisy.

• Tuberculosis and Respiratory Diseases
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• v.47 no.3
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• pp.331-338
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• 1999

Background: Nearly 10% of cancer patients will develop a second primary cancer within ten years after surgical removal of the primary tumor. The detection of risk factors for developing multiple primary tumors would be important This study was conducted to evaluate the clinical characteristics and abnormal p53 expression of lung cancer associated with multiple primary cancer(MPC). Method: Clinical characteristics and abnormal p53 expression were compared between 20 cases of lung cancer(NSCLC ; 16 cases, SCLC ; 4 cases) associated with MPC and 26 cases of primary non-small cell lung cancer. Result: MPC associated with lung cancer was gastric cancer(8), lung cancer(2), esophageal cancer(2), colon cancer(2), laryngeal cancer(1), bladder cancer(1), small bowel cancer(l), adrenal cancer(1), hepatocellular carcinoma(1), and breast cancer (1) in order. The clinical stage of primary NSCLC was relatively advanced, but NSCLC associated with MPC was even distribution at each stage. The detected incidences of abnormal p53 expressions were 62.5% in NSCLC associated with MPC and 76.9% in primary NSCLC(p>0.05). Conclusion: There was no difference in abnormal p53 expression between non-small cell carcinoma associated with multiple primary cancer and primary non-small cell carcinoma.