Yukiko Hashimoto

A case of ichthyosis linearis circumflexa successfully treated with topical tacrolimus

We report a case of ichthyosis linearis circumflexa (ILC) without the typical atopic manifestations and deformities of the hair shaft. The patient responded positively to treatment with topical tacrolimus, suggesting that abnormalities in the immunoregulatory mechanism may be involved in the pathogenesis of ILC.

Sulfhydryl oxidase (SOx) from mouse epidermis: molecular cloning, nucleotide sequence, and expression of recombinant protein in the cultured cells.

Skin sulfhydryl oxidase (SOx) is an enzyme that catalyzes disulfide (S-S) cross-linking through the oxidation of sulfhydryl compounds in the skin. In this study, using the enzyme purified from rat seminal vesicle, we obtained peptide sequences for SOx by mass spectrometry. We then searched for SOx nucleotides corresponding highly to the rat peptide sequences by assembling murine-expressed sequence tags (ESTs) from the GeneBank database. The assembled mouse SOx cDNA has an open reading frame of 1704-bp nucleotides, translating into a size of 568 amino acids. The calculated molecular mass of the mouse SOx protein is 65 kDa. This mouse sequence can be amplified from total RNAs of various mouse tissue samples by reverse transcription polymerase chain reaction, especially highly amplified from those of the seminal vesicles and epidermis. The cDNA fragment was subsequently cloned into the mammalian expression vector (pTARGET-MSSOx), allowing us to express mouse recombinant SOx protein in cultured cells. When pTARGET-MSSOx was transfected, Western blot analysis using anti-SOx antiserum could detect a 65 kDa-band of recombinant SOx in both samples from the whole cell extract and the medium after the harvest of the HEK cells. In immunohistochemical analysis, the Pt-K2 cells, following the introduction of pTARGET-MSSOx, seemed to generate a SOx protein reactive to anti-SOx antiserum in the cells. Moreover, the indirect staining of the S-S bonds using N-(7-dimethylamino-4-methyl coumarinyl) maleimide (DACM), following the addition of N-ethylmaleimide and dithiothreitol, showed that the formation of S-S bridges almost matched the localization of SOx expression in the Pt-K2 cells after the transfection. In essence, we cloned skin SOx cDNA and characterized it as one of the S-S cross-linking enzymes. The SOx clone from mouse epidermis seems to be useful for investigating the potential function of the enzyme in the epidermis, especially for understanding the physiological role of SOx in the differentiation of keratinocytes.

Immunohistochemical localization of sulfhydryl oxidase correlates with disulfide crosslinking in the upper epidermis of rat skin

Striking morphological changes occur during the terminal stages of epidermal differentiation, such as the loss of major cellular organelles, the aggregation of keratin filaments and the formation of the cornified cell envelope (CCE). The CCE is a highly specialized structure in the cell periphery [1–3], and serves as a physical barrier for the organism and helps to maintain the structural integrity of the upper epidermis. The CCE is rendered insoluble by various post-translational modifications including isopeptide crosslinking and disulfide (S-S) bonding. Isopeptide crosslinking is mainly catalyzed by a membrane-associated transglutaminase specific for the epidermis. During the formation of the CCE this enzyme crosslinks different precursor proteins via N-(gamma-glutamyl)-lysine isopeptide bonds [4–6]. On the other hand, S-S bonding is thought to cause conformational changes of the membrane-associated proteins [7]. We have been interested in S-S crosslinking reactions in the epidermis and have reported in this journal [8, 9] on the clear presence of S-S bonds in human skin as determined using a new fluorescent thiol reagent, N-(7-dimethylamino-4-methyl coumarinyl)-maleimide (DACM; Wako, Tokyo), which specifically binds to thiol groups (SH) causing fluorescence [8, 9]. Using this method we have shown that free -SH groups are distributed in the cytoplasm of all living layers of the epidermis. However, SS bridges are only barely detectable in the living layer, but appear suddenly in the periphery of epidermal cells localized in the transition zone of the living and cornified layers of human skin. Based on this fact, we have suggested that -SH groups suddenly become oxidized to S-S bonds at the junction of the granular and cornified layers [8, 9]. Yukiko Hashimoto · Yasushi Suga · Shouichi Matsuba · Masayuki Mizoguchi · Kenji Takamori · Juergen Seitz · Hideoki Ogawa

Salicylic Acid Peels in Polyethylene Glycol Vehicle for the Treatment of Comedogenic Acne in Japanese Patients

It is now widely accepted that the following four distinct pathogenetic processes underlie the development of acne, namely, increased proliferation, cornification and shedding of the follicular epithelium, increased sebum production, colonization of the follicle with Propionibacterium acnes, and induction of inflammatory responses by bacterial antigens and cell signals. The acne lesions observed during the earlier noninflammatory stage due to hyperproliferation and inadequate separation of the ductal corneocytes are called comedones.

A Case of Antiepiligrin Cicatricial Pemphigoid Successfully Treated by Plasmapheresis

We report the case of a 73-year-old Japanese woman suffering from antiepiligrin (laminin 5) cicatricial pemphigoid (CP) with typical clinical and immunopathological features. Histologically, the lesional mucous membrane showed a subepidermal blister formation. When indirect immunofluorescence techniques with skin split by 1 M NaCl as the substrate were used, the patient’s serum reacted only to the dermal side. Immunoprecipitation studies demonstrated that the patient’s serum contained IgG autoantibodies directed against a set of polypeptides that corresponded to epiligrin (laminin 5). After corticosteroids and immunosuppressive agents had been administered systemically, the patient’s autoantibody titer decreased and the cutaneous and mucosal blister formations were suppressed. However, the ocular lesions persisted in spite of these therapeutic regimens. After combining these treatments with double-filtration plasmapheresis, the ocular lesions improved and showed almost no progression. Plasmapheresis may thus present a new option for the treatment of CP.

Two Japanese cases of localized involutional lipoatrophy

We present two Japanese cases of involutional lipoatrophy. The first case is that of a 30‐year‐old woman, who first appeared at our hospital complaining of a localized, well‐demarcated depression, approximately 3 × 4 cm in size, normal to slightly erythematous in coloration, on the lateral side of the left upper arm ( Fig. 1a ). The condition was asymptomatic, and she had noticed this anomaly a month prior to consultation. She received intramuscular injections of corticosteroids of unknown dosage at the affected site for the treatment of allergic rhinitis 4 months prior to her present consultation.

Immunohistological characterization of a Japanese case of pityriasis rotunda.

SIR, Mycosis fungoides (MF) is characterized by clonal helper ⁄ memory (CD4+ CD45RO+) T-cells in the epidermis, whereas follicular mucinosis or alopecia mucinosis has perifollicular T-cell infiltrates and may clinically resemble alopecia areata. Bexarotene is the first retinoid X receptor (RXR)-selective retinoid shown to be effective for cutaneous T-cell lymphoma. Bexarotene has recently been shown to induce T-cell apoptosis in vitro. Although bexarotene oral and topical gel are effective for MF, this is the first report, to our knowledge, of reversal of associated alopecia. Five patients with alopecia secondary to MF or follicular mucinosis were observed among a cohort of over 90 patients receiving bexarotene therapy at the M.D. Anderson Cancer Center. Their demographic data, degree of hair loss, skin biopsy results and drug administration are shown in Table 1. The location of the hair loss was confined to the scalp in four patients and to the extremities in a fifth. All of the skin biopsy specimens revealed atypical CD4+ CD8+ perifollicular lymphocytic infiltrates, and two showed mucin deposits consistent with follicular mucinosis. Three patients had scaling with negative fungal cultures. Patients with early stage MF were treated with topical bexarotene therapy and advanced stage patients with oral bexarotene. The MF as well as the alopecia improved in all five patients, irrespective of the route of delivery. Hair regrowth began within 2–9 months and full regrowth was evident by 1Æ5 years. Patient 1. A 77-year-old Native American woman presented with a 3-month history of a single patch of alopecia accompanied by pruritus and mild tenderness, generalized xerosis, fatigue and a 4Æ5-kg unintentional weight loss. Asthma and childhood eczema were noted. There was a 4 · 5 cm alopecia areata-like lesion with scaling on the scalp (Fig. 1a) and macular erythema of less than 1%. An atypical CD4+ CD8– clonal lymphocytic infiltrate and mucin deposits were present in the follicular epithelium. After applying 1% bexarotene gel daily to the leg and scalp lesions, partial hair regrowth was present at 3 months (Fig. 1b), with full regrowth of terminal grey hair covering the former patch of alopecia at 5 months (Fig. 1c). Patient 2. A 64-year-old Hispanic man with dermatitis for 30 years developed generalized exfoliative erythroderma, patchy alopecia, and a skin biopsy consistent with MF. He had increased fatigue, chills, night sweats and intense pruritus. On examination, he had generalized exfoliative erythroderma and lymphadenopathy. On the scalp, multiple round alopecia areata lesions, patches of white hair, and exclamation point hairs were observed (Fig. 2a,b). An atypical CD4+ CD8+ dermal infiltrate with epidermotropism and a clonal T-cell receptor gene rearrangement were observed in