Yoko Sogabe

Basic fibroblast growth factor stimulates human keratinocyte motility by Rac activation.

Topical application of human recombinant basic fibroblast growth factor (bFGF) promotes wound healing. bFGF, however, has been reported to have little in vitro effects on keratinocyte compared with other cell types such as endothelial cells or fibroblasts. The aim of this study was to investigate the mechanism(s) of bFGF‐stimulated keratinocyte migration. Normal human keratinocytes, seeded on coverslips that were noncoated or coated with type I collagen or fibronectin, were stimulated with bFGF to evaluate their ability to spread. Keratinocyte migration was measured using a Boyden chamber assay. The lysates of keratinocytes, which were plated on noncoated, type I collagen‐coated or fibronectin‐coated plastic dishes and stimulated with bFGF, were subjected to pulldown assays to detect guanine triphosphate‐loaded Rac. Morphologically, keratinocytes formed lamellipodia only when they were stimulated with bFGF on the collagen‐coated coverslips. Keratinocyte migration was significantly enhanced by bFGF. Guanine triphosphate‐loaded Rac was detected only in the lysate of bFGF‐stimulated keratinocytes on collagen‐coated dishes. This in vitro study shows that bFGF exerts a stimulatory effect on keratinocyte migration in the presence of type I collagen as a scaffold, and, at least, Rac activation is involved.

Evidence that PI3K, Rac, Rho, and Rho kinase are involved in basic fibroblast growth factor-stimulated fibroblast–Collagen matrix contraction

Fibroblast–collagen matrix contraction has been used as a model system to study how cells organize connective tissue. Previous work showed that lysophosphatidic acid (LPA)‐stimulated floating collagen matrix contraction is independent of Rho kinase while platelet‐derived growth factor (PDGF)‐stimulated contraction is Rho kinase‐dependent. The current studies were carried out to determine the signaling mechanisms of basic fibroblast growth factor (bFGF)‐stimulated fibroblast–collagen matrix contraction. Both bFGF and LPA promoted equally collagen matrix contraction well. Three different inhibitors, LY294002 for phosphatidylinositol‐3‐kinase (PI3K), C3 exotransferase for Rho and Y27632 for Rho kinase, suppressed the bFGF‐stimulated fibroblast–collagen matrix contraction. With bFGF stimulation, fibroblasts spread with prominent stress fiber network formation and focal adhesions. In the presence of Rho kinase inhibitor, focal adhesions and stress fibers were mostly lost. We demonstrated that bFGF stimulation for fibroblast caused transient Rac and Rho activation but did not activate Cdc42. In addition, bFGF enhanced fibroblast migration in wound healing assay. The present study implicates PI3K, Rac, Rho, and Rho kinase as being involved in bFGF‐stimulated collagen matrix contraction. The elucidation of bFGF‐triggered signal transduction may be an important clue to understand the roles of bFGF in wound healing. J. Cell. Biochem. 102: 1290–1299, 2007.

Successful treatment with cyclosporin administration for persistent benign migratory glossitis

We herein describe a 54 year‐old female patient with a 5‐year history of persistent and painful benign migratory glossitis (BMG), which was remarkably improved by systemic administration of cyclosporin. She had noted some white patches leaving smooth denuded red areas with whitish elevated borders on the dorsum of her tongue, and finally felt strong pain. The lesion was refractory to the previous treatment with topical corticosteroid treatment for the last 2 years. Because clinicopathological findings were compatible with BMG, systemic administration of 20 mg/day prednisolone and topical 0.1% dexamethasone application were started, however, she suffered a severe relapse after tapering the dosage of predonisolone to 10 mg/day. Because some investigations have suggested that BMG is an oral manifestation of psoriasis, we introduced cyclosporin administration. The systemic treatment of cyclosporin microemulsion pre‐concentrate, 3 mg/kg/day, resulted in a satisfactory improvement. Two months later, we could reduce cyclosporin microemulsion pre‐concentrate dosage to 1.5 mg/kg/day for maintenance therapy, and the disease has been well controlled so far.

Clinical usefulness and patient satisfaction for treatment with low-dose cyclosporin administration in patients with moderate psoriasis vulgaris

The Japanese guidelines for psoriasis therapy with cyclosporin microemulsion preconcentrate (CyA MEPC) has been revised, and the clinical application of CyA MEPC is being expanded to include mild to moderate psoriasis. In this study, we aimed to confirm the clinical efficiency of low‐dose cyclosporin therapy in patients with moderate psoriasis vulgaris. After informed consent was obtained, 19 patients with psoriasis vulgaris were enrolled in this study. Each patient basically administrated CyA MEPC, 2.5 mg/kg/day, orally over 12 weeks. When the psoriasis area and severity index (PASI) score showed a 75% reduction from the initial value, the dosage of CyA MEPC was reduced to 1.5 mg/kg/day and added a topical application of active vitamin D3 ointment. We interviewed the patients as to their satisfaction for the usefulness and cost of the treatment. All patients obtained improvement within 12 weeks. In 10 patients whose PASI score reduced over 75%, we could reduce CyA MEPC dosage. No adverse effects were noted in any patients during the treatment. It is of note that the cost for 1.5 mg/kg/day administration of CyA MEPC was accepted by all the patients. In conclusion, this preliminary study suggests that the CyA MEPC is effective, safe and would provide patients with acceptable costs.

Harlequin Sign (Hemifacial Flushing and Contralateral Hypohidrosis) in a 4‐year‐old Girl with Horner Syndrome

News and Notices will be accepted for publication pending approval of the notice by the Publisher and the Editors. Notices should be of interest to pediatricians and dermatologists or those working in related fields. They should be limited to the pertinent information for the meeting or event. All notices will be edited by the editorial staff and edited copy will not be sent to the author for approval prior to publication. Submit 3 copies of notices at least 12 weeks prior to publication. Pediatric Dermatology is a bimonthly publication.

Daily versus intermittent application of high-concentration tacalcitol ointment in combination with low-dose cyclosporin for psoriasis vulgaris.

In this study, we aimed to compare the clinical effectiveness of highly‐concentrated tacalcitol ointment daily versus intermittent application in patients with psoriasis vulgaris who simultaneously took a low dose of cyclosporin. All the patients in both groups showed significant improvements, and the patients in the intermittent application group obtained more patient satisfaction in cost performance. The treatment cost of low‐dose cyclosporin and intermittent application of highly‐concentrated tacalcitol ointment was less than half of that of high‐dose cyclosporin and daily application of highly‐concentrated tacalcitol ointment. This preliminary study suggests that the combination therapy with low‐dose cyclosporin administration and intermittent application of highly‐concentrated tacalcitol is effective, safe and provides acceptable costs for the treatment.

Functions of the stratum corneum in systemic sclerosis as distinct from hypertrophic scar and keloid functions

Both transepidermal water loss (TEWL) and skin surface high-frequency conductance are functions of the skin barrier. Systemic sclerosis (SSc) and hypertrophic scar (HS)/keloid are characterized by abnormal fibrotic changes in the dermis. Since the close interrelationship between the epidermis and the dermis has been well established, we analyzed the stratum corneum functions of forearm skin in 39 SSc patients after assessing the degree of the skin thickening and compared those functions with 10 age-matched normal controls. We also analyzed the stratum corneum functions of HS or keloid lesions in seven patients using the same methods, and compared those functions to adjacent or contralateral normal skin in identical patients. Neither the TEWL, nor high-frequency conductance of forearm skin in SSc patients were significantly different from those in normal controls. There was no correlation between the levels of TEWL or high-frequency conductance and the degree of skin thickening in SSc. In HS or keloid conditions, high-frequency conductance was significantly elevated (42.5+/-8.9 vs. 26.4+/-5.7, P<0.001). Although TEWL was elevated, there was no statistical significance (48.6+/-39.7 vs. 25.1+/-10.1). Our results revealed that stratum corneum functions are distinct between SSc and HS or keloid. This may reflect the various natures of dermal changes, which in turn differentiate the functions of the stratum corneum in the diseases.

Clinical analysis of leg ulcers and gangrene in rheumatoid arthritis.

Leg ulcers are often complicated in patients with rheumatoid arthritis (RA), however, the etiology is multifactorial. We examined the cases of leg ulceration or gangrene in seven RA patients who were hospitalized over the past 3 years. One patient was diagnosed as having pyoderma gangrenosum. Although vasculitis was suspected in three patients, no histological evidence was obtained from the skin specimens. In these patients, angiography revealed the stenosis or occlusion of digital arteries. In the remaining three patients, leg ulcers were considered to be due to venous insufficiency. Treatment should be chosen depending on the causes of leg ulcers.

Pityriasis circinata Toyama successfully treated with high-concentration tacalcitol ointment.

To the Editor: We describe here a case of pityriasis circinata Toyama whose cutaneous lesions were remarkably improved with topical high-concentration tacalcitol. This disease is a rare dermatosis characterized by multiple, round to oval, scaly macules. The trunk and extremities are usually affected, but the scalp, face, hands, and feet are spared. Although this disease was first reported by Toyama in 1913 (1), some cases have been reported under the name of pityriasis rotunda (2). For the last 30 years, most cases have been reported from Japan and South Africa (3). The standardized treatment for the disease is emollients such as topical urea; however, only a few patients respond well to this treatment (4). Tacalcitol is a vitamin D3 analogue with an excellent safety profile that has been widely used for the treatment of ichthyosis, pityriasis rosea, and palmoplantar pustulosis as well as psoriasis vulgaris. In addition, its clinical efficacy has been reported in other dermatoses such as nevus comedonicus (5) and confluent and reticulated papillomatosis (6). A 74-year-old Japanese female had noted multiple round or oval pigmentations for the last two years. The lesions were resistant to the previous treatment with corticosteroid ointment. She was otherwise well except for asteatotic eczema, and none of her family members had ichthyotic lesions. Her physical examination revealed multiple, round or oval well-demarcated, scaly brownish macules, approximately 3–7 cm in diameter on the lateral sides of her upper arms and abdomen (Fig. 1a). After obtaining informed consent, a skin biopsy was taken from the lesional skin. Histopathological examination revealed a moderate degree of compact hyperkeratosis without a granular layer (Fig. 2), and follicular plugs within some hair follicles. There were no abnormalities in hematological or urinological examinations or in systemic computerized tomography. Because the clinico-pathological findings were considered to be compatible to pityriasis circinata Toyama, topical application of high-concentration vitamin D3 (tacalcitol) ointment was started. Two months later, her skin lesions had remarkably improved with the treatment and have The Journal of Dermatology Vol. 32: 153–155, 2005

A Case of Polypoid Dermatofibroma

Dermatofibroma is a common benign cutaneous tumor that usually appears as a slowly growing firm nodule. Polypoid nodular dermatofibroma is a variant type that is rarely encountered. We reported a case of polypoid dermatofibroma with a review of the previously reported cases. Polypoid dermatofibroma tends to arise on the leg, especially below the knee. Its size is often larger than that of common dermatofibroma. It is speculated that both the underlying firm tissue and long‐term development may lead the tumor to form a polypoid appearance.