Tomoko Syuto

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.

Association of antiphosphatidylserine/prothrombin antibodies with neuropsychiatric systemic lupus erythematosus

Neuropsychiatric manifestations in patients with systemic lupus erythematosus (SLE) are well-recognized symptoms although the pathophysiology of neuropsychiatric SLE (NPSLE) is unclear. Since an association with antiphospholipid antibodies has been reported, we examined the prevalence of antiphosphatidylserine–prothrombin antibodies (anti-PS/PT Abs), lupus anticoagulant (LA), anticardiolipin/β2-glycoprotein I antibodies (anti-β2-GPI Abs), and antiribosomal P protein antibodies (antiribosomal P Abs) in 68 SLE patients and analyzed their associations with neuropsychiatric manifestations. The prevalence of LA was significantly higher in the patients with neuropsychiatric (NP) features than those without NP features (P < 0.02). The levels of anti-PS/PT antibody were also significantly higher in the patients with NP features than those without NP features (P < 0.01). The results indicate that LA positivity and higher levels of anti-PS/PT antibody can be predictive markers for NPSLE.

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.

Aplasia cutis congenita after methimazole exposure in utero successfully treated with basic fibroblast growth factor

factor A 3-day-old girl was referred for dermatologic consultation because of one skin defect on the scalp. She was born at the 36th week of gestation (weight 2834 g) and the Apgar score was 10 at 5 min. The pregnancy was uneventful until the end of gestation. There was no family history for congenital abnormalities. Her mother had been taking methimazole (MTZ) for her autoimmune hyperthyroidism at a dose of 30 mg/kg/d for 2 years, which was reduced to 10 mg/kg/day from the 11th week to the end of the pregnancy. At birth, the patient had one skin ulcer and one hairless atrophic scar on the parietooccipital region (Fig. 1). The round defective lesion was well-marginated, 18·11 mm without any colobomas of the skull and the dura. The hairless atrophic scar was approximately 7·7 mm just lateral to the midline and close to the defective lesion. Physical and ultrasound examinations did not indicate any other malformation. The scalp defect was washed daily with sterile physiological saline and topical recombinant human basic fibroblast growth factor (bFGF) was sprayed to promote granulation as well as epithelialization of the scalp defect. The scalp defect was completely healed 10 days after starting bFGF application (Fig. 2). The cause of aplasia cutis congenita (ACC) is unknown, whereas multiple etiologies have been documented. Our

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.

Clinical usefulness of a supplementary cyclosporin administration with a topical application of maxacalcitol ointment for patients with moderate psoriasis vulgaris

In this study, we aimed at confirming the clinical usefulness of a supplementary additional cyclosporin microemulsion preconcentrate (CyA MEPC) administration in 15 patients with psoriasis vulgaris whose disease activity had been unchanged or exacerbated with topical maxacalcitol treatment. Each patient took a supplementary CyA MEPC administration, 2.5 mg/kg per day in addition to maxacalcitol ointment therapy. When the Psoriasis Area and Severity Index (PASI) score revealed over a 75% decrease against the initial value, the administration of CyA MEPC was tapered off, and a topical application of maxacalcitol ointment was continued for the maintenance phase. All patients could obtain improvement within 12 weeks. In 12 patients whose PASI score reduced over 75%, CyA MEPC was tapered off. Of those, five patients remained in remission by maxacalcitol ointment for over 12 months and three patients for 6 months. In conclusion, this preliminary study may suggest that supplementary therapy of short‐term CyA MEPC administration in combination with topical vitamin D3 treatment may be worth trying for patients with moderate psoriasis vulgaris.

Improvement of quality of life and clinical usefulness of cyclosporin administration in patients with nail psoriasis

Dear Editor, No trials have investigated the effect on the quality of life (QOL) of patients receiving cyclosporin A (CyA) microemulsion preconcentrate (MEPC) treatment for nail involvement. In this clinical study, we aimed at confirming the clinical usefulness of low-dose CyA MEPC administration in psoriatic patients with nail involvement that was unchanged or exacerbated by other treatments. We also investigated the effect of CyA treatment on the QOL of patients with nail involvement. After informed consent was obtained, 32 patients (26 men and six women) with nail psoriasis were enrolled in this study. The patients were 24–85 years of age (mean, 49.9 years), and the duration of nail psoriasis ranged 1–31 years. Twenty-nine of the 32 patients were not responsive to previous treatments, including topical (corticosteroids or vitamin D3 ointments) or systemic retinoids, CyA (Sandimmun; Novartis Pharma, Tokyo, Japan) treatment or psoralen and ultraviolet A therapy therapies. The patients were treated with CyA MEPC (Neoral; Novartis Pharma) at a dose of 3.0 mg ⁄kg per day twice a day before meals. The patients did not receive any other systemic or topical treatments or phototherapy. Evaluation of the nail Psoriasis Area and Severity Index (PASI) score, blood tests and blood pressure monitoring were performed every 2–4 weeks. When the nail PASI score showed a 75% decrease from the initial value, the dose of CyA MEPC was reduced to 1.5 mg ⁄kg per day. When the nail PASI score dropped to zero, the administration of CyA MEPC was tapered off. The final evaluation of the clinical findings was classified as complete recovery (nail PASI score, 0), significant improvement (percentage clearance of nail PASI score; 50–100%), slight improvement (0–50%) or no change (0%). The health-related QOL was evaluated in 14 patients who consented to the evaluation using the Psoriasis Disability Index (PDI), which is the most commonly used disease-specific instrument for this purpose. The patients’ assessment of their QOL using the PDI was conducted at the beginning and end of the study. Statistical analyses of the group data were performed by the Mann–Whitney U-test. Thirty of the 32 patients obtained an improvement of their symptoms (Fig. 1). In the eight patients whose nail changes had completely resolved, the treatment with CyA MEPC was ceased. Six of these patients had no relapse during the follow-up period of 8–24 months. Although two patients had a slight relapse 2 months later, they did not wish to resume the CyA treatment. Among the 16 patients whose nail changes showed significant improvements, we reduced the dosage of CyA MEPC from 3.0 to 1.5 mg ⁄kg per day. All patients maintained a stable condition during the 24-month follow-up period. No

Transitory pigmented purpuric dermatoses in a young Japanese female

We report a 23‐year‐old female patient with a 4‐month history of transitory pigmented purpuric dermatoses (PPD). She was otherwise healthy and reported no history of previous medication intake and none of her family members had any disorders. Clinical examination revealed well‐demarcated, brownish hyperpigmented, reticulated pigmentation with pinhead‐sized purpura. The histopathological specimen was characterized by a mild epidermal hyperkeratosis, elongated rete ridges, papillomatosis and mild mononuclear cell infiltration in the superficial dermis with focal extravasations of red blood cells without siderophage. Despite prominent extravasations of red blood cells and edema both in the papillary dermis and the subpapillary layer, no definite capillaritis was seen. Based on these clinicohistopathological findings, the diagnosis of transitory PPD was considered to be most compatible. Clinicians should recognize the unique but rarely acknowledged disease as a subtype of pigmented purpuric dermatoses.

An unusual case of erythema elevatum diutinum with penile and laryngeal manifestations

Erythema elevatum diutinum (EED) is a rare disorder of chronic cutaneous vasculitis. Skin lesions consist of red or brownish plaques and nodules with a symmetrical distribution on the extensor surfaces of the extremities [1]. However, atypical locations have been reported, such as the penis [2], oral mucosa [3, 4], and cornea [5]. In this study, we report an EED patient with classic cutaneous lesions and their unusual distribution on the larynx and penile shaft.A 64-year-old man with recurrent painful [...]