• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2707-2712
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• 2015

Background: The human homologue of the mouse double minute 2 (MDM2) gene is a negative regulator of Tp53. MDM2-309T>G a functional promoter polymorphism was found to be associated with overexpression thereby attenuation of Tp53 stress response and increased cancer susceptibility. We have planned to evaluate the possible role of MDM2-309T>G polymorphism with risk and response to chemotherapy in AML. Materials and Methods: A total of 223 de novo AML cases and 304 age and sex matched healthy controls were genotyped for the MDM2-309T>G polymorphism through the tetra-primer amplification refractory mutation system (ARMS)-PCR method. In order to assess the functional relationship of -309T>G SNP with MDM2 expression level, we quantified MDM2 mRNA in 30 primary AML blood samples through quantitative RT-PCR. Both the (-309T>G) genotypes and the MDM2 expression were correlated with disease free survival (DFS) rates among patients who have achieved complete remission (CR) after first induction chemotherapy. Results: MDM2-309T>G polymorphism was significantly associated with AML development (p<0.0001). The presence of either GG genotype or G allele at MDM2-309 confered 1.79 (95% CI: 1.12-2.86; p<0.001) and 1.46 fold (95%CI: 1.14-1.86; p= 0.003) increased AML risk. Survival analysis revealed that CR+ve cases with GG genotype had significantly increased DFS rates (16months, p=0.05) compared to CR+ve TT (11 months) and TG (9 months) genotype groups. Further, MDM2 expression was also found to be significantly elevated in GG genotype patients (p=0.0039) and among CR+ve cases (p=0.0036). Conclusions: The MDM2-309T>G polymorphism might be involved in AML development and also serve as a good prognostic indicator.

• Journal of Genetic Medicine
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• v.6 no.1
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• pp.38-55
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• 2009

Purpose: This study was undertaken to provide the framework for development of a genetic counseling training program, and an accreditation and certification process suitable for non-M.D. genetic counselors in Korea. Materials and Methods: Global standards of genetic counseling curriculums, training program accreditation (TPA), and the certification process for genetic counselors (CPGC) in the U.S.A and Japan were reviewed, and a questionnaire survey was performed to elicit opinions among health-care providers including physicians, nurses, technicians, researchers, and educators. In addition, input from professional communities, including the Korean Society of Medical Genetics (KSMG) and Institute for Genetic Testing Evaluation, was sought in formulating the framework of this study. Results: Comparison of U.S.A. and Japan educational systems showed similarities in curriculum, accreditation, and certification programs. Analysis of 117 respondents opinions showed a high level of agreement in the area of global standards; 88% indicated that KSMG should be in charge of TPA and CPGC, while 77% favored a certification exam composed of both written exam and interview components. Conclusion: Based upon this study we propose that the KSMG should be in charge of providing the TPA and CPGC for non-MD genetic counselors. Requirements for the entrance to a Master's degree genetic counseling program should be open to successful four year undergraduate students in all areas, provided the candidates demonstrate the abilities to master the graduate level of study in human genetics, clinical genetics, statistics, psychology, and other required subjects. Eligibility for certification should include qualified candidates of genetic counseling with no formally approved education, but a sufficient amount of clinical experience, in addition to accredited program graduates. Certification examinations should be carried out every two years and the certification should be good for five years, as is the case in Japan.

• Journal of Life Science
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• v.26 no.6
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• pp.727-736
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• 2016

Rice (Oryza sativa L.) is one of the major cereal crops for consumption by the world’s population. Recently, various colored rice, such as white, red, brown, green, and black rice, have caught the attention of world consumers. The commercial name ‘black rice’ contains a high amount of anthocyanins in pericarp, which increases nutritional value. Moreover, anthocyanin in black rice possesses biomedical properties, including anti-oxidant, anti-cancer, and anti-inflammatory effects in humans. In genetics, black rice has a dominant PURPLE PERICARP (Prp) trait governed by two genes, Pb and Pp, which are involved in the synthesis of cyanidin-3-O-glucoside (C3G). Since the publication of a report by Nagai at 1921, the genetics and physiological studies of black rice driven by Prp traits are still unable to understand the relevant genes and their roles. However, with the increased demand for anthocyanin-rich black rice as a functional food for human health, it has become urgent to develop highyielding anthocyanin-rich varieties of rice. We explored many years in the genetics of purple pericarp trait, anthocyanin biosynthesis in pericarp during seed development, and, consequently, their products in relation to different physiological and agronomic traits. In this review, we summarized the anthocyanin biosynthesis in pericarp, emphasizing the inheritance pattern of the trait and functions of their products on different physiological and agronomic traits, including the yield of black rice.

• Journal of Life Science
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• v.16 no.5
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• pp.716-722
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• 2006

Superoxide dismutase (SOD) is physiologically important in regulating cellular homeostasis and apoptotic cell death, and its mutations are the cause of familial amyotrophic lateral sclerosis (FALS). Mitochondrial serine protease HtrA2 has a pro-apoptotic function and has known to be associated with neurodegenerative disorders. To investigate the relationship between genes associated with apoptotic cell death, such as HtrA2 and SOD1, we utilized the pGEX expression system to develop a simple and rapid method for purifying wild-type and ALS-associated mutant SOD1 proteins in a suitable form for biochemical studies. We purified SOD1 and SOD1 (G93A) proteins to approximately 90% purity with relatively high yields (3 mg per liter of culture). Consistent with the result in mammalian cells, SOD1 (G93A) was more insoluble than wild-type SOD1 in E. coli, indicating that research on the aggregate formation of SOD1 may be possible using this pGEX expression system in E. coli. We investigated the HtrA2 serine protease activity on SOD1 to assess the relationship between two proteins. Not only wild-type SOD1 but also ALS-associated mutant SOD1 (G93A) were cleaved by HtrA2, resulting in the production of the 19 kDa and 21 kDa fragments that were specific for anti-SOD1 antibody. Using protein gel electrophoresis and immunoblot assay, we compared the relative molecular masses of thrombin-cleaved GST-SOD1 and HtrA2-cleaved SOD1 fragments and can predict that the HtrA2-cleavage sites within SOD1 are the peptide bonds between leucine 9-lysine 10 (L9-K10) and glutamine 23-lysine 24 (Q23-K24). Our study indicates that SOD1 is one of the substrate for HtrA2, suggesting that both HtrA2 and SOD1 may be important for modulating the HtrA2-SOD1-mediated apopotic cell death that is associated with the pathogenesis of neurodegenerative disorder.

• Journal of mucopolysaccharidosis and rare diseases
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• v.4 no.1
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• pp.11-13
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• 2018

In Malaysia, diagnosis and treatment of patients with mucopolysaccharidoses (MPS) is mainly localized at Hospital Kuala Lumpur, which is the national referral center for rare diseases. To date there are 83 patients diagnosed with MPS in our center, with MPS II being the commonest. The Malaysian National Medicines Policy second edition has a specific section on the orphan drugs which includes recombinant human enzyme for enzyme replacement therapy (ERT) in MPS. So far, National Pharmaceutical Regulatory Agency Malaysia has approved recombinant human enzyme for MPS types I (Loranidase), II (idursulfase), IVA (elosulfase alfa), and VI (Galsufase). Access to Idursulfase beta (another recombinant human enzyme for MPS II) and vestronidase alfa-vjbk (MPS VII) required special authorization on named patient basic. Currently there are 25 patients receiving ERT, 70% of the funding are from Ministry of Health (MOH), the remaining 30% are from various charitable funds and humanitarian programs. Thirteen newly diagnosed patients have to queue for an additional fund. Four patients have been treated with Hematopoietic stem cell transplant. MOH has also published guidelines regarding the patient selection criteria for ERT and treatment monitoring schedule.

• Journal of Radiation Protection and Research
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• v.46 no.4
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• pp.151-159
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• 2021

Background: Computed tomography (CT) is one of the crucial diagnostic tools in modern medicine. However, careful monitoring of radiation dose for CT patients is essential since the procedure involves ionizing radiation, a known carcinogen. Materials and Methods: The most desirable CT dose descriptor for risk analysis is the organ absorbed dose. A variety of CT organ dose calculators currently available were reviewed in this article. Results and Discussion: Key common elements included in CT dose calculators were discussed and compared, such as computational human phantoms, CT scanner models, organ dose database, effective dose calculation methods, tube current modulation modeling, and user interface platforms. Conclusion: It is envisioned that more research needs to be conducted to more accurately map CT coverage on computational human phantoms, to automatically segment organs and tissues for patient-specific dose calculations, and to accurately estimate radiation dose in the cone beam computed tomography process during image-guided radiation therapy.

• Journal of Genetic Medicine
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• v.18 no.1
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• pp.1-7
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• 2021

The oocyte quality is of great importance in infertility as it reflects the follicle developmental potential and further affects the embryo development, clinical pregnancy outcomes. The analysis of gene expression in somatic cells is an important study to better clinical in vitro fertilization (IVF) outcomes in embryo selection reflecting the appropriate communication between the oocyte and somatic cells. Specifically, somatic cell transcriptomic technology can help assess biomarkers of oocyte and embryo ability. The present article aims to overview the basic aspect of folliculogenesis and review studies involving changes in candidate gene expression of cumulus or granulosa cell related to clinical outcomes in human IVF.

• BMB Reports
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• v.40 no.4
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• pp.467-474
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• 2007

Autosomal recessive polycystic kidney disease (ARPKD) is one of the important genetic disorders in pediatric practice. Mutation of the polycystic kidney and hepatic disease gene 1 (PKHD1) was identified as the cause of ARPKD. The gene encodes a 67-exon transcript for a large protein of 4074 amino acids termed fibrocystin, but its function remains unknown. The neoplastic-like in cystic epithelial proliferation and the epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) axis overactivity are known as the most important characteristics of ARPKD. Since the misregulation of $Ca^{2+}$ signaling may lead to aberrant structure and function of the collecting ducts in kidney of rat with ARPKD, present study aimed to investigate the further mechanisms of abnormal proliferation of cystic cells by inhibition of PKHD1 expression. For this, a stable PKHD1-silenced HEK-293T cell line was established. Then cell proliferation rates, intracellular $Ca^{2+}$ concentration and extracellular signal-regulated kinase 1/2 (ERK1/2) activity were assessed after treatment with EGF, a calcium channel blocker and agonist, verapamil and Bay K8644. It was found that PKHD1-silenced HEK-293T cell lines were hyperproliferative to EGF stimulation. Also PKHD1-silencing lowered the intracellular $Ca^{2+}$ and caused EGF-induced ERK1/2 overactivation in the cells. An increase of intracellular $Ca^{2+}$ in PKHD1-silenced cells repressed the EGF-dependent ERK1/2 activation and the hyperproliferative response to EGF stimulation. Thus, inhibition of PKHD1 can cause EGF-induced excessive proliferation through decreasing intracellular $Ca^{2+}$ resulting in EGF-induced ERK1/2 activation. Our results suggest that the loss of fibrocystin may lead to abnormal proliferation in kidney epithelial cells and cyst formation in ARPKD by modulation of intracellular $Ca^{2+}$.

• Proceedings of the Korean Society of Plant Biotechnology Conference
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• 2003.10a
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• pp.63-63
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• 2003

• Korean Journal of Animal Reproduction
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• v.24 no.4
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• pp.343-346
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• 2000

Transgenic animals are very useful for scientific, pharmaceutical, and agricultural purposes. In livestock, transgenic technology has been used forth genetic alteration of farm animals, the production of human proteins inlarge quantities in the milk of transgenic farm animals (Clark et al., 1989; Ebert et al., 1991; Kimpenfort et al., 1991; Wall et al., 1991; Kimpenfort et al., Well et al,m 1991; Hill et al., 1992; Velander et al., 1994; Chen et al.), and the generation of animals with organs suitable for xenotransplantation (Pinkert, 1994; Chen et al., 1999). (omitted)