LAMP-3 (Lysosome-Associated Membrane Protein 3) Promotes the Intracellular Proliferation of Salmonella typhimurium

Joong-Kook Choi,Eun-Ju Lee,Kwan-Sik Park,전인숙,Jae-Woon Choi,Sang Jeon Lee,Hyun E. Choy,Ki-Duk Song,Hak-Kyo Lee 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.7

Lysosomes are cellular organelles containing diverse classes of catabolic enzymes that are implicated in diverse cellular processes including phagocytosis, autophagy, lipid transport, and aging. Lysosome-associated membrane proteins (LAMP-1 and LAMP-2) are major glycoproteins important for maintaining lysosomal integrity, pH, and catabolism. LAMP-1 and LAMP-2 are constitutively expressed in Salmonella-infected cells and are recruited to Salmonella-containing vacuoles (SCVs) as well as Salmonella-induced filaments (Sifs) that promote the survival and proliferation of the Salmonella. LAMP-3, also known as DC-LAMP/CD208, is a member of the LAMP family of proteins, but its role during Salmonella infection remains unclear. DNA microarray analysis identified LAMP-3 as one of the genes responding to LPS stimulation in THP-1 macrophage cells. Subsequent analyses reveal that LPS and Salmonella induced the expression of LAMP-3 at both the transcriptional and translational levels. Confocal Super resolution N-SIM imaging revealed that LAMP-3, like LAMP-2, shifts its localization from the cell surface to alongside Salmonella. Knock-down of LAMP-3 by specific siRNAs decreased the number of Salmonella recovered from the infected cells. Therefore, we conclude that LAMP-3 is induced by Salmonella infection and recruited to the Salmonella pathogen for intracellular proliferation.

Venous-cavernous angioleiomyoma on the upper lip

( Joong Woon Choi ),( Dong Woo Suh ),( Bark Lynn Lew ),( Woo Young Sim ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

Angioleiomyomas are vascular variant of leiomyomas which are benign tumors derived from smooth muscle and commonly develops on the lower extremities of middle-aged persons. They are rarely found in the oral cavity and if they are found, most commonly occur on the lower lip and the palate. Angioleiomyoma on the upper lip is seldom affected and, to our knowledge, only few cases have been reported. We report here a 53-year-old man presented with a chief complaint of a growth in his left side of upper lip for 20 years duration. The lesion was asymptomatic and clinical examination presented as a well circumscribed submucosal nodule of approximately 2.5cm in diameter on the upper lip. Histopathologic examination revealed well-circumscribed and encapsulated tumor characterized by proliferation of smooth muscle cells and large amount of dilated vascular spaces of varying sizes with single layer of endothelial lining. Immunohistochemical staining of CD31 for endothelial cells and alpha-smooth muscle actin for smooth muscle cells were reactive. Based on these findings, a diagnosis of angioleiomyoma was made. The location of an upper lip as well as oral angioleiomyoma, the rare case, made the clinicians to misdiagnosis about labial mass. Dermatologists should be aware of this entity when large labial mass has occurred in the upper lip.

Efficacy and utility of wet wrap dressing for patients with pediatric atopic dermatitis

( Joong-woon Choi ),( Min-jeong Kang ),( Seung-hee Loh ),( Bark-lynn Lew ),( Woo-young Sim ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.2

Background: Wet wrap dressing (WWD) is an interesting alternative for short-term control in patients with severe or refractory flares that avoids the use of systemic treatments. Objectives: This study was done to compare the efficacy of wet wrap dressing group with topical steroid agents with control and estimate the utility of WWD Methods: Total 40 cases with moderate to severe atopic dermatitis (mean eczema area and severity index, EASI≥7) and less than 13 years old were included in this study. The improvement of severity was evaluated by EASI and transepidermal water loss (TEWL). We compared two groups at 1 week treatment using analysis of covariance (ANCOVA) and t-test. Furthermore, we surveyed the questionnaire about the utility and adverse effect of WWD to evaluate the subjective outcomes of WWD. Results: After 1 week of WWD treatment, the statistically significant reductions in mean EASI (-6.138, 95% CI -7.328 to -4.947, p=0.013), and TEWL (-26.714, 95% CI -31.162 to -22.266, p=0.002) were observed compared to EASI (-4.048, 95% CI -5.205 to -2.892) and TEWL (-15.359, 95% CI -19.807 to -10.911) of control group. Patient self-assessment and visual analogue scale (VAS) were improved in both group, but there was no statistically significance between both groups in the VAS. Utility of WWD through the questionnaire was satisfactory. Conclusion: WWD has superior therapeutic effects than conventional steroid application in the treatment of atopic dermatitis of children

Simvastatin/Ezetimibe Therapy for Recalcitrant Alopecia Areata: An Open Prospective Study of 14 Patients

( Joong-woon Choi ),( Dong-woo Suh ),( Bark-lynn Lew ),( Woo-young Sim ) 대한피부과학회 2017 Annals of Dermatology Vol.29 No.6

Background: Simvastatin belongs to the statin family, whose members have immunomodulatory activities. Ezetimibe have synergetic effects when co-administered with simvastatin. In several case reports, alopecia totalis and alopecia universalis were successfully treated with simvastatin/ezetimibe, suggesting that this combination could be a new efficient therapy for recalcitrant alopecia areata (AA). Objective: To verify the efficacy of the simvastatin/ezetimibe combination therapy for recalcitrant AA and investigate the relationship between various treatment responses and prognostic factors. Methods: This prospective open study was performed in patients with recalcitrant AA with the bald surface exceeding 75%. All patients took simvastatin (40 mg) and ezetimibe (10 mg) daily. The extent of hair regrowth expressed as percentage of the bald area was used to evaluate the effectiveness of the therapy. Results: Of 14 enrolled patients, 4 patients (28.6%) were judged as responders showing regrowth of 30% to 80% after 3 months of treatment. The mean age of onset in non-responders was significantly lower than in responders. The total score of prognostic factors, calculated as a sum of factors related to poor prognosis, was much lower in responders than in non-responders. Conclusion: The remission rate in this study was unsatisfactory. However, since the recruited patients had not responded to any other treatments for AA, simvastatin/ezetimibe can still be considered as an alternative treatment for recalcitrant AA. The total scores of the prognostic factors were statistically different between responders and non-responders. These results can be used to predict the outcome of treatment with simvastatin/ ezetimibe and anticipate prognosis. (Ann Dermatol 29(6) 755∼760, 2017)

Efficacy study of simvastatin/ezetimibe in recalcitrant alopecia areata

( Joong Woon Choi ),( Dong Woo Suh ),( Bark Lynn Lew ),( Woo Young Sim ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Alopecia areata (AA) is a chronic, organ-specific autoimmune disease, mediated by T cells,which affects hair follicles. Simvastatin is a member of the statins or 3-hydroxy-3 methylglutaryl coenzyme A reductase inhibitors. Statins act as immunomodulatoryagents participating in the repression of MHC class 2 molecule mediated T lymphocyte activation. Ezetimibe is a drug that lowers plasma cholesterol levels. Ezetimibe has been shown possibly synergetic anti-inflammatory effects when given with simvastatin. It was observed in a fewreports that simvastatin/ezetimibe successfully treated severe cases of alopecia areata including alopecia totalis and universalis. Objectives: To evaluate the efficacy of simvastatin/ezetimibe in patients with recalcitrant AA Methods: Medical records of AA patients treated with simvastatin/ezetimibe, seen between June 2006 and August 2015 and didn’t show any responses to previous treatment modalities, were reciprocally reviewed. Treatment durationgreater than 3 months was considered the inclusion criteria, finally. Results: Two of eight enrolled patients were judgedresponders and showed weak responses about 15% and 20%. Responders showed limited disease duration different significantly with 10 years, a median duration, of non-responders. Conclusion: The remission rate of simvastatin/ezetimibe for AA was unsatisfactory. However, clinicians should not conclude that simvastatin/eztimibe is not effective for AA, as the patients was recalcitrant.

Efficacy study of hydroxychloroquine in recalcitrant alopecia areata

( Joong Woon Choi ),( Dong Woo Suh ),( Bark Lynn Lew ),( Woo Young Sim ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Alopecia areata (AA) is a nonscarring hair loss of unknown etiology, with a multifactorial autoimmune pathogenesis. Hydroxychloroquine, an antimalarial and immune modulator, is used in thetreatment of different scarring alopecia. The efficacy of hydroxychloroquine for AA remains unpredictable. Just two cases of successful treatment of AT with hydroxychloroquine have been reported. Objectives: To evaluate the efficacy of hydroxychloroquine in patients with recalcitrant AA. Methods: Medical records of AA patients treated with hydroxychloroquine, seen between June 2006 and August 2015 and didn’t show any responses to previous treatment modalities, were reciprocally reviewed. Treatment duration greater than 3 months was considered the inclusion criteria, finally. Hair regrowth was quantified as no response, 1% to 29% (weak response), 30% to 59% (moderate response), or 60% to 100% (good to excellent response). Results: Three of eighteen enrolled patients were judged responders and 3 responders showed different clinical results each other, weak, moderate, good to excellent responses according the quantification of hair regrowth. The median duration of current AA episode before starting treatment was 4 years and this is different significantly from 8 years of non-responders. Conclusion: The remission rate of hydroxychloroquine for AA was unsatisfactory. However, clinicians should not conclude that hydroxychloroquine is not effective for AA, as the patients was recalcitrant.

Angioleiomyoma Occurred on the Ear Lobe: A Case Report and Literature Review

( Joong-woon Choi ),( Dong-woo Suh ),( Bark-lynn Lew ),( Woo-young Sim ) 대한피부과학회 2018 大韓皮膚科學會誌 Vol.56 No.1

Development of squamous cell carcinoma on actinic keratosis after Ingenol Mebutate gel

( Joong Woon Choi ),( Young Jun Oh ),( Dong Woo Suh ),( Bark Lynn Lew ),( Woo Young Sim ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.1

Ingenol mebutate (Picato@) gel is a new short term topical treatment approved in 2012 by the US food and Drug Administration (FDA). A 79-year-old female presented with numerous patches and plaques on her face. During the physical examination, nine lesions were found with well-defined erythematous patches and plaques with crusts. Biopsy specimens were consistent with actinic keratosis. We applied 0.015% ingenol mebutate gel on the affected area with a 0.5 cm margin once daily for 3 days consecutively. Most of the lesions were improved clinically, but one lesion located on the forehead was mildly aggravated. The lesion was presented with a well-defined hyperkeratotic erythematous plaque measuring 1.5x1.5 cm with crusts on her forehead after 2 months. Wide local excision was performed and the histopathologic result showed the extension of atypical keratinocytes into the dermis with nests of tumor cells consistent with squamous cell carcinoma. When only the effects of inflammatory responses stimulate the dysplastic epidermal cells of AK dominantly at low dose concentration, the AK can be rather progress to rapidly growing SCCs through the activation of inflammatory substances, IL-1β and MMPs. The progression of AK by the inflammatory triggering effects at low concentration of ingenol mebutate should be acknowledged and clinicians should not hesitate to change the treatment to surgical excision when the lesions progress abruptly.

P156 Histpathologic features of alopecia areata

( Joong-woon Choi ),( Seung-hee Loh ),( Bark-lynn Lew ),( Woo-young Sim ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

<div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div> Background: AA have many histologic features, including the absence of the classic findings according to the phase, type and current duration of AA, and these various features confuse many clinicians and pathologists for diagnosis of AA Objectives: To establish the histologic features of alopecia areata in scalp biopsy specimens taken from different types and duration of AA Methods: The pathology archives of Kyung hee university hospital at Gang-dong were searched for alopecia areata in the diagnostic field from the period of 2006 to 2016 with sections suitable for review. The specimens were sectioned by Tyler technique Results: Of the 450 cases initially selected, 8 cases were excluded because of lack of available representative sections. Peribulbar lymphocytic infiltrate in acute, subacute, chronic stages was 57 cases (92%), 62 cases (78%) and 216 cases (76%), and in patchy, acute diffuse and total alopecia areata (ADTA), alopecia totalis (AT) was 211 cases (98%), 22 cases (100%), 95cases (72%), respectively. Eosinophilic infiltrate was prominent 19 cases (31%) in acute phase and decreased relatively in alopecia totalis (AT) with 8 cases (6%). Less than 1 of anagen/telogen ratio was observed predominantly in more than 1year of current duration. Conclusion: Prominent peribulbar lymphocytic infiltrate (92%) and relatively decrease of anagen/telogen ratio are observed in acute patchy type AA. We found that total hair counts were decreased prominently at more than 5 years of current duration.

P155 Histopathologic features of ophiasis-type alopecia areata

( Joong-woon Choi ),( Seung-hee Loh ),( Bark-lynn Lew ),( Woo-young Sim ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

<div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div><div style="display:none">fiogf49gjkf0d</div> Background: Ophiasis is a type of alopecia areata identified as a turban or snake-like pattern of hair loss, and it is often refractory to conventional treatments and has a less favorable prognosis. Objectives: To establish the histologic features of ophiasis-type alopecia areata in scalp biopsy specimens and sought to correlate between histopathologic features and clinical prognosis. Methods: The pathology archives of Kyung hee university hospital at Gang-dong were searched for the term ‘ophiasis’ from the period of 2006 to 2016 with sections suitable for review. The specimens were sectioned by Tyler technique. Results: Total 22 cases were included in this study. Quantification of the follicular counts revealed development of more miniaturized hairs and prominent disappearance of terminal hairs. Peribulbar lymphocytic infiltrate and eosinophilic infiltrate were observed 12 cases (56%) and 8 cases (36%), respectively. The mean miniaturized hair counts were 6.6 hairs and anagen/telogen percentage was 14/86%, relatively very low ratio. Total hair follicle counts and follicular units decreased slightly with 12.4 hairs and 3 units, respectively. Lymphocytic infiltration around bulge area was observed in 10 cases (45%) Conclusion: Forty five percentages (10 cases) of lymphocytic infiltration around bulge area is relatively high ratio than other type AA (20%). These histologic characteristics of specimens can explain the causes of poor prognosis of ophiasis-type AA.