• Journal of Life Science
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• v.16 no.1
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• pp.12-16
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• 2006

Genetic alternation of Brca1 predispose of breast and ovarian cancer. Brca1 plays critical role in cell cycle regulation following DNA damage. Previous studies revealed that Brca1 plays an important role in S phase and G2/M checkpoint regulation. However, whether Brca1 involves in spindle checkpoint is unclear. In this study, the role of Brca1 in cell cycle response following nocodazole, which is a reagent that depolymerizes microtubules and activates the spindle checkpoint, has been examined using wild type $p53^{-/-}\;and\;p53^{-/-}Brca1^{-/-}$ mouse embryonic fibroblasts (MEFs). While wild type and Brca1-proficient MEFs showed an acute mitotic arrest, Brca1-deficient MEFs failed to arrest at mitotic phase in response to nocodazole treatment. In double-thymidine block and nocodazole treatment experiment, a portion of $p53^{-/-}\;Brca1^{-/-}$ MEFs were clearly by-passed nocodazole induced mitotic arrest. Consistent with this, in morphologic analysis, $p53^{-/-}\;Brca1^{-/-}$ MEFs showed growing cell morphology after nocodazole treatment. Taken together, these results suggest that Brca1 protein is an important component for normal induction of spindlecheckpoint and impairment of Brca1 function could induce dysregulation of mitotic cell cycle that ultimately results in genomic instability.

• Journal of Genetic Medicine
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• v.5 no.1
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• pp.26-33
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• 2008

Purpose : Phenylketonuria(PKU) is an inborn error of metabolism and a genetic disorder resulting from a deficiency of phenylalanine hydroxylase(PAH) and decreased activity of tetrahydrobiopterin(BH4).In this study the correlation between the DNA mutation and clinical manifestations was investigated and PAH DNA mutations were compared bewteen Asian and Caucasian populations. Methods : DNA was isolated from peripheral leukocytes. The PAH gene was amplified by Polymerase Chain Reaction(PCR) and the sequence was analyzed with Multiplex Ligation-dependent Probe Amplification(MLPA). Results : We characterized the PAH gene of 102 independent Korean patients with PKU. PAH nucleotide sequence analysis revealed 44 different mutations, including 10 novel mutations comprising 9 missense mutations(N207D, K95del, A447P, G344D, P69S, S391I, A202T, G103S, and I306L) and 1 novel splice-site variant mutation(IVS10-3C>G). R243Q was the most prevalent mutation in this study. A259T has not previously been reported in Asian populations, but we found that this mutation had a frequency of 10.1% in our study. Furthermore, the genotypes of $BH_4$ responsive patients were analyzed and were divided into two groups: $BH_4$ medication-only group and $BH_4$ medication with diet therapy group. In the $BH_4$ medication-only group and $BH_4$ medication with diet therapy group, R241C was the most common mutation. Conclusion : Novel mutations in the PAH gene of PKU patients are still being discovered. Additional information as to the frequency of mutations in the tetrahydrobiopterine responsive gene is also accumulating. We anticipate that knowledge of these PKU gene mutations will assist the diagnosis, genetic counseling, and therapeutic treatment of PKU patients in future.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.25 no.2
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• pp.1-19
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• 2012

Objective : The purpose of this study is to investigate about comparison of Eastern-Western medicine on the acne. Methods : We searched Eastern and Western medicine books for acne. We analyzed these books and examined category, definition, etiology, classification, internal and external methods of treatment of acne. Results : The results were as follows. 1. In Eastern medicine, Acne belongs to the category of the Bunja(粉刺), Jwachang(痤瘡), Pyepungbunja(肺風粉刺). In Western medicine, the other name of Acne is acne vulgaris. 2. In Eastern medicine, the definition of Acne includes manual extraction of comedones and skin appearance. In Western medicine, Acne is a common skin disease during adolescence and a chronic inflammatory disease of pilosebaceous unit of self localization. It is characterized by noninflammatory, open or closed comedones and by inflammatory papules, pustules, and nodules and it affects the areas of skin with the densest population of sebaceous follicles, these areas include the face, neck, back, and the upper part of the chest. 3. In Eastern medicine, the cause and mechanism of Acne arose from the state of internal dampness-heat and spleen-stomach internal qi deficiency due to dietary irregularities and then invaded external pathogen such as wind-dampness-heat-cold-fire in lung meridian lead to qi and blood heat depression stagnation. So it appears in skin. In Western medicine, the etiology and pathogenesis of Acne is clearly not identified, but there are most significant pathogenic factors of blood heat depression stagnation. So it appears in skin. In Western medicine, the etiology and pathogenesis of Acne is clearly not identified, but there are most significant pathogenic factors of Acne; Androgen-stimulated production of sebum, hyperkeratinization and obstruction of sebaceous follicles, proliferation of Propionibacterium acnes and inflammation, abnormaility of skin barrier function, genetic aspects, environmental factors etc. 4. In Eastern medicine, differentiation of syndromes classifies clinical aspects, and cause and mechanism of disease; the former is papular, pustular, cystic, nodular, atrophic, comprehensive type; the latter is lung blood heat, intestine-stomach dampness-heat, phlegm-stasis depression, thoroughfare-conception disharmony, heat toxin type. In Western medicine, it divides into an etiology and invasion period, and clinical aspects; Acne neonatorum, Acne infantum, Acne in puberty and adulthood, Acne venenata; Acne vulgaris, Acne conglobata, Acne fulminans, Acne keloidalis. 5. In Eastern medicine, Internal methods of treatment of Acne are divided into five treatments; general treatments, the treatments of single-medicine and experiential description, the treatments depending on the cause and mechanism of disease, and clinical differentiation of syndromes, dietary treatments. In Western medicine, it is a basic principles that regulation on production of sebum, correction on hyperkeratinization of sebaceous follicles, decrease of Propionibacterium acnes colony and control of inflammation reaction. Internal methods of treatment of Acne are antibiotics, retinoids, hormone preparations etc. 6. In Eastern medicine, external methods of treatment of Acne are wet compress method, paste preparation method, powder preparation method, pill preparation method, acupuncture and moxibustion therapy, ear acupuncture therapy, prevention and notice, and so on. In Western medicine, external method of treatments of Acne are divided into topical therapy and other surgical therapies. Topical therapy is used such as antibiotics, sebum regulators, topical vitamin A medicines etc and other surgical therapies are used such as surgical treatments, intralesional injection of corticosteroids, skin dermabrasion, phototherapy, photodynamic therapy, and so on. Conclusions : Until now, there is no perfect, effective single treatment. We think that Eastern medicine approach and treatment can be helpful to overcome the limitations of acne cure.

• Journal of Genetic Medicine
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• v.16 no.2
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• pp.85-89
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• 2019

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder. HHH is caused by a deficiency of the mitochondrial ornithine transporter protein, which is encoded by the solute carrier family 25, member 15 (SLC25A15) gene. Recently, government supported Korean newborn screening has been expanded to include a tandem mass spectrometry (MS/MS) measurement of ornithine level. We report a case of a neonate with HHH syndrome showing a normal MS/MS measurement of ornithine level. A female newborn was admitted to neonatal intensive unit due to familial history of HHH syndrome. Her parents were consanguineous Parkistani couple. The subject's older sister was diagnosed with HHH syndrome at age of 30 months based on altered mental status and liver dysfunction. Even though the subject displayed normal ammonia and ornithine levels based on MS/MS analysis, a molecular test confirmed the diagnosis of HHH syndrome. At 1 month of age, amino acid analysis of blood and urine showed high levels of ornithine and homocitrulline. After 11 months of follow up, she showed normal growth and development, whereas affected sister showed progressive cognitive impairment despite no further hyperammonemia after protein restriction and standard therapy. Our report is in agreement with a previous Canadian study, which showed that neonatal samples from HHH syndrome patients demonstrate normal ornithine levels despite having known mutations. Considering the delayed rise of ornithine in affected patients, genetic testing, and repetitive metabolic testing is needed to prevent patient loss in high risk patients.

• BMB Reports
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• v.42 no.1
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• pp.59-64
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• 2009

Hepatitis B virus (HBV) infection is highly prevalent worldwide. The major challenge for current antiviral treatment is the elevated drug resistance that occurs via rapid viral mutagenesis. In this study, we developed AAV vectors to simultaneously deliver two or three shRNAs targeting different HBV-related genes. These vectors showed markedly better antiviral effects than ones that delivered a single shRNA in vitro. A dual shRNA expression vector (AAV-157i/1694i), which simultaneously expressed two shRNAs targeted the S and X genes of HBV, reduced HBsAg, HBeAg and HBV DNA levels by $87{\pm}4$, $80.3{\pm}2.6$ and $86.2{\pm}7%$ respectively, eight days post-transduction. In a mouse model of prophylactic treatment, HBsAg and HBeAg were reduced to undetectable levels and the serum HBV DNA level was reduced by at least 100 fold. These results indicate that AAV-157i/1694i generates potent anti-HBV effects and that the strategy of constructing multi-shRNA expression vectors may lead to enhanced anti-HBV efficacy and overcome the evading mechanism of the virus and thus the development of drug resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6605-6611
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• 2013

Background: WEE1 is a G2/M checkpoint regulator protein. Various studies have indicated that WEE1 could be a good target for cancer therapy. The main aim of this study was to asssess the tumor suppressive potential of WEE1 silencing in two different breast cancer cell lines, MCF7 which carries the wild-type p53 and MDA-MB468 which contains a mutant type. Materials and Methods: After WEE1 knockdown with specific shRNAs downstream effects on cell viability and cell cycle progression were determined using MTT and flow cytometry analyses, respectively. Real-time PCR and Western blotting were conducted to assess the effect of WEE1 inhibition on the expression of apoptotic (p53) and anti-apoptotic (Bcl2) factors and also a growth marker (VEGF). Results: The results showed that WEE1 inhibition could cause a significant decrease in the viability of both MCF7 and MDA-MB-468 breast cancer cell lines by more than 50%. Interestingly, DNA content assays showed a significant increase in apoptotic cells following WEE1 silencing. WEE1 inhibition also induced upregulation of the apoptotic marker, p53, in breast cancer cells. A significant decrease in the expression of VEGF and Bcl-2 was observed following WEE1 inhibition in both cell lines. Conclusions: In concordance with previous studies, our data showed that WEE1 inhibition could induce G2 arrest abrogation and consequent cell death in breast cancer cells. Moreover, in this study, the observed interactions between the pro- and anti-apoptotic proteins and decrease in the angiogenesis marker expression confirm the susceptibility to apoptosis and validate the tumor suppressive effect of WEE1 inhibition in breast cancer cells. Interestingly, the levels of the sensitivity to WEE1 silencing in breast cancer cells, MCF7 and MDA-MB468, seem to be in concordance with the level of p53 expression.

• Clinical and Experimental Pediatrics
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• v.59 no.sup1
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• pp.25-28
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• 2016

Phelan-McDermid syndrome is a rare genetic disorder caused by the terminal or interstitial deletion of the chromosome 22q13.3. Patients with this syndrome usually have global developmental delay, hypotonia, and speech delays. Several putative genes such as the SHANK3, RAB, RABL2B, and IB2 are responsible for the neurological features. This study describes the clinical features and outcomes of Korean patients with Phelan-McDermid syndrome. Two patients showing global developmental delay, hypotonia, and speech delay were diagnosed with Phelan-McDermid syndrome via chromosome analysis, fluorescent in situ hybridization, and multiplex ligation-dependent probe amplification analysis. Brain magnetic resonance imaging of Patients 1 and 2 showed delayed myelination and severe communicating hydrocephalus, respectively. Electroencephalography in patient 2 showed high amplitude spike discharges from the left frontotemporoparietal area, but neither patient developed seizures. Kidney ultrasonography of both the patients revealed multicystic kidney disease and pelviectasis, respectively. Patient 2 experienced recurrent respiratory infections, and chest computed tomography findings demonstrated laryngotracheomalacia and bronchial narrowing. He subsequently died because of heart failure after a ventriculoperitoneal shunt operation at 5 months of age. Patient 1, who is currently 20 months old, has been undergoing rehabilitation therapy. However, global developmental delay was noted, as determines using the Korean Infant and Child Development test, the Denver developmental test, and the Bayley developmental test. This report describes the clinical features, outcomes, and molecular genetic characteristics of two Korean patients with Phelan-McDermid syndrome.

• Journal of Life Science
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• v.17 no.11
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• pp.1492-1496
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• 2007

In vitro IgE class switching could be induced through co-culture of CD40L-expressing KU812 cells and CD40-expressing B cells in the presence of IL-4 or IL-13. It has been generated several B cell lines, which produce rice allergen (RA)-specific IgM antibody by in witγo immunization (IVI) using peripheral blood lymphocyte (PBL). In this study, induction of RA-specific IgE antibody by KU812 cells was attempted. Before co-culture, we determined the CD40 expression in RA-specific B cell lines, RA9G11 and the CD40 ligand (CD40L) expression in activated KU812 cells by treatments with phorbol myristate acetate (PMA) and ionomycin for 6 hrs. Flow cytometric analysis shown that RA9G11 and activated KU812 cells expressed high level of CD40 and CD40L, respectively. RA9G11 cells were cultured with activated KU812 cells for 12 days in the presence of IL-4 for IgE class switching. Mature $C{\varepsilon}$ mRNA level and RA-specific IgE spot forming cells (SFC) were observed in all culture condition, and especially, high level of RA-specific IgE synthesis was determined the same ratio of RA9G11 and activated KU812 cells in the presence of 50U IL-4. Therefore, induction of RA-specific IgE synthesis by activated KU812 cells can be contributed in the application for allergic therapy and prevention.

• The Korean Society of Law and Medicine
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• v.23 no.1
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• pp.121-148
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• 2022

CRISPR-Cas9 is one of the gene-editing technologies that infinite potential. It may provide human beings with many benefits or cause unanticipated challenges. The governance as standards setting or regulation of gene-editing technologies can contribute to keeping a balance between scientific value and ethical commitments. Guaranteeing public participation provides an additional opportunity to think about ethical and moral considerations: For whose benefit the internationally discussed governance of gene-editing technologies is directed at? There is a doubt regarding whether the governance justifies scientific researchers' gene-editing research. Suppose that governance promotes the advancement of CRISPR-Cas9, it should also encourage greater research responsibility. If not, there may be tragedies brought about by the misconduct of researchers. Thus, the essential matter on the governance for the research of CRISPR-Cas9 is the researchers' responsibility.

• Korean Journal of Psychosomatic Medicine
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• v.20 no.1
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• pp.32-39
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• 2012

Objective : Psychiatry in North Korea is believed to seem very different from psychiatry in South Korea. However, there is nearly no information regarding psychiatry in North Korea until now. Our study aimed to get information about North Korean psychiatry. Methods : Three North Korean defectors in South Korea, whose clinical experience as medical doctors in North Korea was over 10 years, were recruited. They underwent the semi-structured interview, content of which included the clinical experience with psychiatric patients, the details of psychiatry, the treatment of psychiatric patients, the stigma of mental illness, and the suicide, in North Korea. Results : In North Korea, psychiatric department was called as 49th(pronounced as Sahsip-gu-ho in Korean). Only patients with vivid psychotic symptoms came to psychiatric department. Non-psychotic depression or anxiety disorders usually were not dealt in psychiatry. The etiology of mental illness seemed to be confined to biological factors including genetic predisposition. Psychosocial or psychodynamic factors as etiology of mental illness appeared to be ignored. Psychiatry was apparently separated from political or ideological issues. The mainstay of psychiatric treatment is the inpatient admission and out-of-date therapy such as insulin coma therapy. Stigma over mental illness was common in North Korea. Suicide is considered as a betrayal to his/her nation, and has been reported to be very rare. Conclusion : The situation of psychiatry in North Korea is largely different from that of South Korea. Although some aspects of North Korean psychiatry are similar to psychiatry in former socialist countries, North Korean psychiatry is considered to have also its unique characteristics.