Seiji Kawana

Wound healing involves induction of cyclooxygenase-2 expression in rat skin.

Cyclooxygenase (COX), an enzyme essential for prostaglandin biosynthesis, has two isoforms, COX-1 and -2. We investigated temporal and spatial changes in localization of these two COX proteins and mRNAs after excisional injury in rat skin. We also quantified the expression of these proteins and studied the effects of a specific COX-2 inhibitor on healing. Immunohistochemistry and in situ hybridization respectively indicated that the COX-2 protein and mRNA were expressed mainly within the basal layer of the epidermis, peripheral cells in the outer root sheath of hair follicles, and fibroblast-like cells and capillaries near epidermal wound edges. Much less intense expression was observed in normal skin than in injured skin. Western analysis demonstrated marked induction of COX-2 protein beginning within 12 hours and peaking 3 days after injury. In contrast, localization of COX-1 protein and mRNA, as well as the amount of protein expression, showed no significant change during wound healing. Administration of the COX-2 inhibitor delayed re-epithelialization in the early phase of wound healing and also inhibited angiogenesis. Thus, COX-2 induction may be important in cutaneous wound healing.

In situ expression of corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin

Systemic stresses induce corticotropin‐releasing hormone (CRH) expression in hypothalamus. CRH is released to the pituitary gland, where it stimulates proopiomelanocortin (POMC) production acting via the CRH receptor (CRH‐R). CRH and POMC peptides are also detected in sites outside of the central nervous system (CNS), such as the skin. However, it has not been elucidated whether these peptides detected in the skin are derived from CNS or are produced locally. Using immunohistochemical and in situ reverse‐transcription (RT)‐PCR techniques, we demonstrated coexpression of CRH and POMC mRNAs in the epidermis and pilosebaceous units of the human skin. This coexpression was confirmed by the combination of laser‐capture microdissection (LCM) with RT‐PCR, analyzing mRNA expressions in captured sebaceous cells. Immunoreactivities and expressions of CRH and POMC mRNAs were strong in inflammatory lesions, melanocytic nevus, seborrheic keratosis, and also in the periphery of the benign tumor. These findings suggest that CRH and POMC peptides are produced locally in the skin and are regulated by inflammatory cells as well as by autocrine mechanisms. The skin may have “a local stress response system,” whose activity is mediated by CRH and POMC peptides, in an equivalent to hypothalamus‐pituitary adrenal axis.

Differences of skin irritation between Japanese and European women.

Background  After using cosmetics, Japanese women frequently complain about sensitive, stinging skin. We wondered whether Japanese womens skin is more sensitive than that of Caucasians.

Mast Cells in Basal Cell Carcinoma Express VEGF, IL-8 and RANTES

Background: Basal cell carcinoma (BCC) is the most common malignant tumor of the skin. Although an increase in mast cell infiltration was observed in BCC lesions, definite evidence of an active role of mast cells in the pathogenesis of BCC is still lacking. BCC is accompanied by cellular infiltrates. Moreover, the stroma in the BCC lesions is characterized by an increased number of mast cells and increased vascularity. The aim of this study was to elucidate the probable role of mast cells in BCC, especially focusing on the relationship between mast cells and lymphocytic infiltration as well as angiogenesis. Methods: We examined the expression and distribution of VEGF, IL-8 and RANTES in 16 nodular BCC lesions by immunohistochemistry. We also examined the lymphocyte subset, and the correlation between VEGF expression and microvessel density in the BCC lesion. mRNA expression of IL-8 and RANTES was examined by the reverse transcriptase-polymerase chain reaction. Results: T cells, especially CD4+/CD45RO+ memory T cells were the predominant infiltrating lymphocyte population in BCC lesions. An increased number of tryptase+ cells (mast cells) was found in the stroma. VEGF+/IL-8+/RANTES+ cells were also found abundantly in the stroma of all BCC lesions. The number of VEGF+, IL-8+ and RANTES+ cells was significantly higher than that in controls. By immunohistochemistry of serial sections, tryptase+ cells were found to express VEGF, IL-8 or RANTES. Messenger RNA expression of IL-8 and RANTES was also observed in the BCC lesions. Conclusion: This study suggests that mast cells may play an active role in the angiogenesis of BCC through the production of VEGF and IL-8. Furthermore, mast cells may also regulate lymphocytic infiltration through the production of IL-8 and RANTES.

Down-regulation of Toll-like receptor expression in monocyte-derived Langerhans cell-like cells: implications of low-responsiveness to bacterial components in the epidermal Langerhans cells.

In the skin, there are unique dendritic cells called Langerhans cells, however, it remains unclear why this particular type of dendritic cell resides in the epidermis. Langerhans cell-like dendritic cells (LCs) can be generated from CD14(+) monocytes in the presence of GM-CSF, IL-4, and TGF-beta1. We compared LCs with monocyte-derived dendritic cells (DCs) generated from CD14(+) monocytes in the presence of GM-CSF and IL-4 and examined the effect of exposure to two distinct bacterial stimuli via Toll-like receptors (TLRs), such as peptidoglycan (PGN) and lipopolysaccharide (LPS) on LCs and DCs. Although stimulation with both ligands induced a marked up-regulation of CD83 expression on DCs, PGN but not LPS elicited up-regulation of expression CD83 on LCs. Consistent with these results, TLR2 and TLR4 were expressed on DCs, whereas only TLR2 was weakly detected on LCs. These findings suggest the actual feature of epidermal Langerhans cells with low-responsiveness to skin commensals.

Sebaceous carcinoma: an immunohistochemical reappraisal.

The rates of distant metastases and tumor death in sebaceous carcinoma (SC) have been reported to be higher than those of other cutaneous carcinomas, such as squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), regardless of whether they occur in ocular or extraocular regions. Therefore, strict differentiation of SC from SCC and BCC is required. In this article, we report immunohistochemical findings of SC and compare these data to those of SCC, BCC, and sebaceoma. An immunohistochemical study was performed using 7 antibodies [anti-carcinoembryonic antigen (CEA), anti-epithelial membrane antigen (EMA), anti-CA15-3, anti-CA19-9, anti-androgen receptor (AR), anti-epithelial antigen (Ber-EP4), and anti-adipophilin (ADP)] on 35 cases of SC (16 cases in ocular and 19 cases in extraocular regions) and 10 cases of each SCC (5 cases in ocular and 5 cases in extraocular regions), BCC (5 cases in ocular and 5 cases in extraocular regions), and sebaceoma (no cases arose on the eyelids). In summary, the typical immunophenotypes of SC were EMA+, CA15-3+, AR+, Ber-EP4−, and ADP+; those of sebaceoma were CEA−, EMA+, Ber-EP4−, and ADP+; those of SCC were CEA−, EMA+, CA19-9−, AR−, Ber-EP4−, and ADP−; and those of BCC were CEA−, EMA−, CA15-3−, Ber-EP4+, and ADP−. Other antibody tests for each neoplasm were positive in about half of the cases. The detection of AR and ADP was useful for differentiating SC from SCC, whereas the determination of EMA, CA15-3, Ber-EP4, and ADP was valuable in differentiating SC from BCC.

420 nm intense continuous light therapy for acne

BACKGROUND: Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy. However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity. Describe here is a high-intensity, narrow-band, blue light (ClearLight) system, and its therapeutic clinical effect is investigated on acne using cutaneous measurements, bacterial observations and ultrastructural changes. MATERIALS AND METHODS: A total of 28 adult healthy volunteers with facial acne (mean age 28.1 years, range 16-56 years) were recruited for this study. They were treated with a total of eight serial biweekly 15-minute treatment sessions. Clinical counts of acne, as well as moisture, sebum and pH measurements were taken between each session. Nine of the 28 patients were followed for 2-3 months after the last treatment. Detection of bacteria in acne pustules was analyzed by culture and by polymerase chain reaction (PCR). Ultrastructural changes were examined in eight patients after four sessions of the light therapy. RESULTS: All patients completed the study. Overall, there was a 64.7% improvement in acne lesions. There were no bacterial changes before or after the therapy, although damaged Propionibacterium acnes were observed at the ultrastructural level. CONCLUSIONS: ClearLight performed eight times over 4 weeks can be useful in the treatment of acne. Further investigation will be needed to elucidate the mechanism of action of ClearLight.

Successful treatment of Kimura's disease with cyclosporine

We report the case of a 29-year-old Japanese woman presenting with recurring Kimuras disease. We began treatment with cyclosporine within 7 days, the nodular lesion had almost cleared. The cyclosporine dose was then gradually reduced and discontinued after 6 months. The patient was reassessed 18 months after the cessation of treatment and there was no evidence of recurrence of the disease. We speculate that the effects of cyclosporine on T helper-2 cells improves Kimuras disease.

Irritant patch testing with sodium lauryl sulphate: interrelation between concentration and exposure time

Background It is well known that the degree of skin reaction to an irritant depends on its concentration and exposure time.

Corticotropin‐releasing factor receptor type 1 is involved in the stress‐induced exacerbation of chronic contact dermatitis in rats

Abstract: Cutaneous diseases such as psoriasis and atopic dermatitis are worsened by psychic stress. We attempted to clarify the involvement of the corticotropin‐releasing factor (CRF) receptor (CRFR) in stress‐induced exacerbation of chronic contact dermatitis in rats. Male Wistar rats, in which chronic contact dermatitis had been induced by 2,4,6‐trinitro‐1‐chlorobenzene (TNCB), were exposed to a 1‐h period of electric foot‐shock following intraperitoneal administration of CRA1000, a selective CRFR type 1 (CRFR1) antagonist, or vehicle everyday for 9 days. Histological examination of the skin showed that the epidermis significantly thickened and the number of mast cells in the dermis significantly increased by repeated exposure to stress, and that these changes were blocked by CRA1000. These results suggest that CRFR1 is involved in the stress‐induced exacerbation of chronic contact dermatitis.