• Title/Summary/Keyword: GCH1

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Neuroprotective Effects of Guh-Poong-Chung-Sim-Hwan on Focal Cerebral Ischemia in Rats

  • Lim, Ha-Sup;Kim, Jeung-Beum
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.1
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    • pp.246-253
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    • 2005
  • This study was designed to investigate the neuroprotective effects of Guh-Poong-Chung-Sim-Hwan(GCH) on ischemia induced by middle cerebral artery occlusion(MCAO) in Sprague-Dawley rats. The effects of GCH administration on the size of the brain infarct and the functional status of the rats after ischemia were examined, as well as the expression of COX-2 in acute phase. The recovery of motor functions for 7 days and the brain infarct were examined to find out the delayed effects of daily GCH-administration as well. In conclusion, we found that GCH reduced both functional deficits and brain damage in the MCAO rat model of stroke. In addition, high doses of GCH reduced COX-2 expression in the penumbra. It is well known that herbal medication including GCH is very safe for humans. Accordingly, our results support the clinical use of this GKM for the treatment of stroke and offer the possibility that a potent neuroprotective agent could be developed from Korean herbal medicines.

Dopa-responsive dystonia with additional unusual clinical features: A case report confirmed by molecular genetics

  • Lee, Woong-Woo;Choi, Jong-Moon;Lee, Cha Gon
    • Journal of Genetic Medicine
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    • v.17 no.1
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    • pp.34-38
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    • 2020
  • The term dopa-responsive dystonia (DRD) is used to describe a group of neurometabolic disorders, which are characterized by dystonia, and are typically associated with diurnal fluctuations and respond to levodopa treatment. Autosomal dominant DRD (DYT5a, MIM# 128230) is caused by a heterozygous mutation in the GTP cyclohydrolase 1 (GCH1) gene (MIM# 600225). GCH1 encodes an enzyme, which is involved in the biosynthesis of tetrahydrobiopterin, an essential co-factor for tyrosine hydroxylase. Herein, we report the case of a 16-year-old girl who was diagnosed with DYT5a. She exhibited additional unusual clinical features, including intellectual disability, depression, multiple skeletal anomalies, and short stature, which are not commonly observed in patients with DYT5a. The patient harbored a heterozygous missense variant, c.539A>C, p.Gln180Pro, in the GCH1 gene, which was identified by targeted gene panel analysis using next-generation sequencing.

Optimization of Expression Conditions Enhances Production of Sepiapterin, a Precursor for Tetrahydrobiopterin Biosynthesis, in Recombinant Escherichia coli

  • Park, Eun-Hee;Lee, Won-Heong;Jang, Mi-Hee;Kim, Myoung-Dong
    • Journal of Microbiology and Biotechnology
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    • v.25 no.10
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    • pp.1709-1713
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    • 2015
  • Sepiapterin is a precursor for the synthesis of tetrahydrobiopterin (BH4), which is a wellknown cofactor for aromatic amino acid hydroxylation and nitric oxide synthesis in higher mammals. In this study, a recombinant Escherichia coli BL21(DE3) strain harboring cyanobacterial guanosine 5’-triphosphate cyclohydrolase 1 (GCH1) and human 6-pyruvoyltetrahydropterin synthase (PTPS) genes was constructed to produce sepiapterin. The optimum conditions for T7 promoter–driven expression of GCH1 and PTPS were 30℃ and 0.1 mM isopropyl-β-D-thioglucopyranoside (IPTG). The maximum sepiapterin concentration of 88.1 ± 2.4 mg/l was obtained in a batch cultivation of the recombinant E. coli, corresponding to an 18-fold increase in sepiapterin production compared with the control condition (37℃ and 1 mM IPTG).

Performance and Ignition Characteristics of a Coaxial Swirl Injector using LOX-$GCH_4$ Propellant (액체산소/기체메탄 추진제를 사용하는 동축형 스월 인젝터의 성능 및 점화특성)

  • Kim, Do-Hun;Lee, In-Chul;Kim, Jin-Kon;Koo, Ja-Ye;Park, Young-Il
    • Proceedings of the Korean Society of Propulsion Engineers Conference
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    • 2010.11a
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    • pp.72-76
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    • 2010
  • To research and develop a high performance injector for LRE, it needs not only cold flow test, but also investigations of combustion performance, optimization of cyclogram and thermo-fluid dynamical characteristics of combustion flow field through hot-fire test. In this study, hot-fire test of LOX-CH4 coaxial swirl injector has been carried out using lab-scale hot fire test stand which can supply and control cryogenic propellant. Ignition and continuous combustion for LOX-$GCH_4$ propellant of 0.19 kg/s total mass flowrate and 2.80 O/F Ratio was achieved through cyclogram optimization. The mean combustion chamber pressure and thrust were measured as approximately 1.43 MPa and 38.7 kgf respectively.

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Configuration Design, Hot-firing Test and Performance Evaluation of 200 N-Class GCH4/LOx Small Rocket Engine (Part II: Steady State-mode Ground Hot-firing Test) (200 N급 GCH4/LOx 소형로켓엔진의 형상설계와 성능시험평가 (Part II: 정상상태 지상연소시험))

  • Kim, Min Cheol;Kim, Young Jin;Kim, Jeong Soo
    • Journal of the Korean Society of Propulsion Engineers
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    • v.24 no.1
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    • pp.9-16
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    • 2020
  • A performance evaluation of the 200 N-class GCH4/LOx small rocket engine was performed through ground hot-firing test. As a result, the combustion pressure and thrust raised with the increase of the oxidizer supply pressure, and thus the specific impulse, characteristic velocity, and their efficiency increased. The characteristic velocity was measured at about 90% performance efficiency. The change of chamber aspect ratio did not affect the performance of the rocket engine in the test condition specified. In addition, uncertainty evaluation was conducted to ensure the reliability of the test results.

The Effect of Dexamethasone on Airway Goblet Cell Hyperplasia and Inflammation in $TiO_2$-Treated Sprague-Dawley Rats ($TiO_2$로 처치된 백서에서 기도내 배상세포 증식과 염증에 대한 Dexamethasone의 효과)

  • Lim, Gune-Il;Kim, Do-Jin;Park, Choon-Sik
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.1
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    • pp.37-48
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    • 2000
  • Backgrounds : The pathophysiology of chronic airflow obstruction, such as bronchial asthma, is characterized by mucus hypersecretion, goblet cell hyperplasia(GCH), smooth muscle hypertrophy, and inflammatory cells infiltration. In fatal asthma patients, one distinct findings is mucus hypersecretion due to GCH. However, the mechanisms of GCH in these hypersecretory diseases remain still unknown. In this study, a rat model was rapidly induced with GCH by instillation of $TiO_2$, intratracheally. We intend to confirm GCH and association of concomitant inflammatory cells infiltration and to observe the effect of potent antiinflammatory agent, that is dexamethasone, on GCH with inflammatory cells. Methods : Twenty-one 8-weeks-old male Sprague-Dawley rats were divided into three groups. Endotoxinfree water was instilled intratracheally in group 1(control) ; $TiO_2$, was instilled in the group 2 ; and dexamethasone was injected intraperitoneally to group 3 before $TiO_2$ instillation. After 120 hours, all rats were sacrificed, and trachea, bronchi, and lungs were resected respectively. These tissues were made as paraffin blocks and stained as PAS for goblet cells and Luna stain for eosinophils. We calculated the ratio of goblet cell to respiratory epithelium and number of infiltrated eosinophils from each tissue. Results : (1) Fraction of goblet cells was significantly increased in group 2 than in group 1 in the trachea and in the main bronchus. (10.19$\pm$11.33% vs 4.09$\pm$8.28%, p<0.01 and 34.09$\pm$23.91% vs 3.61$\pm$4.84%, p<0.01, respectively). (2) Eosinophils were significantly increased in the airway of group 2 than that of group 1. (5.43$\pm$3.84% vs 0.17$\pm$0.47 in trachea and 47.71$\pm$16.91 vs 2.71$\pm$1.96 in main bronchi). (3) There was a positive correlation between goblet cells and eosinophils(r=0.719, p=0.001). (4) There was significant difference in the decrease of goblet cells after dexamethasone injection between group 2 and group 3 (p<0.01). Also, infiltration of eosinophils was suppressed by dexamethasone. Conclusion : We made an animal model of $TiO_2$-induced goblet cell hyperplasia. GCH was observed mainly in the main bronchi with concomitant eosinophilic infiltration. Both goblet cell hyperplasia and eosinophilic infiltration were suppressed by dexamethasone. This animal model may serve as a useful tool in understanding of the mechanism of GCH in chronic airway diseases.

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A Study on the Labeling Efficiency and Cytotoxicity of Hepatocyte-targeting Galactosylated Chitosan Compounds (간세포 지향성 Galactosylated Chitosan 화합물의 표지 수율 향상 및 세포 독성에 대한 연구)

  • Kim, Dae-Weung;Jeong, Hwan-Jeong;Kim, Eun-Mi;Kim, Se-Lim;Kang, Yun-Hee;Kim, Min-Woo;Kim, Chang-Guhn;Sohn, Myung-Hee
    • The Korean Journal of Nuclear Medicine
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    • v.39 no.5
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    • pp.278-283
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    • 2005
  • Purpose: In prior study, we synthesized $^{99m}Tc$-galactosylated chitosan (GC) and performed in vivo biodistribution study, showed specific targeting to hepatocyte. The aim of this study is to evaluate the labeling efficiency and cytotoxicity of modified galactosylated chitosan compounds, galactosyl methylated chitosan (GMC) and HYNIC-galactosylated chitosan (GCH). Materials and Methods: GC, GMC and GCH were synthesized and radiolabeled with $^{99m}Tc$. Then, they were incubated for 6 hours at room temperature and human serum at $37^{\circ}C$. Labeling efficiencies were determined at 15, 30 m, 1, 2, 3 and 6 h after radiolabeling. To evaluate cytotoxicity, MTT assay was performed in HeLa and HepG2 cells. Results: In comparison with them of $^{99m}Tc$-GC labeling efficiencies of $^{99m}Tc$-GMC were significantly improved (100, 97 and 89%) in acetone and 96.3, 95.8 and 75.6% in saline at 15 m, 1 and 6 h, respectively). Moreover, $^{99m}Tc$-GCH showed more improved labeling efficiencies (>95% in acetone and human serum and >90% in saline at 6 h). In MTT assay, cytotoxicity was very low and not different from that of controls. Conclusion: These results represent that these compounds are radiochemically compatible radiopharmaceuticals, can be used in hepatocyte specific imaging study and in vivo gene or drug delivery monitoring.

Configuration Design, Hot-firing Test and Performance Evaluation of 200 N-Class GCH4/LOx Small Rocket Engine (Part I: A Preliminary Design and Test Apparatus) (200 N급 GCH4/LOx 소형로켓엔진의 형상설계와 성능시험평가 (Part I: 예비설계와 시험장치))

  • Kim, Young Jin;Kim, Min Cheol;Kim, Jeong Soo
    • Journal of the Korean Society of Propulsion Engineers
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    • v.24 no.1
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    • pp.1-8
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    • 2020
  • In this study, a configuration design of a CH4/LOx small rocket engine was made and test system was established for the performance evaluation. A coaxial swirl injector was chosen because of its remarkable atomization performance and low combustion instability. Three aspect ratios for the combustion chamber configuration, i.e., 1.5, 1.8, and 2.1 were also set for the comparison of the combustion efficiency. The reliability of the thrust measurement rig was enhanced by pre-and post-calibration process. From the preliminary ground hot-firing test, the measured thrust and specific impulse values were 89.2 N and 181.8 s, respectively, which were 21.6% lower than the ideal values. In addition, the efficiency of characteristic velocity was measured as 84.2%.

A Comparative Analysis for the Performance of 200 N-class Gaseous Methane-Liquid Oxygen Small Rocket Engine According to the Characteristic Length Variation (특성길이 변화에 따른 200 N급 기체메탄-액체산소 소형로켓엔진의 성능 비교 분석)

  • Kang, Yun Hyeong;Ahn, Hyun Jong;Kim, Jeong Soo
    • Journal of the Korean Society of Propulsion Engineers
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    • v.24 no.6
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    • pp.85-92
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    • 2020
  • Ground hot-firing tests were conducted to analyze the combustion performance according to the characteristic lengths 1.37 m, 1.71 m, and 2.06 m of the combustion chamber in 200 N-class GCH4-LOx small rocket engine. Thrust, specific impulse, and characteristic velocity at the steady-state could be obtained as the key performance parameters of the rocket engine. The performance characteristics acquired through the test were compared and analyzed with the theoretical performance calculated from CEA analysis. Observation of the influence of characteristic length on the combustion performance indicates that an optimal characteristic length shall remain between 1.71 m and 2.06 m.

Analysis of Gene Expression in Carcinogen-induced Acute Hepatotoxicity

  • Oh, Jung-Hwa;Park, Han-Jin;Lee, Eun-Hee;Heo, Sun-Hee;Cho, Jae-Woo;Kim, Yong-Bum;Yoon, Seok-Joo
    • Molecular & Cellular Toxicology
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    • v.5 no.1
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    • pp.58-66
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    • 2009
  • The 2-year rodent carcinogenicity test involves long-term, repetitive dosing of animals that is both time consuming and expensive. Alternative approaches have been attempted using specific transgenic or knockout mice or toxicogenomics to predict carcinogenicity without conducting a 2-year rodent test. In addition, toxicogenomic analysis of carcinogen-treated animals could also enhance our understanding of molecular mechanisms and aid in the diagnosis of acute toxicity induced by carcinogens. Therefore, we investigated transcription profiles after administering the carcinogens 4,4-dimethylformamide (DMF) and 4-biphenylamine (ABP). BALB/c male mice were treated once with DMF (650 mg/kg i.p.) or ABP (120 mg/kg p.o.). Standard blood biochemistry and histological changes were observed. Gene expression profiles in the livers of mice treated with either vehicle or the carcinogens were analyzed using the Affymetrix $GeneChip^{(R)}$ assay. In all, 1,474 differentially expressed genes in DMF- or ABP-treated mice were identified as being either up- or down-regulated over 1.5-fold (P< 0.01), and these genes were analyzed using hierarchical clustering and Ingenuity Pathways Analysis. Of these, 107 genes were consistently regulated in both carcinogen-treated groups. Genes associated with cancer were upregulated (Por, S100a10, Tes, Ctcf, Ddx21, Eapp, Nel, and Pa2g4) or downregulated (Cbs and Gch1). Toxicological function analysis also identified genes involved in organ toxicity, including hepatotoxicity. These data may help to identify molecular markers for acute hepatotoxicity induced by carcinogens.