Kee Yang Chung

An AP-1 binding sequence is essential for regulation of the human α2(I) collagen (COL1A2) promoter activity by transforming growth factor-β

Previous studies have shown that transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) modulate type I collagen gene expression in fibroblasts. To fine-map the corresponding response elements in the human α2(I) collagen (COL1A2) promoter, we have generated a series of 5′ deletion promoter/chloramphenicol acetyltransferase (CAT) reporter gene constructs. Transient cell transfection assays using human dermal fibroblasts and stable transfection experiments using NIH 3T3 fibroblasts identified the region located between residues −265 and −241, as critical for TGF-β response. Specifically, we demonstrate that this 25-base pair region mediates the up-regulatory effect of TGF-β on COL1A2 promoter activity and allows antagonistic activity of TNF-α on the TGF-β effect. Gel mobility shift assays indicate that nuclear factor binding to this 25-base pair region of COL1A2 promoter is competed by AP-1, but not NF-1 or NF-κB, oligonucleotides. Transient cell transfection experiments with plasmid constructs in which the potential AP-1-binding site located within this short region of promoter was modified by sitedirected mutagenesis indicated that this element plays a significant role in the basal activity of the promoter. Furthermore, this sequence is essential for TGF-β response and does not require the presence of the three Sp-1-binding sites located further upstream, between nucleotides −273 and −304. In addition, overexpression of c-jun in co-transfection experiments with COL1A2 promoter/CAT constructs blocks the TGF-β response, further implicating AP-1 in the regulation of COL1A2 gene expression. Our results clarify the molecular mechanisms involved in the regulation of type I collagen gene expression and further emphasize the importance of AP-1 in mediating some of the TGF-β effects on gene transcription.

Efficacy of allergen-specific immunotherapy for atopic dermatitis: A systematic review and meta-analysis of randomized controlled trials

BACKGROUND Allergen-specific immunotherapy (allergen-SIT) is the only treatment directed at the cause of IgE-mediated allergic diseases. However, there is controversy over the use of SIT for patients with atopic dermatitis. OBJECTIVE We performed a systematic review and meta-analysis to assess the efficacy of SIT for patients with atopic dermatitis. METHODS We performed manual searches of reference lists and computerized searches of the MEDLINE, EMBASE, CINAHL, Web of Science, and Cochrane databases (through December 10, 2012) for randomized controlled trials that compared SIT with placebo for patients with atopic dermatitis. The outcome of interest was a dichotomous variable, in terms of treatment success; a meta-analysis was performed by using a random-effects analysis. Subgroup analyses were carried out to evaluate the effects of long-term treatment (more than 1 year), SIT for severe atopic dermatitis, SIT for children, and subcutaneous and sublingual administration of immunotherapy. RESULTS We analyzed 8 randomized controlled trials that comprised a total of 385 subjects. We found that SIT has a significant positive effect on atopic dermatitis (odds ratio [OR], 5.35; 95% CI, 1.61-17.77; number needed to treat, 3; 95% CI, 2-9). SIT also showed significant efficacy in long-term treatment (OR, 6.42; 95% CI, 1.50-27.52) for patients with severe atopic dermatitis (OR, 3.13; 95% CI, 1.31-7.48), and when administered subcutaneously (OR, 4.27; 95% CI, 1.36-13.39). CONCLUSIONS A meta-analysis provides moderate-level evidence for the efficacy of SIT against atopic dermatitis. However, these findings are based on an analysis of a small number of randomized controlled trials, with considerable heterogeneity among trials.

Xeroderma Pigmentosum-Variant Patients from America, Europe, and Asia

Xeroderma pigmentosum-variant (XP-V) patients have sun sensitivity and increased skin cancer risk. Their cells have normal nucleotide excision repair, but have defects in the POLH gene encoding an error-prone polymerase, DNA polymerase eta (pol eta). To survey the molecular basis of XP-V worldwide, we measured pol eta protein in skin fibroblasts from putative XP-V patients (aged 8-66 years) from 10 families in North America, Turkey, Israel, Germany, and Korea. Pol eta was undetectable in cells from patients in eight families, whereas two showed faint bands. DNA sequencing identified 10 different POLH mutations. There were two splicing, one nonsense, five frameshift (3 deletion and 2 insertion), and two missense mutations. Nine of these mutations involved the catalytic domain. Although affected siblings had similar clinical features, the relation between the clinical features and the mutations was not clear. POLH mRNA levels were normal or reduced by 50% in three cell strains with undetectable levels of pol eta protein, indicating that nonsense-mediated message decay was limited. We found a wide spectrum of mutations in the POLH gene among XP-V patients in different countries, suggesting that many of these mutations arose independently.

Comparison of Mohs Micrographic Surgery and Wide Excision for Extramammary Paget's Disease: Korean Experience

BACKGROUND Extramammary Pagets disease (EMPD) is an uncommon tumor that usually occurs on the genitalia. It almost always extends beyond clinically apparent margins and has a high rate of recurrence. OBJECTIVE To establish treatment guidelines for EMPD in Asian patients. METHODS A retrospective review was done on pertinent demographic data, tumor data, treatment characteristics, and follow-up data of 35 patients between 1996 and 2006. Review of literature for treatment modalities and recurrence rates of EMPD was also performed. RESULTS Thirty-four of the 35 patients (30 men and 5 women) had lesions in the genital area and one patient in the axilla. Mean follow-up duration was 62.7 months (8–156 months) and two of 11 (18.2%) recurred after Mohs micrographic surgery (MMS), compared with eight recurrences of 22 (36.4%) after standard wide excision. Two patients treated with nonsurgical modalities did not achieve complete remission. Estimated 5-year tumor-free rate using Kaplan-Meier graph was 69.7% in all patients, with a rate of 81.8% for MMS and 63.6% for wide excision. CONCLUSIONS MMS is more effective, with lower recurrence rate than wide excision, and should be regarded as the first-line treatment for nonmetastatic EMPD.

Early postoperative treatment of thyroidectomy scars using a fractional carbon dioxide laser

BACKGROUND Ablative carbon dioxide fractional laser systems (CO2 FS) have been effectively used to improve the appearance of scarring after surgical procedures, but an optimal treatment time has not been established. OBJECTIVE To evaluate the efficacy and safety of CO2 FS in early postoperative thyroidectomy scars. METHODS Twenty‐three Korean women with thyroidectomy scars were enrolled in this study. All patients underwent a single session of two passes of a CO2 FS with a pulse energy setting of 50 mJ and a density of 100 spots/cm2 2 to 3 weeks after surgery. RESULTS Mean Vancouver Scar Scale (VSS) scores were statistically significantly lower after laser treatment. Three months after CO2 FS treatment of thyroidectomy scarring, 12 of 23 participants showed clinical improvement of more than 51% from 2 to 3 weeks after surgery. The mean grade of clinical improvement based on independent clinical assessment was 2.6 ± 0.9. CONCLUSION Early postoperative CO2 FS treatment of thyroidectomy scars is effective and safe. The authors have indicated no significant interest with commercial supporters.

Infraorbital Dark Circles: Definition, Causes, and Treatment Options

BACKGROUND Infraorbital dark circles refer to the conditions that present with darkness of the infraorbital eyelids. Although it is not a medical concern, it can be a cosmetic concern for a large number of individuals. Moreover, clear definition and possible causes have not been elucidated. OBJECTIVE To review the possible causes and treatment options for infraorbital dark circles. METHODS The article is based on a review of the medical literature and the authors clinical experience in treating infraorbital dark circles. CONCLUSION Possible causative factors of infraorbital dark circles include excessive pigmentation, thin and translucent lower eyelid skin overlying the orbicularis oculi muscle, and shadowing due to skin laxity and tear trough, but because multiple factors cause infraorbital dark circles in the majority of patients, it is essential to identify the cause and choose the appropriate treatment according to the cause. The authors have indicated no significant interest with commercial supporters.

Collagen fibril formation; a new target to limit fibrosis

We present a concept for reducing formation of fibrotic deposits by inhibiting self-assembly of collagen molecules into fibrils, a main component of fibrotic lesions. Employing monoclonal antibodies that bind to the telopeptide region of a collagen molecule, we found that blocking telopeptide-mediated collagen/collagen interactions reduces the amount of collagen fibrils accumulated in vitro and in keloid-like organotypic constructs. We conclude that inhibiting extracellular steps of the fibrotic process provides a novel approach to limit fibrosis in a number of tissues and organs.

Treatment and Outcomes of Melanoma in Acral Location in Korean Patients

Purpose A retrospective study was conducted to review the treatment and outcomes of mainly melanomas in acral location in a single institution in Korea, and to evaluate the prognostic significance of anatomic locations of the tumor. Materials and Methods A retrospective review was completed on 40 patients between 2001 and 2006 to obtain pertinent demographic data, tumor data, treatment characteristics, and follow-up data. Results Forty melanoma patients were identified and analyzed. Of these, 18 were male and 22 were female patients and the mean age at the time of diagnosis was 55.9 years. Of the tumors, 65% were located on the hands and feet with acral lentiginous melanoma being the most common histological subtype. Univariate analysis for the overall melanoma survival revealed that the thickness of the tumor and the clinical stage have prognostic significances. The most significant factor as analyzed by a multivariate analysis was shown to be the advanced clinical stage. Acral melanomas did not show statistically significant differences in the age at diagnosis, thickness of the tumor, stage, ulceration, and survival rates compared to non-acral melanomas. There was also no significant difference in the survival rate between the patients treated by amputation versus wide local excision in acral melanomas. Conclusion In Korean melanoma patients, thickness and advanced stages are significant factors for poorer prognosis. However, the location of melanoma did not have a significant prognostic value. In treating the melanomas in acral location, local wide excisions resulted in a similar prognosis compared to amputations.

Mohs micrographic surgery for extramammary Paget disease: A pooled analysis of individual patient data

BACKGROUND Extramammary Paget disease (EMPD) is a rare intraepithelial neoplasm of the skin characterized by ill-defined margins and high recurrence rates after wide local excision. Although Mohs micrographic surgery (MMS) has been proposed to decrease the rate of local recurrence, the efficacy of MMS for this condition has not yet been established. OBJECTIVE We sought to assess the efficacy of MMS for the treatment of EMPD. METHODS A comprehensive systematic review and individual patient data meta-analysis was performed including all available clinical studies and case reports with 5 or more subjects describing the use of MMS for EMPD. RESULTS Eight studies were identified and included in the current review: 3 retrospective studies and 5 case series. In all, 81 patients with 90 cases of MMS were included from these 8 studies. The overall recurrence rate for EMPD after MMS was 12.2% correlating with an estimated 5-year tumor-free rate of 83.6% by using Kaplan-Meier curve analysis. The treatment of EMPD with MMS resulted in significantly lower recurrence rates than wide local excision in this meta-analysis of 3 observational studies with comparators (odds ratio 0.20; 95% confidence interval 0.05-0.81). LIMITATIONS Limitations include lack of controlled trials, small sample sizes in the included studies, and publication bias. CONCLUSION The current evidence supports the efficacy of MMS in the treatment of EMPD. Further controlled clinical trials are needed.

Behçet's syndrome associated with bullous necrotizing vasculitis

We recently saw a case of Behçets syndrome in an 11-year-old Korean boy who had severe bullous necrotizing vasculitis as a skin manifestation. The patient exhibited three major criteria of the Shimizu classification, namely, oral and genital ulcerations, uveitis, and bullous necrotizing vasculitis as the skin manifestation. Immunologic laboratory data showed an increased OKT4/OKT8 ratio and a lymphocyte stimulation index with phytohemagglutinin. A skin specimen taken from a developing lesion showed features of lymphocytic vasculitis extending into the panniculus.