A case of febrile ulceronecrotic Mucha-Habermann disease requiring debridement of necrotic skin and epidermal autograft.

We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a 21-year-old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization.

Cutaneous lymphomas in Tokyo: analysis of 62 cases in a dermatology clinic.

BACKGROUND: The epidemiology of cutaneous lymphomas revealed that the incidence of lymphomas differed depending on various factors including area, race, and sex, among others. OBJECTIVE: This study was undertaken to analyse the incidence of cutaneous lymphomas in Tokyo. METHODS: The clinical records and histologic material from 50 patients with lymphomas of the skin and 12 patients with lymphomatoid papulosis seen during the last 10 years at the Department of Dermatology, The Jikei University School of Medicine, Tokyo, have been reviewed. RESULTS: T-cell lymphomas including mycosis fungoides (MF)-Sézary's syndrome (SS) complex and adult T-cell leukemia/lymphoma (ATL) were more frequent than B-cell lymphomas. The incidence of ATL is associated with the number of human T-cell lymphotropic virus type 1 (HTLV-1) carriers in the general population. Cutaneous B-cell lymphoma (CBCL) is not as rare as previously thought in Japan. CONCLUSIONS: Although the frequency of these cases depends on many unrelated factors, these values can provide a rough indication of the incidence of cutaneous lymphomas in Tokyo. The incidence of cutaneous lymphomas may be influenced by changes in environmental factors including viral infections.

Distinctive distribution of human papillomavirus type 16 and type 20 DNA in the tonsillar and the skin carcinomas of a patient with epidermodysplasia verruciformis.

BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare skin disease characterized by disseminated pityriasis versicolor-like or flat wart-like lesions and by the development of skin carcinomas. It is well established that specific cutaneous human papillomaviruses (EV-HPVs) are associated with both benign and malignant skin lesions in EV patients. However, little is known of the relationship between HPV and the mucosal lesions of EV patients. OBJECTIVES: To detect and identify HPV types associated with skin and mucosal lesions of an EV patient. PATIENT/METHODS: We investigated the skin carcinoma and the coexisting tonsillar carcinoma of a 41-year-old man with EV. Histopathologically, both lesions were squamous cell carcinomas. We analysed these two lesions by immunohistochemistry, in situ hybridization, and by molecular virology. RESULTS: Neither skin nor tonsillar lesions exhibited positivity for HPV capsid antigen by immunohistochemistry. By Southern blot hybridization, however, the skin carcinoma harboured 'EV-specific' HPV20 DNA, while the tonsillar carcinoma harboured 'genital' HPV16 DNA. In addition, in situ hybridization localized the respective viral DNA in the corresponding lesion. CONCLUSIONS: The results indicate that EV-HPV could be responsible for the development of the skin carcinoma, but not the mucosal carcinoma in this patient.

A case of pemphigus vulgaris successfully treated with single filtration plasmapheresis: a correlation of clinical disease activity with serum antibody levels.

We report a patient with pemphigus vulgaris (PV) successfully treated with single filtration plasmapheresis. A 40-year-old man with PV was started on therapy with prednisolone (PSL). Although the dosage of PSL was doubled, and both cyclosporin A (CyA) and pulse therapy were added, the disease was not controlled. After single filtration plasmapheresis began, most of the eroded lesions on the trunk reepithelialized. A switch to double filtration was followed by recurrence. Finally, additional treatments with single filtration plasmapheresis were required to obtain remission. To evaluate the efficacy of the treatment, circulating antibodies were measured by immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) using recombinant desmoglein (Dsg) 3. IIF titer and the ELISA scores correlated with the clinical disease activity. It is suggested that ELISA was more sensitive than IIF.

Molecular mechanism of carcinogenesis by human papillomavirus-16.

Human papillomaviruses (HPVs) are common DNA viruses in humans. Recently, epithelial cancers associated with HPV infection have been used as models of virus-induced carcinogenesis. HPVs can be divided into two groups, mucosal and cutaneous. HPV-16 is the most frequent mucosal type associated with cervical cancer. Although the molecular mechanisms of carcinogenesis by HPV-16 have not been completely elucidated, it is apparent that HPV infection is the major risk factor in cervical carcinogenesis. Two viral early genes, E6 and E7, and an upstream regulatory region (URR) are preserved in cervical carcinoma cell lines as well as in clinical samples of cervical cancer, indicating that these regions are important in cancer development. E6 and E7 function as transforming genes. E6 protein binds to and promotes degradation of the tumor suppressor protein, p53, while E7 protein complexes and inactivates the Rb protein; together, they disrupt cell cycle regulation. E6 and E7 are transcribed from a promoter, P97. P97 is regulated by complex interactions between multiple, positive and negative, cellular factors and the viral E2 product. E2 disruption caused by the integration into the cellular genome may induce overexpression of E6 and E7. The E6 and E7 proteins are thought to act as critical factors in cervical carcinogenesis by inactivating the two tumor suppressor proteins, p53 and Rb, which are commonly mutated in other human cancers.

trans activation by the full-length E2 proteins of human papillomavirus type 16 and bovine papillomavirus type 1 in vitro and in vivo: cooperation with activation domains of cellular transcription factors.

Papillomaviral E2 genes encode proteins that regulate viral transcription. While the full-length bovine papillomavirus type 1 (BPV-1) E2 peptide is a strong trans activator, the homologous full-length E2 product of human papillomavirus type 16 (HPV-16) appeared to vary in function in previous studies. Here we show that when expressed from comparable constructs, the full-length E2 products of HPV-16 and BPV-1 trans activate a simple E2- and Sp1-dependent promoter up to approximately 100-fold in human keratinocytes and other epithelial cells as well as human and animal fibroblasts. Vaccinia virus-expressed, purified full-length HPV-16 and BPV-1 E2 proteins bound a consensus E2 site with high specific affinities (Kd = approximately 10(-9) M) and stimulated in vitro transcription up to six- to eightfold. In vivo and in vitro trans activation by either E2 protein required cooperation with another activator, such as Sp1, or other factors that interact with papillomavirus promoters, such as AP-1, Oct-1, nuclear factor 1/CTF, transcriptional enhancer factor 1, or USF. The glutamine-rich domain B of Sp1 or the mutually unrelated activation domains of other transcription factors were necessary and sufficient for cooperation with either E2 factor. We conclude that like BPV-1 E2, the HPV-16 E2 protein has the potential to function as a strong activator of viral gene expression in cooperation with cellular transcription factors.

Transcriptional enhancer factor (TEF)-1 and its cell-specific co-activator activate human papillomavirus-16 E6 and E7 oncogene transcription in keratinocytes and cervical carcinoma cells.

The human papillomavirus (HPV)-16 oncogenes, E6 and E7, are transcribed preferentially in keratinocytes and cervical carcinoma cells due to a 5' enhancer. An abundant peptide binding to a 37 nt enhancer element was purified from human keratinocytes by sequence-specific DNA chromatography. This protein was identified as transcriptional enhancer factor (TEF)-1 by complex mobility, binding to wild-type and mutant SV40 and HPV-16 enhansons and antigenic reactivity with two anti-TEF-1 antibodies. TEF-1 is cell-specific, but its transactivation also depends on a limiting, cell-specific TEF-1 'co-activator'. We show that both TEF-1 and the TEF-1 co-activator are active in human keratinocytes and essential for HPV-16 transcription. TEF-1 binding in vivo was necessary for HPV-16 P97 promoter activity. Excess TEF-1 and chimeric GAL4-TEF-1 specifically inhibited the P97 promoter by 'squelching', indicating that HPV-16 transcription also requires a limiting TEF-1 co-activator. TEF-1 and the TEF-1 co-activator functions mirrored HPV-16 transcription by their presence in keratinocytes and cervical carcinoma cells and their absence from lymphoid B-cells, but also functioned in liver cells where the HPV-16 promoter is inactive. TEF-1 and its associated co-activator are thus part of a complex mechanism which determines the restricted cell range of the HPV-16 E6 and E7 oncogene promoter.

[Polyclonal antibody to human papillomavirus-related antigens specific to epidermodysplasia verruciformis].

We have developed a polyclonal antibody for human papillomavirus (HPV)-related antigens specific to epidermodysplasia verruciformis (EV). Using this antibody, immunohistochemical studies on 12 EV patients were performed. The polyclonal antibody was obtained from rabbits immunized with roughly purified virions of HPV from an EV patient. Sections from 12 EV patients were treated with the polyclonal antibody and then the peroxidase-antiperoxidase method was used to observe the reaction. The observations revealed not only papillomavirus genus-specific common structural antigen (pgs-antigen) but also HPV-related antigens specific to EV. Pgs-antigen was observed in the nuclei of the upper keratinized cells of the benign lesions and HPV-related antigens specific to EV were observed in the nuclei and cytoplasm of both keratinizing cells of the benign lesions and malignant skin tumor cells. HPV-related antigens specific to EV were observed in sections of all 12 EV patients infected by HPV-5, 5-related, 14, 20, 21 and 38, but not in sections of other HPV infections. Using the immunoblot technique, we detected the main papillomavirus structural polypeptide (MW, 58 Kd) and two other unknown proteins (MW, 42 Kd and 33 Kd) in the benign lesion of an EV patient. Two proteins (MW, 42 Kd and 33 Kd) were also detected in the malignant tumor of the EV patients we consider these proteins to be HPV-related antigens specific to EV.