• Journal of The Korean Society of Inherited Metabolic disease
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• v.14 no.2
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• pp.178-181
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• 2014

Hunter syndrome (mucopolysaccharidosis type II, MPS II) is a X-linked lysosomal storage disease caused by a deficiency in the lysosomal enzyme, iduronate-2-sulfatase (IDS), leading to accumulation of glycosaminoglycans within lysosomes of many organs and tissues. Since the enzyme replacement therapy was approved and available in the treatment of MPS I, II, VI, early diagnosis and early therapy can bring the better prognosis of disease and the better quality of life in patients. We described a 2.5 year old child presented with frequent otitis media and developmental delay including speech impairment, who was diagnosed as Hunter syndrome with IDS NM_000202.5:c. 263G>A(p.Arg88His) mutation.

• Applied Microscopy
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• v.32 no.2
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• pp.149-156
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• 2002

For investigation of the activated carbon in the rat liver toxicated by lead. Aniamls used $7{\sim}8$ weeks to Sparague-Dewley rat (150 g). The lead acetate (500 ppm) were injected and activated carbon (40 mg/kg) were treated orally for four and eight weeks, respectivelly, and observed by the electron microscope. The group with only lead for 4 weeks, The mitochondria and rough endoplasmic reticulum (rER) were extended and ribosomes dropped from the rER. The group with lead-activated carbon for 4 weeks, The number of lysosomes increased. The shapes of nucleus and rough endoplasmic reticulum observed almost similar with nomally. The group with only lead for 8 weeks, The mitochondria and rough endoplasmic reticulum (rER) were more extended. The group with lead-activated carbon for 8 weeks, the nucleus and rough endoplasmic reticulum was observed nomally.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.2
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• pp.50-54
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• 2020

Vici syndrome is a rare, autosomal recessive multisystem disorder characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, hypopigmentation, immunodeficiency, and delayed development. We report the case of a 3-year-old boy diagnosed with Vici syndrome. He initially presented with hypotonia and sucking problem. Whole-exome sequencing identified novel compound heterozygous mutations, namely c.2254C>T (p.Gln752Ter) and c.5511-5518+2 del TATGCAAAGT in the EPG5 gene. The diagnostic challenges can be attributed to the diverse clinical manifestations. Thus, whole-exome sequencing is a useful diagnostic tool for the genetically and clinically heterogeneous Vici syndrome. This is the first Korean report of a patient with Vici syndrome.

• Journal of Acupuncture Research
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• v.19 no.2
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• pp.51-64
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• 2002

We have compared(using the same series of experimental tissue samples) the levels of proteolytic enzyme activities and free radical-induced protein damage in synovial fluid from RA and CPH cases. Many protease types showed significantly increased (typically by a factor of approximately 2-3-fold) activity in RA, compared to normal rats. However, CPH significantly reduced the cytoplasmic enzyme activities of arginyl aminopeptidase, leucyl aminopeptidase, pyroglutamyl aminopeptidase, tripeptidyl aminopeptidase, and proline endopeptidase to almost about 1/10 each. For the Iysosomal proteases, synovial fluid samples from RA rats, CPH significantly reduced the enzyme activities of cathepsin B, dipeptidyl aminopeptidase I and dipeptidyl aminopeptidase II. In extracellular matrix degrading(collagenase, tissue elastase) and leukocyte as sociated proteases (leukocyte elastase, cathepsin G), CPH decreased these enzyme activities of collagenase, tissue elastase and leukocyte associated elastase in RA. In cytoplasmic and lysosomal protease activities in plasma from RA. CPH and normal plasma samples were not significantly different, suggesting that altered activity of plasma proteases (particularly those enzymes putatively involved in the immune response) is not a contributory factor in the pathogenesis of RA. In addition, the level of free radical induced damage to synovial fluid proteins was approximately twice that in RA, compared with CPH. CPH significantly decreased the level of ROS induced oxidative damage to synovial fluid proteins (quantified as protein carbonyl derivative). Therefore we conclude that both proteolytic enzymes and free radicals are likely to be of equal potential importance as damaging agents in the pathogenesis of inflammatory joint disease, and that the design of novel therapeutic strategies for patients with the latter disorder should include both protease inhibitory and free radical scavenging elements. In addition, the protease inhibitory element should be designed to inhibit the action of a broad range of protease mechanistic types (i.e. cysteine-, metallo- and serine- proteinases and peptidases). However, increased protein damage induced by ROS could not be rationalised in terms of compromised antioxidant total capacity, since the latter was not significantly altered in RA synovial fluid or plasma compared with CPH.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.63-68
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• 2017

Gaucher disease (GD) is caused by the deficiency of glucocerebrosidase. In pediatric patients with GD, especially Type I GD, enzyme replacement therapy (ERT) can reduce the hepatosplenomegaly and improve the hematologic finding and growth velocity. Herein, we report a 2-year-old girl with Type I GD presented with hepatosplenomegaly, bone pain and growth retardation. A 2 year-old-girl was referred to our hospital due to severe hepatosplenomegaly and growth retardation. She suffered from both leg pain and chronic fatigue. Simple x-ray showed widened distal long bones like that of an 'Erlenmeyer flask' which is associated with GD. The laboratory test showed anemia and thrombocytopenia. The enzyme activity was markedly reduced and the direct sequencing of the GBA gene showed the compound heterozygous mutations, p.G46E and p.L444P. As the G46E have been considered as the protective gene against neuronopathic genotype, we could assess the Type I GD in this patient. After one year of ERT, the growth velocity became 11 cm per year. Bone pain and fatigue disappeared. The volume of liver and spleen was reduced from $683cm^3$ and $703cm^3$ to $590cm^3$ and $235cm^3$, respectively. Although GD is an extremely rare disease in Korea, growth retardation and bone pain in children are the important signs which lead to early detection of GD and a simple radiologic finding is helpful to assess the GD at outpatient clinic. We highlight that the early diagnosis and early ERT is important for good growth and outcome for pediatric patients with GD.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.17 no.2
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• pp.55-62
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• 2017

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by beta-glucosidase deficiency. An 18 month-old male with hepatosplenomegaly, anemia, thrombocytopenia, and growth retardation referred to our hospital. The patient showed neurological symptoms, such as supranuclear gaze palsy and developmental delay. Bone marrow biopsy performed to rule out malignancy and the results revealed no malignant cell; however, abnormal histiocytes suggesting storage disease was noted. Based on hepatosplenomegaly, bicytopenia and unexplained neurologic manifestations, enzyme activity and genetic analysis were conducted emergently with a strong suspicion of GD. Beta-glucosidase activity in leukocyte was decreased. GBA sequencing to confirm the diagnosis revealed compound heterozygous pathogenic variants (i.e., c.754T>A, c.887G>A), both previously reported as the cause of neuronopathic GD. Under the diagnosis of type 3 GD, the patient immediately received enzyme replacement therapy (ERT). After 17 months of ERT, the size of spleen decreased, and hemoglobin and platelet count returned to normal. In addition, the activity of chitotriosidase and angiotensin converting enzyme decreased. However, myoclonic movement and generalized seizure occurred at the age of 19 months and antiepileptic drug was started. Other neurological deterioration including supranuclear gaze palsy and developmental delay also persisted. A new therapy to overcome neurologic problems should be developed for patients with type 3 GD.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.20 no.1
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• pp.1-13
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• 2020

Purpose: Gaucher disease (GD), which is the most prevalent lysosomal storage disorder worldwide, is caused by mutations in the glucocerebrosidase gene (GBA). GD is divided into three clinical subtypes based on the appearance of neurological symptoms. Type 1 GD is a chronic non-neuronopathic disease, and types 2 and 3 are acute neuronopathic and chronic neuronopathic forms, respectively. Neuronopathic GD types 2 and 3 are characterized by increased levels of glucosylceramide (GlcCer) and glucosylsphingosine (GlcSph) in the brain, leading to massive loss of neurons. Methods: DNA damage and subsequent apoptosis of H4 cells were observed following neuroglioma H4 cell culture with GlcCer or GlcSph. Neuronal cell apoptosis was more prominent upon treatment with GlcSph. Results: When H4 cells were treated with GlcSph in the presence of tubacin, a histone deacetylase 6 inhibitor (HDAC6i), attenuation of both DNA damage and a reduction in the protein expression levels of GlcSph-induced apoptosis-associated factors were observed. Conclusion: These findings indicated that GlcSph played a prominent role in the pathogenesis of neuronopathic GD by inducing apoptosis, and that HDAC6i could be considered a therapeutic candidate for the treatment of neuronopathic GD.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.8
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• pp.3541-3546
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• 2011

Autophagy is an evolutionarily conserved lysosomal pathway for degrading cytoplasmic proteins, macromolecules, and organelles in addition to recycling protein and ATP synthesis. Although autophagy is very important during embryogenesis, the mechanism underlying the dynamic development during this process remains largely unknown. In order to obtain insights into autophagy in early embryo development, we analyzed gene expression levels of autophagy-related genes (ATGs) in mouse embryos developing in vitro. Using real time RT-PCR technique, ATGs including Atg2a, Atg3, Atg4b, Atg5, Atg6, Atg7, Atg9a, and Wipi3, as maternal transcripts, were only up-regulated in 1-cell embryo stage before zygotic genomic activation (ZGA), and then expression decreased from 2-cell to blastocyst embryo stage. ATGs including Dram and Atg9b were expressed abundantly in 1-cell embryo state and in blastocyst embryo stage, athough Atg8 and Ulk1 were constantly expressed during preimplantation stage. However, Atg4d were only up-expressed from 4-cell to blastocyst stage. These results suggest that autophagy is related in mouse embryo, which possibly gives an important role for early development.

• Journal of Acupuncture Research
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• v.19 no.5
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• pp.161-175
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• 2002

봉독은 거풍습(祛風濕), 지통(止痛), 해경평천(解痙平喘), 소종강압(消腫降壓)의 효능으로 오랫동안 통증과 염증성 질환을 치료하는데 이용되어져 왔는데 최근에는 면역관련질환치료에 응용하여 좋은 결과가 보고되고 있다. 본 연구는 Rheumatoid arthritis와 유사한 형태의 대표적 실험모델로 알려진 실험용 쥐의 Type II collagen 유발 관절염(Type II collagen induced arthritis : CIA)의 활액에서 봉독약침이 단백분해효소와 유리기 손상에 미치는 면역억제효과를 알아보기 위해 실행되었다. 본 실험에서는 CIA가 유발된 실험용 쥐에 봉독약침($5{\mu}l/kg$)을 처리한 실험군과 대조군으로서 CIA 유발 쥐에 생리식염수를 처리한 군(CIA군), 정상적인 쥐에 생리식염수로 처리한 군(정상군)으로 구분하여 각 군들의 일련의 표본에서 세포질, 리소좀, 간질성 단백분해효소의 활성과 유리기로 인한 단백질 손상정도를 (carbonyl 유도체를 측정하여)서로 비교하였다. 그 결과 각 군의 활액표본에서는 많은 종 류의 단백분해효소가 정산군보다 CIA군에서 유의하게 활성이 높았으며, 봉독약침($5{\mu}l/kg$)을 처리한 군에서 효소들의 활성이 유의하게 감소하였다. 그러나 각 군들의 혈장표본에서는 이 효소들의 활성은 서로 유의한 차이가 없었다. 이는 혈장속의 면역반응과 연관되리라고 추측되는 단백분해효소들의 활성변화는 병인적 측면에서 RA와 같은 염증성관절 질환과는 큰 상관성이 없다는 것을 의미한다. Carbonyl 유도체 측정으로 평가한 유리기 손상은 활액과 현장표본에서 모두 봉독약침($5{\mu}l/kg$)을 처리한 군에서 유의성 있게 감소하였다. 이상의 결과로 볼 때 단백분해효소와 유리기의 활성은 RA의 병인학적 측면에서 모두 잠재적인 중요성을 가지고 있으므로 향후 새로운 RA치료법은 이들 단백분해효소의 활성저해와 유리기의 소거능을 포함해야 한다고 사료되며 봉독약침은 이러한 2가지 효능을 포함한 효과적인 치료라고 평가된다.

• Journal of Life Science
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• v.20 no.8
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• pp.1281-1286
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• 2010

Gaucher disease (GD) is caused by glucocerebrosidase functional deficiency and the most prevalent lysosomal storage disorder (LSD), with an incidence of about 1 in 20,000 new births. Resveratrol, one kind of phytoalexin, is a produced naturally by several plants and has anti-tumor, anti-aging, anti-inflammatory and neuro-protective effects. In this paper we provide the cellular protective effect of resveratrol in both type I and type II Gaucher disease cells. Resveratrol treatment did not show any significant change in the p21 and p53 mRNA expression level, however expression level of the p21 protein, a cell cycle arrest factor, shows significant increment in both types of Gaucher disease cells. These cell cycle arrest patterns were confirmed by both MTT assay measurement and microscopy detection. In comparison, expression level of poly ADP ribose polymerase (PARP), an apoptosis indicator protein, was significantly decreased in both type I and II Gaucher disease cells after treatment with resveratrol. This result indicates that resveratrol relievescellular apoptotic stress fromtype I and II Gaucher disease cells. Therefore, we demonstrate that resveratrol inhibits cell proliferation via p21 activity and activates cellular repair systems for Gaucher disease cells. Our results provide at least one of the molecular mechanisms of Gaucher disease and may allow the verification of potential drug targets for therapeutic trials.