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Background/Purpose Although measuring transepidermal water loss (TEWL) is important to assess the barrier function of the stratum corneum (SC), the commercially available instruments are rather expensive. Recently launched Model H4500 employs a closed-chamber system to measure TEWL and is more reasonably priced compared to devices currently in general use. Methods To check the reproducibility of the obtained data with H4500, we conducted measurements on the volar forearms of healthy volunteers and compared these data with those measured with Vapometer® and Tewameter®. Then, we checked the correlations between the TEWL data obtained with these different devices on the same volar forearms of 15 healthy volunteers before and after the artificial production of barrier damage of the SC by tape stripping or by 0.5% aqueous solution of sodium lauryl sulfate. Results The obtained intra-class correlation coefficient (ICC, [1, 1]) with 95% CI of H4500 was 0.927 (0.835-0.978). Namely, an excellent correlation could be found in the values of TEWL measured with these three different instruments not only on healthy skin but also on the artificially barrier-damaged skin. Conclusions H4500 is considered to be practical for daily use because of its performance as well as its reasonable price as compared with conventional devices.

Background and Objectives With the increasing elderly population in Japan, skin problems have become a greater concern. A heparinoid-containing moisturiser is frequently used in Japan, but there is a lack of evidence for its efficacy in treating senile xerosis. To determine whether there is a correlation between age and the hydration state of the stratum corneum (SC) assessed by skin capacitance, and to evaluate the efficiency of a heparinoid-containing moisturiser and a bed bath to treat senile xerosis. Methods We recruited 73 individuals to assess the hydration state of the SC on their flexor forearm by measuring their skin capacitance. To evaluate the efficacy of a heparinoid-containing moisturiser on senile xerosis, we recruited seven inpatients with an inactive daily life (IDL) who had senile xerosis. They were treated with the moisturiser in addition to a bed bath in two different protocols, and we measured the skin capacitance on their flexor forearms on days 0, 7 and 14. Results There was a weak negative correlation (−0.3854, P

Cellular schwannoma (CS) is a variety of schwannoma with a predominantly cellular growth, normally developing in middle-aged patients. In this report, we describe a 15-month-old infant with primary cutaneous CS on the knee. Because of its histologically malignant features, CS is sometimes overdiagnosed as a malignant nerve tumor. Therefore, awareness of this variant of schwannoma is important for dermatologists to avoid needless treatments for patients with CS.

Background/purpose This multicenter study assessed the impact of two types of extreme seasons (i.e. summer and winter) on the facial skin of female subjects living in different regions of Asia. Methods Facial skin of female subjects of various Asian ethnicities was characterized during summer and winter using dermatological assessments of the cheek and instrumental evaluations of the forehead and cheek. Approximately, 100 female subjects each from five cities in Asia (Harbin and Shanghai in China; New Delhi, India; Seoul, South Korea; and Sendai, Japan) ranging in age from 14 to 75 years were included in this study. Results Dermatologist assessments revealed a general decrease in severity of roughness, wrinkles, pigmentation, and lentigines during winter compared with summer. Instrumental assessments revealed significant differences in various parameters in winter vs. summer such as reductions in melanin index and skin surface hydration, and increases in transepidermal water loss, skin pH, redness, and sebum production. Conclusion Facial skin in female subjects living in different Asian cities exhibited a wide range of changes and worsening of various biophysical parameters in response to the low temperature and humidity during the winter season as compared with summer.

Background Atopic dermatitis (AD) shows dry skin. Water-soluble, low molecular weight components, collectively known as natural moisturizing factor (NMF), play an important role in maintaining the stratum corneum (SC) hydration. Previous studies focused on reduced levels of free amino acids (FAAs) in NMF from AD skin. It remains unknown, however, whether other NMF components are also altered in AD. Objective To characterize the levels of various NMF components in the SC of healthy subjects and in mild AD adult patients. Methods NMF components were extracted from three sequential tape-stripped SC samples obtained from the volar forearm. NMF components which were decreased in AD skin were topically applied to examine their contribution to SC moisturization in AD skin. Results We found that although FAAs levels were not remarkably reduced, levels of pyrrolidone carboxylic acid (PCA), lactate, urea, sodium and potassium were significantly decreased in NMF from mild AD skin. Among those components, only the topical application of potassium lactate effectively increased skin surface hydration indicating that reductions of lactate and potassium influence dry skin in mild AD patients. Unlike the distribution of filaggrin-derived FAAs and PCA, lactate, urea, potassium and sodium were abundant in the surface layer of the SC compared with the inner layer of the SC. Such findings strongly suggest that those components are supplied from outside the SC, i.e. they originate from sweat. Conclusion The reduced levels of sweat-derived NMF components in mild AD patients suggests that impaired sweat function might in part result in the SC dryness.

Cutaneous botryomycosis is a chronic focal infection characterized by a granulomatous inflammatory response to bacterial pathogens such as Staphylococcus aureus. Treatment requires antibiotic therapy and may also require surgical debridement. We employed topical heat therapy and oral minocycline. The lesions became flattened and pigmented after 1 month. We consider that this simple treatment can be an effective and harmless complementary therapy for cutaneous botryomycosis.

Reduced collagen matrix in the dermis constitutes one of the characteristic features of chronologically aged skin, which is further enhanced on the sun-exposed portions of the body by chronic ultraviolet light (UV) irradiation, inducing the unique changes associated with skin photoageing. The zinc salt of l-pyrrolidone carboxylate (Zinc PCA) has long been used as a cosmetic ingredient, because of its astringent and anti-microbial properties. In the present study, by employing cultured normal human dermal fibroblasts, we found that Zinc PCA suppressed UVA-induced activation of activator protein-1 (AP-1) and reduced matrix metalloproteinase-1 production in these cells, which is thought to be involved in collagen degradation in photoaged skin. Moreover, Zinc PCA treatment of the cells increased the expression of an ascorbic acid transporter mRNA, SVCT2, but not SVCT1, resulting in the enhanced production of type I collagen. Based on these in vitro findings, we consider Zinc PCA to be a promising candidate for an anti-skin ageing agent.

Malignant fibrous histiocytoma (MFH) is the most common fibroblastic tumor, but its cutaneous metastasis, especially in-transit metastasis, is extremely rare. We describe the case of a 30-year-old Japanese man with a recurrent MFH on the scalp accompanied by in-transit metastasis, which had been treated as a benign skin tumor 8 years before. The main bulk of the recurrent tumor was located in the dermis, but the metastatic tumor was mainly located in the subcutis. Generally, atypical fibroxanthoma, also known as cutaneous MFH, is rarely metastasized and presents a benign clinical course. Since there is a great difference between the prognosis of MFH and atypical fibroxanthoma, precise diagnosis of the primary tumor is essential., Article, Case reports in dermatology.3:164-169(2011)

The Japanese Dermatological Association established an advisory committee in 1995 to develop a severity scoring system for atopic dermatitis (AD). Its interim and concluding reports were published in Japanese in the Japanese Journal of Dermatology (108: 1491–1496, 1998 and 111: 2023–2033, 2001). Because of the strong demand for an English version, we have decided to publish the reports in English. This manuscript is the English version of the concluding report. The interim report suggested that eruption components such as erythema, papule, erosion, crust, excoriation and lichenification with extent of involved areas in five body regions, including the head and neck, anterior and posterior trunks, and upper and lower limbs, were important items for assessing AD severity. Additionally, it was recommended that streamlining of eruption components was mandatory for improving the statistical validity and reliability. The committee members subsequently concentrated their efforts on this task, and finally proposed an Atopic Dermatitis Severity Classification Criteria of the Japanese Dermatological Association.

The Japanese Dermatological Association established an advisory committee in 1995 to set up severity scoring systems for atopic dermatitis (AD). Its interim report was published in Japanese in the Japanese Journal of Dermatology (108: 1491-1496, 1998) by Chairman Hikotaro Yoshida. Because of the strong demand for an English version, we have decided to publish the report in English. This prospective study was designed to evaluate the status of 259 AD patients using Method 1, which involves a simple global evaluation of disease severity; Method 2, which involves global evaluation by summing severity scores obtained from five body regions (i.e. the head and neck, anterior and posterior trunks, and upper and lower limbs); Method 3, which consists of both assessment of the extent of involved areas at each of the five body regions and that of the severity scores of each eruption component observed in the most severely affected body region; and Method 4, which consists of the evaluation of only subjective components (daytime pruritus and sleep disturbance). Employing the results obtained with Method 1 as a tentative benchmark, we analyzed its correlation with those of Methods 2, 3 and 4 to statistically assess the validity and reliability of these methods. Method 2, Method 3 and the portion of Method 4 involving evaluation of only the subjective symptom of daytime pruritus but not the sleep disturbance were considered useful in evaluating AD severity.

Background: Contact hypersensitivity quantitative risk assessment (QRA) for fragrance ingredients is being used to establish new international standards for all fragrance ingredients that are potential skin sensitizers. Objective: The objective was to evaluate the retrospective clinical data on three fragrance ingredients in order to provide a practical assessment of the predictive value of the QRA approach. It is important to have data to assess that the methodology provides a robust approach for primary prevention of contact sensitization induction for fragrance ingredients identified as potential sensitizers. Methods: This article reviews clinical data for three fragrance ingredients cinnamic aldehyde, citral, and isoeugenol to assess the utility of the QRA approach for fragrance ingredients. Results: This assessment suggests that had the QRA approach been available at the time standards were established for these fragrance ingredients, the clinical response might have been noticeably improved. Prospectively, with the establishment of QRA-derived standards, there should be a continued downward trend in patch test-positive rates for cinnamic aldehyde, citral, and isoeugenol over time. Conclusion: While it is recognized that the availability of retrospective data is limited, a longitudinal review of these data gives confidence that the QRA approach should be an effective tool for primary prevention. This study also highlights the importance of continued active monitoring of clinical patch-test data for fragrance ingredients. (Less)

University of Missouri (Kansas City), c/o American Dermatology Associates, LLC, 6333 Long Avenue, Third Floor, Shawnee, KS 66216, USA Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Avenue, New York, NY 10032, USA Malmo University Hospital, Department of Occupational and Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden Roskilde University, Isafjordvej 66, Roskilde, DK 4000, Denmark e Technical University of Munich, Institute for Toxicology and Environmental Hygiene, Hohenbachernstrasse 15-17, Freising-Weihenstephan D-85354, Germany Oregon Health Sciences University, Department of Dermatology, Mail Code CH16D, 3303 SW Bond Avenue, Portland, Oregon 97239-4501, USA Boston University School of Medicine, Department of Pathology and Laboratory Medicine, 715 Albany Street, L-804, Boston, MA 02118-2526, USA Hospital Cantonal Universitaire, Clinique et Policlinique de Dermatologie, 24, Rue Micheli-du-Crest, Geneve 14 1211, Switzerland Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA 3-27-1 Kaigamori, Aoba-ku, Sendai 981-0942, Japan

Toll-like receptors (TLRs) on keratinocytes are important cell surface receptors involved in the innate and acquired immune response to invading microorganisms. In acne vulgaris, TLR2 activation by Propionibacterium acnes (P. acnes) may induce skin inflammation via induction of various proinflammatory molecules that stimulate the invasion of inflammatory cells. Although corticosteroids themselves exert immunosuppressive or anti-inflammatory effects, it is well known clinically that systemic or topical glucocorticoid treatment provokes an acneiform reaction. Nevertheless, the effect of steroids on TLR2 expression in human keratinocytes remains unknown. Here, we found that the addition of glucocorticoids, such as dexamethasone and cortisol, to cultured human keratinocytes increased their TLR2 gene expression. Moreover, these glucocorticoids markedly enhanced TLR2 gene expression, which was further stimulated by P. acnes, tumor necrosis factor-alpha, and IL-1alpha. Gene expression of mitogen-activated protein kinase (MAPK) phosphatase-1 was also increased by the addition of dexamethasone. By using several inhibitors and activators, we found that TLR2 gene induction by glucocorticoids was mediated by the suppression of p38 MAPK activity following induction of MAPK phosphatase-1. These findings strongly suggest that steroid-induced TLR2 together with P. acnes existing as normal resident flora plays an important role in the exacerbation of acne vulgaris as well as in possible induction of corticosteroid-induced acne or in that of rosacea-like dermatitis.

Topical tretinoin formulation is still unavailable in Japan. Because topical retinol, which is less potent but may cause less irritation, is available here, we have performed a randomized, blinded, vehicle-controlled study on the face using a once-nightly regimen for the treatment of mild photoaging in middle-aged Japanese females. First, a 26-week study was conducted in 57 subjects with a 0.075% retinol cream and its vehicle on each half side of the face. Three of the 57 subjects withdrew from the study due to irritation, although this rate was much smaller than that noted in our previous study with topical tretinoin. After 26 weeks, the rates of photoaging improvement were significantly higher on the retinol side: 27 out of 54 (50%) versus 13 (24%) for the fine wrinkling and 15 out of 54 (28%) versus 1 (2%) for deep wrinkling. A similar trial with a 0.04% retinol cream for 13 weeks revealed less prominent improvements in fine wrinkling but minimal irritation. From these data, we think that retinol creams, especially 0.04% cream, are suitable for daily use in the general population because of the low irritancy, even for those with sensitive skin.

An evaluation and review of a structurally related group of fragrance materials. (C) 2008 Published by Elsevier Ltd.

University of Missouri (Kansas City), c/o American Dermatology Associates, LLC, 6333 Long Avenue, Third Floor, Shawnee, KS 66216, USA Columbia University Medical Center, Department of Dermatology, 161 Fort Washington Avenue, New York, NY 10032, USA Malmo University Hospital, Department of Occupational and Environmental Dermatology, Sodra Forstadsgatan 101, Entrance 47, Malmo SE-20502, Sweden d Institute for Miliovurdering, Environmental Assessment Institute, Linnesgade 18, 1st Floor, Copenhagen 1361K, Denmark e Technical University of Munich, Institute for Toxicology and Environmental Hygiene, Hohenbachernstrasse 15-17, Freising-Weihenstephan D-85354, Germany Oregon Health Sciences University, Department of Dermatology L468, 3181 SW Sam Jackson Park Road, Portland, OR 97201-3098, USA Boston University School of Medicine, Department of Pathology and Laboratory Medicine, 715 Albany Street, L-804, Boston, MA 02118-2526, USA Hospital Cantonal Universitaire, Clinique et Policlinique de Dermatologie, 24, Rue Micheli-du-Crest, Geneve 14 1211, Switzerland Department of Pharmacology, University of Arizona, College of Medicine, 1501 North Campbell Avenue, P.O. Box 245050, Tucson, AZ 85724-5050, USA 3-27-1 Kaigamori, Aoba-ku, Sendai 981-0942, Japan

Skin undergoes self-renewal throughout life. Terminally differentiated keratinocytes, namely the corneocytes, are continually shed from the surface of the skin, whereas immature cells produce progeny that proceed through the differentiation process. Notch signaling controls a number of cellular processes including cell fate decision, proliferation, differentiation and survival/apoptosis. Hence, Notch and its ligands are expressed in multiple tissues including the skin, where they are abundantly expressed in the epidermis. Notch activation results in the promotion of growth arrest and the onset of differentiation, therefore suggesting that specific Notch activation may regulate skin homeostasis by balancing these processes, i.e. Notch signaling functions as a molecular switch that controls the transition of cells between skin layers during the epidermal differentiation process. Recent advances in the study of Notch signaling have confirmed that there is cross-talk between the Notch signaling pathway and a variety of other signaling molecules including Sonic hedgehog (Shh), beta-catenin and the p53 family member, p63. The absence of Notch activity allows Wnt and Shh signaling to persist in a tissue where they are normally repressed. In addition, Notch counteracts the action of p63 to maintain immature cell characteristics. However, aberrant Notch signaling results in the development of psoriasis and skin cancers such as squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Future efforts to further define how Notch controls cell proliferation and differentiation may lead to the application of Notch in new therapies for various skin diseases.

Evaluation of: Sugiyama M, Arakawa H, Ozawa K et al. Early-life risk factors for occurrence of atopic dermatitis during the first year. Pediatrics 119(3), 716–723 (2007).The pathogenesis of atopic dermatitis (AD) involves the interaction between environmental aeroallergens and immune-mediated skin hypersensitivity, in which preceding skin barrier dysfunction has been speculated to facilitate the permeation of large molecular aeroallergens into the skin. The paper under evaluation presents a prospective birth cohort study that planned to search for perinatal predictors of infantile AD. Fetal cord blood analyses for cytokines have demonstrated a negative relationship between the concentration of macrophage inflammatory protein-1β and later AD development, which seems to be compatible with the reported decrease of macrophage inflammatory protein-1β production by both CD4+ and CD8+ T cells under the dominance of Th2 responses over Th1 responses. However, no reduced stratum corneum (SC) hydration has been foun...

Background/purpose: The eyelid constitutes a unique area on the face because of its soft, smooth and thin skin distinct from that of other facial portions. Its softness facilitates their easy compliance to blinking movement, which is indispensable to protect the wet surface of the eyeball. Moreover, the skin of the eyelid does not show any prominent follicular orifices or an oily appearance even in adults. Despite such uniqueness, its biophysical characteristics have remained unclear as compared with other facial skin. Methods: We conducted non-invasive instrumental measurements on the skin of the upper eyelid of 22 healthy Japanese adults in comparison with those of the adjacent facial skin, i.e. the cheek and nose. Additionally, we examined 10 adult patients with atopic dermatitis (AD) whose facial skin remained clinically free from skin lesions for at least 2 months. Results: The eyelid skin showed high transepidermal water loss like other facial skin. Its skin surface hydration state was as high as that of the adjacent skin, despite the fact that the eyelid skin revealed extremely low amounts of surface lipids unlike its neighboring skin regions. However, in contrast to small corneocytes found in other facial areas, the corneocytes of the eyelid skin displayed a significantly larger surface size, suggesting that slow turnover of its stratum corneum (SC) takes place to allow sufficient maturation of the corneocytes, enabling them to exert efficient water-binding capacity. Its pH tended to be higher than that of the adjacent skin. Its superficial blood flow was significantly higher than that of others, although skin color assessment showed lower color values for redness than those of the other facial skin sites. In clinically non-lesional skin of adult AD patients, we found increased blood circulation and a higher parameter for redness, suggesting the presence of invisible mild inflammation in the dermis even long after subsidence of visible inflammatory changes. Conclusion: Our present biophysical findings suggest that, although the eyelid skin is poor in surface lipids, its extraordinary large superficial corneocytes play an important role in maintaining sufficient hydration state of its skin surface to keep it soft and flexible, enabling its good compliance with the blinking movement.

Summary Background Repeated mechanical stresses, such as scratching and rubbing, on a lesional skin area induce a rough skin condition known as lichenification in patients with chronic eczematous dermatitis. For ethical reasons, the pathomechanisms involved are difficult to study, so an animal model is required. Objectives To study the pathomechanisms of the unique rough skin changes seen in chronic eczematous dermatitis, we established a mouse skin model by repeated tape stripping to inflict stratum corneum (SC) barrier disruption. The skin characteristics of the model were investigated biologically, histologically and pharmacologically. Methods Tape stripping was done on mouse back skin three times a week for 4 weeks. The skin changes were studied by obtaining negative replicas, haematoxylin and eosin staining, immunostaining for CD31 and BrdU, and measuring epidermal and cutaneous thickness and skin capacitance. Activities of matrix metalloproteinase (MMP)-2, 9 and urokinase-type plasminogen activator (uPA) in the skin tissues were analysed by zymography. The effects of MMP inhibitor and glycine were assessed. Results The repeated tape stripping produced crusting and desquamation at 48 h, followed 1 week later by the formation of shallow furrows, which became much deeper after 4 weeks, appearing as fine and regular wrinkles. The resultant wrinkled skin resembled lichenified skin seen in patients with chronic eczematous dermatitis. Histopathologically, we found acanthosis, hypergranulosis and hyperkeratosis even at 48 h, and the skin was 2·5 times thicker than untreated control skin at 4 weeks. We observed angiogenesis in the upper dermis at 1 and 4 weeks. Skin capacitance, a parameter of SC hydration, displayed consistently low levels throughout the experimental period. Although the dermis was also thickened, the activity of MMP-9 was sharply increased only at 24 and 48 h after tape stripping, declining thereafter to the control level. Topical applications of CGS-27023A (CGS), an MMP inhibitor, failed to suppress this tape-stripping-induced wrinkle formation. In contrast, topical applications of a barrier recovery accelerator, glycine, effectively inhibited the wrinkle formation induced by repeated tape stripping. Conclusions The induction of fine and regular wrinkles by inflicting chronic SC barrier disruption in this model involves mainly epidermal changes, which is in sharp contrast to the mainly dermal changes induced by chronic ultraviolet B irradiation.

p53 homologue, p51/p63, predominantly expressed in keratinocyte stem cells, is indispensable for the formation of epidermis. Notch1, another such gene indispensable for the process, induces growth arrest and differentiation in keratinocytes. We found that exogenous expression of DeltaNp51B (DeltaNp63alpha), one of the isoforms of p51 specifically expressed in basal keratinocytes, blocked Notch 1-dependent growth arrest and differentiation in mouse keratinocytes by inhibiting p21 expression and maintaining integrins expression. Furthermore, DeltaNp51B by itself was found to have ability to induce expression of integrin alpha6beta4, which promotes attachment of basal cells to basal membrane thereby keeping the cells in immature state. Therefore, we conclude that DeltaNp51B expression warrants integrin expression even under the influence of Notch1 and that DeltaNp51B is a long-sought factor required to maintain basal cell keratinocytes immaturity by inhibiting Notch1 activity. We will postulate a plausible model explaining the maintenance of the squamous epithelium architectures as well as offering mechanistic explanations for pathological features of skin diseases, including cancers, psoriasis along with physiological wound healings.

An evaluation and review of a structurally related group of fragrance materials. (C) 2007 Published by Elsevier Ltd.

The treatment of chronic intractable ulcers constitutes crucial topics in dermatological practice. We describe here nine cases of different types of therapy-resistant ulcers that were successfully treated with the employment of spraying with basic fibroblast growth factor once daily. When it was initiated, we could easily find in all the cases that the healing process of the ulcers was greatly accelerated by this therapy with the resultant achievement of complete epithelialization in a relatively short time. This therapeutic modality is useful not only for chronic ulcers but also for acute extensive ulcers.

An evaluation and review of a structurally related group of fragrance materials.

We report a 65-year-old Japanese woman who presented with a nodule on the nose near the left eye. Histological examination of the totally resected lesion revealed the typical features of necrobiotic xanthogranuloma (NXG). However, her laboratory investigation revealed no paraproteinemia. We believe that the present case represents a cutaneous variant of NXG without accompaniment of paraproteinemia or any systemic involvement.

Fatty acids are shown to be important in various skin functions. Fatty acid binding protein (FABP) is postulated to serve as a lipid shuttle, solubilizing hydrophobic fatty acids and delivering them to the appropriate metabolic system. Among the FABP family proteins, epidermal-type FABP (E-FABP) is solely expressed in keratinocyte but its specific role in skin is not yet fully established. We found an elevated expression of E-FABP in regenerative keratinocytes of healing wounds. However, E-FABP null mice showed no marked differences compared to wild type mice in the process of wound closure, in vivo. On the other hand, in keratinocyte culture, E-FABP gene disruption decreased the cell motility, but did not affect the cell proliferation. E-FABP deletion may be compensated for in vivo by the microenvironment comprised of various cells such as fibroblasts and endothelial cells around the wound. Our analyses suggest that the E-FABP elevation may be necessary for the activation of cell motility within regenerative epidermis during wound healing.

Although diabetes mellitus is known to induce many pathophysiological changes in the skin, none of the earlier studies has focused on the state of the stratum corneum (SC) in patients with diabetes. In our previous report on a diabetic mouse model, we described a decreased SC hydration state and abnormalities in the function of the sebaceous gland together with a normally retained barrier function of the SC.To examine the functional changes of the SC in patients with diabetes.The following values were measured in 49 patients with diabetes: fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c); skin surface lipid level on the forehead; and high-frequency conductance (HFC) and transepidermal water loss (TEWL) of the SC of the volar forearm and extensor surface of the lower leg. These functions of the SC were compared in two pairs of patient groups, i.e. between groups with high and low FPG, and between groups with high and low HbA1c.The HFC levels on the extensor leg and volar forearm were significantly lower in the group with high FPG (FPG110 mg dL(-1)) than in the group with low FPG (FPG110 mg dL(-1)), although TEWL values were almost the same in these two groups. The skin surface lipids on the forehead were significantly lower in the former than in the latter. The HFC did not differ significantly between the group with high HbA1c (HbA1c5.8%) and the group with low HbA1c (HbA1c5.8%), whereas the TEWL of the volar forearm was slightly lower in the former than in the latter.These new results as well as our earlier results with diabetic mice suggest that patients with diabetes mellitus tend to show a reduced hydration state of the SC together with decreased sebaceous gland activity, without any impairment of the SC barrier function.

Myxofibrosarcoma or myxoid malignant fibrous histiocytoma is one of the most common fibroblastic sarcomas in older patients. It is characterized by a tendency for predominantly subcutaneous, multinodular, diffusely infiltrative growth, which may extend to the overlying dermis and present as a cutaneous lesion. Histologically, it comprises a spectrum ranging from hypocellular low-grade myxoid to high-grade pleomorphic sarcoma. Because the dermal presentation usually appears relatively banal, accurate diagnosis is sometimes challenging. In this report, we present two cases of myxofibrosarcoma with dermal involvement.

a Department of Dermatology, College of Physicians and Surgeons of Columbia University, 161 Fort Washington Avenue, New York, NY 10032, USA b Department of Animal and Plant Sciences, The University of Sheffield, Alfred Denny Building, Western Bank, Sheffield S10 2TN, UK c Institute of Toxicology and Environmental Hygiene, Technical University of Munich, Hohenbachernstrasse 15-17, D-85354 Freising, Germany d Department of Dermatology L468, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201-3098, USA e Boston University School of Medicine, Department of Pathology and Laboratory Medicine, 715 Albany Street, Boston, MA 02118-2394, USA f Department of Dermatology, University Hospital Geneva, CH-1211 Geneva 14, Switzerland g University of Arizona, Health Sciences Center, College of Pharmacy, 1703 East Mable Street, Tucson, AZ 85721, USA h Imperial College of Science, Technology and Medicine, Division of Biomedical Sciences/Molecular Toxicology Section, Alexander Fleming Building, South Kensington, London SW7 2AZ, UK i Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku Sendai 980, Japan

This paper is a study on the development of an active haptic sensor for monitoring skin conditions. The base of the tactile sensor is an aluminum cylinder, around which a polyurethane rubber, a PVDF film, a protective surface layer of an acetate film and lace are stacked in sequence. The sensor is set on the rotation axis of a stepping motor, which is driven at a constant speed. The sensor is first pressed against an object, and then it slides over the definite position. The features on the data are extracted by calculating both the variance and the time delay of the appearance of a peak in the sensor output. Experimental results show that the present sensor system works well as a haptic sensor for monitoring skin conditions.

Background: Munro’s microabscesses are a characteristic histopathologic feature of psoriasis vulgaris; however, the pathomechanisms underlying the migration of transepidermal leukocytes (PMNs) have not been fully elucidated yet. Objective and Methods: Since the lesional scale extracts contain potent chemoattractants, such as IL-8 and C5a fragments, we studied their location in the lesions of psoriasis vulgaris and PPP with immunohistochemical techniques. Results: Localization of IL-8 was not detected in the subcorneal keratinocytes but was demonstrated only in the basal keratinocytes together with migrating PMNs. In contrast, the presence of a complement fragment, C3b, was observed on the cell membranes of subcorneal keratinocytes, suggesting that these were the sites of complement activation. Conclusion: Such distinct localization of IL-8 and complement components suggests that the intraepidermal migration of PMNs takes place first according to the concentration gradient of IL-8, and thereafter they are guided by complement components to the final destination, the subcorneal portion of the lesional skin.

BACKGROUND/AIM The measurement of transepidermal water loss (TEWL) is frequently used to evaluate the barrier function of the stratum corneum (SC) of diseased skin in vivo, as well as normal skin damaged by external injurious agents. For this purpose, most people use biophysical instruments, based on an open chamber system, measuring the water vapor pressure gradient produced above the skin surface by vapor passing through the SC barrier. Recently, we tested a new portable device (Model H4300 NIKKISO-YSI CO., LTD., Tokyo, Japan) based on a closed chamber system. Its measuring principle is based on a computed TEWL estimation, from the progressive increase in relative humidity inside a closed chamber, due to continuous water evaporation from the skin surface on which the chamber is placed. METHODS We conducted an in vivo comparative study between the new portable device and a conventional method, using the DermaLab (Cortex Technology, Hadsund, Denmark), on both healthy and diseased skin surfaces, under well-controlled, standardized, experimental conditions (21 degrees C and 50% relative humidity). RESULTS We found that the sensitivity of the new device was similar to that of the DermaLab. For example, the poor SC barrier function of normal facial skin was clearly demonstrated by significantly higher TEWL values than those of the extremities (P

Although ultraviolet B (UVB) induces apoptosis and functional perturbations in dendritic cells (DC), for example, Langerhans cells (LC), it also stimulates some LC into maturation after irradiation in vivo. To analyze its reciprocal effects on DC, we elucidated the direct effect of UVB on DC in vitro using human monocyte-derived DC (MoDC). UVB from 50 to 200 J per m2 stimulated the maturation of MoDC with (1) augmented expression of CD86 and HLA-DR, (2) enhanced production of IL-1beta, IL-6, IL-8, and TNF-alpha at both the mRNA and protein levels, and (3) enhanced allostimulatory capacity on a per-cell basis, whereas the exceeded doses induced apoptotic cell death. Western-blot analysis of MoDC after UVB demonstrated a concentration-dependent phosphorylation of p38- and c-JUN N-terminal kinase (JNK)-mitogen-activated protein kinases (MAPK), but not that of extracellular signal-regulated kinases. p38 MAPK-inhibitor, SB203580, inhibited both UVB-induced maturation and apoptosis of MoDC. Interestingly, MoDC that had undergone apoptosis exhibited an augmented expression of HLA-DR without upregulation of CD86 antigen, suggesting their tolerogenic phenotype. Thus, our study revealed a dual effect of UVB, to stimulate maturation or to induce apoptosis in MoDC, depending on the dosage, via p38 MAPK pathway.

To elucidate the biological significance of activating mutations of BRAF in human malignant tumors, we performed a mutation analysis using 43 cell lines established from tumors that had developed in several kinds of human organs. Because the same V599E point mutation was observed in three of six melanoma cell lines and no such mutations were observed in other types of cancers, we focused further on melanoma, performed mutation analyses of NRAS, KRAS, CTNNB1, and p16/p14(ARF) in these cell lines, and found one NRAS mutation and three p16/p14(ARF) mutations. We further searched for mutations of BRAF and NRAS in 35 primary sporadic melanomas from 35 Japanese patients and detected the V599E BRAF point mutation in only nine (26%) of them. Significant differences in mutation frequency were observed among four histological subtypes; four (50%) of eight superficially spreading melanoma and five (33%) of 15 acral lentiginous melanoma had the mutation, whereas none of 12 other types (six nodular melanoma, five lentigo melanoma, and one mucosal melanoma) had it. The BRAF mutation was observed frequently even in small lesions, indicating that activation of this gene may be one of the early events in the pathogenesis of some melanomas.

We report a case of a late-developing cutaneous mass on the chest wall that proved to be non-specific mixed cell granuloma adjacent to the lead-electrode parts of a permanent cardiac-pacemaker that had been implanted in the left chest of an 81-year-old man 6 years previously. The lesion was treated by cardiac surgeons, whose management consisted of cutting only the intradermal part of the lead-electrodes followed by tissue curettage, leaving the other portion embedded in the subendocardium because its removal could cause serious complications. Dermatologists should be alert to such late complications of embedded permanent pacemakers. Their removal requires close cooperation with cardiac surgeons to avoid unexpected complications.

Embryonic cells are expected to possess high growth/differentiation potential, required for organ morphogenesis and expansion during development. However, little is known about the intrinsic properties of embryonic epithelial cells due to difficulties in their isolation and cultivation. We report here that pure keratinocyte populations from E15.5 mouse embryos commit irreversibly to differentiation much earlier than newborn cells. Notch signaling, which promotes keratinocyte differentiation, is upregulated in embryonic keratinocyte and epidermis, and elevated caspase 3 expression, which we identify as a transcriptional Notch1 target, accounts in part for the high commitment of embryonic keratinocytes to terminal differentiation. In vivo, lack of caspase 3 results in increased proliferation and decreased differentiation of interfollicular embryonic keratinocytes, together with decreased activation of PKC-δ, a caspase 3 substrate which functions as a positive regulator of keratinocyte differentiation. Thus, a Notch1-caspase 3 regulatory mechanism underlies the intrinsically high commitment of embryonic keratinocytes to terminal differentiation.

Leukemic dendritic cells (DC) were induced from the peripheral blood (PB) or bone marrow (BM) of leukemia patients by culture with (i) GM-CSF + IL-3 (neutral condition); (ii) GM-CSF + IL-3 + IL-12 + IFN-gamma (type 1-condition); or (iii) GM-CSF + IL-3 + IL-4 (type 2-condition). Although leukemic cells rapidly differentiated into adhesive leukemic DC in all culture conditions, type1-conditions were the most suitable for inducing leukemic DC expressing high levels of HLA and costimulatory molecules. Addition of IL-2 after 2 days of culture induced a preferential growth of minor T cell populations interacting with leukemic DC. In particular, IFN-gamma-producing CD4+ Th1 cells were efficiently expanded in type 1 culture conditions but nor in neutral or type 2-conditions. However, CD4+ T cells expanded in neutral conditions showed Th1-like functions if they were pulsed with IFN-gamma for 2 days before harvest. Such Th1 cells produced IFN-gamma and exhibited cytotoxicity in response to autologous leukemia cells. We further demonstrated that IFN-gamma production of leukemia-specific Th1 cells was blocked by anti-HLA-DR mAb. Thus, we established a novel culture system for inducing leukemia-specific Th1 cells.

We describe an 88-year-old Japanese patient with pilotropic T cell lymphoma involving the peripheral blood as well as lymph nodes. This patient presented with multiple red follicular papules, confluent, infiltrated erythematous plaques and nodules. Moreover, he was conspicuous for the presence of total alopecia of the scalp and eyebrows. Histopathologically, the lesional skin showed dense follicular and perifollicular infiltrates of atypical lymphocytes. The flow cytometry disclosed the presence of weakly CD4+ CCR4+ cell populations that would not be detected in the peripheral blood from healthy controls. The patient responded well to topical PUVA and systemic etretinate (retinoid-PUVA) and intravenous IFN-γ. Parallel with the decrease in atypical cells in the peripheral blood, the percentage of weakly CD4+ CCR4+ T cells declined. However, about 1 week after we discontinued this treatment because of the side effects, the lymph node swelling became prominent, and, 4 weeks later, the patient died before restarting any specific chemotherapy.

Acute cutaneous barrier disruption of the skin elicits various homeostatic repair responses in the epidermis. Although several candidates for the signaling mechanisms that induce these responses have been reported, e.g. the calcium and ion concentration, peroxisome proliferator-activated receptor-a, and TNF-a signaling mediated by sphingomyelinases, the exact nature of the signals remains undetermined. Therefore, assuming that an important group of serine/threonine-signaling kinases, mitogen-activated protein kinases (MAPKs), such as p44/42 MAPK, p38 MAPK, and SAPK/JNK, might link the barrier disruption to the subsequent homeostatic responses, the activation of three MAPKs in hairless guinea pig or in human skin after barrier disruption was investigated. The epidermal barrier was insulted with tape stripping or organic solvents, and the activation of these MAPKs was examined with immunohistochemistry, Western blotting, and immune complex kinase assay. In the skin of hairless guinea pigs, p44/42 MAPK and p38 MAPK, but not SAPK/JNK, were activated in epidermal keratinocytes immediately after tape stripping, and continued to be activated for at least 180 min. The activation of p44/42 MAPK was well correlated with an increase in transepidermal water loss, which was positively correlated with the number of tape strippings, whereas the covering of the stripped skin with occlusive dressing or with Ca 2+ + K + +sucrose solution suppressed its activation. The activation of p44/42 MAPK was also induced by treatment of the skin with organic solvents. In a similar fashion, p44/42 and p38 MAPKs were found to be activated in human skin after tape stripping. These results strongly suggest that the activation of p44/42 and p38 MAPKs links the stimuli of barrier disruption to the subsequent homeostatic responses to repair the barrier defect.

Factor XIIIa-positive dendrocytes are abundant within the dermis and have been implicated in the pathogenesis of various disorders, including AIDS-related Kaposi's sarcoma. Purified cultures of factor XIIIa-positive normal dermal dendrocytes have not as yet been achieved. 12E2 is a cloned cell line derived from superficial murine dermis where factor XIIIa-positive dendrocytes are abundant. Subconfluent cultures of 12E2 demonstrate polydendritic cell contours with thin, elongated membranous projections. These cells express Factor XIIIa and VCAM-1 by immunohistochemistry and by Western blot analysis of 12E2 cell lysates. 12E2 cells also constitutively express the Langerhans-cell-related epitope DEC-205, detected by NLDC-145 antibody and the CD80 co-stimulatory molecule, as well as Ia antigen on exposure to interferon-γ. Cells so treated exhibit significant ability to present alloantigens in vitro . 12E2 cells are shown to express mRNA for numerous cytokines, including interleukin (IL)-1α, IL-1β, IL-5, IL-6, IL-7, tumor necrosis factor-α and granulocyte macrophage-colony stimulating factor, by reverse-transcriptase polymerase chain reaction followed by Southern blot hybridization. Microinjection of 12E2 cells, but not 3T3control fibroblasts, into footpads of syngeneic and SCID mice results in lesions that mimic the histology and immunohistochemistry of human Kaposi's sarcoma. In aggregate, these data indicate that 12E2 cells 1) share lineage characteristics with factor XIIIa-positive dermal dendrocytes, 2) produce mRNA for numerous cytokines and are cytokine responsive to interferon-γ, and 3) behave in vivo in a manner that resembles Kaposi's sarcoma, a condition known to involve proliferation of human dermal dendrocytes.