• Journal of Veterinary Science
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• 제22권1호
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• pp.7.1-7.13
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• 2021

Background: Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. Objectives: The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. Methods: We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. Results: Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. Conclusions: iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.

• Asian Pacific Journal of Cancer Prevention
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• 제16권9호
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• pp.3595-3604
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• 2015

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

• 한국컴퓨터정보학회논문지
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• 제17권3호
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• pp.51-57
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• 2012

간 혈관 구조는 간에 대한 질병을 판단하거나 간 수술 계획을 세우는 데 중요한 요소이다. 특히 생체간이식에서 간 혈관 구조는 기증자와 수혜자의 안전을 보장하기 위하여 수술 전 환자의 간 상태를 파악하고 좌우엽의 체적을 계산하는 중요한 근거로 활용된다. 본 연구는 조영제를 투여한 복부 MDCT 영상에서 추출된 간 영상으로부터 간 혈관을 자동추출하기 위하여 노이즈에 강한 Canny edge detection을 활용할 수 있는 방안을 제안한다. 환자마다 달라질 수 있는 간 영상의 밝기와는 독립적으로 간 내부의 혈관을 추출하기 위하여 간 영상의 히스토그램과 평균 픽셀값을 이용하여 Canny 알고리즘에 사용되는 최적의 파라미터들을 정의한다. 간 영상의 밝기에 따라 파라미터를 수동으로 조절하는 경우보다 시간을 절약할 수 있다. 찾아진 혈관의 경계선에서픽셀의 밝기를 이용하여 후보 혈관을 추출한다. 최종적으로 수평과 수직방향으로 연결된 혈관이나 고립된 혈관을 검색하는 시스템을 이용하여 추출에 실패한 혈관을 추가하고 노이즈를 제거한다. 그 결과로써 환자마다 나타나는 다양한 혈관 모양을 정확하게 3차원으로 재구성한다.

• 한국수정란이식학회지
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• 제32권3호
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• pp.73-79
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• 2017

Transplantation is considered to be a very useful approach to improve human welfare and to prolong life-span. Heterologous organ transplantation using pig organs which are similar to human beings and easy to make mass-production has known as one of the alternatives. To ensure potential usage of the pig organ for transplantation application, it is essentially required to generate transgenic pig modifying immuno-related genes. Previously, we reported production of heterozygous ${\alpha}1,3$-galactosyltransferase (GalT) knock-out and human membrane cofactor protein (MCP) expressing pig ($GalT^{-MCP/+}$), which is enforced for suppression of hyperacute and acute immunological rejection. In this study, we reported generation of homozygous pig ($GalT^{-MCP/-MCP}$) by crossbreeding $GalT^{-MCP/+}$ pigs. Two female founders gave birth to six of $GalT^{-MCP/-MCP}$, and seven $GalT^{-MCP/+}$ pigs. We performed quantitative real-time PCR, western blot, and flow cytometry analyses to confirm GalT and MCP expression. We showed that fibroblasts of the $GalT^{-MCP/-MCP}$ pig do not express GalT and its product Gal antigen, while efficiently express MCP. We also showed no expression of GalT, otherwise expression of MCP at heart, kidney, liver and pancreas of transgenic pig. Taken together, we suggest that the $GalT^{-MCP/-MCP}$ pig is a useful candidate to apply xenotransplantation study.

• 한국임상수의학회지
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• 제15권1호
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• pp.62-74
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• 1998

In feedlot cattle the abrupt change of diet from roughage to a large quantity of grain for the purpose to improve production often results in increased occurrence of rumen acidosis or acute carbohydrate encouragement enterotoxemia, bloats diarrhea liver abscess and laminitis or robot disease. The common management practice to control these problem is to increase the amount of concentrates in the diet in a stepwise manner until the animals are adapted to a high-grain ration. However this practice requires at least about 3 weeks adaptation period and specially prepared adaptation rations which contain various amount of concentrates. Present experiment was undertaken in order to findout the more simple and rapid adaptation method of cattle to a high grain ration. Nineteen Korean calves aging from four to six month were fed artifical hay (Youngchoun Chuk-Hyup, Korea) which contains 10% of concentrates or alfalfa and rye grass hays for two months and randomly alloted to three experimental groups and two control groups. The experimental group-1 was inoculated by stomach tube for two days with li500 ml/day of ruminal fluid fished from Korean beef cattle that had been previously adapted to a high-energy ration. The experimental group-2 was inoculated by trocalization for two days with the same ruminal fluid. The experimental group-3 was inoculated by trocalization with 1,500 ml/day of bacterial culture which contained 2$\times $10$^{9}$/m1 of Gram-negative bacteria derived from adapted luminal fluid. The two control groups were treated with normal saline solution by the same methods. All animals were fed high-energy ration that contained 80% of grain ad libitum for 30-74 days beginning on the third of the treatment. The effect of the inoculation on the adaptation was observed clinicopathologically with the following results; All of the experimental calves inoculated with the ruminal fluid or Gram-negative bacterial culture derived from adapted cattle did not show any signs of rumen acidosis or other related diseases, while most of the control calves did show diarrhea and bloat and a calf laminitis. The average daily weight gain and feed efficiency of experimental calves were slightly improved compared with control calves. Following the feeding of high-grain rational the pH of the ruminal fluid was lowered in both the experimental and control groups. However severe acidosis with the pH of below 5.0 was observed in only a control group-2. The protozoal number in ruminal fluid was markedly decreased during the high-grain feeding in both the experimental and control calves. However the decrease was mere severe in control calves compared with the experimental calves. The activation of the protozoa were completely disappeared within nine hours at the refrigerator temperature (4"C). No significant differences in heamatological and blood chemical values between the experimental and control calves were recognized. However in one control calf which showed clinically laminitis marked elevations of serum glutamic oxaloacetate transaminase and lactic dehydrogenase activities and a decrease of serum glucose level were observed. From these results it would be concluded the intraruminal transplantation of unadapted calves with the adapted ruminal fluid from cattle previously adapted to a high-energy ration prevents disease problem associated with high-grain feeding and improve weight gain and feed efficiency.ency.

• Clinical and Experimental Pediatrics
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• 제45권2호
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• pp.247-255
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• 2002

목 적 : 태아 간세포는 면역학적으로 미숙하여 이식에 따른 거부반응이 잘 일어나지 않으므로 조혈모세포 이식, 특히 자궁내 이식의 좋은 공여세포로 이용할 수 있으나 아직 국내에서는 이를 위한 기초연구가 미미한 실정이다. 연구자는 태아 간 단핵세포를 이용하여 면역조직학적 염색과 체외배양 결과를 분석하여 태아 간의 거핵구 집락형성과 관련된 기초자료를 마련하고자 이 연구를 시행하였다. 방 법: 임신중절시 수집한 태아 간조직과 특발성 혈소판 감소성 자반증 및 범혈구 감소증 환아의 골수에서 단핵세포를 분리한 후 $MegaCult^{TM}-C$ 배지에서 12일간 배양 후 성장인자 첨가에 따른 거핵구 집락형성을 관찰하였고, 5일간의 Flask 배양 후 유세포 분석기를 이용하여 CD34, CD41 양성세포를 측정하였으며, methylcellulose 배지를 이용하여 $37^{\circ}C$ 5% $CO_2$ 배양기에서 배양한 후 제 7일과 14일에 성장인자 첨가에 따른 CFU-GM 집락 수를 조사하였다. 결 과 : 태아 간의 단핵세포 수는 재태주령 11주에 비해서 19주에서 더 많았으며 세포생존율은 $91.2{\pm}3.4%$였다. $MegaCult^{TM}-C$ kit를 이용하여 12일간 배양시 재태주령 11주의 태아 간이 19주에 비해서 거핵구 집락 수가 많았고, 4례 모두 성장인자의 첨가에 따른 집락증폭의 상승효과는 없었으며 배양 후 형성된 거핵구 집락 수는 태아 간, 특발성 혈소판 감소성 자반증 환아의 골수, 범혈구 감소증 환아의 골수 순이었다. 거핵구 집락 중 순수집락 수는 태아 간이 특발성 혈소판 감소성 자반증 및 범혈구 감소증 환아의 골수에 비해서 유의하게 높았으며, 순수집락 중 large CFU-Mk의 비율은 태아 간이 특발성 혈소판 감소성 자반증 및 범혈구 감소증 환아의 골수에 비해서 높았으나 유의성은 보이지 않았다. 태아 간 단핵세포를 5일간 flask 배양한 후 CD34 양성세포의 발현율은 증가하였으나 성장인자의 첨가에 따른 집락증폭의 상승효과는 TPO 투여군에서만 있었고, CD41 양성세포의 발현율 역시 배양 후 증가하였으나 성장인자 첨가군에 비해서 대조군의 발현율이 너무 높은 결과를 보였다. Methylcellulose 배지를 이용한 단핵세포 배양에서 CFU-GM 집락 수는 태아 간의 경우 배양 7일에 비하여 14일에 감소하였고, 성장인자의 첨가에 따른 집락증폭의 상승효과는 태아 간에서는 모든 군에서 보였으나 특발성 혈소판 감소성 자반증에서는 GM-CSF 투여군에서만 있었으며 범혈구 감소증 환아의 골수에서는 없었다. 결 론: $MegaCult^{TM}-C$ 배지를 이용하여 태아 간세포를 배양하고 면역조직학적 염색으로 거핵구 집락형성을 성공적으로 관찰하였으며, 태아 간에서 얻은 거핵구 집락이 특발성 혈소판 감소성 자반증 및 범혈구 감소증 환아의 골수에서 얻은 집락에 비하여 집락수나 순수집락의 분포, 집락의 크기 등에서 우수한 것으로 나타났으나 태아 간 조혈모세포 이식의 실제적인 임상적용을 위해서는 체계적인 더 많은 연구가 필요할 것으로 생각된다.

• Archives of Plastic Surgery
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• 제43권6호
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• pp.570-574
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• 2016

Background Fractional $CO_2$ laser is an effective treatment for scars, but most patients complain about sharp burning pain, even after the application of lidocaine ointment. This study analyzed the impact of a vibrating device to nonpharmacologically reduce the acute pain of laser treatment, in accordance with the gate control theory of pain management. Methods This is a prospective study performed from May 2013 through March 2014. Fifty-three patients (mean age, 26.7 years; range, 16-44 years) who had donated livers for liver transplantation were treated with a fractional $CO_2$ laser (10,600 nm; model $eCO_2$, Lutronic Corp) for their abdomen scars. Laser treatment was applied 4 months after surgery. A commercially available, locally applied vibrating device (model UM-30M, Unix Electronics Co. Ltd.) was used, in an on-and-off pattern, together with the $CO_2$ laser. A visual analogue scale (VAS; 0, no pain; 10, most severe pain) of pain sensation was assessed and statistically analyzed using a paired t-test. Results The average VAS score for pain with the vibrating device was 4.60 and the average VAS score without the vibrating device was 6.11. The average difference between scores was 1.51 (P=0.001). Conclusions A locally applied vibrating device was demonstrated to be effective in reducing pain when treating with a fractional $CO_2$ laser. Vibration treatment could be helpful when treating scars with fractional $CO_2$ laser in pain-sensitive patients, particularly children.

• 대한수의학회지
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• 제35권4호
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• pp.659-670
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• 1995

Cyclosporin A extracted from fungus Trichoderma polysporum Rifai and Cyclindrocarpon lucidum Booth serves as an important immunosuppressive drug in transplantation surgery. Systemic treatment with cyclosporin A induces an impairment of the biliary excretion of the bile salts and cholestasis. This study was designed to observe the Ultrastural changes of the hepatocytes and the bile canaliculi in cyclosporin A-induced intrahepatic cholestasis in rats. Cyclosporin A was injected into male Wistar rats intraperitoneally 50mg per kg body weight and rats were necropsied at 1, 3, 6, 9, 12, 24 hours. The liver tissues were observed with transmission and scanning electron microscopes and the results were as follows. Transmission electron microscopy: After cyclosporin A injection, SER and lysosomes were increased in the hepatocytes until 9 hours. At 12 hours after injection of cyclosporin A, RER with dilated cistern were increased, and SER, lysosomes in the cytoplasm were decreased. From 1 hour to 24 hours after injection of cyclosporin A, there were dilation of bile canalliculi and decreased or lost microvilli. At 24 hours the dilation of bile canaliculi were decreased. Scanning electron microsocopy: After cyclosporin A injection, the bile canaliculi were dilated and the microvilli were shortened, decreased or lost according to the sites. At 24 hours, the microvilli packing the bile canaliculi were observed. These observations suggest that cyclosporin A-induced cholestasis is associated with the dilation of bile canaliculi, increased microfilaments of the pericanalicular region and decreased or lost microvilli.

• 대한장애인치과학회지
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• 제3권1호
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• pp.17-21
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• 2007

Allagille 증후군은 담즙분비의 감소로 인한 간의 손상, 황달, 황색종, 소양증 등의 다양한 문제들을 가진다. 구강영역의 문제점으로는 출혈 및 감염, 치아의 변색을 들 수 있다. 또한 증례의 환아와 같이 간이식을 할 경우 지속적인 면역억제제의 사용으로 인한 감염의 위험성은 평생 동안 계속되게 된다. 따라서, Alagille 증후군 환자에 있어서는 다음과 같은 사항들이 치과치료에서 필요하다고 생각된다. 의과 및 치과병력을 정확히 파악하고, 내원마다 전 치아들에 대한 평가를 철저히 실시하며, 발견되는 우식은 더 이상 진행이 되지않도록 즉시 치료해야 한다. 예방적 항생제를 투여하더라도 감염과 출혈을 예방하기위해 치료 시 최소한의 외상이 가해지도록 하며, 치료 후에도 감염의 소지가 있을 수 있는 치아는 제거하는 편이 유리하다. 성장이 끝난 후에는 심미적 기능적인 문제를 해결하기 위해 전 치열에 대한 재건이 필요하며 환자 스스로 구강위생에 신경을 쓸 수 있도록 예방 교육에 힘써야 할 것으로 생각한다.

• 생명과학회지
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• 제31권8호
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• pp.710-718
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• 2021

태반유래 중간엽줄기세포(PD-MSCs)는 재생의학에서 세포기반치료제로 잘 알려진 세포군이다. PD-MSCs의 손상된 부위로의 이동과 호밍 기능은 MSC 생착의 중요한 특성이다. miRNA는 최근 MSC의 증식, 생존 이동과 같은 중요한 기능을 조절하는 것으로 알려져 있다. 본 연구의 목적은 담관결찰(BDL) 쥐 모델에서 PD-MSCs 호밍에 관련된 miRNA 및 표적 유전자를 동정하는 것으로, 마이크로어레이 분석을 이용하여 PD-MSCs 호밍에 관여하는 유전자 표적 miRNA를 선별하였다. BDL 쥐모델에 PD-MSCs을 이식한 일주일 후 간 조직에서 PD-MSCs 생착여 부는 면역형광분석법과 qRT-PCR에 의한 인간 Alu유전자 발현으로 확인되었다. 저산소 및 정상조건(Hyp/Nor)에서 이동한 PD-MSC에 비하여, PD-MSCs 이식한 BDL군 간 조직에서 miRNAs 발현의 차이가 크게 나타났으며, PD-MSCs 호밍 관련 miRNA와 표적유전자를 검증하였다. miR199a-5p 및 miR-148a-3p에 대한 표적 유전자 인테그린 α4 (ITGA4)와 α5 (ITGA5)의 발현은 이식(Tx)그룹에서(p<0.05) 유의하게 상향 조절되었다. 또한 인테그린 β1 (ITGB1)과 β8 (ITGB8)의 발현은 miR-183-5p 및 miR-145-5p억제에 의하여 크게 증가되었다. 따라서 이러한 결과는 BDL에 의해 손상된 쥐간에서 PD-MSCs가 호밍효과을 위해 인테그린 그룹과 관련된 miRNA 발현 조절에 관여함을 나타내었다. 본 연구결과는 miRNA에 의한 인테그린 그룹 조절기능이 BDL에 의해 유도된 간섬유증 쥐모델에서 PD-MSCs의 치료효과에 기여할 수 있음을 시사한다.