Tadashi Tezuka

Acne phototherapy with a high-intensity, enhanced, narrow- band, blue light source: an open study and in vitro investigation

The purpose of this study was to investigate the efficacy of phototherapy with a newly-developed high-intensity, enhanced, narrow-band, blue light source in patients with mild to moderate acne. An open study was performed in acne patients who were treated twice a week up to 5 weeks. Acne lesions were reduced by 64%. Two patients experienced dryness. No patient discontinued treatment due to adverse effects. In vitro investigation revealed that irradiation from this light source reduced the number of Propionibacterium acnes (P. acnes), but not Staphylococcus epidermidis that were isolated from the acne patients. Phototherapy using this blue light source was effective and well tolerated in acne patients and had an ability to decrease numbers of P. acnes in vitro, suggesting that this phototherapy may be a new modality for the treatment of acne.

Decreased expression of filaggrin in atopic skin.

The amounts of the epidermal proteins filaggrin, involucrin, cystatin A and Tad-H-1 antigen produced during the terminal differentiation of keratinocytes were immunohistochemically measured in lesional and nonlesional skin of atopic dermatitis (AD) patients. In addition, the amount of filaggrin in the skin of the inner surface of the upper arm of AD patients (nonlesional skin) and normal controls, obtained by punch biopsy, was measured by an enzyme-linked immunosorbent assay (ELISA) technique. The immunohistochemical study showed that all four proteins were decreased in lesional skin. By contrast, only filaggrin was decreased in nonlesional skin of AD patients. The ELISA showed that the amount of filaggrin in the skin of the inner surface of the upper arm was 2.48±0.45 μg/7 mm2 (n=8) in AD patients, which was 32% of that in the normal controls (7.7±0.55 μg/7 mm2;n=4). This decrease in filaggrin production in atopic skin may be one of the reasons why atopic skin can easily become dry, because filaggrin is thought to be the precursor protein of the emollient factors in the stratum corneum. The evidence that only the expression of filaggrin was suppressed in AD patients, though the genes of filaggrin and involucrin are localized to a very restricted portion of the same gene 1q21, indicates that the filaggrin gene does not share regulatory elements with the involucrin gene.

A survey of psoriasis patients in Japan from 1982 to 2001

BACKGROUND The Japanese Society for Psoriasis Research has conducted an annual survey of psoriasis patients in Japan from 1982 to 2001. OBJECTIVE To perform the epidemiological study about a survey of psoriasis patients conducted in Japan for twenty years. METHODS A sample of 28628 cases was collected from 148 dermatology centers throughout Japan. The reports from each center were analyzed. RESULTS Males (65.8%) were predominant over females (34.2%) in number. The vast majority of cases (86.0%) had plaque-form of psoriasis vulgaris, and 812 cases (2.8%) showed guttate psoriasis. Psoriatic erythroderma (0.8%), generalized pustular psoriasis (0.9%), and localized pustular psoriasis (0.5%) were rare. Three hundred of the patients (1.0%) manifested psoriatic arthritis. Local corticosteroids (67.8%) were the most used modalities, whereas local vitamin D(3) preparations (2.4%) were rarely used. For photo-therapeutic treatments, topical (12.1%) and systemic (7.5%) PUVA were predominant over UVB therapy (0.5%). In systemic treatments, drugs from the herbal medicine was the first (14.2%), followed by etretinate (7.6%), nonsteroidal anti-inflammatory drugs (4.4%), oral corticosteroids (4.1%), methotrexate (2.8%), cyclosporine (1.6%), and anti-cancer drugs (1.4%). CONCLUSION This survey was the first epidemiological study throughout Japan.

Involvement of dectin-2 in ultraviolet radiation-induced tolerance.

Hapten sensitization through UV-exposed skin induces hapten-specific tolerance which can be adoptively transferred by injecting T cells into naive recipients. The exact phenotype of the regulatory T cells responsible for inhibiting the immune response and their mode of action remain largely unclear. Dectin-2 is a C-type lectin receptor expressed on APCs. It was postulated that dectin-2 interacts with its putative ligands on T cells and that the interaction may deliver costimulatory signals in naive T cells. Using a soluble fusion protein of dectin-2 (sDec2) which should inhibit this interaction, we studied the effect on contact hypersensitivity (CHS) and its modulation by UV radiation. Injection of sDec2 affected neither the induction nor the elicitation phase of CHS. In contrast, UV-induced inhibition of the CHS induction was prevented upon injection of sDec2. In addition, hapten-specific tolerance did not develop. Even more importantly, injection of sDec2 into tolerized mice rendered the recipients susceptible to the specific hapten, indicating that sDec2 can break established tolerance. FACS analysis of spleen and lymph node cells revealed a significantly increased portion of sDec2-binding T cells in UV-tolerized mice. Furthermore, transfer of UV-mediated suppression was lost upon depletion of the sDec2-positive T cells. Taken together, these data indicate that dectin-2 and its yet unidentified ligand may play a crucial role in the mediation of UV-induced immunosuppression. Moreover, sDec2-reactive T cells appear to represent the regulatory T cells responsible for mediating UV-induced tolerance.

Phosphorylated cystatin α is a natural substrate of epidermal transglutaminase for formation of skin cornified envelope

Both keratohyalin granules (KHG) and cornified envelopes were stained histochemically in an indirect immunofluorescent study by antiphosphorylated cystatin α antibody, indicating that phosphorylated cystatin α is a component of the cornified envelope proteins. When phosphorylated cystatin α (P‐cystatin α) was incubated with epidermal transglutaminase (TGase) and Ca2− ions, polymerized protein was produced by formation of ϵ‐(γ‐glutamyl)lysine cross‐linking peptide bonds between lysine residues of cystatin α and glutamine residues of suitable protein(s) in the enzyme preparation. However, phosphorylated and non‐phosphorylated cystatins were polymerized to similar extents by the TGase. Immunofluorescent and immunoelectron microscopic observations revealed that P‐cystatin α could be detected in vivo in the KHG and cornified envelopes. Treatment of sphingosine, a specific inhibitor of protein kinase C, markedly suppressed the incorporation of cystatin α into KHG. Thus phosphorylation of cystatin α by protein kinase C may play an important role in targeting cystatin α into KHG.

Therapeutic guidelines for the treatment of generalized pustular psoriasis (GPP) based on a proposed classification of disease severity.

Generalized pustular psoriasis (GPP) is a rare but notoriously recalcitrant cutaneous diseases. Therefore, there have been few reports of more than ten patients with GPP who were treated at the same institution. The severity of this disease and its response to each therapeutic modality vary among patients. In some GPP is life-threatening, but in others it may show a benign, chronic course for a long period of time. Before starting treatment, a knowledge of the therapeutic efficacy and side effects of each drug used in the treatment of GPP is necessary. In our multicenter study, we compared the effectiveness of and adverse reactions to several systemically administered drugs. Following the development of a unique classification of the disease severity based on scoring the clinical symptoms and the laboratory findings, we propose here therapeutic guidelines for the treatment of GPP.

Immunohistochemical detection for nuclear β‐catenin in sporadic basal cell carcinoma

Background Despite the increasing incidence of basal cell carcinoma (BCC), its pathogenesis has remained largely unknown. Recently, it was reported that genes involved in tissue morphogenesis, such as sonic hedgehog or patched, were found to be mutated in BCC, suggesting the involvement of those molecules in the pathogenesis of this tumour. Furthermore, there is evidence that the Wnt‐mediated signalling pathway may be one of the downstream targets of sonic hedgehog‐mediated signalling, which has led us to focus on molecular events on the Wnt pathway in BCC. Among the signal transducers involved in the Wnt pathway, it is clear that β‐catenin plays a pivotal role in the promotion of morphogenesis and cell growth. In respect to this, it has been reported that, in particular circumstances, as in colorectal cancers, β‐catenin migrates to the nuclei, where it exerts an ability to activate the transcription of various genes.

Inhibition of growth and cysteine proteinase activity of Staphylococcus aureus V8 by phosphorylated cystatin α in skin cornified envelope

The activity of a cysteine proteinase purified from Staphylococcus aureus V8 (SAV8) was inhibited by phosphorylated cystatin α (P‐cystatin α) and by purified cornified envelope protein of newborn rat, a conjugated form of P‐cystatin α. Immunohistochemical analysis demonstrated a marked decrease in P‐cystatin α content in cornified envelope treated with sphingosine. The inhibition of papain activity by proteins from sphingosine‐treated skin was much weaker than that exerted by proteins from the untreated skin. The suppression of SAV8 colony formation inoculated on the sphingosine‐treated skin was examined. Colony formation on the sphingosine‐treated skin was enhanced compared to that on normal skin. These findings suggest that P‐cystatin α in the cornified envelope may have a bacteriostatic barrier function against bacterial infection, such as that with SAV8.

The content of free amino acids in the stratum corneum is increased in senile xerosis

Xerosis is one of the characteristics of aged skin. Xerosis may be caused by a decrease in the stratum corneum free amino acids which are natural moisturizing factors derived from filaggrin. In aged skin, filaggrin is immunohistochemically decreased compared with the levels in young skin. However, the differences in stratum corneum amino acids between aged and young skin have not been analyzed quantitatively. Therefore, in this study we determined the stratum corneum amino acids per 1000 stratum corneum cells in aged and young skin by high-performance liquid chromatography. The amount of filaggrin mRNA in the epidermis was also compared between aged and young skin using RT-PCR. The total amount of amino acids in the stratum corneum was larger in aged senile xerosis skin than in young skin. Only a few amino acids were found in the stratum corneum of ichthyosis vulgaris patients (control skin). The expression of filaggrin mRNA in aged skin was, however, similar to that in young skin. These findings suggest that the immunohistochemical decrease in filaggrin in aged skin may be caused by promotion of filaggrin proteolysis in the upper layers of the stratum spinulosum.

Videomicroscopic and histopathological investigation of intense pulsed light therapy for solar lentigines.

A noncoherent, broadband, intense pulsed light source has been effective for symptoms of photoaging skin as a nonablative method. The purpose of this study was to investigate the mechanism of efficacy of intense pulsed light for solar lentigines, a symptom of photoaging skin, with videomicroscopy and histopathology. Skin lesions of patients with solar lentigines who received one treatment of intense pulsed light were examined. Sixteen of 20 patients showed tiny crusts clinically. These tiny crusts were confirmed to be micro-crust formation after epidermal injury with sequential observation using videomicroscope and histopathology. Drop-off of micro-crusts with ample melanin pigments lead to clinical improvement of skin lesions. Intense pulsed light with absorption spectrum for melanin induced injury of melanin-containing epidermal cells via photothermal effects, suggesting that intense pulsed light may be a new modality for solar lentigines.