Akiko Watabe

Sweat constitutes several natural moisturizing factors, lactate, urea, sodium, and potassium.

BACKGROUND Amino acids (AAs) play important roles in maintaining an optimal hydration state of stratum corneum (SC) as a natural moisturizing factor (NMF). Recently, however, we have reported that lactate and potassium significantly affect the hydration state of SC. OBJECTIVE To explore the source of lactate and potassium in SC, we compared the concentration of various NMFs such as AAs, pyrrolidone carbonic acid (PCA), lactate, sodium, and potassium in SC between anhidrotic and adjacent hidrotic areas of patients with acquired idiopathic generalized anhidrosis or segmental anhidrosis. METHODS We examined 13 anhidrotic areas and the adjacent hidrotic skin of 10 different patients. We first determined anhidrotic and hidrotic areas of each patient by the iodine starch method and examined the hydration state of SC by measuring the high-frequency conductance. Then we obtained SC by tape stripping and measured the content of AAs, PCA, lactate, urea, sodium, and potassium in SC obtained from the anhidrotic and hidrotic areas. We examined the effect of increased insensible perspiration on the SC hydration and the concentrations of NMFs. RESULTS The SC of anhidrotic areas showed significantly low hydration. Among NMFs, lactate, urea, sodium, and potassium were significantly decreased in the SC of anhidrotic areas, while AAs and PCA were not significantly different between hidrotic and anhidrotic areas. Increased insensible perspiration increased SC hydration as well as NMFs other than AAs and PCA. CONCLUSION Sweat constitutes lactate, urea, sodium, and potassium in NMFs and plays a crucial role in maintaining the physiological hydration state of SC.

The possible interaction between periostin expressed by cancer stroma and tumor‐associated macrophages in developing mycosis fungoides

Mycosis fungoides (MF) starts as an indolent disease, progresses from a patch stage to confluent plaques and ultimately develops skin tumors. Tumor‐associated macrophages (TAMs) play roles in maintaining the tumor microenvironment in MF. The purpose of this study was to elucidate the involvement of TAMs in the lesional skin of different stages of MF. First, we immunohistologically examined the percentage of CD163+ macrophages and CD206+ cells, as well as the levels of periostin and IL‐4 in cancer stroma. The percentage of CD206+ cells increased in parallel with tumor progression, while there was no significant difference in the percentage of CD163+ cells. Periostin was prominent in the stromal area at the patch and plaque stages but decreased at the tumor stage. In contrast, IL‐4 was prominently stained at both plaque and tumor stages. To further elucidate the molecular mechanisms of the effects of these stromal factors on TAMs, we examined their effects on mRNA expression in monocyte‐derived macrophages in vitro. Based on microarray analysis and gene ontology, we examined a series of chemokines and MMPs whose expression was strongly connected with periostin stimulation. The DNA microarray results were verified in M2 macrophages using real‐time PCR. We further examined the mRNA expression of these chemokines and MMPs in the presence of periostin and IL‐4 to simulate the advanced stages of MF and validated their protein expression by ELISA. Our present report suggests possible roles of periostin on TAMs in establishing the tumor microenvironment in MF.

Epithelioid Sarcoma-like Haemangioendothelioma: A Case Report

© 2009 The Authors. doi: 10.2340/00015555-0599 Journal Compilation

Successful treatment of syringotropic CD8+ mycosis fungoides accompanied by hypohidrosis with vorinostat and retinoids.

We describe a 34‐year‐old Japanese man with syringotropic CD8+ mycosis fungoides (MF) accompanied by hypohidrosis who was treated with vorinostat and retinoids. Interestingly, immunohistochemical staining for dermcidin revealed a decrease of sweat in the eccrine glands, and a sweat test by the iodine starch method proved hypohidrosis in the MF‐affected areas. Six months after treatment with this combination therapy, the patients advanced MF was under control.

Successful Treatment of HER-2-Positive Metastatic Apocrine Carcinoma of the Skin with Lapatinib and Capecitabine

© 2012 The Authors. doi: 10.2340/00015555-1354 Journal Compilation

Successful Treatment of Adult-Onset Erythromelalgia with Steroid Pulse and Pregabalin

Adult-onset erythromelalgia (EM) is a rare disease characterized by episodic bouts of burning pain and erythema for which the optimal therapy is unclear. In this report, we describe a 68-year-old Japanese woman with adult-onset EM. Intravenous administration of methylprednisolone sodium succinate 1,000 mg/day dramatically improved her pain as evaluated by the visual analog scale. Although the patient’s pain gradually developed again, it could be controlled with pregabalin. Our present case might suggest a possible, optimal therapy for adult-onset EM.

Mitochonic Acid 5 (MA-5) Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases

Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015). MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model “Mitomouse” (JASN, 2016). To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96%) were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial.

Interferon‐α is effective for CD4+, CCR4– mycosis fungoides

Mycosis fungoides (MF), a cutaneous T‐cell lymphoma, is usually characterized by cell features of T‐helper‐2 (Th2) lymphocytes. MF has recently been reported to show increased CCR4 expression, a chemokine receptor specifically expressed in Th2. Previously, we have reported the effectiveness of interferon‐γ (IFN‐γ) for the treatment of CCR4+ MF. In this report, we describe two cases of CD4+, CCR4– MF successfully treated with IFN‐α, but not IFN‐γ. Although MF usually displays a Th2 profile, the tumor cells in our two cases did not express CCR4. Our cases suggest the effectiveness of IFN‐α, but not IFN‐γ, for CCR4– MF.

Successful Treatment of Segmental Vitiligo in Children with the Combination of 1-mm Minigrafts and Phototherapy

Background: Minigrafts using a 1-mm biopsy punch (1-mm minigrafts) are being increasingly used to treat vitiligo. However, there have been few reports of the use of 1-mm minigrafts in pediatric patients. Objective: To examine the effectiveness of combination therapy with 1-mm minigrafts and phototherapy in children with segmental vitiligo. Methods: Minigrafts were placed in 13 patients aged ≤16 years with segmental vitiligo. Following surgery, 11 patients underwent irradiation with excimer laser light and 2 with narrow-band ultraviolet B light. Results: A mean repigmentation of 81.6% was obtained. A particularly high mean repigmentation of 87.9% was seen in patients aged ≤12 years, indicating greater efficacy in these patients than in patients aged ≥13 years (mean, 67.5%). Although a transient cobblestone appearance occurred as an adverse effect, it improved over time. Conclusions: Combined treatment of segmental vitiligo with 1-mm minigrafts and phototherapy can be performed safely and is highly effective in young patients.

Successful Treatment of CD30+Lymphomatoid Papulosis using a 308-nm Excimer Light

We describe a 61-year-old Japanese patient with Lymphomatoid papulosis (LYP) successfully archived complete remission, using a 308-nm Excimer light. Interestingly, immunohistochemical staining revealed that CD30+ anaplastic tumor cells were surrounded by CD163+ macrophages and CCL18 producing cells, both of which were reported to correlate with the prognosis of CTCL. Our present study sheds light on the possible pathogenesis of LYP and the possibility of a 308-nm Excimer light phototherapy for LYP.