악성 갑상선 우연종의 임상상 및 초음파 소견의 진단적 가치

강한욱,김광원,이병완,강보현,김형훈,김범진,정재훈,민용기,이명식,이문규 대한내분비학회 2002 Endocrinology and metabolism Vol.17 No.5

연구배경: 최근 갑상선 초음파 검사의 빈번한 시행으로 갑상선 우연종의 발견이 증가하고 있다. 이러한 갑상선 우연종은 임상적으로 어떻게 접근하고 치료를 해야 하는지 적지 않은 문제가 되고 있다. 본 연구에서는 직경 1.5㎝ 이하의 갑상선 우연종의 유병률, 입상적 특징 및 초음파 특성, 그리고 가장 효율적인 진단적 접근에 대해 알아 봤다. 방법: 1999년 1월부터 2000년 12월까지 삼성서울병원 내과 및 일반외과로 갑상선 결절을 주소로 내원한 1457명을 대상으로 후향적 연구를 시행하였다. 우연히 발견된 직경 1.5㎝ 이하의 갑상선 결절을 가지는 환자들에서 갑상선 결절의 촉지 유무, 갑상선 기능검사, 항갑상선 항체, 갑상선 초음파 및 미세침 흡인세포검사, 99m^Tc 갑상선 스켄, 수술 조직검사 및 병기를 검토하였다. 결과: 분석한 갑상선 결절 1475예 중 갑상선 우연종의 유병률은 13.4%(198예)였다. 갑상선 우연종에서 악성률은 28.8%(57예)으로 나왔다. 양성 및 악성 갑상선 우연종에서 나이, 성별, 갑상선 기능검사, 결절 크기에는 의미 있는 차이는 없었다. 갑상선 스켄은 갑상선 우연종의 감별에 적합하지 않았다. 갑상선 결절의 초음파 지표 점수만이 양성 및 악석 갑상선 우연종의 감별에서 초음파 지표 점수의 민감도는 88.9%, 특이도는 74.4%, 양성 예측률은 92.4%로 나왔고 진단적 정환도는 85.5%였다. 갑상선암으로 수술을 받은 50명중 stage 1은 34명, stage 2는 6명, stage 3은 10명으로 대부분의 악성 갑상선 우연종은 낮은 TNM 병기로 나타났으나, 상당수에서는 국소 침범의 소견을 보였다. TNM 병기의 3기 환자 전부는 45세 이상이였고, 주로 갑상선암의 피막 침범에 의한 것이었다. 임파절 전이는 6명의 환자에서 나왔다. 결론: 악성 갑상선 우연종은 비교적 흔히 접할 수 있는 질환이며 양성 우연종과는 임상적으로 구별이 안 된다. 악성 갑상선 우연종은 발견 당시 대부분 낮은 병기이나, 갑상선의 피막 침범 및 임파절 전이가 상당수에서 발견되었다. 갑상선 우연종의 초음파 소견은 향후의 진단 방향을 제시하는 중요한 길잡이가 될 수 있다. 초음파 지표 점수 2점 이상의 갑상선 우연종에서만 초음파 유도 미세침 흡입검사를 권장한다. Background: High-resolution ultrasonography has made the detection of asymptomatic small thyroid possible. Recent increases in the detection of incidentalomas have created a clinical dilemma on how to properly manage such incidental nodules. We investigated the prevalence, clinical and ultrasonographic characteristics, and optimal diagnostic approach toward incidentally detected benign and malignant thyroid nodules of less than 1.5㎝ in size. Methods: A retrospective review was undertaken on the 1,475 patients who had visited Samsung Medical Center, Seoul Korea between January 1999 and December 2000. The review consisted of a physical examination of the thyroid gland, thyroid function test, antithyroid antibodies, thyroid ultrasonography, fine-needle aspiration biopsy, pathology and TNA staging of the incidentally detected thyroid nodules of less than 1.5㎝ in size. Results: The prevalence of thyroid incidentalomas was 13.4% and the malignancy rate within them was 28.8%. There were no significant differences in age, sex, thyroid function test and size between the benign and malignant incidentalomas. Ultrasonographic characteristics showed meaningful diagnostic value for the detection of malignancy in incidentalomas. Most malignant incidentalomas were of a low stage. Conclusion: Occult thyroid cancers are fairly common finding. There are no clinical difference between benign and malignant thyroid nodules less than 1.5㎝; however, ultrasonographic findings can be used to decision of optimal management strategies (J Kor Soc Endocrinol 17:649∼656, 2002).

Investigation of Immune-Regulatory Effects of Mageumsan Hot Spring via Protein Microarray In Vitro

( Hyung Jin Hahn ),( Jung Soo Kim ),( Yeong Ho Kim ),( Young Bok Lee ),( Dong Soo Yu ),( Jin-wou Kim ) 대한피부과학회 2018 Annals of Dermatology Vol.30 No.3

Background: Empirical evidences for efficacy of hot spring (HS) water in inflammatory skin disorders have not been substantiated with sufficient, immunological “hard evidence”. Mageumsan HS water, characterized by its weakly-alkaline properties and low total dissolved solids content, has been known to alleviate various immune-inflammatory skin diseases, including atopic dermatitis (AD). Objective: The trial attempted to quantitatively analyze in vitro expression levels of chemical mediators in cutaneous inflammation from HaCaT cell line treated with Mageumsan HS, and suggest the likely mode of action through which it exerts the apparent anti-inflammatory effects in AD. Methods: Using membranebased human antibody array kit, customized to include 30 different, keratinocyte-derived mediator proteins, their expression levels (including interleukin [IL]-1, IL-6, IL-8, thymic stromal lymphopoietin, thymus and activation-regulated chemokine, and granulocyte macrophage colony-stimulating factor) were assessed in vitro. Selected key proteins were further quantified with enzyme-linked immunosorbent assay. Results: There was a clear pattern of overall suppression of the mediators, especially those noted for their pro-inflammatory role in AD (monocyte chemoattractant protein [MCP]-1, regulated on activation, normal T cell expressed and secreted, cutaneous T-cell-attracting chemokine, Eotaxin, and macrophage inflammatory protein-1α, etc.). Also, reduced expression of involucrin and cytokeratin 1 was also reduced in the HS-treated group. Conclusion: The present study has shown that Mageumsan HS water may exert its effects on inflammatory skin disorders through regulation of proinflammatory cytokines. These evidences are to be supported with further future investigations to elucidate immunological mechanism behind these beneficial effects of HS water in the chronically inflamed skin of AD. (Ann Dermatol 30(3) 322∼330, 2018)

Disseminated cutaneous gout: a rare clinical presentation

( Jin Young Choi ),( Sae Mi Park ),( Hyung Jin Hahn ),( Young Bok Lee ),( Dong Soo Yu ),( Jin Wou Kim ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

Gout is a form of arthritis which culminates from a buildup of uric acid crystals in the joints. Four distinct stages of gout are generally recognized. A 58-year-old man with chronic gouty arthritis presented with tender, multiple, firm, erythematous and yellowish nodules over erythematous patches on both upper and lower extremities for 1 week. He also had been complaining of general weakness and fever. Blood tests revealed elevated renal function test, hyperkalemia (7.9 mEq/L), leukocytosis (25.36 109/L), and elevated segment neutrophils (91%). A deep punch biopsy of the nodule revealed chalk-like whitish materials. Histologic examination revealed amorphous pinkish crystalline material surrounded by granulomatous inflammation in the dermis. On polarized light microscopy, strong, negatively-birefringent needle-shaped crystals were seen. Unfortunately, the patient’s renal function deteriorated, with the laboratory makers pointing to development of sepsis. The patient ultimately expired from ventricular tachycardia. In our patient, disseminated gout lesions were broadly distributed including nonarticular sites, and severe leukocytosis implying bacterial infection was present. Although the exact cause of sepsis is unclear, there is a possibility that cutaneous infection of gouty nodules may have played a significant role. Herein, we report a case of severe, disseminated tophaceous gout that may have led to systemic infection.

Transoral Cross-Lip (Abbe-Estlander) Flap as a Viable and Effective Reconstructive Option in Middle Lower Lip Defect Reconstruction

( Hyung Jin Hahn ),( Hyun Jee Kim ),( Jin Young Choi ),( Soo Young Lee ),( Young Bok Lee ),( Jin Wou Kim ),( Dong Soo Yu ) 대한피부과학회 2017 Annals of Dermatology Vol.29 No.2

The Abbe-Estlander flap surgery is a cross-lip procedure that is valuable in repairing a defect on the lower lip using a full-thickness flap, consisting of the skin, muscle and muco-sa, from the upper lip. As usefulness and practicality of the flap in reconstruction of lower lip surgical defects in Asian ethnicity have not been documented, the authors present a case of successful lower lip reconstruction with a staged, Abbe-Estlander lip switching flap with commissuroplasty as an illustrative example. A 71-year-old male has presented with an ulcerating lip nodule in the middle one third of the lower lip, measuring about 1.5×2 cm across its long and short axes. Wide excision of the tumor was followed by de-lineation of the triangular Abbe-Estlander flap from the upper lip, in which the medial hinge point of the base was chosen as the pedicle. Then, the flap elevation was carried out from the lateral commissure and then was transferred into the low-er lip defect. Three weeks later, commissuroplasty was per-formed to correct the rounding at the new commissure. The patient is currently performing his daily activities with no ap-parent compromise in orbicularis oris strength or oral continence. Given the size of the primary defect and the flap-to-defect ratio of size, the degree of microstomia was acceptable. Even with other myriad of reconstructive options at surgeons` disposal, the Abbe-Estlander lip-switching flap is a reliable, and less morbid method of lower lip re-construction for Asian surgical candidates. The authors illus-trate an exemplary case in which a relatively large lower lip defect was successfully repaired using an upper lip flap of a significantly smaller size in an Asian subject of advanced age, without any remarkable long term sequelae which have traditionally been associated with the trans-oral lip switching flap technique. (Ann Dermatol 29(2) 210∼214, 2017)

P004 : Oridonin protects HaCaT keratinocytes against hydrogen peroxide-induced oxidative stress by altering microrna expression

( Hyung Jin Hahn ),( Kyu Joong Ahn ),( Sung Kwan An ),( In Sook An ),( Hwa Jun Cha ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Background: Oridonin, a diterpenoid isolated from Rabdosia rubescens, has been shown to exhibit anti-cancer, antimicrobial, and anti-inflammatory properties and mediate ROS production. Meanwhile, many reports demonstrate that miRNAs are key regulators in diverse biological processes in human keratinocytes. However, the relationship between ROS and miRNAs in these cells remains unclear. Objectives: We sought to demonstrate that oridonin can reduce ROS production and induce a protective effect against H2O2-induced HaCaT keratinocyte damage. Methods: Normal human HaCaT keratinocytes were treated with different doses of oridonin and a fixed dose of H2O2. Then, we used miRNA microarray and bioinformatics tools to elucidate the molecular mechanism that leads to protection against oxidative stress. Results: The data reveal that low doses of oridonin can protect against H2O2-mediated apoptosis in a concentrationand time-dependent manner. Moreover, oridonin markedly decreases H2O2-induced reactive oxygen species production in HaCaT cells. Oridonin mediates these effects by altering miRNA expression. In addition, the target genes are likely involved in cell growth and anti-apoptosis. Conclusion: In this study, we demonstrate that oridonin, a diterpenoid compound isolated from Rabdosia rubescens protects human HaCaT keratinocytes from oxidative stress induced by H2O2 exposure.

Pretreatment of Ferulic Acid Protects Human Dermal Fibroblasts against Ultraviolet A Irradiation

( Hyung Jin Hahn ),( Ki Bbeum Kim ),( Seunghee Bae ),( Byung Gon Choi ),( Sungkwan An ),( Kyu Joong Ahn ),( Su Young Kim ) 대한피부과학회 2016 Annals of Dermatology Vol.28 No.6

Background: Approximately 90%∼99% of ultraviolet A (UVA) ray reaches the Earth`s surface. The deeply penetrating UVA rays induce the formation of reactive oxygen species (ROS), which results in oxidative stress such as photoproducts, senescence, and cell death. Thus, UVA is considered a primary factor that promotes skin aging. Objective: Researchers investigated whether pretreatment with ferulic acid protects human dermal fibroblasts (HDFs) against UVA-induced cell damages. Methods: HDF proliferation was analyzed using the water-soluble tetrazolium salt assay. Cell cycle distribution and intracellular ROS levels were as-sessed by flow cytometric analysis. Senescence was eval-uated using a senescence-associated β-galactosidase assay, while Gadd45α promoter activity was analyzed through a luciferase assay. The expression levels of superoxide dis-mutase 1 (SOD1), catalase (CAT), xeroderma pigmentosum complementation group A and C, matrix metalloproteinase 1 and 3, as well as p21 and p16 were measured using quanti- tative real-time polymerase chain reaction. Results: Inhibi-tion of proliferation and cell cycle arrest were detected in cells that were irradiated with UVA only. Pretreatment with ferulic acid significantly increased the proliferation and cell cycle progression in HDFs. Moreover, ferulic acid pretreat-ment produced antioxidant effects such as reduced DCF in-tensity, and affected SOD1 and CAT mRNA expression. These effects were also demonstrated in the analysis of cell senescence, promoter activity, expression of senescent markers, and DNA repair. Conclusion: These results demon-strate that ferulic acid exerts protective effects on UVA-in-duced cell damages via anti-oxidant and stress-inducible cel-lular mechanisms in HDFs. (Ann Dermatol 28(6) 740∼748, 2016)

Association of total plasma IgE level with MIF (macrophage migration inhibitory factor) polymorphisms in Atopic dermatitis patients

( Jin Young Choi ),( Hyun Jee Kim ),( Hyung Jin Hahn ),( Young Bok Lee ),( Dong Soo Yu ),( Jin Wou Kim ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and significantly elevated in patients with AD. The MIF gene polymorphisms such as -173 G to C and -794 CATT5-8 MIF have been implicated in AD. Objectives: The aim of this study is to evaluate the relationship between -173 G to C and -794 CATT5-8 MIFgene polymorphisms and total plasma immunoglobulin E (IgE) level in AD patients. Methods: We performed polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) analysis from 178 patients with AD and 80 controls. The total plasma MIF level was determined by ELISA. Logistic regression analyses were performed. Results: Compared with GG homozygotes of MIF-173G/C polymorphism, odds ratio (OR) for CC homozygotes was 9.3 (p=0.048), and OR for GC heterozygotes was 2.5 (p=0.031). Compared with MIF G/5-CATT haplotype, OR for MIF C/5-CATT haplotype was 9.7 (p=0.009), and OR for MIF C/7-CATT haplotype was 4.5 (p=0.005). The IgE level was highly associated with age and sex among AD patients with the MIF -794 7-CATT polymorphism (p=0.043), while MIF C/7-CATT haplotype was associated with decreased IgE level (p=0.036). Conclusion: Our results shows that the MIF promoter polymorphisms in -173 C allele and MIF C/5-CATT and MIF C/7-CATT haplotype are associated with increased risk for AD. In contrast, the -794 7-CATT locus and MIF C/7-CATT haplotype was associated with decreased total plasma IgE level in AD patients.

Merkel cell carcinoma of the arm with spontaneous regression

( Jin Young Choi ),( Jin Hee Kang ),( Hyung Jin Hahn ),( Young Bok Lee ),( Jin Wou Kim ),( Dong Soo Yu ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

Merkel cell carcinoma is a rare malignant cutaneous neuroendocrine carcinoma of aggressive behavior with high rate of metastasis and recurrence. The carcinoma presents as a solitary, non-tender, firm, reddish orskin-colored, dermal papule or nodule commonly affecting the head and neck or the extremities in older people. It grows rapidly within 1 to 3 months in spite of its deceptively innocuous appearance. A 75 year-old women presented with a tender, solitary, 3 x 3 cm-sized, erythematous, firm, dermal nodule on the left arm for months. A 3 mm-sized punch biopsy was performed. Histopathologic evaluation showed dense dermal infiltrates of hyperchromatic lymphoid cells and medium sized bluish cells containing scanty amount of cytoplasms. Mitotic figures were also observed. The tumor cells stained positive for pancytokeratin, CK20, synaptophy in, CD56a, and NSE and negativity for LCA, CK7, and S-100. Diagnosis of merkel cell carcinoma was made on the clinical and histopathological grounds. Two months after biopsy, the primary tumor lesion was downsized to 1 x cm without any intervention. Spontaneous regression of merkel cell carcinoma is a rare event with incidence estimated to be 1.5%. Herein, we report a rare and interesting case of merkel cell carcinoma which has spontaneously regressed after biopsy with no activemedical or surgical treatment.

Protective effects of rosmarinic acid against hydrogen peroxide-induced cellular senescence and the inflammatory response in normal human dermal fibroblasts

Hahn, Hyung Jin,Kim, Ki Bbeum,An, In-Sook,Ahn, Kyu Joong,Han, Hyun Joo SPANDIDOS PUBLICATIONS 2017 MOLECULAR MEDICINE REPORTS Vol.16 No.6

<P>Hydrogen peroxide (H2O2) is a reactive oxygen species (ROS) that induces numerous cellular events, including cellular senescence and inflammatory responses. Therefore, the aim of this study was to investigate the protective effect of Rosmarinic acid (RA) in H2O2-induced oxidative stress in normal human dermal fibroblasts (NHDFs). Cytotoxicity assays were performed using a water-soluble tetrazolium salt, and senescence-associated beta-galactosidase activity was determined to investigate the proportion of senescent cells. Antioxidant capacities were evaluated via H2O2-scavenging activity, reverse transcription-quantitative polymerase chain reaction, NRF2 luciferase reporter gene activity and intracellular ROS scavenging assays. Cytokine-coded gene expression analysis and nuclear factor-kappa B luciferase activity were determined to verify the anti-inflammatory effect of RA. As a result, the present study demonstrated that rosmarinic acid inhibited H2O2-induced oxidative stress and inflammatory responses in normal human dermal fibroblasts. Initially, the doses of RA that exerted minimal cytotoxic effects in NHDFs were determined using a cytotoxicity assay. Subsequently, pretreatment with the appropriate doses of RA significantly reversed the H2O2-induced decrease in NHDF cell viability and decreased cellular senescence of NHDFs. In addition, RA inhibited H2O2-induced ROS production in NHDFs, as determined by a ROS scavenging assay. The protective effects of RA were mediated by the inhibition of nuclear factor erythroid-derived 2-like 2, a transcription factor that functions as a key regulator of redox sensitivity. Furthermore, RA suppressed H2O2-induced inflammation in NHDFs and significantly rescued H2O2-induced downregulation of sirtuin 1. RA also inhibited nuclear factor (NF) -kappa B transcriptional activity and the expression of NF-kappa B target genes, including tumor necrosis factor-a and interleukin-6, in H2O2-exposed NHDFs. Taken together, these data indicate that RA inhibits H2O2-induced cellular damage in NHDFs.</P>

P106 : Current situation of atopic dermatitis(AD)-related information on the internet in Korea

( Hyung Jin Hahn ),( Hye Rim Ko ),( Hyun Jee Kim ),( Yong Jun Lee ),( Young Bok Lee ),( Dong Soo Yu ),( Jin Wou Kim ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Background: Patients with atopic dermatitis (AD) often resort to the Internet for related information. We believe that doctors in dermatology must stay informed about the current situation of such information available to patients, which might mislead them to wrong decisions. Objectives: The study was carried out in order to know the nature of related information available on the Internet in Korea, and to identify any change since our last research in 2005. The quality of information offered and the involvement of medical doctors in certain websites were also investigated. Methods: Taking account of the current search engine market share in Korea, we gathered the search results with the key word ‘atopy’ in three major search engines, and investigated the nature of the information offered. Results: The search results showed less commercial sites than our previous study in 2005. There is a dramatic increase in the number of public bodies offering information about AD. Also, the quality of information available online improved since our last research. Conclusion: The phenomenon of ‘commercial overcrowding’ seems to have stabilized. As AD becomes a social phenomenon, patients are better informed than before. However, the information offered in the Internet still need to be complemented by doctors in dermatology. We believe that a self-regulation in a form such as the HON Code can improve the quality of online information exposed to the patients with AD in Korea.