Min-Geol Lee

Treatment of Bowen's disease with a specially designed radioactive skin patch

Abstract.Bowen’s disease can be treated by various methods, including surgical excision, cryosurgery, laser ablation, curettage, Mohs’ microsurgery and ionizing radiation. Radiotherapy has been a useful therapeutic modality in the treatment of Bowen’s disease and other skin cancers in areas which are difficult to excise, especially the central areas of the face, including eyelids, nose and lips. To overcome some of the disadvantages of external radiotherapy, a specially designed skin patch coated with high-energy beta-emitter holmium-166 was made for topical application at our institute. Twenty-nine sites of Bowen’s disease in eight patients, confirmed by skin biopsy, were treated with 166Ho patches. The patches were applied to the surface of skin cancers for 30–60 min for a total radiation dose of 35 Gy (3500 rads). One to two weeks after application of the 166Ho patch, desquamation, erythema or erosion developed in treated sites, but these acute radiation reactions healed gradually with epithelial regeneration, and they showed good functional and cosmetic results without any complications. Follow-up biopsies were performed 1–5 months after 166Ho patch therapy, and they did not show any signs of Bowen’s disease. One to two years after treatment with 166Ho skin patches, there were no recurrences of Bowen’s diseases and no late complications. The 166Ho patch is an effective and convenient alternative method for the treatment of Bowen’s disease that yields good cosmetic and functional results.

Striatal dopamine loss and discriminative sensory dysfunction in Parkinson's disease

Patients with Parkinsons disease (PD) have higher‐order discriminative sensory dysfunction including prolonged somesthetic temporal discrimination threshold (sTDT). We studied the effect of striatal dopamine loss on the prolongation of sTDT and also studied the impact of prolonged sTDT values on the various parkinsonian motor deficits.

Nevus comedonicus with hidradenoma papilliferum and syringocystadenoma papilliferum in the female genital area

Background Nevus comedonicus is an uncommon malformation of the pilosebaceous unit. Association of nevus comedonicus with tumors originating from the apocrine gland has not previously been reported.

Mitochondrial ATP synthase is a target for TNBS-induced protein carbonylation in XS-106 dendritic cells

ROS are produced in dendritic cells (DCs) during antigen presentation in contact hypersensitivity (CHS). As a result, ROS cause a number of nonenzymatic protein modifications, including carbonylation, which is the most widely used marker of oxidative stress. 2,4,6‐Trinitrobenzene sulfonic acid (TNBS) is a well‐characterized contact allergen that results in the formation of ROS. However, proteins that are carbonylated in DCs in response to TNBS have not been identified. To study ROS‐dependent protein carbonylation in response to TNBS, we used the well‐established mouse DC line, XS‐106. We focused on the effects of TNBS on oxidation by examining selected oxidative markers. We identified TNBS‐induced ROS and myeloperoxidase (MPO) proteins and demonstrated that the increase in ROS resulted in IL‐12 production. The increase in oxidation was further confirmed by an oxidation‐dependent increase in protein modifications, such as carbonylation. In fact, TNBS strongly induced carbonylation of mitochondrial adenosine triphosphate (ATP) synthase in XS‐106 DCs, as determined by MALDI‐TOF analysis and 2‐D Western blotting. ROS production and protein carbonylation were confirmed in human monocyte‐derived DCs (Mo‐DCs). Furthermore, glutathione (GSH) decreased ROS and protein carbonylation in Mo‐DCs. Carbonylation of ATP synthase in DCs may contribute to the pathophysiology of CHS.

Different characteristics of reactive oxygen species production by human keratinocyte cell line cells in response to allergens and irritants

Abstract:  Keratinocytes mount immune responses through the secretion of a variety of inflammatory cytokines, soluble proteins and reactive oxygen species (ROS). However, the role of ROS in keratinocytes in response to allergens and irritants has not yet been elucidated. In this study, we investigated the (i) ROS production; (ii) potential sites of ROS production; (iii) expression of cell surface molecules; (iv) secretion of cytokines; and (v) ROS‐dependent protein carbonylation in chemical‐treated human keratinocyte cell line (HaCaT) cells. Treatment of HaCaT cells with 2,4‐dinitrochlorobenzene (DNCB) and benzalkonium chloride (BKC) increased ROS levels in a time‐ and dose‐dependent manner, as determined with dichlorodihydrofluorescein diacetate (CM‐H2DCFDA), without reducing cell viability. Potential sources of ROS production were evaluated with pretreatment of diphenylene iodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase; rotenone, an inhibitor of the mitochondrial electron transport chain complex or allopurinol, a xanthine oxidase inhibitor. The DNCB‐induced ROS was related to both NADPH oxidase and mitochondrial electron transport chain complex. Conversely, BKC‐induced ROS was related to NADPH oxidase only. Western blotting using an anti‐DNP antibody revealed ROS‐dependent protein carbonylation in response to DNCB but not BKC. Both DNCB and BKC increased the secretion of IL‐1α from HaCaT cells; however, ROS production as well as other changes, except DNCB‐induced secretion of IL‐1α, was not inhibited by antioxidants. Although the role of ROS in keratinocytes in response to chemicals was inconclusive, our results suggest that the characteristics of ROS produced by keratinocytes in response to chemicals might differ.

CC chemokines as potential immunologic markers correlated with clinical improvement of atopic dermatitis patients by immunotherapy

Please cite this paper as: CC chemokines as potential immunologic markers correlated with clinical improvement of atopic dermatitis patients by immunotherapy. Experimental Dermatology 2010; 19: 246–251.

Increased expression of CC chemokine ligand 18 in extrinsic atopic dermatitis patients.

Background:  Although most patients with atopic dermatitis (AD) show high total and allergen‐specific serum immunoglobulin E (IgE) levels, a small subgroup of AD patients have normal total IgE levels and negative serum allergen‐specific IgE. This subgroup has been termed ‘intrinsic’ AD (IAD) as a counterpart to ‘extrinsic’ AD (EAD). However, the difference of chemokines between IAD and EAD has not yet been evaluated.

Corticotropin‐releasing factor decreases IL‐18 in the monocyte‐derived dendritic cell

Abstract:  Recent evidence suggests that crosstalk between mast cells, nerves and keratinocytes might be involved in the exacerbation of inflammatory conditions by stress, but the mechanism by which this occurs remains unclear. Corticotropin‐releasing factor (CRF), which activates the hypothalamo‐pituitary‐adrenal (HPA) axis under stress, also has pro‐inflammatory peripheral effects. However, there have been no reports about CRF receptor expression and the functional role of CRF in the dendritic cell (DC), which is considered to be the link between allergen uptake and the clinical manifestations of allergic diseases, such as atopic dermatitis. The purpose of this study was to investigate the expression of CRF receptors and the functional role of CRF in the monocyte‐derived DC (MoDC) of atopic dermatitis patients and non‐atopic healthy controls. In this study, mRNAs for CRF‐R1α and 1β, as well as the CRF‐R1 protein, were detected in MoDCs. CRF‐R2α (but not R2β or R2γ) mRNA and the CRF‐R2 protein were present in MoDCs. Exposure of DCs to CRF resulted in a decrease of IL‐18 in both atopic dermatitis patients and non‐atopic healthy controls. However, CRF did not alter the expression of IL‐6, CCL17, CCL18, and CCL22. Therefore, our results demonstrate that CRF could modulate immune responses by acting directly upon DCs.

Sinus histiocytosis (Rosai-Dorfman disease) clinically limited to the skin.

Sinus histiocytosis with massive lymphadenopathy (SHML) is an idiopathic proliferation of unique histiocytes that have vesicular nuclei and voluminous pale cytoplasm, often with emperipolesis. Pure cutaneous involvement is very rare. We describe a patient with SHML limited to the skin whose lesion has spontaneously regressed. A 35-year-old Korean male visited the Department of Dermatology due to facial rash for 2 months. A 3 x 3.5 cm-sized well-demarcated dark erythematous nontender plaque was noted on the right cheek. Skin biopsy showed dense, nodular infiltrates of histiocytes with abundant cytoplasm and vesicular nuclei rimmed by lymphoplasma cell aggregates throughout the upper and mid-dermis. The histiocytes were immunohistochemically positive for S-100 protein and CD68, but negative for CD1a. Laboratory tests and a thorough physical examination revealed no abnormalities. These findings suggested that this was a case of SHML clinically limited to the skin. The skin lesion was initially resistant to steroid therapy, but began to regress 10 months after the onset without further treatment.

Statins inhibit chemotactic interaction between CCL20 and CCR6 in vitro: possible relevance to psoriasis treatment

Abstract:  Psoriasis is a chronic IL‐23/Th17 pathway‐associated skin disease. An increased expression of lesional CCL20 can recruit CCR6+ Th17, and lesional cytokine milieu persistently activates keratinocytes to produce CCL20. Lipid‐lowering drugs, statins, are known to possess immune‐modulating functions. In this study, we explored an inhibitory effect of statins on CCL20/CCR6 interaction. We demonstrated that IL‐1β, TNF‐α, and IL‐17A significantly increased CCL20 production from HaCaT cells. However, these increments were markedly inhibited by fluvastatin and simvastatin, but not by pravastatin. In the chemotaxis migration assay, pretreatment with fluvastatin and simvastatin inhibited the migration of human CD4+ T cells towards CCL20. However, the level of CCR6 surface expression in memory CD4+ T cells was not affected. Our results suggest that not all, but specific types of statins may be of benefit in alleviating psoriasis partially via interrupting CCL20/CCR6 chemotactic interaction, the mechanism which may eventually lessen the infiltration of Th17 cells.