• Journal of Life Science
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• v.23 no.2
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• pp.157-166
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• 2013

This study aimed to investigate whether nociceptin contributes to the alterations in cerebral blood flow (CBF) regulation following postnatal exposure to ethanol in Sprague-Dawley rats. Animals received ethanol twice a day, 2 hr apart, on postnatal 6, 7 and 8 days. The changes in regional CBF (rCBF) in response to the changes in mean arterial blood pressure were determined at 4-, 8-, and 12-week of age by laser-Doppler flowmetry. Hypotension was induced by the gradual withdrawal of blood from arterial catheter, and the reversal of blood pressure was produced by the reinfusion of blood. Expression of nociceptin-like immunoreactivity was determined in dura mater and cerebral cortex using immunohistochemistry. Postnatal exposure to ethanol almost abolished the autoregulation of rCBF in all age groups. Pretreatment with nociceptin but not with [$Nphe^1$]nociceptin(1-13)$NH_2$, a selective competitive nociceptin receptor antagonist, 5 min prior to ethanol administration preserved the autoregulation of rCBF in all age groups. Postnatal exposure to ethanol markedly increased the expressions of nociceptin-like immunoreactivity in the dura mater and cerebral cortex, both of which were significantly inhibited by pretreatment with 7-nitroindazole monosodium salt as well as aminoguanidine 5 min prior to ethanol administration in all age groups. The values of arterial blood gas analysis were not significantly different from the basal levels in all groups. These results suggest that nociceptin deeply contributes to the compensatory mechanisms for the nitric oxide-dependent alterations in CBF autoregulation following postnatal exposure to ethanol.

• Journal of Acupuncture Research
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• v.25 no.2
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• pp.91-103
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• 2008

목적 : 중완과 족삼리 자침이 neonatal-streptozotocin 모델 실험동물에서 혈당과 베타세포 손상에 대한 보호효과를 알아보고자 하였다. 방법 : 비-비만 제2형 당뇨모델인 neonatal STZ 실험동물을 무처치 대조군, 임의혈 대조군, 중완 자침군, 족삼리 자침군으로 나누어 90일 동안 실험하였다. 체중과 혈당을 3일에 한 번씩 측정하였으며, 90일이 경과 후 혈중 인슐린을 측정하고 당부하 검사를 실시한 후 동물을 희생시켜 이자 조직을 적출하고 표본을 제작하였다. 면역세포화학법을 통하여 이자의 베타세포 손상에 대한 세포보호효과를 관찰하였다. 결과 : 중완 자침군과 족삼리 자침군은 대조군에 비해 유의한 혈당 강하 효과가 관찰되었다. 인슐린 농도는 모든 군에서 상승하였으며 당부하 검사에서는 임의혈 자침군과 중완 자침군 및 족삼리 자침군에서 내당능이 있는 것으로 나타났다. 조직 검사에서는 무처치 대조군과 임의혈 대조군에서는 베타세포 손상이 심했으나, 중완 자침군과 족삼리 자침군에서는 베타세포 손상에 대한 세포보호 효과가 현저하게 관찰되었다. 결론 : 중완과 족삼리 자침은 비-비만 제2형 당뇨모델에서 손상된 베타세포를 회복하고 인슐린 분비를 촉진하여 혈당을 강하시키는 효과가 있는 것으로 사료된다.

• Korean Journal of Food Science and Technology
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• v.36 no.6
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• pp.991-994
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• 2004

Effects of formulation KTG075 from edible plants on intestinal function, particularly on Mucin 2 secretion, were examined by loperamide-induced constipation method using Sprague Dawley rats (SD rats, male). Crypt epithelial cells containing more mucus and mucus layer stained with alcian blue were significantly thicker in KTG075 group than control group. When Biogenex AM358 of antibody against Mucin 2 was used, crypt epithelial cells secreted more Mucin 2 in KTG075 group than control group. The Mucus layer at fecal surface was thinner and less mucus was recovered from mucosal surface in constipated rats than in KTG075 group. Mucus production of crypt epithelial cells and mucus contents at fecal and mucosal surfaces were reduced by loperamide-induced constipation. These results indicate formula KTG075 accelerates evacuation and activates intestines.

• Tuberculosis and Respiratory Diseases
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• v.53 no.3
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• pp.253-264
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• 2002

Background : It has been reported that the expression of protein which influences on the cell cycle is significantly involved in the development, progress, treatment response, and survival of cancer, and also that the degree of expression of p27 and CDK4 is related to the prognosis. Recent research has revealed that uteroglobin, tumor suppressor gene, is related to cell cycle. This study is focused on the relations between expression of proteins related to cell cycle and clinical index of and survival of NSCLC. Methods : We examined immunohistochemically specimens of 110 surgically resected NSCLCs for expression of p27, CDK, Uteroglobin. Tissue array slide were obtained from 110 surgically resected NSCLCs. Immunohistochemical staining was performed by immuno-peroxidase technique using avidin-biotinylated horseradish peroxidase complex. Results : In 110 patients with resected NSCLCs, the ratio of male to female was 87:13, the median age was $56.43{\pm}9.41$ yrs. The positive staining of p27 was detected in 75% of the cases. A non-statistically significant trend toward increased p27 expression was observed in smoker and squamous cell cancer. The positive staining of CDK4 was detected in 89%, which was the highest expression of protein among 3 types. The survival ratio of CDK4 negative staining group was higher than that of positive staining group, which was significant diffrernce(P<0.05). There was no association between p27 or uteroglobin expression and survival. Conclusion : The expression degree of CDK4 is related to the prognosis. This findings suggests that the measurement of CDK4 may be useful in identifying patient at high risk for disease recurrence and survival.

• The Journal of the Korea Contents Association
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• v.19 no.3
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• pp.365-374
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• 2019

Unlike benign tumors, malignant tumors are capable of metastasis, easy to relapse, poor survival, and low quality of life. In Korea, here is a tendency to treat the tumors collectively according to the General Principles of Cancer Chemotherapy(GPCC) of the Health Insurance Review & Assessment Service (HIRA). But recently, companion diagnostics(CDx) is recommended rather than unilateral medication because biomarker-based molecular diagnostics is possible to predict the drug response of patients before drug treatment. Not only domestic but also overseas Food and Drug Administratio (FDA) recommends the development of the CDx system at the stage of drug development to ensure the responsiveness and safety of medicines. In this study, I focused on the necessity of CDx development direction as well as CDx development status through literature review. Furthermore I also discussed CDx types according to the molecular diagnostic technology such as immunohistochemistry (IHC), polymerase chain reaction (PCR), in situ hybridization (ISH), and next-generation sequencing (NGS) not only in the approved CDx but also in the developing one by US FDA. And I suggested the technology issue of CDx development process such as a selection of molecular diagnostics at the time of release, a clear understanding of the CDx mechanism, and a convergence of drug with CDx development. The necessity of social insurance system also was proposed for CDx development.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.12 no.2
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• pp.177-182
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• 2009

Purpose: Colitis is a condition associated with a spectrum of altered morphologic changes and cellular adhesion. E-cadherin plays a key role in the establishment and maintenance of epithelial tissue structure and cell-cell adhesion. The purpose of this study is to evaluate E-cadherin expression in colonic epithelium of various colitis in children. Methods: The expressions of E-cadherin were examined in 39 cases of colonic mucosal biopsy specimen using immunohistochemical staining. When more than 50 percent of cells exhibited uniformly the same intensity and pattern of immunostaining as the adjacent normal mucosa, the antigen expression was considered normal. Abnormal expression was defined when less than 50 percent of cells stained, when cells showed a heterogeneously weak or altered distribution, or when complete absence of staining was observed. Results: Fifteen cases with non-specific colitis (38.5%), 7 cases of with Crohn's disease (17.9%), 5 cases of infectious colitis and milk protein sensitive proctocolitis (12.8%), 3 cases of ulcerative colitis (7.7%), 2 cases of Henoch-Schonlein purpura colitis (5.1%), one case of Behcet's disease and ischemic colitis (2.6%) were included in this study. E-cadherin expression was decreased in all kinds of colitis. Reduced expression of E-cadherin was observed in 77 percent of cases. E-cadherin was weaker or no expression in reparative epithelium and "ulcer associated cell lineage". Conclusion: Altered expression of E-cadherin occurs during mucosal inflammation in any kinds of colitis. These changes may be involved in promoting cell migration during epithelial restitution of the gastrointestinal mucosa.

• Applied Microscopy
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• v.37 no.4
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• pp.271-280
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• 2007

Tonicity-responsive enhancer binding protein(TonEBP) is a transcriptional factor essential in the function and development of the renal medulla. TonEBP plays a critical role in protecting renal medullary cells from the deleterious effect of hypertonicity. TonEBP is a key regulator of urinary concentration via stimulation of transcription of urea transporter(UT) in a manner independent of vasopressin. UT in the renal inner medulla is important for the conservation of body water due to its role in the urine concentrating mechanism. Mongolian gerbil(Meriones unguiculatus) has been as an model animal for studying the neurological disease such as stroke and epilepsy because of the congenital incomplete in Willis circle, as well as the investigation of water metabolism because of the long time-survival in the condition of water-deprived desert condition, compared with other species animal. In this study, we divide 3 groups of which each group include the 5 animals. In the study of 7 or 14 days water restricted condition, we investigated the TonEBP and UT-A by using a immunohistochemistry in the kidney. In the normal kidney, the distribution of TonEBP is generally localized on nuclei of inner medullary cells. Nuclear distribution of TonEBP is generally increased throughout the medulla in 7 and 14 days dehydrated group compared with control group. Increased nuclear localization was particularly dramatic in thin limbs. In control groups, UT-A was expressed in inner stripe of outer medulla(ISOM) and inner medulla(IM). UT-A was present in the terminal part of the short-loop of descending thin limbs (DTL) in ISOM and also present in the inner medullary collecting duct(IMCD), where the intensity of it gradually increased toward the papillary tip. In the dehydrated kidney, UT-A immunoreactivity was increased in the short-loop of DTL in ISOM and in the long-loop of DTL in the initial part of IM, where was expressed moderate positive reaction in the normal kidney. Also it was up regulated in the IMCD in initial & middle part of IM. However UT-A down regulated in the IMCD, where the intensity of it gradually decreased toward the papillary tip. These findings suggest that increased levels of TonEBP in medulla and UT-A in shot-loop of DTL and IMCD play a important role for maintain fluid balance in the water-deprived mongolian gerbil kidney.

• Nuclear Medicine and Molecular Imaging
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• v.40 no.1
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• pp.9-15
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• 2006

Purpose: Previous studies have not showed consistent results for the level of expression of sodium/iodide symporter (NIS) in thyroid diseases, especially malignant tumor. We undertook this study to evaluate the distribution of NIS expression in malignant thyroid diseases and compare with that in benign thyroid disease. Materials and Methods: Total patients were 119 cases (Men 15, $48{\pm}13$ yrs). Total number of samples were 205 pieces. In malignant thyroid disease, there were 153 samples: 90 in papillary carcinoma, 4 in follicular carcinoma, 2 in medullary carcinoma and 57 in metastatic lymph node. In benign thyroid disease, there were 52 samples: 36 in goiter/cyst, 11 in thyroiditis and 5 in follicular adenoma. Using immunohistochemical methods, we probed 205 samples with monoclonal anti-NIS Ab. Grading of staining was stored as 0 (negative or absent), 1 (weakly positive), 2 (moderately positive) or 3 (strongly positive). Expression rate (ER) of NIS positivity in individual disease entity was expressed as percentage of total number divided by number in 2 plus 3 grade. Results: ERs of malignant thyroid diseases were 63% in papillary carcinoma, 81% in metastatic lymph node, 71% in follicular carcinoma and 100% in medullary carcinoma. ERs of benign thyroid disease were 53% in goiter/cyst, 64% in thyroiditis and 40% in follicular adenoma. ER of malignant thyroid diseases was higher than benign thyroid diseases (71% vs 54%). Grading of NIS expression in papillary carcinoma or goiter/cyst was heterogeneously distributed in considerable cases. Normal tissue also showed heterogeneous distribution of NIS expression, which was not correlated with that of primary lesion. Conclusion: In papillary thyroid carcinoma, distribution of NIS expression was heterogeneous and increased, and not different compared with that of benign thyroid disease.

• Development and Reproduction
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• v.5 no.1
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• pp.81-88
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• 2001

Gonadotropin-releasing hormone (GnRH) has been known to play a role in the regulation of hCG secretion by human placenta. Recently, a gene encoding the second f개m of GnRH (GnRH-II) was identified in human. Herein, we demonstrate that GnRH-II is expressed in human placenta and assess GnRH-II expression by nested RT-PCR and immunohistochemistry in human placenta during the first trimester. We found that two altematively spliced transcripts of GnW-II mRNA were expressed in human placental tissues of first trimester and the shorter variant had a 21-bp deletion in GnRH-associated peptide (GAP). Immunoreactive GnRH-II was localized in both cytotrophoblastic and syncytiotrophoblastic cytoplasm. The immunostaining intensity was stronger in cytotrophoblast. Villous stromal cells also showed GnRH-II immunoreactiyiry. The results of our study report that the second isoform of GnRH (GnRH-II) is expressed in the first trimester human placenta and we suggest that GnRH-II may also play a regulatory role in maintenance of early pregnancy and hCG secretion in human placenta.

• Clinical and Experimental Pediatrics
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• v.45 no.3
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• pp.354-361
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• 2002

Purpose : Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We first investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase(HSV-TK) gene to murine neuroblstoma cell line(neuro-2a) in vitro and in vivo. Second, we examined the mechanism and its enhancement of the bystander effect in murine neuroblastoma. Methods : To investigate the bystander effect, we studied tumor growth and survival time after HSV-TK/ganciclovir(GCV) treatment in a syngenic A/J mouse neuroblastoma model by mixing various ratios of HSV-TK-expressing neuro-2a cells with wild type neuro-2a cells followed by GCV treatment. To investigate the mechanism of the bystander effect in murine neuroblastoma, immunohistochemistry using connexin 43, CD4 and CD8-specific monoclonal antibodies was analyzed. We studied whether IL-2-secreting neuro-2a cells(neuro-2a/IL-2) would potentiate the bystander effect. Results : A strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma was dependent on the immune response rather than connexin-mediated gap junction. Neuro-2a/IL-2 treatment enhanced the bystander effect in the HSV-TK/GCV system in murine neuroblastoma model. Conclusion : We conclude that the bystander effect in murine neuroblastoma depends on immune response and is enhanced by neuro-2a/IL-2.