Library

Notes: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic and dry skin lesions with elevated serum IgE levels. AD is characterized by predominant infiltration of Th2 type cells secreting cytokines such as interleukin-4 (IL-4) and IL-5. Chemokines are chemotactic cytokines that regulate leukocyte trafficking into the inflamed tissues and are divided into four families: CC, CXC, C and CX3C. Among CC chemokines, thymus and activation regulated chemokine (TARC)/CCL17 and monocyte derived chemokine (MDC)/CCL22 attracts Th2 type T cells. This is produced by dendritic cells, endothelial cells and T cells. We have examined the expression of TARC in lesional skin. We have identified that keratinocytes (KCs) are major sources of TARC when stimulated by IFN-γ and TNF-α. We next examined the serum levels of TARC levels in AD patients [4]. Forty patients with AD, 20 healthy controls and 20 patients of psoriasis were examined. The serum TARC levels with AD patients were significantly higher than healthy controls and psoriasis patients (〈link href="#f1-15"〉Fig. 1). The average levels of the serum TARC of AD was 2338.0 ± 302.8 pg mL–1, whereas that of healthy controls was 215.3 ± 26.8 pg mL–1 and that of psoriasis was 256.3 ± 25.3 pg mL–1. We compared serum TARC levels among three different stages (mild, moderate, and severe) of AD. Serum TARC levels of severe AD patients were significantly higher than those of mild and moderate group. The average levels of TARC in the mild, moderate and severe groups were 540.8 ± 111.6 pg mL–1, 2056.2 ± 290.3 pg mL–1, and 4812 ± 491 pg mL–1, respectively. The patients with old age who suffered from AD for a long period showed severe eruptions and the serum TARC levels of these aged group showed relatively higher CCL17 levels compared with those of young patients (2182.1 ± 312.0 pg mL–1, 1103.3 ± 240.2 pg mL–1). To determine the CCL17 localization in lesional skin, immunohistochemical analysis was performed using biopsy samples. Immunoreactive TARC was detected in the epidermal KC and dermal infiltrating cells in the acute and chronic lesional skin.〈figure xml:id="f1-15"〉1〈mediaResource alt="image" href="urn:x-wiley:01425463:ICS254_15_15:ICS_254_f1-15"/〉Serum TARC levels in patients with atopic dermatitis (AD psoriasis vulgaris and healthy controls.To elucidate the source of TARC producing cells in peripheral blood mononuclear cells (PBMCs) in AD patients, we purifed CD4+ T cell, CD8+ T cell, and monocytes. Both CD4+ and CD8+ T cells expressed TARC mRNA, and the level of TARC mRNA expression was more predominant in CD4+ T cells. Monocyte did not express TARC mRNA. Monocyte derived dendritic cells (MoDCs) were produced from monocytes cultured with both IL-4 and GM-CSF for 5 days. MoDCs expressed CD11c, CD1c, CD13 and HLA-DR antigen. MoDCs expressed TARC mRNA and produced TARC protein in high levels in healthy controls. The level of TARC protein by MoDCs was more prominent in AD patients compared with healthy controls (20146.2 pg/ml vs 15654.7 pg/ml). The levels of TARC by MoDCs in different ages were examined and that was 24,281 pg/ml (10∼20 years old), 21389.7 pg/ml (20∼30 years old) and 18733.3 g/ml (30∼40 years old), respectively. MDC/CCL22 is another chemokine which attracts Th2 type T cells. We also examined the levels of MDC in the culture supernatants of MoDCs in AD patients. These were also higher in AD patients compared to healthy controls. The levels of MDC produced by MoDCs increased according to the aged people of AD patients as follows: 41,698 pg/ml (10∼20 years old), 41,987 pg/ml (20∼30 years old), 50,533 pg/ml (30∼40 years old). These results suggest that MDC, produced by MoDCs in AD patients, showed high levels in the aged people in severe AD, indicating that MDC is a good marker for the sensitive skin in AD.KCs can produce various kinds of cytokines and chemokines such as TARC and MDC. IFN-γ induced TARC and MDC production by KCs, and this is augmented by additional stimulation of TNF-α. We examined that the activity of transcription factors such as NFkB and STAT-1 in KCs in in vitro system. We showed that NFkB and STAT-1 DNA binding activity in KCs significantly increased under the stimulation of IFN-γ and TNF-α by gel shift analysis. The NFkB DNA binding activity was partially blocked by genistein and LY294002, indicating that tyrosine kinase inhibitor and PI3kinase inhibitor can regulate NFkB DNA binding activity in KCs. Interestingly, TARC production by KCs, when stimulated by IFN-γ and TNF-α, was also inhibited by additional genistein and LY294002. These data indicated that TARC production in KCs was regulated by NFkB pathways.CC chemokine receptor-4 (CCR4) is a specific ligand for TARC/CCL17 and MDC/CCL22. We examined CCR4 and CXCR3 expression on peripheral blood memory T cells and found that the percentage of CCR4 expression on memory T cells was significantly higher in AD patients compared with normal controls and psoriasis patients [5]. The positivity of CCR4 expression on CD4+ CD45RO+ T cells in AD patients was 23.4 ± 18.1%, whereas that of healthy controls and patients with psoriasis was 5.3 ± 3.5%, 6.5 ± 5.0%, individually. The positivity of CCR expression on CD8+ CD45RO+ T cells in AD patients was 7.6 ± 5.3%, whereas that of healthy controls and patients with psoriasis was 4.9 ± 1.1%, 2.9 ± 5.2%, individually (AD versus control: P 〈 0.0005).CCR4 expression in the severe group was significantly higher than that seen in the healthy controls (P 〈 0.05). An immunohistochemical study of CCR4 and CXCR3 expression was also performed. In acute and chronic lesions, CCR4 was expressed on more than 70% of CD4+ T cells which had a higher ratio compared with that of psoriasis and healthy control. Taken together, these data indicate CCL17 and CCR4 play an important role in the pathogenesis of AD and may reflect the disease severity of AD.〈section xml:id="abs1-1"〉〈title type="main"〉References1. Vestergaard, C., Yoneyama, H., Murai, M., Nakamura, K., Tamaki, K., Terashima, Y., Imai, T., Yoshie, O., Irimura, T., Mizutani, H. and Matsushima K. Overexpression of Th2-specific chemokines in NC/Nga mice exhibiting atopic dermatitis-like lesions. J. Clin. Invest. 104, 1097–105 (1999).2. Zheng, X., Nakamura, K., Tojo, M., Akiba, H., Oyama, N., Nishibu, A., Kaneko, F., Tsunemi, Y., Kakinuma, T., Saeki, H. and Tamaki, K. Ultraviolet A irradiation inhibits thymus and activation-regulated chemokine (TARC/CCL17) production by a human keratinocyte HaCaT cell line. Eur. J. Dermatol.13, 348–53 (2003).3. Zheng, X., Nakamura, K., Oyama, N., Kaneko, F., Tsunemi, Y., Saeki, H. and Tamaki, K. The mechanism of the effects of UVB irradiation on TARC/CCL17 production by a human keratinocyte HaCaT cell line (submission).4. Kakinuma, T., Nakamura, K., Wakugawa, M., Mitsui, H., Tada, Y., Saeki, H., Torii, H., Asahina, A., Onai, N., Matsushima, K. and Tamaki, K. Thymus and activation-regulated chemokine in atopic dermatitis: serum thymus and activation-regulated chemokine level is closely related with disease activity. J. Allergy Clin. Immunol.107, 535–541 (2001).5. Wakugawa, M., Nakamura, K., Kakinuma, T., Onai, N., Matsushima, K. and Tamaki K. CC chemokine receptor 4 expression on peripheral blood CD4+ T cells related disease activity of atopic dermatitis. J. Invest. Dermatol.117, 188–196 (2001).

Notes: The photolightening behavior of red hair was investigated. Red hair was found to lighten to a similar extent by irradiation from both ultraviolet (UV) and visible (VIS) light. Under the same irradiating conditions, blond hair was lightened by VIS light but did not lighten by UV light until it was washed after irradiation. These different photolightening behaviors of red and blond hair are supposed to be due to differences in their melanin compositions. The dominant type of melanin in red hair is pheomelanin; while blond hair investigated in the previous work contained both eumelanin and pheomelanin, with mainly eumelanin. Consequently, in this investigation, the photolightening behaviors of red and blond hair were compared to clarify the differences in photosensitivity between the two types of melanin. It has been proven that chemically intact melanin in red hair is considerably more photolabile to UV light than VIS light. Also, it is much more easily decomposed by UV light than melanin granules in blond hair, although they are both similarly decomposed by VIS light. This indicates that pheomelanin is far more sensitive to UV light than eumelanin, while these two types of melanin are similarly sensitive to VIS light. This leads to the following hypothetical photolightening mechanism of red hair: When UV light is irradiated on red hair, the light is absorbed by hair protein and attenuated before it reaches the melanin granules. However, since pheomelanin is highly sensitive to UV light, even the attenuated UV light decomposes the pheomelanin to some extent. As a result, UV light lightens red hair without the need for subsequent washing, in contrast to blond hair, which consists of mainly eumelanin.

Notes: Removing makeup is considered to be the first step in the skincare process. Makeup that has served its purpose is a kind of impurity that should ideally be removed completely to maximize the effects of skincare products applied afterwards. However, the use of silicone resins has significantly improved the long-lasting property of makeup with the result that makeup can hardly be removed efficiently either with surfactant-type cleansers like soaps or with oil-based cleansers like liquid crystalline cleansers. Furthermore, oil-based makeup removers do not leave the skin feeling fresh but oily, and often have been used in combination with surfactant-type cleansers. In other words, complete makeup removal and a fresh skin feel are considered to be incompatible in conventional formulation technologies. To obtain compatible systems, we investigated the applicability of a system known as the bicontinuous phase and eventually succeeded in developing a novel system for a makeup remover. This phase can be prepared with a specific composition with a complete hydrophilic-lipophilic balance in an oil/surfactant/water system by using cyclo-siloxane, which dissolves silicone resin well. The bicontinuous phase has an oil- and water-continuous microstructure, showing affinity for both aqueous and oily substances. This bicontinuous phase was applied to the development of a novel makeup remover. Determination of remover cap-ability and fresh skin feel revealed that the makeup could be completely removed and that the amount of oil remaining on skin surface after wash-off was much less than with previous oil-based removers. The results of the sensory test also supported the finding that the remover was far superior to conventional products. This makeup remover is the first example of the application of the bicontinuous phase technology to a cosmetic product and clearly seems to provide the best conditions for subsequent skin care, meaning that it is suitable for the first step in the skincare process.

Notes: It is well known that two different photobiologic processes mainly take place when the human skin is exposed to ultraviolet (UV) light. The long waves of UVA and visible light (320–400 nm) irradiation causes skin tanning by melanocytic activation and the short waves of UVB (280–320 nm) can elicit variety of biologic action in cutaneous keratinocytes, melanocytes and other skin component cells. The sensitivity to the UV lights is generally depending on the three kinds of the skin type classified by the proposal of Pathak et al. [1]. The skin sensitivity of Japanese population, however, seems to be different from that of Caucasian's population because of the differences in genetic background and skin color, as indicated by Satoh and Kawada [2]. They tried to classify into three groups as J-I (always burn and rarely tan), J-II (moderately burn and moderately tan) and J-III (never burn and always tan) by the skin types to UV lights for the sun-tanning and sun-burning. Comparing these two criteria, a general concern indicates that J-I–III may correspond to the skin type II–IV of the Fitzpatrick's classification, respectively. Based on the Japanese skin types, the incidence of skin cancers and precancerous lesions related to the long-term exposure of sun-light was epidemiologically estimated by Araki et al. [3]. According to their results for several years (1992–1998), the overall number of skin cancers and precancerous states in Japanese was demonstrated to be small in comparison with the incidence of Caucasian's population, even though the people sets in areas of higher ambient solar radiation. However, working outdoors having J-I and/or a history of severe sunburn during childhood were found to be important risk factors, particularly among people of over 60 years of age. Regarding skin cancers and sun-exposed areas, we compared between 20 patients with skin cancers (males 13 and females seven) (average 65 years old) (〈link href="#t1-14"〉Table I) and 24 controls (males 10 and females 14), who were selected as similar ages to the patients at random, in their skin types and life environments by a questionnaire system. The skin types of the patients were J-I (15%), J-II (40%), and J-III (35%) and those of controls were J-I (4.2%), J-II (62.5%), and J-III (4.2%), respectively. The patient group tended not to protect from sun exposure and most of them were farmers. UV exposure is known to induce modulation of the skin immune system which Langerhans cells decrease in number in the epidermis, and on the other hand it is supposed that interleukin IL-10 producing macrophages (CD11b+) expand in the dermis. Not only IL-10, but also tumor necrosis factor (TNF)-α from macrophages and mast cells in the dermis seem to increase and suppress Th1 immune responses of the epidermis and Th2 immune responses might be induced by UV irradiation [4]. Recently, it has been reported, however, that in patients with polymorphous light eruption (PLE), the expression of TNF-α, IL-4, and IL-10 is reduced by UVB irradiation and that PLE appearance is related to UVB-induced immunosuppression [5].〈tabular xml:id="t1-14"〉I〈title type="main"〉 Twenty patients with skin cancers (average ages: 65 years old) (Department of Dermatology, Fukushima Medical University Hospital, 2001–2002) 〈table frame="topbot"〉〈tgroup cols="2" align="left"〉〈colspec colnum="1" colname="col1"/〉〈colspec colnum="2" colname="col2"/〉〈thead valign="bottom"〉〈row rowsep="1"〉Skin cancersNumber of patients〈tbody valign="top"〉Malignant melanoma8Squamous carcinoma4Bowen's disease4Basal cell carcinomas3Eccrine porocarcinoma1Location of skin cancersSun-exposed areas9Non-exposed areas11Then, we attempted to study UVB effects on atopic disease and chronic inflamed skin diseases in the therapeutic advantage, although it is harmful for the patients to be cutaneous carcinogenesis. The epidermal keratinocytes are capable of producing CC chemokines in the local Th2 response, as seen in atopic dermatitis, mycosis fungoides, etc. [6]. Thymus and activated-related chemokine (TARC) is one of the chemokines produced by keratinocytes which selectively activate lymphocytes of Th2 subset expressing CCR4 (receptor for TARC) [7]. Accumulating evidence has suggested that these chemokines have primary pathogenic importance in Th2 skin diseases. In order to find the effects of UVB irradiation on the production of TARC, we used a human keratinocyte HaCaT cell line. As assessed by RT-PCR and ELISA, UVB irradiation significantly decreased the expression of TARC mRNA and protein in HaCaT cells stimulated with interferon-γ (IFN-γ) and TNF-α in a dose-dependent manner. The down-regulation of TARC expression may be mediated in part by activation of the particular transcription, signal transducer and activator of transcription 1 (STAT 1), since it has shown that STAT 1 DNA-binding was down-regulated by UVB irradiation. Our results suggest that STAT 1 and other transcription factors play an important biological role in immune system of human skin irradiated by UVB and may support the results of Kolgen et al. [5].In this point of view, UVB irradiation will be a therapeutic tool for skin diseases related to Th2 type reaction, such as atopic dermatitis, mycosis fungoides, etc., although we need to optimize adequately the use of UVB in patients with J-I skin type or those of whom have the episode of severe sun-burn after UVB irradiation.〈section xml:id="abs1-1"〉〈title type="main"〉References1. Pathak, M.A., Nghiem, P. and Fitzpatrick, T.B. Acute and chronic effects on the skin. In: Fitzpatrick's Dermatology in General Medicine, 5th edn (Freedberg, I.M., Eisen, A.Z., Wolf, K., Austen, K.F., Goldsmith, L.A., Katz, S.I. and Fitzpatrick, T.B. eds), pp. 1598–1607. McGraw-Hill, New York (1999).2. Satoh, Y. and Kawada, A. Action spectrum for melanin pigmentation to ultraviolet light, and Japanese skin typing. In: Brown Melanoderma: Biology and Diseases of Epidermal Pigmentation (Fitzpatrick, T.B., Wick, M.M. and Toda, K. eds), pp. 87–95. University of Tokyo Press, Tokyo (1986).3. Araki, K., Nagano, T., Ueda, M., Washio, F., Watanabe, S., Yamaguchi, N. and Ichihashi, M. Incidence of skin cancers and precancerous lesions in Japanese- Risk factors and prevention. J. Epidemiol. 9, S14–S21 (1999).4. Teunissen, M. B., Piskin, G., Nuzzo, S. et al. Ultraviolet B radiation induces a transient appearance of IL-4+ neutrophils, which support the development of Th2 responses. J Immunol. 168, 3732–3739 (2002).5. Kolgen, W., van Meurs, M., Jongsma, M. et al. Differential expression of cytokines in UVB-exposed skin of patients with polymorphous light eruption. Arch. Dermatol. 140, 295–302 (2004).6. Kakinuma, T., Sugaya, M., Nakamura, K., Kaneko, F., Wakugawa, M., Matsushima, K. and Tamaki, K. Thymus and activation-regulated chemokine (TARC/CCL17) in mycosis fungoides: serum TARC levels reflect the disease activity of mycosis fungoides. J. Am. Acad. Dermatol. 48, 23–30 (2003).7. Imai, T., Nagira, M., Tkagi, S. et al. Selective recruitment of CCR4-binding Th2 cells toward antigen-presenting cells by the CC chemokins thymus and activation-regulated chemokine and macrophage-derived chemokine. Int. Immunol. 11, 81–88 (1999).

Notes: Background  Although there have been several reports on the prevalence of atopic dermatitis (AD) in Japanese schoolchildren based on questionnaires, there has been no nation-wide study of the frequency of this condition diagnosed by dermatologists in regular health check-ups of schoolchildren.Objectives  The objective of this work was to evaluate precisely the prevalence of AD in elementary schoolchildren in Japan based on regular health check-ups by dermatologists.Methods  In 2001/2, elementary schoolchildren: first graders (age 6–7 years) and sixth graders (age 11–12 years) were examined by dermatologists in eight prefectures of Japan (Hokkaido, Iwate, Tokyo, Gifu, Osaka, Hiroshima, Kochi and Fukuoka). In each prefecture, public elementary schools were randomly selected from urban and rural districts. We planned to examine about 700 schoolchildren in each of urban first, urban sixth, rural first and rural sixth grades from the eight areas, a total of 22 400 children (700 × 4 × 8). AD was diagnosed by the dermatologists based on the Japanese Dermatological Association criteria for the disease.Results  The point prevalence of AD was 11·2% overall (2664 of 23 719) ranging from 7·4% (Iwate) to 15·0% (Fukuoka) in the eight areas. Seventy-four per cent, 24%, 1·6% and 0·3% of those afflicted were in the mild, moderate, severe and very severe groups, respectively. Overall, the prevalence of first graders was slightly higher than that of sixth graders (11·8% vs. 10·5%, P 〈 0·01). There was no apparent difference in prevalence between urban and rural districts, or between boys and girls.Conclusions  The prevalence of AD in Japanese elementary schoolchildren was about 10%, three-quarters of those being mildly affected. This is the first nation-wide study made of Japanese elementary schoolchildren examined by dermatologists to evaluate the frequency of AD.

Notes: Background : It has been reported that inhibitors of gastric acid secretion prevent bleeding after endoscopic mucosal resection for mucosal gastric neoplasm. However, uncertain whether an histamine2-receptor antagonist or proton-pump inhibitor is more effective.Aim : To evaluate prospectively the effectiveness of famotidine or omeprazole for ulcer management after endoscopic mucosal resection.Methods : From July 2003 to October 2004, 57 patients were randomly assigned to famotidine or omeprazole for the management of endoscopic mucosal resection. Both drugs were given intravenously for the first 2 days, thereafter by mouth. The bleeding rates after endoscopic mucosal resection, the effects on the healing of endoscopic mucosal resection-induced ulceration, and cost-benefits were compared.Results : Twenty-eight patients received famotidine and 29 received omeprazole. No significant difference was observed between the two groups in patient characteristics. The bleeding rates after endoscopic mucosal resection were not significantly different (18% vs. 14%) between the groups. Similarly, no differences were seen in the size of the endoscopic mucosal resection-induced ulceration at 1, 30 and 60 days after resection between groups. The total costs of anti-secretory agents demonstrated a significant cost-benefit to those treated with famotidine (10 420 yen vs. 17 782 yen).Conclusions : Famotidine is suggested as a better alternative to omeprazole for the management of endoscopic mucosal resection, as it showed a clear cost-benefit, and the healing results after endoscopic mucosal resection were similar for the two treatment strategies.

Notes: We have proposed a novel model of hydrogen etching of SiC based on thermalequilibrium and have confirmed the validity of our model through the analysis of H2 etchingexperiments. The experimental results obtained showed that the etching rate is expressed by a linearequation with the H2 flow rate, by an exponential function with the reciprocal of the temperatureand by a power law with the pressure. These results agree well with the theoretical behaviorsderived from our model