• BMB Reports
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• 제55권5호
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• pp.238-243
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• 2022

Autism or autism spectrum disorder (ASD) is a behavioral syndrome characterized by persistent deficits in social interaction, and repetitive patterns of behavior, interests, or activities. The gene encoding Methyl-CpG binding protein 2 (MeCP2) is one of a few exceptional genes of established causal effect in ASD. Although genetically engineered mice studies may shed light on how MeCP2 loss affects synaptic activity patterns across the whole brain, such studies are not considered practical in ASD patients due to the overall level of impairment, and are technically challenging in mice. For the first time, we show that hippocampal MeCP2 knockdown produces behavioral abnormalities associated with autism-like traits in rats, providing a new strategy to investigate the efficacy of therapeutics in ASD. Ketamine, an N-Methyl-D-aspartate (NMDA) blocker, has been proposed as a possible treatment for autism. Using the MeCP2 knockdown rats in conjunction with a rat model of valproic acid (VPA)-induced ASD, we examined gene expression and ASD behaviors upon ketamine treatment. We report that the core symptoms of autism in MeCP2 knockdown rats with social impairment recovered dramatically following a single treatment with ketamine.

• Anatomy and Cell Biology
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• 제56권4호
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• pp.421-427
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• 2023

Bladder exstrophy is a rare congenital condition of the pelvis, bladder, and lower abdomen that opens the bladder against the abdominal wall, produces aberrant growth, short penis, upward curvature during erection, wide penis, and undescended testes. Exstrophy affects 1/30,000 newborns. The bladder opens against the abdominal wall in bladder exstrophy, a rare genitourinary condition. This study is vital to provide appropriate therapy choices as a basis to improve patient outcomes. This study may explain bladder exstrophy and provide treatment. Epispadias, secretory placenta, cloacal exstrophy, and other embryonic abnormalities comprise the exstrophy-spades complex. The mesenchymal layer does not migrate from the ectoderm and endoderm layers in the first trimester, affecting the cloacal membrane. Embryological problems define the exstrophy-aspidistra complex, which resembles epimedium, classic bladder, cloacal exstrophy, and other diseases. Urogenital ventral body wall anomalies expose the bladder mucosa, causing bladder exstrophy. Genetic mutations in the Hedgehog cascade pathway, Wnt signal, FGF, BMP4, Alx4, Gli3, and ISL1 cause ventral body wall closure and urinary bladder failure. External factors such as high maternal age, smoking moms, and high maternal body mass index have also been associated to bladder exstrophy. Valproic acid increases bladder exstrophy risk; chemicals and pollutants during pregnancy may increase bladder exstrophy risk. Bladder exstrophy has no identified cause despite these risk factors. Exstrophy reconstruction seals the bladder, improves bowel function, reconstructs the vaginal region, and restores urination.

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2503-2508
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• 2013

Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as well as a classical chemotherapeutic drug 5 -fluorouacil (5-FU) were used in this study. Cell proliferation was determined by sulforhodamine assay. $IC_{50}$ and $IC_{20}$ were then analyzed for each agent and cell line. Moreover, synergistic potentional of VPA or SAHA in combination with 5-FU at sub toxic does ($IC_{20}$) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which was less senstitive to classical chemotheraoeutic 5-FU was highly was sensitive to HDAC inhibitors. Simultaneous combination of subtoxic doses of HDAC inhibitors and 5-FU signiicantly inhibited cell proliferation in CCA cell lines compared to single sgent treatment($P{\leq}0.01$), while sequentially combined treatments were less effective. The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic antitumor potential demonstrated by simultaneous combination of VPA or SAHA with 5-FU, suggesting a novel alternative therapeutic strategy in effective treatment of CCA.

• Clinical and Experimental Pediatrics
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• 제48권4호
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• pp.406-410
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• 2005

목 적 : 항경련제는 여러 가지 부작용을 갖고 있으며, 그 중 일부는 혈청 내 미량 원소의 항상성 장애이다. 미량 원소는 신체 내에 낮은 농도로 존재하며, 조직의 작은 부분을 구성하지만 중추와 말초 신경계에서 중요한 역할을 한다. 저자들은 6개월 이상 항경련제를 복용하고 있는 간질 환아의 혈청 구리와 아연농도를 측정하여 항경련제가 신체 내 미량 원소의 항상성에 미치는 영향을 알아보고자 하였다. 방 법 : 1997년 1월부터 2003년 12월까지 충남대학교병원 소아과에서 간질 진단 하에 항경련제를 복용 중인 환아 64명(남 : 29, 여 : 35)과 정상 대조군 20명(남 : 12, 여 : 8)을 대상으로 하였고 정맥혈을 채취하여 혈청 구리와 아연의 농도를 측정하였다. 항경련제를 복용하고 있는 간질 환아 군을 VPA 단일 복용군, VPA를 포함하는 복합 복용군, VPA 외의 항경련제 복용군의 세 군으로 나누어 비교하였다. 결 과 : 혈청 구리 농도는 VPA 단일 복용군에서 $81.56{\pm}20.92{\mu}g/dL$, VPA를 포함하는 복합 복용군에서 $80.89{\pm}19.31{\mu}g/dL$, VPA 외의 항경련제 복합 복용군에서 $82.14{\pm}25.74{\mu}g/dL$로서 세 군 모두 대조군의 혈청 구리 농도 $102.13{\pm}32.80{\mu}g/dL$에 비하여 유의하게 낮은 양상을 보였다(P<0.05). 혈청 아연 농도는 항경련제 종류에 따라 분류한 상기 세 군에서 대조군보다 낮았으나, 유의한 차이는 없었다(P>0.05). 혈청 구리와 아연 농도는 항경련제의 종류 및 복용 기간에 의한 차이를 보이지 않았다(P>0.05). 결 론 : 항경련제 복용 환아군에서 정상 대조군보다 혈청 구리의 농도는 유의하게 낮았고, 혈청 아연의 농도는 정상 대조군과 유의한 차이를 보이지 않았다. 항경련제로 치료받는 간질 환아의 경우 혈청 구리 농도가 낮아질 수 있다.

• 한국발생생물학회지:발생과생식
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• 제17권4호
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• pp.379-387
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• 2013

Embryonic stem (ES) cells can self-renew and differentiate to various cells depending on the culture condition. Although ES cells are a good model for cell type specification and can be useful for application in clinics in the future, studies on ES cells have many experimental restraints including low transfection efficiency and transgene expression. Here, we observed that transgene expression after transfection was enhanced by treatment with histone deacetylse (HDAC) inhibitors such as trichostatin A, sodium butyrate, and valproic acid. Transfection was performed using conventional transfection reagents with a retroviral vector encoding GFP under the control of CMV promoter as a reporter. Treatment of ES cells with HDAC inhibitors after transfection increased population of GFP positive cells up to 180% compared with untreated control. ES cells showed normal expression of stem cell markers after treatment with HDAC inhibitors. Transgene expression was further enhanced by modifying transfection procedure. GFP positive cells selected after transfection were proved to have the stem cell properties. Our improved protocol for enhanced gene delivery and expression in mouse ES cells without hampering ES cell properties will be useful for study and application of ES cells.

• Asian-Australasian Journal of Animal Sciences
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• 제33권6호
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• pp.1023-1033
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• 2020

Objective: The efficiency of the knock-in process is very important to successful gene editing in domestic animals. Recently, it was reported that transient loosening of the nucleosomal folding of transcriptionally inactive chromatin might have the potential to enhance homologous recombination efficiency. The objective of this study was to determine whether histone deacetylases (HDAC) inhibitor and RAD51 recombinase (RAD51) expression were associated with increased knock-in efficiency on the β-casein (bCSN2) gene locus in mammary alveolar-large T antigen (MAC-T) cells using the transcription activator-like effector nucleases (TALEN) system. Methods: MAC-T cells were treated with HDAC inhibitors, valproic acid, trichostatin A, or sodium butyrate for 24 h, then transfected with a knock-in vector, RAD51 expression vector and TALEN to target the bCSN2 gene. After 3 days of transfection, the knock-in efficiency was confirmed by polymerase chain reaction and DNA sequencing of the target site. Results: The level of HDAC 2 protein in MAC-T cells was decreased by treatment with HDAC inhibitors. The knock-in efficiency in MAC-T cells treated with HDAC inhibitors was higher than in cells not treated with inhibitors. However, the length of the homologous arm of the knock-in vector made no difference in the knock-in efficiency. Furthermore, DNA sequencing confirmed that the precision of the knock-in was more efficient in MAC-T cells treated with sodium butyrate. Conclusion: These results indicate that chromatin modification by HDAC inhibition and RAD51 expression enhanced the homologous recombination efficiency on the bCSN2 gene locus in MAC-T cells.

• 대한장애인치과학회지
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• 제13권2호
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• pp.91-94
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• 2017

본 증례는 다발성 과백악질증 및 영구치의 맹출 지연을 나타내는 뇌성마비 병력 환자에 대해 보고이다. 현재 환자는 큰 불편감 없이 유구치를 유지하고 있으며 방사선 사진 검사를 통해 매복 영구치의 낭종 발생 여부를 확인하고 잔존 유치를 최대한 보존해야 한다.

• 생물정신의학
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• 제1권1호
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• pp.40-59
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• 1994

The introduction of lithium salts for the treatment of mood disorder by Code in 1949 was a major therapeutic breakthrough. Yet it is far from the universal therpeutic agent in the treatment of mood disorders. Indeed, some acutely manic patients do not respond adeqately to lithium and some individuals experience breakthrough affective episodes during lithium maintenance. In the last decode, it has become c1ear that a significant number of patients with more highly recurrent disorders may require alternative or enhanced forms of prophylactic treatment. For these reasons, a variety of other drugs hove been employed for the treatment and prophylaxis of mood disorders. Efforts to develop new pharmacologic strategies for mood disorder hove included a diverse array of medications, ranging from potent benzodiazepines to novel neuroleptics and from anticonvulsants to calcium channel blockers. The anticonvulsants appear particularly useful in cases of dysphoric mania and rapid cycling state, subforms of bipolar disorder that respond quite poorly to conventional treatments. Among all of these new pharmacologic strategy, carbamazepine and sodium valproate have received the broadest clinical applications as maintenance therapies. The data documenting the short-term antimanic effectiveness of the calcium channel blocker verapamil and benzodiazepins such as clonazepam and lorazepam appear also promising. A number of other theoretically interesting, as well as clinically relevant therapies, which are not presently employed routinly, hove also been studied, including 2 blocker clonidine, atypical antipsychotic clozapine, cholinomimetics, 5-HT enhancers, thyroid and magnesium preparations. Now prophylaxis in mood disorder remains a considerable therapeutic challenge. Controlled testing of the prophylactic efficacy of compounds such as carbamazepine, valproic acid, and the calcium channel blockers represent important next step in the clinical trials for mood disorder.

• 한국경영과학회:학술대회논문집
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• 한국경영과학회 2000년도 추계학술대회 및 정기총회
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• pp.325-328
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• 2000

LG 경제연구원이 발표한 보고서에 의하면, 국내 인터넷 쇼핑몰 시장이 2003년에는 1조 7000억원 규모를 상회할 것으로 예측되고 있다. 그러나 급격한 성장세를 보이고 있는 인터넷 쇼핑 시장규모에 비해 아직까지도 소비자와 관련된 연구는 많이 부족한 실정이다. 특히, 인터넷 쇼핑과 관련된 자료를 보면 소비자들은 인터넷을 통한 제품구매 시 여전히 불안감을 가지고 있는 것으로 나타나고 있음에도 불구하고 인터넷쇼핑에서의 지각된 위험에 대한 연구는 간헐적으로 이루어지고 있을 뿐이며, 이들 연구 역시 인터넷 쇼핑에서의 지각된 위험과 그 유형을 규명하는 데에만 초점을 맞추고 있어 지각된 위험수준에 따라 소비자의 구매행동이 어떻게 달라지는지에 대해서는 논의가 제대로 이루어지지 않고 있다. 따라서 본 연구에서는 지각된 위험수준에 따른 소비자의 구매행동을 브랜드와 가격 의존도로 한정시켜 이들 요인들간의 상대적 중요성 지각을 살펴볼 것이다. 본 연구에서 다룰 연구문제를 정리하면 다음과 같다. 첫째, 인터넷 쇼핑몰에서 제품 구매시 제품유형과 인터넷 쇼핑몰의 명성 그리고 인터넷 쇼핑경험의 세 변수는 소비자의 지각된 위험에 각각 어떤 영향을 미치며, 탐색재와 경험재, 인터넷 쇼핑몰 명성의 정도 그리고 인터넷 쇼핑경험의 유무에 따라 어떤 차이점이 존재하는가\ulcorner 둘째, 소비자의 지각된 위험의 수준과 브랜드와 가격의 상대적 중요성 지각과는 어떤 관계가 있는가\ulcorner 셋째, 브랜드와 가격의 상대적 중요성 지각정도에 두 매개변수인 제품 정보량과 제품 친숙도가 어떤 역할을 하는가\ulcorner 등이다.bition of severity of convulsions, decrease of seizures threshold, decrease of audiogenic seizures in rats of different strains and normalization of cerebral blood flow (measured by hydrogen test) were demonstrated in rats after i.c.v., intraperitoneally and orally administration, respectively. The antiepileptical effects by the combination of compounds from ginseng; were compared with the iuluence of Rg1, Rb1, Rc and with the well known antiepileptical drugs such as carbamazepine, valproic acid. The base for the research is obtained by using the WAG/Rij strain (Luijtelaar, Coenen, Kuznetcova), an excellent genetic model for human generalized absence epilepsy. The improving action of gensinosides was effectively demonstrated on the model of electrical kindling of amygdala of WA

• Annals of Clinical Neurophysiology
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• 제4권1호
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• pp.51-55
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• 2002

Background : An increased frequency of reproductive endocrine disorders and polycystic ovary(PCO) has been reported in women with epilepsy. A possible role of the seizure disorder or, of the use of antiepileptic drugs(AEDs) has been suggested as the pathogenic mechanism. The objective of the present study was to assess the prevalence of reproductive endocrine disorders, such as PCO or menstrual abnormalities, in a series of women with epilepsy, examining the possible relationships of these disturbances with different epilepsy syndromes and AED treatment. Methods : Thirty epileptic women, all of reproductive age and none pubertal, pregnant, or lactating, were evaluated by clinical endocrinological assessment, and pelvic ultrasonography. Seven patients were on valproic acid(VPA), nineteen on carbamazepine(CBZ), and four on diphenylhydantoin(DPH) treatment, respectively. Results : Menstrual irregularity was observed in 8 women(26.7%), dysmenorrhea in 7(23.3%), and premenstrual syndrome in 1(3.3%). Ultrasonographic examination revealed that one women(3.3%) showed polycystic ovary, 4(13.3%) had ovarian cyst(s), and 2(6.7%) had uterine myoma, respectively. There was no difference in the prevalence of menstrual abnormalities or polycystic ovary according to the different preparations of AEDs. Conclusions : Data from this investigation suggest that, in Korean reproductive age women, the treatment of AEDs and the kind of medication may not have a significant effect on the prevalence of menstrual abnormalities or ultrasonographic polycystic ovary.