• Title/Summary/Keyword: genetic safety

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Beneficial Effects of Growth Hormone Treatment in Prader-Willi Syndrome

  • Kim, Jinsup;Yang, Aram;Cho, Sung Yoon;Jin, Dong-Kyu
    • Journal of mucopolysaccharidosis and rare diseases
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    • v.3 no.2
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    • pp.41-43
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    • 2017
  • Prader-Willi syndrome (PWS) is a genetic disorder that is considered, especially on child, to cause poor feeding, hypotonia, failure to thrive, developmental delay and hypogonadism which is known to affect between 1 in 10,000 and 30,000 people. The children with PWS are viewed as affected by growth hormone (GH) insufficiency, although the exact mechanisms of GH deficiency are not fully understood. However, the benefits of GH treatment in children with PWS are well established. Myers, et al. (2006), Grugni, et al. (2016) indicated its positive effects on linear growth, body composition, motor function, respiratory function and psychomotor development. Despite of its effectiveness and advantages had been well known and proven in many other studies, there is only one recombinant GH product that is approved for PWS in Korea, $Genotropin^{(R)}$, till now. A phase III clinical study of GH treatment with $Eutropin^{TM}$, in 34 Korean PWS children is in progress, which is expected to have comparable effects and safety profile with the active control by assessing auxological changes such as height standard deviation score, body composition changes such as lean body mass and percent body fat, motor and cognitive development using Bayley scale, and safety profiles.

Prediction of golden time for recovering SISs using deep fuzzy neural networks with rule-dropout

  • Jo, Hye Seon;Koo, Young Do;Park, Ji Hun;Oh, Sang Won;Kim, Chang-Hwoi;Na, Man Gyun
    • Nuclear Engineering and Technology
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    • v.53 no.12
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    • pp.4014-4021
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    • 2021
  • If safety injection systems (SISs) do not work in the event of a loss-of-coolant accident (LOCA), the accident can progress to a severe accident in which the reactor core is exposed and the reactor vessel fails. Therefore, it is considered that a technology that provides recoverable maximum time for SIS actuation is necessary to prevent this progression. In this study, the corresponding time was defined as the golden time. To achieve the objective of accurately predicting the golden time, the prediction was performed using the deep fuzzy neural network (DFNN) with rule-dropout. The DFNN with rule-dropout has an architecture in which many of the fuzzy neural networks (FNNs) are connected and is a method in which the fuzzy rule numbers, which are directly related to the number of nodes in the FNN that affect inference performance, are properly adjusted by a genetic algorithm. The golden time prediction performance of the DFNN model with rule-dropout was better than that of the support vector regression model. By using the prediction result through the proposed DFNN with rule-dropout, it is expected to prevent the aggravation of the accidents by providing the maximum remaining time for SIS recovery, which failed in the LOCA situation.

Mutagenicity and Genotoxicity Assessment of Leuconostoc lactis DMLL10 Isolated from Kimchi

  • Heejung Park;Seoyeon Lee;Sojeong Heo;Do-Won Jeong
    • Journal of Microbiology and Biotechnology
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    • v.34 no.9
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    • pp.1803-1809
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    • 2024
  • Leuconostoc lactis DMLL10 is a microorganism specific to kimchi fermentation. In this study, we sought to evaluate the toxicity of this strain, which was newly isolated from kimchi, to determine its safety as a food ingredient. Bacterial reverse mutation assay, chromosomal aberration assay, and mammalian cell in vitro micronucleus assay were performed to assess the genetic toxicity of Leu. lactis DMLL10. The strain did not induce mutagenicity in Salmonella typhimurium TA98, TA100, TA1535, TA1537, or Escherichia coli WP2uvrA, with or without metabolic activation of S9 mixture. The oral administration of Leu. lactis DMLL10 also did not significantly increase the number of micronucleated polychromatic erythrocytes, or the mean ratio of polychromatic to total erythrocytes. Additionally, Leu. lactis DMLL10 did not cause a significant chromosomal aberration in CHU/IL cells in the presence or absence of S9 activation. Therefore, Leu. lactis DMLL10 can be suggested as a functional food ingredient with reliability and safety.

Stem Cells and Cell-Cell Communication in the Understanding of the Role of Diet and Nutrients in Human Diseases

  • Trosko James E.
    • Journal of Food Hygiene and Safety
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    • v.22 no.1
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    • pp.1-14
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    • 2007
  • The term, "food safety", has traditionally been viewed as a practical science aimed at assuring the prevention acute illnesses caused by biological microorganisms, and only to a minor extent, chronic diseases cause by chronic low level exposures to natural and synthetic chemicals or pollutants. "food safety" meant to prevent microbiological agents/toxins in/on foods, due to contamination any where from "farm to Fork", from causing acute health effects, especially to the young, immune-compromised, genetically-predisposed and elderly. However, today a broader view must also include the fact that diet, perse (nutrients, vitamins/minerals, calories), as well as low level toxins and pollutant or supplemented synthetic chemicals, can alter gene expressions of stem/progenitor/terminally-differentiated cells, leading to chronic inflammation and other mal-functions that could lead to diseases such as cancer, diabetes, atherogenesis and possibly reproductive and neurological disorders. Understanding of the mechanisms by which natural or synthetic chemical toxins/toxicants, in/on food, interact with the pathogenesis of acute and chronic diseases, should lead to a "systems" approach to "food safety". Clearly, the interactions of diet/food with the genetic background, gender, and developmental state of the individual, together with (a) interactions of other endogenous/exogenous chemicals/drugs; (b) the specific biology of the cells being affected; (c) the mechanisms by which the presence or absence of toxins/toxicants and nutrients work to cause toxicities; and (d) how those mechanisms affect the pathogenesis of acute and/or chronic diseases, must be integrated into a "system" approach. Mechanisms of how toxins/toxicants cause cellular toxicities, such as mutagenesis; cytotoxicity and altered gene expression, must take into account (a) irreversible or reversal changes caused by these toxins or toxicants; (b)concepts of thresholds or no-thresholds of action; and (c) concepts of differential effects on stem cells, progenitor cells and terminally differentiated cells in different organs. This brief Commentary tries to illustrate this complex interaction between what is on/in foods with one disease, namely cancer. Since the understanding of cancer, while still incomplete, can shed light on the multiple ways that toxins/toxicants, as well as dietary modulation of nutrients/vitamins/metals/ calories, can either enhance or reduce the risk to cancer. In particular, diets that alter the embryo-fetal micro-environment might dramatically alter disease formation later in life. In effect "food safety" can not be assessed without understanding how food could be 'toxic', or how that mechanism of toxicity interacts with the pathogenesis of any disease.

Allele Frequencies of the Single Nucleotide Polymorphisms Related to the Body Burden of Heavy Metals in the Korean Population and Their Ethnic Differences

  • Eom, Sang-Yong;Lim, Ji-Ae;Kim, Yong-Dae;Choi, Byung-Sun;Hwang, Myung Sil;Park, Jung-Duck;Kim, Heon;Kwon, Ho-Jang
    • Toxicological Research
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    • v.32 no.3
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    • pp.195-205
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    • 2016
  • This study was performed to select single nucleotide polymorphisms (SNPs) related to the body burden of heavy metals in Koreans, to provide Korean allele frequencies of selected SNPs, and to assess the difference in allele frequencies with other ethnicities. The candidate-gene approach method and genome-wide association screening were used to select SNPs related to the body burden of heavy metals. Genotyping analysis of the final 192 SNPs selected was performed on 1,483 subjects using the VeraCode Goldengate assay. Allele frequencies differences and genetic differentiations between the Korean population and Chinese (CHB), Japanese (JPT), Caucasian (CEU), and African (YIR) populations were tested by Fisher's exact test and fixation index ($F_{ST}$), respectively. The Korean population was genetically similar to the CHB and JPT populations ($F_{ST}$ < 0.05, for all SNPs in both populations). However, a significant difference in the allele frequencies between the Korean and CEU and YIR populations were observed in 99 SNPs (60.7%) and 120 SNPs (73.6%), respectively. Ten (6.1%) and 26 (16.0%) SNPs had genetic differentiation ($F_{ST}$ > 0.05) among the Korean-CEU and Korean-YIR comparisons, respectively. The SNP with the largest $F_{ST}$ value between the Korean and African populations was cystathionine-${\beta}$-synthase rs234709 ($F_{ST}$: KOR-YIR, 0.309; KOR-CEU, 0.064). Our study suggests that interethnic differences exist in SNPs associated with heavy metals of Koreans, and it should be considered in future studies that address ethnic differences in heavy-metal concentrations in the body and genetic susceptibility to the body burden of heavy metals.

Concrete Mixture Design for RC Structures under Carbonation - Application of Genetic Algorithm Technique to Mixture Conditions (탄산화에 노출된 콘크리트 구조물의 배합설계에 대한 연구 - 유전자 알고리즘 적용성 평가)

  • Lee, Sung-Chil;Maria, Q. Feng;Kwon, Sung-Jun
    • Journal of the Korea Concrete Institute
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    • v.22 no.3
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    • pp.335-343
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    • 2010
  • Steel corrosion in reinforced concrete (RC) structures is a critical problem to structural safety and many researches are being actively conducted on developing methods to maintain the required performance of the RC structures during their intended service lives. In this study, concrete mixture proportioning technique through genetic algorithm (GA) for RC structures under carbonation, which is considered to be serious in underground site and big cities, is investigated. For this, mixture proportions and diffusion coefficients of $CO_2$ from the previous researches were analyzed and fitness function for $CO_2$ diffusion coefficient was derived through regression analysis. This function based on the 12 experimental results consisted of 5 variables including water-cement ratio (W/C), cement content, sand percentage, coarse aggregate content per unit volume of concrete in unit, and relative humidity. Through genetic algorithm (GA) technique, simulated mixture proportions were proposed for 3 cases of verification and they showed reasonable results with less than relative error of 10%. Finally, assuming intended service life, different exposure conditions, design parameters, intended $CO_2$ diffusion coefficients, and cement contents were determined and related mixture proportions were simulated. This proposed technique is capable of suggesting reasonable mix proportions and can be modified based on experimental data which consider various mixing components like mineral admixtures.

Biomonitoring Human Exposure to VOCs : Using Individual Susceptibility Markers

  • Kim, Jung-Hyun;Kim, Dae-Seon;Park, Jae-Sung;Kang, Tack-Shin
    • Proceedings of the Korean Environmental Health Society Conference
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    • 2003.06a
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    • pp.187-191
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    • 2003
  • In this study, biomonitoring methods were developed to measure BTEXs exposure level in the air, metabolites of benzene and toluene in human urine, individual susceptibility markers in human blood for evaluation of the health effects about environmental pollution. We have also performed a small-scaled molecular epidemiology study on residents in Chuncheon and workers in workplace for these method applications. The workers in workplace were surveyed as study areas, and the residents in Chuncheon which is in the suburban area were surveyed as comparative areas in this study. Actually, 31 workers in as target group and 33 residences in as control group this epidemiological study. The results obtained from this study were as follows: 1. Benzene is a well-known carcinogen, it's median concentrations were 0.00024∼0.02057ppm at suburban area and 0.002∼00.654ppm at work place, These benzene concentrations were not exceed the OSHA(Occupational Safety and Health Administration) threshold benzene level of 1ppm in the states. 2. Metabolites product of benzene(t,t-Muconic Acid) and toluene(Hippuric Acid) were not significant both in suburban and workplace area. The median concentration of t,t-MA and HA were 0.0122, 1.44277g/g creatinine, respectively. 3. In the case of individual susceptibility markers as CYPlAl, 41.8% of them has homozygous wild type(W) and who has heterozygous variant type(H) was 35.4% and 22.8% of homozygous variant type(M) genetic type. In the case of CYP2E1, 62.82% of them has homozygous wild type(D) type, 34.62% of each has heterozygous variant type (DC) and 2.56% of them has homozygous variant type (CC). Who doesn't have GSTM1 gene was 46.25% and who has GSTM1 gene was 53.75%. Who doesn't have GSTT1 gene was 40.0% in study groups and who has GSTT1 gene was 60.0%. Who has W genetic type, which is homozygous wild type of GSTP1, was 69.18% and H genetic type, which is heterozygous variant type was 28.4%. M genetic type which is homozygous variant type was 2.4%. 4. Concentration differences of metabolites such as t,t-MA and HA in urine, which is generated by individual susceptibility marker of GSTM1, GSTT1, GSTP1 gene of Phase I and CYP1A1, CYP2E1 gene of Phase II, was examined. As a result, GSTP1 and GSTM1 indicate slight differences depend on the amount of metabolites in urine, it was not statistically significant.

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Survey of Asbestos-Related Disease on Chest Radiograph of Workers Exposed to Asbestos in Ship Repair (조선수리업종 석면노출 근로자들의 흉부방사선상 석면관련 폐질환 소견의 발생양상)

  • Lee Hyun Jae;Hong Young Seoub;Son Ji Eun;Lee Young Ill;Kim Sang Hoon;Im Hyoung June;Kim Jung Man;Kim Joon Youn
    • Journal of Life Science
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    • v.16 no.1
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    • pp.58-63
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    • 2006
  • There was cross-sectional study on investigating the factors related asbestos-related disease on chest radiograph of workers exposed to asbestos in ship repair. According to Occupational Safety & Health Administration asbestos standard, medical surveillance, chest radiologic study, pulmonary function test and medical questionnaire are performed in 118 subjects exposed to asbestos for 10 years or more in ship repair. The sixteen out of 118 subjects $(13.6\%)$ were observed asbestos-related disease finding on chest radiography. Significant factors related to those finding on chest radiography were abnormal pulmonary function test, cough, sputum, past history of respiratory disease, work duration. Workers with Significant factors related asbestos-related disease finding on chest radiography should be managed on a strict program. Further, factors unrelated with asbestos-related disease finding on this study should be evaluated prospectively for medical surveillance program of workers exposed to asbestos.

In vivo Genotoxicity of Silver Nanoparticles after 90-day Silver Nanoparticle Inhalation Exposure

  • Kim, Jin-Sik;Sung, Jae-Hyuck;Ji, Jun-Ho;Song, Kyung-Seuk;Lee, Ji-Hyun;Kang, Chang-Soo;Yu, Il-Je
    • Safety and Health at Work
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    • v.2 no.1
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    • pp.34-38
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    • 2011
  • Objectives: The antimicrobial activity of silver nanoparticles has resulted in their widespread use in many consumer products. Yet, despite their many advantages, it is also important to determine whether silver nanoparticles may represent a hazard to the environment and human health. Methods: Thus, to evaluate the genotoxic potential of silver nanoparticles, in vivo genotoxicity testing (OECD 474, in vivo micronuclei test) was conducted after exposing male and female Sprague-Dawley rats to silver nanoparticles by inhalation for 90 days according to OECD test guideline 413 (Subchronic Inhalation Toxicity: 90 Day Study) with a good laboratory practice system. The rats were exposed to silver nanoparticles (18 nm diameter) at concentrations of $0.7\;{\times}\;10^6$ particles/$cm^3$ (low dose), $1.4\;{\times}\;10^6$ particles/$cm^3$ (middle dose), and $2.9\;{\times}\;10^6$ particles/$cm^3$ (high dose) for 6 hr/day in an inhalation chamber for 90 days. The rats were killed 24 hr after the last administration, then the femurs were removed and the bone marrow collected and evaluated for micronucleus induction. Results: There were no statistically significant differences in the micronucleated polychromatic erythrocytes or in the ratio of polychromatic erythrocytes among the total erythrocytes after silver nanoparticle exposure when compared with the control. Conclusion: The present results suggest that exposure to silver nanoparticles by inhalation for 90 days does not induce genetic toxicity in male and female rat bone marrow in vivo.