Topical cholesterol treatment ameliorates hapten-evoked cutaneous hypersensitivity by sustaining expression of 11β-HSD1 in epidermis.

Changes in the stratum corneum extracellular matrix impair epidermal barrier function and may cause dermatoses. The aim of this study was to examine the effect of exogenous cholesterol application on skin barrier function and cutaneous inflammation. Skin barrier-disrupted or hapten-stimulated mice were treated with topical cholesterol.

Recent advances and developments in the antitumor effect of the HVJ envelope vector on malignant melanoma: from the bench to clinical application.

Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope; HVJ-E) are considered to be safe and efficient non-viral vectors used for drug delivery, since they can incorporate DNA, RNA, proteins and drugs. We have recently found that HVJ-E has a novel antitumor immune effect using a colon cancer model. HVJ-E has also been shown to have both direct and immune-mediated indirect actions against malignancy.

Anti-CCR4 mAb selectively depletes effector-type FoxP3+CD4+ regulatory T cells, evoking antitumor immune responses in humans.

CD4(+) Treg cells expressing the transcription factor FOXP3 (forkhead box P3) are abundant in tumor tissues and appear to hinder the induction of effective antitumor immunity. A substantial number of T cells, including Treg cells, in tumor tissues and peripheral blood express C-C chemokine receptor 4 (CCR4). Here we show that CCR4 was specifically expressed by a subset of terminally differentiated and most suppressive CD45RA(-)FOXP3(hi)CD4(+) Treg cells [designated effector Treg (eTreg) cells], but not by CD45RA(+)FOXP3(lo)CD4(+) naive Treg cells, in peripheral blood of healthy individuals and cancer patients.

Karyopherin alpha2 is essential for rRNA transcription and protein synthesis in proliferative keratinocytes.

Karyopherin proteins mediate nucleocytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest KPNA2 expression is induced in tumor cells and is strongly associated with prognosis, although the precise roles and mechanisms of KPNA2 overexpression in proliferative disorders have not been defined. We found that KPNA2 expression is induced in various proliferative disorders of the skin such as psoriasis, Bowen's disease, actinic keratosis, squamous cell carcinoma, Paget's disease, Merkel cell carcinoma, and mycosis fungoides.

Decreased sudomotor function is involved in the formation of atopic eczema in the cubital fossa.

Background: Eczema in the cubital fossa, which is susceptible to sweat, is frequently observed in atopic dermatitis (AD). However, there has been no direct evidence that sweating causes eczema in the cubital fossa.

Methods: To investigate this issue, axon reflex-mediated sweating volume (AXR) and skin barrier function in the cubital fossa were measured in subjects with AD and in healthy volunteers, and were applied to clinical feature of the cubital fossa.

11β-Hydroxysteroid dehydrogenase 1 contributes to the pro-inflammatory response of keratinocytes.

The endogenous glucocorticoid, cortisol, is released from the adrenal gland in response to various stress stimuli. Extra-adrenal cortisol production has recently been reported to occur in various tissues. Skin is known to synthesize cortisol through a de novo pathway and through an activating enzyme.

Electric field detection of phase-locked near-infrared pulses using photoconductive antenna.

We have demonstrated that a photoconductive antenna gated with 5-fs ultrashort laser pulses can detect electric field transients of near-infrared pulses at least up to 180 THz. Measured sensitivity spectrum of the antenna shows a good agreement with a simple calculation, demonstrating the promising capability of the antenna to near infrared spectroscopy. Using this setup, near-infrared time-domain spectroscopy and characterization of phase controlled near-infrared pulses are demonstrated.

First left-right comparative study of topical rapamycin vs. vehicle for facial angiofibromas in patients with tuberous sclerosis complex.

Background: Tuberous sclerosis complex (TSC) is an autosomal dominant disorder causing multiple hamartomas. Treatment of TSC lesions with mammalian target of rapamycin inhibitors is effective. Recently, several reports have shown the efficacy of topical rapamycin (sirolimus) for angiofibromas.

Dynamic analysis of histamine-mediated attenuation of acetylcholine-induced sweating via GSK3β activation.

Sweating has been associated with the exacerbation of atopic dermatitis (AD) in diverse ways. Acetylcholine (ACh)-mediated sweating is known to be attenuated in AD, but its cause remains obscure. To address this issue, the impact of histamine on ACh-induced sweating was evaluated.

Anti-tumor effects of inactivated Sendai virus particles with an IL-2 gene on angiosarcoma.

Cutaneous angiosarcoma is a life-threatening tumor that is resistant to conventional therapies. The therapeutic effects of Sendai virus particles (hemagglutinating virus of Japan envelope: HVJ-E) carrying IL-2 gene (HVJ-E/IL-2) were examined in a mouse model of angiosarcoma. Intra-tumoral injection of HVJ-E/IL-2 effectively inhibited the growth of angiosarcoma cells (ISOS-1) inoculated in mice and improved tumor-free rates.

Alopecia areata: infiltration of Th17 cells in the dermis, particularly around hair follicles.

Background: The precise pathogenesis of alopecia areata remains unknown, although this disease seems to be triggered by helper T cell infiltration in hair follicles. Recent studies of psoriasis and vitiligo have demonstrated the involvement of Th17 cells. Psoriasis and vitiligo occasionally develop concomitantly or inversely in patients with alopecia areata.

Development and clinical study of a self-dissolving microneedle patch for transcutaneous immunization device.

Purpose: We previously reported the safety and efficacy in animal experiments of transcutaneous immunization (TCI) using a self-dissolving microneedle patch (MicroHyala; MH) made of hyaluronic acid and collagen. However, this MH was an unsuitable TCI device for the human skin, as collagen is suspected to induce inflammation. In this study, we developed an improved collagen-free MH (new-MH) and conducted clinical study to evaluate the fundamental properties and safety in human.

Trends in the prevalence of tuberous sclerosis complex manifestations: an epidemiological study of 166 Japanese patients.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder with multi-system involvement and variable manifestations. There has been significant progress in TSC research and the development of technologies used to diagnose this disorder. As a result, individuals with mild TSC are now being diagnosed, including many older adults who have not developed seizures or cognitive abnormalities.

Barrier abnormality due to ceramide deficiency leads to psoriasiform inflammation in a mouse model.

It has been recognized that ceramides are decreased in the epidermis of patients with psoriasis and atopic dermatitis. Here, we generated Sptlc2 (serine palmitoyltransferase long-chain base subunit 2)-targeted mice (SPT-cKO mice), thereby knocking out serine palmitoyltransferase (SPT), the critical enzyme for ceramide biosynthesis, in keratinocytes. SPT-cKO mice showed decreased ceramide levels in the epidermis, which impaired water-holding capacity and barrier function.

Increased frequency of skin-infiltrating FoxP3+ regulatory T cells as a diagnostic indicator of severe atopic dermatitis from cutaneous T cell lymphoma.

Differential diagnosis of cutaneous T cell lymphoma (CTCL) and severe atopic dermatitis (AD) is often difficult because of the similarity in their skin manifestations. However, such differentiation is extremely important because of the differences in remedy and prognosis. The aim of this study was to investigate new, helpful diagnostic aids for distinguishing CTCL from AD.

Guidelines for the diagnosis and treatment of vitiligo in Japan.

Vitiligo is an acquired pigment disorder in which depigmented macules result from the loss of melanocytes from the involved regions of skin and hair. The color dissimilarity on the cosmetically sensitive regions frequently induces quality of life impairment and high willingness to pay for treatment in patients with vitiligo. The Vitiligo Japanese Task Force was organized to overcome this situation and to cooperate with the Vitiligo Global Issues Consensus Conference.

Expression profiles of cortisol-inactivating enzyme, 11β-hydroxysteroid dehydrogenase-2, in human epidermal tumors and its role in keratinocyte proliferation.

The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) catalyzes the interconversion between hormonally active cortisol and inactive cortisone within cells. There are two isozymes: 11β-HSD1 activates cortisol from cortisone and 11β-HSD2 inactivates cortisol to cortisone. 11β-HSD1 was recently discovered in skin, and we subsequently found that the enzyme negatively regulates keratinocyte proliferation.