Shijima Taguchi

LINEAR CHILDHOOD DISCOID LUPUS ERYTHEMATOSUS FOLLOWING THE LINES OF BLASCHKO: SUCCESSFULLY TREATED WITH TOPICAL TACROLIMUS

Abstract:  The linear arrangement of discoid lupus erythematosus is uncommon. Here, we report a 6‐year‐old Japanese girl with linear discoid lupus erythematosus following the lines of Blaschko on her face and neck. Topical tacrolimus treatment improved the eruptions. The present case also indicated the important role of epidermal and dermal cells as well as immune cells in the pathogenesis of cutaneous lupus erythematodes.

Overexpression of the Transcription Factor Yin-Yang-1 Suppresses Differentiation of HaCaT Cells in Three-Dimensional Cell Culture

Yin-Yang-1 (YY1) is a member of the GLI-Krüppel family of transcription factors, and both YY1 mRNA and protein expression have been identified in a number of different tissues and cell types suggesting that it is expressed both constitutively and ubiquitously. In epidermal tissue, however, we reported previously that YY1 protein is expressed at high levels in undifferentiated basal keratinocytes and is downregulated during differentiation toward the suprabasal layers. This differential expression pattern during keratinocyte differentiation suggests that YY1 may have an important role in regulating keratinocyte differentiation. In this study, we examined the role of YY1 in differentiation of the human keratinocyte cell line HaCaT using air-liquid interface three-dimensional culture. The constitutive overexpression of YY1 in HaCaT cells during air exposure-induced differentiation resulted in an undifferentiated phenotype, thickening of the stratified layers, suppression of differentiation marker expression, and retention of proliferative activity. These findings suggested that YY1 may have an important role in maintenance of the undifferentiated phenotype of keratinocytes in the basal epidermal layer, and that reduction of YY1 expression in the suprabasal layers may allow keratinocytes to differentiate and move toward the upper layers of the epidermis.

Pituitary Tumor Transforming Gene 1 Induces Tumor Necrosis Factor-α Production from Keratinocytes: Implication for Involvement in the Pathophysiology of Psoriasis

Proliferation and differentiation in the epidermis must be tightly regulated. This regulation is known to involve a range of transcription factors, including pituitary tumor transforming gene 1 (PTTG1), a ubiquitously distributed transcription factor that regulates keratinocyte proliferation and differentiation. Psoriasis is a common but refractory skin disorder, the pathophysiology of which is characterized by hyperproliferation and impaired differentiation in the epidermis. The present study was conducted to clarify the less well-known roles of PTTG1 in the pathophysiology of psoriasis, focusing on its relationship with tumor necrosis factor-α (TNF-α), which is a critical mediator of the disease. The levels of PTTG1 expression were increased in the psoriatic epidermis. Overexpression of PTTG1 resulted in the overproduction of TNF-α, and TNF-α itself had an inductive effect on PTTG1 expression, suggesting that their expression may involve autoinduction. Moreover, overexpression of PTTG1 involved augmented the expression of cyclin A and B1 proteins in both cultured keratinocytes and the psoriatic epidermis. Therefore, enhanced expression of PTTG1 in the psoriatic epidermis may result in aberrant regulation of the cell cycle and impaired differentiation via the interplay between PTTG1 and TNF-α.

Pituitary Tumor-Transforming Gene 1 Enhances Proliferation and Suppresses Early Differentiation of Keratinocytes

The epidermis is a self-renewing tissue, the homeostasis of which is dependent upon the tight balance between proliferation and differentiation based on appropriate regulation of the cell cycle. The cell cycle regulation is dependent on the interactions among a number of cell cycle regulatory molecules, including the pituitary tumor-transforming gene 1 (PTTG1), also known as securin, a regulator of sister chromatid separation and transition from metaphase to anaphase. This study was conducted to clarify the less-known functions of PTTG1 in the epidermis by the use of keratinocytes cultured under two-dimensional (2D) or three-dimensional (3D) conditions. Forced overexpression of PTTG1 caused upregulation of cyclin B1, cyclin-dependent kinase 1 (CDK1), and c-Myc, resulting in enhanced proliferation and suppression of early differentiation without apparent alterations in terminal differentiation, and the exogenous PTTG1 was downregulated in association with cell cycle exit. In contrast, depletion of PTTG1 caused their downregulation and constrained proliferation with retention of differentiation capacity. These findings suggested that PTTG1 could alter the proliferation status by modulating the expression levels of the other cell cycle regulatory proteins, and excess PTTG1 primarily affects early differentiation of keratinocytes under the stability regulation associated with cell cycle exit.

Pituitary tumor-transforming gene 1 as a proliferation marker lacking prognostic value in cutaneous squamous cell carcinoma

Non‐melanoma skin cancer is the most frequently occurring type of cancer worldwide and is caused by epidermal carcinogenesis and malignant progression that involve dysregulated expression of proto‐oncogenes and tumor suppressor genes. The proto‐oncogene pituitary tumor‐transforming gene 1 (PTTG1) is a ubiquitously expressed transcription factor that can promote enhanced proliferation of cultured epidermal keratinocytes. To investigate the potential roles of PTTG1 in epidermal carcinogenesis and malignant progression, the expression of PTTG1 was analysed by immunohistochemistry along with Ki67, keratin 10 (K10) and p53 in tissue samples of cutaneous squamous cell carcinomas (SCC), actinic keratoses (AK) and Bowens disease (BD). Expression levels of PTTG1 were compared among these disease groups to test for correlations with proliferation, differentiation capacity or the existence of mutated tumor suppressor genes in each disease group. In each disease group, the expression levels of PTTG1 correlated positively with those of Ki67, although the differentiation status, measured by K10 expression, did not show any correlation. In contrast, the existence of mutated p53 proteins showed a positive correlation only in the SCC group. Moreover, the expression levels of PTTG1 in SCC did not correlate with known prognostic factors such as TNM staging or tumor thickness. These results suggest that PTTG1 may represent a proliferation marker associated with mutated p53 proteins but is not an informative predictor of poor clinical outcomes in SCC.

Superimposed segmental dermatitis with chronic prurigo

Common acquired skin diseases with a polygenic background, such as lichen planus, may show linear or segmental manifestations of underlying systemic skin disease. The linear arrangement in such cases is usually consistent with the lines of Blaschko. Happle summarized the various types of segmental arrangement of common polygenic diseases and proposed a novel designation of superimposed segmental dermatosis. Here, we report a unilateral linear dermatitis distributed along the lines of Blaschko on the leg, which was not self-healing and persisted for at least 6 years without complete remission, and was accompanied by preceding chronic prurigo on the extremities. Histological examination showed subacute spongiotic dermatitis and epidermal infiltration of CD4-positive cells. This case report presents a superimposed segmental dermatitis that arose based on systemic eczematous conditions, such as chronic prurigo.

Epidermal pseudocarcinomatous hyperplasia with underlying epidermal growth factor–producing cutaneous CD30-positive lymphoproliferative disorder

© 2008 The Authors JEADV 2009, 23, 169–243 Journal compilation

Localized bullous pemphigoid associated with dipeptidyl peptidase-4 inhibitor treatment

EJD, vol. 28, n◦ 2, March-April 2018 had tense blisters [6-9], while one case had no blisters over the entire body [10]. In our case, multiple flaccid blisters, but no tense blisters, were observed, and the mechanisms of the flaccid blister formation in our case is unknown. There are also three previous reports of BP with IgG antibodies to LAD-1, but not to BP180 NC16a or BP230 [2, 6, 7]. Future studies of more cases with exclusive IgG reactivity to LAD-1 are needed to clarify the clinical features and pathogenesis in these patients.

Pedunculated dermatofibrosarcoma protuberans: an unusual presentation.

Dermatofibrosarcoma protuberans (DFSP) is a rare skin tumor with a lowto intermediate-grade of malignancy, characterized by an indolent, slow, but infiltrative growth, and a tendency for local recurrence. DFSP usually presents clinically as an indurated plaque or a raised slowly growing firm, nodular dermal-subcutaneous mass [1–3]. We recently encountered a pedunculated DFSP, an exceptional presentation that has only been reported once previously.

Lipoma adjacent to scapula in an elderly

An 81-year-old man complained a soft mass in right back, which was noticed a week ago. He had been diagnosed as having chronic obstructive pulmonary disease seven years previously and treated with longacting muscarinic antagonistat our hospital. On physical examination, an egg-sized soft mass was palpable in right back. It seemed to be fixed to the underlying structure or overlying skin. A chest CT scan showed a 5 x 5 cm homogenous low density mass, which had the same density as fat, adjacent to right scapula (Figure 1). The lesion was completely removed surgically and it was diagnosed as lipoma pathologically. Retrospectively, not only low attenuation area in both lungs but also the tumor was observed in a chest CT scan taken 6 years previously (Figure 2).