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      • The role of neuroimmune interaction in pathophysiology of Granulomatous rosacea

        ( Eun Hye Hong ),( Min Kyun An ),( Yo Sup Shin ),( Eun Byul Cho ),( Eun Joo Park ),( Kwang Ho Kim ),( Kwang Joong Kim ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

        Background: Granulomatous rosacea (GR) is categorized as a separate disease variant of rosacea because of its unique histopatholiogic findings. However, the pathogenesis of granulomatous rosacea has not been clearly demonstrated. Objectives: The aim of this study was to investigate the expression of toll-like receptor (TLR) 2, mast cell (MC), and neurofilament (NF) in GR. Methods: Facial biopsy specimens were obtained from 12 patients with erythematotelangiectatic rosacea (ETR), 11 patients with GR, and 11 patients as control group. Biopsy tissue blocks were stained with immunohistochemical staining using antibodies to TLR2, MC, and NF. Results: In GR, expression of MC was significantly increased than ETR and the control group. Also, GR group showed increased expression of TLR2 than the control group. In ETR group, expression of TLR2 was also increased than the control group and expression of NF was also increased than the control group, although the differences between other groups were not statistically significant. Conclusion: The results of this study suggest that the increased expression of MC may be a sign of chronic, later stage in GR compared to other subtypes. Also, increased expression of TLR2 suggests that cathelicidin-induced neuroimmune pathogenesis also contributes to the pathophysiology of GR.

      • Prediction of drug-induced immune-mediated hepatotoxicity using hepatocyte-like cells derived from human embryonic stem cells

        Kim, Dong Eon,Jang, Mi-Jin,Kim, Young Ran,Lee, Joo-Young,Cho, Eun Byul,Kim, Eunha,Kim, Yeji,Kim, Mi Young,Jeong, Won-il,Kim, Seyun,Han, Yong-Mahn,Lee, Seung-Hyo Elsevier 2017 Toxicology Vol.387 No.-

        <P><B>Abstract</B></P> <P>Drug-induced liver injury (DILI) is a leading cause of liver disease and a key safety factor during drug development. In addition to the initiation events of drug-specific hepatotoxicity, dysregulated immune responses have been proposed as major pathological events of DILI. Thus, there is a need for a reliable cell culture model with which to assess drug-induced immune reactions to predict hepatotoxicity for drug development. To this end, stem cell-derived hepatocytes have shown great potentials. Here we report that hepatocyte-like cells derived from human embryonic stem cells (hES-HLCs) can be used to evaluate drug-induced hepatotoxic immunological events. Treatment with acetaminophen significantly elevated the levels of inflammatory cytokines by hES-HLCs. Moreover, three human immune cell lines, Jurkat, THP-1, and NK92MI, were activated when cultured in conditioned medium obtained from acetaminophen-treated hES-HLCs. To further validate, we tested thiazolidinedione (TZD) class, antidiabetic drugs, including troglitazone withdrawn from the market because of severe idiosyncratic drug hepatotoxicity. We found that TZD drug treatment to hES-HLCs resulted in the production of pro-inflammatory cytokines and eventually associated immune cell activation. In summary, our study demonstrates for the first time the potential of hES-HLCs as an <I>in vitro</I> model system for assessment of drug-induced as well as immune-mediated hepatotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Generation and characterization of hES-HLCs for evaluation of drug-induced immune cell-mediated hepatotoxicity. </LI> <LI> The secretion of inflammatory cytokines is highly enhanced from APAP-treated hES-HLCs. </LI> <LI> Immune cells are activated and produce pro-inflammatory cytokines by conditioned medium from hES-HLCs cultured with APAP. </LI> <LI> Hepatotoxic results in hES-HLCs are consistent with those of primary human hepatocytes. </LI> <LI> Hepatotoxic drugs such as TZD, and non-hepatotoxic drugs such as aspirin and metformin, are also validated with our drug screening system. </LI> </UL> </P>

      • SCOPUSKCI등재

        Histopathological Concordance Rate between Punch Biopsy and Excision in Basal Cell Carcinoma

        ( Eun Hye Hong ),( Eun Byul Cho ),( Eun Joo Park ),( Kwang Joong Kim ),( Kwang Ho Kim ) 대한피부과학회 2020 大韓皮膚科學會誌 Vol.58 No.2

        Background: Accuracy in histological subtyping of basal cell carcinoma (BCC) is crucial for determining the appropriate treatment modality. Previous studies have assessed the concordance rateof punch biopsy and excision in subtyping BCC however, they did not calculate this rate according to the BCC location or in Asian populations. Objective: This study compared the concordance rate of punch biopsy and excision for each BCC location. Methods: This study included 192 patients who underwent both punch biopsy and excision. BCC subtypes identified by punch biopsy and excision were compared to calculate the concordance rate. The differences in the rates of misdiagnosis according to the BCC location were also determined. Results: The overall concordance rate of punch biopsy and excision was 78.1% (150/192). The proportion of aggressive type was higher for excision than for punch biopsy. The false-positive rate, defined as the rate of misidentified nonaggressive type, was 19.7% (26/132) and was highest for nodular-type BCC. Additionally, most discrepancies occurred in BCCs located in the face, especially in the H-zone. Conclusion: Owing to the inconsistencies in the results of punch biopsy and excision and the high false-positive rate of punch biopsy, dermatologists should be aware of the possibility of an aggressive type BCC even if it is identified as anonaggressive type in punch biopsy. Moreover, more aggressive treatment should be considered in cases of BCCslocated on the face, especially in the H-zone, as the discrepancy rate is higher. (Korean J Dermatol 2020;58(2):97∼101)

      • SCIESCOPUSKCI등재

        A Rare Case of Cutaneous T-Cell Lymphoma Accompanied by Acute Monoblastic Leukemia and Diffuse Large B-Cell Lymphoma

        ( Eun Hye Hong ),( Ye Ji Jang ),( Eun Byul Cho ),( Eun Joo Park ),( Kwang Joong Kim ),( Kwang Ho Kim ) 대한피부과학회 2021 Annals of Dermatology Vol.33 No.2

        A 70-year-old female was referred for brown-to-gray colored papules and nodules on her lower legs. She had been diagnosed with diffuse large B-cell lymphoma (DLBCL) in her stomach, and myelodysplastic syndrome (MDS) by bone marrow biopsy. Three years after complete remission of DLBCL, she experienced DLBCL recurrence in her small bowel and was hospitalized. MDS had been stationary, but during the treatment of DLBCL, her laboratory findings suggested signs of leukemia. Bone marrow biopsy was done, and acute monoblastic leukemia (AMoL) was diagnosed. After 1 cycle of chemotherapy for AMoL, skin lesions developed, and her skin biopsy showed cutaneous T-cell lymphoma (CTCL). Terminal deoxynucleotidyl transferase staining and CD123 staining were negative, and bone marrow re-biopsy conducted after the skin lesion developed still showed monoblastic proliferation. Whether the CTCL represented with an AMoL lineage switch could not be completely proved due to the absence of molecular or clonal marker evaluations, but the possibility of coexistence of three different malignancies was higher. During treatment, a neutropenic fever developed, and the patient died due to sepsis. We herein report a rare case of CTCL accompanied by AmoL and DLBCL. (Ann Dermatol 33(2) 178∼181, 2021)

      • Effect of platelet-rich plasma on proliferation and migration in human dermal fibroblasts

        ( Eun Hye Hong ),( Min Kyun An ),( Yo Sup Shin ),( Eun Byul Cho ),( Eun Joo Park ),( Kwang Ho Kim ),( Kwang Joong Kim ) 대한피부과학회 2018 대한피부과학회 학술발표대회집 Vol.70 No.2

        Background: Platelet-rich plasma (PRP) is a blood fraction that contains high concentrations of several growth factors. PRP has been recently used in skin wound healing and rejuvenation. However, the precise molecular mechanisms underlying PRP-induced wound healing are unknown. Objectives: This study aimed to evaluate the effects of PRP on extracellular matrix remodeling, which requires the activation of dermal fibroblasts. Methods: Cell proliferation and migration assay, enzyme-linked immunosorbent analysis, and western blotting were performed on PRP-treated human skin fibroblasts. Results: Platelet numbers were enhanced by 4.6-fold in PRP compared to that in whole blood. PRP stimulated the proliferation and migration of human dermal fibroblasts, and increased the expression of human procollagen I alpha 1, elastin, MMP-1, and MMP-2 in human dermal fibroblasts. PRP-treated human dermal fibroblasts also showed a dramatic reduction in the phosphorylation of c-Jun N-terminal kinase (JNK), whereas total JNK levels were not significantly reduced. Conclusion: Collectively, PRP induced increased expression of type I collagen, elastin, MMP-1, and MMP-2, thereby accelerating wound healing. Our findings reveal basic mechanisms underlying PRP-mediated tissue remodeling. Thus, these results could be exploited for clinical dermatology and skin rejuvenation.

      • MicroRNA-99a Attenuates HCV Replication through the Downregulation of Subtilisin Kexin Isozyme-1 (SKI-1) / Site-1 Protease (S1P)

        ( Eun Byul Lee ),( Seung Kew Yoon ),( Jung-hee Kim ),( Wonhee Hur ),( Sung Min Kim ),( Joon Ho Lee ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

        Aims: MicroRNAs modulate various biological processes through dysfunction of target genes. Accumulating evidence indicates that a number of miRNAs can regulate or be regulated by hepatitis C virus (HCV) infection. Recently, it has been reported that expression level of miR-99a was inversely correlated with sustained virological response in patients with chronic hepatitis C. However, the exact role of miR-99a and its target in the pathogenesis of HCV infection remains unexplored. Here, we investigated the restrictive effects of miR-99a on the replication of HCV in relation to lipid metabolism and identified subtilisin kexin isozyme-1/site-1 protease (SKI1/S1P) as a novel target of miR-99a. Methods: The levels of miR-99a were evaluated in the serum of patients with chronic HCV infection, Huh7 cells infected with HCVcc and HCV full-genomic replicon (FGR) cells by miRNA quantitative real- time PCR (qRT-PCR). In addition, the effect of miR-99a-5p on HCV replication was analyzed by measuring the levels of HCV RNA after treatment with miR-99a-5p mimics in Huh7 cells infected with HCVcc and FGR cells. The levels of miR-99a target genes involved in lipid metabolism were also assessed by western blot analysis and qRT-PCR. The change of lipid accumulation by miR-99a-5p over-expression was quantitatively measured by Nile Red staining. Results: The expression level of miR-99a-5p was significantly down-regulated in sera from patients chronically infected with HCV compared to healthy subjects. Moreover, the expression level of miR-99a was decreased in both of FGR cells and Huh7 cells infected with HCVcc. Notably, treatment with miR-99a-5p mimics significantly down-regulated HCV replication. In this study, we identified SKI1/S1P as a novel target of miR-99a in relation to HCV replication. SKI1/S1P expression was significantly suppressed by treatment with miR-99a-5p mimics in HCV replicating cells. Regarding the role of SKI1/S1P in lipogenesis, the forced expression of miR-99a-5p attenuated the increase in the amount of intracellular lipid droplets after oleic acid treatment. Conclusions: Our data provide new mechanistic insights of role of miR-99a as an anti-viral host factor on HCV replication by suppression of lipid accumulation through down-regulated of SKI1/S1P. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2015R1C1A1A020 37212)

      • SCIESCOPUSKCI등재

        A Case of Generalized Lichen Sclerosus et Atrophicus

        ( Eun Hye Hong ),( Min Kyun An ),( Eun Byul Cho ),( Eun Joo Park ),( Kwang Joong Kim ),( Kwang Ho Kim ) 대한피부과학회 2020 Annals of Dermatology Vol.32 No.4

        A 62-year-old female, with previous history of asthma and hypertension, presented with generalized hyperpigmented skin lesion, found a year ago. Physical examination revealed brown colored lichenified and sclerotic patches on the lower abdomen and flexural areas of extremities. Punch biopsy was performed and histopathological examination revealed hyperkeratosis, follicular plugging and thinning in epidermis. In dermoepidermal junction, cleft like space separating atrophic epidermis and dermis was seen. Also, lichenoid lymphocytic infiltration was observed in mid-dermis. Based on clinical and histopathological findings, a diagnosis of generlaized lichen sclerosus et atrophicus (LSA) was made. Other laboratory examinations were unremarkable. As there is no standard treatment for LSA, the patient received various treatments including topical steroid, tacrolimus and narrow- band ultraviolet B therapy. The skin lesion has softened and its color improved after treatment. LSA is defined as infrequent chronic inflammatory dermatosis with anogenital and extragenital manifestations. Generalized type is rare and genital involvement is the most frequent and often the only site of involvement. We report this case as it is an uncommon type of LSA with generalized hyperpigmented and sclerotic skin lesion in a postmenopausal female patient. (Ann Dermatol 32(4) 327∼330, 2020)

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