Yoichiro Hamasaki

Quantitative fluorescence in situ hybridization measurement of telomere length in skin with/without sun exposure or actinic keratosis

Chromosomal and genomic instability due to telomere dysfunction is known to play an important role in carcinogenesis. To study telomere shortening in the epidermis surrounding actinic keratosis, we measured telomere lengths of basal, parabasal, and suprabasal cells in epidermis with actinic keratosis (actinic keratosis group, n = 18) and without actinic keratosis (sun-protected, n = 15, and sun-exposed, n = 13 groups) and in actinic keratosis itself as well as in dermal fibroblasts in the 3 groups, using quantitative fluorescence in situ hybridization. Among the 3 cell types, telomeres of basal cells were not always the longest, suggesting that tissue stem cells are not necessarily located among basal cells. Telomeres of basal cells in the sun-exposed group were shorter than those in the sun-protected group. Telomeres in the background of actinic keratosis and in actinic keratosis itself and those of fibroblasts in actinic keratosis were significantly shorter than those in the controls. Our findings demonstrate that sun exposure induces telomere shortening and that actinic keratosis arises from epidermis with shorter telomeres despite the absence of any histologic atypia.

UVA IRRADIATION FOLLOWING TREATMENT WITH TOPICAL 8-METHOXYPSORALEN IMPROVES BLEOMYCIN-INDUCED SCLERODERMA IN A MOUSE MODEL, BY REDUCING THE COLLAGEN CONTENT AND COLLAGEN GENE EXPRESSION LEVELS IN THE SKIN

BACKGROUND Recent studies have demonstrated that systemic or topical PUVA therapy, i.e., ultraviolet A (UVA) irradiation following treatment with 8-methoxypsoralen (8-MOP), is effective against the sclerotic skin lesions in systemic sclerosis. However, the mechanisms still remain unknown. OBJECTIVE To clarify the mechanisms of this therapy, we created a mouse model of bleomycin (BLM) injection-induced scleroderma and evaluated the effects of PUVA on the fibrotic lesions of scleroderma in this mouse model. METHODS BLM was injected subcutaneously once a day into the mice for 24 days. During the injection period, one group of mice was irradiated with UVA following local application of 8-MOP. Control groups were also set up, which were injected with phosphate-buffered saline, instead of BLM. Skin tissue samples examined histopathologically changes, measured of the content of hydroxyproline, and checked for the expression of genes encoding type I collagen, type III collagen, and transforming growth factor-β1 (TGF-β1). RESULTS The mouse models of scleroderma was found to show an increase in the density of the collagen fibers and thickening of the dermis and increased expressions of type I collagen, type III collagen, and TGF-β1. However, the combination of BLM treatment and topical PUVA treatment mice appeared reduced the dermal thickness and hydroxyproline content, down-regulation of expressions of the type I and type III collagen genes was observed while the expression of the TGF-β1 gene remained unchanged. CONCLUSION These results suggest that the effectiveness of topical PUVA therapy is attributable to the down-regulation of the expressions of the collagen genes by this treatment. The results additionally suggest that is not mediated by down-regulated expression of the TGF-β1.

Lupus miliaris disseminatus faciei successfully treated with tranilast: Report of two cases

We report two cases of lupus miliaris disseminatus faciei (LMDF) in which oral tranilast was effective. In case 1, the patient was a 33‐year‐old woman who had developed pale red papules on her face, especially around her eyes and lower jaw, approximately 7 months previously. Examination of a skin biopsy specimen revealed epithelioid cell granulomas accompanied by caseous necrosis, and a diagnosis of LMDF was made. The patient was treated successively with azithromycin, roxithromycin and minocycline hydrochloride, but there was no improvement. When we tried oral tranilast therapy, flattening of the papules was observed 2 weeks after the start of treatment, and by 1 month the papules had almost disappeared. In case 2, the patient was a 39‐year‐old man who had broken out in erythematous papules on both upper and lower eyelids, with some accompanied by scaling, 2 years before the initial examination. Pathological specimen revealed epithelioid cell granulomas accompanied by caseous necrosis, and a diagnosis of LMDF was made. There was no improvement when treated orally with minocycline hydrochloride or doxycycline hydrochloride, and treatment was switched to oral tranilast therapy. After 1 month of treatment, the papules had almost disappeared. We concluded that oral tranilast therapy should be tried as a treatment for intractable LMDF.

Fixed drug eruption caused by noscapine

Dear Editor, A fixed drug eruption characteristically recurs at the same site or sites each time the offending drug is administrated; however, with each exposure, the number of involved sites may increase. The number of drugs capable of producing fixed drug eruptions is very large; however, most fixed drug eruptions are caused by a limited number of substances. An earlier series incriminated particularly analgesics, sulphonamides and tetracyclines. In a report from Finland, phenazones were reported to be the cause of most eruptions, with barbiturates, sulphonamides, tetracyclines and carbamazepine causing reactions in a smaller number of patients. A series from India implicated acetylsalicylic acid as the most common cause of fixed drug eruptions in children. Many of the antitussive agent-induced fixed drug eruptions are caused by tipepidine hibenzate. Noscapine is a centrally-acting non-opioid antitussive agent and is contained in many over-the-counter (OTC) cold medications. However, only one case of fixed drug eruption caused by noscapine has been reported to date. We report a case of fixed drug eruption with unique clinical features caused by noscapine. A 57-year-old man visited our department on 16 October 2007 complaining of a pruritic eruption on the right lower leg. Past medical and family histories were unremarkable. The patient reported taking OTC drugs whenever he suffered from the symptoms of common cold; he was currently on no medication. He had first noticed a pruritic erythematous lesion measuring approximately 50 mm in diameter on the inner aspect of the right lower leg approximately 1 year prior, and the lesion had gradually increased in size. Physical examination at presentation revealed an elliptical erythematous lesion, 140 mm · 110 mm in size, on the inner aspect of the right lower leg (Fig. 1a). The margin of the erythema showed pigmentation with scales, and the center of the erythema

Usefulness of topical immunotherapy with squaric acid dibutylester for refractory common warts on the face and neck

Dear Editor, Common warts are benign proliferations of the skin caused by infection with human papillomaviruses (HPV). They are traditionally treated using tissuedestructive treatment modalities, such as cryotherapy. Refractory common warts may not only develop on the hands and feet, but also often occur on the face and neck. It is impossible, from the cosmetic point of view, to employ tissue-destructive modalities, such as cryotherapy, for the treatment of these lesions. Treatment of common warts on the face and neck thus poses a difficult challenge. In recent years, topical immunotherapy with squaric acid dibutylester (SADBE) for refractory alopecia areata has drawn attention. While there have also been some successful attempts at the treatment of refractory common warts by topical immunotherapy with SADBE, there are no reports of the use of this modality for the treatment of common warts on the face. We treated two cases with numerous refractory common warts on the face and neck by topical immunotherapy with SADBE and obtained favorable results. These cases are reported herein. In case 1, a 57-year-old man with no particular underlying disease, presented to us with a history of warts on his face and neck for 2 years and warts on his hands for 1 year. He had received cryotherapy at the previously visited clinic, but there had been no improvement. At the initial examination at our hospital, numerous dark-brown papules with a papilliform surface were found on the face and neck, with a maximum diameter of 8 mm. Numerous lightbrown papules with a verrucous surface were also found on the dorsum of the hand, with a maximum diameter of 1.0 cm. Histopathological examination of the lesions revealed epidermal hyperkeratosis, acanthosis and papillomatosis, vacuolar cells in the

Patient with extensive Mongolian spots, nevus flammeus and nevus vascularis mixtus: A novel case of phacomatosis pigmentovascularis.

ketoprofen suggested his photosensitivity was induced by cross-sensitization to photoproducts of fenofibrate and ketoprofen. It became well known that ketoprofen is a causative agent of photosensitization since it was marketed. Recently, cross-photosensitization between ketoprofen and related NSAIDs, such as tiaprofenic acid or suprofen, has proved by photopatch test. Tiaprofenic acid and suprofen both have a similar structure to ketoprofen. Meanwhile, ketoprofen and fenofibrate both have a benzophenone structure (Fig. 1b). Cross-photosensitization between fenofibrate and ketoprofen has likewise demonstrated by photopatch test. The action spectrum of ketoprofen photosensitivity is in UVA, whereas that of fenofibrate has been reported in UVA or UVB or both. In our case, photopatch tests of fenofibrate and ketoprofen were positive in both UVA and UVB. In Japan, although the drug information of ketoprofen has warned this cross-reactivity, there is no description in that of fenofibrate. Thus, we have submitted a drug safety information report to the Ministry of Health, Labour and Welfare, Japan. We should be aware that fenofibrate can cause photosensitivity in patients whom it has been treated with ketoprofen before. CONFLICT OF INTEREST: None declared.

Patient with the vascular type of Ehlers–Danlos syndrome, with a novel point-mutation in the COL3A1 gene

reported fact that there is no correlation between clinical severity and emotional QOL in female AA. The PIADS and VAS scores of the responders (RS 1) and non-responders (RS 0) were not significantly different by Mann–Whitney’s Utest and the PIADS and VAS scores did not correlate with the RS by Spearman’s rank correlation coefficient. However, this may be ascribed to insensitivity of the RS. Overall, mean standard deviation of the VAS was 7.91 1.74, indicating patients’ sufficient satisfaction with wigs. According to the recent British guidelines for AA, a wig or hairpiece is recommended as a good practice point but its evidence is only based on expert opinion or consensus. Here, we quantitatively and statistically examined whether wigs or hairpieces are useful by using PIADS and found that wigs or hairpieces improve perceived competence, adaptability and self-esteem, and the effect correlates with the extent of satisfaction with appearance using wigs.

Function analysis of the promoter gene of the human COL1A1 and analysis of DNA binding factors in the transcription enhancement region

WNT10A is a key signaling molecule that regulates cell–cell interactions and which is involved in multiple developmental processes in embryogenesis [11]. In adult tissues it inhibits the b-catenin degradation complex and is involved in hair follicle and tooth morphogenesis [11]. Demonstration of the homozygous nonsense mutation p.Cys107X in an adult with SSPS underscores the molecular basis of this ectodermal dysplasia syndrome and provides a biological and clinical illustration of the consequences of disrupted WNT10A function in human skin and its appendages.

Effect of erythromycin A and its new derivative EM201 on type I collagen production by cultured dermal fibroblasts

Thinning of the dermis is the principal histological change in atrophic skin disorders and aged skin. It is caused due to a decreased amount of collagen in the dermis. Macrolides have been reported to exert various pharmacological activities, including anti-inflammatory activity, tumor angiogenesis inhibition and growth inhibition of fibroblasts, in addition to antimicrobial activity. In this study, we investigated the effects of erythromycin A (EMA) and its new derivative EM201 on type I collagen production by cultured dermal fibroblasts. Dermal fibroblasts were cultured with 10−9 M-10−5 M EMA or EM201, and collagen production was measured by incubation with radioactive proline, SDS-polyacrylamide gel electrophoresis and fluorography. mRNA levels were measured by Northern blots analysis, and to investigate transcriptional levels luciferase assays were also performed. The results showed that both EMA and EM201 increased collagen production and type I collagen mRNA level (to a maximum of 200% with EMA and 250% with EM201) in a dose-dependent manner in cultured dermal fibroblasts. Transcription of the type I collagen gene was also increased by both macrolides. These results suggest that EMA and EM201 have the potential to improve the thinning of the dermis in atrophic skin disorders and aged skin.

Palmoplantar pustulosis and pustulotic arthro-osteitis treatment with potassium iodide and tetracycline, a novel remedy with an old drug: a review of 25 patients

The use of potassium iodide (KI) to treat palmoplantar pustulosis (PPP) and pustulotic arthro‐osteitis (PAO) has not previously been reported. Here, we report the first successful treatment of PPP and PAO with KI.