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A Case of Citrin Deficiency Presenting with Recurrent Hypoglycemia: Diagnosed by Targeted Exome Sequencing (반복적인 저혈당으로 엑솜 시퀀싱을 통해 31개월에 진단된 Citrin 결핍증 1례)

  • Kim, Chiwoo;Hwang, Jeongyun;Yang, Aram;Kim, Jinsup;Lee, Taeheon;Jang, Ja-Hyun;Cho, Sung Yoon;Jin, Dong-Kyu
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.17 no.2
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    • pp.69-76
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    • 2017
  • Citrin deficiency is an autosomal recessive disorder caused by mutations in the SLC25A13 gene on chromosome 7q21.3, and a type of urea cycle disorder that causes hyperammonemia. Although neonatal intrahepatic cholestasis and adult-onset type II citrullinemia, a type of citrin deficiency, have been described well in many articles for several decades, failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), the other type of citrin deficiency, has been only identified recently. There was previously no case report about FTTDCD in Korea. Patients with FTTDCD could present with loss of appetite, fatigue, failure to thrive, hypoglycemia, hypercitrullinemia, dyslipidemia, and an increased lactate/pyruvate ratio. Routine evaluation may not reveal the cause of hypoglycemia caused by citrin deficiency. We recently had a case that presented with recurrent hypoglycemia in a 30-month-old boy. Chemistry profiling, urine organic acid analysis, plasma acylcarnitine analysis, and hormone studies indicated values within the normal range or non-specific findings. Mutation analysis to identify the cause of hypoglycemia identified the subject as a compound heterozygote carrying each of the c.852_855del ($p.Met285Profs^*2$), and c.1177+1G>A mutant alleles. We report here on this unusual case of citrin deficiency presenting with FTTDCD for the first time in Korea.

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Cytologic Features of Endometrial Hyperplasia : Comparison with Normal Endometrium and Endometrial Adenocarcinoma (자궁내막증식증의 세포학적 고찰: 정상자궁내막세포 및 자궁내막선암종과 비교)

  • Hong, Sung-Ran;Seon, Mee-Im;Kim, Yee-Jeong;Chun, Yi-Kyeong;Kim, Hye-Sun;Kim, Hy-Sook
    • The Korean Journal of Cytopathology
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    • v.11 no.1
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    • pp.1-10
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    • 2000
  • The purpose of this study is to describe the cellular characteristics of endometrial hyperplasia without/with atypia in cervical smears. These cellular features were compared with those of normal endometrium and endometrial carcinoma. We reviewed 265 cervical smears : 64 normal proliferative endometrium, 118 endometrial hyperplasia without atypia, 21 endometrial hyperplasia with atypia, and 62 endometrial adenocarcinoma. Of these smears, 72(27.2%) smears which had diagnostic endometrial epithelial cells were selected for this study. The cytologic abnormalities about cellularity, background, changes in cellular architecture, alterations in nuclear size, anisokaryosis, chromatin pattern, nucleoli, cytoplasmic vacuoles, and mitosis were observed. Nuclear enlargement(1.6 to 2 times of the nucleus in the intermediate squamous cell) and anisokaryosis(${\geq}$2 fold in size variation) were highly suggestive of endometrial hyperplasia without/with atypia. The nuclei from endometrial hyperplasia with atypia were more coarsely granular in chromatin patterns than hyperplasia without atypia(33.3% vs 3.4%). Micronucleoli were observed in all endometrial conditions, but the presence of macronucleoli were more suggestive of hyperplasia with atypia(22.2%) and adenocarcinoma(55%). The changes in cellular architecture(loss of polarity, uneven internuclear distance, overlapping and loose arrangement) were seen in hyperplasia with atypia and adenocarcinoma. Characteristically, bloody background was seen in endometrial hyperpiasia, and cellular detritus or granular proteinaceous material was only observed in endometrial adenocarcinoma. Mitoses were also observed in adenocarcinoma. In conclusion, although there is no single parameter useful for the cytologic differential diagnosis of endometrial lesions, combined cytologic evaluation can be used to diagnose hyperplasia cytologically.

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Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

  • Lee, JooBuom;Lee, Kyungsun;Choe, Keunbum;Jung, Hyunseob;Cho, Hyunseok;Choi, Kiseok;Kim, Taegon;Kim, Seojin;Lee, Hyeong-Seok;Cha, Mi-Jin;Song, Si-Whan;Lee, Chul Kyu;Chun, Gie-Taek
    • Toxicological Research
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    • v.31 no.4
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    • pp.371-392
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    • 2015
  • TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

Effect of the redox flow battery and electrode characteristics according to the heat treatment temperature of a carbon felt (탄소펠트의 열처리 온도에 따른 레독스흐름전지와 전극 특성에 미치는 영향)

  • Yoo, Hyosung;You, Hyunjin;Yu, Kihyun;Kang, Junyoung;Park, Hongsik;Choi, Woonghwi;Yoo, Dong Jin
    • Journal of Energy Engineering
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    • v.24 no.3
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    • pp.89-95
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    • 2015
  • Carbon felts manufactured by (Co)CNF were subjected to heat treatment under different temperatures to use for the electrode of a redox-flow battery. BET and weight loss were tested to investigate the physical properties of the carbon felt according to the heat treatment conditions. SEM and XPS were also analyzed to characterize their surface area. In addition, electrical resistance, CV (cyclic voltammetry) and RFB charge on the electrode properties were examined in accordance with the heat treatment conditions with the discharge performance. The changes of physical properties on the carbon felt surface was confirmed via SEM and BET analysis, The most addition of oxygen functional groups on the carbon felt surface was obtained when one hour heat treatment at $550^{\circ}C$ and it was confirmed by XPS analysis. After resulting the CV tests, the active area of the electrode was the largest at $550^{\circ}C$ heat treatment. The heat treatment experiment of vanadium redox flow battery using the carbon felts were tested at $400^{\circ}C$, $500^{\circ}C$ and $550^{\circ}C$. As a result, the charge-discharge energy efficiency of the heat treatment electrode was 72.9% and 79.8%, at $400^{\circ}C$ and $500^{\circ}C$, respectively. The efficiency of the heat treatment electrode at $550^{\circ}C$ was the best as 79.8% at $550^{\circ}C$.

Review of Failure Mechanisms on the Semiconductor Devices under Electromagnetic Pulses (고출력전자기파에 의한 반도체부품의 고장메커니즘 고찰)

  • Kim, Dongshin;Koo, Yong-Sung;Kim, Ju-Hee;Kang, Soyeon;Oh, Wonwook;Chan, Sung-Il
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.18 no.6
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    • pp.37-43
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    • 2017
  • This review investigates the basic principle of physical interactions and failure mechanisms introduced in the materials and inner parts of semiconducting components under electromagnetic pulses (EMPs). The transfer process of EMPs at the semiconducting component level can be explained based on three layer structures (air, dielectric, and conductor layers). The theoretically absorbed energy can be predicted by the complex reflection coefficient. The main failure mechanisms of semiconductor components are also described based on the Joule heating energy generated by the coupling between materials and the applied EMPs. Breakdown of the P-N junction, burnout of the circuit pattern in the semiconductor chip, and damage to connecting wires between the lead frame and semiconducting chips can result from dielectric heating and eddy current loss due to electric and magnetic fields. To summarize, the EMPs transferred to the semiconductor components interact with the chip material in a semiconductor, and dipolar polarization and ionic conduction happen at the same time. Destruction of the P-N junction can result from excessive reverse voltage. Further EMP research at the semiconducting component level is needed to improve the reliability and susceptibility of electric and electronic systems.

Effects of dietary marigold extract supplementation on growth performance, pigmentation, antioxidant capacity and meat quality in broiler chickens

  • Wang, Shuhao;Zhang, Lin;Li, Jiaolong;Cong, Jiahui;Gao, Feng;Zhou, Guanghong
    • Asian-Australasian Journal of Animal Sciences
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    • v.30 no.1
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    • pp.71-77
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    • 2017
  • Objective: This experiment was conducted to investigate the effects of dietary supplementation with marigold extract on growth performance, pigmentation, antioxidant capacity and meat quality in broiler chickens. Methods: A total of 320 one-day-old Arbor Acres chickens were randomly divided into 5 groups with 8 replicates of 8 chickens each. The chickens of control group were fed with basal diet and other experimental groups were fed with basal diet supplemented with 0.075%, 0.15%, 0.30%, and 0.60% marigold extract respectively (the corresponding concentrations of lutein were 15, 30, 60, and 120 mg/kg). Results: The results showed that marigold extract supplementation increased the yellowness values of shank, beak, skin and muscle and the redness ($a^*$) value of thigh muscle (linear, p<0.01). Marigold extract supplementation significantly increased the total antioxidant capacity, and the activities of superoxide dismutase in liver and thigh muscle (linear, p<0.01) and significantly decreased the malondialdehyde contents of liver and thigh muscle (linear, p<0.01). Marigold extract supplementation significantly decreased the drip loss and shear force of thigh muscles (linear, p<0.01). There was no significant effect on growth performance with marigold extract supplementation. Conclusion: In conclusion, dietary supplementation of marigold extract significantly increased the yellowness values of carcass, antioxidant capacity and meat quality in broiler chickens.

Treatment Strategies for Primary Central Nervous System Lymphoma (원발성 중추신경계 림프종의 치료전략)

  • Kim, Il-Man;Lee, Chang Young;Son, Eun Ik;Kim, Dong Won;Yim, Man Bin;Kim, Sang Pyo
    • Journal of Korean Neurosurgical Society
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    • v.30 no.3
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    • pp.334-341
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    • 2001
  • Objective : We have currently changed treatment strategies to methotrexate(MTX)-based preirradiation chemotherapy with subsequent planned radiation for the initial therapy of primary central nervous system lymphoma (PCNSL). The aim of this study was to evaluate the results of treating PCNSL with chemotherapy plus radiotherapy (CRT) or radiotherapy(RT) alone. Method and Material : This study involved 10 females and 3 males patients with a mean age of 54.2 years. All patients underwent surgery, open(8 cases) or stereotactic biopsy(5 cases) for histological diagnosis. Eleven tumors were diffuse large B-cell lymphomas. Tumor volume change in the follow-up images and survival time were evaluated in patients treated with CRT and RT alone. In the beginning, two patients received ProMACE-Cytabom chemotherapeutic regimen, but did not complete the course and died of progressive tumor 8 and 9 months after diagnosis, respectively. One patient died at 6 months before chemotherapy. These three were excluded from the survival analysis. Five patients(RT group) completed full courses of cranial irradiation with or without boost. For the current combined modality treatment, high-dose MTXbased chemotherapy(systemic and intrathecal MTX, IV vincristine, and oral procarbazine) followed by whole brain irrdiation to 45Gy to tumor was introduced in 5 patients of CRT group. Result : A complete response was achieved in three of five who received RT only and in all of five who received CRT. All patients in CRT groups are in disease free status at a mean 23 months following therapy. The RT group patients refused any additional salvage therapy at tumor relapse and survived at mean 20 months from diagnosis. The Karnofsky performance status improved in eight of ten patients with treatment. The treatment toxicity included leukoencephalopathy in RT group and severe leukopenia, transient hepatitis, avascular necrosis of femoral head, hearing loss, and amenorrhea in CRT group, respectively. Conclusion : The combined modality therapy of MTX-based chemotherapy plus radiotherapy for PCNSL may enhance tumor response and improve patient survival. The patients who received CRT should be carefully followed up because of the higher risk of treatment-induced late neurotoxicity.

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Sedum sarmentosum Enhances Hyaluronan Synthesis in Transformed Human Keratinocytes and Increases Water Content in Human Skin (돌나물추출물에 의한 사람 각질형성세포에서의 Hyaluronan Synthesis 촉진과 인체 피부의 보습력 증진)

  • Sim, Gwan-Sub;Kim, Jin-Hwa;Lee, Dong-Hwan;Na, Young;Lee, Geun-Soo;Pyo, Hyeong-Bae
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.1 s.60
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    • pp.17-22
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    • 2007
  • In this study, we investigated the effects of Sedum sarmentosum extract on the expression of hyaluronan synthase (HAS) genes and hyaluronan (HA) production in HaCaT keratinocytes. We also assessed water content (electrical capacitance) and transepidermal water loss (TEWL) in human skin after topical treatment with Sedum sarmentosum extract. Sedum sarmentosum extract increased expression of HAS-2 and HAS-3 genes in HaCaT cells, when assayed by real-time reverse-transcriptase polymerase chain reactions (RT-PCR). Sedum sarmentosum extract induced HA production in HaCaT cells, when determined by enzyme-linked immunosorbent assay (ELISA). Finally, treatment of Sedum sarmentosum extract on human skin increased the skin hydration and decreased TEWL when measured using Corneometer and Tewameter. Our study suggests that Sedum sarmentosum extract should be a very useful cosmetic ingredient, as a skin moisturizer.

The Fragments of Fibronectin (Fn-fr's 70, 45 kDa) Increase MMP-1 Expression and MMP-2 Activity in Normal Human Fibroblasts (사람 피부 섬유아세포에서의 파이브로넥틴 조각(70, 45 kDa)에 의한 MMP-1 발현 증가와 MMP-2 활성 증가 연구)

  • Hwang, Jae-Sung;Kim, Hyae-Kyoung;Son, Eui-Dong;Lee, Jin-Young;Kang, Hak-Hee;Chang, Ih-Seop
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.4
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    • pp.245-249
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    • 2007
  • The alternation of extracellular matrix (ECM) protein in aging process is associated with symptoms such as wrinkling and loss of elasticity in skin. Now, the major target proteins for anti-aging have been metalloproteases and the structural proteins such as collagen and elastin. Recently, the interaction of cell and ECM proteins (collagen, fibrillin, and fibronectin) is reported to have an important role in survival, proliferation and tissue reconstruction. Fibronectin is a matrix adhesion protein which binds to collagen and integrin and degraded by serine proteases. It has been reported that fragments of fibronectin (Fn-fr's) were involved in matrix metalloproteases (MMPs) expression in osteoblast. But, the role of Fn-fr's in human skin and in skin cells has not been reported yet. Therefore, we investigated the differences of fibronectin fragmentation pattern between young and aged human skin, and demonstrated that the fragmentation of fibronectins is significantly increased in aged human skin. Also, treatment of Fn-fr's (70, 45 kDa) increased MMP-1 expression and MMP-2 activity in human dermal fibroblasts. Our results suggest that Fn-fr's as a potential new factor to accelerate skin aging.

Application of Au-Sn Eutectic Bonding in Hermetic Rf MEMS Wafer Level Packaging (Au-Sn 공정 접합을 이용한 RF MEMS 소자의 Hermetic 웨이퍼 레벨 패키징)

  • Wang Qian;Kim Woonbae;Choa Sung-Hoon;Jung Kyudong;Hwang Junsik;Lee Moonchul;Moon Changyoul;Song Insang
    • Journal of the Microelectronics and Packaging Society
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    • v.12 no.3 s.36
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    • pp.197-205
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    • 2005
  • Development of the packaging is one of the critical issues for commercialization of the RF-MEMS devices. RF MEMS package should be designed to have small size, hermetic protection, good RF performance and high reliability. In addition, packaging should be conducted at sufficiently low temperature. In this paper, a low temperature hermetic wafer level packaging scheme for the RF-MEMS devices is presented. For hermetic sealing, Au-Sn eutectic bonding technology at the temperature below $300{\times}C$ is used. Au-Sn multilayer metallization with a square loop of $70{\mu}m$ in width is performed. The electrical feed-through is achieved by the vertical through-hole via filled with electroplated Cu. The size of the MEMS Package is $1mm\times1mm\times700{\mu}m$. By applying $O_2$ plasma ashing and fabrication process optimization, we can achieve the void-free structure within the bonding interface as well as via hole. The shear strength and hermeticity of the package satisfy the requirements of MIL-STD-883F. Any organic gases or contamination are not observed inside the package. The total insertion loss for the packaging is 0.075 dB at 2 GHz. Furthermore, the robustness of the package is demonstrated by observing no performance degradation and physical damage of the package after several reliability tests.

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