원전 : 태아 피부의 발달과정에서 데스모글레인-3 표현에 대한 면역조직화학적 연구

김준범 ( June Bum Kim ),박향준 ( Hyang Joon Park ),이재승 ( Jae Seung Lee ),조옥자 ( Ok Ja Joh ),송계용 ( Kye Yong Song ) 대한피부과학회 2010 대한피부과학회지 Vol.48 No.7

Background: Desmogleins are calcium-dependent transmembrane glycoproteins of the desmosome that form an import component of the junction complexes of epithelial cells. Desmogleins are involved in maintaining the structural integrity of tissues. So far, four different desmogleins (Dsg1, Dsg2, Dsg3 and Dsg4) have been identified. Objective: The purpose of this study was to observe the distribution pattern of desmoglein-3 in the fetal skin during development. Methods: Skin was obtained from the sole, scalp and lip of 34 fetuses that ranged in age from 10 to 39 weeks of gestational age. Immunohistochemical staining was performed on the paraffin embedded tissue using anti-human monoclonal antibody against the desmoglein-3. Results: The expression of desmoglein-3 in the epidermis appeared in the basal layer of the sole at the 10th week of gestation age. Thereafter, a stronger expression was noted in the middle layer of the sole and scalp epidermis. The basal layer had a stronger expression than did the other layers of the epidermis, followed by the middle and superficial layers. A stronger expression of desmoglein-3 in hair was noted in the outer root sheath, the bulge cells and the eccrine duct cells. The expression of desmoglein-3 in the lip mucosa was strong in both the basal and middle layers, while the skin side of the mucosa showed a stronger expression in basal layer. Conclusion: These results suggested that desmoglein-3 plays an important role in the development and differentiation of the epidermis and skin adnexa in the fetal stage, and especially in basal and suprabasal layers. (Korean J Dermatol 2010;48(7):558∼566)

Channelopathies

김준범(Kim June-Bum) 대한의학유전학회 2014 대한의학유전학회 학술대회 논문집 Vol.1 No.1

Ion channels 1. Function Regulation of membrane excitability > Functional modulation of excitable cells

피부로 전이된 악성 섬유성 조직구종

김준범 ( June Bum Kim ),김지혜 ( Ji Hye Kim ),김학주 ( Hak Ju Kim ),김혜경 ( Hye Kyoung Kim ),고유수 ( Yoo Soo Ko ),이재승 ( Jae Seung Lee ),조옥자 ( Ok Ja Joh ),송계용 ( Kye Yong Song ) 대한피부과학회 2009 대한피부과학회지 Vol.47 No.1

Malignant fibrous histiocytoma (MFH) is the most common soft tissue sarcoma. It is regarded as an undifferentiated pleomorphic sarcoma with an unproven histogenesis. It most commonly occurs in the skeletal muscles of the extremities or the retroperitoneum of adults. It often metastasizes to the lungs, lymph nodes, bones and liver, but rarely to the skin. We report here a case of malignant fibrous histiocytoma that metastasized to the skin. (Korean J Dermatol 2009;47(1):75~79)

Sorafenib 복용 후 발생한 백혈구 파쇄성 혈관염

김학주 ( Hak Ju Kim ),김지혜 ( Ji Hye Kim ),김준범 ( June Bum Kim ),김혜경 ( Hye Kyoung Kim ),고유수 ( Yoo Soo Ko ),조옥자 ( Ok Ja Joh ),이재승 ( Jae Seung Lee ),송계용 ( Kye Yong Song ) 대한피부과학회 2008 대한피부과학회지 Vol.46 No.5

Sorafenib (Nexavar(R)) is an oral multikinase inhibitor that was recently approved for use in metastatic renal cancer. It is currently undergoing investigation for the treatment of locally advanced renal cancer and in other tumor types. It has a broad spectrum of activity in treating multiple tyrosine kinases, including angiogenic factors VEGFR and PDGFR. Common cutaneous toxicities experienced with sorafenib include facial and scalp erythema, hand-foot syndrome, splinter hemorrhages, and alopecia. We report a case of a 57 year-old man diagnosed as renal cell carcinoma with distant metastaisis, who developed a leukocytoclastic vasculitis on the extremities after use of sorafenib. (Korean J Dermatol 2008;46(5):648∼651)

가족성 저칼륨성 주기성마비 환자의 골격근 세포내 Kir6.2의 발현 및 분포 양상

Sung-Jo Kim(김성조),Dong-Ho Yoon(윤동호),June-Bum Kim(김준범) 한국생명과학회 2010 생명과학회지 Vol.20 No.3

가족성 저칼륨성 주기성마비는 간헐적으로 발생하는 저칼륨혈증을 동반한 가역적 이완성 근육마비를 특징으로 하는 상염색체 우성 유전질환이다. 골격근 세포막에 위치한 KATP 채널의 활성도 감소가 저칼륨성 주기성 마비의 발병과 관련 있는 것으로 보고되고 있으나 아직까지 명확한 기전이 밝혀져 있지 않다. 본 연구에서는 KATP 채널을 구성하는 단위체인 Kir6.2를 대상으로 가족성 저칼륨성 주기성마비 환자의 골격근 세포에서 KATP 채널의 활성도 감소가 발생하는 분자생물학적 기전을 알아보고자 하였다. 환자와 정상인의 골격근 세포내 Kir6.2 단위체의 유전자인 KCNJ11의 mRNA발현 수준과 단백질 발현양상을 확인한 결과, 정상 세포외 칼륨 농도인 4 mM 칼륨 완충용액에 노출된 경우 KCNJ11 mRNA와 단백질 수준의 정량적 차이는 관찰되지 않았다. 그러나 환자에서 마비를 유발할 수 있는 저칼륨 농도인 1 mM의 칼륨 완충용액에 노출시킨 경우 정상세포는 KCNJ11 mRNA의 발현이 감소하였고, 그 산물인 Kir6.2 단백질의 정량적 차이를 확인한 결과 세포막에 존재하는 단백질의 양 또한 유의하게 감소하였다. 그러나 환자의 경우 1 mM의 칼륨 완충용액에 노출시 KCNJ11 mRNA 발현수준에 차이가 없었고, 더불어 세포막과 세포질 상의 Kir6.2 단백질 분포에도 변화가 나타나지 않았다. 이는 환자 세포의 경우 세포막 단백질이 세포질로 회수되지 못하여 KATP 채널의 폐쇄가 유지되어 탈분극이 지속되며 이로 인해 환자에서 마비 증상을 유발할 수 있음을 시사하는 결과로 본 질환의 새로운 발병 기전을 설명할 수 있는 근거로 생각된다. Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant disorder characterized by reversible flaccid paralysis and intermittent hypokalemia. Although it has been reported that decreased activity in the KATP channels of the skeletal muscle cell membrane plays a role in the pathogenesis of HOKPP, a clear mechanism has not yet been established. This study aimed to investigate the molecular biological mechanism underlying the decreased activity of KATP channels in the skeletal muscles of familial HOKPP patients by studying the levels of the KATP channel subunit Kir6.2. We found that when cells obtained from healthy individuals (normal cells) and HOKPP patients (patient cells) were treated with 4 mM potassium buffer, there was no quantitative change in the KCNJ11 mRNA levels and no difference in the Kir6.2 protein expression in the cytosol and cell membrane. On the other hand, when 1 mM potassium buffer was used, normal cells showed decreased expression of KCNJ11 mRNA as well as decreased expression of Kir6.2 protein in the cell membrane. However, patient cells treated with the same buffer showed no quantitative change in the levels of KCNJ11 mRNA or in the levels of Kir6.2 protein in the cytosol and cell membrane. Thus, in HOKPP patients, the Kir6.2 protein cannot be transported from the cell membrane to the cytosol, leading to closure of the KATP channels, induction of depolarization, and subsequently, to the paralytic symptoms observed in the patient. Our findings thus provide new insights into the pathogenesis of HOKPP.

가족성 저칼륨성 주기성 마비에서 세포외 칼륨농도가 지연성 정류형 채널을 형성하는 KCNQ3와 KCNQ5 단백질에 미치는 효과

김성조(Sung-Jo Kim),김동현(Donghyun Kim),김준범(June-Bum Kim) 한국생명과학회 2009 생명과학회지 Vol.19 No.10

가족성 저칼륨성 주기성 마비란 상염색체 우성 유전 질환으로 저칼륨혈증을 동반한 간헐적인 가역적 이완성 근육 마비를 특징으로 한다. 세포내 저류된 칼륨으로 인해 저칼륨혈증이 지속되고 근세포 활성이상으로 인해 마비가 발생하는 것으로 알려져 있다. 이러한 증상발현의 분자생물학적 기전을 확인하기 위해 세포 내 칼륨이온을 세포 밖으로 이동시키는 지연성 정류형 채널 단백질의 일종인 KCNQ3와 KCNQ5를 대상으로, 정상인과 환자에서 채취한 골격근 세포를 생리적 세포외 정상 칼륨농도인 4 mM과 탈분극 유도를 위한 고칼륨농도인 50mM에 노출시켜 단백질의 양적 변화 유무를 확인하였다. 유전자 발현양상을 확인하기 위해 mRNA의 양적 변화를 확인한 결과 모든 조건에서 유의한 변화가 관찰되지 않아 정상 칼륨조건과 고칼륨조건이 두 유전자발현의 변화를 야기하지 않음을 확인하였다. 그러나 단백질 양을 관찰한 결과 환자의 골격근 세포가 50 mM의 칼륨농도에 노출되는 경우 KCNQ3 단백질은 세포질 내에서 증가하고 세포막 내에서 감소하였다. 이는 환자의 골격근 세포가 고농도의 세포외 칼륨에 의해 탈분극 되는 경우 재분극에 중요한 기능을 담당하는 KCNQ3 채널 단백질이 세포질 내로 이동하여 재분극 형성의 장애를 초래하고 이로 인해 근세포 활성이 일어나지 않게 되어 마비를 유발할 수 있음을 시사하는 결과로 본 질환의 새로운 발병 기전을 설명할 수 있는 근거로 생각된다. Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant muscle disorder characterized by episodic attacks of muscle weakness with concomitant hypokalemia. Mutations in either a calcium channel gene (CACNA1S) or a sodium channel gene (SCN4A) have been shown to be responsible for this disease. The combination of sarcolemmal depolarization and hypokalemia has been attributed to abnormalities of the potassium conductance governing the resting membrane potential. To understand the pathophysiology of this disorder, we examined both mRNA and protein levels of delayed rectifier potassium channel genes, KCNQ3 and KCNQ5, in skeletal muscle fibers biopsied from patients with HOKPP. Our results showed an increase in the cytoplasmic level of KCNQ3 protein in patients' cells exposed to 50 mM external concentration of potassium. However, mRNA levels of both channel genes did not show significant change in the same condition. Our results suggest that long term exposure of skeletal muscle cells in HOKPP patients to high extracellular potassium alters the KCNQ3 localization, which could possibly hinder the normal function of this channel protein. These findings may provide an important clue to understanding the molecular mechanism of familial hypokalemic periodic paralysis.

1형 나반응을 보인 근결핵양나

김학주 ( Hak Ju Kim ),김준범 ( June Bum Kim ),김혜경 ( Hye Kyoung Kim ),고유수 ( Yoo Soo Ko ),조옥자 ( Ok Ja Joh ),이재승 ( Jai Seoung Lee ),송계용 ( Kye Yong Song ) 대한피부과학회 2007 대한피부과학회지 Vol.45 No.11

While leprosy is usually a chronic disease, leprosy reactions may lead to acute problems. These reactions most often occur after initiation of therapy, but can also develop before treatment. We report a case of leprosy type 1 reaction as the first manifestation of borderline tuberculoid leposy. The patient was a 71-year-old woman who had never received treatment for leprosy. She developed multiple erythematous, swollen lesions on has face, extremities and trunk within a few weeks and suffered from paresthesia, numbness and tenderness on those sites. General symptoms were accompanied by fever, malaise, fatigue and loss of appetite. Histological examination revealed multiple tuberculoid granulomas along with neurovascular bundles. A few acid-fast bacilli were detected on AFB stain. The disease was classified as borderline tuberculoid leprosy. The acute neuritis followed by skin lesions represented leprosy with type 1 reaction. (Korean J Dermatol 2007;45(11):1206∼1209)

Phosphatidylcholine Formula를 이용한 지방종의 치료 경험

김지혜 ( Ji Hye Kim ),김준범 ( June Bum Kim ),박향준 ( Hyang Joon Park ),이재승 ( Jae Seung Lee ),조옥자 ( Ok Ja Joh ),김학주 ( Hak Ju Kim ),손호찬 ( Ho Chan Son ),송계용 ( Kye Yong Song ) 대한피부과학회 2010 대한피부과학회지 Vol.48 No.8

Background: Lipomas are benign neoplasms composed of mature fat cells. Current treatments are invasive and carry the risk of scarring. For this reason, phosphatidylcholine (PPC) formula has been widely used to treat areas of localized fat accumulation. However, there are few reports on injection lipolysis with injection of PPC formula. Objective: The purpose of this study was to investigate whether injection lipolysis with PPC formula is an effective therapeutic option for patients with lipoma. Methods: Twenty-two lipomas in 7 patients were included. Three sessions at intervals of 6 to 8 weeks were done. Sonographic measurements of lipoma size were repeated before each session. Any side-effects and the patients` satisfaction were noted. In one lipoma, histological changes after lipolysis were described. Results: After three sessions, a significant reduction in lipoma size of 47.4% was achieved. Histology showed a fibrosis with loss of adipocytes. Inflammation occurred in one case, so the patient was excluded from this study. Transient burning sensation and swelling at the injection site were the most common adverse effects. No severe side-effects or systemic reactions were observed. Conclusion: Treatment of lipoma with PPC formula has the potential to be a patient-friendly and well-tolerated therapy that can achieve cosmetically pleasing treatment outcomes. (Korean J Dermatol 2010;48(8):672~677)

음경에 발생한 전이성 위암

김지혜 ( Ji Hye Kim ),최지현 ( Ji Hyun Choi ),김준범 ( June Bum Kim ),김학주 ( Hak Ju Kim ),박향준 ( Hyang Joon Park ),이재승 ( Jae Seung Lee ),조옥자 ( Ok Ja Joh ),송계용 ( Kye Yong Song ),최준정 ( Jun Jeong Choi ) 대한피부과학회 2010 대한피부과학회지 Vol.48 No.4

Metastatic carcinoma of the penis is rare and in most cases is associated with primary malignancy of the pelvic organs with widespread metastasis. A 64-year-old man presented with a 2 month history of skin-colored papules on his penis. He also had a history of total gastrectomy and chemotherapy due to advanced gastric carcinoma. Skin biopsy from the lesion revealed atypical polygonal cells with hyperchromatic & pleomorphic nuclei in the dermis. Results of immunohistochemical staining showed a positive reaction of CK7, and a negative reaction of CK20, PSA, and CD68. We report herein a case of metastatic cancer of the penis from gastric carcinoma. (Korean J Dermatol 2010;48(4):306~309)

가성혈관형 방추세포 지방종

김혜경 ( Hye Kyoung Kim ),김준범 ( June Bum Kim ),김학주 ( Hak Ju Kim ),이재승 ( Jae Seung Lee ),조옥자 ( Ok Ja Joh ),송계용 ( Kye Yong Song ) 대한피부과학회 2008 대한피부과학회지 Vol.46 No.3

Spindle cell lipoma, an entity first described in 1975, accounts for about 1.5% of adipocytic neoplasms and is outnumbered by conventional benign lipomas by approximately 60 to 1. We report an unusual pseudoangiomatous variant of spindle cell lipoma on the right thigh of a 78-year-old man. The lesion had the features of typical spindle cell lipoma which was composed of mature fat cells and uniform spindle cells in a mucoid matrix with collagen bundles. In addition, the lesion exhibited irregular, branching spaces with villiform connective tissue projections, giving a striking angiomatoid appearance. Immunohistochemically, the spindle cells were positive for CD34, and lining cells of pseudoangiomatous spaces were negative for CD31, factor VIII-Ag. (Korean J Dermatol 2008;46(3):401∼404)