Effects of imatinib mesylate on cutaneous neurofibromas associated with neurofibromatosis type 1.

Imatinib mesylate seemed to inhibit development of cutaneous neurofibromas (c-NFs) and promote growth of pre-existing c-NFs in our neurofibromatosis type 1 case. This report potentially provides new findings in the effects of imatinib mesylate.

Expression of T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain on CD4+ T cells in patients with atopic dermatitis.

The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4+ T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4+ T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT+ cells among CD4+ T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT+ cells among CD4+ T cells was negatively correlated with both serum thymus and activation-regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4+ T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4+ T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway-based therapeutic approach for AD.

Human papillomavirus type 6/11 identified in an epidermoid cyst of the scrotum.

To date, epidermoid cysts associated with human papillomavirus (HPV) infection have been described mainly in palmoplantar locations, and have involved HPV types 60 and 57. In contrast, HPV-6/11 is a major cause of condyloma acuminatum. Here, we report the case of a healthy 31-year-old man who presented to our clinic with a 1-month history of a 1-cm, reddish-brown, cystic scrotal tumor with a punctum. The lesion was studied histologically, immunohistochemically and by DNA-DNAin situ hybridization. Histology revealed an epidermoid cyst with vacuolated keratinocytes with shrunken nuclei (koilocytes) in the cyst wall. Immunostaining was positive for HPV antigens and in situ hybridization revealed HPV-6/11 DNA in the koilocytes. This is the first report of an HPV-6/11-associated epidermoid cyst in the anogenital skin of an immunocompetent individual.

Malignant melanoma originating on the female nipple: a case report.

We report a very rare case of malignant melanoma arising on a female nipple. A 42-year-old housewife had suffered from a small dark brown nevus on her left nipple for about thirty years without any changes. Six months before her initial visit it had begun to enlarge and rapidly changed from dark brown to black. A small bleeding ulcer was also present in the center of the lesion. Malignant melanoma rather than mammary Paget's disease was suggested based on its clinical course. Excisional biopsy was performed to differentiate between mammary Paget's disease and malignant melanoma. The histopathological examination revealed malignant melanoma, about 4 mm in thickness. She then underwent wide excision with axillary lymph node dissection. The surgical margin was made in a 3 cm radius around the biopsy site. The excision included nipple, areola, and part of the underlying breast parenchyma, adipose tissue and corresponding superficial layer of fascia. Microscopy showed metastasis in one of 13 axillary lymph nodes. After the operation, the patient received adjuvant DAV-Ferron therapy. In such a case, conserving surgery based on correct diagnosis can achieve a good cosmetic result and optimal tumor control.

A cardiac allograft recipient with Bowen's disease on a finger and concurrent perianal bowenoid papulosis.

We report a patient who developed Bowen's disease of the finger and bowenoid papulosis of the perianal area after cardiac transplantation. Human papillomavirus (HPV) type 16 only, not any skin-related or epidermodysplasia verruciformis-related types, was detected in both lesions by in situ hybridization and polymerase chain reaction. The same virus type was identified in both the tumor of the finger and the perianal area, which suggests contact transmission. HPV 16 has often been associated with malignant changes and may be at least one source of the malignancies that are more common in immunosuppressed patients. The presence of a potentially oncogenic type of the HPV in an immunosuppressed patient highlights the importance of regular follow-up of such patients.

Impact of disease severity on work productivity and activity impairment in Japanese patients with atopic dermatitis.

Atopic dermatitis (AD) is a common inflammatory skin disease that is characterized by chronic and persisting pruritic and eczematous lesions. There has been no study of work productivity and activity in AD patients in relation to disease severity. The purpose of this study was to examine the impact of disease severity on work productivity and activity impairment (WPAI) in adult AD patients using the Japanese version of the questionnaire. Data were collected from 112 AD patients who visited the Jikei University Hospital. Outcomes as measured by the questionnaire included employment status, total work productivity impairment (TWPI) and total activity impairment (TAI). We investigated the correlation between TWPI or TAI scores and severity scoring of AD (SCORAD) for disease severity and dermatology life quality index (DLQI) for quality of life impairment. Both TWPI and TAI scores were significantly correlated with the SCORAD and DLQI scores (P < 0.001), indicating disease severity is significantly associated with WPAI in Japanese adult AD patients. Further studies are necessary to evaluate the effects of treatments on WPAI for severe AD patients.

The truncated C-terminal E2 (E2-TR) protein of bovine papillomavirus (BPV) type-1 is a transactivator that modulates transcription in vivo and in vitro in a manner distinct from the E2-TA and E8

The E2 open reading frame of bovine papillomavirus (BPV)-1 encodes a 410 amino acid (aa) transcriptional activator, E2-TA, and collinear polypeptides--E2-TR (243 aa) and E8^E2 (196 aa). E8^E2 and E2-TR share the DNA-binding domain of E2-TA, and both have been defined as transcriptional repressors. Although purified E2-TR and E8^E2 proteins specifically bound E2 sites with similar affinities, only the E2-TR stimulated transcription. Here we show that E2-TR trans-activates E2-dependent promoters 5 to 10-fold in cooperation with cellular factors and in a dose-dependent fashion in epithelial cells and fibroblasts of animal or human origin while E2-TA activated >100-fold and the E8^E2 had no effect. However, in contrast to E2-TA, E2-TR activated transcription from a promoter-proximal position. E2-TR also partially inhibited the BPV-1 P89 or heterologous promoters whereas E8^E2 led to complete repression. Thus, the BPV-1 E2-TR modulates viral gene expression in a manner distinct from other E2 proteins.

Cellular factors are required to activate bovine papillomavirus-1 early gene transcription and to establish viral plasmid persistence but are not required for cellular transformation.

Transcription from the major upstream early gene promoter, P89, of bovine papillomavirus (BPV)-1 is detectable in transfected cells lacking viral gene products yet also responds to viral E2 proteins. In contrast to human papillomaviruses (HPVs), the BPV upstream regulatory region (URR) functions as a transcriptional enhancer in epithelial cells and fibroblasts of bovine, murine or human origin. Mutations of Sp1 and/or two novel transcriptional enhancer factor (TEF)-1 sites within the 5' URR of the intact BPV-1 genome dramatically reduced P89-initiated mRNA levels, leading to decreased BPV-1 plasmid amplification and inefficient formation of transformed cell foci. However, cell lines transformed with wt or mutant BPV-1 genomes contained similar levels of unintegrated BPV-1 DNA, P89 mRNA and E2-dependent transactivation. We conclude that cellular factors necessary for activating viral early gene transcription, establishment of viral plasmid replication and cell immortalization are not required during the maintenance phase of BPV-1 infection.

Meningococcemia without meningitis in Japan.

We report a case of meningococcemia without meningitis, which is a rare infectious disease in Japan. A 32-year-old woman was referred to our hospital with fever and joint pain. Her clinical presentation and the results of laboratory examination on admission suggested viral infection. However, her condition rapidly progressed to septic shock with fulminans purpura. Blood culture grew Neisseria meningitidis. She received antimicrobial therapy and underwent localized therapy for skin lesions. Meningococcal infection should be considered in patients who have fever along with skin rash or petechiae even when there are no signs of meningitis. In this report, we also review case reports of meningococcemia without meningitis in Japan.